There has been a substantial improvement in the outcomes for preterm infants over the past few decades. This improvement reflects the advances made in antenatal, perinatal, and neonatal care. It is crucial to audit and benchmark local data on clinical outcomes with international standards.1 One of the largest neonatal databases, the Vermont Oxford Network (VON), has been collecting and maintaining data on very-low-birth-weight (VLBW) infants and infants who fulfil other eligibility requirements from all over the world since 1989 (website: https://public.vtoxford.org).2 Queen Mary Hospital (QMH) in Hong Kong has been participating in the VON since 1998. Today, QMH is one of almost 1000 centres all over the world participating in the network.3

There is a paucity of data reporting neonatal outcomes for preterm/VLBW local infants. These data are valuable in providing centre- and gestational age (GA)–specific information that can be used for parental counselling about high-risk infants, and facilitate decision making by neonatologists, obstetricians, and parents.

The primary aim of this study was to evaluate the survival rate on discharge and morbidity in preterm/VLBW infants (born between 23+0 and 29+6 weeks and/or birth weight of <1500 g) at a tertiary perinatal centre in Hong Kong over a decade. We also compared the neonatal outcomes with the VON database, aiming to identify key areas for quality improvement in the local community.

The study was conducted at QMH, Hong Kong, which is a tertiary referral perinatal centre with an annual delivery rate of approximately 3500 to 4500. The hospital provides care for preterm infants who are predominantly of Chinese ethnicity. This study was done in accordance with the principles outlined in the Declaration of Helsinki.

Perinatal/neonatal data of all infants born alive at QMH with GA of 23+0 to 29+6 weeks and/or birth weight of <1500 g between 1 January 2005 and 31 December 2014 were collected. These infants were part of the VON database. Infants born outside of QMH were not included in this study. Data were collected retrospectively from the Clinical Management System and Clinical Information System and entered into the VON database by members of the QMH neonatal team.

Definitions for maternal and infant characteristics were provided in the manual “Nightingale Data Definitions” by the VON. In this study, GA was determined as the best obstetric estimate using ultrasonography and/or date of the last menstrual period. If no antenatal data were available, GA was estimated by postnatal neonatal assessment. Intrauterine growth restriction, defined as birth weight of <10th percentile for gender and GA, was determined using growth charts published by Fenton and Kim.4 Maternal obstetric data included data on antenatal steroid use, presence of chorioamnionitis, and mode of delivery. Antenatal steroid therapy was considered to be given if it was provided to the mother during pregnancy at any time prior to delivery. Chorioamnionitis was diagnosed on histopathological findings.

The survival rate was defined as neonates who survived to the time of discharge. Surfactant was used as early rescue therapy for infants with respiratory distress syndrome (RDS), defined by the presence of clinical and radiological features within the first 24 hours of life. Conventional mechanical ventilation use at any time was defined as intermittent positive pressure ventilation through an endotracheal tube with a conventional ventilator at any time after leaving the delivery room. Rescue postnatal steroids were used beyond 2 weeks of age at our centre to facilitate extubation of ventilator-dependent neonates with oxygen requirement of >40% and significant radiological features of persistent lung disease. Data on infants discharged with oxygen were also collected.

Early-onset sepsis was defined as blood or cerebrospinal fluid culture–positive bacterial sepsis occurring within 72 hours of life. Haemodynamically significant patent ductus arteriosus (PDA) on two-dimensional echocardiography was treated with intravenous ibuprofen (only data from 2010 to 2014 were collected as ibuprofen was used as medical treatment for PDA at QMH since 2010) or surgical ligation if medical treatment was unsuccessful or contra-indicated. Severe retinopathy of prematurity was defined as stage III or above according to international classification.5

The major morbidities included severe neurological injury (defined as grade 3 or 4 intraventricular haemorrhage [IVH], or periventricular leukomalacia [PVL]), bronchopulmonary dysplasia (BPD; defined as supplemental oxygen use at a postmenstrual age [PMA] of 36 weeks), pneumothorax (defined as extrapleural air diagnosed by chest radiograph or needle aspiration), necrotising enterocolitis (NEC; defined as stage ≥2 of Bell’s criteria), and late-onset infection (defined as bacterial or fungal infection after day 3 of life).

Data from QMH were compared with those of all neonatal centres in the VON database in a single year in 2013, the latest data available at the time of the study.

The Chi squared test was used to compare the categorical QMH data with that of VON. All P values were two-tailed, and a P value of <0.05 was considered statistically significant.

A total of 449 infants with GA of 23+0 to 29+6 weeks and/or birth weight of 345 g to 1890 g who were born at QMH between 1 January 2005 and 31 December 2014 were included in this study. This study compared survival rate and morbidity of these infants from QMH against 38 754 infants in the VON database in 2013. A significantly greater proportion of infants was delivered at 23 weeks of gestation in the VON group compared with the QMH group, which is contrary to the two groups at 27 and 29 weeks of gestation (P=0.0002). The proportion of infants born at 24 to 26 weeks and 28 weeks was similar for both groups (Table 1).

Overall, 31.0% of the cohort subjects at QMH were multiple births (no difference between the QMH and VON group; P=0.061). Fewer infants in the QMH group were delivered by caesarean section compared with the VON group (58.6% vs 68.2%; P=0.0001). Antenatal steroids were given to 90.4% of mothers in QMH; rate of prenatal steroid use increased with increasing GA, from 73% at 23 weeks, to 82%-89% between 24 and 25 weeks and 90%-96% between 26 and 29 weeks. There was no significant difference in prenatal steroid use between the two groups (P=0.065). Chorioamnionitis was confirmed by placental histology in 24.3% of mothers at QMH, which was significantly more than that in the VON group (17.9%; P=0.0006).

Infants at QMH were predominantly born to Asian (mainly Chinese) mothers whereas the majority of the VON group were of White origin (P<0.001). In QMH, 11.8% of the neonates were born small for GA, similar to the VON group (9.2%, P=0.07) [Table 2].

In QMH, 78% of the infants were being intubated for delivery room resuscitation. At 23 weeks, all infants underwent intubation in the delivery room. Around half of the infants delivered at 29 weeks and 20% at 28 weeks did not need intubation in the delivery room, whereas 83%-97% of infants born between 24 and 27 weeks needed intubation at birth. Compared with infants with GA of ≥26 weeks, the proportion of infants with GA of <26 weeks with Apgar score of ≤3 at 1 minute was higher. Only 16% of the infants were able to achieve a target core temperature of 36.5°C to 37.5°C upon admission to the neonatal intensive care unit (vs 51% in the VON group; P<0.0001).

In QMH, 87% of the 449 infants survived to discharge. Rates of survival increased with increasing GA, from 27% at 23 weeks to 96% at 29 weeks. Overall survival rate of the QMH group was significantly higher than that in the VON group (87% vs 80%; P=0.0006). In QMH, morbidity-free survival rate increased from 0% at 23 weeks to 65% at 29 weeks (Table 3). Survival without major morbidity was similar when comparing the QMH and VON data (40% vs 44%; P=0.105) [Table 3].

In QMH, 86% of infants experienced RDS and 83% needed surfactant therapy. Rate of mechanical ventilation at any time decreased from 100% at 23 weeks to 69% at 29 weeks. There was no significant difference in the incidence of RDS between QMH and VON groups (P=0.808). Significantly more infants in the QMH, however, were given surfactant therapy for RDS and put on mechanical ventilation, compared with VON (83% vs 74%; P=0.0001). The overall frequency of pneumothorax was similar in both groups (P=0.57).

Use of postnatal steroids for BPD was lower in QMH compared with VON (3% vs 14%; P=0.0001) although the QMH rate for BPD was higher (40% vs 34%; P=0.011) and rate of home oxygen use was lower (10% vs 18%; P=0.0001) [Table 4].

In QMH, rates of early- and late-onset sepsis were 3% and 10%, respectively. No significant difference was noted in the incidence of early-onset sepsis between QMH and VON (P=0.792) although QMH had a significantly lower rate of late-onset sepsis (10% vs 16%; P=0.0002) [Table 5].

In QMH, NEC developed in 5% of infants (≥stage 2) and 10% of infants were diagnosed as having severe retinopathy of prematurity (≥stage 3). The overall frequencies of NEC and severe retinopathy of prematurity were similar in the QMH and VON groups (P=0.693 and P=0.100, respectively) [Table 5].

In QMH, PDA was diagnosed in 44% of infants, of whom 36% were treated with ibuprofen (in 2010-2014), and 7% with surgical closure. For management of PDA, QMH had higher rates of ibuprofen treatment than the VON group (36% vs 12%; P=0.0001), whereas the rates of PDA ligation were similar (P=0.936) [Table 5].

In QMH, 7% of sonograms indicated severe IVH (grade 3 or 4); PVL was observed in 3% of infants. There were no significant differences in the incidence of severe IVH or PVL between QMH and VON groups (P=0.070 and P=0.963, respectively; Table 5).

In QMH, the length of hospital stay among survivors decreased with increasing GA, from 19 weeks at GA 23 weeks to 8 weeks at GA of 29 weeks. Similarly, PMA at discharge decreased from 42 weeks for surviving infants born at GA of 23 weeks, to 41 weeks at GA of 24 weeks, 39 to 40 weeks at GA of 25 to 27 weeks, 38 weeks at GA of 28 weeks, and 37 weeks at GA of 29 weeks.

Growth failure (body weight <10th centile for age and sex) was evident in 84% of infants at QMH (vs VON 42%; P=0.0001) upon discharge.

This study reports the mortality and morbidity in the neonatal intensive care unit in QMH over a 10-year period (2005-2014). As the only intensive care centre from China participating in the VON, QMH data provide an important source of local epidemiological information. Data recorded at QMH were compared with the entire VON database. This allows the benchmarking of our neonatal care and clinical outcomes for preterm infants internationally. Local centre–specific information about preterm infants based on GA facilitates parental counselling about high-risk infants and aids decision making.

Our study revealed that the survival rate on discharge of preterm/VLBW infants (≤29+6 weeks and/or birth weight of <1500 g) from QMH was higher than that from VON, with comparable morbidity-free survival. The higher survival rate on discharge from QMH may be partly explained by the higher proportion of 23-week GA infants in the VON (3.3% vs 6.5%; P=0.0002). Advances in perinatal and neonatal care have contributed to improved survival among preterm infants. The goal in the care of these babies should be to improve intact survival without morbidities. Among the key morbidities (severe IVH, PVL, BPD, NEC, pneumothorax, any late infection), BPD was the only clinical entity with a significantly higher incidence at QMH compared with VON (40% vs 34%; P=0.011). Reducing the risk of BPD will have a great impact on morbidity-free survival in our population.6 Of note, BPD is a condition with multifactorial causes and preterm infants are predisposed to lung injury including ventilator-induced lung injury, infection, and inflammation.7 8 9 The higher rate of BPD in QMH compared with VON could be related to the higher prevalence of chorioamnionitis, a known risk factor that inhibits alveolar development.10 As we were ventilating more infants than VON (as evidenced by the higher rate of surfactant use for RDS and use of conventional mechanical ventilation at any time), the risk of ventilator-associated lung injury was increased. Haemodynamically significant PDA was present in a greater proportion of infants at QMH compared with VON (44% vs 39%; P=0.015); PDA increases pulmonary blood flow and causes interstitial oedema. The mechanical ventilator setting and oxygen requirement increase as a result and provide a foundation for BPD. The risk of BPD is also influenced by growth restriction. Growth failure upon discharge was present in 84% of our infants. With poor nutrition in these infants, normal lung growth, maturation, and repair are inhibited. Postnatal steroid was used less frequently in QMH compared with VON (3% vs 14%), and may explain in part the decreased incidence of BPD in VON.

In order to reduce the incidence of BPD in our population, modifiable risk factors need to be reduced. In recent years, our unit has been managing RDS more with continuous positive airway pressure support with subsequent selective surfactant administration—that is, INSURE (INtubation, SURfactant administration, then Extubation)—in order to avoid unnecessary or prolonged ventilation, thereby reducing ventilator-associated lung injury and BPD.11 12 Targeted oxygen saturation has also been used in our centre to minimise oxygen toxicity associated with BPD.13 14

We had a significantly higher proportion of infants who were small for GA upon discharge compared with the VON group (84% vs 42%; P=0.0001). Apart from affecting lung growth and maturation, postnatal growth failure is associated with poor long-term neurocognitive outcome.15 16 One possible explanation for growth failure in our population is the lack of guidelines about preterm infant nutrition (eg timing of feeding initiation and milk volume advancement, prescription of total parenteral nutrition etc). Without such guidelines, a preterm infant’s caloric intake may be suboptimal with consequent compromise of growth. In order to improve the growth of our preterm infants, a standardised nutritional pathway for the VLBW infants has been in use since 2015. Its effect has yet to be evaluated.

A limitation of our study is the lack of adjustment for potential confounding factors. The two groups, QMH and VON, were not directly comparable, for instance, the higher survival rate of preterm infants in our centre could be partly affected by the lower proportion of GA of 23 weeks in our study population.

The majority of neonatal outcomes for preterm/VLBW infants at QMH were comparable with VON, with the exception of BPD and growth failure upon discharge. Regular auditing and benchmarking of clinical outcomes will help ensure quality improvement with implementation of new interventions and projects in our unit.

All authors have disclosed no conflicts of interest.

1. Horbar JD, Plsek PE, Leahy K; NIC/Q 2000. NIC/Q 2000: establishing habits for improvement in neonatal intensive care units. Pediatrics 2003;111(4 Pt 2):e397-410.

2. Horbar JD. The Vermont-Oxford Neonatal Network: integrating research and clinical practice to improve the quality of medical care. Semin Perinatol 1995;19:124-31. Crossref

3. Annual report for infants born in 2014. Center 320. Vermont Oxford Network; 2015.

4. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013;13:59. Crossref

5. An international classification of retinopathy of prematurity. The Committee for the Classification of Retinopathy of Prematurity. Arch Ophthalmol 1984;102:1130-4. Crossref

6. Greenough A, Ahmed N. Perinatal prevention of bronchopulmonary dysplasia. J Perinat Med 2013;41:119-26. Crossref

7. Jobe AH, Ikegami M. Mechanisms initiating lung injury in the preterm. Early Hum Dev 1998;53:81-94. Crossref

8. Kallapur SG, Jobe AH. Contribution of inflammation to lung injury and development. Arch Dis Child Fetal Neonatal Ed 2006;91:F132-5. Crossref

9. Kinsella JP, Greenough A, Abman SH. Bronchopulmonary dysplasia. Lancet 2006;367:1421-31. Crossref

10. Thomas W, Speer CP. Chorioamnionitis is essential in the evolution of bronchopulmonary dysplasia—the case in favour. Paediatr Respir Rev 2014;15:49-52. Crossref

11. Morley CJ, Davis PG, Doyle LW, et el. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008;358:700-8. Crossref

12. Committee on Fetus and Newborn; American Academy of Pediatrics. Respiratory support in preterm infants at birth. Pediatrics 2014;133:171-4. Crossref

13. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics 2000;105:295-310. Crossref

14. Askie LM, Henderson-Smart DJ, Irwig L, Simpson JM. Oxygen-saturation targets and outcomes in extremely preterm infants. N Engl J Med 2003;349:959-67. Crossref

15. Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006;117:1253-61. Crossref

16. Franz AR, Pohlandt F, Bode H, et al. Intrauterine, early neonatal, and postdischarge growth and neurodevelopmental outcome at 5.4 years in extremely preterm infants after intensive neonatal nutritional support. Pediatrics 2009;123:e101-9. Crossref

Varicella zoster virus (VZV) is a member of the Herpesviridae family and is an enveloped double-stranded DNA virus. Primary infection with VZV causes varicella, commonly known as chickenpox. The virus migrates to the sensory ganglia and establishes latency, by which the affected individual becomes asymptomatic. Reactivation of the virus causes herpes zoster (HZ), also known as shingles.1

Infection with VZV is the highest reported notifiable infectious disease in Hong Kong, with 8879 cases reported in 2016.2 A study in 1994 showed that antibodies against VZV were found in more than 90% of children by 8 years of age,3 illustrating that latent infection was highly prevalent. These individuals would be at risk of HZ.

Studies report the lifetime prevalence of HZ to be approximately 10% to 32%.1 4 The University of Hong Kong estimated the prevalence of HZ to be 16.8%.5 The incidence of HZ is positively correlated with age.6 Individuals who are immunocompromised7 or have a chronic disease8 may be at a greater risk of having HZ.

The viral disease HZ presents with a rash with dermatomal distribution, accompanied by vesicular eruption and neuropathic pain.7 A number of complications can result from HZ.9 Post-herpetic neuralgia, a persistent neuropathic pain in the area affected by HZ, can develop particularly in older adults.9 10 Other serious sequelae include HZ ophthalmicus, HZ oticus and bacterial skin infections, all of which adversely affect the quality of life of patients.9 These also place a significant economic burden on the health care system.11 In 2009, a study estimated the cost of treating new HZ cases in the US to be over one billion US dollars each year.12 Active HZ can be treated by antiviral therapy, such as acyclovir.7 13

The vaccine for HZ is a live vaccine approved by the Food and Drug Administration (FDA) of the US in 2006 for the prevention of HZ in immunocompetent patients aged 60 years or above.14 The vaccine has been approved for use in Hong Kong since 2007.13 The FDA approved the use of the vaccine in individuals aged 50 to 59 years in 2011.15 According to the Shingles Prevention Study,16 HZ vaccine lowered the incidence of HZ by 51% and reduced the pain and discomfort of postherpetic neuralgia by 66% when compared with placebo. Similar studies to assess public awareness of HZ and its vaccination were then carried out. The Herpes Zoster Global Awareness Survey from 22 countries17 and a knowledge, attitude, and practice study in South Korea18 were conducted in 2009 and 2015, respectively. Factors promoting or limiting the prevalence of vaccination against HZ were also investigated in the latter study.18

There has been limited research conducted in the Hong Kong population to assess the knowledge of and attitudes towards HZ and the practice of vaccination. This study aimed to explore these areas.

A cross-sectional survey was conducted in 11 clinic sessions during 24 July to 12 August 2015 at the Sai Ying Pun Jockey Club General Outpatient Clinic (GOPC). The GOPC is open to the general public and serves all patients who comprise mainly those with chronic or episodic disease. There were 6330 patients attending the clinic during the study period, of which approximately three quarters aged 50 years or above. These patients in the waiting area of the clinic were selected by convenience sampling to participate in this study. No additional criteria were set to allow for a higher degree of generalisability. Participants were asked to complete a face-to-face questionnaire after giving written informed consent. They were allowed to either complete the questionnaire themselves, or listen to the researcher reading the questions aloud without any additional interpretation, then answer the question verbally. Approval was obtained from the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster and the GOPC prior to commencement of this study.

A questionnaire consisting of 30 items was designed; this included questions on demographics (n=3), medical history (n=4), whether the respondent had heard about HZ (n=1), knowledge of HZ (n=8) and HZ vaccination (n=6); attitudes towards preventing HZ (n=7); and whether the respondent would consider vaccination against HZ (n=1).

To estimate the proportions of participant responses to the questions about knowledge of HZ, for 95% confidence level with an expected true proportion of 50% and 5% margin of error, a sample size of 385 was obtained using the formula:
N=Z²p(1−p)/C²
where N=sample size, Z=Z value, p=population variance, and C=margin of error

To analyse the number of correct responses associated with five demographic factors with an effect size (f²) of 0.15 and a statistical power of 0.8, an a-priori analysis was employed to obtain the sample size of 92 to achieve a 5% margin of error, using G*Power (version 3.1.9.2) and the following formulae19:
N=λ/f² and N=v+u+1
where N=sample size, λ=non-centrality parameter, f²=effect size, v=degree of freedom of the denominator of the F ratio, and u=number of predictors

Statistical analysis was performed with SPSS (Windows version 23.0; IBM Corp, Armonk [NY], US). Demographic data, medical history, respondents’ attitude towards preventing HZ and decision about HZ vaccination were analysed by descriptive statistics. Regarding knowledge of HZ, the number of correct responses out of eight questions was calculated. Multiple linear regression analysis was used to evaluate the association of the number of correct responses with age, gender, educational attainment, history of HZ, and history of chronic diseases. Chi squared tests were applied to evaluate the associations in giving correct response to each question among the same five variables. A P value of <0.05 was considered significant.

A total of 496 persons were invited to participate in the study, of whom 430 agreed which corresponded to a response rate of 87%; 408 valid responses were collected. The sample was not weighted by the population because the male-to-female ratio was similar to that of the population (48:52).20 The demographic data are shown in Table 1. Approximately 40% of respondents did not know their history of chickenpox despite its high prevalence, whereas over 95% had heard of the condition of HZ. Although some respondents did not understand the medical terminology “herpes zoster”, most of them knew the Cantonese colloquial name (生蛇).

Table 2 summarises the responses to the eight questions pertaining to the knowledge of HZ, in which 16 respondents who had never heard of the condition were excluded. Only 29.6% knew that chickenpox and HZ are related. Over half were unsure of the lifetime prevalence of HZ. Immunocompromised state was a well-known risk factor of HZ (84.7%). Over 70% were aware that VZV can reactivate in young ages. Rash, blisters, and neuropathic pain were the most commonly known symptoms of HZ, identified by 85.7% of respondents. Nonetheless 13.3% did not know the symptoms of HZ even though they had heard of the disease.

There is a saying in Chinese society that death will ensue when the rash of HZ circumvents the body. Worryingly, only slightly less than half (48.7%) knew that this was untrue, 18.9% thought the statement was true and the remaining were unsure. Additionally, 69.6% gave the correct response that contacts of HZ patients could not acquire HZ infection directly, and 72.2% knew that HZ was treatable.

Respondents scored a mean (±standard deviation [SD]) of 4.96 (±1.72) correct responses out of eight. Over half of all subjects answered five or six questions correctly.

Of 392 participants who had heard of HZ, 11 respondents who were uncertain of their history of HZ were excluded from the multivariate regression analysis regarding the knowledge of HZ (Table 3a). The number of correct responses was positively correlated with educational attainment (P=0.026) and history of HZ (P=0.038), but negatively correlated with age per year (P<0.001) and male gender (P=0.029).

The results of the Chi squared tests and the corresponding odds ratios are shown in Table 3b. Respondents aged 65 years or above were half as likely as those aged 50-64 years to give correct responses regarding the relationship between chickenpox and HZ (P=0.007), the higher risk of HZ among immunocompromised individuals (P=0.027), and the misconception of death associated with a circumventing rash  (P=0.003). In contrast, participants with higher educational attainment were more likely than those without to give appropriate answers to the latter two questions (P=0.008 and P<0.001, respectively).

Respondents with a history of HZ (P=0.001) and those with higher educational attainment (P=0.028) were more likely to correctly identify the symptoms of HZ.

Of 392 respondents, 148 (37.8%) had heard of the HZ vaccine. Only this subgroup was asked to answer four additional questions about the vaccine (Table 4). One respondent who did not answer the questions was excluded. On average, 1.73 (±1.00) out of four responses were correct.

Nearly half of these respondents (46.9%) correctly identified the target age-group for HZ vaccination and 24.5% thought there was no age limit. Most subjects did not know that vaccination is possible regardless of history of chickenpox or HZ. Around two thirds (68.0%) were aware that the vaccine can significantly reduce the incidence of HZ, but only 49.7% knew that the vaccine is not indicated for treatment of active disease.

Table 5 gives a breakdown of the seven questions about attitudes of respondents to HZ. Over half (52.2%) of 391 respondents (with one participant who did not answer the questions being excluded) thought they had an insufficient understanding of HZ. Almost two thirds were interested in learning more about the disease (66.2%) and its prevention (66.0%). A similar percentage of subjects (64.5%) remarked that there were inadequate channels to learn about prevention of the disease. While 76.7% believed that HZ could affect their health significantly, only 35.0% were worried about getting the disease. Almost one third (30.4%) said that they could afford the HZ vaccine.

Among the subgroup who had heard of the HZ vaccine, 140 (94.6%) replied that their doctor had not mentioned or recommended the vaccine.

This study compared the vaccination rate for HZ with that of influenza and pneumococcus. The latter two vaccines are recommended by the Centre for Health Protection for those aged above 65 years and are included in the Elderly Vaccination Subsidy Scheme.21 Enquiry revealed that 26.9% and 14.3% of 391 respondents had taken the influenza vaccine in the past year and pneumococcal vaccine in the past 5 years, respectively. The figures were much higher than that for HZ vaccination (2.8%).

When asked about the reasons for not having HZ vaccination, approximately half (47.1%) replied that they were unaware of its availability. This was followed by inadequate promotion from doctors and public education (32.4%), the relatively high cost of the vaccine (28.4%), and good self-perceived health (20.3%). Lastly, 17.2% replied that they would consider HZ vaccination in the future.

This study attempted to investigate the knowledge, awareness, and attitudes towards HZ and its vaccination among citizens aged 50 years or above in Hong Kong. The results were informative. They revealed that the general public do not have adequate knowledge about the diseases caused by VZV or awareness regarding the prevention of HZ. This corroborates the general opinion of having an inadequate understanding of the disease. Similar findings have been observed in other countries according to a global survey,17 in which around 67% subjects stated they had little or no knowledge about HZ.

Few respondents in this study knew that chickenpox (varicella zoster) and shingles (HZ) are caused by the same virus. Similar results have been reported by the Public Opinion Programme, the University of Hong Kong (HKUPOP).5 Certain misconception about the disease persists—death from a rash circumventing the body—is still a commonly believed myth among the middle-aged and the elderly people. This study found that the proportions of respondents who were aware of HZ and its vaccination were comparable with those reported by a study in South Korea.18

There was a significant association between educational attainment and the correct responses regarding knowledge of HZ. The positive correlation between a history of HZ and the number of correct responses, however, was only marginally significant. There may be several reasons. Physicians may not have given patients enough information about the disease with consequent persistence of misconceptions. Patients who have had the disease should not be presumed to have a better understanding than those who have not. Moreover, participants might be relatively less aware of HZ due to its less life-interfering nature: only 35% were concerned about getting the disease. Despite the relatively low perceived risk, approximately 77% opined that HZ would have a significant effect on their health, whilst 66% admitted an interest in knowing more about the disease and its prevention. Similar observations have been reported in other countries,17 where 26% predicted that they were likely to have HZ in the future, and 70% indicated that they would ask their doctors about HZ vaccination.

This study found that over 60% of respondents showed disagreement regarding whether there was sufficient accessibility to information about the prevention of HZ. This may contribute to a lack of awareness of the HZ vaccine as the most common reason in our study for non-vaccination. This serves to emphasise the substantial role of doctors in health promotion regarding HZ in future.

According to the study conducted in South Korea,18 although 85.8% of participants would consider vaccination against HZ initially, the figure fell to 59.6% when they took account of the associated cost. On the contrary, HZ vaccination was considered by 17.2% and 36.0% of respondents in this study and in the survey led by HKUPOP,5 respectively, suggesting that HZ vaccination is currently not widely accepted by the community. The situations in Hong Kong and South Korea are similar to some degree since participants expressed some interest in vaccination but associated cost and recommendations from doctors were key influences on a decision about whether or not to vaccinate.

This study could be subject to selection bias because participants were recruited via convenience sampling in one clinic only. The results obtained from this study may have limited generalisability to the GOPC setting and the general population. In future studies, representative samples may be recruited from clinics in various districts and specialties to achieve a more diverse group of people and to further confirm the associations.

Several survey responses were invalidated. For instance, some people claimed that they had not had chickenpox before but had had HZ. This is biologically implausible and may be because most people got chickenpox as an infant or child.1 3 8 This hinders accurate recall unless family member can help. Recall bias is another recognised limitation of this study. Patients with a history of HZ or other chronic diseases usually pay greater attention to their health. Their medical history was subject to self-reported bias since such information could not be retrieved from their medical records.

Another source of bias comes from non-response. Those who refused to participate in the survey (13%) stated that they were unfamiliar with the disease. The results of this study may also be affected by responses that were speculative, as reflected by the observation that some respondents tended to guess rather than answer “uncertain or do not know”. These factors may overvalue the level of understanding of the disease among the general public that could have been improved by a pilot study to design questions with clear wordings and simple language. A pilot study would help identify respondents’ strategies in answering specific questions that required recall, to better evaluate their understanding of HZ, and establish the limits of recollection, with the effect of minimising bias, and enhancing accuracy and response completeness.

Further studies may be initiated to investigate the epidemiology of HZ in Hong Kong, and clarify whether there are significant associations of HZ knowledge with specific socio-demographic groups. Similar studies should also be conducted in younger adults.

Since 2014, the varicella zoster vaccine has been incorporated into the Hong Kong Childhood Immunisation Programme, under which children will be vaccinated against chickenpox at 1 year of age and during their first year of primary education.22 23 While this may offer protection against chickenpox and HZ for future generations, more studies are needed to determine whether it is also cost-effective to offer HZ vaccination to the population aged 50 years or above. This may have notable implications for its acceptance and practice.

Hong Kong people generally have some knowledge about the symptoms of HZ, and are aware that treatment is available for active disease. Nonetheless, there remains unsatisfactory understanding of the disease progression from chickenpox to HZ, and misconceptions about the disease remain prevalent, particularly in the older age-group. The lack of knowledge that HZ is preventable may be pertinent to the relatively low awareness and acceptance of the HZ vaccine compared with that for vaccines for other important diseases such as influenza and pneumococcal pneumonia. Further public education about varicella zoster and HZ, covering both disease features and effective prevention, will help to empower health, rectify misconceptions, and reduce disease burden in Hong Kong.

The authors would like to thank Dr Wendy WS Tsui and Dr Alfred SK Kwong from the Department of Family Medicine and Primary Health Care, Queen Mary Hospital, for their kind permission to conduct the study in the Sai Ying Pun GOPC. We thank Dr LW Tian from the Division of Epidemiology and Biostatistics, School of Public Health, the University of Hong Kong, for his invaluable feedback and support. This study was conducted by medical students as a Health Research Project submitted to the School of Public Health, Li Ka Shing Faculty of Medicine, the University of Hong Kong.

All authors have disclosed no conflicts of interest.

1.Straus SE, Ostrove JM, Inchauspé G, et al. NIH conference. Varicella-zoster virus infections. Biology, natural history, treatment, and prevention. Ann Intern Med 1988;108:221-37. Crossref

2. Number of notifiable infectious diseases by month in 2016. Centre for Health Protection, Department of Health, Hong Kong SAR Government. Available from: http://www.chp.gov.hk/en/data/1/10/26/43/5128.html. Accessed 11 May 2017. 

3. Kangro HO, Osman HK, Lau YL, Heath RB, Yeung CY, Ng MH. Seroprevalence of antibodies to human herpesviruses in England and Hong Kong. J Med Virol 1994;43:91-6. Crossref

4. Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57(RR-5):1-30. 

5. Survey on herpes zoster vaccine. Public Opinion Programme, The University of Hong Kong; 2013. Available from: https://www.hkupop.hku.hk/english/report/prppl/index.html. Accessed 29 Dec 2015. 

6. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis 2007;44 Suppl 1:S1-26. Crossref

7. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med 2002;347:340-6. Crossref

8. Joesoef RM, Harpaz R, Leung J, Bialek SR. Chronic medical conditions as risk factors for herpes zoster. Mayo Clin Proc 2012;87:961-7. Crossref

9. Sampathkumar P, Drage LA, Martin DP. Herpes zoster (shingles) and postherpetic neuralgia. Mayo Clin Proc 2009;84:274-80. Crossref

10. Johnson RW, Wasner G, Saddier P, Baron R. Postherpetic neuralgia: epidemiology, pathophysiology and management. Expert Rev Neurother 2007;7:1581-95. Crossref

11. Panatto D, Bragazzi NL, Rizzitelli E, et al. Evaluation of the economic burden of Herpes Zoster (HZ) infection. Hum Vaccin Immunother 2015;11:245-62. Crossref

12. Yawn BP, Itzler RF, Wollan PC, Pellissier JM, Sy LS, Saddier P. Health care utilization and cost burden of herpes zoster in a community population. Mayo Clin Proc 2009;84:787-94. Crossref

13. Compendium of pharmaceutical products 2015. Drug Office, Department of Health, Hong Kong SAR Government; 2015. 

14. FDA licenses new vaccine to reduce older Americans’ risk of shingles. US Food and Drug Administration; 2006. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108659.htm. Accessed 29 Dec 2015. 

15. FDA approves Zostavax vaccine to prevent shingles in individuals 50 to 59 years of age. US Food and Drug Administration; 2011. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm248390.htm. Accessed 29 Dec 2015.

16. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005;352:2271-84. Crossref

17. Paek E, Johnson R. Public awareness and knowledge of herpes zoster: results of a global survey. Gerontology 2010;56:20-31. Crossref

18. Yang TU, Cheong HJ, Song JY, Noh JY, Kim WJ. Survey on public awareness, attitudes, and barriers for herpes zoster vaccination in South Korea. Hum Vaccin Immunother 2015;11:719-26. Crossref

19. Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009;41:1149-60. Crossref

20. 2011 Population Census summary results. Census and Statistics Department, Hong Kong SAR Government; 2012.

21. Elderly Vaccination Subsidy Scheme. Centre for Health Protection, Department of Health, Hong Kong SAR Government; 2015. Available from: http://www.chp.gov.hk/tc/view_content/21839.html. Accessed 29 Dec 2015. 

22. Chickenpox vaccine recommended for Childhood Immunisation Programme. Information Services Department, Hong Kong SAR Government; 2013. Available from: http://www.info.gov.hk/gia/general/201302/25/P201302250272.htm. Accessed 29 Dec 2015. 

23. Hong Kong Childhood Immunisation Programme. Family Health Service, Department of Health, Hong Kong SAR Government; 2015. Available from: http://www.fhs.gov.hk/english/main_ser/child_health/child_health_recommend.html. Accessed 29 Dec 2015.

With improved living standards and advances in medical treatment, the respective life expectancies of males and females in Hong Kong have increased from 72.3 years and 78.5 years in 1981, to 81.2 years and 86.7 years in 2014.1 Aortic stenosis is one of the most common valvular heart diseases in the ageing population.2 The prevalence of aortic stenosis is up to 4.6% in people older than 75 years.2 After onset of symptoms, including the classic triad of chest pain, heart failure or syncope, patients with severe aortic stenosis are at very high risk of sudden death with 2-year mortality rate of up to 50% if left untreated.3 4 5 Surgical aortic-valve replacement (SAVR) is the gold standard of treatment for patients with symptomatic severe aortic stenosis.3 4 6 7 Many do not receive surgical treatment, however, because of advanced age or multiple co-morbidities.8 Transcatheter aortic valve implantation (TAVI) has recently been developed as an option for these patients who are inoperable or at high risk of SAVR.9 10

Queen Elizabeth Hospital is the first hospital in Hong Kong to perform TAVI since December 2010. This study aimed to assess the efficacy and safety of this procedure in the Hong Kong Chinese population.

In order to introduce TAVI into Hong Kong, a Structural Heart Team comprising cardiologists, cardiac surgeons, cardiac anaesthesiologists, radiologists and cardiac nurses, was formed in early 2010 in Queen Elizabeth Hospital, which is a regional hospital in Hong Kong. All potential patients were assessed and interviewed independently by cardiologists and cardiac surgeons. Clinical assessment of functional status, transthoracic echocardiogram, transoesophageal echocardiogram (TEE), computed tomographic (CT) scan, and conventional angiogram were performed according to the protocol to assess the risks of SAVR and suitability for TAVI. The Structural Heart Team would undertake these investigations to assess whether the risks of the patients were too high for SAVR and if they were suitable for TAVI.

The correct size of the TAVI device was based on the aortic annular dimensions measured by TEE and CT scan. The preferred route of device introduction was via the femoral artery. Based on findings such as the vessel diameter, degree of calcification and tortuosity found on CT imaging, the subclavian artery or direct aortic approach was also a valid alternative. The device was implanted under fluoroscopic guidance and the correct position monitored by fluoroscopy and TEE. Patients underwent transthoracic echocardiogram prior to discharge to assess device function and exclude pericardial effusion. Post-discharge, regular clinic visits, and serial transthoracic echocardiograms were arranged to assess progress and monitor any adverse events. All complications were reported to an independent Safety Monitoring Committee of the hospital.

The first TAVI device was used in December 2010 and was a self-expanding Medtronic CoreValve device (Medtronic, Minneapolis [MN], US) [Fig 1a]. Subsequent to the introduction of its second-generation Evolut R (Medtronic, Minneapolis [MN], US) in 2015 (Fig 1b), it was used in most cases due to its improved design of recapture/repositioning ability and its smaller sheath size (18 Fr vs 14 Fr). We obtained another self-expanding device with recapture/repositioning ability (St Jude Medical Portico; St Jude Medical, Minneapolis [MN], US; Fig 1c), and a balloon-expandable device (Edwards SAPIEN XT; Edwards Lifesciences, Irvine [CA], US) [Figs 1d and 1e] in 2015. This enhanced the ability to treat a broad spectrum of patients with a wide variety of clinical and anatomical challenges. The choice of valve type was made by the Structural Heart Team, based on the anatomy of the native aortic valve, size, and calcification of iliofemoral vessels and need for alternative access.

All patients who underwent TAVI during the study period were entered into the TAVI registry of our hospital. Their baseline characteristics, procedural details, device used, and clinical outcomes were recorded. They attended for regular follow-up in our structural heart disease clinic as well as regular echocardiographic monitoring. Follow-up data were also added to the registry. Any patient who defaulted follow-up was contacted; if they had died, cause of death was retrieved from their electronic patient record of Hospital Authority of Hong Kong.

We retrieved and analysed the data of the TAVI registry. Descriptive statistics were used to report baseline characteristics, procedural results, and clinical outcomes. Analysis was performed using the Microsoft Office Excel (Mac version 2011; Microsoft, Washington, US). The study was performed in accordance with the principles outlined in the Declaration of Helsinki.

From December 2010 to September 2015, a total of 56 patients with symptomatic severe aortic stenosis underwent TAVI. Their baseline characteristics are outlined in Table 1. Their mean (± standard deviation) age was 81.9 ± 4.8 years, and the majority (64.3%) were male. The prevalence of severe co-morbidities was predicted as high, with a mean logistic EuroSCORE of 22.6% ± 13.4% and a mean Society of Thoracic Surgeons score of 7.0 ± 4.4. Several variables were taken into account when calculating these risk scores, such as age, symptoms at presentation, current haemodynamic status, left ventricular systolic function, baseline renal function, New York Heart Association (NYHA) functional class, and presence of other co-morbidities such as peripheral artery disease, pulmonary disease, and cerebrovascular disease. The mean left ventricular ejection fraction (LVEF) was 54.8% ± 12.9%. Most patients had various degrees of heart failure symptoms with 22 (39.3%), 26 (46.4%), and six (10.7%) patients in NYHA class II, III, and IV, respectively. All patients had severe aortic stenosis on echocardiography, defined by standard criteria with a mean aortic valve area of 0.7 cm² ± 0.2 cm² and mean aortic transvalvular pressure gradient of 49.0 mm Hg ± 12.9 mm Hg.

The procedural outcomes are summarised in Table 2. Successful implantation was completed in 98.2% of patients and all procedures were performed under general anaesthesia. Transfemoral access was successful in most cases (54 patients, 96.4%) although one (1.8%) patient was treated via the subclavian approach and one (1.8%) via a direct aortic approach. The most commonly used TAVI device was a 26-mm prosthesis. A second valve was required during the index procedure in nine (16.1%) patients due to suboptimal position of the first device. Most patients (32/56, 57.1%) had no or trivial aortic regurgitation following implantation and 23 (41.1%) had mild aortic regurgitation. None had moderate or severe aortic regurgitation.

The safety endpoints and clinical outcomes are outlined in Table 3. Conversion to open heart surgery after the procedure was necessary in two patients, one of whom had a calcified valvular leaflet that dislodged into the left atrium after device implantation and required open exploration. The other patient had incessant ventricular fibrillation, possibly due to coronary obstruction during the procedure, and required emergent cardiopulmonary bypass and open heart surgery. Pre-procedural CT revealed adequate coronary height (both left coronary and right coronary ostium >16 mm above annular plane) and adequate sinus of Valsalva diameters. The coronary obstruction was thought to be due to dislodged calcified nodules from the aortic valve leaflets. This patient eventually died despite SAVR under extracorporeal membrane oxygenation support, and was the only hospital mortality (1.8%).

Stroke occurred in one (1.8%) patient within 30 days. New conduction abnormalities requiring permanent pacing were present in seven (12.5%) patients. There were major access-related vascular complications in five (8.9%) patients and three (5.4%) had acute kidney injury stage 2 although none required long-term dialysis and no patient had acute kidney injury stage 3 (Table 3).

Most patients (55/56, 98.2%) either had regular follow-up or died. Only one patient who relocated to Mainland China was lost to follow-up, although his doctor keeps us updated regularly about his condition. The longest follow-up period was 5 years. The 30-day mortality rate was 1.8%. The NYHA functional class of patients at baseline and at 30 days is outlined in Figure 2; 92% of patients improved by at least one functional class. The mean LVEF was 57.9% ± 10.9% at 30 days. The mean aortic valve area improved to 1.94 cm² ± 0.37 cm² and mean aortic transvalvular pressure gradient improved to 8.1 mm Hg ± 3.4 mm Hg (Fig 3). These improvements persisted at 6-month and 1-year follow-up assessment. The 6-month all-cause and cardiovascular mortalities were 8.9% and 5.4%, respectively. The 1-year all-cause and cardiovascular mortalities were 12.5% and 7.1%, respectively (Table 3). Causes of 1-year mortality included myocardial infarction, heart failure with cardiogenic shock, liver failure, pneumonia, and sepsis with disseminated intravascular coagulopathy.

This is the first report to describe the clinical experience of TAVI in a major tertiary referral hospital, which is also the first hospital in Hong Kong to introduce this technology and having the largest case volume in Hong Kong up until the end of 2015. The clinical outcomes of our cohort show very promising results.

Since 2010, there have been several landmark clinical trials describing the initial clinical outcome of TAVI in both high-surgical-risk and inoperable patients. The PARTNER 1 was a multicentre prospective randomised controlled trial to investigate the balloon-expandable Edwards SAPIEN valve (Edwards Lifesciences). PARTNER 1B arm randomised inoperable patients to TAVI or best medical treatment and showed a 20% absolute reduction in mortality rate at 1 year with TAVI.9 The PARTNER 1A arm randomised patients with high surgical risk to either TAVI or SAVR and TAVI was shown to be non-inferior to SAVR in terms of mortality rate at 1 year (24% vs 26.8%; P=0.44).11 The US CoreValve pivotal trial randomised patients with high surgical risk to either TAVI using the self-expanding CoreValve or SAVR and demonstrated a significant reduction in mortality rate at 1 year in the TAVI group compared with the SAVR group (14.2% vs 19.1%; P=0.04).10 The relatively high 1-year mortality rate in those clinical trials is mainly due to their baseline multiple co-morbidities and the advanced age (mean age, 80 years) of patients. The 1-year mortality rate of 12.5% in our cohort compares well with these landmark trials. The risk profile of our patient group is nonetheless not lower (logistic EuroSCORE of 22% in our group vs 18% in CoreValve pivotal trial). This high baseline risk factor accounts for the high 1-year mortality rate although a significant proportion was related to non-cardiac causes (3 out of 7). The current view is to avoid treating the patients with too high risk and who will not benefit from this high-risk procedure. A reasonable 1-year expected survival is also a prerequisite.12 13

Other complication rates of our cohort also compared well with the landmark trials. Significant aortic regurgitation secondary to paravalvular leak (PVL) is a unique problem not uncommonly encountered following TAVI in contrast to patients who undergo SAVR in whom there is usually no residual leakage.14 15 One study showed that even mild PVL after TAVI is associated with higher mortality rate at 2 years.16 Treatment of significant PVL is by post-dilation, putting in another valve (so called ‘valve in valve’) or using a vascular plug. The rate of moderate or severe PVL in both the PARTNER 1B9 and US CoreValve pivotal trial10 was approximately 7%. No moderate or severe PVL was noted in our study due to the high rate of using two valves (‘valve in valve’) in 16% of our cohort compared with the reported 4% rate in the US CoreValve pivotal trial. With increasing experience and availability of a repositionable device, however, progressively fewer cases required more than one valve.

Some of the complications after TAVI are more disabling than others, such as stroke. The major stroke rate in both the PARTNER and US CoreValve pivotal trial was approximately 5%.9 10 Major stroke rate in one meta-analysis of more than 10 000 patients was 3.3%.17 Clinical stroke occurred in only one (1.8%) patient in our cohort. This is probably because of our small sample size, as well as the random and unpredictable nature of this complication. More cases of stroke would be expected if more patients were treated. The latest clinical trial using next-generation TAVI devices resulted in a much lower rate of stroke after TAVI (0.9% at 30 days and 2.4% at 1 year for high-risk patients).18 The aetiology of stroke after TAVI is multifactorial and includes embolism of valvular material during balloon valvuloplasty, device manipulation across an atheromatous aorta, and atrial fibrillation.19 Multiple strategies to reduce periprocedural stroke have been attempted including direct stenting, avoidance of pre- or post-dilation, use of cerebral protection devices and different antithrombotic regimens.20 21 Currently, randomised trials are underway to determine whether cerebral protection devices are useful in reducing periprocedural stroke.22

Conduction abnormality is another common event following TAVI. The reported rate of permanent pacemaker implantation to treat high-grade heart block varies from 10% to 30% and it depends very much on type and implantation depth of the device.23 24 25 26 The rate reported in the US CoreValve pivotal trial was 20% at 1 month and 22% at 1 year.10 The permanent pacemaker implantation rate in our cohort was 12.5% with the majority of our cases having a self-expandable valve. In our cohort, most pacemakers were implanted earlier on in the study period when we were more cautious about treating post-procedural conduction abnormalities.

Major vascular complications occurred in approximately 6% of patients in the US CoreValve pivotal trial and 11% in PARTNER 1 trial.9 10 Rates of major vascular complications in different observational and randomised trials range from 5% to 17%.27 The lower rate in the US CoreValve pivotal trial can be explained by the smaller size of the introducer sheath for CoreValve (18 Fr) compared with the much bigger 22-24 Fr sheath for the first-generation SAPIEN device in the PARTNER 1 trial.9 For the same reason and the relative smaller size of peripheral vessels in an Asian population, we would expect a higher rate of vascular complications. Indeed, the major vascular complication rate in our cohort was 8.9%, which is compatible with the worldwide standard. This is the result of our comprehensive use of CT angiogram for all cases from the beginning of the cohort to delineate the size of the peripheral vessels and better plan of procedural strategies.

Overall, the success of the procedure depends not only on the technical requirement in a very high-risk group of patients but also a comprehensive, multidisciplinary team approach. This ‘heart team’ approach is the cornerstone of the rapidly developing field of structural heart intervention and preferred strategies in dealing with anticipated complications.27

After the success in treating high-risk patients with aortic stenosis, the recently published PARTNER 2 trial evaluated TAVI and SAVR in patients with intermediate surgical risk. It randomised patients with intermediate surgical risk to either TAVI or SAVR; TAVI was non-inferior to SAVR in terms of all-cause mortality and disabling stroke at 2 years (19.3% in TAVI group vs 21.1% in SAVR group; P=0.25).28 Another major trial testing TAVI in intermediate-risk patients, the SURTAVI Trial (ClinicalTrials.gov number NCT01586910), has completed patient recruitment and the results will be available very soon.

The limitations of the current study include the relatively small sample size and a single-centre early experience. The technology is evolving and lower- or intermediate-risk patients are being treated in various clinical trials. With an increasing awareness of the disease and referrals from around the territory, the population being treated is expected to increase in the coming years.

The technique TAVI has been developed as an alternative treatment for patients with symptomatic severe aortic stenosis who are deemed inoperable or high risk for surgery. It has been proven in major randomised controlled trials to have an acceptable complication rate and durability in the medium term. Our results are very promising and comparable with those of major clinical trials. Long-term clinical outcomes should be diligently monitored.

All authors have disclosed no conflicts of interest.

1. Women and men in Hong Kong—key statistics. 2015 Edition. Available from: http://www.statistics.gov.hk/pub/B11303032015AN15B0100.pdf. Accessed 26 Jun 2016.

2. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005-11. Crossref

3. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57-185. Crossref

4. Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012): the joint task force on the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42:S1-44. Crossref

5. Turina J, Hess O, Sepulcri F, Krayenbuehl HP. Spontaneous course of aortic valve disease. Eur Heart J 1987;8:471-83. Crossref

6. Kvidal P, Bergström R, Hörte LG, Ståhle E. Observed and relative survival after aortic valve replacement. J Am Coll Cardiol 2000;35:747-56. Crossref

7. Kvidal P, Bergström R, Malm T, Ståhle E. Long-term follow-up of morbidity and mortality after aortic valve replacement with a mechanical valve prosthesis. Eur Heart J 2000;21:1099-111. Crossref

8. Bouma BJ, van Den Brink RB, van der Meulen JH, et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-8. Crossref

9. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597-607. Crossref

10. Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med 2014;370:1790-8. Crossref

11. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98. Crossref

12. Miller DC. TAVI has a limited role in the treatment of AS. American Association of Thoracic Surgery 2012 Annual Meeting; 2012 Apr 29; San Francisco, United States.

13. Gilard M, Eltchaninoff H, Lung B, et al. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med 2012;366;1705-15. Crossref

14. Lerakis S, Hayek SS, Douglas PS. Paravalvular aortic leak after transcatheter aortic valve replacement: current knowledge. Circulation 2013;127:397-407. Crossref

15. Généreux P, Head SJ, Hahn R, et al. Paravalvular leak after transcatheter aortic valve replacement: the new Achilles’ heel? A comprehensive review of the literature. J Am Coll Cardiol 2013;61:1125-36. Crossref

16. Kodali SK, Williams MR, Smith CR, et al. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med 2012;366:1686-95. Crossref

17. Eggebrecht H, Schmermund A, Voigtländer T, Kahlert P, Erbel R, Mehta RH. Risk of stroke after transcatheter aortic valve implantation (TAVI): a meta-analysis of 10,037 published patients. EuroIntervention 2012;8:129-38. Crossref

18. Herrmann HC. SAPIEN 3: Evaluation of a balloon-expandable transcatheter aortic valve in high-risk and inoperable patients with aortic stenosis with aortic TCT. San Francisco 2015 Oct 15.

19. Mastoris I, Schoos MM, Dangas GD, Mehran R. Stroke after transcatheter aortic valve replacement: incidence, risk factors, prognosis, and preventive strategies. Clin Cardiol 2014;37:756-64. Crossref

20. Ghanem A, Naderi AS, Frerker C, Nickenig G, Kuck KH. Mechanisms and prevention of TAVI-related cerebrovascular events. Curr Pharm Des 2016;22:1879-87. Crossref

21. Schmidt T, Schlüter M, Alessandrini H, et al. Histology of debris captured by a cerebral protection system during transcatheter valve-in-valve implantation. Heart 2016;102:1573-80. Crossref

22. Kodali S. Cerebral embolic protection devices: Sentinel dual filter device. Update of US Pivotal Clinical Trial. TCT 2015; 2015 Oct 11-15; San Francisco, United States.

23. Webb JG, Altwegg L, Boone RH, et al. Transcatheter aortic valve implantation: impact on clinical and valve-related outcomes. Circulation 2009;119:3009-16. Crossref

24. Piazza N, Grube E, Gerckens U, et al. Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval. EuroIntervention 2008;4:242-9. Crossref

25. Jilaihawi H, Chin D, Vasa-Nicotera M, et al. Predictors for permanent pacemaker requirement after transcatheter aortic valve implantation with the CoreValve bioprosthesis. Am Heart J 2009;157:860-6. Crossref

26. Kanmanthareddy A, Buddam A, Sharma S, et al. Complete heart block after transcatheter aortic valve implantation: a meta-analysis. Circulation 2014;130:A15832.

27. Toggweiler S, Leipsic J, Binder RK, et al. Management of vascular access in transcatheter aortic valve replacement: part 2: Vascular complications. JACC Cardiovasc Interv 2013;6:767-76. Crossref

28. Leon MB, Smith CR, Mack M, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016;374:1609-20. Crossref

Total hip arthroplasty (THA) is considered one of the most effective therapies for a variety of hip joint diseases. The cemented THA has been successfully performed since the 1960s but has been widely criticised in several postoperative follow-up studies for its later loosening.1 2 During the 1970s, cementless THA with different principles of fixation and various new materials was introduced. This prosthesis had good biocompatibility and its specific surface structure could achieve secondary fixation to bone that could avoid later loosening.3

The Zweymüller-Plus system (Smith & Nephew Orthopaedics AG; Rotkreuz, Switzerland), a kind of cementless THA that comprises the SL-Plus stem and Bicon-Plus cup, was introduced in 1993 as a successor to the Alloclassic system.4 It has been widely used for primary THA. Because of aseptic loosening due to polyethylene wear, alternative bearings were introduced.5 6 These alternative bearings included metal-on-metal, ceramic-on-ceramic, and ceramic-on-polyethylene articulation.7 8 The Zweymüller-Plus THA system with the ceramic-on-polyethylene bearing has been reported to have superior survival and durability at 10 years’ follow-up than other bearings.9 Additionally, in the mid-1990s in mainland China, the Zweymüller-Plus THA with ceramic-on-polyethylene bearing was the most common type of hip prosthesis. We report the results after a minimum of 12.4 years of an independent series using Zweymüller-Plus THA with ceramic-on-polyethylene bearing in a historical follow-up study.

Between October 1994 and April 2000, a total of 207 Zweymüller-Plus total hip replacements (Smith & Nephew Orthopaedics AG) with ceramic-on-polyethylene bearings were performed in 185 consecutive patients at Peking University People’s Hospital in China. The institutional review board of Peking University People’s Hospital approved this study, with the requirement of patient informed consent waived because of its retrospective nature.

Data on the patients including gender, age, hip distribution, initial diagnosis, complications, reason for revisions, and clinical outcome were obtained from the hospital database and retrospectively reviewed. Basic demographic data and indications for implantation of the prosthesis were collected.

The acetabular component was the Bicon-Plus cup (Smith & Nephew Orthopaedics AG), a biconical threaded cup made of hot-forged pure titanium (Fig 1). The Bicon-Plus cup has a microroughness of 4-6 µm and no coating on the microporous outer surface. The polyethylene inlay of the Bicon-Plus cup is made of conventional ultra-high-molecular-weight polyethylene that has been sterilised by gamma irradiation.

The femoral component was the SL-Plus stem, a cementless, rectangular, dual-tapered straight stem made of a wrought Ti-6Al-7Nb alloy with a microporous surface roughness of 4-6 µm (Smith & Nephew Orthopaedics AG; Rotkreuz, Switzerland; Fig 1). The femoral head with a diameter of 28 mm was made of high-grade alumina ceramics (the third-generation alumina ceramics). The edges of the SL-Plus stem were rounded to reduce the occurrence of distal femoral cortical thickening. The combination of polyethylene inlay with the 28-mm diameter ceramic femoral head constituted the ceramic-on-polyethylene bearing surface.

All THAs were performed by the senior surgeon (BL Kou) through a modified Hardinge direct lateral approach. The mean (± standard deviation) desired acetabular position was 45° ± 10° of abduction and 15° ± 10° of anteversion, the femoral position was 5°-10° of anteversion: both were evaluated by postoperative X-ray. In order to facilitate optimal insertion of the bone, the bone had to be shaped to the Bicon-Plus cup by matched directional devices. All patients received prophylactic antibiotics prior to surgery and subcutaneous low-molecular-weight heparin calcium for prophylaxis against thrombosis for 2 weeks postoperatively. Patients were discharged after a mean of 5 days after surgery. Mobilisation with full weight-bearing was encouraged the day after surgery. At postoperative 6 weeks, rehabilitation exercises were commenced and the hip joint mobilised.

The Harris Hip score (HHS),10 which is a disease-specific health-related quality-of-life instrument and widely used to evaluate physical function and pain relief in patients with various hip diseases, was used to clinically evaluate patients preoperatively, postoperatively, and at the most recent follow-up. Anteroposterior and lateral supine radiographs of the hip and femur were analysed for radiolucencies, osteolysis, and migration of the components, and compared with radiographs taken 2 weeks after surgery. Osteolytic areas and radiolucencies adjacent to the SL-Plus and Bicon-Plus were evaluated using the zones described by Gruen et al11 and DeLee and Charnley,12 respectively. Osteolysis was described as a sharply demarcated radiolucent space with rounded or scalloped appearance that was >2 mm wide.13 The migration of the cup was defined as movement of ≥3 mm in a horizontal or vertical direction and stem migration was defined as a change in position of >4 mm relative to the mid-lesser trochanter. Femoral implant stability was assessed by the radiographs according to the criteria of Engh et al,14 as stable with osseointegration or fibrous tissue ingrowth, or as unstable. Heterotopic ossification was evaluated using the criteria described by Brooker et al.15 Liner wear was determined by subtracting the thickness of the polyethylene on the first radiograph of the hip postoperatively in the standing position from the last available control radiograph corrected for enlargement and determined in relation to the diameter of the head component.15 We only included cases of annual liner wear of >0.1 mm/year due to the lack of precision of these measurements.

Demographic and X-ray variables were assessed with descriptive statistics. Kaplan-Meier survival analyses16 with 95% confidence intervals (CI) were used to determine the survival rate with the use of several end-points: revision for any reason or revision for aseptic loosening for each component of the THA system. All patients were included in the Kaplan-Meier analysis. Patients who died were censored at their date of death and patients who were lost to follow-up were censored at the date of last assessment. Continuous variables of HHS were compared using a two-sided Student’s t test. The Statistical Package for the Social Sciences (Windows version 19.0; IBM Corp, Armonk [NY], United States) was used to analyse the collected data. A P value of <0.05 was considered significant.

Demographic data of patients and indications for implantation of the prosthesis are listed in Table 1. There were 95 women and 90 men, and the mean age (± standard deviation) at the time of the index surgery was 57.8 ± 13.8 years (range, 16-72 years). Overall, 161 patients (183 hips) underwent primary THA only and the most common indication was ischaemic femoral head necrosis (58 hips). Other indications included ankylosing spondylitis and femoral neck fracture (Table 1). Another 24 hips underwent surgery for revision (15 for aseptic loosening, 6 for migration of the acetabular component, and 3 for deep infection) and the mean time between the primary THA and this revision was 3.2 years.

As shown in Figure 2, two patients (two hips) died without a revision prior to death for reasons unrelated to the surgery; the time between operation and death were 4.2 years and 5.1 years, respectively. Twenty-five patients (28 hips) were lost to follow-up. The main cause for patients lost to follow-up was change of residence and/or phone number. Revision was performed in two patients (two hips). A total of 156 patients (175 hips) were available for clinical and radiological evaluation, with a mean time between operation and final evaluation of 14.1 years (range, 12.4-16.5 years).

There were two (0.97%) revisions in the whole series of 207 hips. An example of good results at 16.5 years of follow-up is shown in Figure 3. The stem alone had not been revised in any hip. The Bicon-Plus cup alone had been revised in two hips, both for aseptic loosening. Radiographs of aseptic loosening of acetabular components before and after revision at 10.7 years until the latest follow-up are shown in Figure 4. Both revision surgeries were performed on men after 10.7 and 16.5 years postoperatively. No perioperative complications were observed after revision and the HHS were 92 and 96 post-revision, respectively.

There were no other re-operations at the time of most recent follow-up. Two hips (two patients), however, showed excessive polyethylene wear of the liner although both were asymptomatic. Liner exchange was recommended but both patients refused. They were closely monitored for observation of wear progression and osteolysis development.

Non-progressive radiolucent lines around the femoral component (<1 mm) were found in seven (4.0%) of 175 stems, all limited to the proximal femur (Gruen zone 7). Comparison of early and late postoperative radiographs revealed no signs of osteolysis in the distal femoral zones or subsidence of femoral prosthesis of >1 mm. Intramedullary ossification was found in five (2.9%) of 175 stems. There was no excessive liner wear in the remaining 173 hips.

Non-progressive radiolucent lines of <2 mm were found around the Bicon-Plus cup in three (1.7%) of 175 hips in DeLee-Charnley zone III. No extensive peri-acetabular osteolysis radiographically of >2 mm was observed in any hip. Heterotopic ossification was found in 23 (13.1%) of 175 hips with various degrees according to the criteria by Brooker et al.15 Among the 23 hips, 11 hips were considered Brooker grade I, eight hips were Brooker grade II, and the remaining four were Brooker grade III.

A total of 156 patients (175 hips) were available for clinical and radiological evaluation. The mean HHS for the 175 hips increased significantly from 39.3 ± 3.8 preoperatively to 94.1 ± 2.5 postoperatively at a mean follow-up of 14.1 years (P<0.05).

Intra-operative complications including pulmonary and deep vein thrombosis were not observed in any patient. Surgical complications including calcar cracks, femoral fracture, deep infection, and dislocation did not occur in any patient. In addition, no medical complications were observed in cardiac, urinary, or psychiatric aspects.

The Kaplan-Meier survival analysis, with the end-point being revision of any component for any reason, estimated the 14.1-year (minimum follow-up of 12.4 years) survival rate at 99.03% (95% CI, 95%-100%). Since the reason for both revisions was aseptic loosening of the Bicon-cup, the survival rate at a minimum of 12.4 years of follow-up with removal of any component for aseptic loosening and the probability of survival of acetabular components with revision for any reason were both 99.03% (95% CI, 95%-100%). In addition, the survival rate of the SL-Plus stem with revision for any reason was 100%. The worst case survival of this ceramic-on-polyethylene THA, when taking the two pending revision cases into account, with removal of any component for any cause as the end-point was 98.07% (95% CI, 84%-100%).

Medium- to long-term follow-up studies are required to evaluate the effectiveness of orthopaedic implants in patients with various hip diseases. The present study was conducted in a group of 207 hips after a mean follow-up of 14.1 years to evaluate the medium-term effectiveness of the Zweymüller-Plus THA with ceramic-on-polyethylene bearings.

The main finding of this study was the relatively high survival rate of both implant components (100% for the femoral component and 99.0% for the acetabular component). The worst survival when taking the pending revisions into account was still 98.1%. Although methodological differences and dissimilar implant designs can limit comparison of different THAs, the survival rate of the stem and cup in our series is comparable or even higher than previous descriptions for other THAs, especially the Alloclassic system (Zimmer, Winterthur, Switzerland). Bonnomet et al17 reported that the 10-year survival with stem revision for any reason as the end-point of the Alloclassic-SL grit-blasted titanium stem in primary THA was 99.2%. For Alloclassic THAs with/without hydroxyapatite coating on the fixation of a cementless femoral stem, the 15-year survival of the stem for the event (revision for any reason) was 98.1%.18 For another cementless Zweymüller-Alloclassic system, a survival rate of 98% for the stem and 85% for the cup at 15 years with revision for any reason as the end-point has been reported.19 Femoral survival and acetabular survival with the Alloclassic system are shown in Table 2.17 18 19 20 Consistent with our results, long survival of Zweymüller-Plus components with ceramic-on-polyethylene bearings has been reported previously. A retrospective analysis of results after a mean follow-up of 11 years by Korovessis et al21 showed that the rate of survival was 100% for the Bicon-Plus and 98% for the SL-Plus. As a successor of the Alloclassic system, there are several improvements in the Zweymüller-Plus system. The sharp edges of the Alloclassic stem have been rounded in the SL-Plus stem and this may avoid distal stress concentration, cortical thickening, and subsequent thigh pain.22 23 Moreover the Bicon-Plus cup has inherent advantages over the Alloclassic cup when implanted in hips with deficient or deformed acetabulum since positioning of the biconical threaded cup does not require removal of so much spherical acetabular bone.21 All these features make the Zweymüller-Plus system hypothetically practical and stable.

The type of bearing couple may be the major limitation for longevity of well-fixed hip implants.24 A previous comparison of four bearings revealed that ceramic-on-polyethylene bearing couple achieved the best results for revision for any reason (98.1%).9 Similar to a previous description, the survival of the ceramic-on-polyethylene bearings in the Zweymüller-Plus system was relatively high in our study (99.0%). Ceramic bearings have several advantages over other bearings such as a low coefficient of friction, low wear rates, and less biologically reactive debris.25 26 27 They also have several drawbacks such as susceptibility to fracture,28 although they avoid the adverse qualities associated with polyethylene.9 In our study, there were no revisions due to ceramic fracture.

The problems with polyethylene wear and osteolysis are often considered to compromise the long-term survival of implants. In an analysis based on the Norwegian Arthroplasty Register, Hallan et al29 showed that high revision rates for polyethylene wear and osteolysis lead to an obvious decline in survival after 10 years. There is an improvement in osteolysis of the Alloclassic cup compared with cemented polyethylene cups with ceramic-on-polyethylene bearing surfaces, since radiolucent lines and osteolysis in the Alloclassic cup were evident in 0% to 6% of cases after 9.3 to 12 years19 30 while osteolysis around cemented cups was present in 11% at 11.2 years.31 In our study, radiolucent lines and osteolysis in the Bicon-Plus cups was 1.7% at 14.1 years, which is lower than that in previous reports.19 30 Additionally, the osteolysis and radiolucent lines were all located proximally and did not extend around the distal part of the stem. The osteolysis rate (4%) of the SL-Plus stem at 14.1 years was also lower.

Our findings were tempered by the limitations inherent in our study design. The retrospective design and the high number of patients lost to follow-up might lead to excessively optimistic results. In addition, patients who died or who were lost to follow-up were not included in the clinical analysis although their data were included in the survival calculation to minimise the bias. Despite these limitations, our study with a relatively long follow-up and a large number of patients provides evidence of the clinical durability of the ceramic-on-polyethylene Zweymüller-Plus THA.

Our results indicate that the Zweymüller-Plus system with ceramic-on-polyethylene bearing showed a long survival and durability at a mean follow-up of 14.1 years, along with an improvement in osteolysis of both the SL-Plus stem and Bicon-Plus cup. Longer follow-up is still necessary to monitor the long-term outcomes for the Zweymüller-Plus system with ceramic-on-polyethylene.

The authors declare that they have no competing interests.

1. Schulte KR, Callaghan JJ, Kelley SS, Johnston RC. The outcome of Charnley total hip arthroplasty with cement after a minimum twenty-year follow-up. The results of one surgeon. J Bone Joint Surg Am 1993;75:961-75. Crossref

2. Severt R, Wood R, Cracchiolo A 3rd, Amstutz HC. Long-term follow-up of cemented total hip arthroplasty in rheumatoid arthritis. Clin Orthop Relat Res 1991;(265):137-45. Crossref

3. Hailer NP, Garellick G, Kärrholm J. Uncemented and cemented primary total hip arthroplasty in the Swedish Hip Arthroplasty Register. Acta Orthop 2010;81:34-41. Crossref

4. Repantis T, Vitsas V, Korovessis P. Poor mid-term survival of the low-carbide metal-on-metal Zweymüller-Plus total hip arthroplasty system: a concise follow-up, at a minimum of ten years, of a previous report. J Bone Joint Surg Am 2013;95:e331-4. Crossref

5. Goldring SR, Clark CR, Wright TM. The problem in total joint arthroplasty: aseptic loosening. J Bone Joint Surg Am 1993;75:799-801. Crossref

6. Harris WH. Wear and periprosthetic osteolysis: the problem. Clin Orthop Relat Res 2001;(393):66-70. Crossref

7. Petsatodis GE, Papadopoulos PP, Papavasiliou KA, Hatzokos IG, Agathangelidis FG, Christodoulou AG. Primary cementless total hip arthroplasty with an alumina ceramic-on-ceramic bearing: results after a minimum of twenty years of follow-up. J Bone Joint Surg Am 2010;92:639-44. Crossref

8. Korovessis P, Petsinis G, Repanti M, Repantis T. Metallosis after contemporary metal-on-metal total hip arthroplasty. Five to nine-year follow-up. J Bone Joint Surg Am 2006;88:1183-91. Crossref

9. Topolovec M, Milošev I. A comparative study of four bearing couples of the same acetabular and femoral component: a mean follow-up of 11.5 years. J Arthroplasty 2014;29:176-80. Crossref

10. Davis KE, Ritter MA, Berend ME, Meding JB. The importance of range of motion after total hip arthroplasty. Clin Ortho Relat Res 2007;465:180-4.

11. Gruen TA, McNeice GM, Amstutz HC. “Modes of failure” of cemented stem-type femoral components: a radiographic analysis of loosening. Clin Ortho Relat Res 1979;(141):17-27.

12. DeLee JG, Charnley J. Radiological demarcation of cemented sockets in total hip replacement. Clin Ortho Relat Res 1976;(121):20-32.

13. Zicat B, Engh CA, Gokcen E. Patterns of osteolysis around total hip components inserted with and without cement. J Bone Joint Surg Am 1995;77:432-9. Crossref

14. Engh CA, Bobyn JD, Glassman AH. Porous-coated hip replacement. The factors governing bone ingrowth, stress shielding, and clinical results. J Bone Joint Surg Br 1987;69:45-55.

15. Brooker AF, Bowerman JW, Robinson RA, Riley LH Jr. Ectopic ossification following total hip replacement. Incidence and a method of classification. J Bone Joint Surg Am 1973;55:1629-32. Crossref

16. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81. Crossref

17. Bonnomet F, Delaunay C, Simon P, et al. Straight femoral taper in cementless primary total hip replacement in less than 65 year-old patients: multicenter study of 115 consecutive implantations at mean 8.2 year follow-up [in French]. Rev Chir Orthop Reparatrice Appar Mot 2001;87:802-14.

18. Delaunay C. Effect of hydroxyapatite coating on the radio-clinical results of a grit-blasted titanium alloy femoral taper. A case-control study of 198 cementless primary total hip arthroplasty with the Alloclassic system. Orthop Traumatol Surg Res 2014;100:739-44. Crossref

19. Grübl A, Chiari C, Giurea A, et al. Cementless total hip arthroplasty with the rectangular titanium Zweymüller stem. A concise follow-up, at a minimum of fifteen years, of a previous report. J Bone Joint Surg Am 2006;88:2210-5. Crossref

20. Lass R, Grübl A, Kolb A, et al. Primary cementless total hip arthroplasty with second-generation metal-on-metal bearings: a concise follow-up, at a minimum of seventeen years, of a previous report. J Bone Joint Surg Am 2014;96:e37. Crossref

21. Korovessis P, Repantis T, Zafiropoulos A. High medium-term survivorship and durability of Zweymüller-Plus total hip arthroplasty. Arch Orthop Trauma Surg 2011;131:603-11. CrossRef

22. Grübl A, Chiari C, Gruber M, Kaider A, Gottsauner-Wolf F. Cementless total hip arthroplasty with a tapered, rectangular titanium stem and a threaded cup: a minimum ten-year follow-up. J Bone Joint Surg Am 2002;84-A:425-31. CrossRef

23. Garcia-Cimbrelo E, Cruz-Pardos A, Madero R, Ortega-Andreu M. Total hip arthroplasty with use of the cementless Zweymüller Alloclassic system. A ten to thirteen-year follow-up study. J Bone Joint Surg Am 2003;85-A:296-303. CrossRef

24. Zywiel MG, Sayeed SA, Johnson AJ, Schmalzried TP, Mont MA. State of the art in hard-on-hard bearings: how did we get here and what have we achieved? Expert Rev Med Devices 2011;8:187-207. Crossref

25. Murphy SB, Ecker TM, Tannast M. Two-to 9-year clinical results of alumina ceramic-on-ceramic THA. Clin Orthop Relat Res 2006;453:97-102. Crossref

26. Affatato S, Traina F, De Fine M, Carmignato S, Toni A. Alumina-on-alumina hip implants: a wear study of retrieved components. J Bone Joint Surg Br 2012;94:37-42. Crossref

27. Revell PA. The combined role of wear particles, macrophages and lymphocytes in the loosening of total joint prostheses. J R Soc Interface 2008;5:1263-78. Crossref

28. Park YS, Hwang SK, Choy WS, Kim YS, Moon YW, Lim SJ. Ceramic failure after total hip arthroplasty with an alumina-on-alumina bearing. J Bone Joint Surg Am 2006;88:780-7. Crossref

29. Hallan G, Dybvik E, Furnes O, Havelin LI. Metal-backed acetabular components with conventional polyethylene: a review of 9113 primary components with a follow-up of 20 years. J Bone Joint Surg Br 2010;92:196-201. Crossref

30. Perka C, Fischer U, Taylor WR, Matziolis G. Developmental hip dysplasia treated with total hip arthroplasty with a straight stem and a threaded cup. J Bone Joint Surg Am 2004;86-A:312-9. Crossref

31. Sugano N, Nishii T, Nakata K, Masuhara K, Takaoka K. Polyethylene sockets and alumina ceramic heads in cemented total hip arthroplasty. A ten-year study. J Bone Joint Surg Br 1995;77:548-56.

Fragility hip fracture is one of the most common fragility fractures and is becoming one of the major health care burdens on a society with an ageing population. Statistics of the Hospital Authority (HA) of Hong Kong (HK) reveal that the incidence of fragility fractures in 2014 (14 000 cases) was much higher than that for acute myocardial infarction (6383 cases) or acute cerebrovascular accident (11 187 cases). Number of patients admitted for hip fracture surgery increased from 3678 in 2000 to 4579 in 2011, ie 24.5% in 11 years.1 Although the annual age-specific risk of hip fracture slightly decreased, it is estimated that with the projected ageing population, fragility hip fractures in HK will number more than 6300 cases in 2020 and 14 500 cases in 2040, a 3-fold increase from 2011.1 Approximately 30% of patients under the age of 80 years were unable to walk independently 1 year after hip fracture and became home-bound; 20% to 40% of patients were admitted to an elderly care home; and all patients suffered both physically and psychologically with re-fracture and fear of falls.2 Hip fracture patients with poor functional recovery are unable to resume their pre-fracture function with a consequent deterioration in quality of life. Mortality at 1 year after hip fracture was as high as 27% in males and 15% in females.1

To monitor the outcomes of management and formulate standards of care in HK for fragility hip fracture, the Coordinating Committee in Orthopaedics & Traumatology of the HA proposed a Fragility Fracture Registry (www.ffr.hk) in 2013. It is hoped that the registry will ultimately help set the standards of care with respect to local demands, monitor patient care and implement preventive measures, thus improving the cost-effectiveness of fragility fracture care.

In the first phase of setting up the Fragility Fracture Registry, a retrospective study was conducted of fragility hip fractures treated at six acute public hospitals under the management of the HA. This study aimed to review the current fragility hip fracture management in HK, and compare the outcomes with the standards set by our working group with reference to the six evidence-based standards set by the British Orthopaedic Association (BOA) for the care of patients with fragility hip fracture.3

All patients with fragility hip fracture and admitted in the calendar year 2012 to the six hospitals in HK—Caritas Medical Centre, Prince of Wales Hospital, Princess Margaret Hospital, Queen Elizabeth Hospital, Queen Mary Hospital, and Tuen Mun Hospital—which are located in different clusters were included. Residents of HK aged 50 years and above with hip fracture sustained by a fall from a standing height were recruited. The number of fragility hip fractures from the six hospitals was approximately 60% of the total fragility hip fractures treated in Hong Kong during 2012. Those with atypical or pathological fracture were excluded. As 98% of patients with fragility hip fracture were managed in public hospitals, eligible patients were identified using the HA Clinical Data Analysis and Reporting System with disease coding of acute hip fracture (ICD-9-CM 820.X).4 Ethical approvals were obtained from all the six hospitals and the study was done in accordance with the principles outlined in the Declaration of Helsinki.

With reference to the National Hip Fracture Database of the United Kingdom (UK NHFD) and Scottish Hip Fracture Audit, the dataset was designed according to the acute, rehabilitation, and post-discharge practices in HK. Information was derived from the HA Clinical Management System and hospital records for the following: demographics, preoperative and postoperative assessments, surgical and discharge details, rehabilitation details, out-patient follow-up consultations and complications up to 1 year after fracture (Table 1). All data were input and managed using the Research Electronic Data Capture (REDCap) tool hosted at the Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong.5

Data were input by research assistants who understood medical terms and abbreviations. Data were validated for one in five cases selected randomly by six liaison teams located in the participating hospitals and composed of orthopaedic surgeons and nurses. Each liaison member was trained by the central research team in data validation and REDCap manipulation.

The data were analysed and compared with the standards set by our working group with reference to the six standards set by the BOA: Care of Patients with Fragility Fractures (known as the Blue Book; Box).3

Descriptive statistics were used to describe the current hip fracture conditions in HK and outcomes compared with standards of care from HK orthopaedic working group with reference to BOA. The percentage was calculated based on the number of follow-up patients available at different time-points. Chi squared test was used to compare categorical data. The Statistical Package for the Social Sciences (Windows version 20.0; IBM Corp, Armonk [NY], US) was used to perform statistical analysis. Significance was set at P<0.05.

A total of 2914 fragility hip fractures were captured in the calendar year 2012 and the mean (± standard deviation) patient age was 82.1 ± 8.6 years (range, 50-104 years). Of the patients, 1979 (67.9%) were female; 2017 (73.7%) came from home and 719 (26.3%) from an elderly care home; 1119 (40.9%), 1541 (56.3%), and 20 (0.7%) patients had an American Society of Anesthesiologists (ASA) score of grade 2, 3, and 4, respectively (Table 2).

The mean time from presentation to the accident and emergency department to orthopaedic care was 2.3 hours (median time, 1.7 hours) with 91.0% patients receiving orthopaedic care within 4 hours. Geriatric or internal medicine review was performed in 764 (27.8%) patients although only 95 (3.5%) were routinely managed by a geriatrician preoperatively.

Surgery was performed in 2774 (96.8%) patients. The mean time to surgery was 62.7 hours (median time, 42.1 hours) with 1678 (60.5%) undergoing surgery in exactly 48 hours and 2172 (78.3%) within 2 calendar working days.

Intracapsular fracture occurred in 1358 (46.6%) patients of whom 277 (9.5%) underwent cannulated screw fixation, 829 (28.4%) uncemented unipolar hemiarthroplasty, and 109 (3.7%) cemented unipolar hemiarthroplasty. Intertrochanteric fracture occurred in 1446 (49.6%) patients of whom 571 (19.6%) underwent compression hip screw fixation and 983 (33.7%) intramedullary fixation (Tables 2 and 3).

During stay in acute hospitals, some of the patients developed acute complications, with nearly one fourth experienced urine retention. A small number of patients developed other complications like pressure sore, delirium, wound infection, and deep vein thrombosis (Table 3).

The mean length of stay in acute hospitals was 12.1 days. With regard to the discharge destination from the acute unit, a majority of patients (2284, 78.4%) were transferred to a rehabilitation unit, 290 (10.0%) to an old-age home, 236 (8.1%) to their previous home, and 77 (2.6%) died during the acute admission (Table 3).

Allied health professionals provided preoperative multidisciplinary care to 1759 (64.0%) patients and postoperative care to 2886 (99.4%). Bone health medication was prescribed to 424 (15.3%) patients preoperatively and 666 (22.9%) postoperatively. Just over half of all patients (n=1573, 57.5%) were discharged to their home and 1163 (42.5%) to an old-age home. Old-age home admission at discharge significantly increased (P<0.001) [Table 4].

There was a declining trend over time for attendance at follow-up; 2179 (74.8%) attended follow-up at 90 days after fracture, 2508 (86.1%) at 180 days, and only 1023 (35.1%) at 1 year. Postoperative mobility compared with premorbid had deteriorated at 90-day, 180-day, and 1-year follow-up in 1689 (77.5%), 2062 (82.2%), and 715 (69.9%) patients, respectively. With those 669 patients available for assessments at both 90-day and 1-year time-points, 511 patients had deterioration at 90 days and 426 patients deteriorated at 1 year. The deterioration was significant at 1-year follow-up (P<0.001) [Table 4]. Pressure sores were evident or developed in 58 (2.0%) patients preoperatively and 150 (5.3%) at 1 year. Presence of pressure sore significantly increased at 1 year (P<0.001) [Table 4].

Fracture complications occurred in 175 (6.0%) patients within a year (Table 3) with 90 (3.1%) requiring revision surgery. A secondary fracture occurred in 117 (4.0%) patients and 505 (17.3%) patients died in 1 year compared with the 1.6% mortality rate for a HK age-matched population.6 7

This report reviewed the management of fragility hip fractures in HK based on the standards of care by our orthopaedic community and compared the outcomes with the standards set by our working group and by BOA in the UK.

The demographics were comparable to previous studies in HK. The mean age of patients with fragility hip fracture in our 2012 data was 82.1 years, unchanged compared with local data from 2000 to 2011.1 The female-to-male ratio was around 2:1 indicating an increase in male fragility hip fractures compared with 2.5:1 from 2001 to 2010.4 8 This may be due to increasing life expectancy of the HK male population9 and bone mineral density (BMD) at the hip in men that decreases with age.10 There were 1257 (46.6%) femoral neck fractures, 1445 (49.6%) intertrochanteric fractures, and 110 (3.8%) subtrochanteric fractures, comparable with a previous local study of 1342 hip fracture patients from 2007 to 2010.8 The majority of patients had an ASA score of 2 and 3, comprising 40.9% and 56.3%, respectively and in line with Lau et al’s study.8 There was a marked increase in hemiarthroplasties and intramedullary fixations with 977 (33.5%) and 983 (3.7%) cases respectively in our study, compared with Lau et al’s study that reported 362 (27%) hemiarthroplasties and 218 (16%) cephalomedullary nail fixations.8 This reflects a change in the surgical treatment, possibly due to a lower re-operation rate,11 better functional outcomes,12 and higher cost-effectiveness13 in patients treated with hemiarthroplasty; and minimal rate of fixation failure, less blood loss, and shorter length of hospital stay in patients treated with intramedullary fixation.14

A low complication rate (6.0%) and revision rate (3.1%) are testimony to the improved standard of routine acute care, which includes early orthopaedic care and early surgeries.

Poor functional recovery was evident in the large proportion of patients (77.5%) with deteriorated mobility at 90-day out-patient clinic follow-up, not improved 1 year after fracture (69.9%). This compares with less than half of treated patients who regained their pre-fracture mobility in another study.15 According to an internal survey conducted at Prince of Wales Hospital, only 22% of patients received out-patient physiotherapy; the major reason (71%) was “not referred”. Inadequate rehabilitation after discharge may explain poor functional recovery after hip fracture. On discharge, HK patients discharged to an old-age home significantly increased from 26.3% to 42.5%, ie a 16.2% increase in institutionalisation compared with only 10.5% in a Spanish study.16 Poor functional recovery after hip fracture may contribute to this high institutionalisation rate, as fractures are significantly associated with mild-to-severe functional limitations.17 Lack of support in the community may mean a lack of sustained rehabilitation after discharge. Family support may also be suboptimal as many elderly are alone at home during the day.

The attendance rate for out-patient clinic follow-up was only 35.1% at 1 year. A high proportion of elderly living alone (12.7% in 2011)18 and a high institutionalisation rate (5.7% in 2014)19 may explain the low follow-up rate due to lack of support. The mortality at 1 year after fracture was 17.3%, comparable with other local studies: 18.6% from 2000 to 20061 and 18.0% from 2001 to 2009,4 which are much higher than that for an age-matched population (1.6%).6 7

Data from this review were also compared with those of the UK NHFD 201220 collected from 180 hospitals across the UK with patients managed according to the UK Blue Book standards.3

Tables 2 and 5 summarise the demographics, surgery details, length of stay in acute hospitals, and comparison of six standards for hip fracture care between HK and UK NHFD, respectively. Major differences in hip fracture management between HK and UK NHFD are identified.

When comparing the demographics, our review showed a larger male hip fracture population (32%) than the UK (26%) while age and ASA grade distribution were similar. Patients treated surgically were similar in both databases; more HK patients had intertrochanteric fracture (49.6% vs 34.3%) and more UK patients had displaced intracapsular fracture (46.8% vs 36.5%). The length of stay in acute hospitals in HK was shorter than in UK (12.1 days vs 15.8 days). The mean length of post-acute stay in the UK was only 4.4 days, however, which is shorter than that in HK (around 3-4 weeks). This may be due to the differences in acute and post-discharge care between HK and the UK. Care by a general practitioner after being discharged from hospital is the usual practice in the UK; in HK, most patients will be cared for by an orthopaedic team in post-acute rehabilitation with follow-up in orthopaedic specialist clinics until discharge.

In HK, 98% of patients underwent a falls assessment on admission, similar to the UK (92%). In HK, a Morse Fall Scale27 will be calculated by orthopaedic nurses on admission; in the UK, a systematic assessment is performed by a geriatrician or a specialist nurse to prevent further falls.8

With regard to the six standards for hip fracture care set by the BOA Blue Book (Box and Table 5), 61% of HK patients had surgery within exactly 48 hours, compared with 35% in Spain21 and less than 10% in China22; in the UK, 83% of patients received surgery within 48 hours and during working hours. The percentage of HK patients who underwent surgery within 2 calendar working days was 30% before 2007 and improved to 62% in 2008 after the establishment of Key Performance Indicator (KPI) by the HA and 78.3% in 2012.23 The aim of KPI is to ensure 70% of hip fracture patients receive surgery within 2 calendar working days.24 25 This may explain why a large proportion of patients had quick hip fracture surgery in HK. The delay in surgery for 22% of patients may have been due to time spent awaiting medical optimisation by physicians or geriatricians.

Very few patients in HK (3.5%) received preoperative assessment by geriatricians in contrast to 43% of patients in the UK. In this review, only one of the six studied hospitals had a geriatrician who routinely assessed hip fracture patients pre- and post-operatively, indicating a lack of geri-orthopaedic co-management in HK. Studies have shown better outcomes after hip fracture when patients receive geri-orthopaedic treatment, with a lower 1-year mortality rate,26 27 reduced acute hospital stay, and less need for further rehabilitation.27 A local study reviewed the effectiveness of geri-orthopaedic co-management and found that in the geri-orthopaedic group, time to surgery was shorter, 1-year mortality rate was lower, and more remained independent in daily living activities.28 Therefore, geri-orthopaedic care should be implemented in all hospitals in HK to achieve better patient care. This will further improve the KPI for fragility hip fractures in all hospitals in HK.

Only 23% of HK patients were discharged with bone protection medication compared with almost 70% in the UK (Table 5) and nearly 40% in Korea (excluding calcium and vitamin D).29 A local study showed that 33% were prescribed medications for osteoporosis in the 6 months after discharge.30 Osteoporosis diagnosis and treatment were driven by BMD measurement, not fracture history.30 This may explain the low prescription rate of bone protection medication when the fracture patient did not undergo BMD measurement for a variety of reasons such as unavailability of dual-energy X-ray absorptiometry (DXA), long queuing time, or lack of referral from orthopaedic doctors. Although the need for DXA measurement prior to prescription of bone health medication to patients with fragility fracture remains controversial, it is clear that DXA measurement is not the only single indication for such medication.31

In view of the low follow-up rate, poor functional recovery, increased institutionalisation, and high mortality after fragility hip fracture, better post-discharge rehabilitation and secondary fracture prevention should be implemented to restore patients’ physical and psychological status.

Fracture Liaison Services (FLS) is a coordinator-based service for sustained rehabilitation in the community and secondary fracture prevention in patients with fragility fractures. It has been implemented in many countries—eg the UK,32 Australia,33 Canada34—and studies reveal that FLS is cost-effective. Implementation of FLS in HK may improve current post-discharge care. Such services include osteoporosis identification and treatment (eg DXA scan and prescription of bone protection medication), education about secondary fracture prevention (exercise, dietary guidelines, and an education programme), and sustainable multidisciplinary services (follow-up by FLS coordinator regularly). With FLS, fragility hip fracture patients with osteoporosis can be identified and treated promptly with good compliance with medications. Patients will be instructed to exercise to improve functional status with a potential consequent decrease in old-age home admission. They will also be taught about falls prevention and sustained rehabilitation, and hence lower the chance of secondary fracture.

This study included approximately 60% of all HK fragility hip fractures. It would be better to include all HK hospitals in future studies to reflect the full situation across the territory. This study retrospectively reviewed medical records from 2012 with data retrieved from electronic and handwritten records so a small percentage of data may have been missing due to illegible records. A standardised electronic format from the Clinical Management System will improve data capture and analysis. A disease registry is important to enable better documentation.

This study reviewed the current fragility hip fracture care in HK. Although acute surgical treatment complies with international standards, standardised geri-orthopaedic co-management will further improve the acute care. Recognising fragility hip fracture as a chronic disease model, the increased rate in old-age home admission, poor functional recovery, low prescription rate of bone health medications, and low attendance rate for follow-up were identified as problems in subsequent management. These may explain the higher 1-year mortality rate, high secondary fracture rate, and deterioration in the quality of life after fracture among these elderly. With an ageing population and increasing longevity, the hip fracture rate is expected to increase continuously. A comprehensive multidisciplinary chronic disease management model that includes geri-orthopaedic co-management and FLS programmes should be implemented to improve patient outcomes, prevent secondary fractures, and reduce the economic burden on HK. The setting up and maintenance of a registry of all fragility fractures is imminent and will help health care professionals monitor and continuously improve the standards of patient care as well as prevent fractures.

This study was partially supported by grant support of Asian Association for Dynamic Osteosynthesis (Ref: AADO-RF2012-001-2Y) and Professional Services Development Assistance Scheme, Commerce and Economic Development Bureau, Government of the Hong Kong Special Administrative Region. The authors would like to thank the liaison teams that comprised doctors and nurses of the Department of Orthopaedics and Traumatology from the six participating hospitals for their help in data validation.

All authors have disclosed no conflicts of interest.

1. Man LP, Ho AW, Wong SH. Excess mortality for operated geriatric hip fracture in Hong Kong. Hong Kong Med J 2016;22:6-10. Crossref

2. Fierens J, Broos PL. Quality of life after hip fracture surgery in the elderly. Acta Chir Belg 2006;106:393-6. Crossref

3. The care of patients with fragility fracture. British Orthopaedic Association; 2007.

4. Chau PH, Wong M, Lee A, Ling M, Woo J. Trends in hip fracture incidence and mortality in Chinese population from Hong Kong 2001-09. Age Ageing 2013;42:229-33. Crossref

5. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377-81. Crossref

6. Population estimates. Census and Statistics Department, Hong Kong SAR Government; 2016.

7. Tables on health status and health services 2012. Department of Health, Hong Kong SAR Government; 2013.

8. Lau TW, Fang C, Leung F. The effectiveness of a geriatric hip fracture clinical pathway in reducing hospital and rehabilitation length of stay and improving short-term mortality rates. Geriatr Orthop Surg Rehabil 2013;4:3-9. Crossref

9. Women and men in Hong Kong key statistics. Census and Statistics Department, Hong Kong SAR Government; 2016.

10. Lau EM, Leung PC, Kwok T, et al. The determinants of bone mineral density in Chinese men—results from Mr. Os (Hong Kong), the first cohort study on osteoporosis in Asian men. Osteoporos Int 2006;17:297-303. Crossref

11. Shields E, Kates SL. Revision rates and cumulative financial burden in patients treated with hemiarthroplasty compared to cannulated screws after femoral neck fractures. Arch Orthop Trauma Surg 2014;134:1667-71. Crossref

12. Gjertsen JE, Vinje T, Engesaeter LB, et al. Internal screw fixation compared with bipolar hemiarthroplasty for treatment of displaced femoral neck fractures in elderly patients. J Bone Joint Surg Am 2010;92:619-28. Crossref

13. Waaler Bjornelv GM, Frihagen F, Madsen JE, Nordsletten L, Aas E. Hemiarthroplasty compared to internal fixation with percutaneous cannulated screws as treatment of displaced femoral neck fractures in the elderly: cost-utility analysis performed alongside a randomized, controlled trial. Osteoporos Int 2012;23:1711-9. Crossref

14. Ma KL, Wang X, Luan FJ, et al. Proximal femoral nails antirotation, Gamma nails, and dynamic hip screws for fixation of intertrochanteric fractures of femur: a meta-analysis. Orthop Traumatol Surg Res 2014;100:859-66. Crossref

15. Vochteloo AJ, Moerman S, Tuinebreijer WE, et al. More than half of hip fracture patients do not regain mobility in the first postoperative year. Geriatr Gerontol Int 2013;13:334-41. Crossref

16. Uriz-Otano F, Pla-Vidal J, Tiberio-López G, Malafarina V. Factors associated to institutionalization and mortality over three years, in elderly people with a hip fracture—An observational study. Maturitas 2016;89:9-15. Crossref

17. Woo J, Ho SC, Yu LM, Lau J, Yuen YK. Impact of chronic diseases on functional limitations in elderly Chinese aged 70 years and over: a cross-sectional and longitudinal survey. J Gerontol A Bio Sci Med Sci 1998;53:M102-6. Crossref

18. Thematic report: older persons. Census and Statistics Department, Hong Kong SAR Government; 2011.

19. Challenges of population ageing. Research Brief, Issue 1, 2015-2016. Hong Kong: Research Office, Legislative Council Secretariat; 2015.

20. National report 2012. The UK National Hip Fracture Database; 2012.

21. Vidán MT, Sánchez E, Gracia Y, Marañón E, Vaquero J, Serra JA. Causes and effects of surgical delay in patients with hip fracture: a cohort study. Ann Intern Med 2011;155:226-33. Crossref

22. Tian M, Gong X, Rath S, et al. Management of hip fractures in older people in Beijing: a retrospective audit and comparison with evidence-based guidelines and practice in the UK. Osteoporos Int 2016;27:677-81. Crossref

23. Lau PY. To improve the quality of life in elderly people. Hong Kong Med J 2016;22:4-5.

24. New framework for key performance indicators (AOM-P530). Hong Kong: Hospital Authority; 2008.

25. Guidebook on key performance indicators. 2nd ed. Hong Kong: Hospital Authority; 2015.

26. Folbert EC, Hegeman JH, Vermeer M, et al. Improved 1-year mortality in elderly patients with a hip fracture following integrated orthogeriatric treatment. Osteoporos Int 2017;28:269-77. Crossref

27. Henderson CY, Shanahan E, Butler A, et al. Dedicated orthogeriatric service reduces hip fracture mortality. Ir J Med Sci 2017;186:179-84. Crossref

28. Leung AH, Lam TP, Cheung WH, et al. An orthogeriatric collaborative intervention program for fragility fractures: a retrospective cohort study. J Trauma 2011;71:1390-4. Crossref

29. Kim SC, Kim MS, Sanfélix-Gimeno G, et al. Use of osteoporosis medications after hospitalization for hip fracture: a cross-national study. Am J Med 2015;128:519-26.e1. Crossref

30. Kung AW, Fan T, Xu L, et al. Factors influencing diagnosis and treatment of osteoporosis after a fragility fracture among postmenopausal women in Asian countries: a retrospective study. BMC Womens Health 2013;13:7. Crossref

31. Ito K, Leslie WD. Cost-effectiveness of fracture prevention in rural women with limited access to dual-energy X-ray absorptiometry. Osteoporos Int 2015;26:2111-9. Crossref

32. McLellan AR, Gallacher SJ, Fraser M, McQuillian C. The fracture liaison service: success of a program for the evaluation and management of patients with osteoporotic fracture. Osteoporos Int 2003;14:1028-34. Crossref

33. Cooper MS, Palmer AJ, Seibel MJ. Cost-effectiveness of the Concord Minimal Trauma Fracture Liaison service, a prospective, controlled fracture prevention study. Osteoporos Int 2012;23:97-107. Crossref

34. Bogoch ER, Elliot-Gibson V, Beaton DE, Jamal SA, Josse RG, Murray TM. Effective initiation of osteoporosis diagnosis and treatment for patients with a fragility fracture in an orthopaedic environment. J Bone Joint Surg Am 2006;88:25-34. Crossref