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.].

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Safety and Effectiveness of Direct Oral Anticoagulants vs Warfarin in People With Atrial Fibrillation and Dementia.

OBJECTIVE: To determine risks of embolic events, bleeding, and mortality with direct oral anticoagulants (DOACs) vs warfarin in people with atrial fibrillation (AF) and dementia. DESIGN: New-user retrospective cohort study using The Health Improvement Network database. SETTING AND PARTICIPANTS: A population-based sample comprising people with AF and dementia prescribed DOACs or warfarin from August 2011 to September 2017. METHODS: Risk of ischemic stroke (IS), ischemic stroke/transient ischemic attack/systemic embolism (IS/TIA/SE), all-cause mortality, intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and other bleeding were compared for DOACs vs warfarin using propensity score-adjusted Poisson regression. Incidence rate ratios (IRRs) and absolute risk differences (ARDs) were calculated. RESULTS: Overall, 2399 people with AF and dementia initiated DOACs (42%) or warfarin (58%). Before propensity score adjustment, patients who initiated DOACs were older and had more comorbidities. After adjustment, DOAC initiators demonstrated similar risks of IS, TIA, or SE; IS alone; and other bleeding but reduced ICB risk (IRR 0.27, 95% CI 0.08, 0.86; ARD -5.2, 95% CI -6.5, -1.0, per 1000 person-years) compared with warfarin. Increased risk of GIB (IRR 2.11, 95% CI 1.30, 3.42; ARD 14.8, 95% CI 4.0, 32.4, per 1000 person-years) and all-cause mortality (IRR 2.06, 95% CI 1.60, 2.65; ARD 53.0, 95% CI 30.2, 82.8, per 1000 person-years) were observed in DOAC initiators compared with warfarin. CONCLUSIONS AND IMPLICATIONS: Among people with AF and dementia, initiating treatment with DOACs compared with warfarin was associated with similar risks of IS, TIA, or SE and IS alone. DOAC-treated patients demonstrated reduced ICB risk but increased GIB and all-cause mortality risks. We cannot exclude the possible impact of residual confounding from channeling of DOACs toward older and sicker people, particularly for the outcome of all-cause mortality. Further safety data are urgently needed to confirm findings.

Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol.

BACKGROUND: Current international guidelines recommend the use of a daily topical exit-site antimicrobial to prevent peritoneal dialysis (PD)-related infections. Although nonantibiotic-based therapies are appealing because they may limit antimicrobial resistance, no controlled trials have been conducted to compare topical antimicrobial agents with usual exit-site care for the prevention of PD-related infections among the Thai PD population. We propose a controlled three-arm trial to examine the efficacy and safety of a daily chlorhexidine gluconate-impregnated patch versus mupirocin ointment versus usual exit-site care with normal saline for the prevention of PD-related infections. METHODS/DESIGNS: This study is a randomized, double-blind, multicenter, active-controlled, clinical trial. Adult patients aged 18 years or older who have end-stage kidney disease and are undergoing PD will be enrolled at three PD Centers in Thailand. A total of 354 PD patients will be randomly assigned to either the 2% chlorhexidine gluconate-impregnated patch, mupirocin ointment, or usual exit-site care with normal saline dressing according to a computer-generated random allocation sequence. Participants will be followed until discontinuation of PD or completion of 24 months. The primary study outcomes are time to first PD-related infection (exit-site/tunnel infection or peritonitis) event and the overall difference in PD-related infection rates between study arms. Secondary study outcomes will include (i) the rate of infection-related catheter removal and PD technique failure, (ii) rate of nasal and exit-site Staphylococcus aureus colonization, (iii) healthcare costs, and (iv) skin reactions and adverse events. We plan to conduct a cost-utility analysis alongside the trial from the perspectives of patients and society. A Markov simulation model will be used to estimate the total cost and health outcome in terms of quality-adjusted life years (QALYs) over a 20-year time horizon. An incremental cost-effectiveness ratio in Thai Baht and U.S. dollars per QALYs gained will be illustrated. A series of probabilistic sensitivity analyses will be conducted to assess the robustness of the cost-utility analysis findings. DISCUSSION: The results from this study will provide new clinical and cost-effectiveness evidence to support the best strategy for the prevention of PD-related infections among the Thai PD population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02547103. Registered on September 11, 2015.

Safety and Tolerability of Antipsychotic Medication in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Antipsychotic medication is a commonly prescribed drug class in individuals with autism spectrum disorder (ASD). However, the safety of these agents has not been fully assessed. OBJECTIVE: Our objective was to investigate the safety and tolerability profile of antipsychotics in individuals with ASD. METHODS: The Cochrane Library, MEDLINE, Embase and PsycINFO databases were searched up to January 2018. We included studies that reported adverse events (AEs) in participants with ASD taking first- or second-generation antipsychotic medication. The studies included in the analysis were randomized controlled trials (RCTs) and observational studies that were comparative or noncomparative and published as full text in the English language. The primary outcome of this review was AEs of any severity reported with antipsychotic use at any dose. Meta-analysis was performed on studies with child and adolescent participants to estimate the pooled prevalence of the overall AEs and the relative risk (RR) of AEs associated with antipsychotic use using a random-effects model. The Cochrane Collaboration tool and the modified Newcastle-Ottawa Scale (NOS) were used to assess the risk of bias of the included RCTs and observational studies, respectively. RESULTS: In total, 54 citations fulfilled the inclusion criteria, of which 40 were RCTs and 14 were observational studies; eight RCTs were included in the meta-analysis to estimate the RR of AEs associated with antipsychotic use and seven observational studies were included to estimate the pooled prevalence of AEs. The RR of AEs with antipsychotic treatment was 22% higher than with placebo (RR 1.22; 95% confidence interval [CI] 1.11-1.34; I2 = 30.6%; p = 0.184). The estimated pooled prevalence of AEs was 50.5% (95% CI 33-67). The most commonly reported AEs were increased appetite and weight gain, which were associated with discontinuation in many participants. CONCLUSION: Antipsychotic-related AEs were common among patients with ASD. Further studies to investigate the implications of antipsychotic-related AEs on health and medication adherence are warranted. PROSPERO registration number: (CRD42018083632).