Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics.

INTRODUCTION: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines. RESEARCH DESIGN AND METHODS: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications. RESULTS: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m2, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes. CONCLUSIONS: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events. TRIAL REGISTRATION NUMBER: NCT04049149.

The combined role of MRI prostate and prostate health index in improving detection of significant prostate cancer in a screening population of Chinese men.

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.

Prevalence and association of chronic musculoskeletal pain on self-management, glycemic control and quality of life among Chinese type 2 diabetes patients in primary care.

AIMS: To examine the prevalence of chronic musculoskeletal (MSK) pain and its association with diabetes self-management, glycemic control and health-related quality of life (HRQoL) in patients with diabetes mellitus (DM) in primary care. METHODS: 329 patients with type 2 DM were recruited at public primary care clinics in Hong Kong. Chronic MSK pain was defined as having MSK pain ≥ 3 months, and the pain severity was measured by Brief Pain Inventory (BPI). Diabetes Management Self-Efficacy Scale (DMSES), hemoglobin A1c (HbA1c) and EuroQuol-5D (EQ5D) were collected. Multivariable regression was used to examine the association between the presence of chronic MSK pain with DMSES, HbA1c and EQ5D, adjusted for baseline confounders such as age, sex, BMI, duration of DM and comorbid depression. RESULTS: Approximately 49.5% of respondents reported chronic MSK pain with a median BPI severity score of 3.5 (2.0-5.0). The presence of chronic MSK pain was associated with lower HRQoL (ß = -0.053, 95% CI -0.087 to -0.018, P = 0.003), but was not associated with the diabetes self-management and glycemic control. Depression was associated with poorer diabetes self-management (ß = -2.776, 95% CI -4.247 to -1.304, P < 0.001) and HRQoL.( ß = -0.018,95% CI-0.025 to -0.012, P < 0.001). CONCLUSIONS: Chronic MSK pain was present in nearly half of the diabetic patients in primary care; however, the degree of pain was mild and had not shown to affect diabetes self-management and glycemic control. Depression was associated with poorer diabetes self-management. Chronic MSK pain and depression were both associated with poorer HRQoL.

Explaining the Psychosocial Effects of COVID-19 Among Older Hong Kong Chinese People-A Qualitative Analysis.

BACKGROUND: Social distancing and "stay-at-home" orders are essential to contain the coronavirus outbreak; however, there are growing concerns about physical and other mental distress in older people. Apart from quantitative data, their feelings, thoughts, and experience are essential to inform the implementation of patient-centered health care policy. AIM: This study explained the psychosocial effects of COVID-19 on Hong Kong Chinese older people. DESIGN AND SETTING: This was a qualitative study. Twenty-three participants aged between 63 and 86 were recruited in primary care through purposive sampling. METHOD: Semi-structured in-depth telephone interviews were conducted to explore participants' experience during the COVID-19 pandemic. Grounded theory was used to analyze the data. RESULTS: Three themes, nine subthemes, and 24 quotes were identified. The 3 themes included the psychological response of fear, annoyance, and worrisome; social isolation leading to loneliness and physical exhaustion; and the coping strategies in adversity. Fear was the major emotional response, which was not entirely explained by the uncertainty of the disease, but also the embedded routines norms and values. Loneliness was aggravated by the depleted family and community support. Physical distancing had intensified ones physical demand on self-care, especially among those with comorbid illnesses. The use of digital tools and telecommunications maintained the social connection, but the overexposure had led to a vicious cycle of anxiety and distress. CONCLUSION: Self-isolation has disproportionately affected older individuals whose only social contact is out of the home. Online technologies can be harnessed to provide social support networks and a sense of belonging, but its adaptive and positive uses should be encouraged. Interventions can also involve more frequent telephone contact with significant others, close family and friends, voluntary organizations, or health-care professionals, or community outreach teams. Enhancing the values of older people's in calamity through active engagement may also potentially reduce the detrimental effect of social isolation.

Prevalence and determinants of potentially inappropriate medication use in Hong Kong older patients: a cross-sectional study.

OBJECTIVES: To assess the prevalence of potentially inappropriate medication (PIM) use in Hong Kong older patients visiting general outpatient clinics (GOPCs) between 2006 and 2014 and to identify factors associated with PIM use among older adults visiting GOPCs in 2014. DESIGN: Cross-sectional study. SETTING: GOPC. PARTICIPANTS: Two study samples were constructed including a total of 844 910 patients aged 65 and above from 2006 to 2014 and a cohort of 489 301 older patients in 2014. MEASUREMENTS: Two subsets of the 2015 American Geriatrics Society Beers criteria-PIMs independent of diagnosis and PIMs due to drug-disease interactions-were used to estimate the prevalence of PIM use over 12 months. PIMs that were not included in the Hospital Authority drug formulary or with any specific restriction or exception in terms of indication, dose or therapy duration were excluded. Characteristics of PIM users and non-PIM users visiting GOPCs in 2014 were compared. Independent associations between patient variables and PIM use were assessed by stepwise multivariable logistic regression analysis. RESULTS: The 12-month period prevalence of PIM use decreased from 55.56% (95% CI 55.39% to 55.72%) in 2006 to 47.51% (95% CI 47.37% to 47.65%) in 2014. In the multivariable regression analysis, the strongest factor associated with PIM use was the number of different drugs prescribed (adjusted OR, AOR 23.01, 95% CI 22.36 to 23.67). Being female (AOR 0.89, 95% CI 0.85 to 0.87 for males vs females) and having a greater number of GOPC visits (AOR 1.83, 95% CI 1.78 to 1.88) as well as more than six diagnoses (AOR 1.43, 95% CI 1.36 to 1.52) were associated with PIM use. CONCLUSIONS: The overall prevalence of PIM use in older adults visiting GOPCs decreased from 2006 to 2014 in Hong Kong although the prevalence of PIM use was still high in 2014. Patients with female gender, a larger number of medications prescribed, more frequent visits to GOPCs, and more than six diagnoses were at higher risk for PIM use.

Effectiveness of nurse-led peri-discharge interventions for reducing 30-day hospital readmissions: Network meta-analysis.

BACKGROUND: Existing systematic reviews have compared the effectiveness of nurse-led peri-discharge interventions comprising different components with usual care on reducing all-cause 30-day hospital readmissions. However, conflicting results were reported. OBJECTIVE: We conducted a network meta-analysis to evaluate the comparative effectiveness of different nurse-led peri-discharge interventions, compared with usual care, for reducing all-cause 30-day hospital readmissions. DESIGN: Network meta-analysis. METHODS: A total of five international databases were searched for systematic reviews of randomized controlled trials. Additional searches for most updated randomized controlled trials published between 2014 to 2019 were conducted. Data from included randomized controlled trials were extracted for random-effect pairwise meta-analyses. Pooled risk ratios with 95% confidence interval were used to quantify impact of nurse-led peri-discharge interventions on all-cause 30-day hospital readmissions. Network meta-analysis was used to evaluate the comparative effectiveness of different interventions. RESULTS: From two systematic reviews and additional randomized controlled trial searches, 12 eligible randomized controlled trials (n=150,840) assessing 15 different nurse-led peri-discharge interventions were included. For reducing all-cause 30-day hospital readmissions, pairwise meta-analysis showed that there was no significant difference between nurse-led peri-discharge interventions and usual care (pooled risk ratios = 0.86, 95% confidence interval: 0.71-1.04, moderate quality of evidence). Network meta-analysis indicated no significant difference across different interventions despite variation in complexity. CONCLUSIONS: Our results indicated that nurse-led peri-discharge interventions were not significantly different from usual care for reducing all-cause 30-day hospital readmissions. Simpler nurse-led peri-discharge interventions are on par with more complex interventions in terms of effectiveness. Benefits of nurse-led peri-discharge interventions may vary across health system context. Therefore, careful consideration is required prior to implementation. REGISTRATION DETAILS: The protocol for this study has been registered in PROSPERO (Registration No. CRD42020186938). Tweetable abstract: This study suggested that nurse-led peri-discharge interventions do not differ from usual care for reducing all-cause 30-day hospital readmissions.

Non-specific effects of acupuncture and sham acupuncture in clinical trials from the patient's perspective: a systematic review of qualitative evidence.

BACKGROUND: Previous clinical trials have demonstrated that both acupuncture and sham acupuncture exert significant, non-specific effects on treatment outcomes when compared to no-treatment controls. A recently developed framework (mechanisms in orthodox and complementary and alternative medicine-MOCAM) suggests that the non-specific effects of acupuncture originate from multiple domains (e.g. patient characteristics, acupuncturist skill/technique, the patient-acupuncturist relationship, and the acupuncture environment). However, it remains to be determined precisely how these domains influence the non-specific effects of treatment among patients receiving acupuncture and sham acupuncture in clinical trials. Therefore, we conducted a systematic review to synthesize existing qualitative evidence on how trial participants randomized to acupuncture and sham acupuncture groups experience non-specific effects, regardless of the types of medical condition investigated. METHODS: This systematic review included primary qualitative studies embedded in randomized controlled trials designed to investigate acupuncture or sham acupuncture interventions. Eligible studies published in English were derived from a search of five international databases. The methodological quality of included studies was evaluated using the Critical Appraisal Skills Programme (CASP) tool. Using a framework synthesis approach, the identified MOCAM framework was adapted based on the synthesis of the available qualitative evidence. RESULTS: A total of 20 studies of high methodological quality were included. Our proposed model indicated that the effects of acupuncture may be increased by maintaining a professional status, applying a holistic treatment approach, practicing empathy, and providing patients with an appropriate explanation of the theory behind acupuncture and sham acupuncture. From the patient's perspective, the efficacy of treatment can be increased by following the lifestyle modification advice provided by acupuncturists, maintaining a positive attitude toward treatment efficacy, actively engaging with acupuncturists during consultation, and making behavioral changes based on experience gained during the trial. CONCLUSION: The results of this study may provide a basis for improving and standardizing key components of non-specific effects in acupuncture treatment, and for improving the isolation of specific effects in future clinical trials involving acupuncture and sham acupuncture.

Characteristics and well-being of urban informal home care providers during COVID-19 pandemic: a population-based study.

OBJECTIVES: Globally, the COVID-19 pandemic has overwhelmed many healthcare systems, which has hampered access to routine clinical care during lockdowns. Informal home care, care provided by non-healthcare professionals, increases the community's healthcare capacity during pandemics. There is, however, limited research about the characteristics of informal home care providers and the challenges they face during such public health emergencies. DESIGN: A random, cross-sectional, population-based, RDD, telephone survey study was conducted to examine patterns of home care, characteristics of informal home care providers and the challenges experienced by these care providers during this pandemic. SETTING: Data were collected from 22 March to 1 April 2020 in Hong Kong, China. PARTICIPANTS: A population representative study sample of Chinese-speaking adults (n=765) was interviewed. PRIMARY AND SECONDARY OUTCOME MEASURES: The study examined the characteristics of informal home care providers and self-reported health requirements of those who needed care. The study also examined providers' self-perceived knowledge to provide routine home care as well as COVID-19 risk reduction care. Respondents were asked of their mental health status related to COVID-19. RESULTS: Of the respondents, 25.1% of 765 provided informal home care during the studied COVID-19 pandemic period. Among the informal home care providers, 18.4% of respondents took leave from school/work during the epidemic to provide care for the sick, fragile elderly and small children. Care providers tended to be younger aged, female and housewives. Approximately half of care providers reported additional mental strain and 37.2% reported of challenges in daily living during epidemic. Although most informal home care providers felt competent to provide routine care, 49.5% felt inadequately prepared to cope with the additional health risks of COVID-19. CONCLUSION: During public health emergencies, heavy reliance on informal home healthcare providers necessitates better understanding of their specific needs and increased government services to support informal home care.

Monotherapy Is Good Enough for Patients with Mild-to-Moderate Alzheimer's Disease: A Network Meta-analysis of 76 Randomized Controlled Trials.

Memantine and the Acetylcholinesterase inhibitors (AChEIs) are two classes of drugs that are used to treat patients with Alzheimer's disease. We conducted a network meta-analysis of randomized controlled trials to compare the treatment effectiveness of monotherapy or combination therapy A total of 23,707 AD patients in 76 randomized trials were identified. In patients with mild-to-moderate AD, monotherapy with donepezil, galantamine or rivastigmine were superior to placebo in enhancing cognitive functions and activities of daily living (ADL), whereas monotherapy with donepezil or memantine were superior to placebo in improving behavioral symptoms. However, combination therapy with AChEIs and memantine did not show additional benefit than monotherapy. In patients with moderate-to-severe AD, neither monotherapy nor combination therapy were superior to placebo in any domain measurement. Combination therapy with memantine and AChEIs is confirmed to have no additional benefits over monotherapy. This article is protected by copyright. All rights reserved.

Prevalence and risk factors of community-associated methicillin-resistant Staphylococcus aureus carriage in Asia-Pacific region from 2000 to 2016: a systematic review and meta-analysis.

OBJECTIVE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging global public health threat. In response to a highlighted strategic priority of the World Health Organization Global Action Plan on Antimicrobial Resistance, to "strengthen the knowledge and evidence base through surveillance and research", we synthesized published articles to estimate CA-MRSA carriage prevalence in the Asia-Pacific region. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD:42017067399). We searched MEDLINE, EMBASE, and PubMed for articles published from 1 January 2000 to 19 May 2017, which reported CA-MRSA carriage (defined as either colonization or infection) in Asia-Pacific region from 2000 to 2016. Studies were stratified according to settings (community or hospital where CA-MRSA was isolated) and study populations (general public or subpopulations with specified characteristics). Ranges of CA-MRSA carriage prevalence were reported for study groups. RESULTS: In total, 152 studies were identified. Large diversity was observed among studies in most study groups. In community-level studies, the CA-MRSA carriage prevalence among the general public ranged from 0% to 23.5%, whereas that ranged from 0.7% to 10.4% in hospital settings. From community-level studies, countries with the highest prevalence were India (16.5%-23.5%), followed by Vietnam (7.9%) and Taiwan (3.5%-3.8%). Children aged ≤6 (range: 0.5%-40.3%) and household members of CA-MRSA carriers (range: 13.0%-26.4%) are subgroups without specific health conditions but with much higher CA-MRSA carriage when compared to the general population. CONCLUSION: Our CA-MRSA prevalence estimates serve as the baseline for future national and international surveillance. The ranges of prevalence and characteristics associated with CA-MRSA carriage can inform health authorities to formulate infection control policies for high-risk subgroups. Future studies should explore the heterogeneities in CA-MRSA carriage prevalence among subgroups and countries to clarify the predominant transmission mechanisms in Asia-Pacific and other regions.

Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis.

Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi-randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.

Patients' experience of Chinese Medicine Primary Care Services: Implications on Improving Coordination and Continuity of Care.

Chinese medicine (CM) is major form of traditional and complementary medicine used by Chinese populations. Evaluation on patients' experience on CM service is essential for improving service quality. This cross sectional study aims (i) to assess how CM clinics with different administrative model differ in terms of quality from patients' perspective; and (ii) to investigate how quality varies with patients' demographic and health characteristics. Five hundred and sixteen patients were sampled from charity and semi-public CM clinics in Hong Kong, and were invited to assess their experience using the Primary Care Assessment Tool (PCAT). Results indicated that overall mean PCAT scoring is satisfactory, achieving 70.7% (91.26/129) of total score. Ratings were lower in areas of "coordination of patient information", "continuity of care", and "range of service provided". Impact of administrative models, including involvement of tax-funded healthcare system and outreach delivery, were minimal after adjusting for patient characteristics. Demographic and health characteristics of patients did not contribute to substantial variations in scoring. To improve patient experience, policy makers should consider strengthening care coordination, continuity and comprehensiveness in CM primary care services. Sharing of electronic records and establishing referral system are potential solutions for linking CM and conventional healthcare services.