INTRODUCTION: This scoping review examined the number, types and characteristics of journal publications on ageing in Singapore from 2008 to 2018 to determine how ageing research in medical and social domains in Singapore has transformed over time. METHODS: Using relevant search terms, articles were extracted from multiple databases and then screened and reviewed for eligibility and inclusion by independent reviewers. Data such as article title, authors, year of publication, name of journal, type of journal, study design and the kind of data used were charted from the included articles for evidence synthesis. RESULTS: Since 2008, there has been a steady increase in the number of publications on ageing in medical and social domains in Singapore. In the medical domain, publications on Ophthalmology (22%) made up the largest proportion of the existing medical literature on ageing in Singapore, followed by Physical Functioning (17%), which involved physiological measurements of physical well-being, and Geriatrics (16%). Non-medical publications comprised 38% of all the included publications, with publications on the social aspects of ageing (43%) forming the largest group in this cluster, followed by publications on Prevention (19%) and Healthcare services (18%). The study design was mostly observational (82%), with only 3% of interventional studies. CONCLUSION While ageing research had expanded in Singapore in the last decade, it was predominantly discipline specific and observational in design. As ageing issues are complex, with biology intersecting with psychology and sociology, we call for greater interdisciplinary collaboration, the conduct of more interventional studies, as well as more research in understudied and emerging areas.
Humans ; Singapore ; Aging ; Geriatrics ; Research Design

Background: Response surface methodology (RSM) is a cost-effective multivariate technique employed in optimization of pharmaceutical formulations. Central composite experiment design is one of the common designs under RSM used for determining optimum nanoparticle formulation parameters. Objectives: To optimize a formulation for meropenem-loaded chitosan alginate nanoparticles using central composite experimental design. Methodology: Meropenem loaded chitosan-alginate nanoparticles were fabricated using aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan, using an optimized formulation derived from a central composite design. The fabricated Mer-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The central composite design has been used to adequately assess the influence of two factors namely meropenem concentration and Alg/CS mass ratio on the responses based on a limited number of 13 triplicate formulation runs. Results: This study successfully formulated meropenem-loaded chitosan/alginate nanoparticles. The optimal formulation of the Mer- CS/Alg NPs was 1.7 mg/mLcurcumin, and a Alg/CS mass ratio of 9.8:1. Based on the predicted values of the response variable, the optimal formulation would have a particle size of 490.64 nm, zeta potential of -28.59 mVand a loading capacity of 76.89%. Conclusion The central composite experimental design successfully optimized the nanoparticle formulation of meropenem and chitosan/alginate polymer solution. The optimum formulation produced nanoparticles with adequate size, high stability, and high drug load.
Meropenem ; Nanoparticles ; Research Design

BACKGROUND

Dengue is a global health concern, particularly in tropical regions such as the Philippines. In 2019,Cebu City reported the highest number of dengue cases in Central Visayas with 3,290 cases and 20 deaths, an 11.8% increase compared to 20181 . To help predict disease outcomes and provide timely management, a scoring system, the Daily Dengue Severity Score (DDSS)² was utilized.

To determine the clinicodemographic profile of dengue patients, determine the accuracy of the DDSS in assessing disease severity, and determine a cut off score that suggests severe dengue.

Patients 1 month to 18 years admitted for dengue at Perpetual Succour Hospital from January 2018 to December 2020 were included. Cases were classified as Dengue without Warning Signs, Dengue with Warning Signs, and Severe Dengue, and scored using the DDSS. Statistical analysis used were Geometric mean and Area Under the Receiver Operating Characteristic (AUROC) curves to analyze the discriminative performance of the DDSS among the different disease severity states.

Out of 327 cases, 34 were classified as Dengue without Warning Signs, 271 Dengue with Warning Signs, and 22 Severe Dengue. The highest mean DDSS was 17.7 ±14.0 at Day -4 among those with Severe Dengue, and the lowest mean DDSS was 1.1 ± 2.0 at Day +3 among those with Dengue without Warning Signs. A cut off point of 10 on Day -1 predicted subsequent Severe Dengue among patients with Dengue with Warning Signs. In 91.39% of cases, there was a significant relationship between the DDSS and dengue classification, and the higher the DDSS, the more severe the disease.

Majority of dengue patients were males, aged 8.1 to 9.2 years. DDSS showed 66.67% sensitivity, 92.86% specificity, a positive likelihood ratio of 9.3, and a cutoff of 10 is predictive of severe dengue among patients with dengue with warning signs.

Qualitative research is a type of research that provides deeper insights into real-world problems. It gathers participants’ experiences, perceptions, and behaviours and answers the how’s and whys instead of how many or how much. It could be structured as a stand-alone study, purely relying on qualitative data or it could be part of mixed-methods research that combines qualitative and quantitative data. Some of the most common methodologies being used in qualitative research include ethnography, grounded theory, phenomenological study, narrative study, historical study and case studies. This article aimed to discuss how to conduct a qualitative study. The steps in conducting a qualitative study include: 1) Create a purpose statement; 2) Formulate the Research Questions; 3) Perform a Literature Review; 4) Choose a qualitative research methodology to use; 5) Identify and Select the Study Population; 6) Develop the data collection procedure; 7) Collect the data and 8) Analyze the data, which if using thematic analysis, can include writing the final report. In writing and appraising qualitative studies, the Consolidated Criteria for Reporting Qualitative Studies (COREQ) can serve as a useful guide. Lastly, like in quantitative studies, researchers doing qualitative studies should be aware of the ethical issues involved in their work, anticipate possible ethical concerns, craft protection strategies, and make the necessary referrals to research ethics committees, appropriate organizations, and other agencies if the need arises.

INTRODUCTION: Although influenza vaccination reduces rates of pneumonia, hospitalisation and mortality, influenza vaccination uptake remains low in older patients. The primary aim was to compare individualised counselling with educational pamphlets alone in improving influenza vaccination uptake. The secondary aims were to evaluate knowledge and attitudes towards influenza vaccination and factors influencing uptake. METHODS: A randomised controlled study was conducted in two government polyclinics with 160 participants per arm. Patients aged 65 years and above attending for doctor consultation were recruited. All participants received an educational pamphlet on influenza vaccination. The intervention group received additional face-to-face counselling. Participants filled a pre- and postintervention questionnaire assessing knowledge of influenza and attitudes towards the vaccine. Follow-up calls and verification of electronic records was done at three months to determine actual vaccine uptake. RESULTS: At three months, 16 (10%) patients in the intervention group and 20 (12.5%) patients in the control group had completed influenza vaccination (P = 0.48). Factors positively associated with vaccine uptake were willingness to receive vaccination immediately after intervention (adjusted odds ratio [OR] 12.15, 95% confidence interval [CI] 4.42-33.38), and male gender (adjusted OR 2.96, 95% CI 1.23-7.12). Individualised counselling was more effective in improving knowledge (P < 0.01). Overall knowledge scores did not influence actual vaccine uptake rates. (adjusted OR 1.10 [0.90-1.3]). CONCLUSION Both arms of patient education increased uptake of influenza vaccination. Individualised counselling was not superior to pamphlets alone in improving uptake. Performing vaccination at the initial point of contact improves actual uptake rates.
Humans ; Male ; Aged ; Influenza Vaccines ; Influenza, Human/prevention & control* ; Vaccination ; Research Design ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.
Acupuncture Therapy ; Acupuncture ; Research Design ; Consensus

OBJECTIVE: To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment. METHODS: The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias. CONCLUSION Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.
Child ; Humans ; Acupuncture Therapy/methods* ; Autistic Disorder ; Moxibustion/methods* ; Publication Bias ; Research Design ; Systematic Reviews as Topic ; Meta-Analysis as Topic

INTRODUCTION: Despite promising trials, catheter ablation is still regarded as an adjunct to antiarrhythmic drugs (AADs) in the treatment of paroxysmal atrial fibrillation (PAF). This study aimed to compare the effectiveness of various ablation therapies and AADs. METHOD: Randomised controlled trials or propensity score-matched studies comparing atrial tachyarrhythmia recurrence among any combination of ablation modalities or AAD were retrieved. Kaplan-Meier curves and risk tables for this outcome were graphically reconstructed to extract patient-level data. Frequentist network meta-analysis (NMA) using derived hazard ratios (HRs), as well as 2 restricted mean survival time (RMST) NMAs, were conducted. Treatment strategies were ranked using P-scores. RESULTS: Across 24 studies comparing 6 ablation therapies (5,132 patients), Frequentist NMA-derived HRs of atrial fibrillation recurrence compared to AAD were 0.35 (95% confidence interval [CI]=0.25-0.48) for cryoballoon ablation (CBA), 0.34 (95% CI=0.25-0.47) for radiofrequency ablation (RFA), 0.14 (95% CI=0.07-0.30) for combined CBA and RFA, 0.20 (95% CI=0.10-0.41) for hot-balloon ablation, 0.43 (95% CI=0.15-1.26) for laser-balloon ablation (LBA), and 0.33 (95% CI=0.18-0.62) for pulmonary vein ablation catheter. RMST-based NMAs similarly showed significant benefit of all ablation therapies over AAD. The combination of CBA + RFA showed promising long-term superiority over CBA and RFA, while LBA showed favourable short-term efficacy. CONCLUSION The advantage of ablation therapies over AAD in preventing atrial tachyarrhythmia recurrence suggests that ablation should be considered as the first-line treatment for PAF in patients fit for the procedure. The promising nature of several specific therapies warrants further trials to elicit their long-term efficacy and perform a cost-benefit analysis.
Humans ; Anti-Arrhythmia Agents/therapeutic use* ; Atrial Fibrillation/surgery* ; Catheter Ablation/methods* ; Heart Atria ; Network Meta-Analysis ; Recurrence ; Treatment Outcome ; Randomized Controlled Trials as Topic

Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Benzofurans/therapeutic use* ; Double-Blind Method ; Treatment Outcome