Efficacy and safety of topical capsaicin in the treatment of osteoarthritis pain: A systematic review and meta-analysis.

Osteoarthritis (OA) affects hundreds of millions of people worldwide. The objective was to critically appraise the efficacy and safety of topical capsaicin in reducing pain in OA. MEDLINE (PubMed) and Embase (Ebsco) were searched from inceptions until February 2023. The eligibility criteria included randomized controlled trials (RCTs), evaluating topical capsaicin in OA patients. Standard Cochrane methods were used to extract data and to appraise eligible studies. Eight double-blind RCTs involving 498 patients were included. Five trials (62.5%) were at an overall low risk of bias, and three (37.5%) were at a high risk of bias. Meta-analysis showed that, in various OA patients, compared with placebo, topical capsaicin (0.0125%-5%) may reduce pain severity measured with visual analog scale (standardized mean difference = -0.84, 95% confidence intervals [CIs] = -1.48 to -0.19, p = 0.01; eight studies). However, topical capsaicin may increase burning sensation at the application site (risk ratio = 5.56, 95% CI = 1.75-17.69, p = 0.004, numbers needed to harm = 3; five studies) when compared with placebo. Limitations include short study durations, small sample sizes, high heterogeneity, and overall low-to-very-low certainty of the evidence. Topical capsaicin may reduce OA pain at follow-ups of up to 3 months. Larger trials, potentially evaluating capsaicin in combination with phytopharmaceuticals having anti-inflammatory effects, with longer follow-ups might be needed to reduce the existing uncertainties. Topical capsaicin might be recommended for short-term management of pain in OA patients intolerant to nonsteroidal anti-inflammatory drugs.

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.

HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity: a systematic review and meta-analysis.

Associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity have been reported. To consolidate the results from all available reports in scientific databases, systematic review and meta-analysis techniques were used to quantify these associations. Studies investigating associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity were systematically searched in PubMed, Human Genome Epidemiology Network, and the Cochrane Library. Primary outcomes were the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. Overall odds ratios (ORs) with the corresponding 95%CIs were calculated using a random-effect model to determine the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. A clear association between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity was identified in our analyses. The summary OR was 6.23 (95%CI = 4.11-9.45). Similar associations were also found in the subgroup analyses by lapatinib treatment regimens. ORs were 10.04 (95%CI = 6.15-16.39), 8.65 (95%CI = 4.52-16.58), and 3.88 (95%CI = 2.20-6.82) in the lapatinib group, lapatinib + trastuzumab group, and lapatinib + chemotherapy or lapatinib + trastuzumab + chemotherapy group, respectively. Since HLA-DRB1*07:01 is associated with lapatinib-induced hepatotoxicity, genetic screening of HLA-DRB1*07:01 in breast cancer patients prior to lapatinib therapy is warranted for patient safety. In addition, further studies should define the risk of HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity in specific ethnicities.

Efficacy and Safety of Centella Asiatica (L.) Urb. on Wrinkles: A Systematic Review of Published Data and Network Meta-Analysis.

Centella asiatica has many applications in cosmetics, including wrinkle treatments, but its effectiveness remains to be clarified. This systematic review study aimed to demonstrate the efficacy and safety of C. asiatica for reducing facial wrinkles. PubMed, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of clinical trials, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Thai Library Integrated System, and Thai university database/journals were searched until May 2019. Five double-blinded randomised controlled trials, including 172 Asian females, were included. Endpoints were wrinkling measured by visual score, image analysis, and participant satisfaction. Two placebo-controlled studies applied gel/creams containing C. asiatica or asiaticoside for 12 w to periorbital skin. Two studies applied tretinoin or Pueraria mirifica contralaterally and by network meta-analysis C. asiatica appeared more effective than P. mirifica but possibly less than tretinoin. Asiaticoside applied as a lipstick for 8 w reduced lip wrinkling. Skin hydration was markedly raised by C. asiatica but not tretinoin. One study reported 10 adverse events for C. asiatica and 35 for tretinoin. Cochrane risk of bias was generally low, reporting was weak, and lack of C. asiatica standardization prevents general application. From the reported data, it is possible to conclude that C. asiatica improved lip and periocular wrinkles, and may replace retinoids if its long-term safety is established and C. asiatica is standardized.

Analysis of medication consultation networks and reporting medication errors: a mixed methods study.

BACKGROUND: To examine characteristics of verbal consultation about medication within social networks of hospital inpatient medication system, and their associations with medication error reporting. METHOD: The setting was a 90-bed provincial district hospital with 4 wards, 7 physicians, 5 pharmacists, 44 nurses, 5 pharmacist assistants, and 4 unskilled ancillary workers. A mixed method comprising (i) a prospective observational study for investigating incidences and the nature of reporting medication errors, and (ii) a social network analysis for patterns of interaction. RESULTS: Out of 5296 prescriptions, 132 medication errors were reported during the one month study period: an incidence rate of 2.5%. Every incident of medication errors was formally documented through pharmacists. The most frequent medication errors were in pre-transcribing (n = 54; 40.9%). The pharmacists were central in the whole network of consultation on medication with the mean in-degree centrality of 35 (SD 14.9) and mean out-degree centrality of 15.4 (SD 11.1). Two bridging participants were identified who were influential communicators connecting the network (betweenness centrality). Medication error reporting were influenced by (i) participants whose advice is sought and viewed as trustworthy (in-degree centrality; p < 0.001), (ii) sex (p = 0.01), and (iii) level of education (p = 0.04). CONCLUSION: In-degree centrality was the most important network characteristic. A culture of medication safety can be fostered by encouraging consultation about the medication of in-patients within the hospital network where reporting of medication errors is essential.

Pharmacovigilance activities in ASEAN countries.

PURPOSE: This study aimed to explore the current landscape and identify challenges of pharmacovigilance (PV) among Association of Southeast Asian Nations (ASEAN) countries. METHODS: This cross-sectional survey collected data from May 2014 to December 2015. Questionnaires seeking to collect information on resources, processes, roles and responsibility, and functions of PV systems were sent to relevant persons in the ASEAN countries. Functions of PV centers were measured using the minimum World Health Organization requirements for a functional national PV system. Performances of PV centers were measured by the following: (1) the indicators related to the average number of individual case safety reports (ICSR); (2) presence of signal detection activities and subsequent action; and (3) contribution to the global vigilance database. RESULTS: Cambodia, Indonesia, Laos, Malaysia, the Philippines, Singapore, Thailand, and Vietnam completed the survey. PV systems in four surveyed countries (Indonesia, Malaysia, Singapore, and Thailand) achieved all aspects of the World Health Organization minimum requirement for a functional national PV system; the remaining countries were deemed to have unclear communication strategies and/or no official advisory committee. Average numbers of recent ICSR national returns ranged from 7 to 3817 reports/year/million population; three countries (Malaysia, Singapore, and Thailand) demonstrated good performance in reporting system and reported signal detection activities and subsequent actions. All participating countries had submitted ICSRs to the Uppsala Monitoring Center during the survey period (2013-2015). CONCLUSIONS: Four participating countries had functional PV systems. PV capacity, functionality, and legislative framework varied depending on local healthcare ecosystem networks. Implementing effective communication strategies and/or technical assistance from the advisory committee are needed to strengthen PV in ASEAN. Copyright © 2016 John Wiley & Sons, Ltd.

Association of HLA-B*5701 genotypes and abacavir-induced hypersensitivity reaction: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to systematically review and quantitatively synthesize the association between HLA-B*5701 and abacavir-induced hypersensitivity reaction (ABC-HSR). METHODS: We searched for studies that investigated the association between HLA-B genotype and ABC-HSR and provided information about the frequency of carriers of HLA-B genotypes among cases and controls. We then performed a meta-analysis with a random-effects model to pool the data and to investigate the sources of heterogeneity. RESULTS: From 1,026 articles identified, ten studies were included. Five using clinical manifestation as their diagnostic criteria, 409 and 1,883 subjects were included as cases and controls. Overall OR was 23.6 (95% CI = 15.4 - 36.3). Whereas, the another five studies using confirmed immunologic test as their diagnostic criteria, 110 and 1,968 subjects were included as cases and controls, respectively. The association of ABC-HSR was strong in this populations with HLA-B*5701. Overall OR was 1,056.2 (95% CI = 345.0 - 3,233.3). CONCLUSIONS: Using meta-analysis technique, the association between HLA-B*5701 and ABC-HSR is strong in the studies using immunologic confirmation to identify ABC-HSR. These results support the US FDA recommendations for screening HLA-B*5701 allele before initiating abacavir therapy.

Hospital admissions/visits associated with drug-drug interactions: a systematic review and meta-analysis.

PURPOSE: To estimate prevalences of hospital admissions/visits associated with actual drug-drug interactions (DDIs) and examine the effect of study design (prospective vs. retrospective), population (all ages or adults), and method of detecting DDIs on reported prevalences. METHODS: PubMed, International Pharmaceutical Abstracts, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature plus, and the Cochrane Database of Systematic Reviews up to October 2013 were searched for observational studies examining actual DDIs, in any language. The outcomes in this study were DDI prevalence rates in total populations, DDI prevalence rates in total adverse drug reaction patients, and frequency (%) of each pair of DDIs. RESULTS: Thirteen studies met our inclusion criteria. The median DDI prevalence rate for hospital admissions was 1.1% (367 DDI cases/47 976 patients, interquartile range [IQR] 0.4-2.4%). The median DDI prevalence rate for hospital visits was 0.1% (20 DDI cases/23 607 patients, IQR 0.0-0.3%). In adverse drug reaction patients, the median DDI prevalence rate for hospital admissions (308 DDI cases/1683 patients) and hospital visits (8 DDI cases/90 patients) were 22.2% (IQR 16.6-36.0%) and 8.9%, respectively. Medical record, interview, drug interaction screening program, adverse reaction report, and electronic medical record were identified as methods used for detecting DDIs. Non-steroidal anti-inflammatory drugs were most commonly involved in hospital admission associated DDIs, whereas warfarin was frequently involved in DDIs detected at hospital visits as outpatients/emergencies. CONCLUSIONS: Drug-drug interactions are a significant cause of hospital admissions and hospital visits. Improved DDI information gathering could help to reduce such adverse effects from DDIs, especially for patients using non-steroidal anti-inflammatory drugs and warfarin.

Depression and adherence to treatment in diabetic children and adolescents: a systematic review and meta-analysis of observational studies.

UNLABELLED: Depression compromises diabetes treatment in juveniles, and this study aimed to identify influential targets most likely to improve adherence to treatment and glycemic control. Prospective observational studies investigating associations between depression and treatment adherence in juveniles with type 1 diabetes were extracted from MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane Central. Nineteen studies comprising 2,935 juveniles met our criteria. Median effect sizes between depression and treatment adherence were 0.22 (interquartile range (IQR), 0.16­0.35) by patient and 0.13 (IQR, 0.12­0.24) caregiver report. Corresponding values for depression/glycemic control were 0.16 (IQR, 0.09­ 0.23) and 0.08 (IQR, 0.04­0.14), respectively. Effect sizes varied with study design, publication year and assessment tools: CES-D yielded a higher effect size than other assessment tools for depression, where associations for depression and either adherence or glycemic control was investigated. Several behaviours influenced adherence and glycemic control. CONCLUSION: This study showed moderate associations between depression and poor treatment adherence. Targeting behaviour and social environments, however, may ultimately provide more cost-effective health gains than targeting depressive symptoms.

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.

Systematic Review on Transdermal/Topical Cannabidiol Trials: A Reconsidered Way Forward.

Introduction: This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Methods: Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Results: Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Eleven more studies were found in clinical trial databases but not accessible. Symptoms targeted were dermatopathologies or safety (two studies), pain (two), and behavior (one). Doses were 50-250 mg or 0.075-1.0% CBD, but coformulated with other ingredients. Risk of bias was high and reporting deficiencies further compromised data reliability. Diverse methodologies and formulations hampered syntheses for CBD dose, efficacy, and safety. Plasma CBD levels in dogs and rodents were 0.01-5 µM translating to <100 nM free, unbound CBD in humans. Adverse events were uncommon and mild, but meaningless without CBD's contribution to efficacy data. Achievable free CBD plasma concentrations ∼100 nM can interact predominantly with high-affinity CBD targets, for example, TRPA1 and TRPM8 membrane channels that are abundantly expressed in pathological conditions. Even if reached, higher CBD concentrations on less susceptible targets risk complex and unsafe CBD therapy. A conceptual framework is proposed where dermal capillary loops create sinking for topical CBD demonstrating parallels between topical and transdermal CBD administration. Conclusions: Users risk generalizing inadequately designed trials to all CBD preparations. New clinical trials are urgently needed: they must demonstrate that outcomes are solely from CBD pharmacology, are reliable, unbiased, safe, and comparable. Measurements of sustained plasma CBD levels are mandatory, irrespective of administration route for successful translation from in vitro systems that express human molecular targets. Placebos must be appropriate. Transcutaneous and topical formulations need preliminary in vitro studies to optimize CBD skin penetration. Then, users can rationally balance efficacy against potential harms and cost-effectiveness of CBD formulations.

Real-World Effectiveness of Four Types of COVID-19 Vaccines.

BACKGROUND: There is a scarcity of evidence regarding the real-world effectiveness of coronavirus disease 2019 (COVID-19) vaccines. This was the first study to evaluate the effectiveness of four types of vaccines against asymptomatic and symptomatic infection, and COVID-19 outcomes among the general population. METHODS: This was a matched comparison group quasi-experimental study conducted in Jordan between 1 January and 29 August 2021. In the first part of the study, 1200 fully vaccinated individuals were matched with 1200 unvaccinated control participants. In order to measure vaccine effectiveness, the infection rates of both vaccinated and unvaccinated groups were calculated. The second part of the study included measuring specific anti-SARS CoV-2 immune cells and antibodies. RESULTS: BNT162b2 (Pfizer, New York, NY, USA) showed a significantly higher effectiveness against asymptomatic COVID-19 infection (91.7%) and hospitalization (99.5%) than BBIBP-CorV (Sinopharm, Beijing, China) (88.4% and 98.7%, respectively) and ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) (84.3%, and 98.9%, respectively). The effectiveness rates of the Sputnik V (Gamaleya Research Institute, Moscow, Russia) vaccine against asymptomatic, symptomatic, and hospitalization were 100%, 100%, and 66.7%, respectively. The highest median anti-spike (S) IgG values were seen in individuals who received BNT162b2 (2.9 AU/mL) and ChAdOx1 nCoV-19 (2.8 AU/mL) vaccines. The levels of anti-S IgG were significantly decreased after 7 months of vaccination with BNT162b2 and BBIBP-CorV. There were significant decreases in the median number of neutralizing antibodies one month and seven months after receiving BNT162b2 (from 88.5 to 75.2 4 Bioequivalent Allergen Unit per milliliter/mL), BBIBP-CorV (from 69.5 to 51.5 BAU/mL), and ChAdOx1 nCoV-19 (from 69.2 to 58.BAU/mL) vaccines. The highest percentage of T cells specific to COVID-19 vaccine was found in individuals who received BNT162b2 (88.5%). CONCLUSION: All four vaccines evaluated in this study showed effectiveness against asymptomatic COVID-19 infection, symptomatic infection, hospitalization, and death. Furthermore, BNT162b2, BBIBP-CorV, and ChAdOx1 nCoV-19 induced high levels of immunology markers within one month of vaccination.

Active Safety Surveillance of Four Types of COVID-19 Vaccines: A National Study from Jordan.

BACKGROUND: Although the Pfizer-BioNTech (BNT162b2), Oxford-AstraZeneca (ChAdOx1 nCoV-19), Sinopharm (BBIBP-CorV), and Sputnik V coronavirus disease 2019 (COVID-19) vaccines have been granted emergency approval in many nations, their safety has never been studied and compared in one community-based study. This study aimed to investigate and compare the incidence, nature, severity, and predictors of adverse events following immunization (AEFIs) with COVID-19 vaccines. METHOD: This was a prospective observational study conducted in Jordan between 1 January and 21 September 2021. A team of pharmacists and nurses (n = 407) collected the local and systemic AEFIs of four COVID-19 vaccines by prospectively contacting participants registered in the national vaccination program platform. A red-flag technology was inserted to classify and track rare and serious AEFIs. RESULTS: This study included 658,428 participants who were vaccinated with 1,032,430 doses; 610,591, 279,606, 140,843, and 1390 participants received the first and second doses of the BNT162b2, BBIBP-CorV, ChAdOx1 nCoV-19, and Sputnik V vaccines, respectively. The overall incidence of AEFIs was 28.8%, and the overall rates of systemic, local, and immediate hypersensitivity AEFIs were 22.2%, 18.8%, and 0.5%, respectively. The highest proportions of immediate hypersensitivity AEFIs and systemic AEFIs were reported after administration of the Sputnik V vaccine and ChAdOx1 nCoV-19 first dose, respectively. The most severe AEFIs were reported after ChAdOx1 nCoV-19 first dose and BNT162b2 second dose. The hospitalization and mortality rates after vaccination were 20 in 10,000 and 1 in 10,000, respectively. Based on red-flag tracking, the top three outcome events were lymphadenopathy (157.9/100,000), anxiety disorders (136.6/100,000), and lower respiratory tract infection (100.9/100,000), with Guillain-Barré syndrome (1.8/100,000), vasculitis (3.0/100,000), and myopericarditis (4.8/100,000) being the least common. CONCLUSION: The incidence rates of local, systemic, and immediate hypersensitivity AEFIs of four COVID-19 vaccines occur frequently. High incidence rates of rare and serious AEFIs were reported in this study. Younger participants, females, those who had previously had COVID-19, and smokers were more likely to encounter AEFIs.

Hospital Admissions Associated With Medication-Related Problems in Thai Older Patients: A Multicenter Prospective Observational Study.

OBJECTIVE: The aim of the study was to estimate the prevalence rate and risk factors of medication-related problems (MRPs) leading to hospital admissions in Thai older patients. METHODS: A prospective observational study was carried out in nine hospitals in Lower Northern Thailand. Participants admitted to internal medicine units were screened for suspected MRPs by clinical pharmacists using medical record review and patient interview. Three experts evaluated suspected MRPs independently using the following four criteria: contribution of MRPs to hospital admissions, causality, severity, and preventability. RESULTS: Of 1776 patients admitted during the study period, 56 patients (3.2%) were deemed to have causal MRPs; 24 (42.9%) were judged as preventable. The medication groups most commonly associated with MRPs were those targeting the endocrine system, especially antidiabetic medications, such as metformin and glipizide. Preventable MRPs were usually manifest as hypoglycemia (n = 15, 62.5%). The variables that contributed to hospital admissions associated with MRPs were age (odds ratio = 1.92; 95% confidence interval [CI] = 1.06-3.47), starting a new drug within 1 week (odds ratio = 2.31; 95% CI = 1.08-4.95), or within 1 month (odds ratio = 2.17; 95% CI = 1.05-4.48). CONCLUSIONS: Hospital admissions associated with MRPs in Thai older patients continue to burden the Thai healthcare system of which nearly half were preventable. Further studies should consider analysis of costs and include hepatic and renal function status of participants.

Hospital Outpatient Visits Associated With Medication-Related Problems in Thailand: A Multicenter Prospective Observational Study.

OBJECTIVES: The aims of the study were to investigate the prevalence of hospital visits associated with medication-related problems (MRPs, i.e., adverse drug events [ADEs], adverse drug reactions [ADRs], nonadherence [NA] to medication, and medication error) and to identify the medications involved in hospital visits associated with MRPs in outpatient departments (OPDs). METHODS: A prospective observational study was carried out in OPD of 11 hospitals in the lower northern region of Thailand. Patients visiting OPDs were screened for suspected MRPs by clinical pharmacists using medical record review supplemented by patient interview. Three experts evaluated suspected MRPs using the following 3 criteria: causality, severity, and preventability. RESULTS: Of the 3069 patients who visited the OPDs during the study period, 113 (3.7%) were deemed to have causal MRPs. Nearly half of the causal MRPs (n = 49, 43.4%) were preventable. The following 4 types of causal MRPs were identified: ADEs (n = 112, 3.7%), ADRs (n = 65, 2.1%), NA to medications (n = 48, 1.6%), and medication errors (n = 1, 0.03%). In nonelective patients (n = 764), 35 patients (4.6%) were judged to have causal MRPs. Of the nonelective patients who experienced causal MRPs, 25 (71.4%) were preventable. The medications commonly associated with ADEs and NA to medication were those targeting the cardiovascular system (especially enalapril, amlodipine, and hydrochlorothiazide), whereas the medications involving ADRs involved the cardiovascular and endocrine systems (especially, enalapril, amlodipine, and metformin). CONCLUSIONS: Outpatient department visits associated with MRPs, particularly in nonelective patients, were preventable. Effective strategies are needed for reducing visits to hospital OPD associated with preventable MRPs.

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.

The diagnostic accuracy of isothermal nucleic acid point-of-care tests for human coronaviruses: A systematic review and meta-analysis.

Many recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (> 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90-0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65-0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (> 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction.

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.

Oral anticoagulants and risk of dementia: A systematic review and meta-analysis of observational studies and randomized controlled trials.

Atrial fibrillation (AF) is a documented risk factor for dementia. However, it is unclear whether oral anticoagulant (OAC) treatment can reduce the development of dementia or cognitive impairment. We conducted a systematic review and meta-analysis of the association between OAC use and subsequent dementia development in AF patients by searching databases from their inception to February 2018 without language restriction. Six studies (one randomized controlled trial and five observational studies) met the inclusion criteria. The pooled adjusted risk ratios (RRs) suggested a protective effect of OAC use in reducing dementia risk (RR 0.79 [95% CI: 0.67 - 0.93], I2 = 59.7%; P = 0.005). Further, high percentage of time in therapeutic range (TTR) was associated with a decreased risk of dementia (RR 0.38 [95% CI 0.22-0.64], I2 = 81.8%; P < 0.001). Our results support the hypothesis that AF-related dementia may be due to silent brain infarcts and micro-embolism that could be prevented by OAC use. Future studies with prospective follow-up with direct comparison of vitamin K antagonists and direct oral anticoagulants are needed.

Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies.

OBJECTIVE: To determine the prevalence of hospital admissions associated with ADRs and examine differences in prevalence rates between population groups and methods of ADR detection. DATA SOURCES: Studies were identified through electronic searches of Cumulative Index to Nursing and Allied Health Literature, EMBASE, and MEDLINE to August 2007. There were no language restrictions. STUDY SELECTION AND DATA EXTRACTION: A systematic review was conducted of prospective observational studies that used the World Health Organization ADR definition. Subgroup analysis examined the influence of patient age groups and methods of ADR detection on reported ADR admission rates. All statistical analyses were performed using STATA v 9.0. DATA SYNTHESIS: Twenty-five studies were identified including 106,586 patients who were hospitalized; 2143 of these patients had experienced ADRs. The prevalence rates of ADRs ranged from 0.16% to 15.7%, with an overall median of 5.3% (interquartile range [IQR] 2.7-9.0%). Median ADR prevalence rates varied between age groups; for children, the ADR admission rate was 4.1% (IQR 0.16-5.3%), while the corresponding rates for adults and elderly patients were 6.3% (IQR 3.9-9.0%) and 10.7% (IQR 9.6-13.3%), respectively. ADR rates also varied depending on the methods of ADR detection employed in the different studies. Studies that employed multiple ADR detection methods, such as medical record review and patient interview, reported higher ADR admission rates compared with studies that used medical record review alone. Anti-infective drugs were most often associated with ADR admissions in children; cardiovascular drugs were most often associated with ADR admissions in adults and elderly patients. CONCLUSIONS: Approximately 5.3% of hospital admissions were associated with ADRs. Higher rates were found in elderly patients who are likely to be receiving multiple medications for long-term illnesses. The methods used to detect ADRs are also likely to explain much of the variation in the reported ADR prevalence rates between different studies.