Serial surveys of Hong Kong medical students regarding attitudes towards HIV/AIDS from 2007 to 2017.

INTRODUCTION: With widespread adoption of antiretroviral therapy, human immunodeficiency virus (HIV) epidemiology has changed since the late 2000s. Accordingly, attitudes towards the disease may also have changed. Because medical students are future physicians, their attitudes have important implications in access to care among patients with HIV/acquired immunodeficiency syndrome (AIDS). Here, we performed a survey to compare medical students' attitudes towards HIV/AIDS between the late 2000s (2007-2010) and middle 2010s (2014- 2017). METHODS: From 2007 to 2010, we surveyed three cohorts of medical students at the end of clinical training to assess their attitudes towards HIV/AIDS. From 2014 to 2017, we surveyed three additional cohorts of medical students at the end of clinical training to compare changes in attitudes towards HIV/AIDS between the late 2000s and middle 2010s. Each set of three cohorts was grouped together to maximise sample size; comparisons were performed between the 2007-2010 and 2014-2017 cohorts. RESULTS: From 2007 to 2010, 546 medical students were surveyed; from 2014 to 2017, 504 students were surveyed. Compared with students in the late 2000s, significantly fewer students in the mid-2010s initially encountered patients with HIV during attachment to an HIV clinic or preferred to avoid work in a field involving HIV/AIDS; significantly more students planned to specialise in HIV medicine. Student willingness to provide HIV care remained similar over time: approximately 78% of students were willing to provide care in each grouped cohort. CONCLUSION: Although medical students had more positive attitudes towards HIV/AIDS, their willingness to provide HIV care did not change between the late 2000s and middle 2010s.

Adherence of nurses to annual seasonal influenza vaccination over a 5-year period.

BACKGROUND: Healthcare workers (HCWs) are at risk of influenza infection with associated nosocomial transmission. Sustained adherence to seasonal influenza vaccination uptake each year is important in epidemic control. AIM: To assess the adherence of nurses to seasonal influenza vaccination over 5 years and its associated factors. METHODS: A cross-sectional study was conducted among nurses after the winter influenza season in Hong Kong in March 2019. Based on influenza vaccine uptake rates in the 2014/15-2018/19 seasons, respondents were stratified into three groups: 'full adherence' (vaccine uptake in five seasons), 'partial adherence' (vaccine uptake in one to four seasons) and 'non-adherence' (no vaccine uptake). Stepwise multi-variable logistic regression was performed to determine the associations between adherence to annual influenza vaccination, respondents' characteristics and considerations for vaccination. FINDINGS: Of 1306 nurses recruited, the majority were female (88%) with a median age of 36 years (interquartile range 30-46 years). The influenza vaccination uptake rate increased from 36% in the 2014/15 season to 47% in the 2018/19 season. After stratification, 39%, 40% and 21% of respondents were non-adherers, partial adherers and full adherers, respectively. Full adherence was significantly associated with female gender [adjusted odds ratio (aOR) 0.60], age ≥40 years (aOR 2.92), long-term care facility nurse (aOR 0.56), uptake during studentship (aOR 3.83), local prevalence of seasonal influenza (aOR 0.51) and expert opinion (aOR 4.04). CONCLUSIONS: A limited proportion of nurses were fully adherent to seasonal influenza vaccination. Monitoring adherence, improving access to vaccines, and interventions targeting less-adherent HCWs are crucial.

Timing of arthrocentesis in the management of temporomandibular disorders: an integrative review and meta-analysis.

The aim of this study was to assess the best timing to perform arthrocentesis in the management of temporomandibular disorders with regard to conservative treatment. A systematic search based on PRISMA guidelines, including a computer search with specific keywords, reference list search, and manual search was performed. Relevant articles were selected after three search rounds for final review based on six predefined inclusion criteria, followed by a round of critical appraisal. Eleven publications, including eight randomized controlled trials and three prospective clinical studies, were included in the review. The studies were divided into three groups based on the timing of arthrocentesis: (1) arthrocentesis as the initial treatment; (2) early arthrocentesis; and (3) late arthrocentesis. Meta-analysis was carried out to compare the efficacy of improvement in mouth opening and pain reduction in the three groups. All three groups showed improvement in mouth opening and pain reduction, with forest plots suggesting that arthrocentesis performed within 3 months of conservative treatment might produce beneficial results. We conclude that there is a knowledge gap in the current literature regarding the preferable timing to perform arthrocentesis in the management of temporomandibular disorders, and more high-quality randomized controlled trials are required to shed light on this subject.

Surgical morbidities of sagittal split ramus osteotomy versus intraoral vertical ramus osteotomy for the correction of mandibular prognathism: a randomized clinical trial.

The sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) are two common orthognathic procedures for the treatment of mandibular prognathism. This randomized clinical trial compared the surgical morbidities between SSRO and IVRO for patients with mandibular prognathism over the first 2 years postoperative. Ninety-eight patients (40 male, 58 female) with a mean age of 24.4±3.5 years underwent bilateral SSRO (98 sides) or IVRO (98 sides) as part or all of their orthognathic surgery. IVRO presented less short-term and long-term surgical morbidity in general. The SSRO group had a greater incidence of inferior alveolar nerve deficit at all follow-up time points (P< 0.01). There was more TMJ pain at 6 weeks (P= 0.047) and 3 months (P= 0.001) postoperative in the SSRO group. The SSRO group also presented more minor complications, which were related to titanium plate exposure and infection. There were no major complications for either technique in this study. Despite the need for intermaxillary fixation, IVRO appears to be associated with less surgical morbidity than SSRO when performed as a mandibular setback procedure to treat mandibular prognathism.

Is there a difference between the thicknesses of the rami in mandibular asymmetry?

The purpose of this retrospective study was to investigate whether the thicknesses of the two rami differ in patients with mandibular asymmetry. Preoperative cone beam computed tomography scans of 78 patients with mandibular asymmetry were assessed for ramus thickness, mandibular length, and mandibular shift. The results showed that the ramus was thinner on the longer side than on the shorter side in 85.9% of the patients. On average, the longer side of the mandible was 2.74mm longer (range 0.07-9.90mm, standard deviation 1.92mm) and 0.55mm thinner (range -0.61 to 2.02mm, standard deviation 0.59mm) than the shorter side (both P<0.001). This study indicates a trend in the discrepancy in ramus thickness between the longer and shorter side of about 8% of the mean thickness of the ramus. Regression analysis showed that for every 1-mm increase in the length of the mandible, the thickness of the superior aspect of the ramus was reduced by 0.041 mm (P=0.009) and the anterior aspect by 0.125 mm (P=0.001). Age and sex did not have a significant influence on the thickness of the mandible. It is concluded that the longer side of the mandible tends to be thinner at the ramus than the shorter side in patients with mandibular asymmetry. The implication of this finding could be important in relation to the sagittal split ramus osteotomy.

Bone regeneration at the distal aspect of the adjacent second molar after lower third molar coronectomy: a long-term analysis.

A residual bone defect at the distal aspect of the adjacent second molar may occur after total removal of the lower third molar. Lower third molar coronectomy has been proved to be a safe alternative to total removal, but the extent of bone regeneration at the adjacent tooth after coronectomy is not well reported. The aim of this prospective study was to investigate the long-term bone regeneration at the distal aspect of the adjacent second molar after lower third molar coronectomy. Preoperative and postoperative cone beam computed tomography scans were measured to assess bone regeneration at the distobuccal (DB), mid-distal (MD), and distolingual (DL) aspects of the lower second molar. Forty-eight coronectomies in 37 patients (23 female) with a mean±standard deviation age of 29.1±7.2 years were assessed. The mean follow-up was 93.2±8.7 months. The mean bone level increase at DB, MD, and DL aspects was 3.2±1.6mm, 3.5±1.5mm, and 3.2±1.6mm, respectively; the bone levels were significantly higher than the preoperative measurements (P<0.001). Age and impaction patterns were not factors affecting bone regeneration. Based on this study, it appears that coronectomy of the lower third molar brings favourable bone regeneration at the distal aspect of the adjacent second molar.

Piloting a partially self-financed mode of human immunodeficiency virus pre-exposure prophylaxis delivery for men who have sex with men in Hong Kong.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg is a proven strategy for preventing human immunodeficiency virus (HIV) transmission in men who have sex with men (MSM). This study aimed to test the feasibility and acceptability of PrEP delivered at a pilot clinic for MSM in Hong Kong, where PrEP service is currently unavailable. METHODS: Partially self-financed PrEP was provided to HIV-negative adult MSM with high behavioural risk of HIV transmission after excluding hepatitis B infection and renal insufficiency. Participants received daily TDF/FTC for 30 weeks at 13.3% of the drug cost. Adherence and behaviours were monitored through questionnaires while creatinine and HIV/STI (sexually transmitted infection) incidence were monitored with point-of-care and laboratory tests. Preference for continuing with PrEP was evaluated at the end of the prescription period. RESULTS: Seventy-one PrEP-naïve MSM were included in the study, of whom 57 (80%) were retained at the end of 28 weeks. Satisfactory adherence and self-limiting adverse events were reported, while none of the participants contracted HIV. Risk compensation was observed, with an STI incidence of 3.17 per 100 person-years. At the end of the prescription period, a majority (89%) indicated interest in continuing with PrEP. Preference for PrEP was associated with age ≥28 years and peer influence (P=0.04), while stigma was a concern. Price was a deterrent to self-financed PrEP, and only half (51%) considered a monthly cost of ≤HK$500 (US$1=HK$7.8) as reasonable. CONCLUSIONS: A partially self-financed mode of PrEP delivery is feasible with good retention in MSM in Hong Kong.

Three-dimensional radiographic evaluation of root migration patterns 4-8.5 years after lower third molar coronectomy: a cone beam computed tomography study.

This prospective study in patients with a follow-up of 4-8.5years aimed to describe the long-term, three-dimensional changes of coronectomized lower third molar roots. Pre- and postoperative cone beam computed tomography (CBCT) scans were compared. The distance of root migration, the direction of root translation and rotation, and the amount of bone regeneration at the adjacent second molar and superficially to the third molar root were recorded. Age, gender, time elapsed following surgery, the status of the retained root including, impaction pattern and depth of impaction were tested to check if they were influencing factors for the above outcomes. A total of 57 coronectomized third molars from 44 patients were included. The distance of the mean root migration was 2.82mm, and they predominantly translated mesially (76.8%). Age negatively correlated with the distance of migration. Root remnants with a soft tissue coverage had less bone regenerated at the adjacent second molar (1.27mm vs. 2.95mm) in comparison to their impacted counterparts. Based on the present radiographic results and the absence of any pathological findings, coronectomy can be recommended for selected cases of third molar removal as a safe procedure with favourable long-term outcomes.

Prevalence of hepatitis C infection and its associated factors in healthy adults without identifiable route of transmission.

While hepatitis C virus (HCV) infection is long known to be associated with parenteral exposure, the specific route of transmission is not identified in a proportion of infected patients. Taking blood donors as the surrogate of healthy adults in the community in Hong Kong, we identified 91 HCV-infected donors (≤0.02% positive rate) in 2014-2016, of whom 46 were recruited in a mixed-method study to examine their transmission routes. A majority (75%) of the recruited donors were HCV RNA positive, with the predominant subtypes being 1b and 6a. From the results of the structured self-administered questionnaire and in-depth interviews, only 14 (30%) recruited donors could be traced to past history of contaminated blood transfusion (n = 9) or injection drug use (n = 5). Case-control analyses with 3 different control groups were performed to examine factors associated with HCV infection in multivariable analyses. High-risk sexual behaviour, body piercing, intramuscular injection and vaccine inoculation abroad, having lived abroad for >3 months were significantly associated with HCV in donors with otherwise nonidentifiable source of infection. While the specific route of transmission cannot be established for each person, associations with multiple parenteral exposures outside Hong Kong were observed. The World Health Organization has advocated for the global elimination of HCV by 2030. With a high proportion of HCV-infected persons who are unaware of their infections, HCV elimination could be hard to achieve.

Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients.

This study investigated the impact of ABCB5, ABCC5 and RLIP76 polymorphisms on doxorubicin pharmacokinetics in Asian breast cancer patients (N=62). Direct sequencing was performed to screen for previously identified ABCC5 polymorphisms as well as polymorphisms in the exons and exon-intron boundaries of ABCB5 and RLIP76 genes. Genotype-phenotype correlations were analyzed using Mann-Whitney U-test. The homozygous variant allele at the ABCC5 g.+7161G>A (rs1533682) locus was significantly associated with higher doxorubicin clearance (g.+7161AA vs g.+7161GG, CL/BSA (Lh-1m-2): 30.34 (25.41-33.60) vs 22.46 (15.04-49.4), P=0.04). Homozygosity for the reference allele at the ABCC5 g.-1679T>A locus was associated with significantly higher doxorubicinol exposure (g.-1679TT vs g.-1679TA, AUC0-∞/dose/BSA (hm-5): 15.48 (6.18-67.17) vs 8.88 (3.68-21.71), P=0.0001). No significant influence of the three newly identified ABCB5 polymorphisms (c.2T>C, c.343A>G and c.1573G>A) on doxorubicin pharmacokinetics was observed. No polymorphisms were identified in the RLIP76 gene. These findings suggest that ABCC5 polymorphisms may explain partially the interpatient variability in doxorubicin disposition.

Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer.

Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R(2): 53%, P<10(-77)). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43-0.91; P=0.013). Low (<14 nM) compared with high (>35 nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04-4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS.

The uncut jade: differing views of the potential of expert users on staff training and rehabilitation programmes for service users in Hong Kong.

BACKGROUND: Service user participation in direct service provision and evaluation has been developing in the western world in the past 20 years. However, this recovery-based care model is relatively new in Asia. AIM: To understand the views and perceptions of the service users and of psychiatric nurses about the recruitment of peer specialists in a regional psychiatric unit in Hong Kong. METHOD: A qualitative study using probe questions to understand the above issues in the form of focus group discussion. A total of 13 psychiatric nurses and 16 mental health service users were recruited from a regional psychiatric unit for the study. RESULTS: Content analysis based loosely on grounded theory has identified several important themes. While service users are generally enthusiastic about the potential contribution of peer specialists in a service setting, they are much concerned about rejection and discrimination by the psychiatric staff. Psychiatric nurses are also sceptical about the involvement of peer specialists in the delivery of service, although for an entirely different set of reasons. In view of the divergent views of the service users and the psychiatric nurses, a second round of focus group discussion was conducted seven months later to understand whether the themes distilled were consistent with their views expressed in the first round of focus group discussion. CONCLUSION: It is encouraging is that, for those psychiatric nurses who worked with volunteer service users in the pilot scheme of 'expert user participation', there was a change in view towards positive acceptance about peer specialist involvement in service delivery. The study provides some insight into the potential obstacles to and opportunities in the implementation of peer specialist services in routine psychiatric services in Hong Kong.

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Relationship between population configuration and the spatial pattern of pandemic influenza A (H1N1) 2009 in Hong Kong.

OBJECTIVE. To investigate the association between population structure and the pandemic influenza A (H1N1) 2009 epidemic in a spatial context. DESIGN. A retrospective case-report series study. SETTING. Hong Kong. PATIENTS. Laboratory-confirmed cases of human influenza A (H1N1) 2009 reported to the Centre for Health Protection between May and September 2009. MAIN OUTCOME MEASURES. A geo-referenced database was established comprising age, gender, and residence location of all influenza A (H1N1) 2009 cases reported in the first 5 months of the Kong Kong epidemic's first wave in 2009. They were divided into four age categories: infant, student, adult, and elderly. Correlation coefficients and odds ratios were calculated to explore the association of H1N1 cases with population configurations in 400 District Council Constituency Areas. RESULTS. Of the 24 414 H1N1 cases reported, students accounted for the highest proportion (54.6%), followed by adults (33.4%), infants (11.1%), and the elderly (0.9%). Transmission was initially concentrated in students which then extended to infants and adults. Except for the elderly, the total population size and that of each age category were significantly associated with the H1N1 cases spatially. Mobility indicators as reflected by the number of students studying outside and adults working outside residential District Council Constituency Areas were also positively associated with H1N1 cases. CONCLUSIONS. Local population structure and mobility were associated with the spatial distribution of the H1N1 epidemic, despite the small size of the territory of Hong Kong. If an influenza epidemic hits again, an examination of these factors spatially would be useful in supporting the planning of interventions.

Phase I pharmacokinetic study of a weekly liposomal paclitaxel formulation (Genexol-PM) in patients with solid tumors.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients. MATERIALS AND METHODS: Patients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m(2) and the maximum administered dose was 200 mg/m(2). RESULTS: The majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m(2). The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m(2). Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (C(max)) and the area under the concentration-time curve from zero to infinity (AUC(0-infinity)) increasing by approximately four- and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m(2). The median total-body clearance of Genexol-PM for all patients was 43.9 l/h. CONCLUSION: The weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously.

Streptococcal cellulitis following preparation of fresh raw seafood.

We describe three zoonotic streptococcal soft tissue infections resulting from fresh seafood contact. One was a localized thumb infection with Streptococcus iniae in an immunocompetent healthy young male resulting from a puncture wound from a crab pincer. The other two were cases of ascending upper limb cellulitis associated with bacteraemia in mastectomy patients. One of these infections was caused by S. iniae while the other was caused by Streptococcus dysgalactiae subsp. dysgalactiae, a species that has not been previously described as a cause of zoonotic infection. Hence when cleaning raw seafood, protective equipment should be used to minimize the risk of percutaneous injuries.

Concurrent chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the oesophagus: a single centre experience.

INTRODUCTION: Data on combined modality treatment for locally advanced squamous cell carcinoma of the oesophagus involving Asian patients are limited. MATERIALS AND METHODS: A retrospective study of 56 consecutive patients with this condition treated with concurrent chemoradiotherapy followed by surgery in a single tertiary institution in Singapore was performed. RESULTS: The median overall survival of the entire cohort was 14.1 months [95% confidence interval (CI); range, 8.6 to 19.6 months]. In patients who underwent successful oesophagectomy after chemoradiotherapy (n = 17), the median survival was 27.8 months compared to 9.8 months for those who did not have surgery (n = 39) (P = 0.046, log-rank test). The median time to first relapse for the entire cohort was 16.1 months (95% CI, 7.7 to 24.5 months). The time to first relapse was 23.9 months in the subgroup of patients with successful surgery and 12.1 months in the group which did not (P = 0.147, log-rank test). The high proportion of patients who were medically unfit for surgery or declined surgery may have conferred a selection bias. CONCLUSION: Concurrent chemoradiotherapy followed by surgery is feasible in selected patients. The benefit of adding of surgery to chemoradiotherapy is still controversial and we await the results of randomised controlled trials comparing chemoradiotherapy with surgery versus chemoradiotherapy alone.

CPT-11 and cisplatin in the treatment of advanced gastric cancer in Asians.

There is no standard chemotherapy for advanced gastric cancer. A combination of CPT-11 and cisplatin was evaluated for response and toxicity in Asians. 38 patients with histologically proven stage IV gastric/gastroesophageal junction adenocarcinoma were treated with CPT-11 50 mg/m2 and cisplatin 30 mg/m2 weekly for 3 weeks. Each cycle was repeated every 28 days. The median number of cycles was 1.66 (range 0.33-4.33). Dose delay was needed in 11 (29%) patients and dose reductions in 19 (50%) patients. The overall response rate was 42%. There was no complete response. Grade 3 and 4 hematological toxicity was 26%. Grade 3 or 4 diarrhea was not common. Median time to progression for all patients was 15 weeks. Median duration of survival of all patients was 42 weeks. Patients with better performance status and no prior chemotherapy did better. CPT-11 and cisplatin is a useful regimen with significant but manageable toxicity that can be administered without a central venous catheter.