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OBJECTIVE: To develop and validate an instrument to assess knowledge and attitudes regarding the use of psychological interventions in primary care. METHODS: A 13-item questionnaire was developed based on literature review and expert panel discussion. Exploratory and confirmatory factor analyses were carried out to test the construct validity of the subscales. Item-scale correlations were used to test the construct validity of the items. Internal reliability was tested by Cronbach's alpha. Responsiveness of the instrument was evaluated by using independent t-test of pre and post program scores. RESULTS: Exploratory factor analysis extracted four factors: skills and knowledge, confidence to provide counseling, willingness to provide counseling, and curriculum needs. Confirmatory factor analysis demonstrated excellent goodness-of-fit. Item scale correlations confirmed convergent and discriminant validity. Good responsiveness was shown on independent t-test of the pre and post responses. CONCLUSIONS: The Attitudes to Psychological Interventions and Counseling in Primary Care (APIC-PC) survey is a valid and responsive instrument for assessing knowledge and attitudes regarding psychological approaches in patient management (mental health care). PRACTICE IMPLICATIONS: Psycho-social counseling skills training is increasingly being recognised as a valuable component of undergraduate primary care medical education. The APIC-PC is a useful tool for evaluating the impact of such programs. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between changes in haemoglobin A1c (HbA1c) and the concurrent incidence of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients., Method: We conducted a retrospective cohort study among T2DM patients with HbA1c measurement after T2DM diagnosis between August 2009 and September 2010. The patients were classified into six subgroups based on baseline HbA1c (<7%; 7%-7.9%; ≥8%) and age (<65; ≥65 years), and then clustered into classes by HbA1c trajectory and CVD incidence over the 12-year follow-up period using joint latent class mixture models. We explored the HbA1c trajectories and CVD incidences in each latent class. Multinomial logistic regression was used to compare the baseline characteristics among different latent classes., Results: A total of 128 843 T2DM patients were included with a median follow-up period of 11.7 years. Ten latent classes were identified in patients with baseline HbA1c ≥ 8% and age <65 years, while seven classes were identified in the other five groups. Among all the identified latent classes, patients with fluctuating HbA1c trajectories, characterized by alternating periods of increase and decrease, had higher CVD incidences. Male patients, and patients with higher baseline HbA1c and use of antidiabetic drugs were more likely to have a fluctuating HbA1c trajectory. More specifically, patients aged < 65 years with younger age or a smoking habit, and patients aged ≥ 65 years with a longer duration of T2DM were more likely to have a fluctuating HbA1c trajectory., Conclusion: We found that T2DM patients with fluctuating HbA1c trajectories could have a higher CVD risk. Different trajectory-associated characteristics in age subgroups highlight the need for individualized management of T2DM patients., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Adverse drug events, encompassing both adverse drug reactions and medication errors, pose a significant threat to health, leading to illness and, in severe cases, death. Timely and voluntary reporting of adverse drug events by healthcare professionals plays a crucial role in mitigating the morbidity and mortality linked to unexpected reactions and improper medication usage., Objectives: To assess the effectiveness of different interventions aimed at healthcare professionals to improve the reporting of adverse drug events., Search Methods: We searched CENTRAL, Embase, MEDLINE and several other electronic databases and trials registers, including ClinicalTrials.gov and WHO ICTRP, from inception until 14 October 2022. We also screened reference lists in the included studies and relevant systematic reviews., Selection Criteria: We included randomised trials, non-randomised controlled studies, controlled before-after studies, interrupted time series studies (ITS) and repeated measures studies, assessing the effect of any intervention aimed at healthcare professionals and designed to increase adverse drug event reporting. Eligible comparators were healthcare professionals' usual reporting practice or a different intervention or interventions designed to improve adverse drug event reporting rate. We excluded studies of interventions targeted at adverse event reporting following immunisation. Our primary outcome measures were the total number of adverse drug event reports (including both adverse drug reaction reports and medication error reports) and the number of false adverse drug event reports (encompassing both adverse drug reaction reports and medication error reports) submitted by healthcare professionals. Secondary outcomes were the number of serious, high-causality, unexpected or previously unknown, and new drug-related adverse drug event reports submitted by healthcare professionals. We used GRADE to assess the certainty of evidence., Data Collection and Analysis: We followed standard methods recommended by Cochrane and the Cochrane Effective Practice and Organisation of Care (EPOC) Group. We extracted and reanalysed ITS study data and imputed treatment effect estimates (including standard errors or confidence intervals) for the randomised studies., Main Results: We included 15 studies (eight RCTs, six ITS, and one non-randomised cross-over study) with approximately 62,389 participants. All studies were conducted in high-income countries in large tertiary care hospitals. There was a high risk of performance bias in the controlled studies due to the nature of the interventions. None of the ITS studies had a control arm, so we could not be sure of the detected effects being independent of other changes. None of the studies reported on the number of false adverse drug event reports submitted. There is low-certainty evidence suggesting that an education session, together with reminder card and adverse drug reaction (ADR) report form, may substantially improve the rate of ADR reporting by healthcare professionals when compared to usual practice (i.e. spontaneous reporting with or without some training provided by regional pharmacosurveillance units). These educational interventions increased the number of ADR reports in total (RR 3.00, 95% CI 1.53 to 5.90; 5 studies, 21,655 participants), serious ADR reports (RR 3.30, 95% CI 1.51 to 7.21; 5 studies, 21,655 participants), high-causality ADR reports (RR 2.48, 95% CI 1.11 to 5.57; 5 studies, 21,655 participants), unexpected ADR reports (RR 4.72, 95% CI 1.75 to 12.76; 4 studies, 15,085 participants) and new drug-related ADR reports (RR 8.68, 95% CI 3.40 to 22.13; 2 studies, 7884 participants). Additionally, low-certainty evidence suggests that, compared to usual practice (i.e. spontaneous reporting), making it easier to report ADRs by using a standardised discharge form with added ADR items may slightly improve the total number of ADR reports submitted (RR 2.06, 95% CI 1.11 to 3.83; 1 study, 5967 participants). The discharge form tested was based on the 'Diagnosis Related Groups' (DRG) system for recording patient diagnoses, and the medical and surgical procedures received during their hospital stay. Due to very low-certainty evidence, we do not know if the following interventions have any effect on the total number of adverse drug event reports (including both ADR and ME reports) submitted by healthcare professionals: - sending informational letters or emails to GPs and nurses; - multifaceted interventions, including financial and non-financial incentives, fines, education and reminder cards; - implementing government regulations together with financial incentives; - including ADR report forms in quarterly bulletins and prescription pads; - providing a hyperlink to the reporting form in hospitals' electronic patient records; - improving the reporting method by re-engineering a web-based electronic error reporting system; - the presence of a clinical pharmacist in a hospital setting actively identifying adverse drug events and advocating for the identification and reporting of adverse drug events., Authors' Conclusions: Compared to usual practice (i.e. spontaneous reporting with or without some training from regional pharmacosurveillance units), low-certainty evidence suggests that the number of ADR reports submitted may substantially increase following an education session, paired with reminder card and ADR report form, and may slightly increase with the use of a standardised discharge form method that makes it easier for healthcare professionals to report ADRs. The evidence for other interventions identified in this review, such as informational letters or emails and financial incentives, is uncertain. Future studies need to assess the benefits (increase in the number of adverse drug event reports) and harms (increase in the number of false adverse drug event reports) of any intervention designed to improve healthcare professionals' reporting of adverse drug events. Interventions to increase the number of submitted adverse drug event reports that are suitable for use in low- and middle-income countries should be developed and rigorously evaluated., (Copyright © 2024 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Since the effects of once-daily antihypertensive (HT) medications are more pronounced within the first few hours of ingestion, evening administration of anti-HT medications can be a feasible treatment for nocturnal HT. However, no relevant meta-analysis has been conducted in patients with nocturnal HT. This meta-analysis included randomized controlled trials involving patients with elevated mean nocturnal blood pressure (BP) and compared evening anti-HT administration with morning administration. Multiple databases, including grey literature (e.g. clincialtrial.gov), were searched. Study selection and data extraction were conducted by two independent authors. Risk of bias assessment and overall quality of evidence were conducted using Cochrane risk-of-bias tool and GRADE by two independent authors. A total of 107 studies were included, 76 of which were investigated in China and had not been identified in previous reviews. Only one trial was ranked low risk-of-bias. Evening administration of anti-HT medications was effective in reducing nocturnal systolic BP (4.12-9.10 mmHg; I2 = 80.5-95.2%) and diastolic BP (3.38-5.87 mmHg; I2 = 87.4-95.6%). Subgroup analyses found that the effectiveness of evening administration was contributed by data from the Hermida group and China. Evening administration did not provide additional nocturnal/daytime/24-h BP reduction in non-Hermida/non-China studies (I2 = 0) and in meta-analyses that included studies with unclear or low risk of bias. The effectiveness of nocturnal BP reduction was similar across different types, doses, and half-lives of medications. Evening administration of anti-HT medications may reduce proteinuria, left ventricular hypertrophy (LVH), nondipping and morning surge. The overall quality of evidence was ranked as very low to low. Our results highlight the scarcity of low risk-of-bias studies and emphasize the need for such trials to evaluate the efficacy of evening dosing of anti-HT medications as a standard treatment for patients with nocturnal HT across diverse populations., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims/introduction: Two Hong Kong Chinese non-laboratory-based prediabetes/diabetes mellitus (pre-DM/DM) risk models were developed using logistic regression (LR) and machine learning, respectively. We aimed to evaluate the models' validity in case finding of pre-DM/DM in a Chinese primary care (PC) population. We also evaluated the validity of a risk-scoring algorithm derived from the LR model., Materials and Methods: This was a cross-sectional external validation study on Chinese adults, without a prior DM diagnosis, who were recruited from public/private PC clinics in Hong Kong. A total of 1,237 participants completed a questionnaire on the models' predictors. Of that, 919 underwent blood glucose testing. The primary outcome was the models' and the algorithm's sensitivity in finding pre-DM/DM cases. The secondary outcomes were the models' and the algorithm's specificity, positive/negative predictive values, discrimination and calibration., Results: The models' sensitivity were 0.70 (machine learning) and 0.72 (LR). Both showed good external discrimination (area under the receiver operating characteristic curve: machine learning 0.744, LR 0.739). The risks estimated by the models were lower than the observed incidence, indicating poor calibration. Both models were more effective among participants with lower pretest probabilities; that is, age 18-44 years. The algorithm's sensitivity was 0.77 at the cut-off score of ≥16 out of 41., Conclusion: This study showed the validity of the models and the algorithm for finding pre-DM/DM cases in a Chinese PC population in Hong Kong. They can facilitate more cost-effective identification of high-risk individuals for blood testing to diagnose pre-DM/DM in PC. Further studies should recalibrate the models for more precise risk estimation in PC populations., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aim: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy., Results: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was -7.1% (-10.7%, -3.6%) and -3.9% (-5.1%, -2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds., Conclusions: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction/objectives: A non-laboratory-based pre-diabetes/diabetes mellitus (pre-DM/DM) risk prediction model developed from the Hong Kong Chinese population showed good external discrimination in a primary care (PC) population, but the estimated risk level was significantly lower than the observed incidence, indicating poor calibration. This study explored whether recalibrating/updating methods could improve the model's accuracy in estimating individuals' risks in PC., Methods: We performed a secondary analysis on the model's predictors and blood test results of 919 Chinese adults with no prior DM diagnosis recruited from PC clinics from April 2021 to January 2022 in HK. The dataset was randomly split in half into a training set and a test set. The model was recalibrated/updated based on a seven-step methodology, including model recalibrating, revising and extending methods. The primary outcome was the calibration of the recalibrated/updated models, indicated by calibration plots. The models' discrimination, indicated by the area under the receiver operating characteristic curves (AUC-ROC), was also evaluated., Results: Recalibrating the model's regression constant, with no change to the predictors' coefficients, improved the model's accuracy (calibration plot intercept: -0.01, slope: 0.69). More extensive methods could not improve any further. All recalibrated/updated models had similar AUC-ROCs to the original model., Conclusion: The simple recalibration method can adapt the HK Chinese pre-DM/DM model to PC populations with different pre-test probabilities. The recalibrated model can be used as a first-step screening tool and as a measure to monitor changes in pre-DM/DM risks over time or after interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Continuity of care (COC) is associated with improved health outcomes in patients with hypertension. Team-based COC allows more flexibility in service delivery but there is a lack of research on its effectiveness for patients with hypertension., Aim: To investigate the effectiveness of team-based COC on the prevention of cardiovascular disease (CVD) and mortality in patients with hypertension., Design and Setting: A retrospective cohort study in a primary care setting in Hong Kong., Method: Eligible patients included those visiting public primary care clinics in Hong Kong from 2008 to 2018. The usual provider continuity index (UPCI) was used to measure the COC provided by the most visited physician team. Cox regression and restricted cubic splines were applied to model the association between the COC and the risk for CVDs and all-cause mortality., Results: This study included 421 640 eligible patients. Compared with participants in the lowest quartile of UPCI, the hazard ratios for overall CVD were 0.94 (95% CI = 0.92 to 0.96), 0.91(95% CI = 0.89 to 0.93), and 0.90 (95% CI = 0.88 to 0.92) in the second, third, and fourth quartiles, respectively. A greater effect size on CVD risk reduction was observed among the patients with unsatisfactory blood pressure control, patients aged <65 years, and those with a Charlson comorbidity index of <4 at baseline ( P interaction<0.05 in these subgroup analyses), but the effect was insignificant among the participants with an estimated glomerular filtration rate of <60 ml/ min/1.73 m 2 at baseline., Conclusion: Team-based COC via a coordinated physician team was associated with reduced risks of CVD and all-cause mortality among patients with hypertension, especially for the patients with unsatisfactory blood pressure control. Early initiation of team-based COC may also achieve extra benefits., (© The Authors.)

Background: Since the early 2010s, there has been a push to enhance the capacity to effectively treat wasting in children through community-based service delivery models and thus reduce morbidity and mortality., Objectives: To assess the effectiveness of identification and treatment of moderate and severe wasting in children aged five years or under by lay health workers working in the community compared with health providers working in health facilities., Search Methods: We searched MEDLINE, CENTRAL, two other databases, and two ongoing trials registers to 24 September 2021. We also screened the reference lists of related systematic reviews and all included studies., Selection Criteria: We included randomised controlled trials (RCTs) and non-randomised studies in children aged five years or under with moderate wasting (defined as weight-for-height Z-score (WHZ) below -2 but no lower than ≥ -3, or mid-upper-arm circumference (MUAC) below 125 mm but no lower than 115 mm, and no nutritional oedema) or severe wasting (WHZ below -3 or MUAC below 115 mm or nutritional oedema). Eligible interventions were: • identification by lay health workers (LHWs) of children with wasting (intervention 1); • identification by LHWs of children with wasting and medical complications needing referral (intervention 2); and • identification by LHWs of children with wasting without medical complications needing referral (intervention 3). Eligible comparators were: • identification and treatment of wasting by health professionals such as nurses or doctors (at health facilities); and • identification and treatment of wasting by health facility-based teams, including health professionals and LHWs., Data Collection and Analysis: Two review authors independently screened trials, extracted data and assessed risk of bias using the Cochrane risk of bias tool (RoB 2) and Cochrane Effective Practice and Organisation of Care (EPOC) guidelines. We used a random-effects model to meta-analyse data, producing risk ratios (RRs) for dichotomous outcomes in trials with individual allocation, adjusted RRs for dichotomous outcomes in trials with cluster allocation (using the generic inverse variance method in Review Manager 5), and mean differences (MDs) for continuous outcomes. We used the GRADE approach to assess the certainty of the evidence., Main Results: We included two RCTs and five non-RCTs. Six studies were from African countries, and one was from Pakistan. Six studies included children with severe wasting, and one included children with moderate wasting. All studies offered home-based ready-to-use therapeutic food treatment and monitoring. Children received antibiotics in three studies, vitamins or micronutrients in three studies, and deworming treatment in two studies. In three studies, the comparison arm involved LHWs screening children for malnutrition and referring them to health facilities for diagnosis and treatment. All the non-randomised studies had a high overall risk of bias. Interventions 1 and 2 Identification and referral for treatment by LHWs, compared with treatment by health professionals following self-referral, may result in little or no difference in the percentage of children who recover from moderate or severe wasting (MD 1.00%, 95% confidence interval (CI) -2.53 to 4.53; 1 RCT, 29,475 households; low certainty). Intervention 3 Compared with treatment by health professionals following identification by LHWs, identification and treatment of severe wasting in children by LHWs: • may slightly reduce improvement from severe wasting (RR 0.93, 95% CI 0.86 to 0.99; 1 RCT, 789 participants; low certainty); • may slightly increase non-response to treatment (RR 1.44, 95% CI 1.04 to 2.01; 1 RCT, 789 participants; low certainty); • may result in little or no difference in the number of children with WHZ above -2 on discharge (RR 0.94, 95% CI 0.28 to 3.18; 1 RCT, 789 participants; low certainty); • probably results in little or no difference in the number of children with WHZ between -3 and -2 on discharge (RR 1.09, 95% CI 0.87 to 1.36; 1 RCT, 789 participants; moderate certainty); • probably results in little or no difference in the number of children with WHZ below -3 (severe wasting) on discharge (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT, 789 participants; moderate certainty); • probably results in little or no difference in the number of children with MUAC equal to or greater than 115 mm on discharge (RR 0.99, 95% CI 0.93 to 1.06; 1 RCT, 789 participants; moderate certainty); • results in little or no difference in weight gain per day (mean weight gain 0.50 g/kg/day higher, 95% CI 1.74 lower to 2.74 higher; 1 RCT, 571 participants; high certainty); • probably has little or no effect on relapse of severe wasting (RR 1.03, 95% CI 0.69 to 1.54; 1 RCT, 649 participants; moderate certainty); • may have little or no effect on mortality among children with severe wasting (RR 0.46, 95% CI 0.04 to 5.98; 1 RCT, 829 participants; low certainty); • probably has little or no effect on the transfer of children with severe wasting to inpatient care (RR 3.71, 95% CI 0.36 to 38.23; 1 RCT, 829 participants; moderate certainty); and • probably has little or no effect on the default of children with severe wasting (RR 1.48, 95% CI 0.65 to 3.40; 1 RCT, 829 participants; moderate certainty). The evidence was very uncertain for total MUAC gain, MUAC gain per day, total weight gain, treatment coverage, and transfer to another LHW site or health facility. No studies examined sustained recovery, deterioration to severe wasting, appropriate identification of children with wasting or oedema, appropriate referral of children with moderate or severe wasting, adherence, or adverse effects and other harms., Authors' Conclusions: Identification and treatment of severe wasting in children who do not require inpatient care by LHWs, compared with treatment by health professionals, may lead to similar or slightly poorer outcomes. We found only two RCTs, and the evidence from non-randomised studies was of very low certainty for all outcomes due to serious risks of bias and imprecision. No studies included children aged under 6 months. Future studies must address these methodological issues., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

The bis(iminoxolene)iridium complex (Diso) 2 IrCl (Diso = N -(2,6-diisopropylphenyl)-4,6-di- tert -butyl-2-imino- o -benzoquinone) reacts with pyridine to give trans -(Diso) 2 Ir(py)Cl as the kinetic product, with cis -(Diso) 2 Ir(py)Cl formed as the exclusive thermodynamic product upon heating. Electronic spectra and density functional theory calculations point to very similar electronic structures for the cis and trans isomers, with a nonbonding iminoxolene-centered HOMO and a metal-iminoxolene π* LUMO. The triplet states of cis -(Diso) 2 Ir(py)Cl and cis -[(Diso) 2 Ir(py) 2 ] + (but not trans -(Diso) 2 Ir(py)Cl) are unusually low in energy (1000-1500 cm -1 above the singlets), as shown by variable-temperature NMR spectroscopy. The low-energy triplets are attributed to a change in dihedral angle in the iminoxolenes, which allows a partial π interaction that cannot be achieved in the trans octahedral compounds. Mechanistic studies of the trans-cis isomerization in toluene indicate that the reaction proceeds via isomerization of the five-coordinate species to a form with cis iminoxolene ligands and an apical oxygen. This form is high in energy due to the loss of a secondary iminoxolene-to-iridium π-donor interaction that is possible in the trans form but not in the cis form for the square pyramidal structures. This stereoelectronic effect, combined with the poorer binding of pyridine in trans -(Diso) 2 Ir(py)Cl due to the interactions of the N -aryl substituents with the pyridine, makes the pyridine dissociate faster from the trans isomer by a factor of 10 8 at room temperature.

Background: Diabetes mellitus-related characteristics, including available medications, onset ages, and newly-introduced management program, have been changing recently in Hong Kong, especially after the introduction of the Risk Assessment and Management Program-Diabetes Mellitus in all outpatient clinics in 2009. To understand the plural change and improve the management of patients with Type 2 Diabetes Mellitus (T2DM) based on the latest data, we examined the trends of clinical parameters, T2DM complications and mortality in patients with T2DM in Hong Kong from 2010 to 2019., Methods: In this retrospective cohort study, we acquired data from the Clinical Management System of the Hospital Authority in Hong Kong. Among adults with T2DM diagnosed on or before Sept 30, 2010, and with at least one attendance in general outpatient clinics between Aug 1, 2009, to Sept 30, 2010, we investigated the age-standardised trends of clinical parameters including haemoglobin A1c, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), body mass index and estimated glomerular filtration rate (eGFR), complications including cardiovascular disease (CVD), peripheral vascular disease (PVD), sight-threatening diabetic retinopathy (STDR), neuropathy, eGFR<45 mL/min/1.73 m 2 and end-stage renal disease (ESRD), and all-cause mortality from 2010 to 2019 and tested the statistical significance of the trends using generalised estimating equation by sex, level of clinical parameters and age groups., Findings: In total, 82,650 males and 97,734 females with T2DM were identified. LDL-C decreased from 3 to 2 mmol/L in both males and females, while other clinical parameters changed within 5% over the full decade from 2010 to 2019. CVD, PVD, STDR, and neuropathy had declining incidences, while ESRD and all-cause mortality had increasing incidences from 2010 to 2019. The incidence of eGFR<45 mL/min/1.73 m 2 increased in males but decreased in females. The odds ratio (OR) of ESRD (1.13, 95% CI [1.12, 1.15]) was highest in both males and females while the ORs of STDR (0.94, 95% CI [0.92, 0.96]) and neuropathy (0.90, 95% CI [0.88, 0.92]) were lowest in males and females, respectively. Complications and all-cause mortality trends varied among baseline HbA1c, eGFR, and age subgroups. In contrast to the findings in other age groups, the incidence of any outcomes did not decrease in younger patients (<45 years) from 2010 to 2019., Interpretation: Improvements were observed in LDL-C and incidences of most complications from 2010 to 2019. Worse performance in the younger age group and increasing incidence of renal complications and mortality need more attention in managing patients with T2DM., Funding: The Health and Medical Research Fund, the Health Bureau, and Government of the Hong Kong Special Administrative Region., Competing Interests: EYFW has received research grants from the Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grant Council, outside the submitted work. EYTY has received research grants from the Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. CLKL has received research grants from the Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, the Hong Kong College of Family Physicians, and Kerry Group Kuok Foundation, outside the submitted work. All other authors declare no competing interests., (© 2023 The Authors.)

Background: Problems with health-related quality of life can affect physicians' ability to work effectively. This study compared the health-related quality of life of Hong Kong physicians to the general population and explored the factors associated with mental and physical health-related quality of life., Methods: This cross-sectional study was conducted from January to April 2016. Medical graduates from the University of Hong Kong participated in a survey containing the Short Form-12 Item Health survey version 2, Patient Health Questionnaire-9, Copenhagen Burnout Inventory, and items on lifestyle behaviors, career satisfaction, and socio-demographics., Results: 496 responses were received. The mean physical component summary score was 53.2 (SD = 7.6), similar to the general population. The mean mental component summary score was 43.6 (SD = 11.8), significantly worse than the general population (P<0.01). Compared to the general population, all Short-Form 12 Health Survey version 2 domains were worse in doctors, aside from bodily pain and general health. Regular exercise was positively associated with physical component summary scores (Coeff 2.024; P = 0.047); but having children and higher personal burnout scores were negatively associated with it (Coeff -1.890; P = 0.036; and Coeff -0.045; P = 0.027, respectively). Poorer mental component summary scores correlated with worse personal (Coeff -0.284; P< 0.001), work-related (Coeff -0.135; P = 0.040), and patient-related burnout (Coeff -0.060; P = 0.041), and higher Patient Health Questionnaire-9 scores (Coeff -9.170; P<0.001). There were significant differences in mental health (P = 0.042) and mental component summary scores (P = 0.012) across age groups, but not with gender., Conclusion: Hong Kong physicians are less impacted by physical health than mental health. Compared to the general population, doctors' mental health has a more significant impact on their lives. Interventions aimed to improve burnout and depression rates in physicians may improve physicians' mental health-related quality of life., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Ng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: To evaluate the association between the number of co-morbidities, all-cause mortality and public health system expenditure in patients with type 2 diabetes (T2D) across different age groups., Materials and Methods: A retrospective observational study of T2D patients using electronic health records in Hong Kong was conducted. Patients were stratified by age (< 50, 50-64, 65-79, ≥ 80 years) and the number of co-morbidities (0, 1, 2, 3, ≥ 4), defined using the Charlson Comorbidity Index and prevalent chronic diseases identified in local surveys. The association between the number of co-morbidities, all-cause mortality and direct medical costs was examined using Cox proportional hazard regression and the gamma generalized linear model with log link function., Results: A total of 262 212 T2D patients with a median follow-up of 10 years were included. Hypertension and dyslipidaemia were the most common co-morbidities in all age groups. After age stratification, cardiovascular diseases dominated the top pair of co-morbidities in the older age groups (65-79 and ≥ 80 years), while inflammatory and liver disease were predominant among younger individuals. Compared with co-morbidity-free T2D patients, the hazard ratios (95% CI) of death for patients aged younger than 50 and 80 years or older with two co-morbidities were 1.31 (1.08-1.59) and 1.25 (1.15-1.36), respectively, and increased to 3.08 (2.25-4.21) and 1.98 (1.82-2.16), respectively, as the number of co-morbidities increased to four or more. Similar trends were observed for medical costs., Conclusions: Age-specific co-morbidity patterns were observed for patients with T2D. A greater number of co-morbidities was associated with increased mortality and healthcare costs, with stronger relationships observed among younger patients., (© 2022 John Wiley & Sons Ltd.)

Objective: The Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) is a protocol-driven, risk-stratified, and individualized management program offered by a multidisciplinary team in addition to usual care for primary care patients with diabetes. This study aimed to evaluate the effectiveness of RAMP-DM for preventing complications and mortality over 10 years., Research Design and Methods: A population-based, prospective cohort study of adult patients with type 2 diabetes managed in the Hong Kong public primary health care system between 2009 and 2010 was conducted. RAMP-DM participants and usual care patients were matched using one-to-one propensity score matching and followed for 10 years. Risks of macrovascular and microvascular complications and all-cause mortality were estimated by Cox proportional hazards regression., Results: A total of 36,746 patients (18,373 in each group) were included after propensity score matching, with a median follow-up of 9.5 years and 306,802 person-years. RAMP-DM participants had significantly lower risks of macrovascular (hazard ratio [HR] 0.52, 95% CI 0.50-0.54) and microvascular (HR 0.68, 95% CI 0.64-0.72) complications and all-cause mortality (HR 0.45, 95% CI 0.43-0.47) than patients who received usual care only. However, the effect of RAMP-DM on macrovascular and microvascular complications attenuated after the 9th and 8th year of follow-up, respectively. RAMP-DM participants also showed better control of hemoglobin A1c, blood pressure, triglycerides, and BMI and a slower decline in renal function., Conclusions: Significant reductions in diabetes-related complications and all-cause mortality were observed among RAMP-DM participants over a 10-year follow-up, yet the effect of preventing complications attenuated after 8 years., (© 2022 by the American Diabetes Association.)

Introduction: More than half of diabetes mellitus (DM) and pre-diabetes (pre-DM) cases remain undiagnosed, while existing risk assessment models are limited by focusing on diabetes mellitus only (omitting pre-DM) and often lack lifestyle factors such as sleep. This study aimed to develop a non-laboratory risk assessment model to detect undiagnosed diabetes mellitus and pre-diabetes mellitus in Chinese adults., Methods: Based on a population-representative dataset, 1,857 participants aged 18-84 years without self-reported diabetes mellitus, pre-diabetes mellitus, and other major chronic diseases were included. The outcome was defined as a newly detected diabetes mellitus or pre-diabetes by a blood test. The risk models were developed using logistic regression (LR) and interpretable machine learning (ML) methods. Models were validated using area under the receiver-operating characteristic curve (AUC-ROC), precision-recall curve (AUC-PR), and calibration plots. Two existing diabetes mellitus risk models were included for comparison., Results: The prevalence of newly diagnosed diabetes mellitus and pre-diabetes mellitus was 15.08%. In addition to known risk factors (age, BMI, WHR, SBP, waist circumference, and smoking status), we found that sleep duration, and vigorous recreational activity time were also significant risk factors of diabetes mellitus and pre-diabetes mellitus. Both LR (AUC-ROC = 0.812, AUC-PR = 0.448) and ML models (AUC-ROC = 0.822, AUC-PR = 0.496) performed well in the validation sample with the ML model showing better discrimination and calibration. The performance of the models was better than the two existing models., Conclusions: Sleep duration and vigorous recreational activity time are modifiable risk factors of diabetes mellitus and pre-diabetes in Chinese adults. Non-laboratory-based risk assessment models that incorporate these lifestyle factors can enhance case detection of diabetes mellitus and pre-diabetes., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Introduction: Diabetes mellitus (DM) is a major non-communicable disease with an increasing prevalence. Undiagnosed DM is not uncommon and can lead to severe complications and mortality. Identifying high-risk individuals at an earlier disease stage, that is, pre-diabetes (pre-DM), is crucial in delaying progression. Existing risk models mainly rely on non-modifiable factors to predict only the DM risk, and few apply to Chinese people. This study aims to develop and validate a risk prediction function that incorporates modifiable lifestyle factors to detect DM and pre-DM in Chinese adults in primary care., Methods and Analysis: A cross-sectional study to develop DM/Pre-DM risk prediction functions using data from the Hong Kong's Population Health Survey (PHS) 2014/2015 and a 12-month prospective study to validate the functions in case finding of individuals with DM/pre-DM. Data of 1857 Chinese adults without self-reported DM/Pre-DM will be extracted from the PHS 2014/2015 to develop DM/Pre-DM risk models using logistic regression and machine learning methods. 1014 Chinese adults without a known history of DM/Pre-DM will be recruited from public and private primary care clinics in Hong Kong. They will complete a questionnaire on relevant risk factors and blood tests on Oral Glucose Tolerance Test (OGTT) and haemoglobin A1C (HbA1c) on recruitment and, if the first blood test is negative, at 12 months. A positive case is DM/pre-DM defined by OGTT or HbA1c in any blood test. Area under receiver operating characteristic curve, sensitivity, specificity, positive predictive value and negative predictive value of the models in detecting DM/pre-DM will be calculated., Ethics and Dissemination: Ethics approval has been received from The University of Hong Kong/Hong Kong Hospital Authority Hong Kong West Cluster (UW19-831) and Hong Kong Hospital Authority Kowloon Central/Kowloon East Cluster (REC(KC/KE)-21-0042/ER-3). The study results will be submitted for publication in a peer-reviewed journal., Trial Registration Number: US ClinicalTrial.gov: NCT04881383; HKU clinical trials registry: HKUCTR-2808; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cardiovascular diseases (CVD) are a long-term sequela of diabetes. Better individual-based continuity of care has been reported to reduce the risk of chronic complications among patients with diabetes. Maintaining a one-to-one patient-physician relationship is often challenging, especially in public health care settings. This study aimed to evaluate the relationship between higher team-based continuity of care, defined as consultations provided by the same physician team, and CVD risks in patients with diabetes from public primary care clinics., Research Design and Methods: This was a retrospective cohort study in Hong Kong of 312,068 patients with type 2 diabetes and without any history of CVD at baseline (defined as the earliest attendance at a doctor's consultation in a public-sector clinic between 2008 and 2018). Team-based continuity of care was measured using the usual provider continuity index (UPCI), calculated by the proportion of consultations provided by the most visited physician team in the 2 years before baseline. Patients were divided into quartiles based on their UPCI, and the characteristics of the quartiles were balanced using propensity score fine stratification weights. Multivariable Cox regression was applied to assess the effect of team-based continuity of care on CVD incidence. Patient demographics, smoking status, physiological measurements, number of attendances, comorbidities, and medications were adjusted for in the propensity weightings and regression analyses., Results: After an average follow-up of 6.5 years, the total number of new CVD events was 52,428. Compared with patients in the 1st quartile, patients in the 2nd, 3rd, and 4th quartiles of the UCPI had a CVD hazard ratio (95% CI) of 0.95 (0.92-0.97), 0.92 (0.89-0.94), and 0.87 (0.84-0.89), respectively, indicating that higher continuity of care was associated with lower CVD risks. The subtypes of CVD, including coronary heart disease and stroke, also showed a similar pattern. Subgroup analyses suggested that patients <65 years of age had greater benefits from higher team-based continuity of care., Conclusions: Team-based continuity of care was associated with lower CVD risk among individuals with type 2 diabetes, especially those who were younger. This suggests a potential flexible alternative implementation of continuity of care in public clinics., (© 2022 by the American Diabetes Association.)

Background: Benefits of intercalation during an undergraduate medical degree are well-recognized. The University of Hong Kong implemented a compulsory Enrichment Year (EY) in its Bachelor of Medicine and Bachelor of Surgery degree programme (MBBS) in 2016. In their third year of study, students could work on an area of interest in any of three programme categories (i) intercalation/ university exchange (IC); (ii) research (RA); (iii) service/ humanitarian work (SH). This study aimed to explore the barriers, enablers, and overall student learning experiences from the first cohort of EY students in order to inform future development of the EY., Methods: An exploratory sequential mixed-method study in 2019-20. Twenty students were purposively selected to attend three semi-structured focus group interviews. Conventional thematic analysis was employed and results assisted the design of a cross-sectional questionnaire. Sixty-three students completed the questionnaire. ANOVA or chi-square test was used to compare the difference in student's characteristics, barriers, enablers and perspectives on EY between programme categories. Adjusting student's characteristics, logistic regressions were conducted to identify the effect of programme categories on the EY experience., Results: Most students (95% in the questionnaire) agreed that EY was worthwhile and more rewarding than expected. EY was positively regarded for enhancing personal growth and interpersonal relationships. The main barriers were financial difficulties, scholarship issues and insufficient information beforehand. A few students had practical (i.e. accommodation, cultural adaptation) problems. Potential enablers included better financial support, more efficient information exchange and fewer assignments and preparation tasks. Similar barriers were encountered by students across all three categories of EY activities., Conclusions: Personal growth was the most important benefit of the EY. Barriers were consistent with those identified in the literature except for cultural adaptation, which could be related to Hong Kong's unique historical context. Financial limitation was the most concerning barrier, as it could result in unequal access to educational opportunities. Better and timely access to scholarships and other funding sources need to be considered., Trial Registration: Ethics approval was obtained from the local Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 19-585 )., (© 2022. The Author(s).)

Introduction: Cardiometabolic risk factors and renal function are monitored regularly for patients with diabetes mellitus (DM)/ hypertension (HT). In addition to risk factor levels at a single time point, their trajectory (changes over time) can also be differentially related to the risk of cardiovascular diseases (CVD) and mortality. This study aimed to systematically examine the evidence regarding the association between risk factor trajectories and risk of CVD/mortality in patients with DM/HT., Method: PubMed, MEDLINE, and Embase were searched for articles from January 1963 to April 2021. Inclusion criteria: studies that 1) analyzed trajectories of risk factors including haemoglobin A1c (HbA1c), blood pressure, estimated glomerular filtration rate (eGFR), body mass index (BMI), and blood lipids; 2) were performed in the DM/HT population and, 3) included risk of CVD/mortality as outcomes. Study quality was assessed using the Newcastle-Ottawa quality assessment scale., Results: A total of 22,099 articles were identified. After screening by title and abstract, 22,027 articles were excluded by irrelevant outcomes, exposure, population, or type of articles. Following full-text screening, 11 articles investigating the trajectories of HbA1c (N = 7), systolic blood pressure (SBP) (N = 3), and eGFR (N = 1) were included for data extraction and analysis. No studies were identified examining the association of BMI or lipid trajectories with CVD/mortality. All included studies were of good quality based on the NOS criteria. In general, stable trajectories within optimal ranges of the risk factors (HbA1c: <7%, SBP: 120-139mmHg, eGFR: >60mL/min/1.73m2) had the lowest CVD/mortality risk compared to an increasing HbA1c trajectory (from 8% to 10%), an increasing SBP trajectory (from 120-139 to ≥140mmHg), or a decreasing eGFR trajectory (from 90 to 70mL/min/1.73m2)., Conclusion: A relatively stable and well-controlled trajectory for cardiometabolic risk factors was associated with the lowest risk of CVD/mortality. Risk factor trajectories have important clinical implications in addition to single time point measurements. More attention should be given to patients with suboptimal control and those with unstable trends of cardiometabolic risk factors., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Eric Wan has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grant Council, outside the submitted work. Esther Yu has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. Professor Cindy Lam has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, the Hong Kong College of Family Physicians, and Kerry Group Kuok Foundation, outside the submitted work.

Bovine leukaemia virus (BLV), which is classified as a Deltaretrovirus , is the aetiologic agent of enzootic bovine leukosis (EBL), a chronic lymphoproliferative disorder with a worldwide distribution. EBL is widespread in dairy herds and causes a direct economic impact due to reduced milk production and the early culling of BLV-infected cattle. The BLV infection status in Taiwan remains largely unknown; a high prevalence of BLV in dairy cows was recently revealed. The present study further investigated BLV infections in beef cattle. Surprisingly, the prevalence of BLV proviral DNA was as low as 11.8% (23/195), which is significantly lower than that noted in dairy cows, which was 42.5% (102/240) ( p < 0.001). Factors associated with BLV infections were subsequently investigated. Due to the differences in herd management, an analysis of risk factors for a BLV infection was independently conducted in these two sectors. Several factors associated with a BLV infection were identified. Age was significantly associated with BLV infection status in dairy cows ( p < 0.001) but not in beef cattle. A high prevalence of BLV was observed in cattle >15.5 months old (57.8%) compared with those ≤15.5 months old (11.4%). Moreover, after stratification analysis, based on the critical age of 15.5 months, as determined by the receiver operating characteristic (ROC) curve, a significantly higher BLV prevalence was demonstrated in lactating dairy cows, cattle undergoing bull breeding, heifers at older ages, and those undergoing routine rectal palpation. Due to the high prevalence of BLV in Taiwan, the development of an effective control program, based on the identified risk factors, is important for interrupting the routes of BLV transmission within herds.

Depression amongst physicians can lead to poor individual and institutional outcomes. This study examined the prevalence and factors associated with depression and suicidal ideation amongst doctors in Hong Kong. Doctors who graduated from medical school at the University of Hong Kong between 1995 and 2014 were invited to participate in a survey measuring depressive symptoms, suicidal ideation and thoughts of self-harm, lifestyle behaviours, career satisfaction and socio-demographic characteristics. Data collection occurred between January and April 2016. The prevalence of screened-positive depression was 16.0% and 15.3% of respondents reported having suicidal ideation. Amongst those with positive depression screening scores, less than half reported having a diagnosed mood disorder. Sleeping fewer hours was associated with higher depression scores (P < 0.001) and an increased odds of meeting the cut-off for depression (P < 0.001). Factors associated with suicidal ideation included being unmarried (P = 0.012) and sleeping fewer hours (P = 0.022). Hong Kong doctors appear to have high rates of undiagnosed depression, and high levels of depressive symptoms and suicidal ideations. There is a need for greater awareness of the morbidity due to depression and to promote better mental health help-seeking among physicians. Barriers to mental health help-seeking need to be addressed and appropriate resources allocated to reduce suffering., (© 2021. The Author(s).)

Objectives: To evaluate the validity and psychometric properties of the Chinese Person-Centred Primary Care Measure (PCPCM) in a Chinese-speaking population., Design: A cross-sectional study., Setting: A primary care clinic in Hong Kong., Participants: 300 Chinese adult patients (150 males and 150 females) were recruited from a primary care clinic to complete a questionnaire containing the PCPCM, Consultation and Relational Empathy (CARE), Patient Enablement Index (PEI) and Adult (short version) Primary Care Assessment Tool (PCAT). The Chinese PCPCM was readministered to 118 participants after 14 days for test-retest reliability., Outcome Measures: The construct validity, reliability and sensitivity of the Chinese PCPCM., Results: The Chinese PCPCM was identified to have a one-factor construct, with good item fit and unidimensionality on Rasch analysis. Internal reliability was high (Cronbach's alpha >0.8) with moderate test-retest reliability (intraclass correlation coefficient=0.622, p<0.001). Significant correlations (0.58, 0.42, 0.48) between the PCPCM and CARE, PEI and Adult (short version) PCAT scores supported good convergent construct validity. PCPCM scores were higher among patients who had known their doctors for a longer period or who were more likely to be able to see the same doctor at every visit, and among those who self-reported to have 'better health' rather than 'worse health'., Conclusion: The Chinese PCPCM appears to be a valid, reliable and sensitive instrument for evaluating the quality of person-centred care among primary care patients in Hong Kong. Further studies are needed to confirm the utility of this instrument in other Chinese-speaking populations around the world., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background The detrimental effects of increased variability in systolic blood pressure (SBP) on cardiovascular disease (CVD) and mortality risk in patients with diabetes mellitus remains unclear. This study evaluated age-specific association of usual SBP visit-to-visit variability with CVD and mortality in patients with type 2 diabetes mellitus. Methods and Results A retrospective cohort study investigated 155 982 patients with diabetes mellitus aged 45 to 84 years without CVD at baseline (2008-2010). Usual SBP variability was estimated using SBP SD obtained from a mixed-effects model. Age-specific associations (45-54, 55-64, 65-74, 75-84 years) between usual SBP variability, CVD, and mortality risk were assessed by Cox regression adjusted for patient characteristics. After a median follow-up of 9.7 years, 49 816 events (including 34 039 CVD events and 29 211 mortalities) were identified. Elevated SBP variability was independently, positively, and log-linearly associated with higher CVD and mortality risk among all age groups, with no evidence of any threshold effects. The excess CVD and mortality risk per 5 mm Hg increase in SBP variability within the 45 to 54 age group is >3 times higher than the 70 to 79 age group (hazard ratio, 1.66; 95% CI, 1.49-1.85 versus hazard ratio, 1.19; 95% CI, 1.15-1.23). The significant associations remained consistent among all subgroups. Patients with younger age had a higher association of SBP variability with event outcomes. Conclusions The findings suggest that SBP visit-to-visit variability was strongly associated with CVD and mortality with no evidence of a threshold effect in a population with diabetes mellitus. As well as controlling overall blood pressure levels, SBP visit-to-visit variability should be monitored and evaluated in routine practice, in particular for younger patients.

Background: Community-based primary-level workers (PWs) are an important strategy for addressing gaps in mental health service delivery in low- and middle-income countries.  OBJECTIVES: To evaluate the effectiveness of PW-led treatments for persons with mental health symptoms in LMICs, compared to usual care.  SEARCH METHODS: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, ICTRP, reference lists (to 20 June 2019).   SELECTION CRITERIA: Randomised trials of PW-led or collaborative-care interventions treating people with mental health symptoms or their carers in LMICs.  PWs included: primary health professionals (PHPs), lay health workers (LHWs), community non-health professionals (CPs).  DATA COLLECTION AND ANALYSIS: Seven conditions were identified apriori and analysed by disorder and PW examining recovery, prevalence, symptom change, quality-of-life (QOL), functioning, service use (SU), and adverse events (AEs).  Risk ratios (RRs) were used for dichotomous outcomes; mean difference (MDs), standardised mean differences (SMDs), or mean change differences (MCDs) for continuous outcomes.  For SMDs, 0.20 to 0.49 represented small, 0.50 to 0.79 moderate, and ≥0.80 large clinical effects.  Analysis timepoints: T1 (<1 month), T2 (1-6 months), T3 ( >6 months) post-intervention.  MAIN RESULTS: Description of studies 95 trials (72 new since 2013) from 30 LMICs (25 trials from 13 LICs).  Risk of bias Most common: detection bias, attrition bias (efficacy), insufficient protection against contamination.  Intervention effects *Unless indicated, comparisons were usual care at T2.  "Probably", "may", or "uncertain" indicates "moderate", "low," or "very low" certainty evidence.   Adults with common mental disorders (CMDs) LHW-led interventions a. may increase recovery (2 trials, 308 participants; RR 1.29, 95%CI 1.06 to 1.56); b. may reduce prevalence (2 trials, 479 participants; RR 0.42, 95%CI 0.18 to 0.96); c. may reduce symptoms (4 trials, 798 participants; SMD -0.59, 95%CI -1.01 to -0.16); d. may improve QOL (1 trial, 521 participants; SMD 0.51, 95%CI 0.34 to 0.69); e. may slightly reduce functional impairment (3 trials, 1399 participants; SMD -0.47, 95%CI -0.8 to -0.15); f. may reduce AEs (risk of suicide ideation/attempts); g. may have uncertain effects on SU. Collaborative-care a. may increase recovery (5 trials, 804 participants; RR 2.26, 95%CI 1.50 to 3.43); b. may reduce prevalence although the actual effect range indicates it may have little-or-no effect (2 trials, 2820 participants; RR 0.57, 95%CI 0.32 to 1.01); c. may slightly reduce symptoms (6 trials, 4419 participants; SMD -0.35, 95%CI -0.63 to -0.08); d. may slightly improve QOL (6 trials, 2199 participants; SMD 0.34, 95%CI 0.16 to 0.53); e. probably has little-to-no effect on functional impairment (5 trials, 4216 participants; SMD -0.13, 95%CI -0.28 to 0.03); f. may reduce SU (referral to MH specialists);  g. may have uncertain effects on AEs (death). Women with perinatal depression (PND) LHW-led interventions a. may increase recovery (4 trials, 1243 participants; RR 1.29, 95%CI 1.08 to 1.54); b. probably slightly reduce symptoms (5 trials, 1989 participants; SMD -0.26, 95%CI -0.37 to -0.14); c. may slightly reduce functional impairment (4 trials, 1856 participants; SMD -0.23, 95%CI -0.41 to -0.04); d. may have little-to-no effect on AEs (death);  e. may have uncertain effects on SU. Collaborative-care a. has uncertain effects on symptoms/QOL/SU/AEs. Adults with post-traumatic stress (PTS) or CMDs in humanitarian settings LHW-led interventions a. may slightly reduce depression symptoms (5 trials, 1986 participants; SMD -0.36, 95%CI -0.56 to -0.15); b. probably slightly improve QOL (4 trials, 1918 participants; SMD -0.27, 95%CI -0.39 to -0.15); c. may have uncertain effects on symptoms (PTS)/functioning/SU/AEs. PHP-led interventions a. may reduce PTS symptom prevalence (1 trial, 313 participants; RR 5.50, 95%CI 2.50 to 12.10) and depression prevalence (1 trial, 313 participants; RR 4.60, 95%CI 2.10 to 10.08);  b. may have uncertain effects on symptoms/functioning/SU/AEs.   Adults with harmful/hazardous alcohol or substance use LHW-led interventions a. may increase recovery from harmful/hazardous alcohol use although the actual effect range indicates it may have little-or-no effect (4 trials, 872 participants; RR 1.28, 95%CI 0.94 to 1.74); b. may have little-to-no effect on the prevalence of methamphetamine use (1 trial, 882 participants; RR 1.01, 95%CI 0.91 to 1.13) and  functional impairment (2 trials, 498 participants; SMD -0.14, 95%CI -0.32 to 0.03); c. probably slightly reduce risk of harmful/hazardous alcohol use (3 trials, 667 participants; SMD -0.22, 95%CI -0.32 to -0.11);  d. may have uncertain effects on SU/AEs. PHP/CP-led interventions a. probably have little-to-no effect on recovery from harmful/hazardous alcohol use (3 trials, 1075 participants; RR 0.93, 95%CI 0.77 to 1.12) or QOL (1 trial, 560 participants; MD 0.00, 95%CI -0.10 to 0.10); b. probably slightly reduce risk of harmful/hazardous alcohol and substance use (2 trials, 705 participants; SMD -0.20, 95%CI -0.35 to -0.05; moderate-certainty evidence); c. may have uncertain effects on prevalence (cannabis use)/SU/AEs. PW-led interventions for alcohol/substance dependence a. may have uncertain effects.  Adults with severe mental disorders *Comparisons were specialist-led care at T1. LHW-led interventions a. may have little-to-no effect on caregiver burden (1 trial, 253 participants; MD -0.04, 95%CI -0.18 to 0.11);  b. may have uncertain effects on symptoms/functioning/SU/AEs.  PHP-led or collaborative-care a. may reduce functional impairment (7 trials, 874 participants; SMD -1.13, 95%CI -1.78 to -0.47); b. may have uncertain effects on recovery/relapse/symptoms/QOL/SU.  Adults with dementia and carers PHP/LHW-led carer interventions a. may have little-to-no effect on the severity of behavioural symptoms in dementia patients (2 trials, 134 participants; SMD -0.26, 95%CI -0.60 to 0.08); b. may reduce carers' mental distress (2 trials, 134 participants; SMD -0.47, 95%CI -0.82 to -0.13);  c. may have uncertain effects on QOL/functioning/SU/AEs. Children with PTS or CMDs LHW-led interventions a. may have little-to-no effect on PTS symptoms (3 trials, 1090 participants; MCD -1.34, 95%CI -2.83 to 0.14); b. probably have little-to-no effect on depression symptoms (3 trials, 1092 participants; MCD -0.61, 95%CI -1.23 to 0.02) or on functional impairment (3 trials, 1092 participants; MCD -0.81, 95%CI -1.48 to -0.13);  c. may have little-or-no effect on AEs. CP-led interventions a. may have little-to-no effect on depression symptoms (2 trials, 602 participants; SMD -0.19, 95%CI -0.57 to 0.19) or on AEs;  b. may have uncertain effects on recovery/symptoms(PTS)/functioning., Authors' Conclusions: PW-led interventions show promising benefits in improving outcomes for CMDs, PND, PTS, harmful alcohol/substance use, and dementia carers in LMICs., (Copyright © 2021 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: The rising prevalence of non-communicable diseases (NCDs) such as diabetes mellitus (DM) and hypertension (HT) has placed a tremendous burden on healthcare systems around the world, resulting in a call for more effective service delivery models. Better continuity of care (CoC) has been associated with improved health outcomes. This review examines the association between CoC and health outcomes in patients with DM and/or HT., Methods: This was a systematic review with searches carried out on 13 March 2021 through PubMed, Embase, MEDLINE and CINAHL plus, clinical trials registry and bibliography reviews. Eligibility criteria were: published in English; from 2000 onwards; included adult DM and/or HT patients; examined CoC as their main intervention/exposure; and utilised quantifiable outcome measures (categorised into health indicators and service utilisation). The study quality was evaluated with Critical Appraisal Skills Programme (CASP) appraisal checklists., Results: Initial searching yielded 21,090 results with 42 studies meeting the inclusion criteria. High CoC was associated with reduced hospitalisation (16 out of 18 studies), emergency room attendances (eight out of eight), mortality rate (six out of seven), disease-related complications (seven out of seven), and healthcare expenses (four out of four) but not with blood pressure (two out of 13), lipid profile (one out of six), body mass index (zero out of three). Six out of 12 studies on diabetic outcomes reported significant improvement in haemoglobin A1c by higher CoC. Variations in the classification of continuity of care and outcome definition were identified, making meta-analyses inappropriate. CASP evaluation rated most studies fair in quality, but found insufficient adjustment on confounders, selection bias and short follow-up period were common limitations of current literatures., Conclusion: There is evidence of a strong association between higher continuity of care and reduced mortality rate, complication risks and health service utilisation among DM and/or HT patients but little to no improvement in various health indicators. Significant methodological heterogeneity in how CoC and patient outcomes are assessed limits the ability for meta-analysis of findings. Further studies comprising sufficient confounding adjustment and standardised definitions are needed to provide stronger evidence of the benefits of CoC on patients with DM and/or HT.

Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution-gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.

This study aimed to evaluate the associations between variability of lipid parameters and the risk of kidney disease in patients with type 2 diabetes mellitus. Low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were specifically addressed in this study. This retrospective cohort study included 105,552 patients aged 45-84 with type 2 diabetes mellitus and normal kidney function who were managed under Hong Kong public primary care clinics during 2008-2012. Those with kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m 2 or urine albumin to creatinine ratio ≥ 3 mg/mmol) were excluded. Variabilities of low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were determined using the standard deviation of the respective parameter obtained from a mixed effects model to minimize regression dilution bias. The associations between lipid variability and renal outcomes including incident kidney disease, renal function decline defined as ≥ 30% reduction in estimated glomerular filtration rate since baseline, and end-stage renal disease (estimated glomerular filtration rate < 15 mL/min/1.73 m 2 ) were evaluated by multivariable Cox regression. After a median follow-up of 66.5 months (0.5 million person-years in total), 49,653 kidney disease, 29,358 renal function decline, and 1765 end-stage renal disease cases were recorded. Positive linear associations between low-density lipoprotein-cholesterol and total cholesterol to high-density lipoprotein-cholesterol ratio variabilities and the risk of all renal outcomes were demonstrated. However, no association between triglyceride variability and any outcome was found. Each mmol/L increase in low-density lipoprotein-cholesterol variability was associated with 20% (Hazard ratio 1.20 [95% CI 1.15-1.25]), 38% (Hazard ratio 1.37 [95% CI 1.30-1.45]), and 108% (Hazard ratio 2.08 [95% CI 1.74-2.50]) higher risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Similarly, each unit increase in total cholesterol to high-density lipoprotein-cholesterol ratio variability was associated with 35% (Hazard ratio 1.15 [95% CI 1.10-1.20]), 33% (Hazard ratio 1.33 [95% CI 1.26-1.40]), and 75% (Hazard ratio 1.75 [95% CI 1.46-2.09]) heightened risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Cholesterol variability may potentially be a useful predictor of kidney diseases in patients with type 2 diabetes mellitus. Attention should be drawn to cholesterol variability when managing diabetic patients and further research is warranted to investigate the modifiable risk factors for lipid variability.

Macrophages comprise the front line of defense against various pathogens. Classically activated macrophages (M1), induced by IFN-γ and LPS, highly express inflammatory cytokines and contribute to inflammatory processes. By contrast, alternatively activated macrophages (M2) are induced by IL-4 and IL-13, produce IL-10, and display anti-inflammatory activity. Adenylate kinase 4 (Ak4), an enzyme that transfers phosphate group among ATP/GTP, AMP, and ADP, is a key modulator of ATP and maintains the homeostasis of cellular nucleotides which is essential for cell functions. However, its role in regulating the function of macrophages is not fully understood. Here we report that Ak4 expression is induced in M1 but not M2 macrophages. Suppressing the expression of Ak4 in M1 macrophages with shRNA or siRNA enhances ATP production and decreases ROS production, bactericidal ability and glycolysis in M1 cells. Moreover, Ak4 regulates the expression of inflammation genes, including Il1b, Il6, Tnfa, Nos2, Nox2 , and Hif1a , in M1 macrophages. We further demonstrate that Ak4 inhibits the activation of AMPK and forms a positive feedback loop with Hif1α to promote the expression of inflammation-related genes in M1 cells. Furthermore, RNA-seq analysis demonstrates that Ak4 also regulates other biological processes in addition to the expression of inflammation-related genes in M1 cells. Interestingly, Ak4 does not regulate M1/M2 polarization. Taken together, our study uncovers a potential mechanism linking energy consumption and inflammation in macrophages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chin, He, Chow, Yu, Lai and Miaw.)

Introduction: Hypertension (HT) and diabetes mellitus (DM) and are major disease burdens in all healthcare systems. Given their high impact on morbidity, premature death and direct medical costs, we need to optimise effectiveness and cost-effectiveness of primary care for patients with HT/DM. This study aims to find out the association of trajectories in disease patterns and treatment of patients with HT/DM including multimorbidity and continuity of care with disease outcomes and service utilisation over 10 years in order to identify better approaches to delivering primary care services., Methods and Analysis: A 10-year retrospective cohort study on a population-based primary care cohort of Chinese patients with documented doctor-diagnosed HT and/or DM, managed in the Hong Kong Hospital Authority (HA) public primary care clinics from 1 January 2006 to 31 December 2019. Data will be extracted from the HA Clinical Management System to identify trajectory patterns of patients with HT/DM. Complications defined by ICPC-2/International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis codes, all-cause mortality rates and public service utilisation rates are included as independent variables. Changes in clinical parameters will be investigated using a growth mixture modelling analysis with standard quadratic trajectories. Dependent variables including effects of multimorbidity, measured by (1) disease count and (2) Charlson's Comorbidity Index, and continuity of care, measured by the Usual Provide Continuity Index, on patient outcomes and health service utilisation will be investigated. Multivariable Cox proportional hazards regression will be conducted to estimate the effect of multimorbidity and continuity of care after stratification of patients into groups according to respective definitions., Ethics and Dissemination: This study was approved by the institutional review board of the University of Hong Kong-the HA Hong Kong West Cluster, reference no: UW 19-329. The study findings will be disseminated through peer-reviewed publications and international conferences., Trial Registration Number: NCT04302974., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs' poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended.

Introduction: Managing chronic musculoskeletal problems usually focuses on pain control using medications, but outcomes are often unsatisfactory and sometimes harmful. Information on a patient's health-related quality of life (HRQOL) may trigger a doctor to tailor management improving quality of life. The aim of this trial is to find out whether routine measurement and reporting of a patient's EuroQoL 5-Dimension 5-Level (EQ-5D-5L) HRQOL data using an electronic platform can improve HRQOL and pain in patients with chronic knee or back problems in primary care. We will also assess the acceptability of routine electronic measurements and reporting of the EQ-5D-5L in primary care settings., Methods: This is a multicentre, prospective, cluster randomised controlled trial set in six public primary care clinics in Hong Kong. At the intervention clinics, subjects will complete an electronic EQ-5D-5L form at recruitment and at each clinic follow-up over 12 months. A report of the patient's longitudinal EQ-5D-5L data will be provided to the doctor. Subjects in the control clinics will receive care as usual. All subjects will complete the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a 10-point Pain Rating Scale and a structured questionnaire to collect sociodemographic information and data on morbidity and service utilisation at recruitment at baseline, 3, 6 and 12 months. Primary outcome is the change in WOMAC total score. Secondary outcomes are change in pain, other patient-reported outcome scores and doctor-rated severity of disease. Group differences in the changes in WOMAC and other outcome scores over time will be analysed using generalised estimating equation model with an intention-to-treat principle., Ethics and Dissemination: Ethics approval has been obtained from The University of Hong Kong/Hospital Authority Hong Kong West Cluster (IRB reference number: UW 18-270). The results of the trial will be submitted for publication in a peer-reviewed journal., Trial Registration Number: NCT03609762., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate the prevalence and severity of burnout and explore the factors associated with burnout among Hong Kong medical graduates up to 20 years post-graduation., Design: Cross-sectional survey., Setting: Hong Kong., Participants: Doctors who graduated from the University of Hong Kong between 1995 and 2014., Primary and Secondary Outcome Measures: Burnout as measured by the Copenhagen Burnout Inventory (CBI), alcohol consumption as measured by the Alcohol Use Disorders Identification Test Version C, lifestyle behaviours (hours of sleep and work, exercise, smoking, substance use), career satisfaction and sociodemographic characteristics were obtained using paper or online questionnaires., Results: Response rate was 30.9% (496/1607). Prevalence of CBI burnout was 63.1% (personal), 55.9% (work-related) and 35.4% (patient-related). The mean CBI subscale scores were 57.4±21.4 (personal), 48.9±7.4 (work-related) and 41.5±21.8 (client-related). Factors associated with personal and patient-related burnout included age (coeff -0.437, 95% CI -0.779 to -0.095 and coeff -0.596, 95% CI -0.965 to -0.228, respectively), practice setting (coeff -5.759, 95% CI -10.665 to -0.853 and coeff -5.317, 95% CI -10.602 to -0.032, respectively) and regular exercise (coeff -6.855, 95% CI -11.102 to -2.608 and coeff -6.769, 95% CI -11.333 to -2.205, respectively). Gender (coeff 5.1, 95% CI 1.382 to 8.818), average hours of sleep per night (coeff -5.200, 95% CI -7.139 to -3.262) and work hours per week (coeff 0.226, 95% CI 0.099 to 0.353) were associated with personal burnout only. No factors were significantly associated with work-related burnout., Conclusion: Burnout is highly prevalent among Hong Kong medical graduates. Younger doctors, women and those working in the public sector appear to be at higher risk for burnout and may benefit from targeted interventions. Policymakers and healthcare authorities should consider measures to help reduce burnout by enabling adequate sleep, reducing work hours and encouraging exercise., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To examine the associations between variability in lipids and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes based on low-density lipoprotein-cholesterol (LDL-C), the total cholesterol (TC) to high-density lipoprotein-cholesterol (HDL-C) ratio and triglycerides (TG)., Materials and Methods: A retrospective cohort study included 125 047 primary care patients with type 2 diabetes aged 45-84 years without CVD during 2008-2012. The variability of LDL-C, TC to HDL-C and TG was determined using the standard deviation of variables in a mixed effects model to minimize regression dilution bias. The associations between variability in lipids and CVD and mortality risk were assessed by Cox regression. Subgroup analyses based on patients' baseline characteristics were also conducted., Results: A total of 19 913 CVD events and 15 329 mortalities were recorded after a median follow-up period of 77.5 months (0.8 million person-years), suggesting a positive linear relationship between variability in lipids and the risk of CVD and mortality. Each unit increase in the variability of LDL-C (mmol/L), the TC to HDL-C ratio and TG (mmol/L) was associated with a 27% (HR: 1.27 [95% CI: 1.20-1.34]), 31% (HR:1.31 [95% CI: 1.25-1.38]) and 9% (HR: 1.09 [95% CI: 1.04-1.15]) increase in the risk of composite endpoint of CVD and mortality, respectively. Age-specific effects were also found when comparing LDL-C variability, with patients aged 45-54 years (HR: 1.70 [95% CI: 1.42-2.02]) exhibiting a 53% increased risk for the composite endpoints than those aged 75-84 years (HR: 1.11 [95% CI: 1.01-1.23]). Similar age effects were observed for both the TC to HDL-C ratio and TG variability. Significant associations remained consistent among most of the subgroups., Conclusions: Variability in respective lipids are significant factors in predicting CVD and mortality in primary care patients with type 2 diabetes, with the strongest effects related to LDL-C and the TC to HDL-C ratio and most significant in the younger age group of patients aged 45-54 years. Further study is warranted to confirm these findings., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objectives: To develop an equivalent Chinese translation of the Person-Centered Primary Care Measure (PCPCM) and to establish its cultural adaptability and content validity through cognitive debriefing., Design: The original English PCPCM was first translated into Chinese by double forward-translation by professional translators. The reconciliated Chinese version was then doubly back-translated into English by two other professional translators blinded to the forward-translation. On affirmation on its linguistic equivalence with the developers of the original English PCPCM, the reconciliated Chinese PCPCM was sent for cognitive debriefing with 20 Chinese-speaking primary care subjects by a trained interviewer using structured probing questions to collect their opinions on the clarity, comprehensibility and relevance of each item and response option in the Measure., Setting: Subjects were invited from a primary care clinic in Hong Kong to undergo the cognitive debriefing interviews. The interviews were divided into four groups chronologically to allow revision of the items to be made in between., Participants: Ten males and 10 females above the age of 18 completed the cognitive interviews. They were all Cantonese-speaking Chinese recruited by convenience sampling. Subjects with cognitive impairment, could not read Chinese, too old or too sick to complete the interviews were excluded from the study., Results: An average of 3.3 min (range 3-4 min) was required for the subjects to self-complete the Measure. All items were generally perceived to be easily understood and relevant. Modifications were made to items with the content validity index (CVI) on clarity or understanding <0.8 in each round of the interviews or if a majority of the subjects suggested rewording. Revisions were made to two items in the Chinese PCPCM throughout the whole cognitive debriefing process before the final version was confirmed. The average CVI on clarity of the Chinese PCPCM items ranged from 0.75 to 1. The average CVI on understanding ranged from 0.7 to 1. The average CVI on relevance ranged from 0.55 to 1., Conclusions: The content validity of the PCPCM was ascertained in terms of its clarity, understandability and relevance to allow further testing of its psychometric properties in a larger Chinese population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the associations of increased variability in glycated haemoglobin (HbA1c) with cardiovascular disease (CVD) and mortality risk in patients with diabetes., Materials and Methods: This prospective cohort study included 147 811 patients aged 45 to 84 years with type 2 diabetes mellitus, without CVD and with at least three HbA1c values recorded before baseline in the period 2008 to 2010. HbA1c variability was evaluated using a mixed effects model to reduce regression dilution bias. Age-specific associations (45- 54, 55- 64, 65- 74 and 75- 84 years) between HbA1c variability and risk of CVD and mortality were assessed by Cox regression, adjusted for patient characteristics and usual HbA1c., Results: After a median follow-up of 7.4 years(1.02 million person-years), an overall incidence of 40 785 events including CVD (incidence 27  793) and all-cause mortalities (incidence 23 175) were identified. Positive log-linear associations between HbA1c variability and CVD and mortality were identified in all age groups. The hazard ratios (HRs) for the composite of CVD and all-cause mortality showed that age was inversely associated with HbA1c variability, with a 28% higher risk per 1% increase in HbA1c variability in the age group 45 to 54 years (all composite outcomes: HR 1.28, 95% confidence interval [CI] 1.21, 1.35), whereas only a 14% higher risk in the 75- 84 age group (all composite outcomes: HR 1.14, 95% CI 1.11, 1.17). Subgroup analysis showed the risk in patients with usual HbA1c <53mmol/mol was about eight times higher than in those with usual HbA1c ≥64mmol/mol., Conclusions: HbA1c variability was strongly related to CVD and mortality in patients with diabetes across all age groups. Whilst pursuing optimal HbA1c targets, attention should be given to patients with high HbA1c variability, especially younger patients with good HbA1c control., (© 2020 John Wiley & Sons Ltd.)

Objective: The relative effects of various cardiovascular diseases (CVDs) and varying severity of chronic kidney disease (CKD) on mortality risk, direct medical cost, and life expectancy in patients with diabetes are unclear. The aim of this study was to evaluate these associations., Research Design and Methods: This was a retrospective cohort study that included 208,792 adults with diabetes stratified into 12 disease status groups with varying combinations of heart disease, stroke, moderate CKD (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m 2 ) and severe CKD (eGFR <30 mL/min/1.73 m 2 ) in 2008-2010. The effect of risk of mortality, annual direct medical costs, and life expectancy were assessed using Cox regression, gamma generalized linear method with log-link function, and flexible parametric survival models., Results: Over a median follow-up of 8.5 years (1.6 million patient-years), 50,154 deaths were recorded. Mortality risks for patients with only a single condition among heart disease, stroke, and moderate CKD were similar. The mortality risks were 1.75 times, 2.63 times, and 3.58 times greater for patients with one, two, and all three conditions (consisting of stroke, heart disease, and moderate CKD), compared with patients without these diseases, suggesting an independent and individually additive effect for any combination. A similar trend was observed in annual public health care costs with 2.91-, 3.90-, and 3.88-fold increased costs for patients with one, two, and three conditions, respectively. Increases in the number of conditions reduced life expectancy greatly, particularly in younger patients. Reduction in life expectancy for a 40-year-old with one, two, and three conditions was 20, 25, and 30 years for men and 25, 30, and 35 years, respectively, for women. A similar trend of greater magnitude was observed for severe CKD., Conclusions: The effects of heart diseases, stroke, CKD, and the combination of these conditions on all-cause mortality and direct medical costs are independent and cumulative. CKD, especially severe CKD, appears to have a particularly significant impact on life expectancy and direct medical costs in patients with diabetes. These findings support the importance of preventing both CVD and CKD in patients with diabetes., (© 2020 by the American Diabetes Association.)

Background The relationship between systolic blood pressure (SBP) and cardiovascular disease (CVD) among patients with diabetes mellitus remains unclear. The study aimed to explore age-specific associations between SBP and CVD. Methods and Results A population-based retrospective cohort study was conducted on 180 492 Chinese adults with type 2 diabetes mellitus in 2008-2010, with follow-up to 2017. Age-specific associations (<50, 50-59, 60-69, and 70-79 years) between the average SBP in the previous 2 years and CVD risk were assessed by adjusted Cox proportional hazards regression with age-specific regression dilution ratios and patient characteristics stratified by subgroups. During a median follow-up of 9.3 years (1.5 million person-years), 32 545 patients developed a CVD, with an incidence rate of 23.4 per 1000 person-years. A positive and log-linear association between SBP and CVD risk was observed among the 4 age groups without evidence of a threshold down to 120 mm Hg, but the magnitude of SBP effect on CVD attenuated with increased age. The CVD risk in the age group <50 years was ≈22% higher than the age group 70 to 79 years (hazard ratio [HR], 1.33 [95% CI, 1.26-1.41] versus HR, 1.09 [95% CI, 1.07-1.11]). Each 10-mm Hg higher SBP was associated with 12% (HR, 1.12 [95% CI, 1.10-1.13]), 11% (HR, 1.11 [95% CI, 1.10-1.13]), and 20% (HR, 1.20 [95% CI, 1.17-1.22]) higher risk of all composite CVD events, individual CVD, and CVD mortality, respectively. Conclusions There is a significant log-linear relationship between baseline SBP and the risk of CVD among patients with diabetes mellitus in China. The risk increases from an SBP of 120 mm Hg onward. Age influences this relationship significantly, with younger patients (<50 years) having a greater risk of CVD for a similar rise in SBP as compared with those who are older. These findings suggest that differential target blood pressures stratified by age maybe useful.

Objective: This study aimed to evaluate the association between visit-to-visit variability of systolic blood pressure (SBP) and cardiovascular disease, chronic kidney disease, and mortality among hypertensive patients., Methods: A population-based cohort included 225 759 Chinese hypertensive adults without diabetes, cardiovascular disease, and chronic kidney disease during 2011-2012. SBP variability was determined based on standard deviations of SBP over the previous 5 years before baseline. Cox regressions adjusted with patients' baseline characteristics, mean, and temporal trend of SBP was applied to the associations between variability and incident cardiovascular disease, chronic kidney disease and all-cause mortality., Results: In all, 25 714 patients with cardiovascular disease, 27 603 with chronic kidney disease, and 16 778 deaths have occurred during the median follow-up of 70.5 months (1.2 million person-years). SBP variability was continuously and positively associated with higher cardiovascular disease, chronic kidney disease and mortality risk among hypertensive patients without evidence of a threshold. Each 10-mmHg increase in SD of SBP was associated with 35% [hazard ratio 1.35, 95% confidence interval (CI) 1.30-1.39], 39% (HR 1.39, 95% CI 1.35-1.43), and 40% (HR 1.40, 95% CI 1.34-1.45) higher risk of cardiovascular disease, chronic kidney disease and mortality, respectively. HRs were attenuated with increased age, mean SBP, and Charlson index, and decreased temporal trend of systolic blood pressure, but it remained significant and consistent in most of the different subgroups., Conclusions: Findings suggested that SBP variability is a significant prognostic value, in addition to baseline or mean of SBP for the risk of cardiovascular disease and mortality.

Purpose: To estimate the prevalence of lower urinary tract symptoms (LUTS) in primary care using the International Continence Society symptom definition; to evaluate the association between LUTS and health-related quality of life (HRQOL); and to evaluate the treatment gaps., Methods: Patients aged 40 and above were randomly recruited in a Hong Kong public primary care. Patients were asked (i) how often they experienced 18 individual LUTS during the past 4 weeks and (ii) whether they had sought treatments for their LUTS. The 12-Item Short Form Health Survey version 2 (SF-12 v2) and the modified Incontinence Impact Questionnaire-Short Form (IIQ-7) were used to measure HRQOL., Results: 500 patients completed the survey. 75.8% of the patients had at least one LUTS "at least sometimes", with patients with a combination of storage, voiding, and post-micturition symptoms being the most prevalent (22.2%), followed by a combination of voiding and storage symptoms (14%). Only 14% of LUTS patients had sought treatments for their LUTS. LUTS was associated with a negative effect in all domains of the SF-12 v2 and IIQ-7 and patients with a combination of storage, voiding, and post-micturition symptoms had the worst HRQOL. Finally, having a combination of storage, voiding, and post-micturition symptoms and poorer HRQOL were factors associated with having sought treatments for LUTS., Conclusion: A high prevalence of LUTS but low treatment-seeking rates implied possible unmet needs of LUTS patients in primary care, suggesting the potential for more active interventions to alleviate the negative impact of LUTS on patients' HRQOL.

Background: Empathy is an important clinical attribute to be assessed during clinical examinations. While simulated patients (SPs) are well positioned to assess empathy in such settings, clinician-examiners are objective observers who are also experts in assessment. In this study, the assessments of student empathy from both examiners and SPs in clinical examinations were compared. Methods: The 10-item CARE measure were used for the assessment of empathy in 158 medical students in the Family Medicine specialty clerkship clinical competency test. The ratings from examiners and SPs were analyzed together with genders of students, examiners and patients, and the examination results. Results: SPs empathy ratings were higher than those from examiners across all ten items of CARE. A weak positive correlation was found between both ratings. Female SPs were more likely to give higher ratings, and examiners were more likely to give higher ratings to female students. SPs rating was moderately correlated with student examination score, while the correlation with examiners rating was strong. Conclusion: Although the inter-rater reliability was weak between the empathy rating from simulated patients and examiners, the evaluation of empathy from the patient's perspective was seen to be more authentic as they are in interaction with the students.

Background: Even though the negative impacts of nocturia on sleep quality and health-related quality of life (HRQOL) have been documented in previous research, their interrelationship has been poorly studied. This study aimed to explore whether nocturia would affect sleep quality, which in turn affects HRQOL., Methods: Participants aged 40 and above were randomly recruited from a Hong Kong public primary care clinic. Participants were asked to report the average number of nocturia (waking up at night to void) pisodes per night over a 1-month period. The Pittsburgh Sleep Quality Index (PSQI) and the 12-Item Short Form Health Survey version 2 (SF-12 v2) were administered. The mediation analysis was tested using multistage regression approach and bootstrap method., Results: Of the 500 subjects who completed the survey, 31.2% reported symptomatic nocturia (having ≥2 nocturia episodes per night), and 60.4% experienced poor sleep quality (a PSQI global score > 5). Respondents with symptomatic nocturia had a poorer HRQOL in the domains of physical functioning (PF), role physical (RP) and social functioning (SF), general health (GH), vitality (VT) and physical component summary (PCS) of the SF-12 v2 than those without. Compared with the respondents without poor sleep quality, those with poor sleep quality had poorer HRQOL across all domains and summaries of the SF-12 v2. Mediation analysis found that sleep quality fully mediated the association between nocturia and the PF, RP and SF domains of the SF-12 v2, respectively, and partially mediated the association between nocturia and the GH, VT and PCS domains of the SF-12 v2, respectively., Conclusions: We found that sleep quality mediated the association between nocturia and HRQOL. To enhance the HRQOL of patients with nocturia, clinicians should not only focus on nocturia symptoms, but also on their sleep quality.

Background: The Burden of Treatment Questionnaire (TBQ) assesses the impact of a patient's treatment workload on their quality of life., Objectives: The aim was to translate and validate the TBQ on Chinese primary care patients with multi-morbidity., Methods: The English TBQ was translated and back-translated using professional translators. Cognitive debriefing interviews were performed on 15 patients. The resulting instrument was tested on 200 primary care patients with multi-morbidity (>1 chronic disease) to examine its psychometric performance including exploratory factor analysis, confirmatory factor analysis, internal consistency and reliability. The EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L), Short-Form Six-Dimension (SF-6D), WONCA COOP Charts and the Global Health Rating Scale were used to assess convergent and divergent validity., Results: Median age of the respondents was 62 years (range 22-95 years) with a median of four conditions. The median TBQ total score was 16 (interquartile range 7.25-30). There was a significant floor effect (>15%) observed for all items. Spearman's correlations was >0.4 for all items demonstrating adequate internal construct validity. TBQ global score correlated with number of conditions (P = 0.034), EQ-5D-5L (P < 0.001), SF-6D (P < 0.001) and the feelings (P = 0.004), daily activities (P = 0.003) and social activities (P < 0.001) domains of the WONCA COOP. There was no significant correlation between global health rating and TBQ global scores (P = 0.298). Factor analysis demonstrated a three-factor structure. There was good internal consistency (Cronbach's alpha = 0.842) and good test-retest reliability (intra-class correlation coefficient = 0.830)., Conclusion: The newly translated Chinese version of the TBQ appears to be valid and reliable for use in Cantonese-speaking, adult primary care patients with multi-morbidity., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: There is limited evidence on the responsiveness of the Short Form-12 Health Survey version 2 (SF-12v2) in hypertensive patients. This study aimed to evaluate both the responsiveness of the SF-12 measures in Chinese hypertensive patients., Methods: A prospective longitudinal study was conducted on hypertensive patients managed in public primary care clinics between 2012 and 2013. A total of 583 and 431 patients were surveyed and completed SF-12v2 at baseline and at 12-month follow-up interviews, respectively. Using global rating of change scale as an external anchor, the responsiveness was assessed by linear mixed effect models, multiple linear regression models, and receiver operating characteristic (ROC) curve analysis., Results: SF-12v2 managed to detect negative changes among hypertensive patients in worsened general health group but failed to identify changes among hypertensive patients in improved general health group. Meanwhile, some domains of SF-12v2 detected a significant difference in difference between patients of worsened and stable/improved group and between patients of stable and improved group, but none of the domains and the summary scales reached the recommended standard of 0.7 in any comparisons in ROC analysis., Conclusions: The SF-12v2 was responsive to worsening of HRQOL but not to improvements in HRQOL among hypertensive patients. The overall responsiveness of SF-12v2 in hypertensive patients is unsatisfactory. Further studies are needed to identify HRQOL measures with good internal and external responsiveness for hypertensive patients.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous and toxic contaminants found in high concentrations in watercourses, and are not well removed by conventional wastewater treatment facilities. This study aimed to evaluate the removal and transformation of BDE-47, one of the environmentally predominant PBDE congener, by a green alga (Chlorella vulgaris) and a cyanobacterium (Microcystis flos-aquae) under different light conditions. Living and autoclaved cultures were exposed to BDE-47 at a concentration of 10 μg L -1 for 7 days. Both species removed >90% of BDE-47 very shortly after spiking. Light intensity affected the transformation of BDE-47 in living cultures of both species, since 5 to 11 times more debromination products were measured at a light intensity of 100 μmol photons m -2 s -1 than at 20 μmol photons m -2 s -1 . Living cultures of M. flos-aquae transformed BDE-47 at a rate of 0.22 day -1 while no transformation was observed in the respective autoclaved cultures. On the contrary, both living and autoclaved cultures of C. vulgaris had similar BDE-47 transformation rates of 0.05-0.06 day -1 . Debromination of BDE-47 was a predominant transformation pathway in cultures of C. vulgaris, with two times higher BDE-28 concentrations measured than in M. flos-aquae, while hydroxylation was more dominant with the cyanobacterium. Most BDE-47 and its debromination product BDE-28 were found on the cell surface of both species. These results reveal that different transformation mechanisms were involved in C. vulgaris and M. flos-aquae cultures and confirm the importance of species selection for the removal of PBDEs from contaminated environments., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The relative effects of combinations of CKD, heart disease, and stroke on risk of mortality, direct medical costs, and life expectancy are unknown., Methods: In a retrospective cohort study of 506,849 Chinese adults in Hong Kong with hypertension, we used Cox regressions to examine associations between all-cause mortality and combinations of moderate CKD (eGFR of 30-59 ml/min per 1.73 m 2 ), severe CKD (eGFR of 15-29 ml/min per 1.73 m 2 ), heart disease (coronary heart disease or heart failure), and stroke, and modeling to estimate annual public direct medical costs and life expectancy., Results: Over a median follow-up of 5.8 years (2.73 million person-years), 55,666 deaths occurred. Having an increasing number of comorbidities was associated with incremental increases in mortality risk and medical costs and reductions in life expectancy. Compared with patients who had neither CKD nor cardiovascular disease, patients with one, two, or three conditions (heart disease, stroke, and moderate CKD) had relative risk of mortality increased by about 70%, 160%, and 290%, respectively; direct medical costs increased by about 70%, 160%, and 280%, respectively; and life expectancy at age 60 years decreased by about 5, 10, and 15 years, respectively. Burdens were higher with severe CKD., Conclusions: This study demonstrated extremely high mortality risk and medical cost increases for severe CKD, exceeding the combined effects from heart disease and stroke. Mortality risks and costs for moderate CKD, heart disease, and stroke were similar individually and roughly multiplicative for any combination. These findings suggest that to reduce mortality and health care costs in patients with hypertension, CKD prevention and intervention merits priority equal to that of cardiovascular disease., (Copyright © 2019 by the American Society of Nephrology.)

The association between systolic blood pressure, cardiovascular disease, and chronic kidney disease remains unclear. This study aimed to evaluate these relationships. A population-based cohort of 267 469 adult patients with hypertension but without diabetes mellitus, cardiovascular disease, or chronic kidney disease were identified. Using baseline and repeated systolic blood pressure (average of all systolic blood pressure measurements in the past 5 years), the risks of cardiovascular disease and chronic kidney disease associated with systolic blood pressure were evaluated by Cox regression. Subgroup analyses were conducted by baseline characteristics. Over 1.4 million person-years follow-up (median 6 years), 29 500 cardiovascular disease and 30 993 chronic kidney disease events diagnosed. A J-shape association between baseline systolic blood pressure and risks of cardiovascular disease and chronic kidney disease was observed. Using repeated systolic blood pressure, a positive and log-linear association was identified. There was no evidence of a threshold down to the repeated systolic blood pressure of 120 mm Hg. Increases of 10 mm Hg of repeated systolic blood pressure was associated with a 16% (hazard ratio, 1.15; [95% CI, 1.13-1.16]), 11% (1.11; [1.08-1.13]), and 22% (1.22; [1.20-1.24]) higher risk of composite of cardiovascular disease and chronic kidney disease, individual cardiovascular disease and chronic kidney disease, respectively. Strength of the associations was similar across different subpopulations. This study showed that hypertensive patients with elevated repeated systolic blood pressure are at increased risk of cardiovascular disease or chronic kidney disease, irrespective of different characteristics. Very low single measurement of systolic blood pressure may be a potential indicator for poor health, but there seems to be no threshold for usual systolic blood pressure.