Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study.

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.

Age-specific associations between the number of co-morbidities, all-cause mortality and public direct medical costs in patients with type 2 diabetes: A retrospective cohort study.

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.

Lay health workers in primary and community health care for maternal and child health: identification and treatment of wasting in children.

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.

Identifying and articulating the student experience in the Intercalated Enrichment Year.

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 ).

Primary-level worker interventions for the care of people living with mental disorders and distress in low- and middle-income countries.

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.

Effects of continuity of care on health outcomes among patients with diabetes mellitus and/or hypertension: a systematic review.

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.

Age-specific associations of glycated haemoglobin variability with cardiovascular disease and mortality in patients with type 2 diabetes mellitus: A 10- year cohort study.

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.

Lower urinary tract symptoms and health-related quality of life in Hong Kong primary care: a cross-sectional study.

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.

Burden of CKD and Cardiovascular Disease on Life Expectancy and Health Service Utilization: a Cohort Study of Hong Kong Chinese Hypertensive Patients.

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 m2), severe CKD (eGFR of 15-29 ml/min per 1.73 m2), 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.

How clinician examiners compare with simulated patients in assessing medical student empathy in a clinical exam setting.

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.

Tree analysis modeling of the associations between PHQ-9 depressive symptoms and doctor diagnosis of depression in primary care.

BACKGROUND: The aim of this study was to explore the relationship between patient self-reported Patient Health Questionnaire-9 (PHQ-9) symptoms and doctor diagnosis of depression using a tree analysis approach. METHODS: This was a secondary analysis on a dataset obtained from 10 179 adult primary care patients and 59 primary care physicians (PCPs) across Hong Kong. Patients completed a waiting room survey collecting data on socio-demographics and the PHQ-9. Blinded doctors documented whether they thought the patient had depression. Data were analyzed using multiple logistic regression and conditional inference decision tree modeling. RESULTS: PCPs diagnosed 594 patients with depression. Logistic regression identified gender, age, employment status, past history of depression, family history of mental illness and recent doctor visit as factors associated with a depression diagnosis. Tree analyses revealed different pathways of association between PHQ-9 symptoms and depression diagnosis for patients with and without past depression. The PHQ-9 symptom model revealed low mood, sense of worthlessness, fatigue, sleep disturbance and functional impairment as early classifiers. The PHQ-9 total score model revealed cut-off scores of >12 and >15 were most frequently associated with depression diagnoses in patients with and without past depression. CONCLUSIONS: A past history of depression is the most significant factor associated with the diagnosis of depression. PCPs appear to utilize a hypothetical-deductive problem-solving approach incorporating pre-test probability, with different associated factors for patients with and without past depression. Diagnostic thresholds may be too low for patients with past depression and too high for those without, potentially leading to over and under diagnosis of depression.

The mediating role of sleep quality in the association between nocturia and health-related quality of life.

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.

Evaluation of the responsiveness of Short Form-12 Health Survey version 2 (SF-12v2) in Chinese patients with hypertension in primary care.

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.

Cultural adaptation and psychometric properties of the Chinese Burden of Treatment Questionnaire (C-TBQ) in primary care patients with multi-morbidity.

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.

Development of a cardiovascular diseases risk prediction model and tools for Chinese patients with type 2 diabetes mellitus: A population-based retrospective cohort study.

AIMS: Evidence-based cardiovascular diseases (CVD) risk prediction models and tools specific for Chinese patients with type 2 diabetes mellitus (T2DM) are currently unavailable. This study aimed to develop and validate a CVD risk prediction model for Chinese T2DM patients. METHODS: A retrospective cohort study was conducted with 137 935 Chinese patients aged 18 to 79 years with T2DM and without prior history of CVD, who had received public primary care services between January 1, 2010 and December 31, 2010. Using the derivation cohort over a median follow-up of 5 years, the interaction effect between predictors and age were derived using Cox proportional hazards regression with a forward stepwise approach. Harrell's C statistic and calibration plot were used on the validation cohort to assess the discrimination and calibration of the models. The web calculator and chart were developed based on the developed models. RESULTS: For both genders, predictors for higher risk of CVD were older age, smoking, longer diabetes duration, usage of anti-hypertensive drug and insulin, higher body mass index, haemoglobin A1c (HbA1c), systolic and diastolic blood pressure, a total cholesterol to high-density lipoprotein-cholesterol (TC/HDL-C) ratio and urine albumin to creatinine ratio, and lower estimated glomerular filtration rate. Interaction factors with age demonstrated a greater weighting of TC/HDL-C ratio in both younger females and males, and smoking status and HbA1c in younger males. CONCLUSION: The developed models, translated into a web calculator and color-coded chart, served as evidence-based visual aids that facilitate clinicians to estimate quickly the 5-year CVD risk for Chinese T2DM patients and to guide intervention.

Evaluation of the internal and external responsiveness of Short Form-12 Health Survey version 2 (SF-12v2) in patients with type 2 diabetes mellitus.

PURPOSE: The evidence on the responsiveness of the Short Form-12 Health Survey version 2 (SF-12v2) in patients with type 2 diabetes mellitus (T2DM) is limited. The aim of this study was to examine both the internal and external responsiveness of the SF-12 measures in Chinese patients with T2DM. METHODS: A prospective longitudinal observational study was conducted on 1443 T2DM patients managed in public primary care clinics between 2012 and 2013. These patients were surveyed at baseline and at 12 months using SF-12v2. The internal responsiveness was evaluated by linear mixed effect models. Meanwhile, the external responsiveness was tested by multiple linear regression models and receiver operating characteristic (ROC) curve analysis. RESULTS: The internal responsiveness of the SF-12v2 to detect negative change was satisfactory among T2DM patients in worsened group, but only the general health domain of SF-12v2 could detect positive change among T2DM patients with improved group. For external responsiveness, the SF-12v2 detected a significant difference-in-difference between patients with worsened and stable/improved group, but not between patients with stable and improved group. The areas under the ROC curve for all domains and summary scales of the SF-12v2 were not statistically different from 0.7. CONCLUSION: This study showed that the responsiveness of SF-12v2 might not achieve the standard. Despite the wide use of the SF-12v2, we would like to urge that both clinicians and researchers should use it with caution in longitudinal study.

Prediction of new onset of end stage renal disease in Chinese patients with type 2 diabetes mellitus - a population-based retrospective cohort study.

BACKGROUND: Since diabetes mellitus (DM) is the leading cause of end stage renal disease (ESRD), this study aimed to develop a 5-year ESRD risk prediction model among Chinese patients with Type 2 DM (T2DM) in primary care. METHODS: A retrospective cohort study was conducted on 149,333 Chinese adult T2DM primary care patients without ESRD in 2010. Using the derivation cohort over a median of 5 years follow-up, the gender-specific models including the interaction effect between predictors and age were derived using Cox regression with a forward stepwise approach. Harrell's C-statistic and calibration plot were applied to the validation cohort to assess discrimination and calibration of the models. RESULTS: Prediction models showed better discrimination with Harrell's C-statistics of 0.866 (males) and 0.862 (females) and calibration power from the plots than other established models. The predictors included age, usages of anti-hypertensive drugs, anti-glucose drugs, and Hemogloblin A1c, blood pressure, urine albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Specific predictors for male were smoking and presence of sight threatening diabetic retinopathy while additional predictors for female included longer duration of diabetes and quadratic effect of body mass index. Interaction factors with age showed a greater weighting of insulin and urine ACR in younger males, and eGFR in younger females. CONCLUSIONS: Our newly developed gender-specific models provide a more accurate 5-year ESRD risk predictions for Chinese diabetic primary care patients than other existing models. The models included several modifiable risk factors that clinicians can use to counsel patients, and to target at in the delivery of care to patients.

Evaluation of the outcomes of care of nurse-led continence care clinics for Chinese patients with lower urinary tract symptoms, a 2-year prospective longitudinal study.

AIM: The aim of this study was to evaluate the 24-month outcomes of a nurse-led continence care service for Chinese primary care patients with lower urinary tract symptoms. BACKGROUND: Most studies evaluating the outcomes of continence care services have had short follow-up durations with limited knowledge on whether benefits are sustained beyond 12 months. DESIGN: Twenty-four month cohort study. METHODS: Two comparison groups were recruited: (1) Patients with lower urinary tract symptoms attending a nurse-led community-based continence care programme; (2) Primary care patients with lower urinary tract symptoms identified by screening, receiving usual medical care. Self-reported symptom severity, health-related quality of life, patient enablement and general health perception were measured at baseline and 24 months. Data collection occurred from March 2013-August 2015. RESULTS: Baseline and 24-month data were available for 170 continence care and 158 usual care subjects. After controlling for baseline characteristics, the continence care group was observed to have greater reductions in symptom severity and larger improvements in disease-specific health-related quality of life, patient enablement and general health perception than the usual care group. Deterioration in the mental components of generic health-related quality of life was observed in the usual care group, but not in the continence care group. CONCLUSION: Over 24 months, when compared with usual medical care, nurse-led continence care services were effective in reducing symptom severity and improving health-related quality of life, patient enablement and general health perception and provided protection against deterioration in the mental components of health-related quality of life in patients with lower urinary tract symptoms.

The 12-Month Incidence and Predictors of PHQ-9-Screened Depressive Symptoms in Chinese Primary Care Patients.

PURPOSE: Evidence regarding the onset of depressive symptoms in primary care is rarely available but can help inform policy development, service planning, and clinical decision making. The objective of this study was to estimate the 12-month cumulative incidence and predictors of a positive screen for depressive symptoms on the 9-item Patient Health Questionnare-9 (PHQ-9) among primary care patients with no history of physician-diagnosed depression. METHODS: We monitored a cohort of 2,929 adult primary care patients with no past history of physician-diagnosed depression and with baseline PHQ-9 scores of 9 or lower by telephone interview at 3, 6, and 12 months. A generalized linear mixed effects Poisson Model was used to explore factors associated with the incidence of PHQ-positive symptoms. RESULTS: The cumulative incidence of positive screening on the PHQ-9 over 12 months was 5.23% (95% CI, 3.83%-6.64%). Positive predictors included being female, coming from a lower-income household, being a smoker, having at least 2 comorbidities, having a family history of depression, and having consulted a physician at least twice in the past 4 weeks. Consulting a physician with qualifications in both family medicine and psychological medicine was a negative predictor. CONCLUSIONS: The cumulative incidence of PHQ-9-screened depressive symptoms in this study population was higher than those reported for depressive disorders in earlier systematic reviews. Groups who may warrant greater treatment attention include women, patients with multimorbidity, smokers, patients with recent high rates of medical consultations, and those who are from lower-income households or who have a family history of depression. Greater physician training may have a protective effect.

Health-related quality of life mediates associations between multi-morbidity and depressive symptoms in Chinese primary care patients.

BACKGROUND: Qualifying the relationship between multi-morbidity, health-related quality of life (HRQOL) and depressive symptoms in primary care can help to inform the development of appropriate interventions and services which can help to enhance HRQOL in patients with chronic disease. OBJECTIVE: The objective of this study was to determine whether the physical aspect of HRQOL mediates the relationship between chronic disease multi-morbidity and depressive symptoms in Chinese primary care patients. METHODS: A cross-sectional survey was conducted on patients recruited from the waiting rooms of 59 primary care clinics distributed across Hong Kong. About 9259 subjects were included for the mediation model analysis. The primary outcome was level of depressive symptoms as measured by the Patient Health Questionniare 9. The mediation model was tested using a bootstrapping method. RESULTS: The prevalence of chronic disease was 50.4%, with 25.4% having two or more co-morbidities. The relationship between multi-morbidity and depressive symptoms was found to be mediated by the Physical Component Summary score of the SF-12 v2. Further analysis found the general health (GH) and role physical domains of the SF-12 were the strongest mediators, followed by bodily pain and physical functioning (PF). CONCLUSION: To enhance the functional capacity of primary care patients with co-existing chronic disease and depressive symptoms, health care interventions should be directed at improving the physical aspects of HRQOL, in particular enhancing patients' GH perception, role functioning and PF, and to better manage chronic pain.