A hierarchical frailty model applied to two-generation melanoma data

We present a hierarchical frailty model based on distributions derived from non-negative Lévy processes. The model may be applied to data with several levels of dependence, such as family data or other general clusters, and is an alternative to additive frailty models. We present several parametric examples of the model, and properties such as expected values, variance and covariance. The model is applied to a case-cohort sample of age at onset for melanoma from the Swedish Multi-Generation Register, organized in nuclear families of parents and one or two children. We compare the genetic component of the total frailty variance to the common environmental term, and estimate the effect of birth cohort and gender. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

The role of circulating serotonin in the development of chronic obstructive pulmonary disease

Oral PresentationBACKGROUND: Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The degree of cigarette smoking mediated the association between serotonin transporter (SERT) gene polymorphism and COPD. However, the interrelation between ...published_or_final_versionThe 17th Medical Research Conference, Department of Medicine, The University of Hong Kong, Hong Kong, 14 January 2012. In Hong Kong Medical Journal, 2012, v. 18 n. 1, suppl. 1, p. 31, abstract no. 4

The Association of Types of Training and Practice Settings with Doctors’ Empathy and Patient Enablement among Patients with Chronic Illness in Hong Kong

Background The increase in non-communicable disease (NCD) is becoming a global health problem and there is an increasing need for primary care doctors to look after these patients although whether family doctors are adequately trained and prepared is unknown. Objective This study aimed to determine if doctors with family medicine (FM) training are associated with enhanced empathy in consultation and enablement for patients with chronic illness as compared to doctors with internal medicine training or without any postgraduate training in different clinic settings. Methods This was a cross-sectional questionnaire survey using the validated Chinese version of the Consultation and Relational Empathy (CARE) Measure as well as Patient Enablement Instrument (PEI) for evaluation of quality and outcome of care. 14 doctors from hospital specialist clinics (7 with family medicine training, and 7 with internal medicine training) and 13 doctors from primary care clinics (7 with family medicine training, and 6 without specialist training) were recruited. In total, they consulted 823 patients with chronic illness. The CARE Measure and PEI scores were compared amongst doctors in these clinics with different training background: family medicine training, internal medicine training and those without specialist training. Generalized estimation equation (GEE) was used to account for cluster effects of patients nested with doctors. Results Within similar clinic settings, FM trained doctors had higher CARE score than doctors with no FM training. In hospital clinics, the difference of the mean CARE score for doctors who had family medicine training (39.2, SD = 7.04) and internal medicine training (35.5, SD = 8.92) was statistically significant after adjusting for consultation time and gender of the patient. In the community care clinics, the mean CARE score for doctors with family medicine training and those without specialist training were 32.1 (SD = 7.95) and 29.2 (SD = 7.43) respectively, but the difference was not found to be significant. For PEI, patients receiving care from doctors in the hospital clinics scored significantly higher than those in the community clinics, but there was no significant difference in PEI between patients receiving care from doctors with different training backgrounds within similar clinic setting. Conclusion Family medicine training was associated with higher patient perceived empathy for chronic illness patients in the hospital clinics. Patient enablement appeared to be associated with clinic settings but not doctors' training background. Training in family medicine and a clinic environment that enables more patient doctor time might help in enhancing doctors' empathy and enablement for chronic illness patients.published_or_final_versio

Help-seeking and antibiotic prescribing for acute cough in a Chinese primary care population: a prospective multicentre observational study

Acute cough is a common reason to prescribe antibiotics in primary care. This study aimed to explore help-seeking and antibiotic prescribing for acute cough in Chinese primary care population. This is a prospective multicentre observational study that included adults presenting with acute cough. Clinicians recorded patients’ presenting symptoms, examination findings and medication prescription. Patients completed symptom diaries for up to 28 days by charting their symptom severity and recovery. Adjusted binary logistic regression models identified factors independently associated with antibiotic prescription. Primary care clinicians (n=19) recruited 455 patients. A total of 321 patients (70.5%) returned their completed symptom diaries. Concern about illness severity (41.6%) and obtaining a prescription for symptomatic medications (45.9%), rather than obtaining a prescription for antibiotics, were the main reasons for consulting. Antibiotics were prescribed for 6.8% (n=31) of patients, of which amoxicillin was the most common antimicrobial prescribed (61.3%), as it was associated with clinicians’ perception of benefit from antibiotic treatment (odds ratio (OR): 25.9, 95% confidence interval (CI): 6.7–101.1), patients’ expectation for antibiotics (OR: 5.1, 95% CI: 1.7–11.6), anticipation (OR: 5.1, 95% CI: 1.6–15.0) and request for antibiotics (OR 15.7, 95% CI: 5.0–49.4), as well as the severity of respiratory symptoms (cough, sputum, short of breath and wheeze OR: 2.7–3.7, all P<0.05). There was a significant difference in antibiotic prescription rates between private primary care clinicians and public primary care clinicians (17.4 vs 1.6%, P=0.00). Symptomatic medication was prescribed in 98.0% of patients. Mean recovery was 9 days for cough and 10 days for all symptoms, which was not significantly associated with antibiotic treatment. Although overall antibiotic-prescribing rates were low, there was a higher rate of antibiotic prescribing among private primary care clinicians, which warrants further exploration and scope for education and intervention.published_or_final_versio

Lifestyle Intervention Using an Internet-Based Curriculum with Cell Phone Reminders for Obese Chinese Teens: A Randomized Controlled Study

Objectives Obesity is an increasing public health problem affecting young people. The causes of obesity are multi-factorial among Chinese youth including lack of physical activity and poor eating habits. The use of an internet curriculum and cell phone reminders and texting may be an innovative means of increasing follow up and compliance with obese teens. The objectives of this study were to determine the feasibility of using an adapted internet curriculum and existing nutritional program along with cell phone follow up for obese Chinese teens. Design and Methods This was a randomized controlled study involving obese teens receiving care at a paediatric obesity clinic of a tertiary care hospital in Hong Kong. Forty-eight subjects aged 12 to 18 years were randomized into three groups. The control group received usual care visits with a physician in the obesity clinic every three months. The first intervention (IT) group received usual care visits every three months plus a 12-week internet-based curriculum with cell phone calls/texts reminders. The second intervention group received usual care visits every three months plus four nutritional counselling sessions. Results The use of the internet-based curriculum was shown to be feasible as evidenced by the high recruitment rate, internet log-in rate, compliance with completing the curriculum and responses to phone reminders. No significant differences in weight were found between IT, sLMP and control groups. Conclusion An internet-based curriculum with cell phone reminders as a supplement to usual care of obesity is feasible. Further study is required to determine whether an internet plus text intervention can be both an effective and a cost-effective adjunct to changing weight in obese youth. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-12002624published_or_final_versio

Sarcopenia and mortality in different clinical conditions: A meta-analysis

Objectives: Sarcopenia is recognized to be a health problem which is as serious as obesity, but its relevance to mortality is unclear. We conducted a meta-analysis of cohort studies on lean mass and mortality in populations with different health conditions. / Methods: In this study, a systematic search of PubMed, Cochrane Library and Embase was performed for cohort studies published before Dec 20, 2017 which examined the relationship between lean mass and mortality. We included studies reporting lean mass measurement by dual-energy X-ray absorptiometry, bioimpedance analysis or computed tomography, as continuous (per standard deviation [SD] decrease) or binary variables (using sarcopenia cutoffs). We excluded studies which used muscle mass surrogates, anthropometric measurement of muscle, rate of change in muscle mass, and sarcopenia defined by composite criteria. The primary study outcome was all-cause mortality. Pooled hazard ratio estimates were calculated using a random effects model. / Results: A total of 9602 articles were identified from the systematic search, and 188 studies with 98 468 participants from 34 countries were included in the meta-analysis. Of the 68 studies included in the present meta-analysis, the pooled HR was 1.36 and 1.74 for every SD decrease in lean mass and in people with low lean mass (cutoffs), respectively. Significant associations were also observed in elderly and all disease subgroups, irrespective of the measurement modalities. / Conclusions: Lower lean mass is robustly associated with increased mortality, regardless of health conditions and lean mass measurement modalities. This meta-analysis highlighted low lean mass as a key public health issue

Hedgehog/notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans

Hirschsprung (HSCR) disease is a complex genetic disorder attributed to a failure of the enteric neural crest cells (ENCCs) to form ganglia in the hindgut. Hedgehog and Notch are implicated in mediating proliferation and differentiation of ENCCs. Nevertheless, how these signaling molecules may interact to mediate gut colonization by ENCCs and contribute to a primary etiology for HSCR are not known. Here, we report our pathway- based epistasis analysis of data generated by a genome-wide association study on HSCR disease, which indicates that specific genotype constellations of Patched (PTCH1) (which encodes a receptor for Hedgehog) and delta-like 3 (DLL3) (which encodes a receptor for Notch) SNPs confer higher risk to HSCR. Importantly, deletion of Ptch1 in mouse ENCCs induced robust Dll1 expression and activation of the Notch pathway, leading to premature gliogenesis and reduction of ENCC progenitors in mutant bowels. Dll1 integrated Hedgehog and Notch pathways to coordinate neuronal and glial cell differentiation during enteric nervous system development. In addition, Hedgehog-mediated gliogenesis was found to be highly conserved, such that Hedgehog was consistently able to promote gliogenesis of human neural crest-related precursors. Collectively, we defined PTCH1 and DLL3 as HSCR susceptibility genes and suggest that Hedgehog/Notch-induced premature gliogenesis may represent a new disease mechanism for HSCR.published_or_final_versio

Genome-wide copy number variation study in anorectal malformations

Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.postprin

Behavioral activation with mindfulness in treating subthreshold depression in primary care: A cost-utility and cost-effectiveness analysis alongside a randomized controlled trial

10.1016/j.jpsychires.2020.10.006Journal of Psychiatric Research132111-11