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Abstract Objective To characterise lifestyle patterns (comprising dietary and movement behaviour aspects) of children in Singapore and examine the correlates of these patterns. Design An observational study approach was used. Children recorded their diet and activities over two weekdays and two weekend days on a validated web-based assessment, My E-Diary for Activities and Lifestyle (MEDAL). Lifestyle patterns were derived using principal component analysis, and the correlations of these with multiple known determinants organised by distal, intermediate, and proximal levels of influence were studied. Setting Children of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Participants Ten-year-old children (n = 397). Results Three lifestyle patterns, “high snacks and processed food”, “balanced” and “mixed”, were identified. We focused on the more health-promoting “balanced” pattern, characterised by lower screen-viewing and higher consumption of fruits, vegetables, wholegrains, and dairy. Among the distal factors, girls were more adherent to the “balanced” pattern compared to boys, and children of parents with lower education levels were less adherent to this pattern. Among intermediate factors, children of mothers with higher diet quality were more adherent to the “balanced” pattern. Among the proximal factors, engagement in active transport, leisure sports, and educational activities outside of school were positively associated with the “balanced” pattern, whereas screen-viewing while travelling was negatively associated with this pattern. Having siblings, pet ownership, mother’s physical activity, parenting style, parental bonding, child’s outdoor time, and breakfast consumption were not associated with children’s lifestyle patterns. Conclusions These findings provide direction for future interventions by identifying vulnerable groups and contexts that should be prioritised.

Abstract Background Dependency on screen viewing (SV) has reached unprecedented levels, and mental health issues are becoming a major public health concern. However, the associations between SV, including variations in purposes, devices, and timing, and mental health remain unclear. This study aims to provide insights into these associations among university students. Methods This analysis used baseline data from a longitudinal cohort study among first-year university students matriculating in the 2021–2022 academic year. Self-reported data on sociodemographics, health behaviors and mental health outcomes alongside anthropometric measurements were collected. Unadjusted and adjusted logistic regression analyses were conducted. Results The average age of the 997 valid students was 20.2 years, with 59.6% being female and 41.4% male. Students spent 14.3 h daily on SV, with females reporting higher SV than males. Daily SV was predominant for study purposes (7.6 h/day). Computer usage was the highest (7.0 h/day), while TV usage was the lowest (1.7 h/day). Poor mental wellbeing was reported by 33.6% of students, while 13.9% experienced psychological distress. Compared to students with low total SV, those with high levels were more likely to have poor mental wellbeing [OR (95% CI): 1.40 (0.99, 1.98)] and psychological distress [1.56 (1.00, 2.44)]. High levels of recreational and study related SV were significantly associated with poor mental wellbeing [1.81 (1.27, 2.56)] and psychological distress [1.75 (1.11, 2.83)], respectively. Those with high levels of computer time were more likely to have poor mental wellbeing [1.44 (1.01, 2.06)], and high weekend day SV was associated with greater odds of psychological distress [2.16 (1.17, 4.06)]. Conclusions SV among university students was high, as was the high prevalence of poor mental wellbeing and psychological distress. Greater SV was associated with poor mental wellbeing and psychological distress. Differences according to purpose of SV were noted. Although recreational SV was associated with poor mental wellbeing, study related SV was associated with psychological distress. Variations across different devices and timing were also noted. This highlights the need for further longitudinal research to understand the impact of SV on mental health and to guide interventions for promoting mental health of university students globally.

Background The prospective association between sleep duration and the development of late-life depressive symptomology is unclear. Aims To investigate sleep duration from midlife to late life in relation to risk of depressive symptoms in late life. Method A total of 14 361 participants from the Singapore Chinese Health Study were included in the present study. Daily sleep duration was self-reported at baseline (mean age of 52.4 years; 1993–98), follow-up 2 (mean age of 65.2 years; 2006–10) and follow-up 3 (mean age of 72.5 years; 2014–16) interviews. Depressive symptoms were evaluated using the Geriatric Depression Scale at follow-up 3 interviews. Modified Poisson regression models were performed to estimate relative risks and 95% confidence intervals of late-life depressive symptoms in relation to sleep duration at baseline and the two follow-up interviews. Results Compared with sleeping 7 h per day, a short sleep duration of ≤5 h per day at baseline (i.e. midlife) was related to a higher risk of depressive symptoms (relative risk 1.10, 95% CI 1.06–1.15), and this risk was not affected by subsequent prolongation of sleep. Conversely, a long sleep duration of ≥9 h per day at baseline was not related to risk of depressive symptoms. At follow-up 3 (i.e. late life), both short sleep (relative risk 1.20, 95% CI 1.16–1.25) and long sleep (relative risk 1.12, 95% CI 1.07–1.18) duration were cross-sectionally associated with depressive symptoms. Conclusion Short sleep duration in midlife, regardless of subsequent prolongation, is associated with an increased risk of depression in late life. Contrariwise, both short and long sleep duration in late life co-occur with depressive symptoms.

Abstract Introduction Malignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs. Methods An electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest. Results A total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication. Conclusion NF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.

Abstract Diabetes mellitus (DM) is the third most common chronic condition associated with frequent hospital readmissions. Predictors of the number of readmissions within 1 year among patients with DM are less often studied compared with those of 30-day readmission. This study aims to identify predictors of number of readmissions within 1 year amongst adult patients with DM and compare different count regression models with respect to model fit. Data from 2008 to 2015 were extracted from the electronic medical records of the National University Hospital, Singapore. Inpatients aged ≥ 18 years at the time of index admission with a hospital stay > 24 h and survived until discharge were included. The zero-inflated negative binomial (ZINB) model was fitted and compared with three other count models (Poisson, zero-inflated Poisson and negative binomial) in terms of predicted probabilities, misclassification proportions and model fit. Adjusted for other variables in the model, the expected number of readmissions was 1.42 (95% confidence interval [CI] 1.07 to 1.90) for peripheral vascular disease, 1.60 (95% CI 1.34 to 1.92) for renal disease and 2.37 (95% CI 1.67 to 3.35) for Singapore residency. Number of emergency visits, number of drugs and age were other significant predictors, with length of stay fitted as a zero-inflated component. Model comparisons suggested that ZINB provides better prediction than the other three count models. The ZINB model identified five patient characteristics and two comorbidities associated with number of readmissions. It outperformed other count regression models but should be validated before clinical adoption.

IntroductionDiabetes and hypertension are prevalent and costly to the health system. We have developed a mobile app (EMPOWER app) which enables remote monitoring and education through personalised nudges. We aim to study the effectiveness of a multi-component intervention comprising the EMPOWER mobile app with health coaching and shared decision-making for diabetes and hypertension.MethodsWe will conduct a two-arm, open-label, pragmatic randomised controlled trial (RCT). Participants with comorbid diabetes and hypertension enrolled from public primary care clinics will be randomised to either intervention or control in a 1:1 ratio. The intervention group participants will have access to health coaching with shared decision-making interventions in addition to the EMPOWER app and their usual primary care. The control group participants will continue to receive usual primary care and will neither receive the EMPOWER app nor health coaching and shared decision-making interventions. Our primary outcome is change in HbA1c level over 9 months. Secondary outcomes include change in systolic blood pressure, quality of life, patient activation, medication adherence, physical activity level, diet, and healthcare cost (direct and indirect) over 9 months.DiscussionOur trial will provide key insights into clinical- and cost-effectiveness of a multi-component intervention comprising EMPOWER mobile app, health coaching and shared decision-making in diabetes and hypertension management. This trial will also offer evidence on cost-effective and sustainable methods for promoting behavioural changes among patients with comorbid diabetes and hypertension.Trial registrationThis study was registered on clintrials.gov on August 3, 2022, with the trial registration number: NCT05486390.

Summary: Background: Good physical and mental health are essential for healthy ageing. Holistic mobile health (mHealth) interventions—including at least three components: physical activity, diet, and mental health—could support both physical and mental health and be scaled to the population level. This review aims to describe the characteristics of holistic mHealth interventions and their effects on related behavioural and health outcomes among adults from the general population. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, Scopus, China National Knowledge Infrastructure, and Google Scholar (first 200 records). The initial search covered January 1, 2011, to April 13, 2022, and an updated search extended from April 13, 2022 to August 30, 2023. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included if they (i) were delivered via mHealth technologies, (ii) included content on physical activity, diet, and mental health, and (iii) targeted adults (≥18 years old) from the general population or those at risk of non-communicable diseases (NCDs) or mental disorders. Studies were excluded if they targeted pregnant women (due to distinct physiological responses), individuals with pre-existing NCDs or mental disorders (to emphasise prevention), or primarily utilised web, email, or structured phone support (to focus on mobile technologies without exclusive human support). Data (summary data from published reports) extraction and risk-of-bias assessment were completed by two reviewers using a standard template and Cochrane risk-of-bias tools, respectively. Narrative syntheses were conducted for all studies, and random-effects models were used in the meta-analyses to estimate the pooled effect of interventions for outcomes with comparable data in the RCTs. The study was registered in PROSPERO, CRD42022315166. Findings: After screening 5488 identified records, 34 studies (25 RCTs and 9 pre-post NRSIs) reported in 43 articles with 5691 participants (mean age 39 years, SD 12.5) were included. Most (91.2%, n = 31/34) were conducted in high-income countries. The median intervention duration was 3 months, and only 23.5% (n = 8/34) of studies reported follow-up data. Mobile applications, short-message services, and mobile device-compatible websites were the most common mHealth delivery modes; 47.1% (n = 16/34) studies used multiple mHealth delivery modes. Of 15 studies reporting on weight change, 9 showed significant reductions (6 targeted on individuals with overweight or obesity), and in 10 studies reporting perceived stress levels, 4 found significant reductions (all targeted on general adults). In the meta-analysis, holistic mHealth interventions were associated with significant weight loss (9 RCTs; mean difference −1.70 kg, 95% CI −2.45 to −0.95; I2 = 89.00%) and a significant reduction in perceived stress levels (6 RCTs; standardised mean difference [SMD] −0.32; 95% CI −0.52 to −0.12; I2 = 14.52%). There were no significant intervention effects on self-reported moderate-to-vigorous physical activity (5 RCTs; SMD 0.21; 95%CI −0.25 to 0.67; I2 = 74.28%) or diet quality scores (5 RCTs; SMD 0.21; 95%CI −0.47 to 0.65; I2 = 62.27%). All NRSIs were labelled as having a serious risk of bias overall; 56% (n = 14/25) of RCTs were classified as having some concerns, and the others as having a high risk of bias. Interpretation: Findings from identified studies suggest that holistic mHealth interventions may aid reductions in weight and in perceived stress levels, with small to medium effect sizes. The observed effects on diet quality scores and self-reported moderate-to-vigorous physical activity were less clear and require more research. High-quality RCTs with longer follow-up durations are needed to provide more robust evidence. To promote population health, future research should focus on vulnerable populations and those in middle- and low-income countries. Optimal combinations of delivery modes and components to improve efficacy and sustain long-term effects should also be explored. Funding: National Research Foundation, Prime Minister's Office, Singapore, under its Campus for Research Excellence and Technological Enterprise (CREATE) Programme and Physical Activity and Nutrition Determinants in Asia (PANDA) Research Programme.

Preclinical and limited epidemiological studies suggest that oxidative stress may be implicated in geriatric depression. Our study investigated the association between midlife dietary total antioxidant capacity (TAC) and depressive symptoms in late life among 13,712 participants in a population-based cohort of Chinese in Singapore. At baseline (1993–1998), intake of antioxidants from diet and supplements at a mean age of 52.4 years was estimated using a validated food frequency questionnaire to derive two dietary TAC indices from vitamins C and E, carotenoids and flavonoids: the Comprehensive Dietary Antioxidant Index (CDAI) and Vitamin C Equivalent Antioxidant Capacity (VCEAC). At follow-up 3 (2014–2016), when participants were at a mean age of 72.5 years, depressive symptoms were assessed using the Geriatric Depression Scale, and depression, defined as having ≥5 symptoms, was presented in 3173 (23.1%) participants. Both CDAI and VCEAC indices were inversely associated with odds of depressive symptoms in a stepwise manner: the OR (95% CI) comparing the extreme quartiles was 0.73 (0.64–0.83; Ptrend < 0.01) for the CDAI and 0.77 (0.68–0.87; Ptrend < 0.01) for the VCEAC. Specifically, higher intakes of vitamin C, carotenoids, and flavonoids were associated with a lower likelihood of depressive symptoms. Our findings support the recommendation of an antioxidant-rich diet for the prevention of depression.

Abstract Background Despite therapeutic advances, treatment of patients with axial spondyloarthritis (axSpA) continue to pose as a challenge as many do not respond well to conventional Western medications, such as nonsteroidal anti‐inflammatory drugs (NSAIDs) and biologic disease‐modifying antirheumatic drugs (bDMARDs). Hence, acupuncture is a possible alternative. Some studies found electroacupuncture to be better than manual acupuncture, though no trials have been conducted in patients with axSpA. This clinical trial aims to evaluate the clinical efficacy, safety, and cost‐effectiveness of electroacupuncture compared to manual acupuncture for patients with axSpA. Methods/Design This randomized controlled trial will recruit 100 patients diagnosed with axSpA, who have active disease despite NSAIDs and bDMARDs. Eligible patients will be randomized to receive either electroacupuncture or manual acupuncture in a 1:1 ratio. All participants will receive standard rheumatologic care in addition to 20 acupuncture sessions. The mean difference in Bath Ankylosing Spondylitis Disease Activity Index score between the 2 groups over 12 weeks will serve as the primary outcome. Secondary outcomes include improvements in other clinical, quality of life, and economic outcomes over 24 weeks. All adverse events will be recorded. Discussion Results from this trial may provide evidence regarding the clinical effectiveness, safety, and cost‐effectiveness of electroacupuncture compared to manual acupuncture for patients with axSpA, and guide implementation into clinical practice. Limitations of this trial include the lack of patient blinding, use of a repeated measures design, and possible variation in acupuncture technique amongst the various Traditional Chinese Medicine practitioners.

BackgroundExisting modes of collecting self-reported 24-hour movement information from children, including digital assessments, have not been demonstrated to be of acceptable validity when compared to objective measurements. My E-Diary for Activities and Lifestyle (MEDAL) is an interactive web-based diary developed to collect time-use information from children aged 10 years and older. ObjectiveThis study evaluated the validity of MEDAL for assessing children’s movement behaviors by comparing self-reported and accelerometer-measured time spent in movement behavior among children in Singapore aged 10-11 years. MethodsFunding for this study was obtained in October 2017, and data were collected between April and August 2020. Participants recorded their daily activities using MEDAL over 2 specified weekdays and 2 weekend days and wore an Actigraph accelerometer on their nondominant wrist throughout the study to objectively assess movement behaviors. Spearman correlation coefficient and intraclass correlation coefficient (ICC) were used to compare the accelerometer measurements and self-reports for each movement behavior. Bland-Altman plots were generated to investigate trends of bias in the self-reports. ResultsAmong the participants aged 10-11 years (29/49, 59% boys), we observed that children reported lower light physical activity (LPA) and higher moderate-to-vigorous physical activity (MVPA), inactivity, and night sleep than that measured by the accelerometer. There was a moderate-to-strong correlation between self-reported and accelerometer-measured MVPA (r=0.37; 95% CI 0.20-0.54), inactivity (r=0.36; 95% CI 0.18-0.54), and night sleep (r=0.58; 95% CI 0.43-0.74); the correlation for LPA was poor (r=0.19; 95% CI 0.02-0.36). Agreement was poor for all behaviors (MVPA: ICC=0.24, 95% CI 0.07-0.40; LPA: ICC=0.19, 95% CI 0.01-0.36; inactivity: ICC=0.29, 95% CI 0.11-0.44; night sleep: ICC=0.45, 95% CI 0.29-0.58). There was stronger correlation and agreement on weekdays for inactivity and night sleep; conversely, there was stronger correlation and agreement for MVPA and LPA on weekend days. Finally, based on Bland-Altman plots, we observed that with increasing MVPA, children tended to report higher MVPA than that measured by the accelerometer. There were no clear trends for the other behaviors. ConclusionsMEDAL may be used to assess the movement behaviors of children. Based on self-reports, the children are able to estimate their time spent in MVPA, inactivity, and night sleep although actual time spent in these behaviors may differ from accelerometer-derived estimates; self-reported LPA warrant cautious interpretation. Observable differences in reporting accuracy exist between weekdays and weekend days.

Abstract Background This process evaluation explored the implementation and mechanisms of impact of a Park Prescription Intervention trial (PPI), including the effects of hypothesised mediators (motivation, social support, recreational physical activity [PA], park use and park PA) on trial outcomes. Methods Participants from the community were randomly allocated to intervention (n = 80) or control (n = 80) group. The intervention included baseline counselling, a prescription of exercise in parks, materials, three-month follow-up counselling and 26 weekly group exercise sessions in parks. Process evaluation indicators were assessed at three- and six-months. Implementation indicators included participation rates in intervention components and survey questions plus focus group discussions (FGDs) to understand which components participants valued. FGDs further assessed barriers and facilitators to intervention participation. To explore mechanisms of impact, linear regression was used to compare objectively measured PA between quantiles of group exercise participation. Structural equation modelling (SEM) explored hypothesised mediation of the significant intervention effects. Framework analysis was conducted for FGDs. Results Participants were middle-aged (mean 51, SD ± 6.3 years), predominantly female (79%) and of Chinese ethnicity (81%). All intervention participants received baseline counselling, the park prescription and materials, whilst 94% received the follow-up counselling. Mean minutes of moderate-to-vigorous PA/week (95% CI) differed by group exercise participation (p = 0.018): 0% participation (n = 18) 128.3 (69.3, 187.2) minutes, > 0–35.9% participation (n = 18) 100.3 (36.9, 163.6) minutes, > 35.9–67.9% participation (n = 17) 50.5 (− 4.9, 105.9) minutes and > 67.9% participation (n = 18) 177.4 (122.0, 232.8) minutes. Park PA at three-months had significant mediating effects (95% CI) on recreational PA 26.50 (6.65, 49.37) minutes/week, park use 185.38 (45.40, 353.74) minutes/month, park PA/month 165.48 (33.14, 334.16) minutes and psychological quality of life score 1.25 (0.19, 2.69) at six-months. Prioritising time with family and preferences for unstructured activities were barriers to intervention participation. Human interaction via follow-up or group exercise were facilitators. Conclusion This process evaluation showed park PA consistently mediated effects of the PPI, suggesting activity in parks was a mechanism of its effects. To optimise effectiveness, participants’ preference for prioritising time with family through family involvement and tailoring the intervention to participants’ preferences for structured or unstructured PA could be considered in future studies. Trial registration ClinicalTrials.gov NCT02615392 , 26 November 2015.

Abstract Background Colorectal cancer patients undergoing surgical resection are at increased short-term risk of post-operative adverse events. However, specific predictors for long-term major adverse cardiac and cerebrovascular events (MACCE) are unclear. We hypothesised that patients who receive chemotherapy are at higher risk of MACCE than those who did not. Methods In this retrospective study, 412 patients who underwent surgical resection for newly diagnosed colorectal cancer from January 2013 to April 2015 were grouped according to chemotherapy status. MACCE was defined as a composite of cardiovascular death, myocardial infarction, stroke, unplanned revascularisation, hospitalisation for heart failure or angina. Predictors of MACCE were identified using competing risks regression, with non-cardiovascular death a competing risk. Results There were 200 patients in the chemotherapy group and 212 patients in the non-chemotherapy group. The overall prevalence of prior cardiovascular disease was 20.9%. Over a median follow-up duration of 5.1 years from diagnosis, the incidence of MACCE was 13.3%. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE (subdistribution hazard ratio, 2.56; 95% CI, 1.48-4.42) and 2.38 (95% CI, 1.36-4.18) respectively. The chemotherapy group was associated with a lower risk of MACCE (subdistribution hazard ratio, 0.37; 95% CI, 0.19-0.75) compared to the non-chemotherapy group. Conclusions Amongst colorectal cancer patients undergoing surgical resection, there was a high incidence of MACCE. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE. Chemotherapy was associated with a lower risk of MACCE, but further research is required to clarify this association.

BackgroundGay, bisexual, and other men who have sex with men (GBMSM) are at disproportionately higher risk of acquiring HIV and other sexually transmitted infections (STI). While HIV/STI testing rates among GBMSM are increasing worldwide, they remain suboptimal in a variety of settings. While many studies have attempted to evaluate the efficacy of a variety of community-based campaigns, including peer and reminder-based interventions on HIV/STI testing, however few have attempted to do so for a web drama series. ObjectiveThis study evaluates the effectiveness of a popular web drama video series developed by a community-based organization in Singapore for GBMSM on HIV and other STI testing behaviors. MethodsThe study is a pragmatic, randomized controlled trial to evaluate a popular web drama video series developed by a community-based organization in Singapore for GBMSM. A total of 300 HIV-negative, GBMSM men in Singapore aged 18 to 29 years old were recruited and block-randomized into the intervention (n=150) and control arms (n=150). Primary outcomes included changes in self-reported intention to test for, actual testing for, and regularity of testing for HIV, syphilis, chlamydia or gonorrhea, while secondary outcomes include changes in a variety of other knowledge-based and psychosocial measures at the end of the study period. ResultsOverall, 83.3% (125/150) of participants in the intervention arm completed the proof of completion survey, compared to 88.7% (133/150) in the control arm. We found improvements in self-reporting as a regular (at least yearly) tester for HIV (15.9% difference, 95% CI, 3.2% to 28.6%; P=.02), as well as chlamydia or gonorrhea (15.5% difference, 95% CI, 4.2% to 26.9%; P=.009), indicating that the intervention had positively impacted these outcomes compared to the control condition. We also found improvements in participants’ intentions to test for HIV (16.6% difference, 95% CI, 4.3% to 28.9%; P=.009), syphilis (14.8% difference, 95% CI, 3.2% to 26.4%; P=.01), as well as chlamydia or gonorrhea (15.4% difference, 95% CI, 4.2% to 26.6%; P=.008), in the next 3 months, indicating that the intervention was effective in positively impacting intention for HIV and other STI testing among participants. ConclusionsThere are clear benefits for promoting intentions to test regularly and prospectively on a broad scale through this intervention. This intervention also has potential to reach GBMSM who may not have access to conventional HIV and other STI prevention messaging, which have typically been implemented at sex-on-premises venues, bars, clubs, and in sexual health settings frequented by GBMSM. When coupled with community or population-wide structural interventions, the overall impact on testing will likely be significant. Trial RegistrationClinicalTrials.gov NCT04021953; https://clinicaltrials.gov/ct2/show/NCT04021953 International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2019-033855

Abstract Background We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC. Methods Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS). Results We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38–3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14–1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15–3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51–1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792). Conclusions The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial. Trial registration The study was registered ( NCT01803503 ) prospectively on clinicaltrials.gov on 4th March 2013.

Background: Medication adherence is crucial for improving clinical outcomes in the treatment of patients. We evaluate the effect of short message service (SMS) reminder on medication adherence and serum hormones in patients with breast cancer on aromatase inhibitors. Methods: An open-label, multi-centre, prospective randomised controlled trial of SMS versus Standard Care was conducted. Medication adherence was assessed via self-report using the Simplified Medication Adherence Questionnaire at baseline, 6 month, and 1 year. Androstenedione, estradiol, and estrone were measured at baseline and 1 year. The χ2 test and mixed effects logistic regression was performed to compare medication adherence between groups. Difference in androstenedione and estrone levels were assessed using analysis of covariance, whereas χ2 test and logistic regression was used for estradiol. Analysis was based on intention-to-treat. Results: A total of 244 patients were randomised to receive weekly SMS reminder (n = 123) or Standard Care (n = 121) between May 2015 and December 2018. The odds of adherence was higher at 6-month in SMS (OR = 1.78, 95% CI 1.04–3.05, p = 0.034), and not significantly different at 1-year (OR = 1.15, 95% CI: 0.67–1.96 p = 0.617). Mixed effects logistic regression analysis showed higher odds of adherence in SMS over the 1-year period (OR = 2.35, 95% CI: 1.01–5.49, p = 0.048). There was no difference in serum hormone levels between groups. Conclusion: SMS reminder improved medication adherence in the short-term but had no effect on serum hormones levels in the longer term. Future studies could investigate the use of tailored SMS intervention according to patient preference to improve its sustainability.

Abstract Background High levels of sedentary behaviour (SB) are associated with non-communicable diseases. In 2016, the estimated total healthcare expenditure from physical activity (PA) in Thailand added up to $190 million in international dollars. The challenge to reduce SB and increase PA among office workers is more urgent now than ever as Thailand is transforming itself from a predominantly rural country to an increasingly urban one. This study will investigate the effectiveness of a multicomponent short break intervention on the reduction of SB during office hours. Methods/design This two-armed Physical Activity at Work (PAW) cluster randomised controlled trial will recruit 360 office workers from 18 offices in the Thailand’s Ministry of Public Health (MOPH). Offices will be randomised to either the intervention group or the control group. The multicomponent intervention is informed by the Social Ecological Model and Behaviour Change Techniques (BCTs) and contains four components: (i) organisational, including heads of the participating divisions leading exercises, sending encouragement text messages and acknowledging efforts; (ii) social, including team movement breaks and team-based incentives; (iii) environmental, including posters to encourage exercise; and (iv) individual components including real-time PA feedback via an individual device. The main intervention component will be a short break intervention. The primary outcome of this study is the sedentary time of office workers. Secondary outcomes include time spent on PA, cardiometabolic outcomes, work productivity, musculoskeletal pain, and quality of life. The study also includes process and economic evaluations from the individual and societal perspective. Discussion The study will be the first experimental study in Thailand to investigate the effect of a short-break intervention at the workplace on SBs of office workers and health outcomes. The study will also include a cost-effectiveness analysis to inform investments on short break interventions under the Universal Healthcare Coverage in Thailand, which includes health promotion and disease prevention component. Trial registration The PAW study has been registered at the Thai Clinical Trials Registry (TCTR) under the study ID TCTR20200604007 . Registered 02 June 2020,

Introduction: Several studies have reaffirmed the use of regular pentoxifylline therapy in increasing the penile brachial pressure index in men affected by erectile dysfunction when compared to placebo. Aim: The aim of this study was to evaluate the efficacy of pentoxifylline as an adjunctive treatment for patients with erectile dysfunction. Methods: This study was a single center, prospective, randomized, double-blind, placebo-controlled trial. Subjects were recruited between April 2014 and November 2016 from the National University Hospital, Singapore. The combination therapy group was given pentoxifylline 400 mg thrice daily orally and the monotherapy group was given placebo capsules thrice daily orally. Both groups continued their on-demand 100 mg sildenafil. The treatment duration was 8 weeks. Efficacy was measured via the International Index of Erectile Function (IIEF-5) questionnaire at the eighth week. Differences in mean IIEF-5 score and the domains of the IIEF at 8 weeks between the 2 treatment groups were compared using independent sample t-test. Main Outcome Measure: Baseline IIEF-5 and the IIEF-15 score vs post-therapy IIEF-5 and the IIEF-15 score. Results: 50 patients were randomized into 2 groups. Patients in the 2 groups were comparable in terms of the demographic and clinical characteristics, comorbidities, and baseline IIEF-5 scores. The mean IIEF-5 score post-therapy of the combination therapy group vs the monotherapy group was 14.11 and 14.87, respectively. There was no significant difference between the outcomes of these 2 groups (unadjusted mean difference -0.76; 95% CI -4.01 to 2.49; P = .641) and the outcomes are the same even after adjusting for baseline IIEF-5 scores. There was a significant improvement in the “overall satisfaction” portion of the IIEF score for the combination therapy group as compared to the monotherapy group (unadjusted mean difference 0.12; 95% CI -1.49 to 1.25) and even after adjustment for baseline scores (adjusted mean difference 1.11; 95% CI 0.10 to 2.12; P = .032) the improvement is significant. Conclusion: Our trial suggests that the use of combination therapy does not improve the management of patients compared to monotherapy.Law YXT, Tai BC, Tan YQ et al. A Small Group Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy of Daily Pentoxifylline in the Management of Patients With Erectile Dysfunction with Suboptimal Treatment Response to Sildenafil. Sex Med 2019;8:14–20. Key Words: Pentoxifylline, Erectile Dysfunction, Placebo-Controlled Trial, Phosphodiesterase-5 Inhibitor

Abstract Background Programs promoting population health through physical activity (PA) and exposure to nature are popular, but few have been evaluated in randomized-controlled trials (RCTs). Objective To investigate the effectiveness of a park prescription intervention (PPI) for improving total moderate-to-vigorous PA (MVPA), other PA related behaviors, quality of life (QoL) and cardio-metabolic health among adults. Methods Healthy individuals aged 40 to 65 years were recruited through community health screenings and randomly assigned to 1) PPI: face-to-face Park Prescription + invitation to weekly exercise sessions in parks, or 2) control: standard PA materials. After the six-month intervention, participants completed accelerometer assessments, questionnaires on health behaviors and QoL, and health screenings. Independent sample t-tests were used to compare outcomes between groups, with secondary analysis adjusted for co-variates via multiple linear regression. A p-value

IntroductionType 2 diabetes mellitus (T2DM) poses huge burden and cost on the healthcare system. Mobile health (mHealth) interventions that incorporate wearables may be able to improve diabetes self-management. The aim of this randomized controlled trial (RCT) is to investigate the clinical and cost-effectiveness of personalized educational and behavioral interventions delivered through an EMPOWER mobile application (app) among patients with T2DM.MethodsThis is a parallel two-arm randomized controlled trial (RCT). Patients with T2DM recruited from primary care will be randomly allocated in a 1:1 ratio to either intervention or control group. The intervention group will receive personalized educational and behavioral interventions through the EMPOWER app in addition to their usual clinical care. The control group will receive the usual clinical care for their T2DM but will not have access to the EMPOWER app. Our primary outcome is patient activation score at 12 months. Secondary outcomes will include HbA1c, physical activity level and diet throughout 12 months; quality of life (QoL), medication adherence, direct healthcare cost and indirect healthcare cost at 6 and 12 months.DiscussionThis RCT will provide valuable insights into the effectiveness and implementation of personalized educational and behavioral interventions delivered through mobile application in T2DM management. Findings from this study can help to achieve sustainable and cost-effective behavioral change in patients with T2DM, and this can be potentially scaled to other chronic diseases such as hypertension and dyslipidemia.

Background: Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations. Therefore, this study aimed to understand public sentiment and different barriers toward organ donation from the perspective of Singapore, a highly diverse and multiethnic Asian society.Methods: A cross-sectional community semi-structured interview was conducted in a public housing estate in Singapore. Pilot test was undertaken before participants were interviewed face-to-face by trained personnel. All statistical evaluations were conducted using Stata. The χ2-test compared subgroups based on patient characteristics while multivariable logistic regression identified predictors of willingness to donate/ assent. Effect estimates were quantified using odds ratio (OR).Findings: Out of 799 individuals, 85% were agreeable to organ donation after death and 81% were willing to assent to donations of family members' organs, which declined by 16% (p < 0.001) after a clinical scenario was presented. Demographic factors including ethnicity, education, marital, and employment status affected willingness to donate and assent. Knowledge correlated significantly with willingness to donate and assent. In particular, knowledge regarding brain death irreversibility had the strongest correlation (AOR 2.15; 95% CI 1.60–2.89).Conclusions: Organ donation rates remain low albeit presumed consent legislation, due to patient-level barriers, including but not limited to knowledge gaps, cultural values, religious backgrounds, and emotional impact at relatives' death. To effectively boost donor rates, it is crucial for policy makers to invest in public education and improve transplant provisions and family protocols.

Abstract Background Loss and grief are experienced by caregivers of persons with dementia (PWD), relating to the ambiguous loss of PWD even when they are still alive and the anticipation of future loss related to their physical death. Such experience of caregiver grief is not easily recognized in clinical practice, despite its association with adverse effects such as caregiver burden, caregiver depression and caregivers’ desire to place the PWD in nursing homes. We constructed a simple screening tool – based on factors associated with caregiver grief – to identify caregivers with high grief. Methods Spouses or children of community-dwelling PWD (n = 403) completed self-administered questionnaires containing a well-established grief scale and information related to the caregiver and PWD. We split the study sample into two – the derivation sample (n = 300) was used to identify factors associated with grief (using logistic regression) and derive a simple tool based on the number of identified factors; the validation sample (n = 103) evaluated the performance of the tool using the receiver-operating-characteristic-curve-analysis (ROC). Results Four key factors were identified by the multivariable regression – more severe dementia (odds ratio, OR 6.9), behavioral problems in PWD (OR 5.0), spousal caregivers (OR 6.0) and daily caregiving (OR 3.0). The screening tool (based on the number of key factors) had an area under ROC of 0.77. At the optimal cut-off of ≥2 key factors, the tool had a sensitivity of 0.91 and a specificity of 0.42. Conclusions The identified factors are consistent with current understanding on caregiver grief. They can be easily integrated into the workflow of routine services to screen for caregivers who are more likely to benefit from further grief-related assessment.

Abstract Background Axial spondyloarthritis (AxSpA) is a chronic disease which results in fatigue, pain, and reduced quality of life (QoL). Traditional Chinese medicine (TCM), especially acupuncture, has shown promise in managing pain. Although a TCM collaborative model of care (TCMCMC) has been studied in cancer, there are no randomized controlled trials investigating TCM in AxSpA. Therefore, we will conduct a pragmatic trial to determine the clinical effectiveness, safety, and cost-effectiveness of TCMCMC for patients with AxSpA. We define TCMCMC as standard TCM history taking and physical examination, acupuncture, and TCM non-pharmacological advice and communications with rheumatologists in addition to usual rheumatologic care. The purpose of this paper is to describe the rationale for and methodology of this trial. Methods/design This pragmatic randomized controlled trial will recruit 160 patients who are diagnosed with AxSpA and have inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). Simple randomization to usual rheumatologic care or the intervention (TCMCMC) with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the TCMCMC arm. All participants will continue to receive usual rheumatologic care. The primary endpoint — spinal pain — will be evaluated at week 6. Secondary endpoints include clinical, quality of life, and economic outcome measures. Patients will be followed up for up to 52 weeks, and adverse events will be documented. Discussion This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of a TCMCMC for patients with AxSpA. Trial registration ClinicalTrials.gov, NCT03420404. Registered on 14 February 2018.

Purpose: We investigated the use of human Cord Lining Mesenchymal Stem Cells (CL-MSCs) (US Patent number 9,737,568), in a rabbit hindlimb ischemia model, and evaluated their potential in stimulating neovascularization. Allogenic human CL- MSCs could potentially be used to treat patients with lower limb ischemia and non-healing wounds.Methods: Twenty rabbits were divided into two separate groups. We created a hindlimb ischemia model surgically. At 21 and 49 days post-operatively, animals in the treatment group were injected with CL-MSCs (500,000 cells per 0.2 ml on each site) at 10 different sites (Quadriceps- 4 sites, Hamstrings- 4 sites and Calf-−2 sites) in the hindlimb muscles. The control group received only saline injection to the corresponding sites at the same time point as the treatment group. We then evaluated the effects of treatment on neovascularization by angiography, laser doppler perfusion imaging, as well as by histology. We evaluated the tissue samples for any signs of local immune reaction to the cell implantation. We also observed the rabbit clinically for any adverse effects after treatment.Results: We found a higher number of CD31 positive cells in the treatment group, with a greater number of capillaries found in the treated muscles. The Rectus Femoris demonstrated a median vessel count/muscle fiber of 0.121 for the treatment group, compared to 0.076 in the control group (median difference 0.04; 95% CI 0.001–0.11; p = 0.041). The Gastrocnemius demonstrated a median vessel count/muscle fiber of 0.175 for the treatment group, compared to 0.089 in the control group (median difference 0.087; 95% CI −0.006 to 0.234; p = 0.07). Blood perfusion quantification through Laser Doppler Perfusion Imaging (LDPI) also demonstrated a non-statistically significant increase in perfusion in favor of the treatment group. CL-MSCs demonstrated no toxicity associated morbidity and minimal local immune reaction to implantation.Conclusion: CL-MSCs have a positive effect on angiogenesis in a rabbit hindlimb ischemia model. This preliminary data is encouraging and paves the way for future large animal studies or for clinical trials.

ObjectiveIndividuals with diabetic peripheral neuropathy (DPN) have functional deficits that increase their risk of falling. However, psychological aspects such as loss of confidence in undertaking activities could also contribute to this risk. We examined correlations between balance confidence and fall risk among individuals with DPN.MethodsThis was a cross-sectional study of 146 individuals with DPN. Elevated fall risk was determined by timed up-and-go test with standard cut-off time of 13.5 seconds, and balance confidence was measured by 16-item Activities Specific Balance Confidence scale. Functional parameters assessed included functional reach, body sway velocity during quiet standing and muscle strength at ankle and toe.ResultsTwenty percent of the DPN patients were at increased risk of falls. Every unit increase in balance confidence was associated with 9% (95% confidence interval: 0.88, 0.95; p

Adult patients with diabetes mellitus (DM) represent one-fifth of all 30-day unplanned hospital readmissions but some may be preventable through continuity of care with better DM self-management. We aim to synthesize evidence concerning the association between 30-day unplanned hospital readmission and patient-related factors, insurance status, treatment and comorbidities in adult patients with DM. We searched full-text English language articles in three electronic databases (MEDLINE, Embase and CINAHL) without confining to a particular publication period or geographical area. Prospective and retrospective cohort and case–control studies which identified significant risk factors of 30-day unplanned hospital readmission were included, while interventional studies were excluded. The study participants were aged ≥18 years with either type 1 or 2 DM. The random effects model was used to quantify the overall effect of each factor. Twenty-three studies published between 1998 and 2018 met the selection criteria and 18 provided information for the meta-analysis. The data were collected within a period ranging from 1 to 15 years. Although patient-related factors such as age, gender and race were identified, comorbidities such as heart failure (OR=1.81, 95% CI 1.67 to 1.96) and renal disease (OR=1.69, 95% CI 1.34 to 2.12), as well as insulin therapy (OR=1.45, 95% CI 1.24 to 1.71) and insurance status (OR=1.41, 95% CI 1.22 to 1.63) were stronger predictors of 30-day unplanned hospital readmission. The findings may be used to target DM self-management education at vulnerable groups based on comorbidities, insurance type, and insulin therapy.

Abstract Objective Framing of fiscal incentives has been suggested to be important in influencing purchase decisions. We aimed to examine the effect of framing a modest price difference between high- and lower-sugar beverages as a tax or a subsidy respectively, using messages placed on vending machines to influence beverage purchases. Design/setting This is an 11-week randomized crossover trial conducted between August and November 2015, with a two-week run-in period before intervention, targeted at students, staff and faculty of a university campus in Singapore. Twenty-one beverage vending machines were used to implement the intervention involving ‘tax message’, ‘subsidy message’ and ‘no message (control)’. The former two messages suggest ‘a tax for high sugar beverages’ or ‘a subsidy for lower sugar beverages’ respectively. Prices of the beverages offered were fixed at baseline and remained the same in all three experimental conditions: lower-sugar beverage options were priced ~ 10% lower than the corresponding high-sugar option. The machines were randomized to one of the 6 sequences of intervention. Each message intervention period was 3 weeks. The effect of messages was assessed by comparing average weekly units of beverages sold between interventions using mixed effects model. Results The average weekly units of high and lower-sugar beverages sold per vending machine were 115 and 98 respectively in the control condition. The percentage of high-sugar beverages sold was 54% in the control, 53% in the tax, and 54% in the subsidy message condition. There was no difference in the weekly units of high-sugar beverages sold for the tax message (− 2, 95% CI -8 to 5, p = 0.61) or the subsidy message (0, 95% CI -10 to 10, p = 0.96) conditions as compared with the control condition. Similarly, there was no difference in the weekly units of lower-sugar beverages sold for the tax message (4, 95% CI -4 to 13, p = 0.32) or the subsidy message (7, 95% CI -4 to 18, p = 0.18) conditions as compared with the control condition. Conclusions The use of tax and subsidy messages to highlight modest price differences did not substantially reduce high-sugar beverage sales in vending machines on an Asian university campus.

Abstract Background Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved. Methods An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy. Results Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference −1.16, 90% CI −1.48 to −0.84, P

Abstract Background Medication adherence refers to whether a patient takes medication according to the frequency prescribed, or continues to take a prescribed medication. Inadequate adherence to medication may cause alterations in risk-benefit ratios, resulting in reduced benefits, increased risks or both, and is significantly associated with adverse clinical outcomes and higher healthcare costs. We aim to examine the effect of a computer generated short message service (SMS) reminder in improving medication adherence, and inhibiting the aromatisation process amongst breast cancer women receiving oral aromatase inhibitor therapy. Methods/Design In this randomised controlled trial, eligible patients will be equally allocated to receive either SMS reminder or standard care. The former receives weekly SMS reminder to take medication while the latter does not receive any. The primary endpoint of medication adherence at 1-year is assessed using the Simplified Medication Adherence Questionnaire, and compared using the χ2 test. Adjustment for baseline covariate and potential confounders will be made using the logistic regression. Secondary outcomes involving estrone and androstenedione levels will be compared using the analysis of covariance, whereas the estradiol levels (

Abstract Background Pre-death grief (PDG) is a key challenge faced by caregivers of persons with dementia (PWD). Marwit-Meuser Caregiver Grief Inventory (MM-CGI) and its abbreviated MM-CGI-Short-Form (MM-CGI-SF) are among the few empirically-developed scales that detect PDG. However, they have not had a Mandarin-Chinese version even though Chinese-speaking populations have among the largest number of PWD. We produced a Mandarin-Chinese version of MM-CGI and evaluated whether it had equivalent scores and similar psychometric properties to the English version. Methods We produced the Chinese MM-CGI through the methods of forward-backward translation and cognitive debriefing. Then, we recruited family caregivers of PWD (n = 394) to complete either the Chinese (n = 103) or English (n = 291) version. The two versions were compared in their score-difference (adjusting for potential confounders using multiple linear regression), internal-consistency reliability (using Cronbach’s α) and test-retest reliability (using intraclass correlation-coefficient), known-group validity (based on the relationship with the PWD and stage of dementia) and construct validity (using Spearman’s correlation-coefficient). Results The two versions showed similar mean scores, with the adjusted score-difference of 1.2 (90% CI -5.6 to 7.9) for MM-CGI and − 0.4 (90% CI -2.9 to 2.1) for MM-CGI-SF. The 90% CI for adjusted score-difference fell within predefined equivalence-margin (±8 for MM-CGI and ± 3 for MM-CGI-SF) and indicated equivalence of the scores. The two versions also demonstrated similar characteristics in reliability and validity. Conclusions The Chinese MM-CGI opens the way for PDG assessment and intervention among Chinese-speaking caregivers. Establishing its measurement equivalence with the English version paves the way for cross-cultural research on PDG in dementia caregiving.

Abstract Background Following Cambodia’s implementation of the 100% condom use program with enforcement of condom use and STI treatment services for sex workers in 2001, sexually transmitted infection and HIV declined markedly. In 2008, Cambodia implemented a law to ban brothel-based sex work. We reported trends in unprotected vaginal intercourse with sex workers among heterosexual men buying sex before (2003–2008) and after (2009–2012) the brothel ban in Cambodia. We also determined the association of brothel ban with these men’s reports of unprotected intercourse with sex workers. Methods In this serial cross-sectional study, we collected yearly behavioural data on random cross-sectional samples of heterosexual men buying sex who attended the only government health centre in Siem Reap for voluntary confidential counselling and testing (VCCT) between 2003 and 2012. We used multivariable Poisson regression analysis on the 10-year data of 976 men to obtain the adjusted prevalence ratio (aPR) of unprotected intercourse in the last 6 months by brothel closure. Results Men buying sex from non-brothel-based sex workers increased almost 3-fold from 17% in 2007–2008 before brothel closure to 55% in 2011–2012 after brothel closure (p

Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic "gray zone" of 4-10 ng ml-1 . False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index (PHI) in Asian men presenting with a total PSA between 4.0 and 10 ng ml-1 . We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1 . Thirty (19.1%) were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHI. The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity (95% CI) of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 (49%) unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHI levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng ml-1 .

Background: Coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus in cohort studies. In addition, coffee components increased insulin sensitivity in animal models. However, data from intervention studies on the effect of coffee consumption on glucose metabolism have been limited by small sample sizes, lack of blinding, short follow-up duration and the use of surrogate indices of insulin sensitivity. We designed the Coffee for Metabolic Health (COMETH) study to evaluate the effect of coffee consumption on insulin sensitivity. Methodology: The COMETH study is a double-blind randomized placebo-controlled 24-week trial. Participants were overweight, male and female habitual coffee consumers who were of Chinese, Malay and Asian-Indian ethnicity. We excluded smokers, persons with diabetes, and persons with low insulin resistance (HOMA-IR

miRNAs can function either as proto-oncogenes or tumour suppressors in several cancers; however their function in tumour initiating cells is unclear. Here, Zhang et al. show that tumour initiating cell-specific miR-1246 and miR-1290 promote lung cancer initiation and metastasis and could serve as prognostic markers.

BACKGROUND:This mixed methods study aims to describe 1) characteristics of the population treated with non-occupational post-exposure prophylaxis (nPEP), 2) predictors of loss to follow-up (LTFU) and nPEP adherence, and 3) to evaluate the nPEP prescribing practices against current management guideline. METHODS:This study was conducted at the Department of Sexually Transmitted Infections Control Clinic in Singapore using clinical data from 2010 to 2016. Explanatory sequential mixed method design was adopted. Predictors of LTFU and nPEP adherence were assessed using modified Poisson regression with robust sandwich variance. Subsequently, nine in-depth interviews with healthcare providers were conducted to gain their insights into barriers and facilitators to nPEP implementation. Transcripts were coded and themes were explored using applied thematic analysis. RESULTS:Of 502 nPEP cases reviewed, 46% were LTFU, 42% were adherent to nPEP and 431 prescription decisions were made in accordance with the guideline. Tourists (aRR, 2.29 [1.90-2.74]; p

Background: Smoking is a known trigger of asthma exacerbation. Yet some patients with asthma continue to smoke. Little is known about their smoking literacy, which is defined as an individual’s capacity to comprehend and use healthcare information relating to smoking. This study aimed to determine the level of smoking literacy amongst patients with asthma, who were smokers (S) and non-smokers (NS). Methods: Standardised questionnaires were administered by trained research assistants to adult multi-ethnic Asian patients with asthma, who were managed in three public primary care clinics (polyclinics) in Singapore. Demographic data and information on a subject’s understanding and effects of smoking on health and complications were collected. The latter were computed into knowledge scores and the mean scores between S and NS were compared using the independent two-sample t-test with adjustment for potential confounders via multiple linear regression. Results: A total of 174 S and 183 NS were recruited with a higher proportion of younger male S. Overall, the knowledge score for S was significantly lower than NS (absolute mean difference (AMD) = −0.95, 95% confidence interval (CI) −1.58 to −0.33, p = 0.003). This was particularly for smoking associated specific respiratory disease (AMD = −0.23, 95% CI −0.44 to −0.02, p =0.034) and asthma symptoms (AMD = −0.73, 95% CI −0.98 to −0.47, p < 0.001). The differences persisted after adjusting for other important factors such as gender and education level. Conclusions: Compared with NS, S generally reported lower scores in their overall knowledge, and the knowledge in the association between smoking and specific respiratory diseases and asthma symptoms. Smoker patients may require measures to raise their smoking literacy during the counselling to optimise their smoking cessation success rates.

Sedative and analgesic practices in intensive care units (ICUs) are frequently based on anesthesia regimes but do not take account of the important patient related factors. Pharmacologic properties of sedatives and analgesics change when used as continuous infusions in ICU compared to bolus or short-term infusions during anesthesia. In a prospective observational cohort study, we investigated the association between patient related factors and sedatives/analgesics doses in patients on mechanical ventilation (MV) and their association with cessation of sedation/analgesia. We included patients expected to receive MV for at least 24 hours and excluded those with difficulty in assessing the depth of sedation. We collected data for the first 72 hours or until extubation, whichever occurred first. Multivariate analysis of variance, multivariate regression as well as logistic regression were used. The final cohort (N = 576) was predominantly male (64%) with mean (SD) age 61.7 (15.6) years, weight 63.4 (18.2) Kg, Acute Physiology and Chronic Health Evaluation II score 28.2 (8) and 30% hospital mortality. Increasing age was associated with reduced propofol and fentanyl doses requirements, adjusted to the weight (p