CONVALESCENT plasma for COVID-19: A meta-analysis of clinical trials and real-world evidence.

BACKGROUND: There is still a lack of consensus on the efficacy of convalescent plasma (CP) treatment in COVID-19 patients. We performed a systematic review and meta-analysis to investigate the efficacy of CP vs standard treatment/non-CP on clinical outcomes in COVID-19 patients. METHODS: Cochrane Library, PubMed, EMBASE and ClinicalTrials.gov were searched from December 2019 to 16 July 2021, for data from clinical trials and observational studies. The primary outcome was all-cause mortality. Risk estimates were pooled using a random-effect model. Risk of bias was assessed by Cochrane Risk of Bias tool for clinical trials and Newcastle-Ottawa Scale for observational studies. RESULTS: In total, 18 peer-reviewed clinical trials, 3 preprints and 26 observational studies met the inclusion criteria. In the meta-analysis of 18 peer-reviewed trials, CP use had a 31% reduced risk of all-cause mortality compared with standard treatment use (pooled risk ratio [RR] = 0.69, 95% confidence interval [CI]: 0.56-0.86, P = .001, I2  = 50.1%). Based on severity and region, CP treatment significantly reduced risk of all-cause mortality in patients with severe and critical disease and studies conducted in Asia, pooled RR = 0.61, 95% CI: 0.47-0.81, P = .001, I2  = 0.0%; pooled RR = 0.67, 95% CI: 0.49-0.92, P = .013, I2  = 0.0%; and pooled RR = 0.62, 95% CI: 0.48-0.80, P < .001, I2  = 20.3%, respectively. The meta-analysis of observational studies showed the similar results to the clinical trials. CONCLUSIONS: Convalescent plasma use was associated with reduced risk of all-cause mortality in severe or critical COVID-19 patients. However, the findings were limited with a moderate degree of heterogeneity. Further studies with well-designed and larger sample size are needed.

Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between antipsychotic use in pregnancy and the risk of congenital malformations in children. DATA SOURCES: Searches of PubMed, EMBASE, PsycINFO and Cochrane Library were conducted from inception to 06 January 2020 using keywords: antipsychotics, pregnancy, pregnancy complication and congenital abnormalities. STUDY SELECTION: Of 38 reports initially identified as being of potential interest, 13 studies met our inclusion criteria: English observational studies that examined the association between gestational antipsychotic use and congenital malformations in children. DATA EXTRACTION: Data were extracted independently by 2 investigators including the publication year, study site, study period, data source, study design, sample size, medication exposure, exposure period and pregnancy definition, exposure as well as outcome ascertainment, selection of study and comparison group, confounding adjustment, statistical analysis, and method of linkage between mother and children. Risk estimates were pooled using a random-effect model and the I2 statistic was used to evaluate the degree of heterogeneity. RESULTS: Thirteen studies met our systematic review inclusion criteria. Six studies with a total of 2 515 272 pregnancy episodes were included in our meta-analysis, which provided a pooled adjusted risk ratio of 1.23, 95% confidence interval: 0.96-1.58. The I2 result showed moderate heterogeneity between studies (I2  = 35.2%, P = .173). CONCLUSION: We did not find strong evidence of an association between prenatal exposure to antipsychotic medications and the risk of congenital malformations in children. We recommend further studies investigate this association, focusing on specific medication classes and dose responses, which would help clinicians decide whether to prescribe certain antipsychotics during pregnancy.

Patterns and factors influencing oral anticoagulant prescription in people with atrial fibrillation and dementia: Results from UK primary care.

AIMS: Oral anticoagulant (OAC) is recommended for preventing stroke in atrial fibrillation (AF). However, the OAC utilisation in AF patients with dementia or cognitive impairment (CI) is limited. This study aimed to examine the prevalence of OAC prescriptions in AF patients with dementia/CI and to identify factors associated with OAC treatment within 180 days after dementia/CI diagnosis. METHODS: Using The Health Improvement Network database, the annual trends of OAC between 2000 and 2015 were calculated. Multivariable logistic regression was performed to identify factors associated with OAC treatment. RESULTS: The prevalence rate of OAC prescriptions increased from 6.1% in 2000 to 45.9% in 2015. Among OAC users, the proportion of direct oral anticoagulants (DOACs) use increased significantly from 0.1% in 2011 to 33.8% in 2015 (P-trend < 0.001), while the proportion of vitamin K antagonist use decreased by 28.6% from 100% in 2000 to 71.4% in 2015 (P-trend < 0.001). In the multivariable analysis, younger age, very old age, female sex, higher Charlson Comorbidity Index, having a HAS-BLED score ≥3, a history of intracranial bleeding, falls and polypharmacy were significantly associated with lower odds of receiving OAC. CONCLUSIONS: In UK primary care, OAC use increased from 2000 to 2015 in AF patients with dementia/CI, with a substantial increase in use of DOACs. Characteristics related to frailty are associated with lower odds of OAC prescription. Given the increasing use of DOACs in patients with dementia/CI, further studies are needed to investigate the safety and effectiveness of DOACs in this important patient group.

Non-vitamin K oral anticoagulants and risk of fractures: a systematic review and meta-analysis.

AIMS: Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains unclear. This study aimed to provide summary relative risk (RR) estimates for associations between NOACs vs. VKAs and fracture risk. METHODS AND RESULTS: PubMed, EMBASE, and Cochrane Library were searched from 2010 to 26 May 2020. Observational studies investigating the association between NOACs vs. VKAs and fracture risk in patients with AF were included. The adjusted effect estimates were pooled using the DerSimonian-Laird random effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiological (MOOSE) guidelines were followed. Five observational studies comprising 269 922 patients and 4289 fractures were included. Non-vitamin K antagonist oral anticoagulants use was associated with a lower risk of any fractures compared to VKAs use, with moderate heterogeneity [pooled RR = 0.83, 95% confidence interval (CI): 0.75-0.92, P < 0.001, I2 = 73.0%]. When comparing individual NOAC to VKAs, a statistically significant lower risk of any fractures was found for rivaroxaban (pooled RR = 0.79, 95% CI: 0.71-0.88, P < 0.001, I2 = 55.2%) and apixaban (pooled RR = 0.75, 95% CI: 0.60-0.92, P = 0.007, I2 = 54.5%), but not dabigatran (pooled RR = 0.87, 95% CI: 0.74-1.01, P = 0.061, I2 = 74.6%). No differences were observed in all head-to-head comparisons between NOACs. CONCLUSION: This large meta-analysis suggests that NOACs use was associated with a lower risk of fractures compared with VKAs. Fracture risks were similar between NOACs. These findings may help inform the optimal anticoagulant choice for patients with AF at high risk of fracture.

Exposure to COVID-19-Related Information and its Association With Mental Health Problems in Thailand: Nationwide, Cross-sectional Survey Study.

BACKGROUND: The COVID-19 pandemic has had a negative impact on both the physical and mental health of individuals worldwide. Evidence regarding the association between mental health problems and information exposure among Thai citizens during the COVID-19 outbreak is limited. OBJECTIVE: This study aimed to explore the relationship between information exposure and mental health problems during the COVID-19 pandemic in Thailand. METHODS: Between April 21 and May 4, 2020, we conducted a cross-sectional, nationwide online survey of the general population in Thailand. We categorized the duration of exposure to COVID-19-related information as follows: <1 h/day (reference group), 1-2 h/day, and ≥3 h/day. Mental health outcomes were assessed using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 scale, the Perceived Stress Scale-10, and the Insomnia Severity Index for symptoms of depression, anxiety, perceived stress, and insomnia, respectively. Multivariable logistic regression models were used to evaluate the relationship between information exposure and the risk of developing the aforementioned symptoms. An ancillary analysis using multivariable multinomial logistic regression models was also conducted to assess the possible dose-response relationship across the severity strata of mental health problems. RESULTS: Of the 4322 eligible participants, 4004 (92.6%) completed the online survey. Of them, 1481 (37.0%), 1644 (41.1%), and 879 (22.0%) participants were exposed to COVID-19-related information for less than 1 hour per day, 1 to 2 hours per day, or 3 or more hours per day, respectively. The major source of information related to the COVID-19 pandemic was social media (95.3%), followed by traditional media (68.7%) and family members (34.9%). Those exposed to information for 3 or more hours per day had a higher risk of developing symptoms of depression (adjusted odds ratio [OR] 1.35, 95% CI 1.03-1.76; P=.03), anxiety (adjusted OR 1.88, 95% CI 1.43-2.46; P<.001), and insomnia (adjusted OR 1.52, 95% CI 1.17-1.97; P=.001) than people exposed to information for less than 1 hour per day. Meanwhile, people exposed to information for 1 to 2 hours per day were only at risk of developing symptoms of anxiety (adjusted OR 1.35, 95% CI 1.08-1.69; P=.008). However, no association was found between information exposure and the risk of perceived stress. In the ancillary analysis, a dose-response relationship was observed between information exposure of 3 or more hours per day and the severity of mental health problems. CONCLUSIONS: These findings suggest that social media is the main source of COVID-19-related information. Moreover, people who are exposed to information for 3 or more hours per day are more likely to develop psychological problems, including depression, anxiety, and insomnia. Longitudinal studies investigating the long-term effects of COVID-19-related information exposure on mental health are warranted.

Gastrointestinal bleeding risk with rivaroxaban vs aspirin in atrial fibrillation: A multinational study.

PURPOSE: Comparative gastrointestinal bleeding (GIB) risk between rivaroxaban and low-dose aspirin is unknown in patients with atrial fibrillation (AF). This study investigated GIB risk with rivaroxaban vs aspirin among two separate AF cohorts in Hong Kong and the United Kingdom, using a common protocol approach. METHODS: This was a population-based cohort study using separate data from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (2010-2018) and The Health Improvement Network (THIN) database in the United Kingdom (2011-2017). Patients with AF newly prescribed aspirin or rivaroxaban were included. Cox proportional hazards regression was used to compare GIB risks for rivaroxaban vs aspirin, accounting for confounders using propensity score fine stratification approach. RESULTS: In CDARS, 29 213 patients were included; n = 1052 (rivaroxaban), n = 28 161 (aspirin). Crude GIB event rates per 100 patient-years in CDARS were 3.0 (aspirin) and 2.6 (rivaroxaban). No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.04, 95%CI = 0.76-1.42), and in dose-stratified analyses (HR = 1.21, 95%CI = 0.84-1.74 [20 mg/day]; HR = 0.80, 95%CI = 0.44-1.45 [≤15 mg/day]). In THIN, 11 549 patients were included, n = 3496 (rivaroxaban) and n = 8053 (aspirin). Crude GIB event rates were 1.3 (aspirin) and 2.4 (rivaroxaban) per 100 patient-years. No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.40, 95%CI = 1.00-1.98) and low-dose rivaroxaban (≤15 mg/day) (HR = 1.00, 95%CI = 0.56-1.30), but increased GIB risk was observed for rivaroxaban 20 mg/day vs aspirin (HR = 1.57, 95%CI = 1.08-2.29). CONCLUSION: In patients with AF, GIB risk was comparable between aspirin and rivaroxaban ≤15 mg/day. GIB risk for rivaroxaban 20 mg/day vs aspirin remains uncertain and warrants further investigation.

Estimating Adverse Events Associated With Herbal Medicines Using Pharmacovigilance Databases: Systematic Review and Meta-Analysis.

BACKGROUND: Herbal medicines (HMs) are extensively used by consumers/patients worldwide. However, their safety profiles are often poorly reported and characterized. Previous studies have documented adverse events (AEs) associated with HMs, such as hepatotoxicity, renal failure, and allergic reactions. However, the prevalence rate of AEs related to HMs has been reported to be low. To date, no systematic review and meta-analysis has comprehensively analyzed the AEs of HMs using published data acquired from pharmacovigilance (PV) databases. OBJECTIVE: This study aimed to (1) estimate the reporting rate of the AEs of HMs using PV databases and (2) assess the detailed data provided in AE reports. METHODS: In this systematic review and meta-analysis, MEDLINE/PubMed, SCOPUS, EMBASE, and CINAHL were systematically searched for relevant studies (until December 2023). The DerSimonian-Laird random effects model was used for pooling the data, and subgroup analyses, the meta-regression model, and sensitivity analysis were used to explore the source of heterogeneity. Crombie's checklist was used to evaluate the risk of bias (ROB) of the included studies. RESULTS: In total, 26 studies met the eligibility criteria. The reporting rate of the AEs of HMs ranged considerably, from 0.03% to 29.84%, with a median overall pooled estimate of 1.42% (IQR 1.12%-1.72%). Subgroup analyses combined with the meta-regression model revealed that the reporting rate of the AEs of HMs was associated with the source of the reporter (P=.01). None of the included studies provided full details of suspected herbal products, only the main ingredients were disclosed, and other potentially harmful components were not listed. CONCLUSIONS: This systematic review and meta-analysis highlighted risks related to HMs, with a wide range of reporting rates, depending on the source of the reporter. Continuous efforts are necessary to standardize consumer reporting systems in terms of the reporting form, education, and follow-up strategy to improve data quality assurance, aiming to enhance the reliability and utility of PV data for monitoring the safety of HMs. Achieving effective monitoring and reporting of these AEs necessitates collaborative efforts from diverse stakeholders, including patients/consumers, manufacturers, physicians, complementary practitioners, sellers/distributors, and health authorities. TRIAL REGISTRATION: PROSPERO (Prospective International Register of Systematic Reviews) CRD42021276492.

Comparative Effectiveness and Safety of Off-Label Underdosed Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: Off-label underdosed direct oral anticoagulants (DOACs) are commonly utilised in Asian patients with atrial fibrillation (AF) since they are prone to bleeding with OACs. However, the efficacy and safety of off-label underdosing DOACs are controversial. This study aimed to compare the effectiveness and safety of off-label underdosed DOACs in Asian patients with AF. METHODS: PubMed, Embase, Cochrane library, and ClinicalTrials.gov were searched from 2010 to July 5, 2024, for randomised controlled trials or observational studies that compared off-label DOACs and on-label/warfarin in Asian patients with AF. The primary outcomes included ischaemic stroke or systemic embolism (ISSE) and major bleeding (MB), while secondary outcomes included all-cause death, gastrointestinal bleeding (GIB), intracranial haemorrhage (ICH), and myocardial infarction (MI). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS: Twenty observational studies were included. Seventeen studies compared off-label underdosed DOACs versus on-label DOACs, whereas five studies compared off-label underdosed DOACs versus warfarin. Off-label underdosed DOACs were associated with higher risk of ISSE (pooled HR [pHR] = 1.17; 95% CI: 1.00-1.38, p = 0.048) and ICH (pHR = 1.27; 95% CI: 1.06-1.52, p = 0.010) versus on-label. Subgroup analysis demonstrated increased ISSE risk with off-label underdosed rivaroxaban compared to on-label (pHR = 1.49; 95% CI: 1.07-2.08). Compared to warfarin, off-label underdosed DOACs were associated with decreased risk of MB (pHR = 0.46; 95% CI: 0.32-0.65, p < 0.001), GIB (pHR = 0.52; 95% CI: 0.29-0.93, p = 0.028), ICH (pHR = 0.60; 95% CI: 0.42-0.86, p = 0.005), and all-cause death (pHR = 0.70; 95% CI: 0.56-0.87, p = 0.001), while illustrating similar ISSE risk. CONCLUSIONS: Off-label underdosed DOACs, particularly rivaroxaban, was associated with increased ISSE risk but did not decrease bleeding compared to on-label. Adherence to appropriate DOAC doses should be emphasised to achieve the best clinical outcomes for Asian patients with AF.

Sex-specific comparative outcomes between oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis.

AIMS: Women with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes of DOACs in AF. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched from January 2008 to November 2022. Sex-specific comparative outcomes of stroke/systemic embolism (SE), major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) between oral anticoagulants were pooled using random effects models. P values for interaction were calculated to examine differences in results between sexes. RCTs and observational studies were meta-analysed separately. RESULTS: 5 RCTs and 33 observational studies were included, totalling 1 085 931 women and 1 387 123 men. Meta-analyses showed that for both sexes, DOAC versus warfarin was generally associated with lower risk of stroke/SE, major bleeding and ICH; in DOAC-DOAC comparisons, rivaroxaban versus dabigatran had higher GIB risk. The only sex-specific difference observed was that when compared with warfarin, women had higher GIB risk with rivaroxaban (women: pooled risk ratio (pRR)=1.34, 95% CI=1.18 to 1.51; men: pRR=0.97, 95% CI=0.85 to 1.10; p value for interaction (p for interaction)<0.001) and possibly dabigatran (women: pRR=1.25, 95% CI=0.92 to 1.70; men: pRR=0.83, 95% CI=0.72 to 0.97; p-for-interaction=0.02). The sex difference in GIB remained for rivaroxaban when a Bonferroni-corrected significance level was used (α=0.003). No sex-specific GIB data for apixaban and edoxaban was available for the meta-analysis. CONCLUSIONS: For both sexes, DOACs generally demonstrated favourable effectiveness and safety over warfarin. However, observational data suggested that women may have higher GIB risk with rivaroxaban and possibly dabigatran than warfarin. Further studies are warranted to verify our findings and elucidate sex-specific GIB risk with apixaban and edoxaban, of which the data is currently lacking. PROSPERO REGISTRATION NUMBER: CRD42022325027.

Efficacy and safety of metformin for melasma treatment: a systematic review and meta-analysis.

Objective: Metformin has recently been demonstrated to have an anti-melanogenic activity. Nevertheless, clinical evidence of the effectiveness of metformin in melasma is lacking. The objective of this study was to assess the efficacy and safety of metformin in the treatment of melasma. Methods: MEDLINE, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, CINAHL, and grey literature databases were searched to 4 October 2022 and updated on 26 February 2023. Randomized controlled trials (RCTs), quasi-RCTs, observational studies, case series, and case reports investigating the efficacy and safety of metformin for melasma were included. The Melasma Area Severity Index (MASI) scores that changed from baseline were pooled using fixed-effects model and expressed as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Three RCTs including 140 patients with melasma were included. The results demonstrated that after 8 weeks, 15% topical metformin significantly reduced the Melasma Area Severity Index (MASI) score compared to placebo (1 trial; n = 60; MD, -0.56; 95% CI, -1.07 to -0.04; p = 0.034). Furthermore, when compared to triple combination cream (TCC), 30% topical metformin demonstrated similar efficacy in reducing the MASI score after 8 weeks (2 trials; n = 80; MD, 0.19, 95% CI, -0.25 to 0.63; p = 0.390). Patients using 30% topical metformin had fewer adverse events compared to TCC users, although no statistical difference was found. Conclusion: Topical metformin was as effective as triple combination cream (TCC) in decreasing changes in the MASI score in patients with melasma, with minimum adverse events. Further studies with larger sample sizes, longer follow-up times, and well-designed trials are required. Systematic Review Registration: Identifier PROSPERO (CRD42022351966).

Corrigendum: Concurrent use of oral anticoagulants and sulfonylureas in individuals with type 2 diabetes and risk of hypoglycemia: a UK population-based cohort study.

[This corrects the article DOI: 10.3389/fmed.2022.893080.].

Optimal dose of misoprostol combined with oxytocin for preventing postpartum hemorrhage in cesarean section: A randomised controlled trial.

Background: The study analyzed an optimal misoprostol dosage in prevention of postpartum hemorrhage (PPH). Also evaluated the side effects that might be related to dose of misoprostol. Material and methods: A randomised study was performed in mothers who received cesarean section. Participants were divided into 3 groups of 400, 600 and 800 µg intrauterine misoprostol insertion combined with oxytocin. Clinical characteristics, laboratory testing and operative data were collected. The primary outcome was the amount of intra-operative blood loss and side effects were assigned as a secondary outcome. Results: There were 357 eligible cases, 119 cases in each group equally. Baseline characteristics were similar in between groups. Higher misoprostol dosage demonstrated lower blood loss. Mean blood loss was 509.1, 465.7 and 441.1 ml in the 400, 600 and 800 µg misoprostol groups respectively which were significant difference (p value 0.027). Post-hoc pairwise t-tests found that 800 µg group diminished blood loss than 400 µg group (p value 0.004). Intra-operative blood loss ≥500 ml occurred less frequently in patients receiving higher misoprostol dosage (p value 0.035). However, PPH was not identified difference between groups (p value 0.707). Nausea and vomiting were complained in less than 1% while none of the cases exhibited shivering. Pyrexia was identified in all groups, however, there was a trend towards lower dosage related to less percentage of pyrexia. Conclusions: Either 400, 600 or 800 µg of misoprostol can prevent PPH similarly. However, the study prefers 400 µg misoprostol because of minimization the side effects.

Concurrent Use of Oral Anticoagulants and Sulfonylureas in Individuals With Type 2 Diabetes and Risk of Hypoglycemia: A UK Population-Based Cohort Study.

Objective: To investigate the association of concurrent use of oral anticoagulants (OACs) and sulfonylureas and the risk of hypoglycemia in individuals with type 2 diabetes mellitus (T2DM). Research Design and Methods: A retrospective cohort study was conducted between 2001 and 2017 using electronic primary healthcare data from the IQVIA Medical Research Data (IMRD) that incorporates data supplied by The Health Improvement Network (THIN), a propriety database of Cegedim SA. Individuals with T2DM who received OAC prescription and sulfonylureas were included. We compared the risk of hypoglycemia with sulfonylureas and OACs using propensity score matching and Cox regression. Results: 109,040 individuals using warfarin and sulfonylureas and 77,296 using direct oral anticoagulants (DOACs) and sulfonylureas were identified and included. There were 285 hypoglycemia events in the warfarin with sulfonylureas group (incidence rate = 17.8 per 1,000 person-years), while in the sulfonylureas only, 304 hypoglycemia events were observed (incidence rate = 14.4 per 1,000 person-years). There were 14 hypoglycemic events in the DOACs with sulfonylureas group (incidence rates = 14.8 per 1,000 person-years), while in the sulfonylureas alone group, 60 hypoglycemia events were observed (incidence rate =23.7 per 1,000 person-years). Concurrent use of warfarin and sulfonylureas was associated with increased risk of hypoglycemia compared with sulfonylureas alone (HR 1.38; 95% CI 1.10-1.75). However, we found no evidence of an association between concurrent use of DOACs and sulfonylureas and risk of hypoglycemia (HR 0.54; 95% CI, 0.27-1.10) when compared with sulfonylureas only. Conclusions: We provide real-world evidence of possible drug-drug interactions between warfarin and sulfonylureas. The decision to prescribe warfarin with coexistent sulfonylureas to individuals with T2DM should be carefully evaluated in the context of other risk factors of hypoglycemia, and availability of alternative medications.

Drug-Related Problems Identified at Patients' Home: A Prospective Observational Study in a Rural Area of Thailand.

OBJECTIVE: The aim of the study was to examine the prevalence rates, nature, and predictors of drug-related problems (DRPs) experienced in participants living at home in a rural Thailand. METHOD: A cross-sectional observational study was undertaken during December 2015 to January 2016. Drug-related problems were identified within a rural township having a population of 5256 by means of home visits by pharmacists. All suspected cases were then assessed for severity and preventability by clinical specialists. Drug-related problems were categorized according to Pharmaceutical Care Network Europe classification (revised 2010).v.6.2. RESULTS: From a systematically recruited cohort of 359 participants, suspected DRPs were identified in 160 participants. After detailed reviews by clinical specialists, 141 cases (39.3%) were deemed to have DRPs. Types of DRPs with prevalence rates were the following: problems of treatment effectiveness (3.7% of DPRs), adverse reactions (15.3%), treatment cost (28.4%), nonadherence to drugs (42.1%), and poor drug storage (10.5%). The most common drug to involve DRPs was those treating cardiovascular disease, especially simvastatin. CONCLUSIONS: Nearly half of community living participants experienced DRPs, especially nonadherence to drugs, and has implications for other rural elderly persons of low education attainment for similar rural economies around the globe. Appropriate interventions should focus on reducing polypharmacy, providing outreach programs, and rigorous pharmacovigilance.

Epidemiology and treatment of atrial fibrillation in patients with type 2 diabetes in the UK, 2001-2016.

Patients with Type 2 diabetes mellitus (T2DM) have an increased risk of atrial fibrillation (AF). The current study aimed to investigate the prevalence and treatment of AF in patients with T2DM, assess the impact of direct oral anticoagulants (DOACs) introduction on oral anticoagulant (OACs) prescribing rates, and factors associated with OAC initiations in patients with T2DM and AF. The Health Improvement Network (THIN) database (2001-2016), was used to examine the annual prevalence and treatment of AF in T2DM. The impact of DOACs introduction on OAC prescribing rates were investigated using interrupted time series analysis (ITS). Factors associated with OAC initiations were also identified using multivariate logistic regression. The prevalence of AF increased from 2.7 [95% confidence intervals (CI) 2.5-2.8] in 2001 to 5.0 (4.9-5.1) in 2016 per 100 persons. OACs prescribing within 30-days of AF diagnosis increased from 21.5% in 2001 to 56.8% in 2016. ITS analysis showed that OAC prescribing increased after DOAC introduction (P < 0.001), however, no immediate change was observed (P = 0.29). T2DM patients with AF, aged 60-79, male gender and BMI ≥ 25 were more likely to receive OAC, adjusted OR 1.3 (1.2-1.5) for aged 60-79, 1.3 (1.2-1.4) for male gender and 2.0 (1.9-2.2) for BMI ≥ 25, respectively. This study highlighted an increase in prevalence of AF in patients with T2DM during the study period. Further studies are warranted to investigate factors contributing to the underuse of OAC in patients with T2DM and AF.

Oral anticoagulant and reduced risk of dementia in patients with atrial fibrillation: A population-based cohort study.

BACKGROUND: Whether oral anticoagulation (OAC) can prevent dementia or cognitive impairment (CI) in patients with atrial fibrillation (AF) remains unclear. OBJECTIVE: The purpose of this study was to investigate the risk of dementia/CI among AF patients with and without OAC treatment. METHODS: We conducted a retrospective cohort study using United Kingdom (UK) primary care data (2000-2017). Participants with newly diagnosed AF without a history of dementia/CI were identified. Inverse probability of treatment weights based on propensity scores and Cox regression were used to compare the dementia outcomes. RESULTS: Among 84,521 patients with AF, 35,245 were receiving OAC treatment and 49,276 received no OAC treatment; of these patients, 29,282 were receiving antiplatelets. Over a mean follow-up of 5.9 years, 5295 patients developed dementia/CI. OAC treatment was associated with a lower risk of dementia/CI compared to no OAC treatment (hazard ratio [HR] 0.90; 95% confidence interval 0.85-0.95; P <.001) or antiplatelets (HR 0.84; 95% confidence interval 0.79-0.90; P <.001). No significant difference in dementia risk was observed for direct oral anticoagulants (DOACs) vs warfarin (HR 0.89; 95% confidence interval 0.70-1.14; P = .373), whereas dual therapy (OAC plus an antiplatelet agent) was associated with a higher risk of dementia/CI compared with no treatment (HR 1.17; 95% confidence interval 1.05-1.31; P = .006). CONCLUSION: OAC use was associated with a lower risk of dementia/CI compared to non-OAC and antiplatelet treatment among AF patients. The evidence for DOAC on cognitive function is insufficient, and further studies including randomized clinical trials are warranted.

Incidence and prevalence of hypoglycaemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis.

BACKGROUND: Previous meta-analysis investigating the incidence and prevalence of hypoglycaemia in both types of diabetes is limited. The purpose of this review is to conduct a systematic review and meta-analysis of the existing literature which investigates the incidence and prevalence of hypoglycaemia in individuals with diabetes. METHODS: PubMed, Embase and Cochrane library databases were searched up to October 2018. Observational studies including individuals with diabetes of all ages and reporting incidence and/or prevalence of hypoglycaemia were included. Two reviewers independently screened articles, extracted data and assessed the quality of included studies. Meta-analysis was performed using a random effects model with 95% confidence interval (CI) to estimate the pooled incidence and prevalence of hypoglycaemia in individuals with diabetes. RESULTS: Our search strategy generated 35,007 articles, of which 72 studies matched the inclusion criteria and were included in the meta-analysis. The prevalence of hypoglycaemia ranged from 0.074% to 73.0%, comprising a total of 2,462,810 individuals with diabetes. The incidence rate of hypoglycaemia ranged from 0.072 to 42,890 episodes per 1,000 person-years: stratified by type of diabetes, it ranged from 14.5 to 42,890 episodes per 1,000 person-years and from 0.072 to 16,360 episodes per 1,000-person years in type 1 and type 2 diabetes, respectively. CONCLUSION: Hypoglycaemia is very common among individuals with diabetes. Further studies are needed to investigate hypoglycaemia-associated risk factors.

Effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on all-cause mortality, cardiovascular death, and cardiovascular events among peritoneal dialysis patients: A protocol for systematic review.

BACKGROUND: Based on the International Society for peritoneal dialysis (PD) recommendations, blockade of renin-angiotensin systems with an angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improves residual kidney function in PD patients. However, the long-term effectiveness of ACEI/ARB use in PD patients has not been fully elucidated. We, therefore, intend to perform a systematic review and meta-analysis to summarize the effects of ACEI/ARB use on long-term mortality, cardiovascular outcomes, and adverse events among PD patients. METHODS: This systematic review will include both randomized controlled trials and non-randomized studies in adult PD patients. We also plan to incorporate data from our cohort study in Thai PD population into this review. We will search PubMed, Medline, EMBASE, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature from inception to February 29, 2019, with no language restrictions. The process of study screening, selection, data extraction, risk of bias assessment, and grading the strength of evidence will be performed independently by a pair of reviewers. Any discrepancy will be resolved through a team discussion and/or consultation with the third reviewer. The pooled effects estimate and 95% confidence intervals will be estimated using DerSimonian-Laird random-effects models. Heterogeneity will be assessed by the Cochran Q test, I index and tau-squared statistics. The funnel plots along with the Begg and Egger test and trim and fill method will be performed to investigate any evidence of publication bias. Preplanned subgroup analyses and random-effects univariate meta-regressions will be performed to quantify the potential sources of heterogeneity based on studies- and patient-characteristics. RESULTS: This will be the first systematic review and meta-analysis to summarize the long-term effectiveness of renin-angiotensin system inhibitors in PD populations. CONCLUSION: In summary, this systematic review and meta-analysis will summarize the effectiveness of ACEI/ARB on long-term mortality, cardiovascular outcomes, and adverse events among adult PD patients by integrated all available evidences. ETHICS AND DISSEMINATION: Based on the existing published data, an ethical approval is not required. The findings will be disseminated through scientific meetings and publications in peer-reviewed journals.PROSPERO registration number: CRD42019129492.

Mental health circumstances among health care workers and general public under the pandemic situation of COVID-19 (HOME-COVID-19).

BACKGROUND: After the spread of the coronavirus disease 2019 (COVID-19) globally, upgraded quarantine and physical distancing strategy, strict infection measures, and government's strict lockdown have been abided to confront the spread of the COVID-19 in Thailand. During the COVID-19 pandemic, concerns about the mental health and psychosocial problems among health care workers and the general population are now arising. Yet, information on mental health and psychosocial problems among health care workers and the general population have not been comprehensively reported in Thailand. As such, we conduct a cross-sectional study, a national online survey to describe the short- and long-term consequences of the COVID-19 pandemic on mental health and psychosocial problems among health care workers and the general population in Thailand. METHODS: This study is a repeated cross-sectional study, an open online voluntary national-based survey during the wave I (April 21-May 4, 2020) follow-up in the wave II (August 3-16, 2020), wave III (November 15-28, 2020), and a 1-year follow-up survey (wave IV: April 21-May 4, 2021) in Thailand. Health care workers at the hospitals and the adult general population will be invited to participate in the online survey via the SurveyMonkey that limits one-time participation per unique internet protocol address. The target sample size of at least 1182 health care workers and 1310 general populations will be required to complete the online survey for each wave of the survey. Sociodemographic characteristics and a set of measurement tools for mental and psychosocial problems for each subcohort including depression, anxiety, stress, resilient copings, neuroticism, perceived social support, wellbeing, somatic symptoms, insomnia, burnout (for healthcare workers), and public stigma toward COVID-19 infection (for the general population) will be collected. For all estimates of prevalence, we will weigh data for all wave analyses under the complex design of the survey. Subgroup analyses stratified by key characteristics will also be done to analyze the proportion differences. For the repeated cross-sectional survey, we will combine the data from the wave I to wave IV survey to analyze changes in the mental health status. We will perform multilevel logistic regression models with random intercepts to explore associations with individual-level and region-level/hospital-level predictors. We also plan to perform an ancillary systematic review and meta-analysis by incorporating data from our findings to all available evidence. RESULTS: Our findings will provide information on the short- and long-term mental health status as well as the psychosocial responses to the COVID-19 outbreak in a national sample of health care workers and the general population in Thailand. CONCLUSION: This prospective, nationally based, a repeated cross-sectional study will describe the mental health status and psychosocial problems among health care workers and the general population in Thailand during the COVID-19 pandemic. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Faculty of Public Health and Faculty of Pharmacy, Chiang Mai University. The findings will be disseminated through public, scientific, and professional meetings, and publications in peer-reviewed journals. THAI CLINICAL TRIALS REGISTRY (TCTR) REGISTRATION NUMBER: TCTR20200425001.

Trends in oral anticoagulant prescribing in individuals with type 2 diabetes mellitus: a population-based study in the UK.

OBJECTIVE: To evaluate oral anticoagulant (OAC) prescribing trends in type 2 diabetes mellitus (T2DM) in the UK from 2001 to 2015. DESIGN: A cross-sectional drug utilisation study. SETTING: Electronic health records from The Health Improvement Network primary care database in the UK. PARTICIPANTS: Individuals with T2DM who received a record of OAC prescription. OUTCOME MEASURES: The prescribing trends of OAC medications in individuals with T2DM were examined from 2001 to 2015, stratified by age, gender and therapeutic classifications. RESULTS: A total of 361 635 individuals with T2DM were identified, of whom 36 570 were prescribed OAC from 2001 to 2015. The prevalence of OAC prescribing increased by 50.0%, from 1781 individuals receiving OAC prescriptions (IROACP) (4.4 (95% CI 4.2 to 4.6) per 100 persons) in 2001, to 17 070 IROACP (6.6 (95% CI 6.5 to 6.7) per 100 persons) in 2015. The prevalence of warfarin prescribing decreased by 14.0%, from 1761 individuals receiving warfarin prescriptions (IRWP) (98.9 (95% CI 98.4 to 99.4) per 100 persons) in 2001, to 14 533 IRWP (85.1 (95% CI 84.6 to 85.7) per 100 persons) in 2015. This corresponded with increased prescribing of direct oral anticoagulants (DOACs), from 18 individuals receiving DOAC prescriptions (IRDOACP) (0.1 (95% CI 0.08 to 0.23) per 100 persons) in 2010, to 3016 IRDOACP (17.6 (95% CI 17.1 to 18.2) per 100 persons) in 2015, during the same period. CONCLUSIONS: Prescribing of OACs in individuals with T2DM increased from 2001 to 2015. Since the introduction of DOACs, there has been a clear shift in prescribing towards these agents. Future studies are needed to assess the safety of coadministration of OAC medications and antidiabetic therapy with T2DM.