Anticoagulation for stroke prevention in elderly patients with non-valvular atrial fibrillation: what are the obstacles?

Hong Kong Med J 2016 Dec;22(6):608–15
DOI: 10.12809/hkmj154803
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE  CME
Anticoagulation for stroke prevention in elderly patients with non-valvular atrial fibrillation: what are the obstacles?
CW Wong, FHKCP, FHKAM (Medicine)
Department of Medicine and Geriatrics, Caritas Medical Centre, Shamshuipo, Hong Kong
 
Corresponding author: Dr CW Wong (chitwaiwong@hotmail.com)
 
 
 Full paper in PDF
 
Abstract
The elderly with atrial fibrillation are more prone to stroke. Oral anticoagulants such as warfarin are effective in the prevention of atrial fibrillation–associated stroke and systemic embolism. The CHADS2 or CHA2DS2-VASc score and HAS-BLED score were developed to stratify stroke risk associated with atrial fibrillation and bleeding risk in a patient with atrial fibrillation, respectively, to facilitate the decision for and safe use of oral anticoagulant. Nonetheless, the decision for anticoagulation is not straightforward and the elderly with non-valvular atrial fibrillation are often precluded from anticoagulant prescription. Advanced age and disadvantages associated with the elderly such as fall, comorbidities, cognitive impairment, and polypharmacy contribute to the over-concern of physicians about bleeding risk. Various treatment options such as low-intensity warfarin and aspirin plus clopidogrel have been suggested but are inferior to dose-adjusted warfarin. Novel oral anticoagulants with promising efficacy and convenience hold great appeal. Optimal management of underlying medical conditions and modifiable stroke risk factors, together with intervention to improve the safe use of oral anticoagulants, are useful.
 
 
[Abstract in Chinese]
 
Introduction
Atrial fibrillation (AF) is common in the elderly. The prevalence tends to increase with age with 1.7% in people aged 60-64 years increasing to 17.8% in those aged ≥85 years.1 A similar trend has been reported in the Chinese population despite a lower prevalence of 1.3% in the 60-69 years’ age-group and 7.5% in those aged 80-89 years.2
 
Atrial fibrillation is an independent risk factor for stroke.3 There is an almost five-fold increase in age-adjusted incidence of AF-associated stroke if no anticoagulation therapy is given. The attributable risk of stroke associated with other cardiovascular risk factors—such as hypertension, congestive heart failure, and ischaemic heart disease—decreases with age. In contrast, the attributable risk for stroke associated with AF increases with age, rising from 1.5% in people aged 50-59 years to 23.5% in those aged 80-89 years. In addition, consequent stroke tends to be more severe with significant disability, and mortality rate is double that of non-AF stroke, especially in people ≥75 years.4 Thus, older patients with AF are particularly prone to stroke and its adverse effects.
 
Antithrombotic therapy is effective in reducing AF stroke risk with oral anticoagulant (OAC) more efficacious than antiplatelet agents.5 Until recently and before the advent of novel OAC, the vitamin K antagonist, warfarin, was the only OAC available and it is still the most common OAC prescribed nowadays. Nonetheless, warfarin is inconvenient to use and its associated bleeding risk is particularly troublesome for the elderly. As a consequence, it is often underutilised in the elderly.
 
Stroke risk assessment
Stroke risk varies widely in AF patients and depends on the presence of stroke risk factors. There are several risk stratification schemes to facilitate the decision to commence antithrombotic therapy of which the CHADS2 or CHA2DS2-VASc score is the most common and easy to use with satisfactory reliability (Table 1).6 7 The CHA2DS2-VASc score is an extension of the CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischaemic attack [TIA]) with the addition of other stroke risk factors (vascular disease in the form of prior myocardial infarction, plaque in aorta and peripheral artery disease, age 65-74 years, and female sex) that enable a more comprehensive stroke risk assessment. Prior stroke or TIA, and age ≥75 years are regarded as major risk factors and score 2 points each while other risk factors are regarded as non-major risk factors and score 1 point each. Recommendation for antithrombotic therapy is based on the presence or absence of risk factors.
 

Table 1. Stroke risk stratified by CHA2DS2-VASc score6 7
 
Anticoagulant use in atrial fibrillation for stroke prevention
An anticoagulant that clears clotting factors from the circulation to prevent blood clot formation is considered the most effective AF stroke preventive therapy. The traditional anticoagulant, the vitamin K antagonist—warfarin—impairs the synthesis of clotting factors II, VII, IX, and X; novel OACs selectively inhibit only thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, and edoxaban).
 
Adjusted-dose warfarin (target international normalised ratio [INR], 2-3) has been shown to reduce stroke risk by 64% while antiplatelet agents to reduce the risk by 22%5; high-risk patients showed larger stroke risk reduction with warfarin. There was a small increase in major extracranial and intracranial haemorrhage (ICH) risk (0.2%-0.3% per year) associated with warfarin but overall mortality was significantly reduced (26%) by warfarin.
 
The European Society of Cardiology incorporated the CHADS2/CHA2DS2-VASc risk stratification scheme into guidelines to help clinicians decide the most appropriate antithrombotic therapy.8 It recommends no treatment rather than aspirin for patients with CHA2DS2-VASc score of 0 (including female <65 years) because aspirin may not be better than no treatment in the reduction of stroke risk and increases the bleeding risk6; OAC is recommended for those who score ≥1.
 
Underutilisation of oral anticoagulant in the elderly
The elderly with AF, especially those aged ≥75 years, are considered to have at least one major risk factor for stroke with a CHA2DS2-VASc score of 2, thus, OAC is certainly recommended. Nonetheless, it is underutilised in the clinical setting. Among older patients with known AF without contra-indications to OAC and admitted for ischaemic stroke, only 40% were prescribed warfarin prior to the stroke event.9 Prescription rate decreased with increasing age, from 75% in those <70 years to 24% in those aged ≥90 years.10
 
Overestimation of the bleeding risk and disadvantages associated with advanced age are barriers to prescription of OAC in the elderly. The most commonly cited reason not to anticoagulate is increased bleeding risk followed by fall risk.11 Advanced age, co-morbidities, and patient compliance have also been reported to influence physician decision on anticoagulation. The inconvenience of frequent monitoring with dose adjustment, and drug and food interactions further contribute to OAC underuse. A small survey in Hong Kong showed that both physician awareness and patient knowledge of anticoagulation for AF stroke prevention is insufficient, which is another barrier to OAC use.12
 
Advancing age
The Birmingham Atrial Fibrillation Treatment of the Aged Study recruited nearly 1000 patients aged ≥75 years with AF to receive either warfarin (INR, 2-3) or aspirin 75 mg daily with a mean follow-up of 2.7 years. It revealed a significant reduction in ischaemic stroke in the warfarin group compared with the aspirin group (relative risk=0.3; 95% confidence interval [CI], 0.13-0.63).13 The main benefit was seen in the reduction of severe or disabling non-fatal stroke. The efficacy of warfarin did not change with increasing age. There was no difference between the two groups in major bleeding rate.
 
Analysis of the Atrial Fibrillation Investigators database revealed that the relative benefit of OAC versus an antiplatelet agent and no antithrombotic therapy did not vary by age for ischaemic stroke prevention whilst the benefit of an antiplatelet agent decreased with age.14
 
Analysis of local registry data from 2339 non-valvular AF Chinese patients aged ≥80 years demonstrated a lower rate of ischaemic stroke and death in patients prescribed warfarin (hazard ratio=0.53; 95% CI, 0.48-0.58) but a higher ICH rate than in those without anti-thrombotic therapy after 2.2 years’ follow-up (1.1% per year vs 0.6% per year).15 Overall, net clinical benefits favoured warfarin for all elderly patients, particularly those at high stroke and ICH risk.
 
Therefore, age alone should not be a reason to exclude anticoagulation.
 
Bleeding
Elderly patients are prone to anticoagulant-associated bleeding. The incidence of life-threatening or fatal bleeding has been shown to be significantly higher in elderly patients aged ≥80 years than in those aged <50 years (relative risk=4.6; 95% CI, 1.2-18.1) on warfarin.16 Major bleeding risk has been shown to rise with increasing age in AF patients regardless of anticoagulant use; patients ≥80 years on warfarin were at particularly high risk of ICH.17 Further, ICH as a consequence of warfarin intake was associated with poor outcome; 3-month mortality was double that of patients not taking warfarin.18 The Chinese population has a higher background haemorrhagic stroke rate that accounts for at least 30% of all strokes.19 Together with a four-fold higher warfarin-associated ICH risk in Asians compared with whites,20 concern about warfarin is even greater in Chinese elderly patients.
 
A simple bleeding risk score, HAS-BLED (hypertension, abnormal renal/liver disease, stroke history, bleeding history, liable INR, elderly >65 years, drugs/alcohol) [Table 2], has been derived to predict major bleeding risk in AF patients21 and incorporated into AF management guidelines as an indicator for bleeding risk.8 A score of 0-1 indicates ‘low risk’ with annual bleeding rate of <2%, a score of 2-3 indicates ‘moderate risk’ with annual bleeding rate of 2%-4%, and a score of ≥4 indicates ‘high risk’ with annual bleeding rate of >4%. It is particularly useful in predicting major bleeding risk in patients who are receiving an antiplatelet agent alone or no antithrombotic therapy prior to the initiation of OAC. Its use is not to exclude patients from OAC but to identify modifiable bleeding risk factors that can then be corrected to minimise bleeding risk. Assessment of both CHA2DS2-VASc and HAS-BLED can help balance the stroke risk and bleeding risk in AF patients, but details of how to incorporate the CHA2DS2-VASc score into the HAS-BLED score to guide the management of AF needs further study.
 

Table 2. Clinical characteristics of the HAS-BLED bleeding risk score21
 
Fall
Fall risk and fall-related head injury with ICH increase with age, which is another concern when considering anticoagulation.
 
Using pooled data from major AF trials, warfarin showed a net benefit of stroke protection in elderly patients with average stroke and fall risk over aspirin or no treatment in terms of higher quality-adjusted life-years.22 Regardless of patient age or baseline stroke risk, fall risk was not an important factor in determining optimal therapy: patients with average fall risk would need to fall 295 times in a year for warfarin not to be the optimal therapy.
 
Another database study of nearly 20 000 elderly AF patients (mean age, 80 years) found that patients at high fall and stroke (CHADS2 score ≥2) risk appeared to have a net benefit from OAC despite an increased baseline ICH risk, in which OAC use was associated with a 25% relative risk reduction in the composite outcome of stroke, any haemorrhage, myocardial infarction and death whilst there was an insignificant reduction in those at high risk for fall but with CHADS2 score of 0 or 1.23
 
A subsequent prospective study showed that among 515 AF patients discharged on OAC, there was no significant increase in major bleeding rate (including fatal haemorrhage and ICH) in patients at high fall risk compared with those at low fall risk at 12 months.24
 
These data suggest that in patients with valid indications for anticoagulation, the benefits outweigh the risk, and fall risk should not be a sole reason to withhold anticoagulation.
 
Narrow therapeutic range, co-morbidities, and polypharmacy
Maintaining INR at 2 to 3 for at least 60% of the time provides effective stroke prevention and minimises bleeding risk.8 Nonetheless, maintaining this optimal range is not easy as it is influenced by both internal and external factors.
 
Consistent dietary intake of vitamin K is important for stable anticoagulation. This is difficult for elderly patients with poor health, who get sick frequently, have a poor diet and fluctuating vitamin K intake, or for patients with cognitive impairment who cannot comply with a diet with constant vitamin K content.
 
Many concurrent diseases can also influence INR control. It is particularly troublesome during the exacerbation of disease or if the disease course is fluctuating. Hepatic dysfunction impairs synthesis of clotting factors and thus potentiates the anticoagulation effects. Hepatic congestion as a result of congestive heart failure can inhibit warfarin metabolism and lead to accumulation of warfarin and over-anticoagulation. Hypermetabolic states such as febrile illness or thyrotoxicosis may increase catabolism of vitamin K–dependent clotting factors and may increase INR level.25 On the contrary, hypothyroidism that decreases the catabolism of vitamin K–dependent clotting factors may decrease INR. Patients with AF with concomitant acute coronary disease and percutaneous coronary intervention require aspirin-clopidogrel dual therapy in addition to warfarin, and this further increases bleeding risk. Patients with severe chronic kidney disease (estimated glomerular filtration rate, <30 mL/min/1.73 kg/m2) who are prescribed warfarin are at higher risk of over-anticoagulation, which is associated with more than double the risk for major bleeding compared with patients with mild or moderate chronic kidney disease.26 Patients with cognitive impairment have difficulty in managing their warfarin intake, coping with dosage adjustment, and being aware of drug and food interactions; all of which may result in over- or under-anticoagulation.
 
Warfarin can interact with many drugs and herbal products. This has clinical implications because polypharmacy and adjustment of medications due to an acute illness is frequent in the elderly. Polypharmacy is an independent risk factor for warfarin-related major bleeding and there is a 12% increase in risk for each additional drug taken.24 It is relatively easier to manage drugs in chronic use than those prescribed for a short period of time or when necessary. Warfarin-drug interaction is through the influence of pharmacokinetics that reduce gastrointestinal absorption or disrupts metabolic clearance and pharmacodynamics that alter the haemostatic response.25 The Box lists the common drugs and food that interact with warfarin.27 It should be noted that the majority of the data are from case series or reports because of the scarcity of randomised controlled trials. Thus, the rate of harm and its generalisation to all warfarin users needs continuous review. Nonetheless, physicians should proceed with caution and frequently monitor INR when prescribing potential offending drugs. There is a group of drugs that potentiate bleeding on their own without alteration of INR that includes antiplatelet drugs, heparin, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, and selective serotonin reuptake inhibitors.
 

Box. Common drug and food interactions with warfarin27
 
Pain syndrome and analgesic use are common in the elderly. Among analgesics, paracetamol is preferred for occasional use when taking warfarin.28 A dose that exceeds 2 g daily for more than a few days may raise INR and increase the bleeding risk, however. The NSAIDs, including COX-2 selective NSAIDs, should be avoided. Non-pharmacological methods of pain relief to minimise the use of analgesics are encouraged.
 
Undiagnosed/occult atrial fibrillation
It is not uncommon for a patient to have AF first diagnosed when ischaemic stroke occurs. Very often, AF is undiagnosed as it is usually asymptomatic; 10% to 40% of AF cases are asymptomatic.29 A population-based study revealed that 20.1% of AF in patients aged >60 years was undiagnosed.30 Paroxysmal AF, which bears a similar stroke risk and benefit from anticoagulation to sustained AF,31 also easily evades ordinary electrocardiography (ECG) screening. Paroxysmal AF is common (up to 16%) in cryptogenic stroke32 that constitutes 25% of ischaemic stroke.33
 
Alternatives to warfarin
Low-intensity warfarin
Intensity of anticoagulation correlates directly with incidence of haemorrhage,34 thus low-intensity warfarin with a subtherapeutic range of INR, such as INR of <2, is suggested for the elderly to lower bleeding risk while still effectively preventing stroke. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators found that low-dose warfarin (target INR, 1.5-2.7) was more effective than placebo in stroke prevention.35 There is a racial difference in response to warfarin—a lower INR target of 1.8 to 2.4 appears to be sufficient in lowering both major bleeding and thromboembolic events in Chinese.36 Japanese studies and their registry data also support the lower INR target and have recommended INR of 1.6 to 2.6 for AF patients of ≥70 years in their AF management guideline.37
 
Aspirin plus clopidogrel
Aspirin (75-100 mg daily)–clopidogrel (75 mg daily) dual therapy has been shown to be better than aspirin alone in stroke prevention in AF patients, reducing stroke risk by 28% compared with aspirin alone.38 Nonetheless, it is inferior to OAC in AF patients with at least one risk factor for stroke; OAC reduced stroke risk by 42% compared with dual therapy.39 Both dual therapy and OAC were associated with similar but higher bleeding risk than aspirin. Therefore, dual therapy may only be considered for patients in whom OAC is unsuitable or for patient preference.8
 
Novel oral anticoagulants
Novel OACs (dabigatran, rivaroxaban, apixaban, and edoxaban) have been approved by the US Food and Drug Administration (FDA) for AF stroke prevention. They have undergone large clinical trials in AF patients (mean age ≥70 years) with at least one additional stroke risk factor. Rivaroxaban, dabigatran 110 mg, and edoxaban were non-inferior whilst both apixaban and dabigatran 150 mg were superior to warfarin in stroke or systemic embolism prevention; overall they significantly reduced the risk by 19% compared with warfarin, mainly due to a large reduction in haemorrhagic stroke.40 All-cause mortality was also significantly reduced by 10%. The newer anticoagulants appear to be safer with at least a similar major bleeding rate and consistently lower ICH rate (>50% fewer) compared with warfarin. The exception is gastrointestinal bleeding risk in dabigatran 150 mg, rivaroxaban and edoxaban 60 mg, occurrence of which was 25% more than with warfarin. The favourable result was sustained across a wide stratum of patients at high risk of both ischaemic and bleeding events. The efficacy and safety of novel OACs are consistent among Asian patients including Chinese41 42 43 as well as Chinese elderly aged ≥80 years.44 Because of the favourable efficacy and safety profile, current guidelines have recommended novel OACs as an alternative to warfarin in primary and secondary stroke prevention in patients with non-valvular AF.8
 
In addition, novel OACs are convenient because of their predictable and reliable anticoagulation properties, with far fewer drug interactions and no food interactions or dietary restrictions. They can be administered at a fixed dose and monitoring of coagulation is unnecessary.
 
Nonetheless, their use is not without drawbacks. They are eliminated renally, thus dose adjustment based on renal function is required and they are not recommended for patients with severely impaired renal function (creatinine-clearance, <15 mL/min). Although drug interactions are fewer than those for warfarin, there is potential interaction with P-glycoprotein and CY3A4 inhibitors or inducers, which include common cardiovascular drugs such as amiodarone, dronedarone and diltiazem (all are combined P-glycoprotein inhibitors and weak/moderate CYP3A4 inhibitors), and anti-infectives such as rifampicin (strong CYP3A4 inducers), clarithromycin and ketoconazole (strong dual inhibitors of P-glycoprotein and CYP3A4), thus caution is required. Because they do not affect INR and there is no readily available measure to monitor their anticoagulation, it is difficult to confirm if patients are compliant with therapy. Thus, good drug compliance is as important as taking warfarin. Besides, the cost of novel OAC is more expensive and long-term evidence is not complete. For those patients already on warfarin who have satisfactory anticoagulation control, whether there is extra benefit in switching to novel OAC needs to be explored.
 
Left atrial appendage closure
Since >90% non-valvular AF stroke inducing thromboemboli are from the left atrial appendage (LAA), LAA closure is considered an alternative to OAC.45 Percutaneous occlusion by placing the WATCHMAN device in the LAA was approved by the US FDA for the prevention of LAA thromboembolism in patients in whom OAC was contra-indicated or in whom management with an OAC was difficult. The WATCHMAN device was shown to be non-inferior to OAC in the composite endpoint of stroke, cardiovascular death, and systemic embolism.46 Main adverse effects are procedure-related, eg pericardial effusion, incomplete LAA closure, dislodgement of device, and blood clot formation on the device that requires prolonged OAC.
 
Decision-making and strategies to improve
The aim of prescribing OAC to AF patients is to prevent stroke or systemic embolism such that patients’ health and functional state can be maintained. The decision to prescribe an OAC in the elderly is complicated, however. It requires not only balancing the stroke risk and bleeding risk from OAC, but also needs to consider the patient’s general health, functional and cognitive ability, availability of a caregiver, and patient’s attitude and preference towards anticoagulation. Elderly patients with AF who are in good health or have few co-morbidities and a good functional state will definitely benefit from OAC; for patients in poor health with multiple co-morbidities who are functionally dependent, OAC is not likely to provide additional benefit and there is a high risk of bleeding. Apart from that, decision making for other clinical scenarios is not easy. Careful assessment and discussion with patients and/or caregivers is essential when deciding whether to prescribe OAC.
 
Better preparation of eligible patients for anticoagulation by optimising their medical condition to reduce the risk of stroke and bleeding, together with education of patients and caregiver to enhance compliance, are also useful. The following are recommendations to improve the safety and optimal effect of OAC:
  • Co-morbidities: optimise underlying medical conditions, increase frequency of anticoagulation monitoring if medical condition changes or during acute illness
  • Cardiovascular risk factors: screening for and proper control of modifiable cardiovascular risk factors
  • Cognitive impairment: encourage involvement of caregiver to ensure compliance
  • Polypharmacy: review and simplify drug regimen; discontinue unnecessary medications, avoid drugs that interact with OAC or use alternative drugs with less potential for interaction; frequent INR monitoring if offending drugs are prescribed or discontinued
  • Bleeding: avoid concomitant medications associated with bleeding such as antiplatelet agent, NSAIDs and alcohol; better control of hypertension to lower ICH risk47; add proton pump inhibitor to lower upper gastrointestinal bleeding risk, especially those at increased risk48
  • Fall prevention: fall risk assessment followed by intervention such as exercises for gait, balance, and strength training; education to increase safety awareness, prescription of appropriate walking aids, correction of vision if necessary, environmental modifications, and minimise or avoid offending medications
  • Undiagnosed AF: liberal recording of ECGs in the elderly, especially those with cardiovascular risk factors, to capture AF49; for those with cryptogenic stroke, vigorously look for occult AF by prolonged ECG monitoring32
  • Regular assessment of patient compliance with OAC, and review of stroke and bleeding risk and adjust the management plan accordingly
  • Continued education for physicians about AF and OAC management
  • Setting up of a warfarin clinic in Hong Kong with a multidisciplinary approach (physicians, pharmacists, and nurses) to provide patient education, regular INR monitoring with warfarin dosage adjustment, monitoring of drug and food interactions, and signs of bleeding have been shown to improve drug compliance, minimise bleeding risk, and maintain INR within the therapeutic range50
Conclusion
The elderly with AF are more prone to stroke than younger patients, especially those aged ≥75 years. Anticoagulation is effective in the prevention of stroke in the elderly despite the increased bleeding risk. Age alone should not exclude anticoagulation. Novel OAC is convenient with comparable efficacy to warfarin and a lower risk for ICH. This may improve the prescription, however, long-term evidence is awaited. The best management of the elderly with AF depends on careful estimation of thromboembolic and bleeding risk, patient’s ability to cope with anticoagulation, and patient preference. Optimal control of other potential risk factors for stroke and bleeding is also important.
 
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43. Goto S, Zhu J, Liu L, et al. Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. Am Heart J 2014;168:303-9. Crossref
44. Chan PH, Huang D, Hai JJ, et al. Stroke prevention using dabigatran in elderly Chinese patients with atrial fibrillation. Heart Rhythm 2016;13:366-73. Crossref
45. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996;61:755-9. Crossref
46. Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534-42. Crossref
47. Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005;36:1588-93. Crossref
48. Lin KJ, Hernández-Díaz S, García Rodríguez LA. Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology 2011;141:71-9. Crossref
49. Samol A, Masin M, Gellner R, et al. Prevalence of unknown atrial fibrillation in patients with risk factors. Europace 2013;15:657-62. Crossref
50. Outcome evaluation of warfarin clinic: safe and feasible care delivery model in primary care setting. Hong Kong Hospital Authority Convention 2008. Available from: http://www3.ha.org.hk/haconvention/hac2008/proceedings/pdf/Free%20Paper/SPP6-1.pdf. Accessed Oct 2016.

Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong

Hong Kong Med J 2016 Oct;22(5):496–505
DOI: 10.12809/hkmj164920
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE  CME
Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong
CW Cheung, MD, FHKAM (Anaesthesiology)1; Timmy CW Chan, FFPM ANZCA, FHKAM (Anaesthesiology)2; PP Chen, FFPM ANZCA, FHKAM (Anaesthesiology)3; MC Chu, FFPM ANZCA, FHKAM (Anaesthesiology)4; William CM Chui, MSc, BPharm (Hon)5; PT Ho, FRCPsych, FHKAM (Psychiatry)6; Flori Lam, BHSc(RN)7; SW Law, FRCSEd(Orth), FHKCOS8; Josephine LY Lee, MSc9; Steven HS Wong, MB, BS, FHKAM (Anaesthesiology)7; Vincent KC Wong, BCPS, MPharm5
1 Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, The University of Hong Kong, Pokfulam, Hong Kong
2 Department of Anaesthesiology, Queen Mary Hospital, Pokfulam, Hong Kong
3 Department of Anaesthesiology and Operating Services, Alice Ho Miu Ling Nethersole Hospital, Tai Po, Hong Kong
4 Department of Anaesthesia, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
5 Department of Pharmacy, Queen Mary Hospital, Pokfulam, Hong Kong
6 Consultation and Liaison Psychiatry Team, Kwai Chung Hospital, Kwai Chung, Hong Kong
7 Department of Anaesthesiology and Operating Theatre Services, Queen Elizabeth Hospital, Jordan, Hong Kong
8 Department of Orthopaedics and Traumatology, Prince of Wales Hospital, Shatin, Hong Kong
9 Occupational Therapy Department, Prince of Wales Hospital, Shatin, Hong Kong
 
Corresponding author: Dr CW Cheung (cheucw@hku.hk)
 
 
 Full paper in PDF
 
Abstract
Opioids are increasingly used to control chronic non-cancer pain globally. International opioid guidelines have been issued in many different countries but a similar document is not generally available in Hong Kong. Chronic opioid therapy has a role in multidisciplinary management of chronic non-cancer pain despite insufficient evidence for its effectiveness and safety for long-term use. This document reviews the current literature to inform Hong Kong practitioners about the rational use of chronic opioid therapy in chronic non-cancer pain. It also aims to provide useful recommendations for the appropriate, effective, and safe use of such therapy in the management of chronic non-cancer pain in adults. Physicians should conduct a comprehensive biopsychosocial evaluation of patients prior to the commencement of opioid therapy. When opioid use is deemed appropriate, the patient should provide informed consent within an agreement that specifies treatment goals and expectations. A trial of opioid can be commenced and, provided there is progress towards treatment goals, then chronic therapy can be considered at a dose that minimises harm. Monitoring of effectiveness, safety, and drug misuse should be continued. Treatment should be stopped when opioids become ineffective, intolerable, or misused. The driving principles for opioid prescription in chronic pain management should be: start with a low dose, titrate slowly, and maintain within the shortest possible time.
 
[Abstract in Chinese]
 
Introduction
Chronic pain is pain that persists beyond the usual time of healing, usually marked as 6 months or even 3 months by the International Association for the Study of Pain (IASP).1 Chronic pain arises from complex changes to central or peripheral nervous system signalling, or both. The perception of pain is modulated by an individual cognitive factors and the environment,2 and can significantly compromise daily function, resulting in an important health issue. Hong Kong survey data estimated the prevalence of chronic pain to affect 10.8% of the population in 2000 and 35% in 2007.3 4 Survey participants with chronic pain from an earlier study reported a significant impact on their daily lives.3 Moreover, chronic pain placed a substantial load on productivity, with an estimated loss of approximately 0.2 working days per person in the working population per year, and on health care resources, with almost three quarters of respondents consulting a health care practitioner. The latter survey found that reports of chronic pain were strongly associated with co-morbid mental health problems and anxiety.4
 
Opioid therapy is accepted for acute pain and cancer pain,5 6 but its effectiveness and safety for chronic non-cancer pain (CNCP) remains contentious. By definition, CNCP refers to non-malignant pain that lasts beyond the time of tissue healing, or longer than 3 months.1 Authors cite weak evidence for opioid use for CNCP due to the lack of randomised controlled trials with long follow-up.7 8 Based on systematic reviews, opioids for CNCP—including neuropathic pain, nociceptive pain, and arthritic pain—confer some benefit by reducing pain intensity and improving functional outcome compared with placebo and other non-steroidal anti-inflammatory drugs,9 10 11 12 13 but high-quality studies are rare, and treatment duration is short, ranging from 2 weeks to 6 months. A proportion of patients in the studies reviewed did not progress to long-term therapy due to adverse effects.12 Discontinuation rates from adverse effects were almost 30%, with the most frequently reported events being constipation, nausea, dizziness, drowsiness, and headache.12
 
The potential to develop opioid abuse or addiction with long-term therapy is also a concern. In studies reviewed, addiction or abuse rates were reported to range from 0.27% to 0.43%.12 14 15 Deaths related to opioid analgesic overdose have been increasing, and is being linked to an increase in opioid prescriptions for pain.16 17 Indeed, chronic opioid exposure from prescription appears to be a strong risk factor for an opioid misuse event in patients just diagnosed with CNCP.18 Other potential harm from chronic opioid use includes increased fracture risk,19 androgen deficiency,20 respiratory depression,21 cognitive impairment,22 impaired immunity,23 and opioid-induced hyperalgesia.24 25
 
Global consumption of opioids for moderate-to-severe pain increased approximately 15-fold from 1980 to 2012.26 Generally, opioid consumption of countries in Asia, including Hong Kong, is low relative to the global picture (Fig27), but showing an increasing trend.27 28 Physicians in Hong Kong may be reluctant to prescribe opioids for long-term therapy due to fear of patient addiction. There may also be a cultural prejudice against opioid use stemming from a history of China’s involvement in the global opium trade in the early part of the century.29 Other possible barriers to prescription and patient care may include inadequate physician education about pain management, and lack of physician-patient communication about the seriousness of the pain problem. The absence of a central registry for opioid prescriptions, and the limited number of addiction specialists are potential local logistical barriers. With the introduction of opioid choices in Hong Kong, however, the prescription of strong opioids for long-term treatment may become more common. Examples of strong opioids for CNCP used in Hong Kong are listed in Box 1.30
 

Figure. Global morphine equivalence consumption (2013)27
The consumption statistics are displayed in milligrams per capita, which is calculated by dividing the total amount of opioid consumed in kilograms by the population of the country for that particular year (cite United Nations population data). This provides a population-based statistic that allows for comparisons between countries
Reproduced with permission from Pain & Policy Studies Group. Opioid consumption maps—Morphine equivalence (ME), mg/capita, 2013
 

Box 1. Strong opioids registered in Hong Kong for chronic pain management30
 
Guidelines governing the use of opioids for patients with CNCP have been issued in different countries according to their needs.31 32 33 34 35 36 37 38 The Hospital Authority has recently introduced an opioid guideline for CNCP for public hospital use. A similar guide is not readily available for physicians who are involved in CNCP management but practise outside Hospital Authority in Hong Kong. This document aims to serve as a resource and uniform guide for the appropriate, effective, and safe use of chronic opioid therapy (COT) in the management of CNCP in adults based on local considerations; COT is regarded as the use of strong opioids for more than 3 months.39 This guideline provides recommendations about patient selection, risk screening, initiation of COT, and monitoring during COT, based on a review of the current literature. The target audience is all physicians, especially non-pain specialists, and other health care professionals involved in the multidisciplinary management of the patient with CNCP, who are considering prescribing COT.
 
General considerations for using opioid in patients with chronic non-cancer pain
The biopsychosocial model describes pain as bodily disruption shaped by an individual’s subjective perception. Biological processes, emotions, and social factors all influence the pain experience.2 Consequently, chronic pain is a complex condition that requires a multidisciplinary approach to both evaluation and management, preferably in a coordinated treatment programme.40 41 The IASP recognises the effectiveness of multidisciplinary pain programmes for chronic pain, and recommended the establishment of multidisciplinary pain clinics or pain centres; the latter of which should be associated with a research or academic programme.40 Staff at both pain centres and clinics should include practitioners from various disciplines deemed expert in pain management. Physicians, nurses, mental health professionals, and physical therapists are among those who comprise a team that coordinates diagnosis and management, with constant communication, preferably in one setting.40 41 Essential elements of multidisciplinary pain programmes address pain management, psychosocial recovery, and physical rehabilitation, and include medication, physical therapy, and cognitive and behavioural strategies.42 Such programmes have been proven clinically effective and cost-effective.43 44 45
 
In fact, COT is just part of the multimodal strategy to manage CNCP. Experts do not recommend opioids for first-line treatment of CNCP.34 36 38 Non-opioid treatment options, both non-pharmacological and pharmacological (eg typical analgesics), should be tried first. Despite limited evidence to support the safe and effective use of opioids in CNCP, they may be considered for selected patients who have moderate-to-severe pain and who have not responded adequately to non-opioid therapy.38 In accordance with the biopsychosocial model, treatment of CNCP should address the physical, psychological, and social aspects of the pain problem.41 Treatment of CNCP should thus aim to reduce pain and support patients’ physical, psychological, social, and work functioning.40 The goals of COT include pain reduction, reduction of pain-associated symptoms such as anxiety and sleep problems, and improvement of daily function.46 47 These goals should be individualised and utilise achievable milestones without excessive use of opioids.46 Indeed, daily function outcomes were deemed important by survey participants with chronic pain,48 and should be targets for improvement along with pain control (Box 2).
 

Box 2. Goals of chronic opioid therapy
 
Recommendations
  • Chronic opioid therapy should be considered only as part of a multidisciplinary pain management strategy.
  • Opioids should be prescribed only after exhausting other pharmacological and non-pharmacological treatment options.
  • Treatment goals acceptable to both patients and their physicians should be set when COT is considered.
  • When prescribed, COT should aim to reasonably reduce pain and its associated symptoms, as well as improve functional outcomes.
 
Patient evaluation and selection
Prior to starting COT, a comprehensive patient evaluation should be carried out to form a diagnosis, establish the cause of pain, describe pain intensity, and determine a patient’s risk profile with the use of opioids.38 46 The evaluation informs on the suitability of a patient for COT, and, if the decision to pursue COT is made, provides the foundation for individualising a treatment plan. A thorough history and physical examination with appropriate investigations are essential. The pain complaint should be thoroughly investigated with regard to characteristics, underlying factors, and effects on the patient’s functional status.38 46 Assessment should include a medical and psychosocial history, including previous medication, general health, family support, and work status. For example, increased use of opioids for pain control prior to spine surgery was found to be associated with worse postoperative outcomes, such as increased demand for opioids after surgery, and decreased incidence of opioid independence 1 year after surgery.49 50 This highlights the need for a complete evaluation and screening of each patient prior to opioid use. Evaluation findings may impact subsequent patient counselling and treatment planning.
 
The rate of problematic opioid use or aberrant drug–related behaviour in patients with CNCP on COT is 11.5%.51 Prevalence of substance use disorder among patients with CNCP, with or without opioid use, ranges from 3% to 48%.52 Because problematic opioid use complicates pain treatment and may cause significant harm, a patient’s risk for opioid abuse, misuse, or addiction must be assessed prior to COT.38 46 53 54 Screening helps the physician to anticipate the patient’s risk of developing aberrant behaviour while on COT.53 54 Family and personal history of substance abuse, a history of psychiatric or mood disorders, and younger age have not been validated as predictive of opioid misuse, but have been shown to potentially increase risk.52 55 56
 
The physician can utilise structured clinical interviews and self-reports to elicit these factors.52 56 Questionnaires such as the Opioid Risk Tool, which assigns weights to predictive factors of opioid misuse, may be useful.57 The presence of apparent predictors of misuse such as a personal or family history of substance abuse or addiction does not necessarily preclude the use of opioids, but may affect structure of therapy (eg closer monitoring, stricter prescription practice) and require additional consultation from specialists, including psychiatrists.54 Urine drug screening (UDS) may be a useful aid in detection of latent drug abuse. Every assessment must be thoroughly documented.
 
According to addiction specialists from the Hong Kong College of Psychiatrists, screening by psychiatrists for suitability of high-risk patients for COT may not be useful, as evidence to support reduced substance abuse risk through conjoint selection by pain specialists and psychiatrists is lacking. There is also inadequate evidence that the future risk of opioid abuse is reduced by treating substance abuse prior to COT; thus, the decision to make this treatment a prerequisite for COT rests on the pain management team (written communication, Clinical Division of Substance Abuse & Addiction Psychiatry, Hong Kong College of Psychiatrists, 2016). Patients with active substance abuse (opioid, non-opioid, or both) and psychological disturbances may be referred to substance abuse clinics (SACs) in Hong Kong for pre-COT psychiatric treatment (Appendix 1).
 

Appendix 1. Referral channels and clinics for patients with opioid misuse, and patients who will need discontinuation of opioid treatment, suggested by the Hong Kong College of Psychiatrists
(written communication, Clinical Division of Substance Abuse & Addiction Psychiatry, Hong Kong College of Psychiatrists, 2016)
 
Recommendations
  • Patients considered for COT should have a thorough physical, psychological, and social assessment.
  • Risk of substance misuse or addiction should also be assessed for appropriate treatment planning.
 
Prescription of chronic opioids
Informed consent and documentation
Guides on COT for CNCP recognise the need for informed consent to explain the benefits, risks, and complications of COT before a trial of opioid therapy, and when the decision to use COT is reached.38 46 Consent in the form of a written plan or treatment agreement, or opioid contract, can set expectations between the physician and patient regarding their actions and treatment targets.13 38 46 The usefulness of a contract in promoting adherence to a COT regimen lacks evidence, however. Also, use of a contract has underlying ethical issues relating to patient autonomy and the assumption of potential opioid abuse.13 58 Nevertheless, if utilised, an agreement should outline information on COT and alternative treatment options, benefits, risks (which include adverse effects, behavioural risks, and medical complications), steps to reach treatment goals, means of monitoring improvements, and conditions for continuing or discontinuing therapy (Appendix 2).13 38 58 Specifically, it may include from whom and where the patients should obtain their prescription, the number and time of office follow-ups, and expectations on use of UDS.46 58 The agreement should be reviewed continually during treatment.46
 

Appendix 2. Sample elements of an opioid informed consent and agreement13 38 58
 
Trial of opioid therapy
An opioid trial assesses patients’ responsiveness to opioids. Dose titration during an opioid trial determines the lowest effective dose with the least or minimal side-effects for an individually tailored programme.59 The choice of opioid should be based on factors related to the individual patient, such as previous response to opioids, health status, treatment goals, predicted risks; on medication-related factors, such as availability and pharmacological and adverse effect profiles; and on physician experience and expertise.33 36 59 Parenteral forms of opioids are not recommended for an opioid trial due to risk of abuse.33 36
 
Opioids should be titrated slowly, for example, at increments of 10 to 50 mg equivalent per day of a long-acting opioid, until the optimal dose that provides benefit with the least side-effects is attained.33 47 60 The optimal dose is suggested to lead to a 30% pain reduction (based on an 11-point scale) that does not cause significant adverse effects.33 61 A trial of therapy may last weeks or months. Duration can be set from 4 to 6 weeks, or up to 90 days in some pain centres.46 47 60 The target results and duration of the trial period should be understood and agreed by the patient.46 60
 
Prescription for special concerns
Driving and work safety are potential concerns when COT is used. Studies have not shown impairment of driving-related activities with opioids,13 62 63 but patients should be informed of factors related to opioid use that may cause impairment, including initiating opioids or changing opioid dose, poor sleep, severe pain, and concomitant intake of alcohol or sedating medications.13 33 38 Patients should be advised to avoid driving or participating in potentially dangerous activities if they show signs of impaired cognition or psychomotor ability, such as somnolence, poor coordination, or decreased concentration.33 38
 
Pregnant patients or patients planning to get pregnant should be counselled on the risks of COT during pregnancy. Such therapy during pregnancy has been found to be associated with neonatal withdrawal syndrome, poor birth outcome, and certain birth defects.64 65 66 Because of this, COT during pregnancy is not encouraged unless the potential benefits outweigh the risks.38 47
 
Recommendations
  • Informed consent should be obtained before an opioid trial as well as before the start of COT.
  • Prior to COT, an opioid trial should be conducted to assess patient response and to determine an optimal opioid dose.
  • The choice of drugs and initial dosing should be individualised according to the drug profile, patient characteristics and goals, and physician experience.
  • Patients on opioids who show signs of impaired cognition or psychomotor activity should be cautioned against driving and other potentially dangerous activities.
  • Use of COT during pregnancy is discouraged because opioids may lead to poor birth outcomes.
 
Monitoring during chronic opioid therapy
Ongoing assessment and regular monitoring during COT allows physicians to characterise patients who continue to benefit from opioids or who may need changes in their treatment programme. During an opioid trial, the patient is regularly monitored, usually at weekly intervals, to assess the four A’s: analgesia, activity, adverse effects, and aberrant behaviour.33 60 67 The dose is adjusted based on changes in pain intensity, improvements in daily function, and development of side-effects and of aberrant behaviour.33 35 46 Validated pain assessment tools such as the Brief Pain Inventory or the Pain, Enjoyment, and General Activity scale may be used at baseline and at regular intervals thereafter to describe changes in pain relief and function.33 46 47 Drug-related behaviour can be monitored through patient interviews, observation, and UDS.
 
Evidence is lacking on the reliability of UDS in predicting aberrant behaviour, and UDS still needs to be evaluated if it improves clinical outcomes.37 Nonetheless, UDS provides important information on adherence to the treatment plan and existence of possible drug misuse when appropriately used with other monitoring tools. Although other biological specimens may be tested, obtaining urine is considered practical and convenient, and results can be obtained within a few days to allow modification of patient care.68 Physicians should be aware of limitations in interpreting results and should maintain communication with testing laboratories to resolve any doubts.68 In addition, differential diagnoses for each result should be considered, for example, absence of prescribed drug in the urine could indicate non-access to required prescription, or diversion of the prescription.37 69 These considerations should facilitate a discussion with the patient in order to improve care. Prior to the onset of opioid therapy, it is important to educate the patient and specify the objectives of UDS in the treatment agreement to avoid confrontation and uphold a strong physician-patient relationship.69
 
There is no agreement on the frequency of UDS, but it should be performed as frequently as necessary according to the patient’s risk for misuse, occurrence of aberrant behaviour, and on availability of the test.37 47 If aberrant drug behaviour is noticed, the patient may need more intensive monitoring and referral to a pain or substance abuse specialist.47 60 Continuation of opioid therapy may be agreed upon by physician and patient if there is note of progress towards the patient’s goals as determined from regular monitoring.60 If the patient is deemed suitable to continue opioids in the long term after an opioid trial has established a stable dose, monitoring of the four A’s is undertaken at regular intervals.60 Intervals can be as far apart as 6 months for patients with no risk issues, or as frequent as monthly for those at risk of opioid misuse, or those taking doses near the threshold level.47
 
Recommendations
  • Monitoring during COT should include documentation of pain intensity, level of functioning, presence of adverse events, and adherence to prescribed therapies.
  • Validated pain assessment tools may be used at baseline and regularly thereafter to describe changes in pain and function.
 
Opioid rotation
Patients who initially responded but have become tolerant despite escalating doses, and those in whom side-effects limit dose increases, may consider an opioid switch or rotation.70 Despite the lack of evidence from controlled studies for the clinical effectiveness of opioid rotation,71 72 the strategy may be useful based on observed differences in individual responses to various opioids.73 This occurrence may be explained by genetic variations in receptor subtypes that modulate drug effects, and that also potentially promote incomplete cross-tolerance among opioids.74
 
Opioid rotation involves selection of a new opioid, determination of its appropriate initial dose, and subsequent titration for a satisfactory balance of efficacy and side-effects.70 Use of an equianalgesic table can facilitate estimation of the new drug’s initial dose.33 75 76 77 78 Its dose should approximate the dose of the previous drug (Table 133 75 76 77 78). Drug potencies reflected by the reference table may be underestimated74; therefore, experts support an initial automatic reduction in the estimated equianalgesic dose of the new drug by 25% to 50% for safety.70 If the previous dose was high, a reduction by at least 50% is recommended by some authors.33 Exceptions to this include a switch to methadone, which should use a reduction of 75% to 90%, and switch to transdermal fentanyl, which does not require a reduction.70 This initial computation should be adjusted or retained based on the patient’s clinical situation. Subsequent drug titration should be based on this initial dose.70
 

Table 1. Conversion factors for equianalgesic dose of selected opioids33 75 76 77 78
 
Recommendations
  • When switching to a new opioid, calculate the equianalgesic dose using a reference equianalgesic table.
  • Reduction of the calculated dose is recommended for safety.
  • Prior to a new opioid trial, adjust the dose further after reassessment of the patient’s clinical situation.
 
Management of side-effects and problematic opioid use
Constipation, nausea, headache, and sedation are the most frequently reported opioid side-effects in clinical trials.12 Many side-effects reportedly diminish over time,12 but some side-effects such as constipation and vomiting may be severe enough to prompt discontinuation from trials. Constipation, in particular, may not diminish and cause significant severe discomfort.79 Opioid dose adjustment, opioid rotation, and proactive therapy (eg stool softeners for constipation) are strategies that can minimise severity of adverse effects.21 79 Common opioid-associated side-effects should be anticipated and managed appropriately when identified to maintain compliance (Table 2).33
 

Table 2. Opioid-associated side-effects and complications33
 
Problematic drug use or aberrant drug behaviour may arise from opioid use. As described previously, patients on COT who are at high risk of opioid misuse or addiction may need additional consultation with addiction experts, and a restructuring of their programme to include frequent, close monitoring.33 46 47 54 In addition to patient interviews, proper drug use may be monitored through methods such as regular visits, pill counts, and UDS.80 Physicians should attempt to identify the cause of behaviour that suggests the possibility of opioid misuse. It is important to be aware of pseudo-addiction, which apparently exhibits the same compulsive behaviours for opioids as in addiction, but is due to inadequate pain relief from undermedication.81
 
When drug misuse is identified, the patient should undergo a complete re-evaluation for treatment modification.33 Repeated, serious aberrant behaviour requires discontinuation of COT and referral to substance abuse specialists for detoxification.33 47 Referral channels and treatment through SACs for patients with significant psychological disturbance or addiction features (eg aberrant drug behaviour, other substance abuse such as benzodiazepines) are available in Hong Kong (Appendix 1).
 
Recommendations
  • Anticipate common side-effects and manage appropriately.
  • If problematic drug use is recognised, re-evaluate the patient and modify treatment.
  • Discontinue COT if aberrant behaviour is present. Referral to substance abuse specialists is warranted.
 
Upper dose limit and exit strategy
The goals of COT should be revisited at regular intervals to see if patients can meet their targets within a defined dose range, determined from the initial daily dose titrated to the lowest effective dose. It is recommended that the upper dose titration limit should not exceed 120 mg of oral morphine or its equivalent, or 200 mg in some centres.33 38 47 60 If the daily dose exceeds this limit, a reassessment of the pain condition, potential for misuse, and need for more frequent monitoring is warranted.33 38 Indications for discontinuation include no change or improvement in therapeutic goals despite escalating doses, intolerance to side-effects, and persistence of aberrant behaviour. If the decision to discontinue opioids is reached, the opioid should be tapered to avoid withdrawal problems.33 46 47 60
 
The tapering plan is variable, but generally, a reduction of 10% per week from the original dose is well tolerated.33 47 60 A faster or slower rate may be suitable depending on the patient’s situation. Physicians should monitor patients for changes in pain and for the appearance of side-effects, withdrawal symptoms, and behavioural issues. These concerns should be properly managed. In some cases, a referral to the appropriate specialists may be warranted. Likewise, patients who fail to benefit from COT and who need discontinuation may be referred to SACs in Hong Kong for detoxification and rehabilitation services (written communication, Clinical Division of Substance Abuse & Addiction Psychiatry, Hong Kong College of Psychiatrists, 2016).
 
Recommendations
  • Chronic opioid therapy should be stopped if patients experience no progress towards treatment goals, experience intolerable side-effects, or are engaged in repeated aberrant drug-related behaviours.
  • Opioids should be tapered to avoid withdrawal.
 
Conclusion
Strong opioids play a role in the multimodal management of CNCP. They may be appropriate for selected patients despite insufficient evidence of effectiveness. Opioid therapy is potentially associated with common side-effects and significant harm; thus, careful patient selection by a thorough patient evaluation prior to treatment, and careful dose titration and monitoring during initiation and long-term therapy, are all recommended steps for rational opioid use in CNCP. Whenever opioid is prescribed for chronic pain management, it should be started with a low dose and titrated slowly, as well as maintained for the shortest possible time.
 
 
Acknowledgements
We would like to thank the Clinical Division of Substance Abuse & Addiction Psychiatry, Hong Kong College of Psychiatrists for their advice and opinions.
 
Declaration
All authors are members of the working group for Guideline for Chronic Opioid Therapy in Chronic Noncancer Pain, Hospital Authority Multidisciplinary Committee on Pain Medicine, Hospital Authority, Hong Kong. All authors have disclosed no conflicts of interest.
 
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49. Lee D, Armaghani S, Archer KR, et al. Preoperative opioid use as a predictor of adverse postoperative self-reported outcomes in patients undergoing spine surgery. J Bone Joint Surg Am 2014;96:e89. Crossref
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51. Fishbain DA, Cole B, Lewis J, Rosomoff HL, Rosomoff RS. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review. Pain Med 2008;9:444-59. Crossref
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53. Højsted J, Sjøgren P. Addiction to opioids in chronic pain patients: a literature review. Eur J Pain 2007;11:490-518. Crossref
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55. Edlund MJ, Steffick D, Hudson T, Harris KM, Sullivan M. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain 2007;129:355-62. Crossref
56. Turk DC, Swanson KS, Gatchel RJ. Predicting opioid misuse by chronic pain patients: a systematic review and literature synthesis. Clin J Pain 2008;24:497-508. Crossref
57. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med 2005;6:432-42. Crossref
58. Arnold RM, Han PK, Seltzer D. Opioid contracts in chronic nonmalignant pain management: objectives and uncertainties. Am J Med 2006;119:292-6. Crossref
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61. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149-58. Crossref
62. Fishbain DA, Cutler RB, Rosomoff HL, Rosomoff RS. Are opioid-dependent/tolerant patients impaired in driving-related skills? A structured evidence-based review. J Pain Symptom Manage 2003;25:559-77. Crossref
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Guidelines for allergy prevention in Hong Kong

Hong Kong Med J 2016 Jun;22(3):279–85
DOI: 10.12809/hkmj154763
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE
Guidelines for allergy prevention in Hong Kong
Alson WM Chan, FHKCPaed, FHKAM (Paediatrics)1; June KC Chan, RD (USA), MSc2; Alfred YC Tam, FHKCPaed, FHKAM (Paediatrics)1; TF Leung, MD, FHKAM (Paediatrics)3; TH Lee, ScD (Cantab), FRCP (Lond)2
1 Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong
2 Allergy Centre, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong
3 Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong
 
This guideline was presented in part at the Symposium on Allergy Prevention that was co-hosted by the Hong Kong Institute of Allergy & the Hong Kong Society for Paediatric Immunology, Allergy and Infectious Diseases, 17 September 2015, Hong Kong.
 
Corresponding author: Dr Alson WM Chan (awmc@hku.hk)
 
 Full paper in PDF
Abstract
Allergic diseases are a global problem. Mothers are advised to enjoy a healthy diet with no restrictions during pregnancy and lactation, as prophylactic dietary restriction is unlikely to reduce the development of atopic disease. Breastfeeding is recommended for the first 6 months of the newborn’s life. Atopic eczema has been shown to be significantly reduced in high-risk infants fed a hydrolysed formula compared with standard cow’s milk formula. Complementary food is also recommended for infants over 4 months if they are developmentally ready. Various environmental factors may influence the prevalence and course of allergic diseases. There is a strong epidemiological association between air pollution from traffic and allergies. Smoking is also a significant risk factor. Home dampness and visible mold are associated with recurrent wheeze and asthma. House dust mite is a possible cause of asthma. Lifestyle factors also play a role. Obesity shows a clear relationship with asthma and eczema. Stressful life events may increase the risk of atopic disease. Immunotherapy has been shown to be effective. It reduces new sensitisations and prevents progression of allergic rhinitis to asthma. Summary of the above recommendations are presented.
 
[Abstract in Chinese]
 
Introduction
There has been a continuous rise over the last 50 years in the prevalence of allergic diseases in both developed and developing countries. The situation is especially dramatic in children. Up to 40% to 50% of schoolchildren are now sensitised to one or more common allergens. The growing burden of allergic diseases has been recognised as a new pandemic of the 21st century.1
 
It has long been acknowledged that genetically predisposed children usually develop various allergic diseases in the typical evolution described as ‘Allergic March’. Cow’s milk and food are the first allergens that infants encounter soon after birth. Their allergies then progress from the gut and skin to the respiratory tract when they grow older and come into contact with more environmental allergens. Prevention strategies applied during infancy or early childhood have been shown to stop the manifestations of allergy and its ‘marching’ from gut to skin and to airway.2
 
Recent studies have shown that induction of immune tolerance is the key to success in allergy prevention. Early food allergen introduction between 4 and 6 months leads to better immune tolerance.3 New evidence is also showing the association of allergy with various environmental and lifestyle factors that might be amenable to manipulation.
 
As the burden of allergic diseases has been increasing and the concept of allergy has been changing quickly over the last few years, there is a need to develop updated guidelines for allergy prevention.
 
Epidemiology of allergic diseases in Hong Kong children
Allergic diseases constitute a major health problem worldwide, with asthma as one of the most common chronic diseases of childhood. The population-based International Study of Asthma and Allergies in Childhood (ISAAC) determined that about one tenth of secondary schoolchildren have asthma and 15% have atopic dermatitis. About one third of Hong Kong children aged 6 to 7 years suffer from rhinitis.4 The phase-2 ISAAC confirmed aeroallergen sensitisation as a major risk factor for childhood allergies,5 but this relationship varied substantially among populations and increased with economic development.
 
There are limited data on the prevalence and risk factors for atopic disorders among Asian preschool children. Using an ISAAC-based questionnaire, we reported the prevalence of ‘ever’ and ‘current’ wheeze among Hong Kong children aged 2 to 6 years to be 16.7% and 9.3%, respectively.6 Consistent with our earlier report for older Chinese children,7 the use of foam pillow and gas as the cooking fuel in infancy were significant risk factors for current wheeze in these young children.
 
The incidence rates of asthma and allergies have been increasing in many developed countries. Our phase-3 ISAAC nonetheless found a reduced asthma prevalence over an 8-year period among Hong Kong secondary schoolchildren.8 The prevalence of asthma ever, wheeze ever, and current wheeze was also similar in local children aged 6 to 7 years between 1995 and 2001, although there was a significant increase in lifetime and current rhinitis, current rhinoconjunctivitis, and lifetime eczema during this period.9
 
A territory-wide questionnaire study investigated the prevalence of adverse food reactions (AFR) among local children attending 21 randomly selected nurseries and kindergartens in 2004/2005.10 The prevalence rates of parent-reported AFR and parent-reported, doctor-diagnosed AFR were 8.1% and 4.6%, respectively. The occurrence of AFR in these pre-schoolers adversely affected their parents’ quality of life.11 Shellfish was the most important food for AFR, followed by egg, peanut, cow’s milk, beef, tree nuts, and fish. Another local study supported these findings.12 These figures suggested similar epidemiology and spectrum of food allergy between our Chinese and Caucasian children. Because questionnaire data may be subject to biased reporting, we also collected data for probable food allergy that was defined by the presence of suggestive clinical features and either positive skin prick test or in-vitro allergen-specific immunoglobulin (Ig) E assays.13 The prevalence of probable food allergy was 2.8% in our primary schoolchildren.14
 
In another more recent study, our group adopted the same sampling strategy and methodology to investigate longitudinal changes in food allergy prevalence among Chinese preschool children.15 The prevalence of parent-reported AFR was 9.7%, but there was no change in parent-reported, doctor-diagnosed AFR. When adjusted for maternal education as a covariate, the prevalence of parent-reported AFR was static whereas that of parent-reported, doctor-diagnosed AFR significantly decreased during this 9-year period.15
 
Maternal diet during pregnancy
It is universally recommended for all mothers to eat a healthy diet without restriction during pregnancy. Prophylactic dietary restriction of potent food allergens should not be encouraged.16
 
During the first trimester, higher maternal intake of peanut, milk, and wheat is associated with a significant reduction in the risk of developing a peanut allergic reaction, asthma and allergic rhinitis, and atopic dermatitis in mid-childhood, respectively.17 In addition, a restrictive diet may have adverse effects on maternal or fetal nutrition.
 
Maternal consumption of fruits and vegetables, fish, long-chain omega-3 fatty acids, a good ratio of omega-3–to–omega-6 fatty acids, and milk fat during pregnancy is associated with a lower prevalence of allergy. The consumption of fruits and vegetables is beneficial for their antioxidants and natural prebiotics that may have prophylactic properties by promoting a more diverse microbiota and consequently a positive effect on fetal immune development.18 The consumption of fish during pregnancy has a protective effect against the development of atopic diseases in children. The current German guidelines recommend that fish consumption is encouraged in pregnancy.19
 
Maternal diet during lactation
Studies that examined the effect of food avoidance during lactation have been criticised for methodological shortcomings and small sample size, and more research is required in this area. Currently, there is no evidence to support maternal dietary avoidance of potent food allergens while breastfeeding as a means of preventing development of food allergy in their children.16
 
Breastfeeding
For all infants, breastfeeding is recommended for at least the first 4 to 6 months of life.19 20 21 Breastfeeding has many health benefits for both mothers and infants, and the World Health Organization recommends that infants should be exclusively breastfed for the first 6 months of life. Evidence suggests that exclusive breastfeeding for at least 3 months reduces the risk of atopic dermatitis in infancy although data are weaker for other allergic diseases.22 When compared with conventional cow’s milk formula, breast milk has a significant protective effect against atopic dermatitis and wheezing in the first 2 years of life and might play a role in the development of oral tolerance.23
 
Formula feeding
The GINI (German Infant Nutritional Intervention) study’s 15-year data show that in high-risk infants, compared with standard cow’s milk formula, the consumption of extensively hydrolysed casein formula is associated with a reduced cumulative incidence of eczema and allergic rhinitis, as well as a reduced prevalence of eczema and asthma in adolescence. The consumption of partially hydrolysed whey formula is associated with a reduced cumulative incidence of eczema and prevalence of allergic rhinitis in adolescence. On the contrary, there is no significant benefit for consumption of extensively hydrolysed whey formula, indicating the degree of hydrolysis alone does not fully explain the preventive power of a formula and further research will be needed in this area.24 There is no evidence for the use of soy formula or goat formula in the prevention of food allergies and amino acid formula has not been well studied.
 
Introduction of complementary foods
Introduction of complementary foods is recommended for infants aged over 4 months. There is no benefit in delaying introduction beyond 4 to 6 months in order to prevent allergic diseases.25 An infant diet consisting of high levels of fruits, vegetables, and home-prepared foods is associated with less food allergy by the age of 2 years.26 When introducing complementary foods, consideration of developmental readiness, parental needs, nutritional needs, and behavioural risks of the infant should be made.
 
Introduction of potential food allergens
There is emerging evidence that delaying solid food introduction beyond 6 months, especially those containing potent food allergens, may increase the risk of food allergy or eczema.23 Data from a Finnish cohort study indicate that late introduction of potatoes, oats, rye, wheat, meat, fish, and eggs was significantly and directly associated with sensitisation to food allergens,27 while late introduction of potatoes, rye, meat, and fish was associated with inhalant allergen sensitisation. Recently, the LEAP (Learning Early About Peanut allergy) study has demonstrated that consumption of peanuts within the first year of life in high-risk infants can lower the chance of peanut allergy compared with avoidance until the age of 5 years.28 Another randomised controlled trial found that infants exposed to whole egg powder daily starting at 4 to 8 months had higher egg-specific IgG4 levels compared with a control group.29 Furthermore, introduction of fish before 9 months of age is associated with a lower risk of eczema and is recommended by one of the national guidelines.19
 
At present, there is insufficient evidence to recommend early introduction of all potential food allergens. The current recommendation is neither to withhold nor encourage early introduction of any food allergens.19 20 21 Breastfeeding during the period of solid food introduction is likely to attenuate any allergic response.33
 
Environmental influence on allergy
Air pollution
It has long been recognised that atmospheric air pollution is associated with exacerbation of asthma and allergic rhinitis, and is blamed for surges in hospital admissions for asthma. In the past decade, much epidemiological evidence has linked exposure to air pollution from traffic, especially diesel exhaust particulates, oxides of nitrogen, and soot (carbon dust) to the development of asthma, allergic sensitisation, and compromised lung function.30 Another report investigated the relationship between traffic-associated pollution and eczema in children aged 6 years. Eczema prevalence was significantly higher in children who lived in traffic-related, highly polluted areas.31
 
Mechanisms implicated in the association between air pollution and paediatric asthma include the up-regulation of allergic immune responses, activation of oxidative stress pathways, and epigenetic regulation.
 
Tobacco smoke
The effect of both active smoking (AS) and passive smoking (PS) on the development of allergic diseases in adults and children has been recently reviewed.32 When all studies including cohort, case-control, and cross-sectional studies were included, allergic rhinitis was not associated with AS, but was associated with PS. Allergic dermatitis was associated with both AS and PS. In children and adolescents in particular, allergic rhinitis was associated with both AS and PS, as was allergic dermatitis. Among cohort studies, PS was significantly associated with an increased risk of food allergy in children and adolescents. From these studies, it can be seen that the effect of tobacco smoke is more severe in children and adolescents compared with adults. In countries with high smoking prevalence, the authors estimated that 14% of allergic rhinitis cases and 13% of allergic dermatitis are attributable to AS.33
 
The European Community Respiratory Health Survey has reported the effects of PS from fetus to adulthood.33 34 Maternal smoking during pregnancy, maternal smoking, or both parents smoking was more likely to be associated with asthma symptoms in offspring, even after accounting for smoking behaviour, exposure to PS, and occupational exposure.32 Total IgE levels were higher in smokers than non-smokers. The smokers were more likely to be sensitive to house dust mite (HDM) but not to cat dander or grass pollen. On the other hand, PS was significantly associated with bronchial responsiveness to methacholine and with current asthma.
 
Indoor environment
The meta-analysis from eight European birth cohorts showed that exposure to visible mold and/or dampness during the first 2 years of life was associated with an increased risk of developing asthma, including early asthma symptoms and asthma later in childhood.35 In another study, high visible mold in the home environment was also associated with recurrent wheeze at the age of 3 years and a positive Asthma Predictive Index.36 Other risk factors at home that have been reported to be associated with recurrent wheezing include use of foam pillow and exposure to gas cooking fuel.6
 
Another recent review and meta-analysis reported an overall 25% reduction in doctor-diagnosed asthma and recurrent wheeze in children exposed to a farming environment.37 The mechanism of effect of farm exposure on allergy development has been thought to be related to raw farm milk consumption and/or exposure to a wider range of micro-organisms in the farm, and its resultant gut microbiome.
 
Allergen exposure, especially to HDM allergen, has been implicated as a possible cause of allergic asthma. Many studies have attempted to prevent allergies and asthma by controlling HDM and other allergens in the home environment. A recent meta-analysis38 reported a significant reduction in physician-diagnosed asthma as a result of interventions to reduce exposure to HDM (relative risk [RR]=0.74; 95% confidence interval [CI], 0.58-0.95). There was, however, no significant effect on parent-reported wheeze (RR=0.95; 95% CI, 0.78-1.15). This may suggest that reduced exposure to HDM prevents the more severe form of asthma but not the more common and milder forms that may not be allergic in origin. A pooled analysis of over 22 000 children participating in 11 European birth cohorts concluded that there was neither an increase nor reduction in the risk of asthma or allergic rhinitis in children in relation to pet ownership in early life.39 The situation with other allergens is not clear.
 
In conclusion, dampness, visible mold, and HDM are important indoor factors in the development of allergic disease. The control of these factors is likely to lead to a lesser chance of development of allergic disease including asthma. Although a farming environment is known to be associated with a lower incidence of allergy, recommendation is still difficult and awaits further analysis of the mechanism of action.
 
Viral respiratory infections
Early viral respiratory infections have been implicated in the development of asthma and other respiratory allergies later in life. Human rhinovirus and respiratory syncytial virus have been found to be associated with a markedly higher risk of persistent wheezing at 6 years of age.40 Another study of over 2000 children confirmed an increased risk of new-onset wheeze at the age of 2 years in those suffering from childhood infections like common cold, fever, and diarrhoea during the first 3 months of life.41 Preventive strategies, apart from general infection control measures, consist of giving respiratory syncytial virus Ig to vulnerable infants.42
 
Lifestyle
Overweight and obesity
A healthy lifestyle with a balanced calorie intake and expenditure should be encouraged. A recent meta-analysis has revealed that being overweight poses an increased risk of asthma. This risk is further elevated in obese subjects with a clear dose-response relationship between body mass index and risk of asthma.43 European birth cohorts recruiting more than 12 000 subjects have demonstrated that a rapid rise of body mass index in the first 2 years of life increased the risk of asthma up to 6 years old (hazard ratio=1.3; 95% CI, 1.1-1.5).44 There is also a significant association between overweight/obesity and eczema.45 Excessive body weight should be avoided to help prevent the development of allergic diseases.
 
Psychosocial factors
A growing number of studies indicate that experiencing stressful life events (eg parental separation, death of a parent, parental unemployment), either during pregnancy or in early childhood, increases the risk of subsequent atopic diseases.46 Early therapeutic counselling may represent a preventive approach in these children.
 
Pharmaceuticals
A population-based study of over 16 000 Finnish patients revealed an increased risk of cow’s milk allergy associated with maternal/child use of antibiotics in a dose-related manner.47 Further studies are needed to confirm this observation in other populations. At present, no causal relationship has been established between the use of pharmaceuticals and the development of atopic disease.
 
Probiotics
Probiotics have been shown in some studies to prevent the development of eczema.48 Nonetheless, more studies are required to confirm their efficacy and most allergy guidelines do not make any recommendations about probiotics.
 
Vaccinations
There is no evidence to show that vaccination practices have any adverse effect on the incidence of allergic diseases in population-based cohort studies.49 It is advised that children are vaccinated according to the current recommended schedule, including high-risk children.
 
Vitamin D
Clinical studies have produced conflicting results with regard to the relevance of vitamin D in the development of allergic diseases. There are currently insufficient data to support any recommendation.
 
Immunotherapy
Immunotherapy, both subcutaneous and sublingual, is an important tool in the secondary prevention of allergic diseases. There is evidence that immunotherapy of allergic rhinitis can prevent the subsequent progression to asthma.50 It can also reduce new sensitisations in patients monosensitised to aeroallergens and has an impact on the natural history of respiratory allergies.51
 
Conclusions
The strengthening of immune tolerance is the current focus of allergy prevention. In addition to allergen avoidance, further studies are now underway to investigate how immune tolerance to different allergens can be boosted, while minimising sensitisation and further allergic responses. In general, the greater the exposure to environmental and commensal microbes in terms of diversity and quantity during infancy and early childhood, the greater the development of immune tolerance and less atopic tendency later on, even in those who are genetically susceptible.52 The allergy prevention measures we recommend are summarised in the Box. For those who are at higher risk of allergy development, that is those with a family history of allergy or the presence of several risk factors (eg breastfeeding for <6 months; maternal AS or PS during pregnancy; delivered by caesarean section), it is recommended that they observe the allergy prevention measures and consult a medical doctor early should they develop clinical features of allergic diseases. Besides recommendations on a personal level, the development of a community-based action plan would be beneficial and cost-effective. The implementation of National Allergy Programme, a new programme designed after the success of the previous Finnish Asthma Programme in 2000 to 2010, has already shown that the burden and cost of allergic diseases can be reduced by a pragmatic public health action plan.53 A successful community-based programme requires contributions from various stakeholders for effective implementation. Educational campaigns and networking between specialists and primary care doctors, pharmacists, nurses, teachers, parents, allergic patients, and the general public should be promoted. The treatment modalities for allergy are relatively limited at present, so prevention is the key to control this pandemic. Allergic diseases in Hong Kong and worldwide have increased dramatically in the past few decades. It is now pressing and timely to implement allergy prevention to promote a healthy lifestyle for the Hong Kong population and beyond.54
 

Box. Allergy prevention measures
 
Declaration
The authors have no conflicts of interest to declare.
 
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16. Kramer MS, Kakuma R. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Evid Based Child Health 2014;9:447-83. Crossref
17. Bunyavanich S, Rifas-Shiman SL, Platts-Mills TA, et al. Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children. J Allergy Clin Immunol 2014;133:1373-82. Crossref
18. Hörmannsperger G, Clavel T, Haller D. Gut matters: microbe-host interactions in allergic diseases. J Allergy Clin Immunol 2012;129:1452-9. Crossref
19. Schäfer T, Bauer CP, Beyer K, et al. S3-Guideline on allergy prevention: 2014 update: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Society for Pediatric and Adolescent Medicine (DGKJ). Allergo J Int 2014;23:186-99. Crossref
20. Muraro A, Halken S, Arshad SH, et al. EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy. Allergy 2014;69:590-601. Crossref
21. Greer FR, Sicherer SH, Burks AW; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008;121:183-91. Crossref
22. Kramer MS. Breastfeeding and allergy: the evidence. Ann Nutr Metab 2011;59 Suppl 1:20S-26S. Crossref
23. Lack G. Update on risk factors for food allergy. J Allergy Clin Immunol 2012;129:1187-97. Crossref
24. von Berg A, Filipiak-Pittroff B, Schulz H, et al. Allergic manifestation 15 years after early intervention with hydrolyzed formulas—the GINI Study. Allergy 2016;71:210-9. Crossref
25. de Silva D, Geromi M, Halken S, et al. Primary prevention of food allergy in children and adults: systematic review. Allergy 2014;69:581-9. Crossref
26. Grimshaw KE, Maskell J, Oliver EM, et al. Diet and food allergy development during infancy: birth cohort study findings using prospective food diary data. J Allergy Clin Immunol 2014;133:511-9. Crossref
27. Nwaru BI, Erkkola M, Ahonen S, et al. Age at the introduction of solid foods during the first year and allergic sensitization at age 5 years. Pediatrics 2010;125:50-9. Crossref
28. Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 2015;372:803-13. Crossref
29. Palmer DJ, Metcalfe J, Makrides M, et al. Early regular egg exposure in infants with eczema: A randomized controlled trial. J Allergy Clin Immunol 2013;132:387-92.e1. Crossref
30. Nordling E, Berglind N, Melén E, et al. Traffic-related air pollution and childhood respiratory symptoms, function and allergies. Epidemiology 2008;19:401-8. Crossref
31. Krämer U, Sugiri D, Ranft U, et al. Eczema, respiratory allergies, and traffic-related air pollution in birth cohorts from small-town areas. J Dermatol Sci 2009;56:99-105. Crossref
32. Accordini S, Janson C, Svanes C, Jarvis D. The role of smoking in allergy and asthma: lessons from the ECRHS. Curr Allergy Asthma Rep 2012;12:185-91. Crossref
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34. European Community Respiratory Health Survey II Steering Committee. The European Community Respiratory Health Survey II. Eur Respir J 2002;20:1071-9. Crossref
35. Tischer CG, Hohmann C, Thiering E, et al. Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative. Allergy 2011;66:1570-9. Crossref
36. Iossifova YY, Reponen T, Ryan PH, et al. Mold exposure during infancy as a predictor of potential asthma development. Ann Allergy Asthma Immunol 2009;102:131-7. Crossref
37. Genuneit J. Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis. Pediatr Allergy Immunol 2012;23:509-18. Crossref
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41. Mommers M, Thijs C, Stelma F, et al. Timing of infection and development of wheeze, eczema, and atopic sensitization during the first 2 yr of life: the KOALA Birth Cohort Study. Pediatr Allergy Immunol 2010;21:983-9. Crossref
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44. Rzehak P, Wijga AH, Keil T, et al. Body mass index trajectory classes and incident asthma in childhood: results from 8 European Birth Cohorts—a Global Allergy and Asthma European Network initiative. J Allergy Clin Immunol 2013;131:1528-36. Crossref
45. Mitchell EA, Beasley R, Björkstén B, Crane J, García-Marcos L, Keil U; ISAAC Phase Three Study Group. The association between BMI, vigorous physical activity and television viewing and the risk of symptoms of asthma, rhinoconjunctivitis and eczema in children and adolescents: ISAAC Phase Three. Clin Exp Allergy 2013;43:73-84. Crossref
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The practice of mediation to resolve clinical, bioethical, and medical malpractice disputes

Hong Kong Med J 2015 Dec;21(6):560–4
DOI: 10.12809/hkmj154615
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE
The practice of mediation to resolve clinical, bioethical, and medical malpractice disputes
Danny WH Lee, MD, JD1; Paul BS Lai, MD, FHKAM (Surgery)2
1 Private practice, Hong Kong
2 Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
 
Corresponding author: Dr Danny WH Lee (dannywhlee@gmail.com)
 
 Full paper in PDF
Abstract
Mediation is a voluntary process whereby a neutral and impartial third party—the mediator—is present to facilitate communication and negotiation between the disputing parties so that amicable settlements can be agreed. Being confidential and non-adversarial in nature, the mediation process and skills are particularly applicable in clinical practice to facilitate challenging communications following adverse events, to assist bioethical decision making and to resolve disputes. Mediation is also a more effective and efficient means of dispute resolution in medical malpractice claims when compared with civil litigation. Health care mediation teams should be set up at individual facilities to provide education and consultation services to frontline staff and patients. At a community level, the Government, the mediation community, and the health care professionals should join forces to promote mediation as a means to settle medical malpractice claims outside of the courtroom.
 
[Abstract in Chinese]
 
Introduction
With rapidly developing technology and ever-increasing patient expectations, frontline health-care professionals face immense challenges. Disputes and conflicts are common in clinical practice. Health care disputes are invariably related to patient dissatisfaction with a health care practitioner or the treatment outcome. Although most of these disputes may be able to be resolved adequately at an early phase, some may evolve into formal complaints or even litigation. In most common law jurisdictions including Hong Kong, victims of medical malpractice (claimants) can seek redress through the formal legal system under the tort of negligence. The journey to a successful negligence claim, however, is usually long and arduous. Claimants do not usually get what they want and deserve as the process is expensive and inefficient.
 
Mediation is an alternative means of dispute resolution where a neutral and impartial third party (the mediator) is present to facilitate communication and negotiation between the disputing parties so that an amicable settlement can be agreed. Mediation has been widely used worldwide to resolve commercial and family disputes outside the courtroom. The use of mediation to settle medical malpractice disputes was pioneered in the US in the mid-1980s after a crisis in malpractice claims.1 Aside from preventing lawsuits, bioethics mediation has also been practised in some states to help patients and their families make difficult clinical decisions, for example, with regard to end-of-life treatment.2 This article aimed first to give an overview of the practice of mediation, and describe the relevance of mediation to our clinical practice. Second, a critical appraisal of the current medical malpractice litigation is submitted with a view to explain why mediation is a better alternative means to settle malpractice claims. Finally, this article offers some suggestions for the provision of mediation services at a facility level and at the wider community level.
 
What is mediation?
Mediation means different things to different stakeholders. In a nutshell, mediation is a voluntary process whereby the disputing parties come together, with the assistance of a neutral third party—the mediator, systematically isolate disputed issues in order to develop options and alternatives, and reach a consensual settlement that both parties can abide by.3 It may take place in different forms or on different scales, ranging from informal community or domestic mediations to large-scale multi-party international mediations. Apart from its obvious application in disputes or conflict resolution, transactional mediation is also commonly used to facilitate commercial negotiations when making business deals. In a medico-legal context, mediation may be used to resolve disputes and difficult communications that arise in clinical practice, to prevent and settle malpractice lawsuits outside the courtroom, and to enable patients and their families to make difficult bioethical decisions.
 
Alexander4 introduced a ‘meta-model’ to describe different mediation practices: settlement mediation, facilitative mediation, transformative mediation, expert advisory mediation, wise counsel mediation, and tradition-based mediation. Depending on which model is adopted by parties and the mediator, mediation may be interactional (eg traditional mediation) or interventional (eg expert advisory mediation) in nature. In Hong Kong, the facilitative (interest-based) mediation model is commonly employed. In this mode of mediation, the mediator will assist and coach the disputing parties to adopt an interest-based negotiation rather than positional-based bargaining. Of note, the mediator will not advise or adjudicate on any matters related to the dispute. In this sense, parties will be more likely to accept and honour their own settlements. In Hong Kong, potential mediators are assessed and accredited based on the facilitative mediation model by the Hong Kong Mediation Accreditation Association Limited.5
 
Why mediation for health care disputes?
Maintaining confidentiality and a collaborative attitude between parties are important values that underlie facilitative mediation and render this mode of mediation particularly suitable for resolving health care–related disputes.4 For obvious reasons, health care professionals and their institutions care about professional image and reputations. Likewise, patients do not usually want social stigma attached to their disease or suffering. Notably, there are express provisions in the new Mediation Ordinance (Cap 620, Laws of Hong Kong) to protect the confidentiality of mediation communications. Even in the worst case scenario where parties fail to reach a settlement, neither party can use any information obtained during the mediation for litigation purposes, except in a few circumstances. Also, in the facilitative mode of mediation, opposing parties can communicate, negotiate, and decide a settlement among themselves with the assistance of the mediator. Conceivably, the doctor-patient relationship will largely be preserved after health care mediations.
 
Apart from mediation process training, almost all accredited mediation training courses provide some training in communication and negotiation skills. Most of these skills—for example, active listening, reframing, acknowledgement of feelings, etc—are relevant to our daily clinical practice where different (or difficult) human interaction is inevitable. Health care professionals who have attended communication training courses find the learning experience fruitful, regardless of whether they complete the accreditation examination.6 Most also enjoy improved communication and a better relationship with their patients, even in the absence of a dispute.7 In 2013/14, the Hospital Authority took the initiative to sponsor 120 and 600 health care staff to participate in accredited mediation courses and applied mediation skills training, respectively.8
 
A number of landmark studies have confirmed that when patients complain or resort to litigation, it is most likely related to miscommunication between themselves and health care professionals.9 10 Frequently, the perception of lack of care offered by health care professionals is the trigger for complaints or litigation, rather than genuine professional negligence in the delivery of care.10 Communication between the patient and the health care professional becomes even more challenging when there are adverse or unanticipated outcomes. Whilst patients and their relatives legitimately expect truthful explanations and honest apologies where appropriate following adverse events, health care professionals are, more often than not, either not ready or comfortable to communicate with them in the aftermath.11 In addition, in Hong Kong it is common practice for legal advisors to advise frontline clinical staff to avoid direct communication with patients or relatives following an adverse medical event in case they inadvertently admit liability. Thus patients or relatives become suspicious when no one responds to their enquiries and an initial wall of silence becomes the prologue to a formal complaint or even a lengthy legal battle.12
 
In a broad sense, the mediation process and skills can play a vital role in difficult communications following a medical adverse event. First, mediation (communication) skills can be employed by frontline staff to calm the emotions of patients and their relatives. Acknowledgement of feelings, active listening, and expression of empathy are important and useful skills for frontline staff to handle emotionally charged patients and their relatives. It has been proven that effective communication following adverse events can reduce the number of patients who initiate legal proceedings against their doctor.13 At the very least, an open and direct dialogue prevents escalation of parties’ emotion and allows healing of a broken relationship at a much earlier phase.14 Second, with the assistance of a mediator, the mediation process can provide a safe and protected environment for patients and health care professionals to communicate directly and frankly without the fear of being prejudiced. Early and honest disclosure of medical events or errors (if any) has been regarded as an important risk management strategy worldwide to prevent escalation of tensions between parties.13 As aforementioned, the Mediation Ordinance stipulates that ‘things that were said or done’ during mediation must remain confidential, and in general, mediation communications will not be admissible as evidence in any subsequent court proceedings. Thus, it is envisaged that mediation can provide an appropriate avenue for health care professionals to offer truthful explanations and apologies without the fear of admitting liability. Hitherto, there is no Apology Legislation in Hong Kong although a public consultation is underway.15 Unless and until such legislation is enacted in Hong Kong, mediation represents an effective mechanism to bridge the legal gap in the context of medico-legal dispute resolution.
 
Apart from claims and complaints management, there is growing interest in the use of health care mediation to assist patients or their relatives to make bioethical decisions such as those that concern end-of-life treatment. Health care professionals and patients often hold conflicting views on sensitive issues such as withholding or withdrawing treatment, Do-Not-Resuscitate orders, and medical futility.16 Although doctors believe their decisions are based on what is in the best interests of the patient, the relatives may not agree. During mediation, a neutral mediator (someone who is not a member of the management team) can help explore the interests and goals of both parties and address them in a collaborative manner. Patients feel respected if they are given the opportunity to express their views and opinions freely. They will also hear first-hand the difficulties or dilemmas faced by health care professionals during the two-way dialogue. Any treatment plans formulated in such a cooperative atmosphere and on a level playing field will be more likely to be accepted by both the patients and their families.
 
Why mediation is preferred to litigation?
English common law provides a robust system—the tort of negligence—that enables aggrieved patients to assert their legal rights in malpractice claims. Nonetheless it is extremely difficult to win such cases. In order to be successful in a claim of negligence against a doctor, the patient (claimant) must prove, on a balance of probability, that the doctor breached his or her duty of care to the patient, and that the doctor’s act or omission materially caused physical and/or psychological damage to the patient.17 It is well known that civil litigation involves complicated and lengthy procedures such as ‘discovery of evidence’ and ‘exchange expert reports’. Any uncooperative party can introduce delaying tactics to increase both the financial and psychological burden on the opposing party. It is not uncommon to see cases dragging on for years before they reach court and the trial stage.18
 
In addition, patients may not find what they want or deserve in a court of law. Beckman et al10 identified the following reasons that explain why patients took legal action against their doctor(s): doctors’ unavailability, discounting patient or family concerns, poor delivery of information, lack of understanding, and perceived lack of caring and/or collaboration in the delivery of health care. Most patients initiated legal proceedings following an adverse medical event because they wanted an honest explanation, and individual and organisational accountability; they also looked for strategies to prevent recurrence of mishaps.19 Regrettably these non-monetary remedies are not available under the current litigation system. Similarly, respondent doctors always suffer from different degrees of emotional disturbance—shame, fear, self-doubt, isolation, difficulty concentrating, etc—regardless of whether or not they believe an adverse medical event is due to their error.20 They also demand quick resolution of any potential claims associated with the events. Unfortunately, litigation will not give doctors any quick relief or reassurance. Even assuming the respondent doctor is exonerated, the psychological stress associated with litigation may irreversibly damage the doctor’s professional life.
 
On the other hand, mediation is usually flexible and less formal in procedural matters, and hence time and cost-saving.18 Unlike litigation, nonmonetary issues such as explanations, apologies, or even future strategies to enhance patient safety can be discussed during mediation.21 Apart from monetary compensation, early resolution also relieves parties’ psychological stress, especially that of doctors. Doctors can resume their normal clinical work without any fear or pressure arising from the claims or, sometimes, the media. In the UK, the National Health Service Litigation Authority (NHSLA) has been asking their representative lawyers to consider and offer mediation in appropriate cases since 2000.21 The NHSLA’s findings suggest that claims may be settled by mediation directly although settlement may not be achieved on the same day of mediation. In a recent survey conducted by the European Hospital and Healthcare Federation, mediation was also widely used in health care disputes in 10 European member states.22 In Hong Kong, with the joint effort of the Hong Kong Medical Association and the Hong Kong Mediation Council, the first successful malpractice mediation was reported in 2006.23 In 2009, the Hong Kong Judiciary introduced Civil Justice Reform with a clear objective to facilitate settlement of civil disputes fairly, effectively, and efficiently.24 Under the new Practice Directions, legal practitioners need to inform their clients of the availability of mediation, and to sign a ‘mediation certificate’ before they can file a claim in court. In addition, the courts may now impose an adverse costs order on any party who unreasonably fails to engage in mediation even if that party subsequently wins the case.25 It is envisaged that all these judiciary measures will further enhance the use of mediation to settle medical malpractice claims.
 
The way forward
At a facility level, a health care mediation team comprising different mediation-trained staff members such as nurses, doctors, allied health professionals, administrators, psychologists, and social workers, could be established to provide education and consultation services to frontline staff, and to assist them in handling difficult communications.26 At times, a formal mediation process can be conducted at the facility when the disputing parties volunteer and agree to do so. The facility should provide a list of in-house accredited mediators for the process from which parties can select. Equally, if parties wish, they can use external accredited mediators.16 At the moment, there is no additional requirement for general mediators to mediate health care–related disputes. It is well known that health care disputes usually involve complex professional issues. It would thus be easier and desirable for mediators to have a medical knowledge base when dealing with health care disputes.23 In any event, early access to mediation may save transaction costs (eg time, money, emotional energy, opportunities lost) in relation to the dispute resolution.1 27
 
Health care professionals should be more receptive to malpractice pre-trial mediation. Mediation aims to help opposing parties to understand their respective interests and goals, to restore a broken relationship, and most importantly to work out a consensual settlement without taking the dispute to the courtroom. Peeples et al28 observed that the term ‘settlement’ might be viewed negatively as ‘admitting fault’ in the eyes of the medical profession during mediation. Nonetheless, the same term is commonly used among the legal profession in dispute resolution processes, and does not have negative connotations. Thus, it is important to rectify this conceptual misunderstanding before health care professionals come to the mediation table. Equally, legal practitioners need to transform their practice during mediations. Traditionally, lawyers are trained to take an adversarial approach to fight for their clients in court. Mediation requires a different mindset and negotiation skills. Lawyers who take part in mediations should assist their clients on legal matters and be responsive to clients’ interests and goals during the negotiations rather than being focused on purely winning the case.29 It is thus vital that all parties who participate in the process understand the underlying fundamentals and values of mediation in order to achieve the maximum benefit.
 
Despite various judiciary measures, the use of mediation to resolve medical malpractice disputes has received much less attention compared with commercial disputes. The Hong Kong SAR Government has supported the setting up of the Financial Dispute Resolution Centre to assist appropriate clients in financial disputes. Hitherto, there is no similar medical dispute resolution centre to coordinate such services although the Steering Committee on Mediation has reported its initiative to devise a medical mediation scheme to support the use of mediation in medical disputes.15 It remains to be seen how much resources the Government is willing to allocate to this ‘new’ means of medical dispute resolution. On the other hand, mediation stakeholders should be mindful of the current situation: while there are alleged advantages to the use of mediation to settle medical malpractice disputes, more empirical research data are needed to support its real effectiveness and efficiency.
 
Conclusion
The mediation process and associated skills may be applied in our daily clinical practice to facilitate challenging communications, to assist bioethical clinical decision making, and to resolve disputes. Individual health care facilities should set up their own mediation teams to coordinate the service to patients and frontline staff. Whilst victims of medical mishaps might assert their legal rights through litigation, it is an ineffective and inefficient way to get what they want and deserve. Nowadays, the Judiciary’s Practice Direction requires parties to participate in meaningful pre-trial mediations in order to settle disputes outside the courtroom. Apart from judiciary measures, the Government and the mediation community should put more effort into promoting the use of mediation to settle medical malpractice claims in the community in order to save time and public resources.
 
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First-trimester medical abortion service in Hong Kong

Hong Kong Med J 2015 Oct;21(5):462–7
DOI: 10.12809/hkmj154525
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE
First-trimester medical abortion service in Hong Kong
Sue ST Lo, MD, FRCOG1; PC Ho, FRCOG, FHKAM (Obstetrics and Gynaecology)2
1 The Family Planning Association of Hong Kong, 10/F, Southorn Centre, 130 Hennessy Road, Wanchai, Hong Kong
2 Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong
Corresponding author: Dr Sue ST Lo (stlo@famplan.org.hk)
 
 Full paper in PDF
 
Abstract
Research on medical abortion has been conducted in Hong Kong since the 1990s. It was not until 2011 that the first-trimester medical abortion service was launched. Mifepristone was registered in Hong Kong in April 2014 and all institutions that are listed in the Gazette as a provider for legal abortion can purchase mifepristone from the local provider. This article aimed to share our 3-year experience of this service with the local medical community. Our current protocol is safe and effective, and advocates 200-mg mifepristone and 400-µg sublingual misoprostol 24 to 48 hours later, followed by a second dose of 400-µg sublingual misoprostol 4 hours later if the patient does not respond. The complete abortion rate is 97.0% and ongoing pregnancy rate is 0.4%. Some minor side-effects have been reported and include diarrhoea, fever, abdominal pain, and allergy. There have been no serious adverse events such as heavy bleeding requiring transfusion, anaphylactic reaction, septicaemia, or death.
 
 
[Abstract in Chinese]
 
Introduction
In Hong Kong, legal abortion can be performed in registered institutions in accordance with the legal requirements stipulated in the Offences against the Person Ordinance Cap 212. In the past, first-trimester pregnancies up to 12 weeks of gestation were terminated by suction evacuation and achieved a complete abortion rate of 99%.1 Possible risks and complications, which could affect future fertility, include heavy bleeding, infection, uterine perforation with or without bowel injury, and cervical trauma.
 
With the introduction of mifepristone, a progesterone antagonist, effective and safe medical abortion became possible. Over the past three decades, various medical abortion protocols have been tested in different countries and Hong Kong has participated in such research since the 1990s. Most institutions recommended the use of mifepristone followed by prostaglandin 24 to 48 hours later to stimulate uterine contraction and expulsion of the conceptus. Mifepristone was first registered for medical abortion in France and China in 1988. By 2013, mifepristone was registered in 60 countries2 and was eventually registered in Hong Kong on 8 April 2014 for medical abortion and cervical priming before first-trimester surgical abortion (Mifegyne; Exelgyn, Paris, France). All institutions listed in the Gazette as a legal abortion provider can purchase mifepristone from a local provider. The provider cannot sell mifepristone to an individual doctor or pharmacy store. Although the posology of Mifegyne indicates its use for first-trimester medical abortion up to 63 days of gestation, the treatment is also effective after 63 days of gestation.3
 
Most regulatory bodies, including Hong Kong, approved the use of 600-mg mifepristone for medical abortion but the International Planned Parenthood Federation (IPPF),4 World Health Organization (WHO),5 and Royal College of Obstetricians and Gynaecologists (RCOG)6 recommended the use of 200 mg as it has similar efficacy and lower cost.7
 
A prostaglandin has to be given after mifepristone to stimulate uterine contractions. Misoprostol is the prostaglandin of choice because it is cheap, effective, and stable at room temperature but the dose, route, and timing of administration is not standardised. The WHO and RCOG recommend 800-µg misoprostol (vaginal, buccal, or sublingual) 24 to 48 hours later.5 6 For women at 50 to 63 days of gestation, the RCOG recommends an additional 400-µg misoprostol (vaginal or oral) 4 hours later if abortion has not occurred.6 The IPPF recommends 800-µg misoprostol (oral, vaginal, buccal, or sublingual) at once or in two doses 2 hours apart, 36 to 48 hours later.4 When compared with vaginal misoprostol, sublingual misoprostol appears to be associated with a higher rate of gastro-intestinal side-effects, and buccal misoprostol appears to be associated with a higher rate of diarrhoea.7
 
The complete abortion rate for medical abortion is approximately 95%,1 which is slightly lower than that for surgical abortion. The chance of ongoing pregnancy is 1% to 2% and the baby may suffer from congenital abnormalities due to prostaglandin. Hence it is recommended that suction evacuation be performed if medical abortion fails. Bleeding and abdominal cramps are inevitable side-effects of medical abortion although <1% of women need emergency curettage because of excessive bleeding1 and 0.1% require blood transfusion.8 In a systematic review of 65 studies with heterogeneous designs, the overall frequency of diagnosed or treated pelvic infection after medical abortion was 0.9%.9 The incidence of suspected or confirmed post-abortion infection (endometritis, pelvic inflammatory disease) quoted in the posology of mifepristone is <5%.10 Very common and common side-effects of mifepristone include nausea, vomiting, diarrhoea, light or moderate abdominal cramps, post-abortion infection, uterine cramps, and heavy bleeding.10 The side-effects of prostaglandin observed during medical abortion include transient fever, chills, nausea, vomiting, diarrhoea, headache, dizziness, and rash.4 The incidence and intensity of prostaglandin side-effects are determined by the dose and route of administration.
 
Our protocols
The Family Planning Association of Hong Kong (FPAHK) piloted a medical abortion service for gestation up to 63 days in November 2011. Routine ultrasound examination was performed to ascertain the gestation and to exclude multiple pregnancies and ectopic pregnancy. Exclusion criteria included hypersensitivity to mifepristone or misoprostol, multiple pregnancies, haemoglobin level of <100 g/L, bleeding tendency, known coagulopathy, use of anticoagulant, current long-term systemic corticosteroid therapy, history of adrenal tumour/steroid-dependent tumour, chronic adrenal failure, porphyria, renal/liver impairment, cardiovascular disease (including arrhythmia, angina, heart failure, Raynaud’s disease, diastolic hypertension of >95 mm Hg, arterial hypotension, history of evidence of thromboembolism), epilepsy, on multiple medications, inherited porphyria, severe asthma uncontrolled by therapy, and breastfeeding.
 
The initial protocol was 200-mg oral mifepristone followed by 800-µg vaginal misoprostol 48 hours later (protocol 1, n=603). Both doses were administered in the FPAHK. The woman was permitted to leave after mifepristone administration provided she did not feel unwell but was required to remain for observation on the day of misoprostol administration. Oral paracetamol, oral mefenamic acid, and intramuscular pethidine were offered for pain relief. Vital signs, hydration status, and blood loss were monitored. Most women passed tissue mass within 4 hours of misoprostol administration. The doctor routinely performed a pelvic examination after 4 hours to remove any tissue mass remaining in the vagina, and to assess blood loss and vital signs. Any tissue mass collected was sent for pathological examination to exclude partial mole. The patient was discharged provided bleeding was not excessive.
 
In January 2013, this protocol was changed to 200-mg oral mifepristone followed by 400-µg sublingual misoprostol 48 hours later (protocol 2, n=890). We changed from vaginal to sublingual administration because vaginal administration is intrusive, and requires more consultation time and more medical consumables. Sublingual administration requires the woman to place two tablets of misoprostol under her tongue and then swallow after 30 minutes. We used a half dose (400 µg) to minimise the severity of gastro-intestinal reactions that might make patients uncomfortable and increase the workload of nursing and auxiliary staff. Since November 2013, women have been given a second dose of 400-µg sublingual misoprostol if abortion has not occurred within 4 hours of misoprostol administration (protocol 3, n=1042). We hope this regimen will reduce the ongoing pregnancy rate by administration of the full dose to selected patients.
 
Surgical evacuation is performed if there is heavy bleeding after misoprostol. Manual vacuum aspiration was introduced as an alternative to electric vacuum aspiration in January 2014.
 
Women return for follow-up after 1 week if abortion has not started on discharge. Other women are followed up 2 to 3 weeks after the abortion. Ultrasound examination is performed in the presence of any abnormal symptoms or signs. Suction evacuation is arranged for ongoing pregnancy. Prior to the introduction of 400-µg sublingual misoprostol after November 2013 (protocol 3), those with persistent bleeding/spotting and/or retained products of gestation were managed expectantly or by curettage. An additional dose of misoprostol is not offered to women with a history of caesarean section. Further follow-up is arranged as required, with final follow-up 6 to 8 weeks after abortion to confirm return of menstruation and assess their compliance with contraception.
 
Women are encouraged to start birth control immediately after misoprostol administration. Hormonal injectables are given on discharge. Women are asked to start oral pills on the evening after misoprostol. A condom should be used consistently and correctly thereafter. Insertion of an intrauterine contraceptive device cannot be performed until abortion has completed and is usually done at the 6-week follow-up.
 
Outcome
Overall, 2535 medical abortions in 2499 women were performed in the 3 years from 2011 to 2014. The median age was 27 years (interquartile range, 11 years). Most women were nulliparous (63.8%), and mean parity was 0.61 (standard deviation, 0.9). Most women had no history of surgical (73.1%) or medical (95.1%) abortion. The demographics are detailed in Table 1.
 

Table 1. Demographic characteristics of women undergoing medical abortion (n=2535)
 
Five women took mifepristone only, without misoprostol. One woman developed palmar erythema and intense itching 30 minutes after vaginal misoprostol administration: misoprostol tablets were removed and douching performed. Allergic signs and symptoms resolved 15 minutes later. Suction evacuation was subsequently performed on that day. This was the 84th case when doctors were still relatively inexperienced and might have overreacted to her symptoms. One woman was admitted to hospital for abdominal pain after mifepristone: ultrasound examination revealed complete abortion and she was not given misoprostol during admission. Another woman was admitted to hospital because of vaginal bleeding: emergency curettage was performed. Two women were admitted to hospital because of persistent vomiting with dehydration. They did not attend the appointment for misoprostol and suction evacuation was arranged.
 
Among 2530 cases admitted for misoprostol, 17 (0.7%) underwent emergency suction evacuation because of heavy bleeding after misoprostol administration with 11 having gestation of 56 days and above. Bleeding stopped after curettage in all women. The outcomes of medical abortion are listed in Table 2. After excluding 159 women who did not return for follow-up, the overall complete abortion rate was 97.0%. The complete abortion rate in those with gestation of ≥56 days was significantly lower than in those with <56 days of gestation (95.7% vs 97.7%; Fisher’s exact test, P=0.007). The complete abortion rate for protocols 1, 2, and 3 was 96.3%, 97.5%, and 97.1% respectively, and the respective mean gestation was 51.3 days, 51.7 days, and 51.3 days (P=0.362). The complete abortion rate did not differ by protocol (P=0.440), parity (P=0.527), or history of miscarriage and termination of pregnancy (P=0.246). Among those who had curettage after medical abortion, 64% were performed within the first 2 weeks, 14% were between third and fourth week, and the remaining 22% were between fifth and 12th week. Curettage within the first 4 weeks was performed for excessive bleeding: those performed later were for retained products of gestation and persistent spotting.
 

Table 2. Outcomes of women who had completed the course of medical abortion using mifepristone and misoprostol
 
The overall ongoing pregnancy rate was 0.4% and gestation was between 52 and 60 days. The ongoing pregnancy rate for protocols 1, 2, and 3 was 0.9%, 0.4%, and 0.2%, respectively (P=0.138). After changing to protocol 3, 97 (9.3%) women received a second dose of misoprostol. During follow-up, 49 women received additional misoprostol—seven during first follow-up for dead fetus in situ, 37 during first 2 weeks for moderate bleeding, one during the fourth week for persistent bleeding, and four for retained products between fourth and eighth week. One required manual vacuum aspiration in the 12th week because of persistent tissue mass despite misoprostol.
 
Minor side-effects that required treatment are listed in Table 3. Treatment for allergic symptoms of varying severity was required in 50 (2.0%) cases. One woman developed back and neck rash after mifepristone and was given oral chlorpheniramine maleate 4 mg when she was admitted for misoprostol. Another woman also reported skin rash after mifepristone that resolved spontaneously and no treatment was required. One or more of the following minor allergic symptoms developed in 94 women after misoprostol: palmar erythema, palmar itchiness, perioral rash, and peri-orbital rash. Symptoms resolved spontaneously in 51 women and 43 required oral chlorpheniramine maleate. Two women received oral chlorpheniramine maleate followed by intramuscular chlorpheniramine maleate 10 mg because symptoms progressed: in both cases a localised body rash progressed and one woman became breathless. Three women received intramuscular chlorpheniramine maleate: one had generalised body rash with shortness of breath, another had generalised facial rash, and the third developed swollen lips and tongue and palmar erythema with itchiness. One woman developed peri-orbital rash with swelling and blurred vision: intramuscular chlorpheniramine maleate was administered. One hour later, her vision normalised but peri-orbital rash with swelling persisted. Symptoms gradually resolved following intramuscular injection of hydrocortisone 100 mg.
 

Table 3. Minor side-effects requiring treatment
 
During follow-up, 53 (2.1%) women were treated with oral antibiotics for clinically suspected pelvic infection—11 (1.8%) had received vaginal misoprostol and 42 (2.2%) had sublingual misoprostol (Table 3). Some were treated by their private gynaecologists and others by doctors in the Hospital Authority when they were admitted for bleeding or abdominal pain. Those who were treated by us during follow-up presented with pelvic excitation tenderness with or without prolonged spotting or bleeding. None of them had fever. Empirical antibiotics were prescribed but no swabs were taken for culture. Four (0.2%) cases of partial mole were reported by the pathologist and these women were referred to a specialist gynaecology clinic of the Hospital Authority. Two women had post-abortion anaemia due to prolonged bleeding for over 4 weeks, with haemoglobin levels of 80 g/L and 86 g/L. In no case was bleeding sufficiently severe to warrant transfusion, and there were no instances of anaphylactic reaction, septicaemia, or death.
 
Following abortion, the three main contraceptives of choice were male condom (38.1%), combined oral contraceptive pill (36.2%), and combined hormone injection (12.3%).
 
Discussion
When we first piloted the service, we adopted the standard protocol of 200-mg oral mifepristone plus 800-µg vaginal misoprostol. The side-effects, complete abortion rate, and ongoing pregnancy rate were as expected. After changing to sublingual administration, the complete abortion rate was similar and the ongoing pregnancy rate was halved that of vaginal misoprostol. This was not a formal study, hence women were not asked to record the intensity of pain, diarrhoea, or discomfort. Nonetheless, the incidence of side-effects for each of the three protocols appears to be similar. Fewer women treated according to protocol 3 required pain relief but the underlying reasons are unclear. The change from protocol 1 to 2 to 3 reduced the ongoing pregnancy rate but the difference was not statistically significant, probably because of the low incidence of ongoing pregnancy. We are continuing to use protocol 3 because it may achieve the best clinical result without increasing patient discomfort. Our nursing staff did not perceive any requirement for increased patient care after changing to sublingual misoprostol. Although one more dose of misoprostol was given in protocol 3, this applied to <10% of patients and did not adversely affect nursing workload. In addition, auxiliary staff did not report any increased need for cleaning after changing to sublingual misoprostol. All patients, including those treated with protocol 3, can be discharged before the ward closes at 5 pm.
 
Unlike a research protocol, there is no time limit for performing surgical curettage during follow-up for incomplete medical abortion. Curettage is recommended if a moderate amount of blood is found in the vagina during speculum examination at follow-up, when prolonged bleeding causes anaemia or if tissue mass is present after 6 weeks. Patients can also request curettage if persistent bleeding is inconvenient.
 
Those who do not pass tissue mass after misoprostol are followed up after 1 week with routine pelvic ultrasound. Those with a live fetus, ie ongoing pregnancy, will undergo suction evacuation. Occasionally, a dead fetus is detected. During the initial phase of service delivery, doctors arranged curettage to remove the dead fetus. Our doctors are accustomed to surgical abortion and hence are anxious to clear any retained products. At our case discussions, they are reassured that retained products of gestation, even a dead fetus, is part of the natural process of medical abortion and they can try expectant management first. In most cases, watchful waiting and subsequent follow-up 2 weeks later will reveal that the fetus has gone. With the adoption of protocol 3, the option of an additional dose of misoprostol can be offered alongside expectant management.
 
Collecting tissue mass passed and sending it for pathological examination is important as a partial mole cannot be diagnosed by ultrasound. The incidence of partial mole is similar to that reported in women undergoing surgical abortion in the FPAHK. Follow-up is important because the failure rate for medical abortion is higher than that for surgical abortion, and misoprostol is potentially teratogenic. The follow-up visits also provide an opportunity to evaluate contraceptive use. To prevent further unplanned pregnancies, contraceptive counselling is provided at each visit. The consistent use of contraceptive is emphasised and women are encouraged to discuss any problems they experience with contraception to maximise compliance.
 
Conclusion
A medical abortion service can be safely provided in a non-hospital setting that also provides emergency suction evacuation.
 
References
1. Medical management of first-trimester abortion. Contraception 2014;89:148-61. Crossref
2. Medical abortion overview. Available from: http://gynuity.org/programs/more/overview/. Accessed 10 Dec 2014.
3. Pazol K, Creanga AA, Zane SB, Burley KD, Jamieson DJ; Centers for Disease Control and Prevention (CDC). Abortion surveillance—United States, 2009. MMWR Surveill Summ 2012;61:1-44.
4. First trimester abortion guidelines and protocols. International Planned Parenthood Federation; 2008.
5. Safe abortion: technical and policy guidance for health systems. 2nd ed. Geneva: World Health Organization; 2012.
6. The care of women requesting induced abortion: evidence-based clinical guideline No. 7. London: Royal College of Obstetricians and Gynaecologists Press; 2011.
7. Kulier R, Kapp N, Gülmezoglu AM, Hofmeyr GJ, Cheng L, Campana A. Medical methods for first trimester abortion. Cochrane Database Syst Rev 2011;(11):CD002855. Crossref
8. Raymond EG, Shannon C, Weaver MA, Winikoff B. First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review. Contraception 2013;87:26-37. Crossref
9. Shannon C, Brothers LP, Philip NM, Winikoff B. Infection after medical abortion: a review of the literature. Contraception 2004;70:183-90. Crossref
10. Mifegyne. Physician leaflet. Exelgyn, France. HK-62757. 8 Apr 2014.

Prevention in primary care is better than cure: The Hong Kong Reference Framework for Preventive Care for Older Adults—translating evidence into practice

Hong Kong Med J 2015 Aug;21(4):353–9
DOI: 10.12809/hkmj144326
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE
Prevention in primary care is better than cure: The Hong Kong Reference Framework for Preventive Care for Older Adults—translating evidence into practice
Cecilia KL Sin, MB, BS, FHKAM (Family Medicine)1; SN Fu, MB, BS, FHKAM (Family Medicine)1; Caroline SH Tsang, MB, ChB, FHKAM (Community Medicine)1; Wendy WS Tsui, MB, ChB, FHKAM (Family Medicine)1; Felix HW Chan, MBBCh, FHKAM (Medicine)2
1 Primary Care Office, Department of Health, Hong Kong
2 Clinical Advisory Group on Reference Framework for Preventive Care for Older Adults in Primary Care Settings, Hong Kong
Corresponding author: Dr Caroline SH Tsang (caroline_tsang@dh.gov.hk)
 
 Full paper in PDF
 
Abstract
An ageing population is posing a great challenge to Hong Kong. Maintaining health and functional independence among older adults is of utmost importance, and requires the collaborative efforts of multiple health care disciplines from both the private and public sectors. The Reference Framework for Preventive Care for Older Adults, developed by the Task Force on Conceptual Model and Preventive Protocols under the auspices of the Working Group on Primary Care, aims to enhance primary care for this population group. The reference framework emphasises a comprehensive, integrated, and collaborative approach that involves providers of primary care from multiple disciplines. In addition to internet-based information, helpful tools in the form of summary charts and Cue Cards are also produced to facilitate incorporation of recommendations by primary care providers into their daily practice. It is anticipated that wide adoption of the reference framework will contribute to improving older adults’ health in our community.
 
 
[Abstract in Chinese]
 
Introduction
Advances in medicine and increased life expectancy mean that Hong Kong is expecting an ageing population, and a significant increase in the number and proportion of older adults. According to the Census and Statistics Department of Hong Kong SAR, it is estimated that by 2041, the number of Hong Kong residents aged 65 years and above will increase from 0.9 million in 2011 (13% of the population) to around 2.6 million (30% of the projected population).1
 
This ageing population poses not only a threat but also a challenge to the current health care system. It is anticipated that the prevalence of common chronic diseases will be further increased with a consequent escalating demand on various health services for older adults. Strategies to promote health, prevent chronic diseases, and preserve functional ability of older adults are therefore vital.
 
In order to provide a general reference for provision of continuous, comprehensive, and evidence-based care for older adults in the primary care setting, the Reference Framework for Preventive Care for Older Adults in Primary Care Settings2 was developed by the Task Force on Conceptual Model and Preventive Protocols under the auspices of the Working Group on Primary Care. It was developed according to the latest research evidence, with contributions from the Clinical Advisory Group that comprises experts from academia, professional organisations, private and public primary care sectors, and patient groups.
 
The reference framework consists of a core document supplemented by a series of modules that address various aspects of disease management and preventive care for older adults.2 To date, the core document, and the modules on health assessment and falls have been developed.
 
This article summarises the main contents and highlights a practical use of this reference framework to enhance the delivery of preventive care for older adults in primary care setting in Hong Kong. Details of the evidence that supports the recommendations are available in the core document of the reference framework.2
 
Role of primary care in the preventive care of older adults
As the first point of contact, primary care providers are in a prime position to promote health, prevent and monitor disease, and reduce functional disabilities.3 Primary care physicians provide health education, risk assessment, and follow-up care for medical conditions. They also advise and refer patients for appropriate health care services as necessary, and provide support and advice to family members and carers. It is firmly established that patient education and counselling in the primary care setting contributes to a better understanding of health and can thus influence an individual to adopt health protective behaviour.4
 
Only 0.5% of clinical encounters among older people at a local primary care level are initiated for a physical checkup.5 It has been suggested that apart from designated appointments in primary care settings, health assessment can be performed opportunistically over time and during multiple visits. Indeed, every clinic visit to a primary care provider should be seen as an opportunity to screen for any physical, psychological, or social problems.6 7 When one considers that 80% of the Hong Kong population have consulted a primary care provider in 1 year, with a mean of eight primary care visits per year,8 there is ample opportunity for primary care providers to discuss preventive care services.
 
Evidence-based preventive care for older adults
The core document2 provides up-to-date evidence-based recommendations for preventive care of older adults in primary care setting. These recommendations can be categorised into various health domains, including vaccination, adoption of a healthy lifestyle, dental health, chronic diseases, cancers, functional disability, mental disorders, polypharmacy and adverse drug reactions, and assessment of social network and support. A summary of the recommendations is listed in Table 1.9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 Although the recommendations aim to support primary care providers in decision-making, the care provided for each patient should also be individualised.
 

Table 1. Summary of recommendations on preventive care for older adults in primary care settings
 
Practice of evidence-based recommendations for older adults with different functional capacity
Older adults vary in their needs and functional capacity. In a healthy active older adult, the emphasis will often be on health promotion and disease-prevention activities. At the other extreme, a frail older adult with additional special needs will require a comprehensive assessment and formulation of an individualised care plan. The needs and condition of an older adult may also change over time. It is not uncommon to see a healthy active older adult suddenly becomes disabled following an untoward event.
 
In order to formulate a personalised care plan and effectively implement the evidence-based recommendations, three categories of functional capacity of older adults have been proposed—independent with no known chronic diseases, independent with chronic diseases, and older adults with disabilities.
 
For all older adults and as far as applicable, promotion of a healthy lifestyle and early identification and appropriate management of risk factors—such as unhealthy diet, physical inactivity, and tobacco use—should form the cornerstone in prevention or management of chronic diseases. A healthy lifestyle is known to be positively associated with better physical and mental health as well as longevity, reduced risk of chronic diseases, and more quality-adjusted life years.33 34 Thus promoting a healthy lifestyle should be one of the main focuses in healthy ageing.
 
For older adults of all functional stages, a healthy lifestyle and modification of behavioural risk factors should be promoted as much as is practical. Table 2 provides a summary of the recommendations.
 

Table 2. Recommendations on lifestyle advice
 
Independent with no known chronic disease
Staying active and healthy is essential to the quality of life. The functional decline that occurs with ageing may be due, at least in part, to lifestyle, behaviour, diet, and the environment, which are all modifiable factors.35
 
The primary objective for this category of older adults is to maintain optimal functional capacity and prevent or delay the development of chronic disease, thus helping to extend a healthy active life. In addition to health education and promotion, a systemic health assessment and early identification of chronic diseases are important.
 
The recommended items for assessment in this category of older adults are listed in Table 3. Details of preventive care can be found in the respective chapter of the core document2 and/or module quoted in brackets.
 

Table 3. Recommendations on preventive care for independent older adults with no known chronic diseases
 
Independent with chronic diseases
Older adults with chronic diseases vary in clinical heterogeneity, number of chronic conditions, severity of illness, and functional limitations. Chronic diseases exert a synergistic effect such that the combined disabling effect of different diseases is greater than the combined effect of each.36 As the number of chronic diseases in an individual increases, the risk of mortality, poor functional status, unnecessary hospitalisations, and adverse drug events also increases.37 38 39 Multiple chronic diseases can be accompanied by loss of function, reduced independence, and increased risk of depressive illness. These subsequently contribute to frailty and disability.37 40
 
The objectives of preventive services in these older adults are to appropriately manage their chronic diseases with reference to both secondary and tertiary prevention, as well as to maintain functional independence. The recommendations on preventive care for independent older adults with chronic diseases are summarised in Table 4. Details about preventive care can be found in the relevant chapter of the core document and/or module quoted in brackets.2
 

Table 4. Recommendations on preventive care for independent older adults with chronic diseases
 
Older adults with disabilities
Older adults who suffer multiple debilitating diseases (such as stroke, dementia, or arthritis) are likely to face disabling barriers that inhibit or prevent their integration into the community. Chronic pain is also common in this group of older adults and invariably jeopardises physical, psychological, and social wellbeing.
 
The approach to this group is early intervention to prevent further loss of function, so as to maintain optimal functional capacity and improve quality of life, and also facilitate integration into society for those who have relatively mild disability. A comprehensive assessment should be offered to this group of older adults with complex needs, and should encompass physical, psychological, and social aspects of care (eg ability in self-care, hearing and visual impairment, incontinence, falls, depression, cognitive impairment, malnutrition, polypharmacy, social support, and carer stress).
 
The recommendations on preventive care for older adults with disabilities are listed in Table 5. Details about preventive care can again be found in the relevant chapter of the core document and/or module quoted in brackets.2
 

Table 5. Recommendations on preventive care for older adults with disabilities
 
The two-page summary
A 2-page summary (Fig) has been developed to provide a quick reference for primary care providers on preventive care for older adults. It provides a summary of the evidence-based recommendations for preventive activities and the practice of recommendations for older adults with different functional capacities. The relevant chapter of the preventive care is stated in the summary for further information and supporting evidence. It can also be downloaded from the Primary Care Office website (http://www.pco.gov.hk/english/resource/files/Summary_page_older_adult.pdf).
 

Figure. Two-page summary of the Hong Kong Reference Framework for Preventive Care for Older Adults in Primary Care Settings
 
Patient education materials
In a busy clinic, patient education material is an effective means to deliver preventive care information to patients and their carers. The resources related to the health care of older adults are available in Annex 3 of the core document.2 These resources provide information for the local community and help primary care providers coordinate care with other professionals and specialists. Families can also be put in touch with community-based services. With appropriate care, older adults can achieve optimum health and improve their quality of life.
 
Conclusion
Effective preventive care of older adults can be achieved through health education and promotion, prevention and monitoring of diseases, and reduction of functional disabilities. Primary care providers play an important role in providing patient-centred, comprehensive, continuing, and coordinated preventive care to older adults in the community. In addition, continued efforts of different health care providers, professional organisations, social service agencies, and all stakeholders are needed to provide a supportive environment for active and healthy ageing. It is hoped that through the development and promotion of this reference framework, more emphasis can be placed on preventive care in older adults. This will improve their health and promote healthy ageing.
 
References
1. Hong Kong Population Projections 2012-2041. Census and Statistics Department, HKSAR. 2012 July. Available from: http://www.statistics.gov.hk/pub/B1120015052012XXXXB0100.pdf. Accessed Jun 2015.
2. Hong Kong Reference Framework for Preventive Care for Older Adults in Primary Care Settings 2012. Available from: http://www.pco.gov.hk/english/resource/files/ref_framework_adults.pdf. Accessed 11 Nov 2014.
3. Brotons C, Bulc M, Sammut MR, et al. Attitudes toward preventive services and lifestyle: the views of primary care patients in Europe. The EUROPREVIEW patient study. Fam Pract 2012;29 Suppl 1:i168-76. Crossref
4. Wallace LS, Rogers ES, Roskos SE, Holiday DB, Weiss BD. Brief report: screening items to identify patients with limited health literacy skills. J Gen Intern Med 2006;21:874-7. Crossref
5. Lo YY, Lam CL, Mercer SW, et al. Patient morbidity and management patterns of community-based primary health care services in Hong Kong. Hong Kong Med J 2011;17(3 Suppl 3):33-7.
6. Canadian Task Force on the Periodic Health Examination. The Periodic Health Examination 1984. A Report of the Periodic Health Examination Task Force. Ottawa, Ontario: Health Services Directorate, Health Services and Promotion Branch, Department of National Health and Welfare; 1984: 15.
7. US Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore, MD: Williams & Wilkins; 1996.
8. Lam CL, Leung GM, Mercer SW, et al. Utilisation patterns of primary health care services in Hong Kong: does having a family doctor make any difference? Hong Kong Med J 2011;17(3 Suppl 3):28-32.
9. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med 2007;357:1373-81. Crossref
10. Moberley SA, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev 2008;(1):CD000422. Crossref
11. Ranney L, Melvin C, Lux L, McClain E, Lohr KN. Systematic review: smoking cessation intervention strategies for adults and adults in special populations. Ann Intern Med 2006;145:845-56. Crossref
12. Lam TH, Li ZB, Ho SY, et al. Smoking, quitting and mortality in an elderly cohort of 56,000 Hong Kong Chinese. Tob Control 2007;16:182-9. Crossref
13. Whitlock EP, Polen MR, Green CA, Orleans T, Klein J; U.S. Preventive Services Task Force. Behavioral counseling interventions in primary care to reduce risky/harmful alcohol use by adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140:557-68. Crossref
14. Elward K, Larson EB. Benefits of exercise for older adults. A review of existing evidence and current recommendations for the general population. Clin Geriatr Med 1992;8:35-50.
15. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the Evidence Report. NIH Publication No. 98-4083. National Institutes of Health–National Heart, Lung and Blood Institute–Obesity Education Initiative; 1998.
16. Kressin NR, Boehmer U, Nunn ME, Spiro A 3rd. Increased preventive practices lead to greater tooth retention. J Dent Res 2003;82:223-7. Crossref
17. Hong Kong Reference Framework for Hypertension Care for Adults in Primary Care Settings. Available from: http://www.pco.gov.hk/english/resource/files/RF_HT_full.pdf. Accessed Jun 2015.
18. Blood Pressure Lowering Treatment Trialists’ Collaboration: Turnbull F, Neal B, Ninomiya T, et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 2008;336:1121-3. Crossref
19. Hong Kong Reference Framework for Diabetes Care for Adults in Primary Care Settings. Available from: http://www.pco.gov.hk/english/resource/files/RF_DM_full.pdf. Accessed Jun 2015.
20. U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;148:846-54. Crossref
21. The Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice 8th edition. Available from: http://www.racgp.org.au/your-practice/guidelines/redbook/. Accessed 17 Apr 2014.
22. U.S. Preventive Services Task Force. Screening for lipid disorders in adults: U.S. Preventive Services Task Force recommendation statement. June 2008. Available from: http://www.uspreventiveservicestaskforce.org/uspstf08/lipid/lipidrs.htm. Accessed 17 Apr 2014.
23. Sasieni PD, Cuzick J, Lynch-Farmery E. Estimating the efficacy of screening by auditing smear histories of women with and without cervical cancer. The National Co-ordinating Network for Cervical Screening Working Group. Br J Cancer 1996;73:1001-5. Crossref
24. The Cancer Expert Working Group (CEWG) on Cancer Prevention and Screening. Recommendations on colorectal cancer screening. Available from: http://www.chp.gov.hk/files/pdf/recommendations_on_crc_screening_2010.pdf. Accessed 17 Apr 2014.
25. Chou R, Dana T, Bougatsos C, Fleming C, Beil T. Screening adults aged 50 years or older for hearing loss: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2011;154:347-55. Crossref
26. Chou R, Dana T, Bougatsos C. Screening older adults for impaired visual acuity: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2009;151:44-58, W11-20.
27. O’Neil B, Gilmour D, Approach to urinary incontinence in women. Diagnosis and management by family physicians. Can Fam Physician 2003;49:611-8.
28. Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2009:(2):CD007146. Crossref
29. O’Connor EA, Whitlock EP, Beil TL, Gaynes BN. Screening for depression in adult patients in primary care settings: a systematic evidence review. Ann Intern Med 2009;151:793-803. Crossref
30. Boustani M, Peterson B, Hanson L, Harris R, Lohr KN; U.S. Preventive Services Task Force. Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2003;138:927-37. Crossref
31. Steinman MA, Landefeld CS, Rosenthal GE, Berthenthal D, Sen S, Kaboli PJ. Polypharmacy and prescribing quality in older people. J Am Geriatr Soc 2006;54:1516-23. Crossref
32. Lou VW. Caregiving burden: congruence of health assessment between caregivers and care receivers. Asian J Gerontol Geriatr 2010;5:21-4.
33. Myint PK, Luben RN, Wareham NJ, Bingham SA, Khaw KT. Combined effect of health behaviours and risk of first ever stroke in 20,040 men and women over 11 years’ follow-up in Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): prospective population study. BMJ 2009;338:b349. Crossref
34. Myint PK, Smith RD, Luben RN, et al. Lifestyle behaviours and quality-adjusted life years in middle and older age. Age Ageing 2011;40:589-95. Crossref
35. Victor CH, Howse K. Effective health promotion with vulnerable groups: older people. London: Health Education Authority; 1999.
36. Scott KM, Von Korff M, Alonso J, et al. Mental-physical co-morbidity and its relationship with disability: results from the World Mental Health Surveys. Psychol Med 2009;39:33-43. Crossref
37. Lee TA, Shields AE, Vogeli C, et al. Mortality rate in veterans with multiple chronic conditions. J Gen Intern Med 2007;22 Suppl 3:403-7. Crossref
38. Vogeli C, Shields AE, Lee TA, et al. Multiple chronic conditions: prevalence, health consequences, and implications for quality, care management, and costs. J Gen Intern Med 2007;22 Suppl 3:391-5. Crossref
39. Wolff JL, Starfield B, Anderson G. Prevalence, expenditures, and complications of multiple chronic conditions in the elderly. Arch Intern Med 2002;162:2269-76. Crossref
40. Von Korff M, Ormel J, Katon W, Lin EH. Disability and depression among high utilizers of health care. A longitudinal analysis. Arch Gen Psychiatry 1992;49:91-100. Crossref

Translating evidence into practice: Hong Kong Reference Framework for Preventive Care for Children in Primary Care Settings

Hong Kong Med J 2015 Jun;21(3):261–8 | Epub 22 May 2015
DOI: 10.12809/hkmj144307
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE
Translating evidence into practice: Hong Kong Reference Framework for Preventive Care for Children in Primary Care Settings
Natalie PY Siu, MB, BS, FHKAM (Family Medicine)1; LC Too, MB, BS, FHKAM (Family Medicine)1; Caroline SH Tsang, MB, ChB, FHKAM (Community Medicine)1; Betty WY Young, MB, BS, FHKAM (Paediatrics)2;
1 Primary Care Office, Department of Health, Hong Kong
2 Clinical Advisory Group on Hong Kong Reference Framework for Preventive Care for Children in Primary Care Settings, Hong Kong
Corresponding author: Dr Caroline SH Tsang (caroline_tsang@dh.gov.hk)
 
 Full paper in PDF
Abstract
There is increasing evidence that supports the close relationship between childhood and adult health. Fostering healthy growth and development of children deserves attention and effort. The Reference Framework for Preventive Care for Children in Primary Care Settings has been published by the Task Force on Conceptual Model and Preventive Protocols under the direction of the Working Group on Primary Care. It aims to promote health and prevent disease in children and is based on the latest research, and contributions of the Clinical Advisory Group that comprises primary care physicians, paediatricians, allied health professionals, and patient groups. This article highlights the comprehensive, continuing, and patient-centred preventive care for children and discusses how primary care physicians can incorporate the evidence-based recommendations into clinical practice. It is anticipated that the adoption of this framework will contribute to improved health and wellbeing of children.
 
 
[Abstract in Chinese]
 
Introduction
Advances in socio-economic conditions and health care delivery have contributed to improvement in child health indices in Hong Kong. For example, the infant mortality rate in Hong Kong is low by world standards, decreasing from 9.7 per 1000 live births in 1981 to 1.5 in 2012. Various problems, however, continue to affect the health of Hong Kong children. For instance, the increasing trend of obesity among primary and secondary school children has become a major public health concern.1 Injury is also a significant cause of mortality and morbidity in children. Many of these problems can be prevented.
 
In order to adopt the life-course approach to chronic disease prevention and health promotion, the Task Force on Conceptual Model and Preventive Protocols under the Working Group on Primary Care has identified two age-group–specific preventive reference frameworks, one of which is the Reference Framework for Preventive Care for Children in Primary Care Settings.2 It was developed according to the latest research evidence and with the support of the Clinical Advisory Group that comprises primary care physicians, specialists such as paediatricians, allied health professionals, and patient groups.
 
Many medical professionals have difficulty assimilating rapidly evolving scientific evidence into their practice. The reference framework provides an interface between research and practice, and aims to support health care professionals to promote health and provide continuing and comprehensive care for children in the community. It consists of a core document supplemented by a series of modules that elaborate on the various domains relevant to child health. This article highlights a practical use of this reference framework to improve the delivery of preventive care to children in the primary care setting.
 
Evidence-based preventive care for children
The core document of the reference framework provides evidence-based recommendations for comprehensive preventive care for children and can be categorised into various health domains, ranging from prenatal care to care for children with special needs. Preventive care activities for children applicable to the primary care setting are summarised in Table 1.
 

Table 1. Recommended preventive care for children in primary care settings
 
Continuing and patient-centred preventive care for children
The commitment of primary care physicians to preventive care of children is vital in the prevention of disease as well as early detection of problems and appropriate intervention. Every encounter with a child and/or the parents/caregivers should be an opportunity to promote healthy practices. Some forms of prevention should be delivered regularly, for example, vaccinations that should adhere to the locally recommended schedule. Other preventive care may be offered opportunistically, such as advice on dental care and physical activity. It is neither possible nor appropriate to initiate all preventive care at a single clinic visit. Nevertheless the long-term relationship between primary care physicians and patients allows provision of comprehensive and continuing care.
 
Practising preventive care for children in primary care
Primary care physicians may not have adequate time to go through the reference framework, especially in a busy clinic setting. It is nonetheless necessary to establish how recommendations of the reference framework can be applied to patient care. Four practical tips on application of the reference framework will be discussed below.
 
Make use of the two-page summary
The Primary Care Office has developed a two-page summary that can be downloaded from its website (Fig 1). Tabulating the various preventive activities according to age-group will enable primary care physicians to provide suitable age-specific preventive measures for their patients. The relevant chapter of the core document is identified for each aspect of preventive care, informing the primary care physician of where to find further information and supporting evidence. A summary can be posted on walls or on the desk in primary care consultation rooms to allow quick reference.
 

Figure 1. Two-page summary of the Hong Kong Reference Framework for Preventive Care for Children in Primary Care Settings
 
Make use of patient-education materials
Patient-based education interventions, especially those that involve patient-education material, have been reported to be effective in the implementation of clinical practice guidelines.3 Patient-education materials can also help more effectively deliver preventive advice. Resources related to the health care of children, such as transitional feeding (Table 2) and oral health (Table 3), are listed in annex 3 of the core document. A link to these resources can be accessed from the electronic version of the core document. These can be introduced to children and parents and enhance patient education.
 

Table 2. Resources on transitional feeding for children aged 6-24 months
 

Table 3. Resources on oral health
 
Record preventive care activities using checklists
Embedding guideline evidence into the processes and documents of patient care can help promote established evidence-based recommendations.4 Checklists of opportunistic preventive care can also be incorporated in patient medical records to allow clear documentation and facilitate any follow-up care. Primary care physicians can prepare their own checklists or utilise the ready-made checklists available in chapter 8 of the Module on Immunisation (Fig 2).
 

Figure 2. One of the checklists of immunisation and opportunistic preventive care from the Module on Immunisation
 
Deliver preventive care according to life stage
 
Childhood can be considered a sequence of life stages, namely prenatal, infancy, preschool, school age, and adolescence. Among the recommendations in Table 1, some items have particular relevance to particular life stages. For the care of an individual child in the primary care setting, preventive activities should be appropriate for age, risk status, and individual needs and values. Chapter 6 of the core document contains tables of preventive care for different life stages, and specifies the timing and action of various activities. Such a tailored approach to recommendations may ensure that the research-based message is more easily translated.5 The practice of preventive care for different life stages in daily practice can be illustrated as follows.
 
Prenatal care
Prenatal care is essential for a healthy outcome of pregnancy and should commence prior to conception. All women planning pregnancy should take daily folic acid supplement at a dose of 400 µg/day for at least 1 month before conception, and continue through the first trimester to reduce the risk of having a baby with neural tube defect.6 7 If the history of vaccination or infection is uncertain, the woman should be screened for rubella susceptibility and, if indicated, rubella vaccine administered 3 months before conception. Influenza vaccination should also be offered.8 In addition, screening for hepatitis B virus, human immunodeficiency virus, and syphilis infections should be offered if it has not been performed.9 10 11
 
Due to their harmful effect on fetal growth and development, women should be questioned about tobacco and alcohol use, and appropriate counselling offered.12 13 Breastfeeding should be promoted with relevant education and support commencing prenatally.14 15
 
Infancy (0-24 months of age)
Children and families experience rapid changes during the period of infancy. Immunisation for various infectious diseases is vital at this stage. Each visit of a child to their primary care physician provides an opportunity to confirm that immunisations are up to date. Other advice on preventive care can also be given at the same time, such as promotion of breastfeeding. Primary care providers can refer to the core document for strategies to promote breastfeeding and the principles of transitional feeding.
 
The long-term relationship between primary care physicians and families allows for surveillance of a child’s growth and development. Serial measurements of the weight and length of an infant should be recorded on a population-specific growth chart. Routine screening for hearing loss should also be arranged.
 
Visits to the primary care physician’s clinic provide an opportunity to observe relationships between parents and their children. Secure parent-child attachment in early childhood can be protective and provide a foundation for exploration and normal development.16 Parents can be helped to understand the concept of attachment and develop appropriate responses to the attachment behaviours of their young children. Parents’ psychosocial wellbeing and parenting capacity should be monitored and assistance given when indicated.
 
Preschool (2-5 years of age)
Young children should be provided with a balanced diet that comprises grains and cereals, vegetables and meat (including its alternatives, eg fish, poultry, eggs, beans, etc) in a ratio of 3:2:1 by volume.17
 
Ongoing surveillance of growth, and physical and psychosocial development should be undertaken in partnership with parents. Screening for vision problems should be offered for all children aged between 3 and 5 years to detect amblyopia or the presence of any risk for its development. Any parental concerns about a child’s development such as hearing, language, gross and fine motor development, and social behaviours should be elicited systematically. Updating a child’s developmental history by direct questioning of a parent or carer can assist in the identification of any abnormalities that warrant further investigation. Parents should also be asked if they have any concerns about their child’s behaviour. Testing for attention-deficit/hyperactivity disorder should be initiated if academic or behavioural problems and symptoms of inattention, hyperactivity, or impulsivity are present.
 
Parenting programmes have been shown to improve both child behaviour and parenting.18 19 20 21 22 As such, they should be promoted to parents.
 
Toddlers are prone to injury as they are active and love to explore their environment. Parents can be given advice on how to maintain a safe environment and prevent accidental injury.23
 
School age (6-12 years of age)
As children grow up, they can be expected to take on additional responsibility for their health. Healthy lifestyle advice, such as eating a healthy balanced diet and taking adequate physical activity, can be discussed during clinical consultations for episodic illnesses. It is recommended that children aged 5 years and above be involved in at least 60 minutes of moderate-to-vigorous–intensity physical activity each day.24 25 26 Children should minimise sedentary activity and avoid screen time of more than 2 hours per day.27 28 29 Differences can be observed in physical growth among children in this life stage. Screening for obesity can be offered for children aged 6 years and older, and appropriate weight maintained by counselling and behavioural intervention where indicated.30
 
School age is the time when learning difficulties or behavioural problems start to manifest. Primary care physicians can ask parents about progress at school and academic performance. Poor school performance may indicate an underlying learning or attention disorder. Children should be referred for detailed assessment if specific learning disabilities are suspected.
 
Adolescence (13-18 years of age)
Adolescence is the key transition stage between childhood and adulthood, a stage of attaining physical and sexual maturity. Adolescents are curious about new things and can be subject to peer pressure with consequent engagement in risk behaviour. When primary care physicians encounter adolescents, they have an opportunity to explore their psychosocial wellbeing. Information can be obtained about social life and extracurricular activities. Healthy activities such as sports and outdoor activities and healthy use of the mass media can be promoted as appropriate. If adolescents express boredom and loss of interest in their usual activities, depression should be suspected. Screening for a major depressive disorder can be conducted when systems are in place to ensure accurate diagnosis, psychotherapy, and follow-up.31
 
Smoking status for all teenagers should be established whenever the opportunity arises. Use of alcohol and illicit drugs should also be assessed using a non-judgemental approach. Adolescents who abuse either should be assisted to quit and referred for further management.32 33 Sexual history can be obtained and preventive counselling on sexual health issues delivered.34 High-intensity behavioural counselling is recommended to prevent sexually transmitted infections in all sexually active adolescents considered to be at increased risk.
 
Adolescents and their families should be encouraged to eat together: frequency of family meals has been inversely associated with poor academic performance, depressive symptoms, and risky behaviour such as tobacco and alcohol use.35
 
Conclusion
Chronic disease prevention and health promotion can begin in childhood. Effective delivery of preventive care to children depends on the combined efforts of health care professionals, social workers, teachers, and parents. Through provision of patient-centred, comprehensive, continuing and coordinated care, primary care physicians play a vital role in preventive care for children. The reference framework provides a common reference and guidance on a spectrum of preventive care activities for children. Adoption of the reference framework, its accompanying two-page summary, patient-education materials, and preventive care checklist enhances delivery of care. Practice of age-appropriate preventive care in different life stages can improve the health and wellbeing of children. Primary care physicians are in a privileged position to incorporate recommendations of the reference framework into clinical practice, and they are encouraged to familiarise themselves with the content of the reference framework. Development of new modules is underway to provide practical tips and information about topical issues already featured in the core document of the reference framework. Health care professionals are encouraged to visit the website of the Primary Care Office at www.pco.gov.hk and watch out for the new modules to be released, as well as information about seminars related to introduction of the reference frameworks. Feedback about implementation of the framework is welcome and will be valuable for revision of the core document and development of future modules.
 

Appendix. Hong Kong Childhood Immunisation Programme
 
References
1. Student Health Service. Newsletter [Internet]. December 2012; 57. Hong Kong SAR: Department of Health. Available from: http://www.studenthealth.gov.hk/english/newsletters/newsletter_57.html. Accessed 18 Mar 2015.
2. Hong Kong reference framework for preventive care for children in primary care settings 2012. Available from: http://www.pco.gov.hk/english/resource/files/ref_framework_children.pdf. Accessed 13 Nov 2014.
3. Davis DA, Taylor-Vaisey A. Translating guidelines into practice. A systematic review of theoretic concepts, practical experience and research evidence in the adoption of clinical practice guidelines. CMAJ 1997;157:408-16.
4. Gerhardt WE, Schoettker PJ, Donovan EF, Kotagal UR, Muething SE. Putting evidence-based clinical practice guidelines into practice: an academic pediatric center’s experience. Jt Comm J Qual Patient Saf 2007;33:226-35.
5. Yana R, Jo RM. Getting guidelines into practice: a literature review. Nurs Stand 2004;18:33-40.
6. Blencowe H, Cousens S, Modell B, Lawn J. Folic acid to reduce neonatal mortality from neural tube disorders. Int J Epidemiol 2010;39(Suppl 1):i110-21. Crossref
7. Wolff T, Witkop CT, Miller T, Syed SB; U.S. Preventive Services Task Force. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2009;150:632-9. Crossref
8. National Center for Immunization and Respiratory Diseases. General recommendations on immunization—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60:26-7.
9. Wong VC, Ip HM, Reesink HW, et al. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study. Lancet 1984;1:921-6. Crossref
10. Chou R, Smits AK, Huffman LH, Fu R, Korthuis PT; US Preventive Services Task Force. Prenatal screening for HIV: A review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2005;143:38-54. Crossref
11. Wolff T, Shelton E, Sessions C, Miller T. Screening for syphilis infection in pregnant women: evidence for the U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med 2009;150:710-6. Crossref
12. Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. Interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev 2009;(3):CD001055. Crossref
13. Whitlock EP, Polen MR, Green CA, Orleans T, Klein J; U.S. Preventive Services Task Force. Behavioral counseling interventions in primary care to reduce risky/harmful alcohol use by adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140:557-68. Crossref
14. Britton C, McCormick FM, Renfrew MJ, Wade A, King SE. Support for breastfeeding mothers. Cochrane Database Syst Rev 2007;(1):CD001141. Crossref
15. Chung M, Raman G, Trikalinos T, Lau J, Ip S. Interventions in primary care to promote breastfeeding: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2008;149:565-82. Crossref
16. Greenberg MT, Speltz ML, DeKlyen M. The role of attachment in the early development of disruptive behavior problems. Dev Psychopathol 1993;5:191-213. Crossref
17. Department of Health, HKSARG. The healthy eating food pyramid—a guide to a balanced diet. Available from: http://www.cheu.gov.hk/eng/info/2plus3_12.htm. Accessed Mar 2015.
18. Thomas R, Zimmer-Gembeck MJ. Behavioral outcomes of Parent-Child Interaction Therapy and Triple P-Positive Parenting Program: a review and meta-analysis. J Abnorm Child Psychol 2007;35:475-95. Crossref
19. Nowak C, Heinrichs N. A comprehensive meta-analysis of Triple P-Positive Parenting Program using hierarchical linear modeling: effectiveness and moderating variables. Clin Child Fam Psychol Rev 2008;11:114-44. Crossref
20. de Graaf I, Speetjens P, Smit F, de Wolff M, Tavecchio L. Effectiveness of the Triple P Positive Parenting Program on behavioral problems in children: a meta-analysis. Behav Modif 2008;32:714-35. Crossref
21. Effective strategies to support positive parenting in community health centers: Report of the Working Group on Child Maltreatment Prevention in Community Health Centers. Washington, DC: American Psychological Association; 2009.
22. Centre for Excellence and Outcomes in Children and Young People’s Services. Improving children’s outcomes by supporting parental physical and mental health. London: Department for Education; 2011.
23. Clamp M, Kendrick D. A randomised controlled trial of general practitioner safety advice for families with children under 5 years. BMJ 1998;316:1576-9. Crossref
24. Physical Activity Guidelines Advisory Committee Report. Washington, DC: US Department of Health and Human Services; 2008.
25. Global Recommendations on Physical Activity for Health. Geneva: World Health Organization; 2010.
26. Janssen I, Leblanc AG. Systematic review of the health benefits of physical activity and fitness in school-aged children and youth. Int J Behav Nutr Phys Act 2010;7:40. Crossref
27. Get up & grow: healthy eating and physical activity for early childhood. Australia: Department of Health and Aging; 2009. Available from: http://www.health.gov.au/internet/publications/publishing.nsf/Content/gug-carer-toc. Accessed Mar 2015.
28. UK physical activity guideline. UK Department of Health. Available from: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_127931. Accessed Mar 2015.
29. Guidelines for Preventive Activities in General Practice. 7th ed. The Royal Australian College of General Practitioners; 2009.
30. US Preventive Services Task Force, Barton M. Screening for obesity in children and adolescents: US Preventive Services Task Force recommendation statement. Pediatrics 2010;125:361-7. Crossref
31. Williams SB, O’Connor EA, Eder M, Whitlock EP. Screening for child and adolescent depression in primary care settings: a systematic evidence review for the US Preventive Services Task Force. Pediatrics 2009;123:e716-35. Crossref
32. Supporting smoking cessation: a guide for health professionals. South Melbourne: The Royal Australian College of General Practitioners; 2011.
33. American Academy of Pediatrics: Committee on Substance Abuse. Alcohol use and abuse: a pediatric concern. Pediatrics 2001;108:185-9. Crossref
34. Preventive services for children and adolescents. 16th ed. Institute for Clinical Systems Improvement; 2010.
35. Eisenberg ME, Olson RE, Neumark-Sztainer D, Story M, Bearinger LH. Correlations between family meals and psychosocial well-being among adolescents. Arch Pediatr Adolesc Med 2004;158:792-6. Crossref

Falls prevention in the elderly: translating evidence into practice

Hong Kong Med J 2015 Apr;21(2):165–71 | Epub 27 Feb 2015
DOI: 10.12809/hkmj144469
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE    CME
Falls prevention in the elderly: translating evidence into practice
James KH Luk, FHKCP, FHKAM (Medicine)1; TY Chan, FHKCP, FHKAM (Medicine)2; Daniel KY Chan, MD, FRACP3
1Department of Medicine and Geriatrics, Fung Yiu King Hospital, Hong Kong
2Department of Medicine and Geriatrics, Kwong Wah Hospital, Yaumatei, Hong Kong
3Faculty of Medicine, University of New South Wales, Ingham Institute; Aged Care & Rehab, Bankstown Hospital, Australia
Corresponding author: Dr James KH Luk (lukkh@ha.org.hk)
 Full paper in PDF
Abstract
Falls are a common problem in the elderly. A common error in their management is that injury from the fall is treated, without finding its cause. Thus a proactive approach is important to screen for the likelihood of fall in the elderly. Fall assessment usually includes a focused history and a targeted examination. Timed up-and-go test can be performed quickly and is able to predict the likelihood of fall. Evidence-based fall prevention interventions include multi-component group or home-based exercises, participation in Tai Chi, environmental modifications, medication review, management of foot and footwear problems, vitamin D supplementation, and management of cardiovascular problems. If possible, these are best implemented in the form of multifactorial intervention. Bone health enhancement for residential care home residents and appropriate community patients, and prescription of hip protectors for residential care home residents are also recommended. Multifactorial intervention may also be useful in a hospital and residential care home setting. Use of physical restraints is not recommended for fall prevention.
 
 
[Abstract in Chinese]
 
Introduction
Falls and imbalance occur commonly in the elderly and fall/instability is indeed one of the ‘giants’ in geriatric medicine.1 A fall is often defined as an event that results in the patient or a body part of the patient coming to rest inadvertently on the ground or other surface lower than the body.2 In Hong Kong, the prevalence in the elderly of having at least one fall in the preceding 12 months is between 18% and 19.3%, with 75.2% sustaining injuries and 7.2% having a serious injury.3 4 Those who fall have significantly more hospitalisations and clinic visits as well as accident and emergency department visits than those who do not. Fear of falling, loss of confidence in walking, social isolation, and depression can also occur. Fall is a predictor for decreased functional state and risk factor for institutionalisation,5 and the elderly who are prone to falling consume more health care resources than non-fallers each year.6
 
Pitfalls in fall management
Despite the potentially severe consequences of falls, under-reporting by the elderly is common.7 Individuals may attribute falling to the ageing process or they may not report falls because of the fear of being restricted in their activities or being institutionalised following a fall. Some older people, especially those with cognitive impairment, may forget the event and consequently fail to inform the health care team. Alternatively, in the absence of an obvious injury, physicians may be unaware of falls. A drawback to the management of falls is that the consequences, such as fractures or head injuries, are treated without finding the cause of the fall. Unless all the underlying risk factors are addressed, falls are very likely to recur.
 
Knowing the risk/precipitating factors for falls
The first step in fall prevention is to identify the risk or precipitating factors for falls. Age by itself is an important risk factor, but not the only one. Falls in the elderly are often due to the interaction of multiple risk factors. One practical way to help clinicians identify risk or precipitating factors is to use a mnemonic. One such mnemonic is shown in the Table.8
 

Table. Mnemonic (A E I O U, A B B C C C) of risk or precipitating factors for falls (A is shared between vowels and ABC)8
 
Fall assessment
As falls are usually under-reported, a proactive approach is to ask “Have you had a fall in the past 6 months?” at every encounter with an elderly patient. Initial medical assessment involves a focused history-taking, detailing the circumstances of fall, precipitating factors, and consequences. A witness can be helpful to identify unrecognised syncope. Other relevant history includes living environment, social support, past medical illnesses, medication, history of falls or near falls, and mobility and functional status. Comprehensive geriatric assessment should follow documentation of history.9 Testing of gait, balance, and lower limb and joint function, alongside cardiovascular and neurological examination should be performed where relevant. Postural blood pressure, vision, feet, and footwear should also be checked. Measurement of postural blood pressure requires a wait of at least 3 minutes between sitting and standing (or lying and sitting), and is often omitted or not done properly. Simple bedside investigations such as electrocardiography should be performed as arrhythmia may be the cause of falls due to syncope. Further investigations should be guided by the history and examination.
 
One simple screening test for mobility is the timed up-and-go test.10 The patient is timed while rising from a 46-cm high armchair, walking 3 metres, turning around, and returning to sit in the chair (total 6 metres). The assessment should be repeated with a walking aid if the patient is found to be unsteady. Patients who require more than 20 seconds to complete the task are at risk of fall. It is prudent to refer ‘fallers’ with multiple risk factors to geriatricians for professional assessment and management. Risk factors, once identified, should then be managed with inter-disciplinary intervention to reduce the risks as soon as possible. For example, if impaired vision due to cataract is identified, an expedited eye consultation and cataract treatment is desirable to reduce the chance of recurrent falls.
 
Practical evidence-based strategies in fall prevention
Exercise
Multi-component exercises, including strength, endurance and balance training, either in a group or home-based, have been shown to reduce both rate and risk of falling.11 The exercises need to be of sufficient intensity to improve muscle strength. Balance retraining appears to be the more important component of any exercise programme designed to decrease falls.12 The balance training can either be specific dynamic balance retraining exercises or a component of a movement programme such as Tai Chi.13 Exercises should be regular and sustainable, and be a part of multifactorial intervention (MFI; see below). One should be aware that prescribing inappropriate exercise may increase falls in the elderly.
 
Tai Chi
The anecdote of Tai Chi in fall prevention is generally well known to the public. Similar to multi-component exercises, Tai Chi reduces both the rate of fall and falling risk according to a Cochrane Review.11 Wolf et al14 also reported the benefit of 10-form Tai Chi in a randomised controlled trial (RCT). Tai Chi is a combination of strength and balance training, with a certain aerobic element.15 In Hong Kong, most people practise the full form that should theoretically be at least effective, if not better. This can be promoted as a territory-wide health recommendation. Nonetheless, not all Tai Chi programmes improve balance. One local RCT revealed no difference in the number of falls between a Tai Chi group and controls after 12 months.16
 
Environmental interventions
Home modifications can effectively reduce risk of falls in the community,11 and include removal of floor mats, painting the edge of steps, reducing glare, installing handles, and improving lighting. Occupational therapists can provide expert advice in this area. For older people with fall risk who live at home, especially those who are usually alone, installation of a safety alarm is recommended so help can be summoned should an accident occur.
 
Medication review
Polypharmacy is common among older people who often have multiple co-morbidities, and is an independent variable that has been linked to falls in older people.17 Many drugs, psychotropic medications and antihypertensive agents in particular, are related to falls. The use of psychotropic medication should be confined to patients who do not respond to non-pharmacological intervention and the lowest dosage should be prescribed. Periodic review of indications and side-effects should be undertaken: gradual withdrawal of psychotropic medication can reduce rate of falls in community-dwelling elderly people.11 Nonetheless drug withdrawal is a complicated intervention that should be implemented by an experienced clinician after carefully weighing the risks and benefits. A standardised and explicit medicine review tool such as the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults and STOPP (Screening Tool of Older Person’s potentially inappropriate Prescriptions) may be useful in reducing falls in older people but the effectiveness of these approaches has not been proven by RCTs.18 19 Although drug withdrawal is beneficial, studies that include RCTs show that many withdrawals (eg sleeping pills) are reversed and patients resume previous therapy. Ongoing monitoring is therefore essential.20
 
Foot and footwear
Foot and footwear problems are common but are often ignored. Footwear influences balance and risk of falls. High-heeled shoes have been shown to increase falls in older people. Anti-slip shoe devices effectively reduce outdoor falls in slippery conditions.21 A systematic review recommends that elderly individuals wear shoes with a low heel and firm slip-resistant soles, both inside and outside the home.22 Podiatrists, and prosthetics and orthotics professionals can give valuable advice in this respect. A recent RCT has shown that multifaceted podiatry intervention with foot orthoses, footwear advice, education, and foot and ankle exercises can reduce the rate of falls in community-dwelling older people.23
 
Vitamin D supplement
The benefit of vitamin D in falls/fractures extends beyond improved bone health. Vitamin D can strengthen muscle and hence reduce falls. Meta-analysis has shown that supplemental vitamin D at a dose of 700 IU to 1000 IU a day reduces the risk of falling among older individuals by 19%.24 The current opinion is that in community-dwelling elderly, vitamin D supplementation reduces the rate of falls or risk of falling in a subgroup of people with low vitamin D levels but its benefit is absent in people without deficiency.11 In the institutionalised elderly, vitamin D supplementation appears to be more effective in reducing falls and the recommendation is to prescribe vitamin D with or without calcium supplements to older people with low vitamin D levels or those who are institutionalised.11 Despite these recommendations, most studies have been conducted in western countries that experience a quite different duration and intensity of sunshine to Hong Kong. Whether the benefit of vitamin D in fall prevention applies equally to Hong Kong Chinese population is not known. Most public hospital laboratories in Hong Kong do not have the means to investigate vitamin D levels and clinicians are required to send blood samples to private laboratories for vitamin D level assay at a cost. Thus in the public health sector, mass screening of the elderly for vitamin D deficiency prior to supplementation is impractical. The pragmatic approach is to encourage a healthy balanced diet that is rich in vitamin D. For older people who are at risk of fall, especially those in residential care home for the elderly (RCHE), a dose of 800 IU of vitamin D3 per day with or without calcium supplementation is recommended, provided there is no contra-indication.11 The clinician should also ask whether the older person is taking any over-the-counter vitamin D–containing drugs before commencing supplementation, as excess vitamin D may result in hypercalcaemia.
 
Correction of vision
Poor visual acuity caused by presbyopia, cataract, macular degeneration or glaucoma, reduction in depth perception and contrast sensitivity are risk factors for falls.25 Maximising vision with cataract surgery is effective in fall prevention. In a UK RCT that compared fast-track (4 weeks) with routine-queue (12 months) first eye cataract surgery, a significant reduction in fall and fracture rate in 1 year was observed in the fast-track group.26 Another RCT by the same team showed that fast-track surgery (4 weeks) for the second eye in older people also produced a tendency to fewer falls compared with the routine queue (12 months) group.27 One should beware, though, that correction of vision may sometimes result in increased falls. One RCT showed that vision assessment and intervention may increase the risk of falls and fractures, possibly due to poor adjustment to new spectacles.28 Multifocal lenses may increase fall risk by reducing contrast sensitivity and depth perception in the lower visual field when mobilising.29 As such, older individuals should wear single lens glasses, especially when performing outdoor activities.
 
Management of cardiovascular risk factors
Cardiovascular investigations and interventions are indicated for those with fall related to syncope and orthostatic hypotension. Neurally mediated syndromes (carotid sinus hypersensitivity, vasovagal syndrome, orthostatic hypotension, postprandial hypotension), arrhythmias (sick sinus syndrome, severe heart block, tachyarrhythmia), and structural cardiac disease (valvular stenosis, hypertrophic obstructive cardiomyopathy, atrial myxoma, aortic dissection) are all risk factors for falls because they cause either attacks of syncope or transient hypotension (pre-syncope).30 Randomised controlled trials in older patients have shown that those with dual-chamber pacemaker implantation for cardio-inhibitory carotid sinus hypersensitivity had significantly fewer falls and fall-related injuries.31 32 It is beyond the scope of this article to describe in detail the investigation and management of individual cardiovascular conditions. Referrals to cardiology colleagues are recommended for certain conditions such as arrhythmias when appropriate. Other conditions such as postural hypotension can usually be managed by a geriatrician.
 
Multifactorial intervention
A MFI programme is a set of interventions designed to address multiple elements of fall risk.33 The elements of MFI usually include multi-component exercises, medical assessment and management of falls, medication adjustment, vitamin D supplementation if appropriate, environmental modifications, and patient education. Since falls are often multifactorial in nature, MFI (rather than a singular approach) is more likely to be effective and is therefore recommended. The intervention can take the form of a general MFI or be an individualised MFI with tailor-made interventions based on specific individual needs.11 Most evidence to support MFI efficacy is in community-dwelling older people. In a community setting, general MFI can achieve a 24% to 31% reduction in fall risk, while individualised MFI may improve this figure to 27% to 41%.10 Multi-factorial intervention may not be effective in fall prevention in other settings, such as in the accident and emergency department.34 A recent Malaysian RCT has just been completed to determine whether MFI is appropriate in an Asian country; the results are pending.35
 
Fracture reduction
Fall-related fractures can be reduced by improving bone strength. Thus assessment of bone health should be performed in older people as part of the comprehensive assessment. If indicated clinically, bone mineral density assessment can be undertaken in patients at risk of fragility fracture.36 In addition to vitamin D and calcium supplementation, specific pharmacological treatment should be considered. The World Health Organization FRAX (Fracture Risk Assessment Tool) score can be used to guide treatment by calculating the 10-year osteoporotic fracture rate.37 It is beyond the scope of this article to describe in detail the management of bone fragility.
 
Another means of fracture protection is the use of hip protectors.38 Most hip protector designs consist of two mechanically proven hard plastic cups or soft pads placed or sewn to each side of a panty. Compliance with their use has been a problem in most studies though, and rates varying from 31% to 68% have been reported, reducing in particular over time.39 One local study reported overall compliance rates of 55% to 70% with an 82% relative risk reduction of hip fracture.40 In Hong Kong, the hot and humid weather makes wearing of hip protectors uncomfortable for a prolonged period of time. Nonetheless a small reduction in hip fracture risk was reported in a systematic review when hip protectors were used in a RCHE with risk ratio of 0.82 (confidence interval, 0.67-1.00).41 No evidence of such benefit was observed in a community setting, hence their use should probably be confined to the RCHE setting.
 
Fall prevention in hospital and residential care home setting
Multifactorial intervention in hospital and the RCHE has been shown in a systematic review to reduce rate of falls.42 The effective components were comprehensive assessment, staff education, assistive devices, and reduction of medications. Older patients or residents should be assessed individually to develop individualised MFI treatment plans. However, the use of screening tools for risk of fall is more controversial in the institutional setting. In Hong Kong, screening tools such as Morse Fall Scale and STRATIFY are mandated in many hospital wards, long-stay wards in particular, with the former more commonly used.43 44 To date though, there is no evidence to support their use in fall prevention in an institutional setting. An experienced nurse’s clinical judgement is just as effective.45 In addition, a disadvantage of screening tools is that they predict fall due to physiological factors, not incidental falls (eg patient slipping or tripping) or unpredictable physiological falls (eg seizures, syncope). Other risk factors for falls such as “impaired judgement in patients with cognitive impairment” may also not be included in traditional screening tools.46
 
Health care providers in hospitals or RCHEs may employ physical restraints to older patients when they are at risk of falling or delirious although evidence suggests these are ineffective, not to mention undignified.47 Further, patients may fall more frequently and sustain more serious injuries. Restraints increase the risk of delirium in the hospital setting and the consequent immobilisation precipitates other problems such as pressure sores, respiratory complications, and death via strangulation and aspiration. Although some long-stay hospitals and institutions in Hong Kong have implemented a restraint reduction programme, they remain commonly used in some institutional settings.48
 
Vitamin D can be considered for all older people who live in RCHEs where the prevalence of deficiency is high. Other strategies for fall prevention that have been used in institutional settings are a chair/bed alarm system, ultra-low beds, and changing of the floor surface from vinyl to carpet. Nevertheless the effectiveness of these methods has not been proven through RCTs.49
 
Fall prevention in the cognitively impaired older people
Although falls are common among the elderly, there is insufficient evidence to recommend MFI or single intervention for cognitively impaired older people in community, hospital, and RCHE settings. The elderly with dementia have often been excluded from large-scale studies of falls. During training for fall prevention, older patients may be required to learn exercise skills and remember instructions; impaired memory can affect the success of fall prevention. Another report concludes that intervention for fall prevention among cognitively impaired older people in RCHEs is ineffective.50 Nonetheless some studies have reported positive effects. A local retrospective study showed that older people with dementia can still benefit from rehabilitation.51 One meta-analysis showed that strategies to prevent falls and fractures in hospitals and RCHEs were not affected by cognitive impairment.52 Another study demonstrated that the number of falls in psychogeriatric RCHE residents could be reduced by a targeted MFI.53 More studies are required to determine the optimum fall prevention strategies for older people with dementia.
 
Conclusion
Evidence-based interventions include multi-component group or home-based exercises, Tai Chi, environmental modifications, medication review, management of foot and footwear problems, vitamin D supplementation, and addressing cardiovascular problems. If possible, these are best implemented in the form of MFI. Bone health enhancement for RCHE and appropriate community patients and prescription of hip protectors for RCHE patients are also recommended. A MFI programme may also be useful in the hospital and RCHE setting. Use of physical restraints is not recommended for fall prevention. More high-quality studies are required to examine fall prevention for older people with cognitive impairment. Modern technology for fall prevention, such as movement alarms and sensor technology, should also be further explored.
 
References
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21. McKiernan FE. A simple gait-stabilizing device reduces outdoor falls and nonserious injurious falls in fall-prone older people during the winter. J Am Geriatr Soc 2005;53:943-7. Crossref
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Prevention of ventilator-associated pneumonia

Hong Kong Med J 2015;21:Epub 16 Jan 2015
DOI: 10.12809/hkmj144367
MEDICAL PRACTICE
Prevention of ventilator-associated pneumonia
Arthur CW Lau, FHKAM (Medicine)1; HM So, FHKAN (Critical Care)1; SL Tang, BSc (Nursing)2; Alwin Yeung, FHKAM (Medicine)2; SM Lam, FHKAM (Medicine)1; WW Yan, FHKAM (Medicine)1; for the Hong Kong East Cluster Task Force on Prevention of Ventilator-associated Pneumonia in Critical Care Areas
1Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
2Cardiac and Intensive Care Unit, Ruttonjee Hospital, Wanchai, Hong Kong
Corresponding author: Dr Arthur CW Lau (laucw3@ha.org.hk)
 Full paper in PDF
Abstract
Ventilator-associated pneumonia is the commonest, yet mostly preventable, infection in mechanically ventilated patients. Successful control of ventilator-associated pneumonia can save hospitalisation cost, and is possible by using a multidisciplinary clinical and administrative approach. The ventilator-associated pneumonia rate should be expressed as the number of ventilator-associated pneumonia days per 1000 ventilator days to take into account the device-utilisation duration for meaningful comparison. Various strategies address the issue, including general infection control measures, body positioning, intubation and mechanical ventilation, oral and gastro-intestinal tract, endotracheal tube, airway pressure, cuff pressure, selective digestive and/or oropharyngeal decontamination, and probiotic or early antibiotic treatment, as well as overall administration at a policy level. The rationale and controversy of these approaches are discussed in this article. The authors suggest that all units treating mechanically ventilated patients should have a ventilator-associated pneumonia prevention protocol in place, and ventilator-associated pneumonia should be seriously considered as a key performance indicator in local intensive care units.
 
 
[Abstract in Chinese]
 
Introduction
Ventilator-associated pneumonia (VAP) is the commonest, yet mostly preventable, infection in mechanically ventilated patients. It contributes to increased morbidity, mortality, and total hospitalisation cost. The estimated overall attributable mortality of VAP was 13%,1 and 52% of VAP was preventable.2 The VAP rate should be expressed as the number of VAP days per 1000 ventilator days to take into account the device-utilisation duration for meaningful comparison. From the reports of the National Health and Safety Network (NHSN) of the US Centers for Disease Control and Prevention (CDC),3 a decreasing trend for VAP has been noted in recent years. For example, from 2002 to 2012, for a mixed medical-surgical intensive care unit (ICU), the rate decreased from 5.1 to 0.9 days per 1000 ventilator days. The highest rates were reported for trauma (from 15.2 to 3.6 days) and burns (from 12.0 to 4.4 days) centres, while neurological and neurosurgical units reported intermediate rates (around 2 to 4 days). European rates are mostly higher, even if the same prevention strategies are used, and some possible reasons are explained below.4
 
Unlike many other conditions for which definitive diagnoses can be made pre-mortem, the gold standard of VAP diagnosis can only be made post-mortem. Clinicians diagnose VAP by radiology, signs and symptoms, with various methods of non-invasive and invasive microbiology sampling (tracheal aspirate, directed or blind broncho-alveolar lavage, protected specimen brush for qualitative and/or quantitative culture), and histology. However, when clinical criteria with microbiology were compared with autopsy findings, both the sensitivity and specificity were approximately 70%.5 Moreover, there has been no convincing evidence that qualitative culture of non-invasive samples, when compared with quantitative culture of invasive samples, produced any significant differences in clinical outcomes.6 In a survey of 27 ICUs of nine European countries, bronchoscopy was performed only in 23.3% of episodes of nosocomial pneumonia.7 Bronchoscopy might be considered more for immunocompromised hosts, both for detection of atypical organisms (if any) and to exclude infection.
 
The definition of VAP is therefore inherently subjective and, hence, contentious. The criteria used, interobserver variability, and subjectivity in chest X-ray interpretation affect the VAP rates by almost two-fold.8 9 All these factors influence findings in preventive trials and hamper comparisons. For surveillance purposes, most institutions use the surveillance definitions of radiology/signs/symptoms to monitor the rates. Commonly used surveillance definitions are those of the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA)10 and the CDC NHSN. The two sets of definitions are similar; the notable difference being that the ATS/IDSA guidelines exclude pneumonias occurring in the first 48 hours after intubation, whereas the CDC NHSN definition includes pneumonias in the first 48 hours; therefore, using the latter definition will result in a higher VAP incidence.
 
In an attempt to overcome the VAP definition’s inherent subjectivity, in 2014, the CDC NHSN started surveillance using the Ventilator-Associated Event protocol,11 under which a ventilator-associated condition (VAC) is defined if there are at least 2 days of stable or decreasing ventilator settings (positive end-expiratory pressure [PEEP] and fraction of inspired oxygen) followed by consistently higher settings for at least 2 days. The sensitivity of the VAC criteria for the detection of VAP was only 25.9%.12 When further microbiological and invasive techniques are employed, a VAC can be further classified into an infection-related VAC, and possible VAP. This modification enables greater objectivity and facilitates automated electronic capture, but captures changes due not only to VAP.
 
Pathophysiology and its implications for prevention strategies
In terms of pathophysiology, VAP is a misnomer because its occurrence is not related to the ventilator per se, but to the presence of the endotracheal tube (ETT). The ETT allows direct access to the lower respiratory tract, impairing the cough reflex and mucociliary clearance, but provides incomplete sealing to secretions above the cuff. Microaspiration (of materials from oropharyngeal cavities, sinuses, gastro-intestinal tract) and biofilm formation are the two most important mechanisms in VAP development, while inhalation, bacteraemia and haematogenous spread play smaller roles. Molecular analysis showed that most VAP patients had the same bacteria with the same sequencing in their oral cavities as in their lungs, and there were even pathogens found in the lungs that could not be detected by conventional culture-based methods.13 Types of bacteria vary with the time of onset; in early-onset VAP, they are commonly Enterobacteriaceae, Candida albicans and Staphylococcus aureus,14 while in late-onset VAP, they are Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli.
 
Evolution of prevention strategies
No single strategy is sufficient to prevent VAP, and several approaches are necessary. The most widely practised and well-known set of strategies is the Ventilator Bundle developed by the Institute for Healthcare Improvement (IHI) in 2001.15 The Ventilator Bundle is often mislabelled as the VAP Bundle, and its original aim was to improve better ventilator care overall, and not VAP alone, although its practice does reduce the VAP rate by 45%.15 The components of the Ventilator Bundle have now become the core of VAP prevention: (1) elevation of the head of bed to between 30° and 45°; (2) daily ‘sedative interruption’ and daily assessment of readiness to be extubated; (3) peptic ulcer disease prophylaxis; (4) deep venous thrombosis prophylaxis (unless contra-indicated); and (5) daily oral care with chlorhexidine. It is practice of the whole ‘bundle’ that decreases VAP, not just the individual components. Some components are not directly related to VAP, namely, deep venous thrombosis and peptic ulcer disease prophylaxis. Although specific data on VAP were not available, in general, the risk of hospital-acquired pneumonia increased when acid-suppressant medications were used. There was a slight trend for reduced VAP with sucralfate compared with a histamine 2 receptor antagonist, and proton pump inhibitors may be related to a higher rate of VAP.16 Therefore, acid-suppressant medications should not be overused. In Hong Kong, the Centre for Health Protection of the Department of Health promulgated a set of recommendations of VAP prevention in 2010.17 In this article, we review the latest literature regarding VAP prevention, and the strategies are summarised in the Table. The rationale and controversy are elaborated in the following discussion.
 

Table. Ventilator-associated pneumonia prevention strategies
Rationale and controversy behind some of the strategies are elaborated in the text. Strategies that have been suggested in the literature, but are not yet widely practised and/or require further research are listed in italics
 
Prevention strategies
Clinical strategies
General
General principles of infection control should be followed. Ventilator tubing should not be changed more frequently than every 1 week unless it is visibly soiled. In an early prospective randomised trial of 447 patients, decreasing the frequency of ventilator circuit changes from 3 times to once per week had no adverse effect on the overall rate of VAP.18 Subsequent trials also showed that circuit change intervals of 7 and 30 days had even lower risks for VAP than 2-day intervals.19 There was evidence that chlorhexidine bathing and hand hygiene compliance reduced global and specific infection rates, including VAP.20 A protocol for microbiological surveillance could be considered to aid in selection of empirical therapy.
 
Body positioning
The semi-recumbent position (30°-45° to the horizontal) is widely practised as one of the components of the IHI Ventilator Bundle, but which was based on only one randomised study with a non–intention-to-treat protocol of 86 mechanically ventilated patients, comparing the supine and semi-recumbent positions, in which the VAP rates were 34% and 8%, respectively.21 Subsequent studies were not able to reproduce these results, and found that a 45° position was difficult to maintain, and the mean angle achievable was only 28°. It has been suggested that avoidance of the supine position was beneficial as, while the semi-recumbent position might reduce gastro-oropharyngeal aspiration, the effect of gravity increases hydrostatic pressure of secretions pooled above the cuff. Recent animal studies found that mucus flow reversed towards the lungs in the semi-recumbent position, but drained out in the horizontal position. In human beings, the trachea/ETT axis is below the horizontal in the lateral Trendelenburg position (ie lying lateral, at 5°-10° below the horizontal). The Gravity VAP-Trial,22 an international randomised controlled trial (RCT) aiming at enrolment of 800 patients, is ongoing to compare the efficacy and safety of the two body positions, namely, the lateral Trendelenburg versus the semi-recumbent positions, in reducing the incidence of VAP. The estimated study completion date is December 2016. Continuous lateral rotation therapy, or kinetic bed therapy, ie lateral rotation of patient to ≥40° on one side (and 80° total arc) using specially designed beds, has been reported to reduce VAP, but was associated with other side-effects such as intolerance to rotation, unplanned extubation, loss of vascular access, and arrhythmias.23
 
Intubation and mechanical ventilation
Non-invasive ventilation (NIV) should be used to avoid the need for invasive ventilation and also shorten its duration. Non-invasive ventilation is particularly beneficial in chronic obstructive pulmonary disease (COPD), immunocompromised patients, and acute pulmonary oedema, and it allows early weaning from invasive ventilation in COPD. Summary estimates from 16 trials of moderate-to-good quality that included predominantly participants with COPD suggested that a weaning strategy that included NIV might reduce mortality and VAP rates without increasing the risk of weaning failure or reintubation.24
 
In a RCT of 128 adult mechanically ventilated patients, daily interruption of sedation resulted in a highly significant reduction in time spent on mechanical ventilation.25 The same authors also showed in the Awakening and Breathing Controlled trial that paired daily spontaneous awakening tests (ie interruption of sedatives) with daily spontaneous breathing tests resulted in better outcomes for mechanically ventilated patients.26 Although there is persistent concern of increased complications with this practice such as self-extubation, subsequent study found that this was not the case. A nurse-implemented sedation protocol has been shown to decrease VAP.27 Our ICU is also performing a nurse-led early weaning trial to aim at shortening the intubation period.
 
Oral and gastro-intestinal tract
Using chlorhexidine mouth rinse or gel as part of oral hygiene care, compared with placebo or usual care, was associated with a reduction in VAP, with a number needed to treat of 15 (95% confidence interval, 10-34).28 There is no consensus for the best practice for oral hygiene care. The optimal concentration of chlorhexidine solution to use is not known. Chlorhexidine has been studied in two strengths: 0.12% and 0.2%, and the US Food and Drug Administration recommends 0.12% oral chlorhexidine for use as mouth rinse. There is no evidence that the following is necessarily better than using chlorhexidine alone: addition of manual or powered tooth brushing, using Listerine (Johnson & Johnson Healthcare Products, New Brunswick [NJ], US), sodium bicarbonate oral rinses, or use of povidone-iodine solution. Povidone-iodine seemed to increase the rate of acute respiratory distress syndrome.29 A local study showed that continuous clearance of oral secretion by the saliva ejector might reduce the rate of VAP, decreasing the duration of mechanical ventilation, and shortening the duration of stay of patients in the ICU.30 Although gastroesophageal aspiration is implicated in VAP development, in an intention-to-treat study of 449 patients on mechanical ventilation, the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of development of VAP (16.7% in the intervention group and 15.8% in the control group), nor were there any significant between-group differences in other ICU-acquired infections, mechanical ventilation duration, ICU stay duration, or mortality.31 There were more VAPs with early enteral feeding, and less with post-pyloric feeding. Further studies are required to confirm this.
 
Endotracheal tube
Novel designs of ETTs target two major mechanisms of VAP, namely, microaspiration and biofilm formation.32 33 Microaspiration is controlled by incorporating changes in cuff shape, material, and addition of a subglottic suction port. Prevention of biofilm formation is managed by addition of coating, surface modification, and removal of biofilm by mechanical means. The conventional ETT cuff (eg Portex; Smiths Medical International Ltd, Ashford, UK) is made of polyvinyl chloride (PVC), of which, when inflated, redundant parts fold on themselves and, because of the thickness of the material (>50 µ), microchannels form through which leakage is possible. By modification of the shape from conical to tapered (eg TaperGuard; Covidien, Irvine [CA], US), better contact of the cuff with the trachea can be achieved, and microchannel formation is reduced. By modification of the material from PVC to the thin 7-µ thick polyurethane (eg Microcuff; Kimberly-Clark Health Care, Roswell [GA], US), microchannel formation can almost be prevented. Our benchtop study showed that the Microcuff consistently outperformed the Portex and the TaperGuard in terms of leakage, especially during zero PEEP mechanical ventilation, laboured breathing, disconnection, and airway suction.34 One disadvantage of the Microcuff is that the material is so thin that even moisture diffuses across, leading to fluid accumulation inside the cuff with resultant blockage of the pilot balloon tube. This can be solved by purging the tube with small amount of air. Other materials being studied are Lycra fibre (Invista, Wichita [KS], US), silicone, and latex. Addition of a subglottic suction drainage (SSD) port removes secretions collected above the cuff (eg TaperGuard Evac, Covidien). In a meta-analysis of 10 RCTs with 2213 patients, SSD significantly reduced the incidence of VAP and early-onset VAP, shortened ventilation duration by 1.55 days, and prolonged time to VAP by 3.90 days.35 Ports of SSD are now available in tracheostomy tubes. One study of such tracheostomy tubes showed that the prevalences of VAP were 56% in the control group and 11% in the suction tracheostomy group.36 The SSD port can be put into intermittent or continuous suction, with similar efficacy of VAP prevention. However, the port could become blocked secondary to suctioned tracheal mucosa in one third of cases, with the possibility of tracheal injury.
 
Of the various coatings of ETT studied, so far, only silver-based coating (eg Agento IC; Bard Medical, Covington [GA], US) has been tested in clinical trials. A meta-analysis identified two high-quality RCTs with a total of 1630 participants, and showed that compared with non-coated ETTs, silver-coated ETTs resulted in a lower incidence of VAP, device-related adverse events, and microbiological burden, with no significant difference in total mortality.37 Recently, an ETT with a newly engineered micro-pattern surface was found to reduce colonisation and biofilm formation of key VAP-associated pathogens in vitro by 99.9% compared with unpatterned control ETTs, including methicillin-resistant S aureus and P aeruginosa biofilm formation.38 Another modification of the ETT is by addition of mucus slurping holes near the distal end of the ETT to keep the inner walls of the ETT free of mucus deposits. Attempts are also being made to develop mechanical means of removing adherent ETT secretions (eg endOclear catheter; endOclear LLC, Petoskey [MI], US), which could even relieve life-threatening ETT obstruction. Another example of mechanical removal is the Mucus Shaver.39
 
Airway pressure
Maintenance of a positive pressure gradient across the ETT cuff is an important factor to prevent secretions collecting above the cuff to trickle down across the cuff-trachea interface due to gravity. This pressure gradient is positive during positive pressure ventilation, but becomes zero during airway disconnection, and periodically negative during laboured inspiration through a narrow ETT or during airway suction. Without positive pressure, leakage around the cuff is significant, especially if the conventional PVC cuff is used and the cuff pressure is less than 30 cm H2O.34 During routine care, disconnections of the airway circuit are frequent, for instance, use of another ventilator for patient transport, change of the heat-and-moisture exchanger, spontaneous breathing trials, and change of ventilator tubing. Such disconnections should be avoided as far as possible. Spontaneous breathing trials should not be unduly prolonged without the intention for resumption of positive pressure ventilation or direct extubation. There is no evidence that the two methods of humidification, namely, using either a heated humidifier or a heat-and-moisture exchanger, affect the VAP rate.
 
Cuff pressure
A polyurethane cuff allows for a much lower sealing pressure than the conventional PVC cuff.34 Periodical manual checking of cuff pressure maintains adequate cuff pressure, but the benefit could be offset if the cuff pressure is accidentally released during checking. To overcome this issue, a continuous cuff pressure maintenance device can be used (Fig). A disposable device called the TRACOE Smart Cuff Manager (TRACOE Medical GmbH, Nieder-Olm, Germany; Fig) can also provide the similar functions of being both a pressure maintenance device (at 30 cm H2O) and a visual indicator of the adequacy of cuff pressure. In the largest study to date on the incidence of VAP comparing a continuous and an intermittent cuff pressure control system on 284 patients, a lower incidence of VAP was found (22.0% vs 11.2%).40
 

Figure. Devices for ventilator-associated pneumonia prevention
(a) Endotracheal tubes, from top to bottom—conventional Portex (polyvinyl chloride material), TaperGuard (with taper-shaped cuff), and Microcuff (with polyurethane cuff); (b) automated cuff pressure maintenance device; (c) the TRACOE Smart Cuff Manager; and (d) TaperGuard Evac—taper-shaped cuff with subglottic secretion drainage port
 
Selective digestive decontamination, selective oropharyngeal decontamination, and probiotic or early antibiotic treatment
Most meta-analyses have shown reductions in VAP with the use of selective digestive decontamination or selective oropharyngeal decontamination, but these interventions are still not being widely implemented because of concerns of emergence of antimicrobial resistance in pathogens. A recent systematic review of 64 studies suggested that such perceived risk of long-term harm could not be justified by the available data, but admitted that the effect on ICU-level antimicrobial resistance rates was understudied.41 Further studies are also required for the use of probiotics regarding efficacy and the risk of colonisation or infection with probiotics. Around 10% to 30% of ventilator-associated tracheobronchitis may progress to VAP, and appropriate antibiotic treatment was independently associated with reduced risk for transition.42 For antibiotic prophylaxis, a prospective cohort study of 129 comatose patients (Glasgow Coma Score ≤8) showed that a single dose of antibiotic within 4 hours of intubation might lower the incidence of early-onset VAP, with no difference in late-onset VAP.43 Further RCTs are needed.
 
Administrative strategies and coordination
Good administrative strategies and coordination are especially important for the implementation of this bundle of strategies all the way from patient care, equipment, infection control, and antibiotic stewardship. Considering the situation in Hong Kong that mechanically ventilated patients are being looked after not only in the ICU, but also in various critical care areas such as high dependency units, respiratory wards, and even general wards, it is imperative that a VAP protocol is in place and diligently adhered to in every such unit, with regular audits to ensure compliance. The existence of written standards for management of mechanically ventilated patients and the availability of VAP surveillance systems were positively associated with compliance with VAP-prevention measures and should be fostered at a policy level.45 Cost-effectiveness data for the whole Ventilator Bundle are scarce and such analysis should be performed in future research. In one Danish cost-effectiveness analysis, implementation of the Ventilator Bundle was found to be potentially cost-effective from the perspective of the hospital, using outcomes of prevention of VAP and prevention of death.46 In view of the necessity for multidisciplinary involvement, VAP surveillance is better coordinated at a higher administrative level. The Hong Kong East Cluster of Hospitals has established a Task Force on Prevention of VAP in Critical Care Areas since 2013. Ventilator-associated pneumonia should also be seriously considered as a key performance indicator in Hong Kong ICUs, as in other advanced countries.
 
Conclusion
Ventilator-associated pneumonia is the commonest, yet mostly preventable, cause of morbidity and mortality in mechanically ventilated patients. Successful control of VAP can save total hospitalisation cost, and is possible by using a multidisciplinary clinical and administrative approach. All units taking care of mechanically ventilated patients should have a VAP-prevention protocol in place, and VAP should be seriously considered to become a key performance indicator in local ICUs.
 
References
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Prevention of ventilator-associated pneumonia

Hong Kong Med J 2015 Feb;21(1):61–8 | Epub 16 Jan 2015
DOI: 10.12809/hkmj144367
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
MEDICAL PRACTICE
Prevention of ventilator-associated pneumonia
Arthur CW Lau, FHKAM (Medicine)1; HM So, FHKAN (Critical Care)1; SL Tang, BSc (Nursing)2; Alwin Yeung, FHKAM (Medicine)2; SM Lam, FHKAM (Medicine)1; WW Yan, FHKAM (Medicine)1; for the Hong Kong East Cluster Task Force on Prevention of Ventilator-associated Pneumonia in Critical Care Areas
1Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
2Cardiac and Intensive Care Unit, Ruttonjee Hospital, Wanchai, Hong Kong
Corresponding author: Dr Arthur CW Lau (laucw3@ha.org.hk)
 Full paper in PDF
Abstract
Ventilator-associated pneumonia is the commonest, yet mostly preventable, infection in mechanically ventilated patients. Successful control of ventilator-associated pneumonia can save hospitalisation cost, and is possible by using a multidisciplinary clinical and administrative approach. The ventilator-associated pneumonia rate should be expressed as the number of ventilator-associated pneumonia days per 1000 ventilator days to take into account the device-utilisation duration for meaningful comparison. Various strategies address the issue, including general infection control measures, body positioning, intubation and mechanical ventilation, oral and gastro-intestinal tract, endotracheal tube, airway pressure, cuff pressure, selective digestive and/or oropharyngeal decontamination, and probiotic or early antibiotic treatment, as well as overall administration at a policy level. The rationale and controversy of these approaches are discussed in this article. The authors suggest that all units treating mechanically ventilated patients should have a ventilator-associated pneumonia prevention protocol in place, and ventilator-associated pneumonia should be seriously considered as a key performance indicator in local intensive care units.
 
 
[Abstract in Chinese]
 
Introduction
Ventilator-associated pneumonia (VAP) is the commonest, yet mostly preventable, infection in mechanically ventilated patients. It contributes to increased morbidity, mortality, and total hospitalisation cost. The estimated overall attributable mortality of VAP was 13%,1 and 52% of VAP was preventable.2 The VAP rate should be expressed as the number of VAP days per 1000 ventilator days to take into account the device-utilisation duration for meaningful comparison. From the reports of the National Health and Safety Network (NHSN) of the US Centers for Disease Control and Prevention (CDC),3 a decreasing trend for VAP has been noted in recent years. For example, from 2002 to 2012, for a mixed medical-surgical intensive care unit (ICU), the rate decreased from 5.1 to 0.9 days per 1000 ventilator days. The highest rates were reported for trauma (from 15.2 to 3.6 days) and burns (from 12.0 to 4.4 days) centres, while neurological and neurosurgical units reported intermediate rates (around 2 to 4 days). European rates are mostly higher, even if the same prevention strategies are used, and some possible reasons are explained below.4
 
Unlike many other conditions for which definitive diagnoses can be made pre-mortem, the gold standard of VAP diagnosis can only be made post-mortem. Clinicians diagnose VAP by radiology, signs and symptoms, with various methods of non-invasive and invasive microbiology sampling (tracheal aspirate, directed or blind broncho-alveolar lavage, protected specimen brush for qualitative and/or quantitative culture), and histology. However, when clinical criteria with microbiology were compared with autopsy findings, both the sensitivity and specificity were approximately 70%.5 Moreover, there has been no convincing evidence that qualitative culture of non-invasive samples, when compared with quantitative culture of invasive samples, produced any significant differences in clinical outcomes.6 In a survey of 27 ICUs of nine European countries, bronchoscopy was performed only in 23.3% of episodes of nosocomial pneumonia.7 Bronchoscopy might be considered more for immunocompromised hosts, both for detection of atypical organisms (if any) and to exclude infection.
 
The definition of VAP is therefore inherently subjective and, hence, contentious. The criteria used, interobserver variability, and subjectivity in chest X-ray interpretation affect the VAP rates by almost two-fold.8 9 All these factors influence findings in preventive trials and hamper comparisons. For surveillance purposes, most institutions use the surveillance definitions of radiology/signs/symptoms to monitor the rates. Commonly used surveillance definitions are those of the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA)10 and the CDC NHSN. The two sets of definitions are similar; the notable difference being that the ATS/IDSA guidelines exclude pneumonias occurring in the first 48 hours after intubation, whereas the CDC NHSN definition includes pneumonias in the first 48 hours; therefore, using the latter definition will result in a higher VAP incidence.
 
In an attempt to overcome the VAP definition’s inherent subjectivity, in 2014, the CDC NHSN started surveillance using the Ventilator-Associated Event protocol,11 under which a ventilator-associated condition (VAC) is defined if there are at least 2 days of stable or decreasing ventilator settings (positive end-expiratory pressure [PEEP] and fraction of inspired oxygen) followed by consistently higher settings for at least 2 days. The sensitivity of the VAC criteria for the detection of VAP was only 25.9%.12 When further microbiological and invasive techniques are employed, a VAC can be further classified into an infection-related VAC, and possible VAP. This modification enables greater objectivity and facilitates automated electronic capture, but captures changes due not only to VAP.
 
Pathophysiology and its implications for prevention strategies
In terms of pathophysiology, VAP is a misnomer because its occurrence is not related to the ventilator per se, but to the presence of the endotracheal tube (ETT). The ETT allows direct access to the lower respiratory tract, impairing the cough reflex and mucociliary clearance, but provides incomplete sealing to secretions above the cuff. Microaspiration (of materials from oropharyngeal cavities, sinuses, gastro-intestinal tract) and biofilm formation are the two most important mechanisms in VAP development, while inhalation, bacteraemia and haematogenous spread play smaller roles. Molecular analysis showed that most VAP patients had the same bacteria with the same sequencing in their oral cavities as in their lungs, and there were even pathogens found in the lungs that could not be detected by conventional culture-based methods.13 Types of bacteria vary with the time of onset; in early-onset VAP, they are commonly Enterobacteriaceae, Candida albicans and Staphylococcus aureus,14 while in late-onset VAP, they are Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli.
 
Evolution of prevention strategies
No single strategy is sufficient to prevent VAP, and several approaches are necessary. The most widely practised and well-known set of strategies is the Ventilator Bundle developed by the Institute for Healthcare Improvement (IHI) in 2001.15 The Ventilator Bundle is often mislabelled as the VAP Bundle, and its original aim was to improve better ventilator care overall, and not VAP alone, although its practice does reduce the VAP rate by 45%.15 The components of the Ventilator Bundle have now become the core of VAP prevention: (1) elevation of the head of bed to between 30° and 45°; (2) daily ‘sedative interruption’ and daily assessment of readiness to be extubated; (3) peptic ulcer disease prophylaxis; (4) deep venous thrombosis prophylaxis (unless contra-indicated); and (5) daily oral care with chlorhexidine. It is practice of the whole ‘bundle’ that decreases VAP, not just the individual components. Some components are not directly related to VAP, namely, deep venous thrombosis and peptic ulcer disease prophylaxis. Although specific data on VAP were not available, in general, the risk of hospital-acquired pneumonia increased when acid-suppressant medications were used. There was a slight trend for reduced VAP with sucralfate compared with a histamine 2 receptor antagonist, and proton pump inhibitors may be related to a higher rate of VAP.16 Therefore, acid-suppressant medications should not be overused. In Hong Kong, the Centre for Health Protection of the Department of Health promulgated a set of recommendations of VAP prevention in 2010.17 In this article, we review the latest literature regarding VAP prevention, and the strategies are summarised in the Table. The rationale and controversy are elaborated in the following discussion.
 

Table. Ventilator-associated pneumonia prevention strategies
Rationale and controversy behind some of the strategies are elaborated in the text. Strategies that have been suggested in the literature, but are not yet widely practised and/or require further research are listed in italics
 
Prevention strategies
Clinical strategies
General
General principles of infection control should be followed. Ventilator tubing should not be changed more frequently than every 1 week unless it is visibly soiled. In an early prospective randomised trial of 447 patients, decreasing the frequency of ventilator circuit changes from 3 times to once per week had no adverse effect on the overall rate of VAP.18 Subsequent trials also showed that circuit change intervals of 7 and 30 days had even lower risks for VAP than 2-day intervals.19 There was evidence that chlorhexidine bathing and hand hygiene compliance reduced global and specific infection rates, including VAP.20 A protocol for microbiological surveillance could be considered to aid in selection of empirical therapy.
 
Body positioning
The semi-recumbent position (30°-45° to the horizontal) is widely practised as one of the components of the IHI Ventilator Bundle, but which was based on only one randomised study with a non–intention-to-treat protocol of 86 mechanically ventilated patients, comparing the supine and semi-recumbent positions, in which the VAP rates were 34% and 8%, respectively.21 Subsequent studies were not able to reproduce these results, and found that a 45° position was difficult to maintain, and the mean angle achievable was only 28°. It has been suggested that avoidance of the supine position was beneficial as, while the semi-recumbent position might reduce gastro-oropharyngeal aspiration, the effect of gravity increases hydrostatic pressure of secretions pooled above the cuff. Recent animal studies found that mucus flow reversed towards the lungs in the semi-recumbent position, but drained out in the horizontal position. In human beings, the trachea/ETT axis is below the horizontal in the lateral Trendelenburg position (ie lying lateral, at 5°-10° below the horizontal). The Gravity VAP-Trial,22 an international randomised controlled trial (RCT) aiming at enrolment of 800 patients, is ongoing to compare the efficacy and safety of the two body positions, namely, the lateral Trendelenburg versus the semi-recumbent positions, in reducing the incidence of VAP. The estimated study completion date is December 2016. Continuous lateral rotation therapy, or kinetic bed therapy, ie lateral rotation of patient to ≥40° on one side (and 80° total arc) using specially designed beds, has been reported to reduce VAP, but was associated with other side-effects such as intolerance to rotation, unplanned extubation, loss of vascular access, and arrhythmias.23
 
Intubation and mechanical ventilation
Non-invasive ventilation (NIV) should be used to avoid the need for invasive ventilation and also shorten its duration. Non-invasive ventilation is particularly beneficial in chronic obstructive pulmonary disease (COPD), immunocompromised patients, and acute pulmonary oedema, and it allows early weaning from invasive ventilation in COPD. Summary estimates from 16 trials of moderate-to-good quality that included predominantly participants with COPD suggested that a weaning strategy that included NIV might reduce mortality and VAP rates without increasing the risk of weaning failure or reintubation.24
 
In a RCT of 128 adult mechanically ventilated patients, daily interruption of sedation resulted in a highly significant reduction in time spent on mechanical ventilation.25 The same authors also showed in the Awakening and Breathing Controlled trial that paired daily spontaneous awakening tests (ie interruption of sedatives) with daily spontaneous breathing tests resulted in better outcomes for mechanically ventilated patients.26 Although there is persistent concern of increased complications with this practice such as self-extubation, subsequent study found that this was not the case. A nurse-implemented sedation protocol has been shown to decrease VAP.27 Our ICU is also performing a nurse-led early weaning trial to aim at shortening the intubation period.
 
Oral and gastro-intestinal tract
Using chlorhexidine mouth rinse or gel as part of oral hygiene care, compared with placebo or usual care, was associated with a reduction in VAP, with a number needed to treat of 15 (95% confidence interval, 10-34).28 There is no consensus for the best practice for oral hygiene care. The optimal concentration of chlorhexidine solution to use is not known. Chlorhexidine has been studied in two strengths: 0.12% and 0.2%, and the US Food and Drug Administration recommends 0.12% oral chlorhexidine for use as mouth rinse. There is no evidence that the following is necessarily better than using chlorhexidine alone: addition of manual or powered tooth brushing, using Listerine (Johnson & Johnson Healthcare Products, New Brunswick [NJ], US), sodium bicarbonate oral rinses, or use of povidone-iodine solution. Povidone-iodine seemed to increase the rate of acute respiratory distress syndrome.29 A local study showed that continuous clearance of oral secretion by the saliva ejector might reduce the rate of VAP, decreasing the duration of mechanical ventilation, and shortening the duration of stay of patients in the ICU.30 Although gastroesophageal aspiration is implicated in VAP development, in an intention-to-treat study of 449 patients on mechanical ventilation, the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of development of VAP (16.7% in the intervention group and 15.8% in the control group), nor were there any significant between-group differences in other ICU-acquired infections, mechanical ventilation duration, ICU stay duration, or mortality.31 There were more VAPs with early enteral feeding, and less with post-pyloric feeding. Further studies are required to confirm this.
 
Endotracheal tube
Novel designs of ETTs target two major mechanisms of VAP, namely, microaspiration and biofilm formation.32 33 Microaspiration is controlled by incorporating changes in cuff shape, material, and addition of a subglottic suction port. Prevention of biofilm formation is managed by addition of coating, surface modification, and removal of biofilm by mechanical means. The conventional ETT cuff (eg Portex; Smiths Medical International Ltd, Ashford, UK) is made of polyvinyl chloride (PVC), of which, when inflated, redundant parts fold on themselves and, because of the thickness of the material (>50 µ), microchannels form through which leakage is possible. By modification of the shape from conical to tapered (eg TaperGuard; Covidien, Irvine [CA], US), better contact of the cuff with the trachea can be achieved, and microchannel formation is reduced. By modification of the material from PVC to the thin 7-µ thick polyurethane (eg Microcuff; Kimberly-Clark Health Care, Roswell [GA], US), microchannel formation can almost be prevented. Our benchtop study showed that the Microcuff consistently outperformed the Portex and the TaperGuard in terms of leakage, especially during zero PEEP mechanical ventilation, laboured breathing, disconnection, and airway suction.34 One disadvantage of the Microcuff is that the material is so thin that even moisture diffuses across, leading to fluid accumulation inside the cuff with resultant blockage of the pilot balloon tube. This can be solved by purging the tube with small amount of air. Other materials being studied are Lycra fibre (Invista, Wichita [KS], US), silicone, and latex. Addition of a subglottic suction drainage (SSD) port removes secretions collected above the cuff (eg TaperGuard Evac, Covidien). In a meta-analysis of 10 RCTs with 2213 patients, SSD significantly reduced the incidence of VAP and early-onset VAP, shortened ventilation duration by 1.55 days, and prolonged time to VAP by 3.90 days.35 Ports of SSD are now available in tracheostomy tubes. One study of such tracheostomy tubes showed that the prevalences of VAP were 56% in the control group and 11% in the suction tracheostomy group.36 The SSD port can be put into intermittent or continuous suction, with similar efficacy of VAP prevention. However, the port could become blocked secondary to suctioned tracheal mucosa in one third of cases, with the possibility of tracheal injury.
 
Of the various coatings of ETT studied, so far, only silver-based coating (eg Agento IC; Bard Medical, Covington [GA], US) has been tested in clinical trials. A meta-analysis identified two high-quality RCTs with a total of 1630 participants, and showed that compared with non-coated ETTs, silver-coated ETTs resulted in a lower incidence of VAP, device-related adverse events, and microbiological burden, with no significant difference in total mortality.37 Recently, an ETT with a newly engineered micro-pattern surface was found to reduce colonisation and biofilm formation of key VAP-associated pathogens in vitro by 99.9% compared with unpatterned control ETTs, including methicillin-resistant S aureus and P aeruginosa biofilm formation.38 Another modification of the ETT is by addition of mucus slurping holes near the distal end of the ETT to keep the inner walls of the ETT free of mucus deposits. Attempts are also being made to develop mechanical means of removing adherent ETT secretions (eg endOclear catheter; endOclear LLC, Petoskey [MI], US), which could even relieve life-threatening ETT obstruction. Another example of mechanical removal is the Mucus Shaver.39
 
Airway pressure
Maintenance of a positive pressure gradient across the ETT cuff is an important factor to prevent secretions collecting above the cuff to trickle down across the cuff-trachea interface due to gravity. This pressure gradient is positive during positive pressure ventilation, but becomes zero during airway disconnection, and periodically negative during laboured inspiration through a narrow ETT or during airway suction. Without positive pressure, leakage around the cuff is significant, especially if the conventional PVC cuff is used and the cuff pressure is less than 30 cm H2O.34 During routine care, disconnections of the airway circuit are frequent, for instance, use of another ventilator for patient transport, change of the heat-and-moisture exchanger, spontaneous breathing trials, and change of ventilator tubing. Such disconnections should be avoided as far as possible. Spontaneous breathing trials should not be unduly prolonged without the intention for resumption of positive pressure ventilation or direct extubation. There is no evidence that the two methods of humidification, namely, using either a heated humidifier or a heat-and-moisture exchanger, affect the VAP rate.
 
Cuff pressure
A polyurethane cuff allows for a much lower sealing pressure than the conventional PVC cuff.34 Periodical manual checking of cuff pressure maintains adequate cuff pressure, but the benefit could be offset if the cuff pressure is accidentally released during checking. To overcome this issue, a continuous cuff pressure maintenance device can be used (Fig). A disposable device called the TRACOE Smart Cuff Manager (TRACOE Medical GmbH, Nieder-Olm, Germany; Fig) can also provide the similar functions of being both a pressure maintenance device (at 30 cm H2O) and a visual indicator of the adequacy of cuff pressure. In the largest study to date on the incidence of VAP comparing a continuous and an intermittent cuff pressure control system on 284 patients, a lower incidence of VAP was found (22.0% vs 11.2%).40
 

Figure. Devices for ventilator-associated pneumonia prevention
(a) Endotracheal tubes, from top to bottom—conventional Portex (polyvinyl chloride material), TaperGuard (with taper-shaped cuff), and Microcuff (with polyurethane cuff); (b) automated cuff pressure maintenance device; (c) the TRACOE Smart Cuff Manager; and (d) TaperGuard Evac—taper-shaped cuff with subglottic secretion drainage port
 
Selective digestive decontamination, selective oropharyngeal decontamination, and probiotic or early antibiotic treatment
Most meta-analyses have shown reductions in VAP with the use of selective digestive decontamination or selective oropharyngeal decontamination, but these interventions are still not being widely implemented because of concerns of emergence of antimicrobial resistance in pathogens. A recent systematic review of 64 studies suggested that such perceived risk of long-term harm could not be justified by the available data, but admitted that the effect on ICU-level antimicrobial resistance rates was understudied.41 Further studies are also required for the use of probiotics regarding efficacy and the risk of colonisation or infection with probiotics. Around 10% to 30% of ventilator-associated tracheobronchitis may progress to VAP, and appropriate antibiotic treatment was independently associated with reduced risk for transition.42 For antibiotic prophylaxis, a prospective cohort study of 129 comatose patients (Glasgow Coma Score ≤8) showed that a single dose of antibiotic within 4 hours of intubation might lower the incidence of early-onset VAP, with no difference in late-onset VAP.43 Further RCTs are needed.
 
Administrative strategies and coordination
Good administrative strategies and coordination are especially important for the implementation of this bundle of strategies all the way from patient care, equipment, infection control, and antibiotic stewardship. Considering the situation in Hong Kong that mechanically ventilated patients are being looked after not only in the ICU, but also in various critical care areas such as high dependency units, respiratory wards, and even general wards, it is imperative that a VAP protocol is in place and diligently adhered to in every such unit, with regular audits to ensure compliance. The existence of written standards for management of mechanically ventilated patients and the availability of VAP surveillance systems were positively associated with compliance with VAP-prevention measures and should be fostered at a policy level.45 Cost-effectiveness data for the whole Ventilator Bundle are scarce and such analysis should be performed in future research. In one Danish cost-effectiveness analysis, implementation of the Ventilator Bundle was found to be potentially cost-effective from the perspective of the hospital, using outcomes of prevention of VAP and prevention of death.46 In view of the necessity for multidisciplinary involvement, VAP surveillance is better coordinated at a higher administrative level. The Hong Kong East Cluster of Hospitals has established a Task Force on Prevention of VAP in Critical Care Areas since 2013. Ventilator-associated pneumonia should also be seriously considered as a key performance indicator in Hong Kong ICUs, as in other advanced countries.
 
Conclusion
Ventilator-associated pneumonia is the commonest, yet mostly preventable, cause of morbidity and mortality in mechanically ventilated patients. Successful control of VAP can save total hospitalisation cost, and is possible by using a multidisciplinary clinical and administrative approach. All units taking care of mechanically ventilated patients should have a VAP-prevention protocol in place, and VAP should be seriously considered to become a key performance indicator in local ICUs.
 
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