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Monitoring for drug-induced liver injury (DILI) via serial transaminase measurements in patients on potentially hepatotoxic medications (e.g., for HIV and tuberculosis) is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care (POC) screening for DILI, we have performed the first field evaluation of a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual measurement of blood alanine aminotransferase (ALT). Our objectives were to assess operational feasibility, inter-operator variability, lot variability, device failure rate, and accuracy, to inform device modification for further field testing. The paper-based ALT test was performed at POC on fingerstick samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read independently by two clinic nurses, were compared with gold-standard automated (Roche Cobas) results from venipuncture samples obtained in parallel. Two device lots were used sequentially. We demonstrated high inter-operator agreement, with 96.3% (95% C.I., 94.3–97.7%) agreement in placing visual results into clinically-defined “bins” (<3x, 3–5x, and >5x upper limit of normal), >90% agreement in validity determination, and intraclass correlation coefficient of 0.89 (95% C.I., 0.87–0.91). Lot variability was observed in % invalids due to hemolysis (21.1% for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma separation membranes. Invalid rates <1% were observed for all other device controls. Overall bin placement accuracy for the two readers was 84% (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual reading–obtained in a target clinical environment, as performed by local practitioners–indicate that the device operation and reading process is feasible and reproducible. Bin placement accuracy and lot-to-lot variability data identified specific targets for device optimization and material quality control. This is the first field study performed with a patterned paper-based microfluidic device and opens the door to development of similar assays for other important analytes. [ABSTRACT FROM AUTHOR]

Introduction: Information on the impact of medicines on breastfeeding and the breastfed infant remains scarce. The aims of this review were to identify databases and cohorts holding this information, and pinpoint current information and research deficits. Method: We searched 12 electronic databases, including PubMed/ Medline and Scopus, using a combination of controlled vocabulary (MeSH terms) and free text terms. We included studies reporting data from databases with information on breastfeeding, medicines exposure, and infant outcomes. We excluded studies not reporting all three parameters. Two reviewers independently selected papers and extracted data using a standardised spreadsheet. Risk of bias was assessed. Recruited cohorts with relevant information were tabulated separately. Discrepancies were resolved by discussion. Results: From 752 unique records, 69 studies were identified for full review. Eleven papers reported analyses from ten established databases with information on maternal prescription or non-prescription drugs, breastfeeding and infant outcomes. Twenty-four cohort studies were also identified. No studies reported educational or long-term developmental outcomes. The data are too sparse to warrant any firm conclusions, beyond the need for more data. The overall picture hints at 1) unquantifiable, but probably rare, serious harms to infants exposed to medicines via breastmilk, 2) unknown long-term harms, and 3) a more insidious but more pervasive harm in terms of reduced breastfeeding rates following medicines exposure in late pregnancy and peri-partum. Implications: Analyses of databases reporting on the full population are needed to quantify any adverse effects of medicines and identify dyads at risk of harm from prescribed medicines while breastfeeding. This information is essential to ensure 1) infants are monitored appropriately for any adverse drug reactions 2) inform breastfeeding patients using long-term medicines as to whether the benefits of breastfeeding outweigh exposure to medicines via breastmilk and 3) target additional support to breastfeeding patients whose medicines may affect breastfeeding. The protocol is registered with the Registry of Systematic Reviews, no.994. [ABSTRACT FROM AUTHOR]

Discrete choice experiments (DCEs) are a way to assess priority-setting in health care provision. This approach allows for the evaluation of individuals’ preferences as a means of adding criteria to traditional quality-adjusted life year analysis. The aim of this systematic literature review was to identify attributes for designing a DCE in order to then develop and validate a framework that supports decision-making on health technologies. Our systematic literature review replicated the methods and search terms used by de Bekker-Grob et al. 2012 and Clark et al. 2014. The Medline database was searched for articles dated between 2008 and 2015. The search was limited to studies in English that reflected general preferences and were choice-based, published as full-text articles and related to health technologies. This study included 72 papers, 52% of which focused on DCEs on drug treatments. The average number of attributes used in all included DCE studies was 5.74 (SD 1.98). The most frequently used attributes in these DCEs were improvements in health (78%), side effects (57%) and cost of treatment (53%). Other, less frequently used attributes included waiting time for treatment or duration of treatment (25%), severity of disease (7%) and value for money (4%). The attributes identified might inform future DCE surveys designed to study societal preferences regarding health technologies in order to better inform decisions in health technology assessment. [ABSTRACT FROM AUTHOR]

Despite the large amount of human and experimental studies no effective (prophylactic) treatment exists for chemotherapy induced peripheral neuropathy (CIPN), a disabling side effect of many cancer treatments. One of the underlying reasons for this could be that often the preclinical animal models used are not the best representation of the clinical situation. We therefore present a systematic summary and comparison of all animal models currently described in literature for CIPN focusing on stimulus evoked pain-like behaviour and neurophysiological alterations in nerve function (650 included papers, and a comparison of 183 models), that resulted in a clear overview of the most effective and robust CIPN models using an administration route used in clinical practice. Using our three-step approach (step 1: efficacy; step; 2 robustness and step 3: mimicking the clinical situation) we show that all mice CIPN models treated with either paclitaxel or cisplatin using an administration route used in clinical practice seem suitable models. Three specific models using paclitaxel or cisplatin that stand out are 1) C57BL/6 female mice receiving paclitaxel and 2) CD1 male mice receiving paclitaxel and 3) C57BL/6 male mice receiving cisplatin. This overview may help scientists selecting suitable CIPN models for their research. We hypothesize that by using effective and robust animal models that mimic the clinical situation as much as possible, the translational value of preclinical study results with respect to the potential of identifying promising treatments for CIPN in the future, will prove. The methodology described in this paper, aimed at comparing animal models, is novel and can be used by scientist in other research fields as well. [ABSTRACT FROM AUTHOR]

Background: cute kidney injury(AKI) is a rapid loss of the kidney's excretory function, resulting in an accumulation of end products of nitrogen metabolism. The causes of AKI in HIV-positive patients are not well investigated, but it may be associated with antiretroviral drug side effects and HIV itself. Even though there were studies that reported the prevalence of AKI among HIV-positive patients in Africa, their findings were inconsistent across the studies. Methods: We searched on PubMed, Embas, Ebsco, OVID, Cochrane Library, and other supplementary search engines, including Google and Google Scholar. Articles published upto July 2023 were included in this review study. The quality of the study was assessed using the Newcastle-Ottawa Scale for cross-sectional, case-control, and cohort studies. The data were extracted using a Microsoft Excel spreadsheet and exported to Stata version 14 for analysis. A random effect meta-analysis model was used to estimate the pooled prevalence of AKI among HIV-positive patients. Heterogeneity was evaluated using Cochrane Q statistics and I squared (I2). Furthermore, the graphic asymmetric test of the funnel plot and/or Egger's tests were computed to detect publication bias. Sensitivity analysis was computed to see the effect of a single study on the summary effects. To treat the publication bias, a trim and fill analysis was carried out. The protocol of this review has been registered in an international database, the Prospective Register of Systematic Reviews (PROSPERO),with reference number CRD42023446078. Results: A total of twenty-four original articles comprising 7913HIV-positive patients were included in the study. The pooled prevalence of AKI among HI-positive patients was found to be 23.35% (95% CI: 18.14–28.56%, I2 = 97.7%, p-value <0.001). Low hemoglobin (Hgb <8mg/dl) was found to be the determinant factor for AKI among HIV-positive patients (AOR = 2.4; 95% CI:1.69–3.4, I2 = 0.0%, p-value = 0.40). In meta-regression analysis, sample size was the possible source of variation among the included studies (AOR = 3.11, 95%CI: 2.399–3.83). Conclusions: The pooled prevalence of AKI among HIV-positive patients was high. HIV-positive patients with low hemoglobin levels are at risk of developing AKI. Hence, regular monitoring of kidney function tests is needed to prevent or delay the risk of AKI among HIV-positive patients. Healthcare workers should provide an integrated healthcare service to HIV-positive patients on the prevention, treatment, and reduction of the progression of AKI to advanced stages and complications. [ABSTRACT FROM AUTHOR]

Background: The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described. Objectives: To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011–2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey. Subjects/Setting: From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS. Results: Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems. Conclusions: Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals. [ABSTRACT FROM AUTHOR]

Many drugs are promiscuous and bind to multiple targets. On the one hand, these targets may be linked to unwanted side effects, but on the other, they may achieve a combined desired effect (polypharmacology) or represent multiple diseases (drug repositioning). With the growth of 3D structures of drug-target complexes, it is today possible to study drug promiscuity at the structural level and to screen vast amounts of drug-target interactions to predict side effects, polypharmacological potential, and repositioning opportunities. Here, we pursue such an approach to identify drugs inactivating B-cells, whose dysregulation can function as a driver of autoimmune diseases. Screening over 500 kinases, we identified 22 candidate targets, whose knock out impeded the activation of B-cells. Among these 22 is the gene KDR, whose gene product VEGFR2 is a prominent cancer target with anti-VEGFR2 drugs on the market for over a decade. The main result of this paper is that structure-based drug repositioning for the identified kinase targets identified the cancer drug ibrutinib as micromolar VEGFR2 inhibitor with a very high therapeutic index in B-cell inactivation. These findings prove that ibrutinib is not only acting on the Bruton's tyrosine kinase BTK, against which it was designed. Instead, it may be a polypharmacological drug, which additionally targets angiogenesis via inhibition of VEGFR2. Therefore ibrutinib carries potential to treat other VEGFR2 associated disease. Structure-based drug repositioning explains ibrutinib's anti VEGFR2 action through the conservation of a specific pattern of interactions of the drug with BTK and VEGFR2. Overall, structure-based drug repositioning was able to predict these findings at a fraction of the time and cost of a conventional screen. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the consistency of adverse events (AEs) and adverse drug reactions (ADRs) reported in the literature, monitoring and social media data. Methods: Using one Chinese patent medicine-Cordyceps sinensis extracts (CSE) as an example, we obtained safety data from the national monitoring system (July 2002 to February 2016), literature (up to November 2016) and social media (May 2019). For literature data, we searched the Chinese National Knowledge Infrastructure Database (CNKI), WanFang database, Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Embase and the Cochrane Library. Social media data was from the Baidu post bar and Sina micro-blog. Two authors independently screened the literature and extracted data by PRISMA Harms checklist was followed. AEs and ADRs were coded using the World Health Organization Adverse Reaction Terminology (WHO-ART). AEs and ADRs were grouped into thirty-one organ-system classes for comparisons. Frequencies, relative frequencies and rank were used as metrics. Radar chart was used to manifest the features of the distributions and proportions. Results: 610 AEs reported in CFDA monitoring data were associated with CSE, of which 537 (88.03%) were suspected ADRs (10.49% certain). 5568 AEs were identified from 172 papers (63% RCTs, 37% other types of studies including case series, case reports, ADR monitoring reports and reviews), in which 86 (1.54%) were ADRs (1.54% certain). 15 AEs (0 certain ADR) were identified from social media. AEs, ADRs and their affected system-organ classes, looked largely similar, but different in every aspect when looking at details. Data from RCTs demonstrated the most disparity. Conclusions: In our study, the most prevalent AEs and ADRs, mainly gastro-intestinal system disorders including nausea, diarrhea and vomiting, in monitoring system were largely similar with those in literature and social media. But data from different sources varied if looked at details. Multiple data sources (the monitoring system, literature and social media) should be integrated to collect safety information of interventions. The distributions of AEs and ADRs from RCTs were least similar with the data from other sources. Our empirical proof is consistent with other similar studies. [ABSTRACT FROM AUTHOR]

Background: Pharmacogenetic testing in routine care could provide benefits for patients, doctors and statutory health insurances. Therefore, the aim of the retrospective, observational study Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung (EMPAR) was to analyze the relationship between pharmacogenetic profiles, the risk of adverse drug reactions, and patients' perceptions of drug therapy in 10748 adult (≥18 years) participants in Germany. Methods: A questionnaire was used to assess views and beliefs about medicines and participants individual perception of sensitivity to drug therapies. The questionnaire consisted of the Beliefs about Medicines Questionnaire (BMQ)-General scales (Overuse, Harm, Benefit), the Perceived Sensitivity to Medicines (PSM), Natural Remedy, and Gene Testing scales. The influence of gender, age, study collective, genotype and phenotype of relevant pharmacogenes on participant's perception were evaluated. Results: Overuse, PSM and Benefit scores were significantly higher among patients of the collective International Classification of Diseases and Health Related Disorders (ICD)-10 Y57.9! diagnosis, which indicates complications related to drugs, compared to the anticoagulant/antiplatelet and cholesterol-lowering drug collective. Age and gender also played a significant role in patients' perceptions, with younger patients and female participants more likely to believe in medication overuse according to the Overuse scale score compared to older and male participants. Female participants compared to male participants and the old age group compared to the young and/or middle-age subgroup, scored higher in PSM and/or Harm scales, respectively. Only a tendency of increased Harm, Overuse and PSM scores was observed in the participant group with five or more relevant actionable variants compared to subgroups with 0 up to 4 variants. Conclusions: In conclusion, patients' beliefs about medicines and their drug sensitivity perceptions are influenced by various factors including age, gender, previous complications with medicines, and with some tendency also pharmacogenetic profiles. The higher association with more negative views related to treatment indicates that there is a need to target the underlying issues in affected patient groups in order to improve compliance to treatment and outcomes in routine care. Trial registration: EMPAR was registered in the German Clinical Trials Register (DRKS) on 06 July 2018 (DRKS00013909). [ABSTRACT FROM AUTHOR]

Background: Adverse drug reaction is one of the emerging challenges in antiretroviral treatment. Determining the incidence rate and predictors among children on antiretroviral treatment (ART) is essential to improve treatment outcomes and minimize harm. And also, evidence regarding the time to major adverse drug reactions and its predictors among children on antiretroviral treatment is limited in Ethiopia. Objective: This study aimed to assess the time to major adverse drug reaction and its predictors among children on antiretroviral treatment at selected public hospitals in Northwest Amhara, Ethiopia, 2023. Method: A retrospective cohort study was conducted among 380 children on antiretroviral treatment who enrolled from June 27, 2017, to May 31, 2022. Data was collected using a structured data extraction checklist. Data were entered into Epidata 4.6 and analyzed using STATA 14. The incidence rate of major adverse drug reactions was determined per person/months. The Cox proportional hazards regression model was used to identify predictors of major adverse drug responses. A p-value less than 0.05 with a 95% CI was used to declare statistical significance. Result: The minimum and maximum follow-up time was 6 and 59 months, respectively. The study participants were followed for a total of 9916 person-months. The incidence rate of major adverse drug reactions was 3.5 /1000 person–months. Advanced clinical stages of HIV/AIDS (III and IV) [adjusted hazard ratio = 7.3, 95% CI: 2.74–19.60)], poor treatment adherence [adjusted hazard ratio = 0.33, 95% CI: 0.21–0.42], taking antiretroviral treatment twice and more [adjusted hazard ratio = 3.43, 955 CI: (1.26–9.33)] and not taking opportunistic infection prophylaxis [adjusted hazard ratio = 0.35, 95% CI: 0.23–0.52)] were predictors of major adverse drug reactions. Conclusion: The incidence rate of major adverse drug reactions among children on antiretroviral treatment was congruent with studies in Ethiopia. Advanced clinical stages of HIV/AIDS, poor treatment adherence, taking antiretroviral treatment medications twice or more, and not taking opportunistic infection prophylaxis were predictors of major adverse drug reactions. [ABSTRACT FROM AUTHOR]

Background: Pyrazinamide (PZA) usage has been associated with adverse drug reactions, prompting its avoidance in treating elderly tuberculosis (TB) patients. This study aims to examine whether the administration of PZA is associated with poor outcomes during TB treatment among elderly individuals. Methods: A retrospective analysis was undertaken on data collected from a prospective cohort conducted between July 2019 and June 2023, which involved tuberculosis patients from 18 institutions across the Republic of Korea. The study aimed to assess the impact of PZA on the incidence of serious adverse events (SAEs), medication interruptions, and becoming loss to follow-up (LTFU) during standard short courses of TB treatment in elderly (≥65 years old) patients. Results: PZA was administered to 356 of 390 elderly patients (91.3%), and 98 of the 390 (25.1%) experienced SAEs. Treatment success was significantly lower in patients not treated with PZA compared to those who received PZA (64.7% vs 89.9%, p < 0.001). The incidence of SAEs, medication interruption, or LTFU was higher in patients not given PZA compared those who received PZA (52.9% vs. 27.2%, p = 0.002). A multivariate logistic regression analysis, factoring in covariates such as age, comorbidities, and baseline laboratory data, revealed that PZA was not a risk factor for SAEs, medication interruption, or LTFU in TB treatment (odds ratio [OR] 0.457, 95% confidence interval [CI] 0.201–1.041). Conclusion: Treating elderly TB patients with PZA did not increase the incidence of SAEs, medication interruptions, or LTFU during the standard short course of TB treatment. Therefore, considering its potential advantages, incorporating PZA into the treatment regimen for elderly TB patients may be advisable. [ABSTRACT FROM AUTHOR]

Over the past decades, immune checkpoint inhibitors (ICIs) have shown dramatic efficacy in improving survival rates in multiple malignancies. Recently, gynecological cancer patients also showed to respond favorably to ICI treatment. This study aimed to evaluate the efficacy, safety, and patient-reported outcomes of ICI therapy in gynecological cancers. We conducted a systematic review and meta-analysis by retrieving literature from multiple electronic databases, such as MEDLINE, ScienceDirect, EBSCO, ProQuest, and Google Scholar. The protocol used in this study has been registered in PROSPERO (CRD42022369529). We included a total of 12 trials involving 8 therapies and 8,034 patients. ICI group demonstrated a longer OS (HR: 0.807; 95% CI: 0.719, 0.907; p = 0.000) and greater PFS improvement (HR: 0.809; 95% CI: 0.673, 0.973; p = 0.024) compared to the control group. There was no significant difference in the incidence of treatment-related adverse events [RR: 0.968; 95%CI: 0.936, 1.001; p = 0.061], but a higher incidence of immune-related adverse events (IRAEs) was observed in the ICI group (RR: 3.093; 95%CI: 1.933, 4.798; p = 0.000). Although the mean changes of QOL score from baseline was not significantly different between both groups (SMD: 0.048; 95% CI: -0.106, 0.202; p = 0.542), the time to definitive QOL deterioration was longer in the ICI group (HR: 0.508; 95% CI: 0.461, 0.560; p = 0.000). Despite having a higher incidence of IRAE, ICI was shown to improve survival rates and QOL of patients. Thus, it should be considered as a new standard of care for gynecologic cancers, especially in advanced stages. [ABSTRACT FROM AUTHOR]

Background: A new contraceptive microarray patch (MAP) for women is in development. Input on this method from potential end-users early in the product development process is important to guide design decisions. This paper presents the qualitative component of a broader study exploring initial acceptability of the MAP and selected product features. The qualitative research was intended to identify product features that are most salient to end-users and to contextualize preferences around them with subsequent research planned to assess quantitatively the relative importance of those features. Methods: We conducted 16 focus group discussions and 20 in-depth interviews with women and 20 IDIs with family planning providers in New Delhi, India, and Ibadan, Nigeria. Input from the MAP developer served to identify plausible features of the MAP to include in the focus group discussions and in-depth interviews. Interviews were audio-recorded, transcribed into English, coded, and analyzed to examine key dimensions of MAP features. Results: Many participants viewed the MAP as potentially easy to use. Interest in self-application after learning correct use was high, especially in India. Participants favored formulations affording protection from pregnancy for three or six months, if not longer. Interest in a shorter-acting MAP was particularly low in Nigeria. Non-desirable MAP features included a potential localized skin rash and pain at application. Views on patch size and location of application were related to the potential for rash and pain, with a desire to permit discreet use and minimize pain. Results indicate that the side effect profile, effectiveness, and pricing are also important factors for acceptability and uptake of a future product. Conclusion: Study findings indicate that a contraceptive MAP is of potential interest to women and that specific MAP attributes will be important to acceptability. [ABSTRACT FROM AUTHOR]

Background: Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. Methods: A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. Results: Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. Conclusion: Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings. [ABSTRACT FROM AUTHOR]

Detecting drug-drug interactions (DDI) is important because information on DDIs can help prevent adverse effects from drug combinations. Since there are many new DDI-related papers published in the biomedical domain, manually extracting DDI information from the literature is a laborious task. However, text mining can be used to find DDIs in the biomedical literature. Among the recently developed neural networks, we use a Recursive Neural Network to improve the performance of DDI extraction. Our recursive neural network model uses a position feature, a subtree containment feature, and an ensemble method to improve the performance of DDI extraction. Compared with the state-of-the-art models, the DDI detection and type classifiers of our model performed 4.4% and 2.8% better, respectively, on the DDIExtraction Challenge’13 test data. We also validated our model on the PK DDI corpus that consists of two types of DDIs data: in vivo DDI and in vitro DDI. Compared with the existing model, our detection classifier performed 2.3% and 6.7% better on in vivo and in vitro data respectively. The results of our validation demonstrate that our model can automatically extract DDIs better than existing models. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADRs) represent a significant barrier to achieve optimal treatment outcomes. Cardiovascular drugs, including antihypertensive drugs, lipid-lowering drugs, and antithrombotic drugs, are among the most prescribed medications in the primary care setting. Objectives: To estimate the prevalence of cardiovascular drug-related ADRs consultations in United Kingdom (UK) primary care and identify risk factors of these ADRs. Methods: This was a cross-sectional study of cardiovascular drug users between 2000–2019 using UK IQVIA Medical Research Data. ADRs consultations were identified using database screening method employing standardised designated codes. The overall and annual age-standardised prevalence was estimated using direct standardisation method using 2019 mid-year UK population. Risk factors of ADRs consultations were estimated using logistic regression model stratified by therapeutic areas. Results: The standardised prevalence of consultations related to cardiovascular drugs ADRs was 10.60 (95% CI. 10.46, 10.75) per 1000 patients. Patients aged 70–79 years had the highest occurrence of ADRs consultations. The most frequently drug classes implicated in the ADRs consultations were statins (n = 9,993 events, 27.09%), beta-blockers (n = 8,538 events, 23.15%), ACEIs/ARBs (n = 8,345 events, 22.62%), and aspirin (n = 6,482 events, 17.57%). Risk factors of ADRs consultations were previous history of cardiovascular diseases, e.g., myocardial infarction and stroke; advanced age, comorbidities; diabetes and dyslipidaemia; and polypharmacy. Conclusions: The burden of cardiovascular drug-related ADRs consultations in primary care was considerable. Statins, beta-blockers, ACEIs/ARBs, and aspirin were the most frequently implicated drug classes. Closer clinical monitoring should be performed for patients affected by the ADRs to mitigate the risk of suboptimal treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: The majority of people with long-term, non-communicable medical conditions experience significant psychological anguish. Poor mental health or psychological distress influences low lifestyle decisions that result in obesity, inactivity, and cigarette use as well as poor health literacy and limited access to health promotion activities. Objectives: The study's purpose was to measure the prevalence of psychological distress and it's predictors in patients with chronic non-communicable diseases who were being treated in selected hospitals in the Sidama region of southern Ethiopia in 2022. Methodology: Institutional based cross-sectional study was carried out using a sample of 844 patients receiving medication for either high blood pressure or diabetes mellitus or both between May1 and August 31, 2022. To gauge psychiatric distress, the Amharic translation and Ethiopian validation of the Kessler 6 scale (K-6) was employed. The analysis was done using binary logistic regression and an odds ratio with the corresponding 95% confidence interval was estimated to measure the strength of the association. P value <0.05 was considered to declare the significance. Result: Patients with diabetic mellitus, hypertension or both had a 49.6% prevalence of psychological distress at selected Sidama hospitals. Age, drug side effects, history medical complications following diabetic mellitus/hypertension, and body mass index of the patient were all significantly linked with psychological distress (P<0.05). Conclusion: According to the results of this study, psychological distress is far more prevalent than it was in past studies in Ethiopia and other African countries. To lessen the problem, all stakeholders must cooperate, but health agencies, policymakers, and NGOs particularly need to put in extra effort. The study also showed a significant association between body mass index, patient age, drug side effects, and history of medical complications following diabetic mellitus /hypertension. [ABSTRACT FROM AUTHOR]

Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions. The possibility that genetic risk, in the form of polygenic risk scores (PGS), could be integrated into prediction of risk of diLQTS has great potential, although it is unknown how genetic risk is related to clinical risk factors as might be applied in clinical decision-making. In this study, we examined the PGS for QT interval in 2500 subjects exposed to a known QT-prolonging drug on prolongation of the QT interval over 500ms on subsequent ECG using electronic health record data. We found that the normalized QT PGS was higher in cases than controls (0.212±0.954 vs. -0.0270±1.003, P = 0.0002), with an unadjusted odds ratio of 1.34 (95%CI 1.17–1.53, P<0.001) for association with diLQTS. When included with age and clinical predictors of QT prolongation, we found that the PGS for QT interval provided independent risk prediction for diLQTS, in which the interaction for high-risk diagnosis or with certain high-risk medications (amiodarone, sotalol, and dofetilide) was not significant, indicating that genetic risk did not modify the effect of other risk factors on risk of diLQTS. We found that a high-risk cutoff (QT PGS ≥ 2 standard deviations above mean), but not a low-risk cutoff, was associated with risk of diLQTS after adjustment for clinical factors, and provided one method of integration based on the decision-tree framework. In conclusion, we found that PGS for QT interval is an independent predictor of diLQTS, but that in contrast to existing theories about repolarization reserve as a mechanism of increasing risk, the effect is independent of other clinical risk factors. More work is needed for external validation in clinical decision-making, as well as defining the mechanism through which genes that increase QT interval are associated with risk of diLQTS. [ABSTRACT FROM AUTHOR]

Objectives: The irrational dispensing practices are responsible for antibiotic abuse and the spread of antibiotic resistance. Thus, the present study aims to evaluate the knowledge, attitudes, and practices of community pharmacists (CPs) regarding dispensing antibiotics without prescription (DAwP). Method: A descriptive, cross-sectional study was conducted between March 1, 2023, and March 31, 2023, in community pharmacy settings of Lahore, Pakistan. A self-administered and pretested questionnaire was used for the data collection. Logistic regression analysis was used to determine the factors associated with the practices of community pharmacists. Data were analyzed using SPSS (version 26) and MS Office (2016). Results: Among 359 respondents, many strongly agreed/agreed with the statements "DAwP is contributing to the development of antimicrobial resistance" (83%, n = 298) and "Antibiotic resistance has become a public health issue" (81.9%, n = 249). Overall, most of the community pharmacists claimed that the unwillingness of patients to visit physicians for non-serious infections (75.2%, n = 270) and good knowledge of pharmacists about the use of antibiotics (51%, n = 183) were the most common reasons attributable to dispensing of antibiotics without prescription. Cephalosporin (n = 260, 72.4%), penicillin (n = 254, 70.8%), and tetracyclines (n = 170, 47.4%) were the most commonly dispensed classes of antibiotics without prescription due to cold, flu and diarrhea. Most community pharmacists never/sometimes warn patients about the potential side effects of medicines (79.1%, n = 284). Logistic regression analysis revealed that community pharmacists 31–40 years of age (OR = 0.568, 95%CI = 0.348–0.927, p-value = 0.024) were significantly less associated with poor practices of dispensing antibiotics without prescription (DAwP) while those who were 'Managers' (OR = 4.222, 95%CI = 2.542–7.011, p-value = <0.001), had 3–5 years of experience (OR = 2.241, 95%CI = 1.183–4.243, p-value = 0.013), dispensed ≤25 antibiotics per day (OR = 12.375, 95%CI = 5.177–29.583, p-value = <0.001), were more likely to be associated with poor practices of dispensing of antibiotics without prescription. Conclusion: The community pharmacists had adequate knowledge, positive attitudes, and poor practices towards DAwP. Demographical factors such as age, job status, and work experience were the determinants of community pharmacists' practices towards dispensing antibiotics without prescription (DAwP). Hence, a multifaceted approach, including educational interventions, is needed to reduce the dispensing of antibiotics without prescription (DAwP). [ABSTRACT FROM AUTHOR]

Several statistical methods have been proposed to detect adverse drug reactions induced by taking two drugs together. These suspected adverse drug reactions can be discovered through post-market drug safety surveillance, which mainly relies on spontaneous reporting system database. Most previous studies have applied statistical models to real world data, but it is not clear which method outperforms the others. We aimed to assess the performance of various detection methods by implementing simulations under various conditions. We reviewed proposed approaches to detect signals indicating drug-drug interactions (DDIs) including the Ω shrinkage measure, the chi-square statistic, the proportional reporting ratio, the concomitant signal score, the additive model and the multiplicative model. Under various scenarios, we conducted a simulation study to examine the performances of the methods. We also applied the methods to Korea Adverse Event Reporting System (KAERS) data. Of the six methods considered in the simulation study, the Ω shrinkage measure and the chi-square statistic with threshold = 2 had higher sensitivity for detecting the true signals than the other methods in most scenarios while controlling the false positive rate below 0.05. When applied to the KAERS data, the two methods detected one known DDI for QT prolongation and one unknown (suspected) DDI for hyperkalemia. The performance of various signal detection methods for DDI may vary. It is recommended to use several methods together, rather than just one, to make a reasonable decision. [ABSTRACT FROM AUTHOR]

Patient profiles suitable for long-term lenvatinib treatment for unresectable hepatocellular carcinoma (uHCC) are yet to be fully understood. This post-hoc analysis aimed to identify such patient characteristics and explore the impact of treatment duration and relative dose intensity (RDI) on treatment outcomes. The data were obtained from 703 patients in a multicenter, prospective cohort study in Japan. Lenvatinib-naïve patients with uHCC were enrolled between July 2018 and January 2019 and were followed up for 12 months. Moreover, patients were dichotomized using the median treatment duration into the longer- (≥177 days; n = 352) or shorter-treatment (<177 days; n = 351) groups. The longer-treatment group often had better performance status, lower Child-Pugh score and better modified albumin-bilirubin grade than the shorter treatment group (p<0.05 for all). The objective response rate (47.6% vs. 28.2%; p<0.001) and disease control rate (92.4% vs. 60.2%; p<0.001) were both significantly higher in the longer-treatment groups than in the shorter-treatment groups. The proportion of patients with any adverse drug reactions was generally similar between the two treatment groups. Within the longer-treatment group, the disease control rate was high regardless of dose modification (i.e., RDI <100% vs. ≥100% during the initial 177 days) (91.2% vs. 98.0%). In conclusion, patients with longer treatment tended to have better overall conditions. Lenvatinib dose modifications at the physician's discretion, considering the balance between effectiveness and safety, may contribute to the long-term treatment. [ABSTRACT FROM AUTHOR]

Introduction: Biologicals have become a cornerstone in rheumatoid arthritis (RA) treatment. The increased risk of serious infections associated with their use is well-established. Non-serious infections, however, occur more frequently and are associated with a high socioeconomic burden and impact on quality of life but have not received the same attention in the literature to date. The aim of this study was to gain insight into the various non-serious infections reported in RA patients using biologicals and their experienced burden. Materials and methods: The Dutch Biologic Monitor was a prospective observational study that included adults with rheumatoid arthritis and biological use who answered bimonthly questionnaires on the adverse drug reactions (ADRs) they experienced from their biological and reported the associated impact score (ranging from 1, no impact, to 5, very high impact). ADRs were assigned a MedDRA code by pharmacovigilance experts and labeled as definite, probable, possible or no infection by infectious disease professionals. Descriptive statistics were performed using medians and interquartile ranges. Results: A total of 586 patients were included in the final analysis. Eighty-five patients (14.5%) reported a total of 421 ADRs labeled as probable or definite infections by the experts. Patient-assigned burden was ADR-specific. Upper respiratory tract infections were most frequently reported and had a high rate of recurrence or persistence, with a median impact score of 3.0 (IQR 2.0–3.0) which remained stable over time. Discussion: Non-serious infections significantly outnumbered serious infections in this real-life cohort of RA patients using biologicals (77.1 non-serious infections and 1.3 serious infections per 100 patient years, respectively). Infections in the upper respiratory tract were rated as having an average burden, which remained constant over a long period of time. Awareness of the impact of recurrent and chronic non-serious infections may enable healthcare professionals to timely treat and maybe even prevent them, which would lessen the associated personal and socioeconomic burden. [ABSTRACT FROM AUTHOR]

Introduction: Prescribed medicinal cannabis (MC) is an increasingly common prescription in Australia for treating pain, anxiety, and sleep disorders. Prescribed MC products generally contain tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in a variety of dose levels and forms. It is unclear whether THC and CBD products are used by patients with different characteristics and for different conditions. Objectives: To examine consumer experiences of using THC- and CBD-containing prescribed MC products to better understand how they are being used within the Australian context. Methods: We utilised data collected from an online anonymous cross-sectional survey of individuals (CAMS-20 survey), consisting of Australian residents using cannabis for therapeutic reasons. We focused on a subgroup of participants (N = 546) receiving prescribed MC products. We utilised linear, logistic, and multinomial regression modelling to analyse responses to survey questions based on the cannabinoid profile of the prescribed product. Results: Participants prescribed THC-dominant MC products were statistically more likely to be younger, male, and to prefer inhaled routes of administration than participants using CBD-dominant products who were older, female, and preferred oral routes of administration. Pain and mental health were the most common reasons for all types of prescribed MC, but were more likely to be treated with THC than CBD despite the significantly higher risk of mild to severe drowsiness, dry mouth and eye irritation. Consumer reported effectiveness of prescribed MC was very positive, particularly for THC-containing products. Consumers on opioids and antipsychotics were statistically more likely to be prescribed THC-containing products than products containing CBD only, despite the greater risk of impairment. Conclusions: This Australia-wide study found clear differences in consumer-reported experiences of prescribed THC- and CBD-containing products. Current prescriptions of these products do not always align with relevant clinical guidance. Educating prescribers around cannabinoid products is essential to ensure optimal prescribing practices and to prevent avoidable drug side effects and interactions. [ABSTRACT FROM AUTHOR]

Background: Diabetes self-care behaviour plays a crucial role in managing the diabetes effectively and preventing complications. Patients with type 2 diabetes mellitus (T2DM) and health care professionals (HCPs) of rural areas often face unique challenges when it comes to diabetes self-care practices (SCPs). Therefore, this study aim to explore the perspectives of patients with T2DM and HCPs on diabetes SCPs. Methods: Eight focus group discussions (FGDs) among individuals with T2DM and In-depth interviews (IDIs) with 15 HCPs were conducted in rural areas of Punjab, North India. Capability, Opportunity, Motivation, and Behaviour model (COM-B) was employed for thematic framework analyses. Results: The study participants perceived that a limited understanding of diabetes mellitus (DM), beliefs in alternative therapies, drug side effects, attitudes towards DM (psychological capability), comorbidities (physical capability), family support (social opportunity), financial and time constraints, and weather conditions (physical opportunity) contributed to lack of DM SCPs. Physicians' guidance and support were motivating them to adhere to SCPs, especially when aligned with their sense of self-efficacy (reflective motivation). HCPs constraints in providing patient-centred care are due to training limitations (psychological capability) and a lack of essential resources (physical opportunities). Participants expressed need for comprehensive diabetes care (automatic motivation) through structured diabetes education intervention to improve diabetes SCPs. Conclusions: The study findings indicate that various factors influence diabetes SCPs from the perspectives of both patients with T2DM and HCPs and emphasizes the need for a multi-faceted approach to improve diabetes SCPs in rural areas. Implementing a structured diabetes self-care intervention strategy in rural areas may help for preventing and mitigating the impact of diabetes-related complications in rural areas. [ABSTRACT FROM AUTHOR]

Data from different agencies share data of the same individuals. Linking these datasets to identify all the records belonging to the same individuals is a crucial and challenging problem, especially given the large volumes of data. A large number of available algorithms for record linkage are prone to either time inefficiency or low-accuracy in finding matches and non-matches among the records. In this paper we propose efficient as well as reliable sequential and parallel algorithms for the record linkage problem employing hierarchical clustering methods. We employ complete linkage hierarchical clustering algorithms to address this problem. In addition to hierarchical clustering, we also use two other techniques: elimination of duplicate records and blocking. Our algorithms use sorting as a sub-routine to identify identical copies of records. We have tested our algorithms on datasets with millions of synthetic records. Experimental results show that our algorithms achieve nearly 100% accuracy. Parallel implementations achieve almost linear speedups. Time complexities of these algorithms do not exceed those of previous best-known algorithms. Our proposed algorithms outperform previous best-known algorithms in terms of accuracy consuming reasonable run times. [ABSTRACT FROM AUTHOR]

Polypharmacy and inappropriate medication use among older adults contribute to adverse drug reactions, falls, cognitive impairment, noncompliance, hospitalization and mortality. While deprescribing - tapering, reducing or stopping a medication - is feasible and relatively safe, clinicians find it difficult to carry out. Deprescribing guidelines would facilitate this process. The aim of this paper is to identify and prioritize medication classes where evidence-based deprescribing guidelines would be of benefit to clinicians. A modified Delphi approach included a literature review to identify potentially inappropriate medications for the elderly, an expert panel to develop survey content and three survey rounds to seek consensus on priorities. Panel participants included three pharmacists, two family physicians and one social scientist. Sixty-five Canadian geriatrics experts (36 pharmacists, 19 physicians and 10 nurse practitioners) participated in the survey. Twenty-nine drugs/drug classes were included in the first survey with 14 reaching the required (≥ 70%) level of consensus, and 2 new drug classes added from qualitative comments. Fifty-three participants completed round two, and 47 participants completed round three. The final five priorities were benzodiazepines, atypical antipsychotics, statins, tricyclic antidepressants, and proton pump inhibitors; nine other drug classes were also identified as being in need of evidence-based deprescribing guidelines. The Delphi consensus process identified five priority drug classes for which expert clinicians felt guidance is needed for deprescribing. The classes of drugs that emerged strongly from the rankings dealt with mental health, cardiovascular, gastroenterological, and neurological conditions. The results suggest that deprescribing and overtreatment occurs through the full spectrum of primary care, and that evidence-based deprescribing guidelines are a priority in the care of the elderly. [ABSTRACT FROM AUTHOR]

Isoflurane was previously the major clinical anesthetic agent but is now mainly used for veterinary anesthesia. Studies have reported widespread sites of action of isoflurane, suggesting a wide array of side effects besides sedation. In the present study, we phenotyped isoflurane-treated mice to investigate the postanesthetic behavioral effects of isoflurane. We applied comprehensive behavioral test batteries comprising sensory test battery, motor test battery, anxiety test battery, depression test battery, sociability test battery, attention test battery, and learning test battery, which were started 7 days after anesthesia with 1.8% isoflurane. In addition to the control group, we included a yoked control group that was exposed to the same stress of handling as the isoflurane-treated animals before being anesthetized. Our comprehensive behavioral test batteries revealed impaired latent inhibition in the isoflurane-treated group, but the concentration of residual isoflurane in the brain was presumably negligible. The yoked control group and isoflurane-treated group exhibited higher anxiety in the elevated plus-maze test and impaired learning function in the cued fear conditioning test. No influences were observed in sensory functions, motor functions, antidepressant behaviors, and social behaviors. A number of papers have reported an effect of isoflurane on animal behaviors, but no systematic investigation has been performed. To the best of our knowledge, this study is the first to systematically investigate the general health, neurological reflexes, sensory functions, motor functions, and higher behavioral functions of mice exposed to isoflurane as adults. Our results suggest that the postanesthetic effect of isoflurane causes attention deficit in mice. Therefore, isoflurane must be used with great care in the clinical setting and veterinary anesthesia. [ABSTRACT FROM AUTHOR]

Objective: The aim of this retrospective study was to evaluate the effectiveness and safety of topical gabapentin solution (250 mg/mL) for the management of burning mouth syndrome (BMS). Study design: A retrospective chart review was conducted of all patients diagnosed with BMS and managed with gabapentin 250 mg/mL solution (swish and spit) between January 2021 and October 2022. Patient-reported outcomes included changes in burning score ranked on a 10-point numeric rating scale (NRS) and reported adverse drug reactions (ADR). Wilcoxon signed-rank test was used to assess differences in the oral burning score ranked on a NRS (0–10) between the baseline visit and the second visit. Results: A total of 19 patients (68.4% females) with BMS were included and evaluated for follow-up at a median of 86 days (range: 29–195). Overall, patients reported a median 2-point burning decrease on a 0–10 NRS between the baseline visit and the second visit (p < 0.01). ADRs were reported by 3 patients (15.8%). Conclusion: Although this was a small retrospective study, BMS management with topical gabapentin (250 mg/mL) appears to be effective and well-tolerated. Future randomized prospective studies are needed to verify these preliminary findings. [ABSTRACT FROM AUTHOR]

Peoples' perception of diseases and pharmaceutical drugs is a critical issue in health research. Beliefs about disease severity influence the compliance with recommendations for convalescence and the motivation to perform proper health-behavior. The estimated effectiveness of drugs and severity of side effects influence medication adherence and contribute to placebo effects. The present paper closes the gap between these effects and the concept of embodied cognition from a metaphor-enriched perspective. In five studies, we demonstrate that the bodily sensation of weight influences our evaluations of diseases and drugs. The experience of heaviness enhanced the estimated seriousness of diseases and the estimated effectiveness of drugs. The perceived seriousness of drug side effects was also affected by weight but only when drug effectiveness was not attended to. Moreover, the incidental sensation of weight shows a novel effect when evaluating weight-related drugs. The results are in line with the idea of embodied metaphors and reveal important boundary conditions which contribute to a better understanding of the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: High-dose chemotherapy using methotrexate (MTX) frequently induces side effects such as mucositis that leads to intestinal damage and diarrhea. Several natural compounds have been demonstrated of their effectiveness in protecting intestinal epithelial cells from these adverse effects. In this paper, we investigated the protection mechanism of lutein against MTX-induced damage in IEC-6 cells originating from the rat jejunum crypt. Methods: The cell viability, induced-apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential in IEC-6 cells under MTX treatment were examined in the presence or absence of lutein. Expression level of Bcl2, Bad and ROS scavenging enzymes (including SOD, catalase and Prdx1) were detected by quantitative RT-PCR. Results: The cell viability of IEC-6 cells exposed to MTX was decreased in a dose- and time-dependent manner. MTX induces mitochondrial membrane potential loss, ROS generation and caspase 3 activation in IEC-6 cells. The cytotoxicity of MTX was reduced in IEC-6 cells by the 24 h pre-treatment of lutein. We found that pre-treatment of lutein significantly reduces MTX-induced ROS and apoptosis. The expression of SOD was up-regulated by the pre-treatment of lutein in the MTX-treated IEC-6 cells. These results indicated that lutein can protect IEC-6 cells from the chemo-drugs induced damage through increasing ROS scavenging ability. Conclusion: The MTX-induced apoptosis of IEC-6 cells was shown to be repressed by the pre-treatment of lutein, which may represent a promising adjunct to conventional chemotherapy for preventing intestinal damages. [ABSTRACT FROM AUTHOR]

Introduction: As the South African province of KwaZulu-Natal addresses a growing multidrug-resistant tuberculosis (MDR-TB) epidemic by shifting care and treatment from trained specialty centers to community hospitals, delivering and monitoring MDR-TB therapy has presented new challenges. In particular, tracking and reporting adverse clinical events have been difficult for mobile healthcare workers (HCWs), trained health professionals who travel daily to patient homes to administer and monitor therapy. We designed and piloted a mobile phone application (Mobilize) for mobile HCWs that electronically standardized the recording and tracking of MDR-TB patients on low-cost, functional phones. Objective: We assess the acceptability and feasibility of using Mobilize to record and submit adverse events forms weekly during the intensive phase of MDR-TB therapy and evaluate mobile HCW perceptions throughout the pilot period. Methods: All five mobile HCWs at one site were trained and provided with phones. Utilizing a mixed-methods evaluation, mobile HCWs’ usage patterns were tracked electronically for seven months and analyzed. Qualitative focus groups and questionnaires were designed to understand the impact of mobile phone technology on the work environment. Results: Mobile HCWs submitted nine of 33 (27%) expected adverse events forms, conflicting with qualitative results in which mobile HCWs stated that Mobilize improved adverse events communication, helped their daily workflow, and could be successfully expanded to other health interventions. When presented with the conflict between their expressed views and actual practice, mobile HCWs cited forgetfulness and believed patients should take more responsibility for their own care. Discussion: This pilot experience demonstrated poor uptake by HCWs despite positive responses to using mHealth. Though our results should be interpreted cautiously because of the small number of mobile HCWs and MDR-TB patients in this study, we recommend carefully exploring the motivations of HCWs and technologic enhancements prior to scaling new mHealth initiatives in resource poor settings. [ABSTRACT FROM AUTHOR]

Background: Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients. Methods: Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO's or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted. Results: Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2-3.2%) had preventable adverse drug reactions and 52% (95% CI: 42-62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1-51%) had preventable adverse drug reactions and 45% (95% CI: 33-58%) of adverse drug reactions were preventable. Conclusions: This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research. [ABSTRACT FROM AUTHOR]

In drug delivery, there is often a trade-off between effective killing of the pathogen, and harmful side effects associated with the treatment. Due to the difficulty in testing every dosing scenario experimentally, a computational approach will be helpful to assist with the prediction of effective drug delivery methods. In this paper, we have developed a data-driven predictive system, using machine learning techniques, to determine, in silico, the effectiveness of drug dosing. The system framework is scalable, autonomous, robust, and has the ability to predict the effectiveness of the current drug treatment and the subsequent drug-pathogen dynamics. The system consists of a dynamic model incorporating both the drug concentration and pathogen population into distinct states. These states are then analyzed using a temporal model to describe the drug-cell interactions over time. The dynamic drug-cell interactions are learned in an adaptive fashion and used to make sequential predictions on the effectiveness of the dosing strategy. Incorporated into the system is the ability to adjust the sensitivity and specificity of the learned models based on a threshold level determined by the operator for the specific application. As a proof-of-concept, the system was validated experimentally using the pathogen Giardia lamblia and the drug metronidazole in vitro. [ABSTRACT FROM AUTHOR]

Background: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1Can resveratrol be recommended in the prevention or treatment of human diseases?; 2Are there observed "side effects" caused by the intake of resveratrol in humans?; 3What is the relevant dose of resveratrol?; 4What valid data are available regarding an effect in various species of experimental animals?; 5Which relevant (overall) mechanisms of action of resveratrol have been documented? Conclusions/Significance: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects. [ABSTRACT FROM AUTHOR]

To our knowledge, there is no report on long-term reproductive and developmental side effects in the offspring of mothers treated with a widely used chemotherapeutic drug such as doxorubicin (DXR), and neither is there information on transmission of any detrimental effects to several filial generations. Therefore, the purpose of the present paper was to examine the long-term effects of a single intraperitoneal injection of DXR on the reproductive and behavioral performance of adult female mice and their progeny. C57BL/6 female mice (generation zero; G0) were treated with either a single intraperitoneal injection of DXR (G0-DXR) or saline (G0-CON). Data were collected on multiple reproductive parameters and behavioral analysis for anxiety, despair and depression. In addition, the reproductive capacity and health of the subsequent six generations were evaluated. G0-DXR females developed despair-like behaviors; delivery complications; decreased primordial follicle pool; and early lost of reproductive capacity. Surprisingly, the DXR-induced effects in oocytes were transmitted transgenerationally; the most striking effects being observed in G4 and G6, constituting: increased rates of neonatal death; physical malformations; chromosomal abnormalities (particularly deletions on chromosome 10); and death of mothers due to delivery complications. None of these effects were seen in control females of the same generations. Long-term effects of DXR in female mice and their offspring can be attributed to genetic alterations or cell-killing events in oocytes or, presumably, to toxicosis in non-ovarian tissues. Results from the rodent model emphasize the need for retrospective and long-term prospective studies of survivors of cancer treatment and their offspring. [ABSTRACT FROM AUTHOR]

Adverse drug reactions (ADR), also known as side-effects, are complex undesired physiologic phenomena observed secondary to the administration of pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a dominant factor is the drug's ability to modulate one or more biological pathways. Understanding the biological processes behind the occurrence of ADRs would lead to the development of safer and more effective drugs. At present, no method exists to discover these ADR-pathway associations. In this paper we introduce a computational framework for identifying a subset of these associations based on the assumption that drugs capable of modulating the same pathway may induce similar ADRs. Our model exploits multiple information resources. First, we utilize a publicly available dataset pairing drugs with their observed ADRs. Second, we identify putative protein targets for each drug using the protein structure database and in-silico virtual docking. Third, we label each protein target with its known involvement in one or more biological pathways. Finally, the relationships among these information sources are mined using multiple stages of logistic-regression while controlling for over-fitting and multiple-hypothesis testing. As proof-of-concept, we examined a dataset of 506 ADRs, 730 drugs, and 830 human protein targets. Our method yielded 185 ADR-pathway associations of which 45 were selected to undergo a manual literature review. We found 32 associations to be supported by the scientific literature. [ABSTRACT FROM AUTHOR]

Background: Although several mathematical models have been proposed to assess the risk:benefit of drugs in one measure, their use in practice has been rather limited. Our objective was to design a simple, easily applicable model. In this respect, measuring the proportion of patients who respond favorably to treatment without being affected by adverse drug reactions (ADR) could be a suitable endpoint. However, remarkably few published clinical trials report the data required to calculate this proportion. As an approach to the problem, we calculated the expected proportion of this type of patients. Methodology/Principal Findings: Theoretically, responders without ADR may be obtained by multiplying the total number of responders by the total number of subjects that did not suffer ADR, and dividing the product by the total number of subjects studied. When two drugs are studied, the same calculation may be repeated for the second drug. Then, by constructing a 2×2 table with the expected frequencies of responders with and without ADR, and non-responders with and without ADR, the odds ratio and relative risk with their confidence intervals may be easily calculated and graphically represented on a logarithmic scale. Such measures represent "net efficacy adjusted for risk" (NEAR). We assayed the model with results extracted from several published clinical trials or meta-analyses. On comparing our results with those originally reported by the authors, marked differences were found in some cases, with ADR arising as a relevant factor to balance the clinical benefit obtained. The particular features of the adverse reaction that must be weighed against benefit is discussed in the paper. Conclusion: NEAR representing overall risk-benefit may contribute to improving knowledge of drug clinical usefulness. As most published clinical trials tend to overestimate benefits and underestimate toxicity, our measure represents an effort to change this trend. [ABSTRACT FROM AUTHOR]

Pharmacogenomic testing may be used to improve treatment outcomes and reduce the frequency of adverse drug reactions (ADRs). Population specific, targeted pharmacogenetics (PGx) panel-based testing methods enable sensitive, accurate and economical implementation of precision medicine. We evaluated the analytical performance of the GenoPharm® custom open array platform which evaluates 120 SNPs across 46 pharmacogenes. Using commercially available reference samples (Coriell Biorepository) and in-house extracted DNA, we assessed accuracy, precision, and linearity of GenoPharm®. We then used GenoPharm® on 218 samples from two Southern African black populations and determined allele and genotype frequencies for selected actionable variants. Across all assays, the GenoPharm® panel demonstrated 99.5% concordance with the Coriell reference samples, with 98.9% reproducibility. We observed high frequencies of key genetic variants in people of African ancestry: CYP2B6*6 (0.35), CYP2C9*8, *11 (0.13, 0.03), CYP2D6*17 (0.21) and *29 (0.11). GenoPharm® open array is therefore an accurate, reproducible and sensitive test that can be used for clinical pharmacogenetic testing and is inclusive of variants specific to the people of African ancestry. [ABSTRACT FROM AUTHOR]

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597–10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110–5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277–46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162–1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339–39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875–0.943) and 0.888 (95% CI = 0.832–0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736–0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed. [ABSTRACT FROM AUTHOR]

Background: Adverse Drug Reactions (ADRs) can occur with all medicines even after successful extensive clinical trials. ADRs result in more than 10% of hospital admissions worldwide. In Ghana, there has been an increase of 13 to 126 ADR reports per million population from 2012 to 2018. ADR Surveillance System (ADRSS) also known as pharmacovigilance has been put in place by the Ghana Food and Drugs Authority (FDA) to collect and manage suspected ADR reports and communicate safety issues to healthcare professionals and the general public. The ADRSS in Ho Municipality was evaluated to assess the extent of reporting of ADRs and the system's attributes; determine its usefulness, and assess if the ADRSS is achieving its objectives. Methods: We evaluated the ADRSS of the Ho Municipality from January 2015 to December 2019. Quantitative data were collected through interviews and review of records. We adapted the updated CDC guidelines to develop interview guides and a checklist for data collection. Attributes reviewed included simplicity, data quality, acceptability, representativeness, timeliness, sensitivity, predictive value positive and stability. Results: We found a total of 1,237 suspected ADR during the period, of which only 36 (3%) were reported by healthcare professionals in the Ho Municipality to the National Pharmacovigilance Centre (NPC). Only 43.9% of health staff interviewed were familiar with the ADRSS and its reporting channel. Staff who could mention at least one objective of the ADRSS were 34.2%, and 12.2% knew the timelines for reporting ADR. Reports took a median time of 41 (IQR = 25, 81) days from reporter to NPC. Reports sent on time constituted 37.5%. Fully completed case forms constituted 77.1% and the predictive value positive (PVP) was 20%. About 53% of ADRs were reported for female patients. Up to 88.9% of ADRs were classified as drug related. Anti-tuberculosis agents and other antibiotics constituted (40.6%) and (18.8%) of all reports. The ADRSS was not integrated into the disease surveillance and response system of Ghana's Health Service and so was not flexible to changes. A dedicated ADR surveillance officer in regions helped with the system's stability. Data from Ghana feeds into a WHO database for global decision making. Conclusions: There was under-reporting of ADRs in the Ho Municipality from January 2015 to December 2019. The ADR surveillance system was simple, stable, acceptable, representative, had a strong PVP but was not flexible or timely. The ADRSS was found useful and partially met its objectives. [ABSTRACT FROM AUTHOR]

Ghana's rate of reporting adverse drug reaction (ADRs) over the past years has consistently been below the WHO standard despite utilizing the spontaneous or voluntary reporting system. While underreporting undermines the pharmacovigilance system and poses a huge threat to public health safety, there is limited information on the perspectives of healthcare workers directly involved in drug administration. The present study investigated the knowledge, attitude and practice of physicians and nurses at the Cape Coast Teaching Hospital (CCTH) towards spontaneous reporting of ADRs (SR-ADRs). A descriptive cross-sectional survey was employed in the study. Pre-tested (Cronbach's alpha value of 0.72) and validated questionnaires comprising 37 open-ended and close-ended questions were administered to 44 doctors and 116 nurses at the CCTH who had been practicing for at least six months prior to study. Out of the 160 administered questionnaires, 86 was administered face-to-face and the remaining via e-mails. Descriptive analysis was performed and the results were presented in simple frequencies and percentages. Binary logistic regression model was used to test association of the independent variables with SR-ADRs. With a response rate of 86.4% for physicians and 59.5% for nurses, 38 (35.5%) physicians and 69 (64.5%) nurses completed the questionnaires and returned same. Majority (82.3%, 88) of the respondents knew that it is their responsibility to report ADRs although their knowledge levels was found to be inadequate (that is ≤80%) in majority (66.7%) of the text items that assessed knowledge levels. On the attitude of respondents, it was found that 57% (61) of them agreed that under-reporting was due to complacency whereas 80.4% (86) of them agreed that it was due the lack of adequate training. On the issues of practice, the prevalence of encountering, assisting in the management, and reporting of ADRs were 26.1% (28), 17.8% (19) and 7.5% (8) respectively. Also, nurses were 1.22 times more likely to encounter a patient with ADRs and twice more likely to fill and forward ADR form than doctors during management. Respondents with more than six months but less than one year of practice experience were more likely (AOR = 1.38, 95% CI: 2.72–7.3) to encounter a patient with ADRs as compared to those with just six months of practice experience. Furthermore, male respondents were more likely (AOR = 2.42, 95% CI: 1–5.85) to encounter patients with ADRs but less likely (AOR = 0.49, 95% CI: 0.91–2.6) to fill and forward ADR form compared to their female counterparts. In conclusion, doctors and nurses at the CCTH had inadequate knowledge about ADRs and its existing pharmacovigilance systems, thus accounting for the low spontaneous ADRs reporting in the facility. [ABSTRACT FROM AUTHOR]

Background: Ginseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC. Methods: Eight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers. Results: A total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p < 0.00001) and disease control (RR = 1.13, 95% CI: 1.08 to 1.19, p < 0.00001) rates than those treated with FBC alone. Additionally, the combination group had a better QoL, higher proportions of CD3+ T cells, CD4+ T cells, and natural killer cells, as well as a higher CD4+/CD8+ T-cell ratio. Furthermore, lower levels of CA19-9, CA72-4, and CEA were confirmed in the combination treatment group. In addition, G-TMPs reduced the incidence of ADRs during chemotherapy. Conclusion: In combination with FBC, G-TMPs can potentially enhance efficacy, reduce ADRs, and improve prognosis for patients with AGC. However, high-quality randomized studies remain warranted. Systematic review registration: PROSPERO Number: CRD42021264938. [ABSTRACT FROM AUTHOR]

Arylamine N-acetyltransferase 2 has been related to drug side effects and cancer susceptibility; its protein structure and acetylation capacity results from the polymorphism's arrays on the NAT2 gene. Absorption, distribution, metabolism, and excretion, cornerstones of the pharmacological effects, have shown diversity patterns across populations, ethnic groups, and even interethnic variation. Although the 1000 Genomes Project database has portrayed the global diversity of the NAT2 polymorphisms, several populations and ethnicities remain underrepresented, limiting the comprehensive picture of its variation. The NAT2 clinical entails require a detailed landscape of its striking diversity. This systematic review spans the genetic and acetylation patterns from 164 articles from October 1992 to October 2020. Descriptive studies and controls from observational studies expanded the NAT2 diversity landscape. Our study included 243 different populations and 101 ethnic minorities, and, for the first time, we presented the global patterns in the Middle Eastern populations. Europeans, including its derived populations, and East Asians have been the most studied genetic backgrounds. Contrary to the popular perception, Africans, Latinos and Native Americans have been significantly represented in recent years. NAT2*4, *5B, and *6A were the most frequent haplotypes globally. Nonetheless, the distribution of *5B and *7B were less and more frequent in Asians, respectively. Regarding the acetylator status, East Asians and Native Americans harboured the highest frequencies of the fast phenotype, followed by South Europeans. Central Asia, the Middle East, and West European populations were the major carriers of the slow acetylator status. The detailed panorama presented herein, expands the knowledge about the diversity patterns to genetic and acetylation levels. These data could help clarify the controversial findings between acetylator states and the susceptibility to diseases and reinforce the utility of NAT2 in precision medicine. [ABSTRACT FROM AUTHOR]

Background: Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI. Methods: We utilized correlation-based network analysis (CNA) to investigate the relationship between medications or their combinations with AKI in a large cohort of critically ill patients in a tertiary medical center between 2007 and 2018. Pairwise medication-AKI correlation analysis was performed to evaluate drug synergistic or additive effects. To investigate the inherent nephrotoxicity of medications, we further analyzed medications that were not paired with any other medications within 24 hours before or after their administration time (isolated medication analysis). Results: Among 147,289 ICU admissions, we identified 244 associations among 1,555 unique medication types. In pairwise analysis, 233 significant correlations were found among 13,150,198 medication pair instances. In isolated medication analysis, ten significant AKI associations were noted. When stratified by eGFR level, substantial differences between eGFR<90 vs. eGFR≥90 patients were observed. This highlights a need to determine eGFR as a risk factor for nephrotoxicity assessment when drug interactions are considered. Conclusions: This large-scale cohort study identified an artificial intelligence model to identify patient-agnostic relationships between medication or their pairs with AKI incidence among critically ill patients. It could be used as a continuous quality assurance tool to monitor drug-associated risk nephrotoxicity. [ABSTRACT FROM AUTHOR]

We apply a heterogeneous graph convolution network (GCN) combined with a multi-layer perceptron (MLP) denoted by GCNMLP to explore the potential side effects of drugs. Here the SIDER, OFFSIDERS, and FAERS are used as the datasets. We integrate the drug information with similar characteristics from the datasets of known drugs and side effect networks. The heterogeneous graph networks explore the potential side effects of drugs by inferring the relationship between similar drugs and related side effects. This novel in silico method will shorten the time spent in uncovering the unseen side effects within routine drug prescriptions while highlighting the relevance of exploring drug mechanisms from well-documented drugs. In our experiments, we inquire about the drugs Vancomycin, Amlodipine, Cisplatin, and Glimepiride from a trained model, where the parameters are acquired from the dataset SIDER after training. Our results show that the performance of the GCNMLP on these three datasets is superior to the non-negative matrix factorization method (NMF) and some well-known machine learning methods with respect to various evaluation scales. Moreover, new side effects of drugs can be obtained using the GCNMLP. [ABSTRACT FROM AUTHOR]

The Morisky Green Levine (MGL) adherence scale is a 4-item tool used for the detection of medication nonadherence among patients with chronic health conditions. Despite being widely used in Arabic-speaking research contexts, it has never been validated in Arabic language. The aim of this study was to translate and validate the MGL tool into Arabic. A standard forward-backward process was used to translate the questionnaire. Cronbach's alpha coefficient was measured to assess internal consistency of the scale. The test-retest reliability measured the consistency of participants' responses over time. Construct validity was evaluated by Explanatory factor analysis (EFA); Kaiser-Meyer-Olkin value and Bartlett's test of sphericity were determined. Convergent validity was assessed using a preexisting medications Arabic Adherence Assessment Tool (AAAT). The model fit was evaluated using confirmatory factor analysis (CFA). Associations between the MGL scale scores and the patient demographic/clinical characteristics were tested by linear regressions. A total of 201 participants were included into the study. The MGL scale categorization revealed that 20.9%, 59.2% and 19.9% of the participants had high, moderate and low levels of adherence respectively. Adequate internal consistency (alpha = 0.593) was observed. A significant strong ICC and Pearson's correlations were generated between responses at time 1 and time 2. EFA results elucidated the suitability of the data for factor analysis. Pearson's coefficient (r) revealed a significant strong correlation between MGL scale and AAAT. CFA results confirmed a good fit for the suggested model. Linear regression revealed higher number of medications, more frequent outpatient clinic visits and not experiencing medication adverse effect factors significantly associated with better adherence. The Arabic version of MLG scale is a reliable valid tool to assess adherence among Arabic-speaking communities. Implementing interventions targeting patients not compliant to regular clinic visits and those at higher risk of experiencing medication side effects can greatly enhance medication adherence. [ABSTRACT FROM AUTHOR]

Background: Prescribing cascades, where a medication is used to treat the side effect of another medication, contribute to polypharmacy and related morbidity. Little is known about clinicians' and patients' experiences with prescribing cascades. In this study, we explored why and how prescribing cascades occur across a variety of care settings and how they are managed. Methods and findings: This descriptive qualitative study employed semi-structured interviews with older adults who may have experienced a prescribing cascade(s), their caregivers, and healthcare providers. Interviewees were recruited through physician referral from a Geriatric Day Hospital, two long-term care homes in Ottawa, Ontario, and through self-referral across Ontario, Canada. An inductive approach was used to code data and determine themes. Thirty-one interviews were conducted for ten unique patient cases. Some interviewees were involved in more than one case, resulting in 22 unique interviewees. Three themes were identified. First, recognition of prescribing cascades is linked to awareness of medication side effects. Second, investigation and management of prescribing cascades is simultaneous and iterative (rather than linear and sequential). Third, prevention of prescribing cascades requires intentional strategies to help people anticipate and recognize medication side effects. Difficulty with recruitment from both long-term care homes and through self-referral was the central limitation. This exemplifies challenges associated with studying a poorly recognized and underexplored phenomenon. Conclusions: In order to better recognize, investigate and manage prescribing cascades, clinicians and patients need to know more about medication side effects; they need to ask 'can this be caused by a drug?' when signs and symptoms arise or worsen; and they need access to information about medication experiences to have benefit-risk discussions and make decisions about deprescribing. Approaches for raising public awareness of prescribing cascades should be trialed to raise the profile of this issue and facilitate continued exploration of the phenomenon. [ABSTRACT FROM AUTHOR]

Allergic reactions to medication range from mild to severe or even life-threatening. Proper documentation of patient allergy information is critical for safe prescription, avoiding drug interactions, and reducing healthcare costs. Allergy information is regularly obtained during the medical interview, but is often poorly documented in electronic health records (EHRs). While many EHRs allow for structured adverse drug reaction (ADR) reporting, a free-text entry is still common. The resulting information is neither interoperable nor easily reusable for other applications, such as clinical decision support systems and prescription alerts. Current approaches require pharmacists to review and code ADRs documented by healthcare professionals. Recently, the effectiveness of machine algorithms in natural language processing (NLP) has been widely demonstrated. Our study aims to develop and evaluate different NLP algorithms that can encode unstructured ADRs stored in EHRs into institutional symptom terms. Our dataset consists of 79,712 pharmacist-reviewed drug allergy records. We evaluated three NLP techniques: Naive Bayes—Support Vector Machine (NB-SVM), Universal Language Model Fine-tuning (ULMFiT), and Bidirectional Encoder Representations from Transformers (BERT). We tested different general-domain pre-trained BERT models, including mBERT, XLM-RoBERTa, and WanchanBERTa, as well as our domain-specific AllergyRoBERTa, which was pre-trained from scratch on our corpus. Overall, BERT models had the highest performance. NB-SVM outperformed ULMFiT and BERT for several symptom terms that are not frequently coded. The ensemble model achieved an exact match ratio of 95.33%, a F1 score of 98.88%, and a mean average precision of 97.07% for the 36 most frequently coded symptom terms. The model was then further developed into a symptom term suggestion system and achieved a Krippendorff's alpha agreement coefficient of 0.7081 in prospective testing with pharmacists. Some degree of automation could both accelerate the availability of allergy information and reduce the efforts for human coding. [ABSTRACT FROM AUTHOR]

Across rural sub-Saharan Africa, people living with HIV (PLHIV) commonly seek out treatment from traditional healers. We report on the clinical outcomes of a community health worker intervention adapted for traditional healers with insight into our results from qualitative interviews. We employed a pre-post intervention study design and used sequential mixed methods to assess the impact of a traditional healer support worker intervention in Zambézia province, Mozambique. After receiving a positive test result, 276 participants who were newly enrolled in HIV treatment and were interested in receiving home-based support from a traditional healer were recruited into the study. Those who enrolled from February 2016 to August 2016 received standard of care services, while those who enrolled from June 2017 to May 2018 received support from a traditional healer. We conducted interviews among healers and participants to gain insight into fidelity of study activities, barriers to support, and program improvement. Medication possession ratio at home (based on pharmacy pick-up dates) was not significantly different between pre- and post-intervention participants (0.80 in the pre-intervention group compared to 0.79 in the post-intervention group; p = 0.96). Participants reported receiving educational and psychosocial support from healers. Healers adapted their support protocol to initiate directly observed therapy among participants with poor adherence. Traditional healers can provide community-based psychosocial support, education, directly observed therapy, and disclosure assistance for PLHIV. Multiple factors may hinder patients' desire and ability to remain adherent to treatment, including poverty, confusion about medication side effects, and frustration with wait times at the health facility. [ABSTRACT FROM AUTHOR]

Background: A diverse range of study designs (e.g. case-control or cohort) are used in the evaluation of adverse effects. We aimed to ascertain whether the risk estimates from meta-analyses of case-control studies differ from that of other study designs. Methods: Searches were carried out in 10 databases in addition to reference checking, contacting experts, and handsearching key journals and conference proceedings. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from case-control studies could be directly compared with the pooled estimate for the same adverse effect arising from other types of observational studies. Results: We included 82 meta-analyses. Pooled estimates of harm from the different study designs had 95% confidence intervals that overlapped in 78/82 instances (95%). Of the 23 cases of discrepant findings (significant harm identified in meta-analysis of one type of study design, but not with the other study design), 16 (70%) stemmed from significantly elevated pooled estimates from case-control studies. There was associated evidence of funnel plot asymmetry consistent with higher risk estimates from case-control studies. On average, cohort or cross-sectional studies yielded pooled odds ratios 0.94 (95% CI 0.88–1.00) times lower than that from case-control studies. Interpretation: Empirical evidence from this overview indicates that meta-analysis of case-control studies tend to give slightly higher estimates of harm as compared to meta-analyses of other observational studies. However it is impossible to rule out potential confounding from differences in drug dose, duration and populations when comparing between study designs. [ABSTRACT FROM AUTHOR]