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INTRODUCTION: Bumetanide, a loop diuretic, was identified as a candidate drug for repurposing for Alzheimers disease (AD) based on its effects on transcriptomic apolipoprotein E signatures. Cross-sectional analyses of electronic health records suggest that bumetanide is associated with decreased prevalence of AD; however, temporality between bumetanide exposure and AD development has not been established. METHODS: We evaluated Medicare claims data using Cox proportional hazards regression to evaluate the association between time-dependent use of bumetanide and time to first AD diagnosis while controlling for patient characteristics. Multiple sensitivity analyses were conducted to test the robustness of the findings. RESULTS: We sampled 833,561 Medicare beneficiaries, 60.8% female, with mean (standard deviation) age of 70.4 (12). Bumetanide use was not significantly associated with AD risk (hazard ratio 1.05; 95% confidence interval, 0.99-1.10). DISCUSSION: Using a nationwide dataset and a retrospective cohort study design, we were not able to identify a time-dependent effect of bumetanide lowering AD risk. HIGHLIGHTS: Bumetanide was identified as a candidate for repurposing for Alzheimers disease (AD). We evaluated the association between bumetanide use and risk of AD. We used Medicare data and accounted for duration of bumetanide use. Bumetanide use was not significantly associated with risk of AD.

The article published in the Journal of Internal Medicine explores the increased risk of hypereosinophilia following the initiation of glucagon-like peptide 1 receptor agonists (GLP1-RA) using Danish health registries. The study found that individuals who initiated GLP1-RA were three times more likely to experience hypereosinophilia compared to before initiation, with no similar association observed for other antidiabetic drugs. The research highlights the need for larger studies to further investigate the potential link between GLP1-RA and clinically manifest hypereosinophilic syndrome. [Extracted from the article]

Introduction: Adverse effects of opioids are common among older individuals, and undertreatment as well as overuse can be an issue. Epidemiological data on opioid use in older individuals are available, but scarce in hospitalized patients. Aims: The aim of this study is to examine the one-day prevalence of opioid use among older inpatients and identify the factors associated with both opioid use and dosage. Materials and methods: One-day cross-sectional study with data collected from geriatric units across 14 Belgian hospitals. The primary focus of the study is to assess the prevalence of opioid use and dosage, along with identifying associated factors. To achieve this, a multiple binary logistic regression model was fitted for opioid use, and a multiple linear regression model for opioid dose. Results: Opioids were used in 24.4% of 784 patients, of which 57.9% was treated with tramadol, 13.2% with oxycodone or morphine and 28.9% with transdermal buprenorphine or fentanyl. The odds for opioid use were 4.2 times higher in patients in orthogeriatric units compared to other patients (OR=4.2, 95% CI=2.50-7.05). The prevalence of opioid use was 34% higher in patients without dementia compared to patients with dementia (OR=0.66, 95% CI=0.46-0.95). The overall mean daily dosage was 14.07 mg subcutaneous morphine equivalent. After adjustment for age, gender and dementia, dosage was only associated with type of opioid: the estimated mean opioid dose was 70% lower with tramadol (mean ratio=0,30,95% CI=0,23-0,39) and 67% lower with oxycodone and morphine (mean ratio=0,33, 95% CI=0,22-0,48) compared to transdermal buprenorphine and transdermal fentanyl. Conclusions: One in four patients received opioid treatment. It is not clear whether this reflects under- or overtreatment, but these results can serve as a benchmark for geriatric units to guide future pain management practices. The utilization of transdermal fentanyl and buprenorphine, resulting in higher doses of morphine equivalent, poses significant risks for side effects. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions People with chronic kidney disease (CKD) have an elevated risk of cognitive impairment (CI). Medications with anticholinergic activity are recognized for their adverse reactions on central nervous system. The putative association between the anticholinergic burden and CI has not previously been evaluated in patients with CKD. The study aimed to (i) describe prescriptions of medications with anticholinergic activity, (ii) analyze factors associated with these prescriptions, and (iii) evaluate the anticholinergic burden's association with cognitive performance.CKD‐REIN, a prospective cohort study, enrolled nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 mL/min/1.73m2). Drug prescriptions were recorded prospectively during the 5‐year follow‐up. Mini Mental State Examination (MMSE) was assessed at baseline and CI was defined as an MMSE score <24/30. For each patient, the anticholinergic burden was determined by summing the Anticholinergic Cognitive Burden (ACB) scores of all prescription drugs at baseline. Multinomial logistic regression was used to analyze factors associated with the ACB score. Logistic regression was used to evaluate the association between the cognitive impairment and the anticholinergic burden at baseline.At baseline, 3007 patients (median age [IQR], 69[60–76]; 65% men) had MMSE data and were included. 1549 (52%) of these patients were taking at least one drug with anticholinergic properties. Most (1092; 70%) had a low anticholinergic burden, 294 (19%) had a moderate anticholinergic burden, and 163 (11%) had a high anticholinergic burden. A history of neurological/psychiatric disorders and a higher number of daily drugs were associated with a greater probability of having a high anticholinergic burden (odds ratio (OR) [95% confidence interval (95% CI)] = 1.88[1.29;2.74] and 1.53[1.45;1.61], respectively). Patients with a high anticholinergic burden had a significantly higher probability of presenting cognitive impairment, compared with patients without an anticholinergic burden (OR[95% CI] = 1.76[1.12;2.75]) after adjustment for sociodemographic factors, comorbidities, laboratory data, and the number of medications taken daily.The results of our study emphasize the need for caution in the prescription of drugs with anticholinergic properties to patients with CKD. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to evaluate Zolpidem and Benzodiazepines prescription and dispensing data in private pharmacies in Brazil from 2014 to 2021. Methods: This retrospective cohort study was carried out with retrospective open data from the Brazilian Federal Government from January 2014 to August 2021 containing medicines registered in the National Controlled Products Management System (SNGPC). Results: Between January 2014 and August 2021, a total of 32,441,392 sales of thirteen drugs from the z-drug and benzodiazepine classes used to treat sleep disorders were recorded in Brazil. Throughout the entire period, clonazepam emerged as the most popular drug, accounting for 29.8% of total sales. Alprazolam followed in second place with 20.6% of sales, while zolpidem came in third with 14.4%. The normal-release form of zolpidem was consistently the highest-selling variant during the evaluation period. However, the fast-acting-release form exhibited the most significant growth, indicated by a noticeable upward trend in sales since 2020. In contrast, the extended-release form of zolpidem remained stable over the years. Conclusion: The increased sales of zolpidem in Brazilian private pharmacies raise concerns about potential misuse and dependence on this drug mainly for the treatment of insomnia. The epidemic of sleeping pills arises in a scenario of expectancy of short-term amelioration of symptoms, with no correspondence in best clinical practice. Education and counseling for both healthcare professionals and the general population are essential to address this growing health concern and ensure the safe and appropriate use of medications for sleep disorders. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Given the high prevalence of both mental health and acute pain conditions during pregnancy, use of antidepressants and analgesic opioids in this period is widespread. Whether single and combined use of these medications is associated with spontaneous preterm birth (sPTB) remains unclear.To investigate the association between maternal prescription opioid and antidepressant medication exposures for co‐occurring mental health and acute pain management, either alone or in combination, and sPTB.We used Tennessee Medicaid data (2007–2019) linked to birth certificates to conduct a nested case–control study among 15‐ to 44‐year‐old pregnant patients with singleton live births. Cases were identified as spontaneous live births between 24 and <37 gestational weeks using a validated birth certificate‐based algorithm. We selected up to 10 controls per case, matched on estimated pregnancy start date and other factors. We identified analgesic opioid and antidepressant pharmacy fills to define medication exposures in the 60 days before index date (case delivery date) and categorised them as unexposed, opioid‐only, antidepressant‐only and combined exposure. We estimated odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression, adjusting for confounders. We assessed the additive interaction between opioids and antidepressants by estimating relative excess risk due to interaction.We identified 25,406 eligible cases of sPTB and 225,771 matched controls. Opioid‐only and combined exposures were associated with higher odds of sPTB relative to unexposed (adjusted OR 1.29, 95% CI 1.23, 1.35 and 1.22, 95% CI 1.06, 1.40, respectively), while antidepressant‐only exposure was not (1.04, 95% CI 0.96, 1.12). No additive interaction was identified for combined exposure.Exposure to prescription opioids during pregnancy, but not antidepressants, was associated with increased relative odds of sPTB. Co‐exposure to opioids and antidepressants did not elevate the odds of sPTB above what we observed for opioid‐only exposure. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance is a significant global health threat. Therefore, robust surveillance systems for antimicrobial consumption (AMC) are essential to develop public health strategies. However, Latin American countries, including Costa Rica, face challenges in regularly reporting AMC data. This study aims to estimate and analyse the overall AMC in Costa Rica for 2019. Methods: This study is a national-level, retrospective, observational, and descriptive analysis of AMC in Costa Rica from 1 January to 31 December 2019. The study followed the World Health Organization (WHO) guidelines for the Surveillance of National AMC. The Anatomical Therapeutic Chemical (ATC) / Defined Daily Doses (DDD) system was used to analyse types of antimicrobials and DDD per 1000 inhabitants per day (DID). Antimicrobial dispensation data from the Costa Rican Social Security Fund (CCSS) represented the public sector, while the private sector data was sourced from IQVIA. The analysis included data from both inpatient and outpatient sectors. Results: A total AMC of 14.32 DID, of which 12.75 DID was within the public sector and 4.12 DID was within the private sector. Penicillins had the highest consumption nationally and in the public sector, while macrolides and lincosamides predominate in the private sector. According to the WHO-AWaRe (Access-Watch-Reserve) classification, antibiotics predominantly consumed nationally (74.7%) and in the public (83.0%) sectors are categorized under Access, whereas the private (61.0%) sector predominates the Watch category. Conclusion: This study illustrates the importance of enhancing AMC surveillance by integrating data from both the public and private sectors. The findings indicate an excessive use of "Watch" antimicrobials in the private sector. To address this issue, all sectors and regulatory authorities must play an active and supportive role, in the development of effective, multisectoral policies. The methodology employed in this study is applicable to other Latin American countries, and therefore should be utilized for future analysis AMC in this region. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Chronic inflammation is a key factor in type 2 diabetes mellitus (T2DM) development. The cholinergic anti‐inflammatory pathway (CAP) reduces inflammation by activating α7 nicotinic acetylcholine receptors (α7nAChRs) on macrophages, suppressing proinflammatory cytokines. Acetylcholinesterase inhibitors (AChEis), primarily used for Alzheimer's disease (AD), may exert anti‐inflammatory effects through the CAP. One AChEi, galantamine, also directly agonizes α7nAChRs, potentially enhancing its anti‐inflammatory properties.This study aimed to investigate the association between AChEi use, particularly galantamine, and T2DM risk in AD patients.We conducted a retrospective analysis of Veterans Health Administration (VA) data, examining early‐ and late‐onset AD patients receiving galantamine or other AD medications. Propensity score matching was used to balance groups and minimize confounding. Cox proportional hazard models assessed T2DM risk for galantamine, other AChEis and memantine.A total of 40 065 AD patients were included in the study. Among early‐onset AD patients, galantamine use significantly reduced T2DM risk (hazard ratio [HR] = 0.80, 95% confidence interval [CI]: 0.66–0.98). Memantine also showed a protective effect (HR = 0.82, 95% CI: 0.69–1) in this group. Neither galantamine nor memantine influenced T2DM risk in late‐onset AD. Other AD medications showed no association with T2DM risk.Galantamine use was associated with a lower risk of T2DM in early‐onset AD patients, potentially due to enhanced anti‐inflammatory effects through both AChE inhibition and direct α7nAChR agonism. Memantine also demonstrated a protective effect. These findings suggest potential new applications for existing AD medications in T2DM prevention, particularly in early‐onset AD patients. Further research, including randomized controlled trials with diverse populations, is needed to confirm these results and the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate mofetil is used for the prevention of solid organ transplant rejection and for other indications, such as systemic lupus erythematosus (SLE). Objective: To determine the prescription patterns of mycophenolate mofetil in a group of Colombian patients. Methods: This was a cross-sectional study of patients receiving mycophenolate mofetil between 2021 and 2022. The data were obtained from a drug dispensing database. Sociodemographic, clinical (diagnostic), and pharmacological variables were identified. Results: A total of 979 patients who underwent treatment were identified; their mean age was 45.9 ± 17.1 years, and 87.4% were women. The main diagnosis associated with the use of mycophenolate mofetil was SLE (39.1%), followed by other rheumatic diseases (8.5%), nephrotic syndrome (7.5%), and solid organ transplantation (6.4%). The relationship between the mean dose and the defined daily dose was 0.75. Ten percent of patients received mycophenolate alone, whereas 32.9% received mycophenolate in combination therapy with conventional disease-modifying antirheumatic drugs and glucocorticoids. A total of 76.2% had polypharmacy (five or more drugs). Conclusions: Mycophenolate mofetil is used mainly in combination therapy for patients with SLE and other rheumatological diseases and for solid organ transplants at doses lower than those recommended. [ABSTRACT FROM AUTHOR]

Understanding patients' degree of frailty is crucial for tailoring clinical care for older adults based on their physiologic reserve and health needs ("frailty‐guided clinical care"). Two prerequisites for frailty‐guided clinical care are: (1) access to frailty information at the point of care and (2) evidence to inform decisions based on frailty information. Recent advancements include web‐based frailty assessment tools and their electronic health records integration for time‐efficient, standardized assessments in clinical practice. Additionally, database frailty scores from administrative claims and electronic health records data enable scalable assessments and evaluation of the effectiveness and safety of medical interventions across different frailty levels using real‐world data. Given limited evidence from clinical trials, real‐world database studies can complement trial results and help treatment decisions for individuals with frailty. This article, based on the Thomas and Catherine Yoshikawa Award lecture I gave at the American Geriatrics Society Annual Meeting in Long Beach, California, on May 5, 2023, outlines our group's contributions: (1) developing and integrating a frailty index calculator (Senior Health Calculator) into the electronic health records at an academic medical center; (2) developing a claims‐based frailty index for Medicare claims; (3) applying this index to evaluate the effect of medical interventions for patients with and without frailty; and (4) efforts to disseminate frailty assessment tools through the launch of the eFrailty website and the forthcoming addition of the claims‐based frailty index to the Centers for Medicare and Medicaid Services Chronic Conditions Data Warehouse. This article concludes with future directions for frailty‐guided clinical care. [ABSTRACT FROM AUTHOR]

Background: Sleep aids are commonly prescribed to treat sleep disturbance, a modifiable risk factor for postoperative delirium in older patients. The use of melatonin receptor agonists in the postoperative period has been increasing. The comparative safety of melatonin receptor agonists, zolpidem, and temazepam remains uncertain. Methods: This retrospective study included 22,083 patients ≥65 years old who initiated melatonin receptor agonists, zolpidem, or temazepam after major surgery in the Premier Healthcare Database 2009–2018. We performed propensity score‐based overlap weighting and estimated the risk ratio (RR) and risk difference (RD) of postoperative delirium as the primary outcome and a composite of delirium or new antipsychotic initiation, pneumonia, and in‐hospital mortality as secondary outcomes. Results: The mean age of the study population was 78 (SD, 7) years and 50% were female. There was no significant difference in the risk of postoperative delirium among patients treated with melatonin receptor agonists (3.4%, reference group), zolpidem (2.9%; RR [95% CI], 0.9 [0.7–1.2]; RD [95% CI] per 100 persons, −0.3 [−1.1 to 0.6]), and temazepam (3.1%; 0.9 [0.7–1.1]; RD [95% CI] per 100 persons, −0.5 [−1.2 to 0.3]). The risks of delirium or new antipsychotic initiation, pneumonia, and in‐hospital mortality were also similar among all groups. Conclusions: Melatonin receptor agonists were not associated with a lower risk of postoperative delirium and other adverse outcomes compared with zolpidem and temazepam in older adults after major surgery. [ABSTRACT FROM AUTHOR]

Introduction Pharmacoepidemiological data suggest that lithium prescriptions for bipolar disorder are gradually decreasing, with less attention having been paid to other indications. Methods We examined lithium prescriptions between 1994 and 2017 in data provided by the Drug Safety in Psychiatry Program AMSP, including psychiatric hospitals in Germany, Austria and Switzerland. We compared lithium use for different diagnoses before and after 2001 and in three periods (T1: 1994–2001, T2: 2002–2009, and T3: 2010–2017). Results In a total of 158,384 adult inpatients (54% female, mean age 47.4±17.0 years), we observed a statistically significant decrease in lithium prescriptions between 1994–2000 and 2001–2017 in patients with schizophrenia spectrum disorder from 7.7% to 5.1% and in patients with affective disorders from 16.8% to 9.6%. Decreases in use were also observed for diagnostic subgroups: schizoaffective disorder (ICD-10 F25: 27.8% to 17.4%), bipolar disorder (F31: 41.3% to 31%), depressive episode (F32: 8.1% to 3.4%), recurrent depression (F33: 17.9% to 7.5%, all: p<0.001) and emotionally unstable (borderline) personality disorder (6.3% to 3.9%, p=0.01). The results in T1 vs. T2 vs. T3 were for F25: 26.7% vs. 18.2% vs. 16.2%, F32: 7.7% vs. 4.2% vs. 2.7%, F33: 17.2% vs. 8.6% vs. 6.6% and for F31: 40.8% vs. 31.7% vs 30.0%, i. e. there was no further decrease for lithium use in bipolar disorder after 2002. Lithium's main psychotropic co-medications were quetiapine (21.1%), lorazepam (20.6%), and olanzapine (15.2%). Discussion In inpatients, the use of lithium has decreased in patients with bipolar disorder and also with various other psychiatric diagnoses. [ABSTRACT FROM AUTHOR]

Real-world evidence (RWE) studies are increasingly used to inform policy and clinical decisions. However, there remain concerns about the credibility and reproducibility of RWE studies. While there is universal agreement on the critical importance of transparent and reproducible science, the building blocks of open science practice that are common across many disciplines have not yet been built into routine workflows for pharmacoepidemiology and outcomes researchers. Observational researchers should highlight the level of transparency of their studies by providing a succinct statement addressing study transparency with the publication of every paper, poster, or presentation that reports on an RWE study. In this paper, we propose a framework for an explicit transparency statement that declares the level of transparency a given RWE study has achieved across 5 key domains: (1) protocol, (2) preregistration, (3) data, (4) code-sharing, and (5) reporting checklists. The transparency statement outlined in the present paper can be used by research teams to proudly display the open science practices that were used to generate evidence designed to inform public health policy and practice. While transparency does not guarantee validity, such a statement signals confidence from the research team in the scientific choices that were made. [ABSTRACT FROM AUTHOR]

Aims/Introduction: A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7‐nitroso‐3‐(trifluoromethyl)‐5,6,7,8‐tetrahydro[1,2,4] triazolo‐[4,3‐a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP‐contaminated sitagliptin, in comparison with other dipeptidyl peptidase‐4 (DPP‐4) inhibitors, is associated with an increased cancer risk. Materials and Methods: This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP‐4 inhibitor therapy (sitagliptin or other DPP‐4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP‐4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods. Results: Sitagliptin users (149,120 patients, 388,356 person‐years) experienced 9,643 cancer incidences (2,483.0/100,000 person‐years) versus 12,621 incidences (2,504.4/100,000 person‐years) among other DPP‐4 inhibitor users (199,860 patients, 503,952 person‐years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97–1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98–1.04). Findings were also consistent across cancer types and sensitivity analyses. Conclusions: We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP‐contaminated sitagliptin, although continued investigation is needed. [ABSTRACT FROM AUTHOR]

Drug repurposing is a methodology used to identify new clinical indications for existing drugs developed for other indications and has been successfully applied in the treatment of numerous conditions. Alzheimer's disease (AD) may be particularly well-suited to the application of drug repurposing methods given the absence of effective therapies and abundance of multi-omic data that has been generated in AD patients recently that may facilitate discovery of candidate AD drugs. A recent focus of drug repurposing has been in the application of pharmacoepidemiologic approaches to drug evaluation. Here, real-world clinical datasets with large numbers of patients are leveraged to establish observational efficacy of candidate drugs for further evaluation in disease models and clinical trials. In this review, we provide a selected overview of methods for drug repurposing, including signature matching, network analysis, molecular docking, phenotypic screening, semantic network, and pharmacoepidemiological analyses. Numerous methods have also been applied specifically to AD with the aim of nominating novel drug candidates for evaluation. These approaches, however, are prone to numerous limitations and potential biases that we have sought to address in the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study, a multi-step framework for selection and validation of potential drug candidates that has demonstrated the promise of STAT3 inhibitors and re-evaluated evidence for other drug candidates, such as phosphodiesterase inhibitors. Taken together, drug repurposing holds significant promise for development of novel AD therapeutics, particularly as the pace of data generation and development of analytical methods continue to accelerate. [ABSTRACT FROM AUTHOR]

Aim: To examine the likelihood of mortality or rehospitalization following acute coronary syndrome with glyburide versus gliclazide use in adults with type 2 diabetes undergoing cardiac catheterization. Research Design and Methods: This retrospective cohort study used clinical data linked with administrative health data from Alberta, Canada between April 2008 and March 2021. Three methods were used to define exposure to glyburide and gliclazide in the year before catheterization. Multivariable logistic regression was used to compare the likelihood of a composite outcome of 1‐year mortality or rehospitalization with use of glyburide versus use of gliclazide. Results: A total of 11 140 individuals with type 2 diabetes had a cardiac catheterization for acute coronary syndrome. Their mean age was 66 years and 31% were female. In the year before catheterization, 5% used glyburide and 19% used gliclazide. Any glyburide or gliclazide exposure in the year before catheterization was associated with a similar likelihood of all‐cause mortality or rehospitalization (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 0.93–1.41; p = 0.20). However, current glyburide exposure (aOR 1.37, 95% CI 1.06–1.79; p = 0.018) and long exposure to glyburide (aOR 1.37, 95% CI 1.03–1.83; p = 0.030) were associated with a higher likelihood of the composite outcome compared to current and long exposure to gliclazide, respectively. Conclusions: Current and long exposure to glyburide was associated with a greater likelihood of mortality or rehospitalization following cardiac catheterization for acute coronary syndrome, when compared to similar gliclazide exposure definitions. This study adds further evidence of the need to avoid using glyburide if a sulphonylurea is required for type 2 diabetes management. [ABSTRACT FROM AUTHOR]

Background/Objectives: Amphotericin B is indicated in deep systemic fungal infections. The aim was to determine the sociodemographic, clinical and pharmacological variables of a group of Colombian patients treated with amphotericin B and factors associated with mo rtality. Methods: A longitudinal observational retrospective study on the use of amphotericin B in Colombia was conducted between January 2015 and December 2022. The multivariate analysis sought to identify variables related to mortality. Results: A total of 310 patients were identified, with a median age of 44.0 years, and 71.0% were women. Conventional amphotericin B was the most used (74.8%). The main uses were cryptococcosis (38.7%), histoplasmosis (31.9%) and candidiasis (29.4%). More than a third of patients died during hospitalization (40.3%). An increase in the Charlson Comorbidity Index score (HR: 1.13; 95% CI: 1.05–1.22) and in the qSOFA score (HR: 1.34; 95% CI: 1.04–1.73), coinfection by Mycobacterium tuberculosis (HR: 2.09; 95% CI: 1.32–3.31) and the requirement of vasopressors (HR: 4.20; 95% CI: 2.16–8.15) or invasive mechanical ventilation (HR: 2.73; 95% CI: 1.40–5.33) increased the probability of in-hospital death. In contrast, those who received systemic corticosteroids (HR: 0.43; 95% CI: 0.26–0.70) had a lower risk. Conventional amphotericin B is the most used drug mainly treating Cryptococcus neoformans infections. Conclusions: The use of amphotericin B was consistent with clinical practice guideline recommendations. In-hospital mortality was common, and factors such as increased comorbidities, higher qSOFA scores, coinfection with Mycobacterium tuberculosis and invasive procedures like mechanical ventilation were linked to increased mortality. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) and machine learning (ML) are important tools across many fields of health and medical research. Pharmacoepidemiologists can bring essential methodological rigor and study design expertise to the design and use of these technologies within healthcare settings. AI/ML‐based tools also play a role in pharmacoepidemiology research, as we may apply them to answer our own research questions, take responsibility for evaluating medical devices with AI/ML components, or participate in interdisciplinary research to create new AI/ML algorithms. While epidemiologic expertise is essential to deploying AI/ML responsibly and ethically, the rapid advancement of these technologies in the past decade has resulted in a knowledge gap for many in the field. This article provides a brief overview of core AI/ML concepts, followed by a discussion of potential applications of AI/ML in pharmacoepidemiology research, and closes with a review of important concepts across application areas, including interpretability and fairness. This review is intended to provide an accessible, practical overview of AI/ML for pharmacoepidemiology research, with references to further, more detailed resources on fundamental topics. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on renal outcomes in individuals with type 2 diabetes, focusing on the changes in eGFR and albuminuria. Methods: This was a multicentre retrospective observational study on new users of diabetes medications. Participant characteristics were assessed before and after propensity score matching. The primary endpoint, change in eGFR, was analysed using mixed-effects models. Secondary endpoints included categorical eGFR-based outcomes and changes in albuminuria. Subgroup and sensitivity analyses were performed to assess robustness of the findings. Results: After matching, 5701 participants/group were included. Participants were predominantly male, aged 61 years, with a 10 year duration of diabetes, a baseline HbA1c of 64 mmol/mol (8.0%) and BMI of 33 kg/m2. Chronic kidney disease (CKD) was present in 23% of participants. During a median of 2.1 years, from a baseline of 87 ml/min per 1.73 m2, eGFR remained higher in the SGLT2i group compared with the GLP-1RA group throughout the observation period by 1.2 ml/min per 1.73 m2. No differences were detected in albuminuria change. The SGLT2i group exhibited lower rates of worsening CKD class and favourable changes in BP compared with the GLP-1RA group, despite lesser HbA1c decline. SGLT2i also reduced eGFR decline better than GLP-1RA in participants without baseline CKD. Conclusions/interpretation: In individuals with type 2 diabetes, treatment with SGLT2i was associated with better preservation of renal function compared with GLP-1RA, as evidenced by slower decline in eGFR. These findings reinforce SGLT2i as preferred agents for renal protection in this patient population. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are significantly underrepresented in clinical trials, yet most of them take medication during pregnancy despite the limited safety data. The objective of this study was to characterize medication use during pregnancy and apply propensity score matching method at scale on patient records to accelerate and prioritize the drug effect signal detection associated with the risk of preterm birth and other adverse pregnancy outcomes. Methods: This was a retrospective study on continuously enrolled women who delivered live births between 2013/01/01 and 2022/12/31 (n = 365,075) at Providence St. Joseph Health. Our exposures of interest were all outpatient medications prescribed during pregnancy. We limited our analyses to medication that met the minimal sample size (n = 600). The primary outcome of interest was preterm birth. Secondary outcomes of interest were small for gestational age and low birth weight. We used propensity score matching at scale to evaluate the risk of these adverse pregnancy outcomes associated with drug exposure after adjusting for demographics, pregnancy characteristics, and comorbidities. Results: The total medication prescription rate increased from 58.5 to 75.3% (P < 0.0001) from 2013 to 2022. The prevalence rate of preterm birth was 7.7%. One hundred seventy-five out of 1329 prenatally prescribed outpatient medications met the minimum sample size. We identified 58 medications statistically significantly associated with the risk of preterm birth (P ≤ 0.1; decreased: 12, increased: 46). Conclusions: Most pregnant women are prescribed medication during pregnancy. This highlights the need to utilize existing real-world data to enhance our knowledge of the safety of medications in pregnancy. We narrowed down from 1329 to 58 medications that showed statistically significant association with the risk of preterm birth even after addressing numerous covariates through propensity score matching. This data-driven approach demonstrated that multiple testable hypotheses in pregnancy pharmacology can be prioritized at scale and lays the foundation for application in other pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The safety of vancomycin in children requires special attention. The evidence from active pharmacovigilance systems about vancomycin-related adverse drug reactions (ADRs) was rare. We aimed to investigate the association between doses of vancomycin and ADRs among children. This retrospective cohort study included a total of 643 inpatient children. Children who received vancomycin were regarded as exposed groups and classified into low-dose, normal-dose, and high-dose groups. Those who did not receive vancomycin and had similar severity of infection were classified into the unexposed group. ADR signal detection was performed by the China Hospital Pharmacovigilance System. Logistic regression analyses were conducted to explore the effect of intravenous vancomycin on ADRs. This study included 156 patients (178 ADR cases) in the exposed group and 487 patients (364 ADR cases) in the unexposed group. The top three reported ADRs were eosinophilia (n = 75, 48.1%), hemoglobin decreased (n = 72, 46.2%), and blood bilirubin increased (n = 13, 8.3%) in the exposed group. Patients in the low-dose, normal-dose, and high-dose groups showed a higher risk of hemoglobin decreased when compared with those in the unexposed group, with the fully adjusted ORs (95% CIs) of 6.91 (3.61, 13.20), 7.80 (3.87, 15.76), and 8.80 (4.08, 19.01), respectively. Besides, compared with patients in the unexposed group, those in the normal-dose and high-dose groups show a significantly higher risk of eosinophilia and blood bilirubin increased, respectively. It is important to monitor eosinophilia, hemoglobin decreased, and blood bilirubin increased in pediatrics receiving vancomycin, especially those receiving normal-dose and high-dose vancomycin. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Medication data are a valuable resource in epidemiological studies. As the most common data collection method of medication data is self‐report, it is important to understand the accuracy of this in comparison with other methods such as dispensing records. The aim of this study was to compare the agreement between two different sources of medication data of older adults with intellectual disability (ID).Self‐report medication data were gathered from the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing and linked to national pharmacy dispensing records. The kappa statistic was used to measure agreement between the two data sources for psychotropic medication.The lowest agreement level was ‘moderate’ for the number of anxiolytics reported (kappa 0.56). The highest level of agreement was ‘almost perfect’ for the binary variable of antipsychotics (kappa 0.91). Other agreement results were ‘substantial’ or ‘almost perfect’.Good agreement was found between the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing medication dataset and national dispensing records. Self‐report medication data appear to be a valid method of data collection in psychotropic medication use in adults with ID. [ABSTRACT FROM AUTHOR]

Background: While traditional medicine (TM) is employed by a significant portion of the global population for managing health issues, clinical guidelines and state recommendations often overlook this practice. The aim of this study was to describe the frequency of use of TM to control 3 metabolic risk factors (MRF): hypertension, hypercholesterolemia, and hyperglycaemia; and the sociodemographic, economic, and clinical characteristics associated with the use of TM. Methods: Cross-sectional descriptive study that analyses data obtained from a representative population survey in 2 health districts, one urban in the south of Quito and another in a forested rural area with diverse ethnic groups in Esmeraldas, Ecuador. We include 602 individuals with at least one MRF. We calculated the proportion of people reporting the regular use of TM (herbal or traditional remedy) to control their MRF and we assessed potential associations with sociodemographic, economic, and clinical characteristics with a multivariable logistic regression model. Results: In two very different sociocultural contexts in Ecuador we found that use of TM to control MRF was frequent (39.4% in Esmeraldas, 31.1% in Quito), frequently in combination with CM. There is a notable percentage of people, 33.9% in Esmeraldas and 39.0% in Quito, who did not take any treatment for their MRF, and the remainder used CM alone. In both settings, an individual's education lever was significantly associated with TM use. Whereas in Quito individuals with higher education more frequently treated their MRF with TM (aOR 2.04, 95% CI 1.03–3.90), in the rural, hard-to-reach context of Esmeraldas, it was more frequent among people with no formal schooling (aOR: 3.76; 95%CI 1.59–8.88), as well as those of younger age (aOR by year: 0.97; 95% CI 0.95–0.99) and afro ethnicity (aOR: 2.13; 95%CI 1.02–4.45). Conclusion: Traditional medicine is used by a significant proportion of the population in Ecuador, highlighting the need for a more accessible and intercultural healthcare approach. The health system should ensure access to the necessary information and resources for the management of their metabolic risk factors. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aimed to investigate trends in antidiabetic drug use and assess the risk of metformin-associated lactic acidosis (MALA) in patients with chronic kidney disease (CKD). Methods: A retrospective observational analysis based on the common data model was conducted using electronic medical records from 2010 to 2021. The patients included were aged ≥18, diagnosed with CKD and type 2 diabetes, and had received antidiabetic medications for ≥30 days. MALA was defined as pH ≤ 7.35 and arterial lactate ≥4 mmol/L. Results: A total of 8318 patients were included, with 6185 in CKD stages 1–2 and 2133 in stages 3a–5. Metformin monotherapy was the most prescribed regimen, except in stage 5 CKD. As CKD progressed, metformin use significantly declined; insulin and meglitinides were most frequently prescribed in end-stage renal disease. Over the study period, the use of SGLT2 inhibitors (13.3%) and DPP-4 inhibitors (24.5%) increased significantly, while sulfonylurea use decreased (p < 0.05). Metformin use remained stable in earlier CKD stages but significantly decreased in stage 3b or worse. The incidence rate (IR) of MALA was 1.22 per 1000 patient-years, with a significantly increased IR in stage 4 or worse CKD (p < 0.001). Conclusions: Metformin was the most prescribed antidiabetic drug in CKD patients in Korea with a low risk of MALA. Antidiabetic drug use patterns varied across CKD stages, with a notable decline in metformin use in advanced CKD and a rise in SGLT2 inhibitor prescriptions, underscoring the need for further optimized therapy. [ABSTRACT FROM AUTHOR]

Aims: To compare the effectiveness of molnupiravir and nirmatrelvir‐ritonavir for non‐hospitalized and hospitalized COVID‐19 patients with type 2 diabetes (T2DM). Materials and Methods: Territory‐wide electronic health records in Hong Kong were used to perform target trial emulation using a sequential trial approach. Patients (1) aged ≥18 years, (2) with T2DM, (3) with COVID‐19 infection, and (4) who received molnupiravir or nirmatrelvir‐ritonavir within 5 days of infection between 16 March 2022 and 31 December 2022 in non‐hospital and hospital settings were included. Molnupiravir and nirmatrelvir‐ritonavir initiators were matched using one‐to‐one propensity‐score matching and followed for 28 days. Risk of outcomes was compared between groups by Cox regression adjusted for baseline characteristics. Subgroup analyses were performed on age (<70 years, ≥70 years), sex, Charlson comorbidity index (<4, ≥4), and number of COVID‐19 vaccine doses (<2 doses, ≥2 doses). Results: Totals of 17 974 non‐hospitalized (8987 in each group) and 3678 hospitalized (1839 in each group) patients were identified. Non‐hospitalized nirmatrelvir‐ritonavir initiators had lower risk of all‐cause mortality (absolute risk reduction [ARR] at 28 days 0.80%, 95% confidence interval [CI] 0.56–1.04; hazard ratio [HR] 0.47, 95% CI 0.30–0.73) and hospitalization (ARR at 28 days 4.01%, 95% CI 3.19–4.83; HR 0.73, 95% CI 0.66–0.82) as compared with molnupiravir initiators. Hospitalized nirmatrelvir‐ritonavir initiators had reduced risk of all‐cause mortality (ARR at 28 days 2.94%, 95% CI 1.65–4.23; HR 0.56, 95% CI 0.40–0.80) as compared with molnupiravir initiators. Consistent findings were found across all subgroups. Conclusions: The use of nirmatrelvir‐ritonavir may be preferred to molnupiravir for COVID‐19 patients with T2DM and without contraindication to either treatment. [ABSTRACT FROM AUTHOR]

The healthcare systems in Scandinavia inform nationwide registers and the Scandinavian populations are increasingly combined in research. We aimed to compare Norway (NO), Sweden (SE), and Denmark (DK) regarding sociodemographic factors and healthcare. In this cross-sectional study, we analyzed aggregated data from the nationwide Scandinavian registers. We calculated country-specific statistics on sociodemographic factors and healthcare use (general practitioner visits, admissions to somatic hospitals, and use of medicines). In 2018, population were 5295,619 (NO), 10,120,242 (SE), and 5781,190 (DK). The populations were comparable regarding sex, age, education, and income distribution. Overall, medication use was comparable, while there was more variation in hospital admissions and general practitioner visits. For example, per 1000 inhabitants, 703 (NO), 665 (SE), and 711 (DK) individuals redeemed a prescription, whereas there were 215 (NO), 134 (SE), and 228 (DK) somatic hospital admissions per 1000 inhabitants. General practitioner contacts per 1000 inhabitants were 7082 in DK and 5773 in NO (-data from SE). The Scandinavian countries are comparable regarding aggregate-level sociodemographic factors and medication use. Variations are noted in healthcare utilisation as measured by visits to general practitioners and admissions to hospitals. This variation should be considered when comparing data from the Scandinavian countries. [ABSTRACT FROM AUTHOR]

Purpose: Galcanezumab is a calcitonin gene‐related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half‐life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real‐world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study. Methods: This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab‐exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations. Results: Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab‐exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory‐committed study timelines. Conclusions: The accrual of a sufficient number of galcanezumab‐exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available. [ABSTRACT FROM AUTHOR]

Abstract Background Antimicrobial resistance is a significant global health threat. Therefore, robust surveillance systems for antimicrobial consumption (AMC) are essential to develop public health strategies. However, Latin American countries, including Costa Rica, face challenges in regularly reporting AMC data. This study aims to estimate and analyse the overall AMC in Costa Rica for 2019. Methods This study is a national-level, retrospective, observational, and descriptive analysis of AMC in Costa Rica from 1 January to 31 December 2019. The study followed the World Health Organization (WHO) guidelines for the Surveillance of National AMC. The Anatomical Therapeutic Chemical (ATC) / Defined Daily Doses (DDD) system was used to analyse types of antimicrobials and DDD per 1000 inhabitants per day (DID). Antimicrobial dispensation data from the Costa Rican Social Security Fund (CCSS) represented the public sector, while the private sector data was sourced from IQVIA. The analysis included data from both inpatient and outpatient sectors. Results A total AMC of 14.32 DID, of which 12.75 DID was within the public sector and 4.12 DID was within the private sector. Penicillins had the highest consumption nationally and in the public sector, while macrolides and lincosamides predominate in the private sector. According to the WHO-AWaRe (Access-Watch-Reserve) classification, antibiotics predominantly consumed nationally (74.7%) and in the public (83.0%) sectors are categorized under Access, whereas the private (61.0%) sector predominates the Watch category. Conclusion This study illustrates the importance of enhancing AMC surveillance by integrating data from both the public and private sectors. The findings indicate an excessive use of “Watch” antimicrobials in the private sector. To address this issue, all sectors and regulatory authorities must play an active and supportive role, in the development of effective, multisectoral policies. The methodology employed in this study is applicable to other Latin American countries, and therefore should be utilized for future analysis AMC in this region.

Oscar Rosenkrantz,1,2 Jannik Wheler,1 Mats Christian Westphal Thrane,3 Lars Pedersen,1 Henrik Toft Sørensen1 1Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; 2Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark; 3Danish Health Data Authority, Copenhagen, DenmarkCorrespondence: Oscar Rosenkrantz, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43, 45, DK, Aarhus N, 8200, Denmark, Tel +45 87 16 72 12, Email oscar.oelrich.rosenkrantz@clin.au.dkBackground: The Danish National Hospital Medication Register (DHMR), one of the first nationwide in-hospital medication registries in the world, contains detailed information on medication administration and dispensing.Objective: To provide an overview of the information recorded in the DHMR and to highlight its strengths and limitations as a pharmacoepidemiological research tool.Methods: We reviewed the registry´s geographic and clinical specialty coverage and medications recorded according to the main groups of the Anatomical Therapeutic Chemical classification system.Results: From May 2018 through December 2023, the DHMR recorded data on more than 1.9 million unique patients from all approximately 50 public hospitals and associated hospital outpatient clinics, totaling 105.3 million recordings of hospital medication use. The registry records detailed data on the indication for medication, medication type, pharmaceutical form, dosage, and administration time, collected through electronic medical record systems. Although the data quality has not yet been evaluated in a scientific context, some potential limitations are known. These include regional differences in the data collection and a lack of data from certain clinical specialties. Due to its recent establishment in 2018, the registered number of patients treated may still be limited for some rarely used medications.Conclusion: The DHMR is an important new resource for research in Denmark. Combined with the Danish National Prescription Registry, which covers all community pharmacies, it offers access to accurate data on medication exposure in the Danish population. Users should be aware of potential issues with lack of information before 2018.Keywords: pharmacoepidemiology, hospital medication system, pharmacotherapy, data source, drug databases, registry data, Denmark

ABSTRACT Aims/Introduction A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7‐nitroso‐3‐(trifluoromethyl)‐5,6,7,8‐tetrahydro[1,2,4] triazolo‐[4,3‐a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP‐contaminated sitagliptin, in comparison with other dipeptidyl peptidase‐4 (DPP‐4) inhibitors, is associated with an increased cancer risk. Materials and Methods This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP‐4 inhibitor therapy (sitagliptin or other DPP‐4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP‐4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods. Results Sitagliptin users (149,120 patients, 388,356 person‐years) experienced 9,643 cancer incidences (2,483.0/100,000 person‐years) versus 12,621 incidences (2,504.4/100,000 person‐years) among other DPP‐4 inhibitor users (199,860 patients, 503,952 person‐years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97–1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98–1.04). Findings were also consistent across cancer types and sensitivity analyses. Conclusions We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP‐contaminated sitagliptin, although continued investigation is needed.

Abstract Background Pregnant women are significantly underrepresented in clinical trials, yet most of them take medication during pregnancy despite the limited safety data. The objective of this study was to characterize medication use during pregnancy and apply propensity score matching method at scale on patient records to accelerate and prioritize the drug effect signal detection associated with the risk of preterm birth and other adverse pregnancy outcomes. Methods This was a retrospective study on continuously enrolled women who delivered live births between 2013/01/01 and 2022/12/31 (n = 365,075) at Providence St. Joseph Health. Our exposures of interest were all outpatient medications prescribed during pregnancy. We limited our analyses to medication that met the minimal sample size (n = 600). The primary outcome of interest was preterm birth. Secondary outcomes of interest were small for gestational age and low birth weight. We used propensity score matching at scale to evaluate the risk of these adverse pregnancy outcomes associated with drug exposure after adjusting for demographics, pregnancy characteristics, and comorbidities. Results The total medication prescription rate increased from 58.5 to 75.3% (P

Abstract Background While traditional medicine (TM) is employed by a significant portion of the global population for managing health issues, clinical guidelines and state recommendations often overlook this practice. The aim of this study was to describe the frequency of use of TM to control 3 metabolic risk factors (MRF): hypertension, hypercholesterolemia, and hyperglycaemia; and the sociodemographic, economic, and clinical characteristics associated with the use of TM. Methods Cross-sectional descriptive study that analyses data obtained from a representative population survey in 2 health districts, one urban in the south of Quito and another in a forested rural area with diverse ethnic groups in Esmeraldas, Ecuador. We include 602 individuals with at least one MRF. We calculated the proportion of people reporting the regular use of TM (herbal or traditional remedy) to control their MRF and we assessed potential associations with sociodemographic, economic, and clinical characteristics with a multivariable logistic regression model. Results In two very different sociocultural contexts in Ecuador we found that use of TM to control MRF was frequent (39.4% in Esmeraldas, 31.1% in Quito), frequently in combination with CM. There is a notable percentage of people, 33.9% in Esmeraldas and 39.0% in Quito, who did not take any treatment for their MRF, and the remainder used CM alone. In both settings, an individual’s education lever was significantly associated with TM use. Whereas in Quito individuals with higher education more frequently treated their MRF with TM (aOR 2.04, 95% CI 1.03–3.90), in the rural, hard-to-reach context of Esmeraldas, it was more frequent among people with no formal schooling (aOR: 3.76; 95%CI 1.59–8.88), as well as those of younger age (aOR by year: 0.97; 95% CI 0.95–0.99) and afro ethnicity (aOR: 2.13; 95%CI 1.02–4.45). Conclusion Traditional medicine is used by a significant proportion of the population in Ecuador, highlighting the need for a more accessible and intercultural healthcare approach. The health system should ensure access to the necessary information and resources for the management of their metabolic risk factors.

PURPOSE: Using a novel, electronic health record (EHR)-based approach, to estimate the prevalence of prescription medication use at 2, 4, and 6 months postpartum among lactating individuals. METHODS: We utilized automated EHR data from a US health system that records infant feeding information at well-child visits. We linked mothers who received prenatal care to their infants born May 2018-June 2019, and we required infants to have ≥1 well-child visit between 31 and 90 days of life (i.e., 2-month well-child visit with a ±1 month window). Mothers were classified as lactating at the 2-month well-child visit if their infant received breast milk at the 2-month well-child visit. For subsequent well-child visits at 4 and 6 months, mothers were considered lactating if their infant was still receiving breast milk. RESULTS: We identified 6013 mothers meeting inclusion criteria, and 4158 (69.2%) were classified as lactating at the 2-month well-child visit. Among those classified as lactating, the most common medication classes dispensed around the 2-month well-child visit were oral progestin contraceptives (19.1%), selective serotonin reuptake inhibitors (8.8%), first generation cephalosporins (4.3%), thyroid hormones (3.5%), nonsteroidal anti-inflammatory agents (3.4%), penicillinase-resistant penicillins (3.1%), topical corticosteroids (2.9%), and oral imidazole-related antifungals (2.0%). The most common medication classes were similar around the 4 and 6-month well-child visits although prevalence estimates were often lower. CONCLUSIONS: Progestin-only contraceptives, antidepressants, and antibiotics were the most dispensed medications among lactating mothers. With routine collection of breastfeeding information, mother-infant linked EHR data may overcome limitations in previous studies of medication utilization during lactation. These data should be considered for studies of medication safety during lactation given the need for human safety data.

Abstract Background The COVID-19 pandemic has had a significant impact on mental health, with evidence suggesting an enduring mental health crisis. Studies worldwide observed increased usage of antidepressants, anxiolytics, and hypnotics during the pandemic, notably among young people and women. However, few studies tracked consumption post-2021. Our study aimed to fill this gap by investigating whether the surge in the number psychotropic drug consumers in France persisted 2 years after the first lockdown, particularly focusing on age and gender differences. Methods We conducted a national retrospective observational study based on the French national insurance database. We retrieved all prescriptions of anxiolytics, hypnotics, and antidepressants dispensed in pharmacies in France for the period 2015–2022. We performed interrupted time series analyses based on Poisson models for five age classes (12–18; 19–25; 26–50; 51–75; 76 and more) to assess the trend before lockdown, the gap induced and the change in trend after. Results In the overall population, the number of consumers remained constant for antidepressants while it decreased for anxiolytics and hypnotics. Despite this global trend, a long-term increase was observed in the 12–18 and 19–25 groups for the three drug classes. Moreover, for these age classes, the increases were more pronounced for women than men, except for hypnotics where the trends were similar. Conclusions The number of people using antidepressants continues to increase more than 2 years after the first lockdown, showing a prolonged effect on mental health. This effect is particularly striking among adolescents and young adults confirming the devastating long-term impact of the pandemic on their mental health.

This article provides an overview of the burden of malaria in pregnancy and recent advancements in prevention and treatment strategies. It highlights the use of intermittent preventive treatment in pregnancy (IPTp) as a targeted approach to administer antimalarial medication to pregnant women in endemic areas. The article also addresses challenges such as accessibility, affordability, and drug resistance in malaria treatment. It emphasizes the need for comprehensive programs and guidelines to effectively address malaria in pregnancy. The article also discusses the safety of antimalarials in pregnancy and explores potential alternatives to quinine-based treatment. Additionally, it calls for more research on the pharmacokinetics and pharmacodynamics of antimalarials in pregnancy and the potential use of malaria vaccines. Overall, the article emphasizes the importance of improved public health infrastructure, updated guidelines, and innovative strategies to tackle the challenges of malaria in pregnancy. [Extracted from the article]

The latest country‐specific regulatory guidance for assessing effectiveness of risk minimization measures (RMM) strategies was identified across five continents—Africa (Egypt, South Africa), Asia (Australia, China, Japan, South Korea, Singapore), Europe (EU‐27, United Kingdom), North America (Unites States, Canada) and South America (Brazil)—and compared to the Reporting recommendation Intended for pharmaceutical Risk Minimization Evaluation Studies (RIMES) checklist, developed to assess the quality of effectiveness evaluations and endorsed by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). RIMES checklist items address study hypothesis, participants, measures, statistical analysis and results. European Medical Agency (EMA) and Food and Drug Administration (FDA) guidance only partially aligned with RIMES, primarily for measures and results. In the absence of country‐specific guidance, most countries recommended following EMA or FDA guidelines; Japan and South Africa mentioned the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH E2E) guideline; Brazil and China had no guidance/recommendations. Worldwide, there was a lack of RMM‐specific guidance and, when guidance existed, they were not harmonized, and alignment with the RIMES checklist was limited. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacovigilance is vital for drug safety. The process typically involves two key steps: initial signal generation from spontaneous reporting systems (SRSs) and subsequent expert review to assess the signals' (potential) causality and decide on the appropriate action. Methods: We propose a novel discovery and verification approach to pharmacovigilance based on electronic healthcare data. We enhance the signal detection phase by introducing an ensemble of methods which generated signals are combined using Borda count ranking; a method designed to emphasize consensus. Ensemble methods tend to perform better when data is noisy and leverage the strengths of individual classifiers, while trying to mitigate some of their limitations. Additionally, we offer the committee of medical experts with the option to perform an in-depth investigation of selected signals through tailored pharmacoepidemiological studies to evaluate their plausibility or spuriousness. To illustrate our approach, we utilize data from the German Pharmacoepidemiological Research Database, focusing on drug reactions to the direct oral anticoagulant rivaroxaban. Results: In this example, the ensemble method is built upon the Bayesian confidence propagation neural network, longitudinal Gamma Poisson shrinker, penalized regression and random forests. We also conduct a pharmacoepidemiological verification study in the form of a nested active comparator case-control study, involving patients diagnosed with atrial fibrillation who initiated anticoagulant treatment between 2011 and 2017. Discussion: The case study reveals our ability to detect known adverse drug reactions and discover new signals. Importantly, the ensemble method is computationally efficient. Hasty false conclusions can be avoided by a verification study, which is, however, time-consuming to carry out. We provide an online tool for easy application: https://borda.bips.eu. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Results from randomized trials suggest benefit of sodium–glucose cotransporter 2 (SGLT2) inhibitor initiation in clinically stable acute heart failure. We aim to examine the real‐world effectiveness of early versus delayed post‐discharge SGLT2 inhibitor initiation in people with acute heart failure and type 2 diabetes.Using linkable administrative databases in Ontario, Canada, individuals aged 66 years or older with type 2 diabetes who were discharged to the community from acute care hospitals for heart failure between 1 July 2016 and 31 March 2020 were included in this retrospective, population‐based cohort study. The primary outcome was hospitalization for heart failure (HHF) or cardiovascular mortality as a composite. Follow‐up started from discharge for maximum 1 year. We compared outcomes between post‐discharge SGLT2 inhibitor initiation within 3 days, 4–90 days, or 91–180 days, versus delayed initiation for at least 180 days. The ‘clone‐censor‐weight’ approach with a target trial emulation framework was used to address time‐related biases. There were 9641 eligible individuals. After cloning and artificial censoring, there were 38 564 clones, 12 439 person‐years, and 7584 events. Compared to delayed initiation for at least 180 days, initiation within 3 days post‐discharge was associated with a lower 1‐year risk of HHF or cardiovascular mortality (risk ratio [RR] 0.65, 95% confidence interval [CI] 0.45–0.83), while initiation 4–90 days (RR 0.83, 95% CI 0.72–0.93) or 91–180 days (RR 0.89, 95% CI 0.79–0.97) showed smaller risk reduction.Real‐world evidence supports early SGLT2 inhibitor initiation to reduce HHF or cardiovascular mortality in acute heart failure and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to examine contemporary trends in the use of, time to, and type of first add‐on anti‐hyperglycaemic therapy to metformin in Australia.We used the dispensing records of a 10% random sample of Pharmaceutical Benefits Scheme (PBS) eligible people. We included people aged 40 years and older initiating metformin from 1 January 2018 to 31 December 2020. Our primary outcome was first add‐on anti‐hyperglycaemic medicine within 2 years of metformin initiation. We analysed time to dispensing of first add‐on therapy. All analyses were stratified by metformin initiation year.Overall, 38 747 people aged 40 years and older initiated metformin between 2018 and 2020. Approximately one‐third (n = 12 946) of people received add‐on therapy with the proportion increasing slightly by year of metformin initiation (32.3% in 2018 to 34.8% in 2020). Amongst people with add‐on therapy following metformin initiation, sodium‐glucose cotransporter 2 inhibitor (SGLT2i) use increased from 28.8% (2018) to 35.0% (2020), and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) increased from 3.0% to 9.6%, respectively. Dipeptidyl peptidase‐4 inhibitors and sulfonylureas as first add‐on therapy decreased and insulin remained stable. One‐third of people with add‐on therapy initiated the therapy on the same day metformin was initiated, i.e. initial combination therapy.Amongst people initiating metformin from 2018 to 2020, there was an increasing proportion of SGLT2i and GLP‐1 RA being used as first add‐on therapy. However, the overall prevalence of add‐on therapy was low. Advocacy to promote add‐on therapy with cardiorenal beneficial medicines is critical to reduce type 2 diabetes morbidity and mortality. [ABSTRACT FROM AUTHOR]

The CARMEN-France registry is a prospective, multicenter registry in France including adult patients with a new diagnosis of immune thrombocytopenia or of autoimmune immune hemolytic anemia (2402 patients included in December 31, 2023). The recording of clinical, biological and treatment data allows detailed epidemiological and pharmacoepidemiological real-world studies. This review summarizes the CARMEN-France registry protocol, gives examples of studies conducted in the registry, and indicates future directions such as inclusion of patient reported outcomes, linkage with the French national health insurance database and linkage with other registries in Europe. [ABSTRACT FROM AUTHOR]

Person-generated health data (PGHD) are valuable for studying outcomes relevant to everyday living, for obtaining information not otherwise available, for long-term follow-up, and in situations where decisions cannot wait for traditional clinical research to be completed. While there is no dispute that these data are subject to bias, insights gained may be better than having an information void, provided the biases are understood and addressed. People will share information known uniquely to them about exposures that may affect drug tolerance, safety, and effectiveness (eg, nonprescription and complementary medications, alcohol, tobacco, illicit drugs, exercise, etc). Patients may be the best source of safety information when long-term follow-up is needed (eg, the 5- to 15-year follow-up required for some gene therapies). Validation studies must be performed to evaluate what people can accurately report and when supplementary confirmation information is needed. However, PGHD has already proven valuable in quantifying and contrasting COVID-19 vaccine benefits and risks and for evaluating disease transmission and the accuracy of COVID-19 testing. Going forward, PGHD will be used for patient-measured and patient-relevant outcomes, including for regulatory purposes, and will be linked to broader health data networks using tokenization, becoming a mainstay for signals about risks and benefits for diverse populations. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Administrative claims databases often do not capture date or fact of death, so studies using these data may inappropriately treat death as a censoring event—equivalent to other withdrawal reasons—rather than a competing event. We examined 1-, 3-, and 5-year inverse-probability-of-treatment weighted cumulative risks of a composite cardiovascular outcome among 34 527 initiators of telmisartan (exposure) and ramipril (referent), who were aged ≥55 years, in Optum (United States) claims data from 2003 to 2020. Differences in cumulative risks of the cardiovascular endpoint due to censoring of death (cause-specific), as compared with treating death as a competing event (subdistribution), increased with greater follow-up time and older age, where event and mortality risks were higher. Among ramipril users, 5-year cause-specific and subdistribution cumulative risk estimates per 100, respectively, were 16.4 (95% CI, 15.3-17.5) and 16.2 (95% CI, 15.1-17.3) among ages 55-64 (difference = 0.2) and were 43.2 (95% CI, 41.3-45.2) and 39.7 (95% CI, 37.9-41.4) among ages ≥75 (difference = 3.6). Plasmode simulation results demonstrated the differences in cause-specific versus subdistribution cumulative risks to increase with increasing mortality rate. We suggest researchers consider the cohort's baseline mortality risk when deciding whether real-world data with incomplete death information can be used without concern. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Aims: The aim of this work is to describe opioid initiation and long‐term use after emergency department (ED) visits or hospitalizations in New South Wales, Australia, by patient, admission and clinical characteristics. Methods: This is a population‐based cohort study, including all hospitalizations and ED visits between 2014 and 2020, linked to medicine dispensings, deaths and cancer registrations (Medicines Intelligence Data Platform), among adults with no opioid dispensings in the previous year. Outcome measures were opioid initiations (dispensed within 7 days of discharge) and long‐term use (90 days of continuous exposure, 90–270 days after initiation). Results: The cohort included 16 153 096 admissions by 4.2 million opioid‐naïve adults; 39.0% were ED presentations without hospital admission, 16.8% hospital admissions via ED and 44.2% direct hospital admissions. Opioids were initiated post‐discharge for 6.2% of ED, 8.3% of hospital via ED and 10.0% of direct hospital admissions; of these 1.0%, 2.5% and 0.5% progressed to long‐term opioid use, respectively. Initiation was lowest in obstetric admissions without surgery (1.0%), and highest among trauma admissions (25.4%), obstetric admissions with surgical intervention (19.8%) and non‐trauma surgical admissions (12.0%). Long‐term use was highest among medical admissions via ED (3.5%), trauma admissions (2.3%) and ED alone (1.0%). From 2014 to 2020, overall opioid initiations decreased 16% from 8.7% to 7.2%, and long‐term opioid use decreased 33% from 1.3% to 0.8%. Conclusions: Both opioid initiation and long‐term use decreased over time; however, the higher rates of long‐term use following trauma, and medical admissions via ED, warrant further surveillance. Strategies supporting appropriate prescribing and access to multidisciplinary pain services will facilitate best practice care. [ABSTRACT FROM AUTHOR]

The most common toxicities associated with cyclin‐dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication‐related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis‐related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib‐induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug‐related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) represents the second most common diagnosed cancer in men. The burden of diagnosis and long-term treatment may frequently cause psychiatric disorders in patients, particularly depression. The most common PC treatment option is androgen deprivation therapy (ADT), which may be associated with taxane chemotherapy. In patients with both PC and psychiatric disorders, polypharmacy is frequently present, which increases the risk of drug–drug interactions (DDIs) and drug-related adverse effects. Therefore, this study aimed to conduct a pharmacoepidemiologic study of the concomitant administration of PC drugs and psychotropics using three drug interaction databases (Lexicomp®, drugs.com®, and Medscape®). This study assayed 4320 drug–drug combinations (DDCs) and identified 814 DDIs, out of which 405 (49.63%) were pharmacokinetic (PK) interactions and 411 (50.37%) were pharmacodynamic (PD) interactions. The most common PK interactions were based on CYP3A4 induction (n = 275, 67.90%), while the most common PD interactions were based on additive torsadogenicity (n = 391, 95.13%). Proposed measures for managing the identified DDIs included dose adjustments, drug substitutions, supplementary agents, parameters monitoring, or simply the avoidance of a given DDC. A significant heterogenicity was observed between the selected drug interaction databases, which can be mitigated by cross-referencing multiple databases in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Since late 2017, the use of ulipristal acetate 5 mg (UPA; Proprietary name: Esmya) has been under review in the European Union, due to an emerging hepatic risk. In February 2018 and in July 2018, the Spanish Agency of Medicines and Medical Devices and the marketing authorization holder put two risk minimization measures (RMM) in place, in order to inform about new safety information and to mitigate this risk. This study aims to assess RMM effectiveness in Spain, by performing an interrupted time‐series (ITS) analyses, between 2014 and 2019. Method: Two quasi‐experimental ITS analyses to examine the use of UPA before and after the RMM release were performed: (a) an ecological study using aggregated data from a drug consumption database; and (b) a study using primary healthcare data gathered from electronic clinical records. Results: Regulatory interventions were associated with an immediate and significant decrease level of DID (the number of DDD dispensed per 100 000 inhabitants and day) and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. However, a change in the slope was not observed and the use started rising again in the last segment of the study period. Conclusion: Despite RMM had an immediate strong impact on UPA use, the last segment upward trend in the long‐term might have been affected by the lack of comparable therapeutic alternatives. Further studies should be performed to confirm the increase trend observed and analyze subsequent measures and additional data. [ABSTRACT FROM AUTHOR]

Purpose: There is increasing recognition of the importance of transparency and reproducibility in scientific research. This study aimed to quantify the extent to which programming code is publicly shared in pharmacoepidemiology, and to develop a set of recommendations on this topic. Methods: We conducted a literature review identifying all studies published in Pharmacoepidemiology and Drug Safety (PDS) between 2017 and 2022. Data were extracted on the frequency and types of programming code shared, and other key open science practices (clinical codelist sharing, data sharing, study preregistration, and stated use of reporting guidelines and preprinting). We developed six recommendations for investigators who choose to share code and gathered feedback from members of the International Society for Pharmacoepidemiology (ISPE). Results: Programming code sharing by articles published in PDS ranged from 1.8% in 2017 to 9.5% in 2022. It was more prevalent among articles with a methodological focus, simulation studies, and papers which also shared record‐level data. Conclusion: Programming code sharing is rare but increasing in pharmacoepidemiology studies published in PDS. We recommend improved reporting of whether code is shared and how available code can be accessed. When sharing programming code, we recommend the use of permanent digital identifiers, appropriate licenses, and, where possible, adherence to good software practices around the provision of metadata and documentation, computational reproducibility, and data privacy. [ABSTRACT FROM AUTHOR]

Background: Hyponatremia is a common electrolyte disturbance and known adverse drug reaction of diuretics. Women tend to be more susceptible for diuretic associated hyponatremia. The aim of this study was to find more evidence whether women have a higher risk of diuretic associated hyponatremia than men measured at hospital admission for specific diuretic groups and whether there is a sex difference in risk of severity of hyponatremia. Methods: All patients using a diuretic and admitted for any reason to Tergooi MC and Haga Teaching hospital in the Netherlands between the 1st of January 2017 and the 31st of December 2021, with recorded sodium levels at admission were included in this study. Cases were defined as patients with a sodium level <135 mmol/L, while control patients had a sodium level =135 mmol/L at admission. Logistic regression analysis was used to calculate odds ratios (OR) with 95% CIs for women versus men and adjusted for potential confounding covariables (age, body mass index, potassium serum level, systolic and diastolic blood pressure, estimated glomerular filtration rate, number of diuretics, comedications and comorbidities). Stratified analyses were conducted for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists), and adjusted for dose. Furthermore, stratified analyses were performed by severity of hyponatremia (severe: <125 mmol/L), mild: 125-134 mmol/L). Results: A total of 2,506 patients (50.0% women) were included, of which 516 had hyponatremia at admission (20.6%, 56.2% women). Women had a statistically significantly higher risk for hyponatremia at admission than men (OR 1.37; 95% CI 1.12-1.66) and after adjustment for potential risk factors (ORadj 1.55; 95% CI 1.22-1.98). Stratified analyses showed increased odds ratios for thiazides (ORadj 1.35; 95% CI 1.00-1.83) and loop diuretics (ORadj 1.62; 95% CI 1.19-2.19) among women. Use of aldosterone antagonists was also increased but not statistically significant (ORadj 1.15; 95% CI 0.73-1.81). Women had a statistically higher risk to develop mild and severe hyponatremia than men (ORadj 1.36; 95% CI 1.10-1.68 and ORadj 1.96; 95%CI 1.04-3.68, respectively). Conclusion: Women have a higher risk of a hospital admission associated with hyponatremia while using diuretics than men. Further research is necessary to provide sex-specific recommendations. [ABSTRACT FROM AUTHOR]