Pharmacoepidemiology and Drug Safety最新文献

Purpose: Clinicians treating patients with atrial fibrillation (AF) on oral anticoagulants who undergo surgery for chronic subdural hematoma (CSDH) face a dilemma: while early postoperative resumption of anticoagulation is necessary to prevent embolism, it may increase the risk of CSDH recurrence. To date, however, no study has evaluated this question while adequately addressing common biases in observational studies. Here, we assessed this issue using target trial emulation framework.

Methods: We identified patients undergoing initial CSDH surgery who had received anticoagulation for AF preoperatively from two hospital-based administrative databases (2014-2022). We compared two treatment strategies: resumption of anticoagulation within 14 days postoperatively versus no resumption during this period. Using a three-step method of cloning, censoring, and weighting, we estimated the risk of CSDH recurrence, along with the risk ratio and risk difference at postoperative day 90.

Results: 291 CSDH patients with AF were eligible, of whom 29 (10.0%) underwent CSDH reoperation. The weighted estimated 90-day reoperation risk was 11.7% (95% confidence interval [CI], 6.0 to 14.3) for resuming anticoagulation within 14 days postoperatively and 9.4% (95% CI, 4.1 to 12.8) for not resuming within 14 days, corresponding to a risk ratio of 1.20 (95% CI, 0.67 to 2.36) and risk difference of 1.9% (95% CI, -4.0 to 6.6).

Conclusions: 90-day risk of CSDH recurrence may not differ between early and non-early resumption of anticoagulation, although early resumption could modestly accelerate recurrence. Allowing for the imprecision of the estimates, these findings provide important insights for clinical decision-making regarding anticoagulation resumption.

Objective: The objective of this study is to estimate the association between physician's age, sex, clinical and communication competencies, and cultural background on benzodiazepines and Z-drugs (BDZ) prescribing to older adults with insomnia.

Methods: A cohort of international medical graduates (IMGs) who completed their pre-residency licensure exam in 1998-2004 were linked to all U.S. Medicare patients they provided care to in 2014-2015. Their care records in Parts A, B, and D from all physicians were extracted. The first outpatient visit for insomnia to a study IMG was identified for each patient in that period. The outcome was incident BDZ prescribing by the study physician following the visit. Main exposures were physician age, sex, citizenship at birth, and clinical and communication competency as measured on the licensure exam. The association between physician characteristics and BDZ prescribing, adjusting for physician and patient covariates, was estimated using generalized estimating equations multivariable logistic regression.

Results: We analyzed 28 018 patients seen by 4069 unique physicians. IMGs born in all other regions of the world were less likely to prescribe BDZs compared to U.S.-born IMGs, with physicians from the United Kingdom being least likely (OR 0.54 [95%CI 0.34-0.85]). Neither physician's clinical competency nor communication ability were associated with BDZ prescribing (OR per 10% increase, respectively: 0.95 [95%CI 0.88-1.02] and 0.98 [95%CI 0.93-1.04]). Older physicians remain more likely to prescribe BDZ (OR per 5-year increase 1.04 [95%CI 1.00-1.08]).

Conclusions: The associations between cultural background and physician's age on BDZ prescribing highlight the potential targets for remedial solutions to reduce the use of potentially inappropriate medications.

Purpose: The purpose of this study was to describe the intensity and patterns of antibiotic drug use among people with multiple sclerosis (pwMS) in the Netherlands.

Methods: People with prevalent MS between 1 January 2018 and 31 December 2020 were identified using ambulatory hospital records from the PHARMO Database Network that contains routinely collected healthcare data from the Netherlands. Out-patient pharmacy dispensing data were used to assess type of antibiotic, dosage, and amounts dispensed. Antibiotic intensity in defined daily doses (DDD)/1000 patient-days (PD) was calculated together with frequency of dispensing of the same (prolongation) or different (switch) antibiotic up to 3 days after the end of the last antibiotic prescription; and stratified by sex, age, polypharmacy (use of > 4 out-patient prescription drugs for > 29 days), type of disease-modifying treatment, and Sars-CoV-2-related lockdown.

Results: A total of 1960 (37.8%) out of 5179 pwMS were dispensed ≥ 1 antibiotic. Of the 8762 dispensing events, 27.6%% were part of a prolongation, and 16.3% of a switch. Overall antibiotic use among pwMS was 18.8 DDD/1000 PD (95% confidence interval [95% CI]: 18.7-19.0) compared to 7.77-8.90 DDD/1000 PD in the general out-patient population, as reported by the Dutch Working Party on Antibiotic Policy. Antibiotic use was higher among women, increased with age, and was higher in people with polypharmacy and lower during lockdown. Nitrofurantoin was the most commonly dispensed antibiotic (41.7%).

Conclusions: The intensity of antibiotic use is considerably higher among pwMS than the general population. This reflects the burden of infection in this susceptible population.

In this article, we review the history and key reasons for new-user comparisons in pharmacoepidemiology, highlighting the target trial framework as a unifying framework. We describe three distinct pharmacoepidemiological new-user study designs: (1) new-user versus non-user; (2) active comparator new-user; (i.e., ACNU) and (3) prevalent new-user (i.e., PNU) designs, and discuss how each relates to key issues of defining time zero, choosing appropriate comparator groups, and potential sources of bias they do and do not account for. We use a clinical example of hormone replacement therapy and the risk of coronary heart disease to illustrate practical considerations surrounding the application of the three designs presented.

Purpose: The underreporting of adverse drug reactions (ADRs) remains a significant challenge in the Philippines. Pharmacists play a crucial role in ensuring medication safety, improving patient outcomes, and enhancing the overall effectiveness of pharmacovigilance (PV) systems. This study explored the barriers and facilitators affecting PV practices among pharmacists in Metro Manila.

Methods: This study employed qualitative research through in-depth interviews using a semi-structured topic guide. Researchers interviewed pharmacists until data saturation was reached, where no new insights emerged. Qualitative data were analyzed inductively, utilizing Braun and Clarke's thematic analysis to identify key themes. MAXQDA was used to facilitate coding and analyzing the qualitative data.

Results: A total of 40 pharmacists (72.5% female) participated in this study, evenly distributed across various practice areas and geographic locations in Metro Manila. The analysis identified four main themes related to pharmacists' nonreporting of ADRs: competency gaps, organizational challenges, reporting issues, and workplace constraints. Pharmacists' limited knowledge of ADRs and lack of experience in ADR reporting appear to be the primary barriers, along with environmental factors. Conversely, critical strategies for improving ADR notifications include capacity building, motivation and rewards, and work optimization.

Conclusion: Pharmacists recognize the importance of reporting ADRs and view it as a professional responsibility. By prioritizing knowledge enhancement, training, and system improvements, the identification and reporting of ADRs can be strengthened, ultimately enhancing patient safety and PV practices. This positive attitude toward ADR reporting lays the groundwork for interventions designed to overcome barriers and promote a culture of active reporting among pharmacists.

Purpose: The largest rural outbreak of human immunodeficiency virus (HIV) in the US was centered in Scott County, Indiana, and linked to injection practices involving the opioid Opana ER (oxymorphone extended release [ER] reformulated). We examined supply trends using pharmacy transactions of Opana ER in Scott and all US counties from January 2007 to December 2019.

Methods: We calculated the monthly morphine milligram equivalents (MME) of Opana ER (and its competitor OxyContin) in pharmacies using the Automation of Reports and Consolidated Orders System (ARCOS) database from the Washington Post. We modeled the MME rate per capita in Scott County and five geographic comparators in seven distinct time periods including the market introduction of abuse deterrent formulations of both drugs and the HIV outbreak period (circa 2014).

Results: After Opana ER introduction, transaction rates surged in Scott County, where annual OxyContin MMEs were already seven-fold higher than Indiana overall (CY2009: 46.8 vs. 6.8 MME/pop., respectively). Immediately after OxyContin's reformulation, the Opana ER growth rate in Scott County surpassed all geographic comparators modeled (~27 times faster than the US, 1.28 vs. 0.047 MME/pop/month, respectively). By 2012, prior to the outbreak, MMEs from Opana ER almost perfectly replaced the diminishing OxyContin supply. When Opana ER with INTAC was subsequently introduced, pharmacy transactions declined precipitously by nearly 50%, persisting through the HIV outbreak period and market withdrawal.

Conclusions: Opana ER rapidly supplanted OxyContin in a vulnerable population that was at heightened risk for HIV who subsequently faced an immediate supply shock after its reformulation. Pharmacy transactions are critical for suspicious order monitoring and pharmacovigilance by US and international agencies especially during deleterious supply shocks in legal and illicit drug markets.

Purpose: Survivors of critical illness are often affected by new or worsened mental health conditions and sleep disorders. We examined the incidence, practice variation and factors associated with new benzodiazepine and z-drug community prescriptions among critical illness survivors.

Methods: A retrospective cohort study using the UK Clinical Practice Research Datalink data included 52 846 adult critical care survivors hospitalised in 2010 and 2018 who were not prescribed benzodiazepines or z-drugs before hospitalisation. We performed multilevel multivariable logistic regression to assess patient factors associated with new (any prescription within 90 days) and with new-and-persistent (2+ prescriptions within 180 days) benzodiazepine or z-drug prescribing, and to evaluate variation by primary care practice.

Results: 5.2% (2769/52846) of treatment-naïve survivors (95% CI 5.1-5.4) were prescribed a benzodiazepine or z-drug, and 2.5% (1311/52846) had new-and-persistent prescribing. A history of insomnia (adjusted OR 1.96; 95% CI 1.74-2.21), anxiety or depression (adjusted OR 1.40; 95% CI 1.28-1.53) and recent prescription opioid use (adjusted OR 1.47; 95% CI 1.34-1.61) were associated with new community prescription. Sex was not associated with new prescriptions and older patients were less likely to receive a prescription. 2.6% of the variation in new prescribing and 4.1% of the variation in new-and-persistent prescribing were attributable to the prescribing practice.

Conclusions: One in twenty critical illness survivors receive a new community benzodiazepine or z-drug prescription. Further research is needed to understand where in the patient care pathway initiation occurs and the risk of adverse events in survivors of recent critical illness.

Introduction: Determining lines of therapy (LOT) using real-world data is crucial to inform clinical decisions and support clinical research. Existing rules for determining LOT in patients with metastatic non-small cell lung cancer (mNSCLC) do not incorporate the growing number of targeted therapies used in treatment today. Therefore, we propose rules for determining LOT from real-world data of patients with mNSCLC treated with targeted therapies.

Methods: LOT rules were developed through expert consensus using a real-world cohort of 550 patients with ALK+ or ROS1+ mNSCLC in the multi-institutional, electronic medical record-based Academic Thoracic Oncology Medical Investigators Consortium's (ATOMIC) Driver Mutation Registry. Rules were subsequently modified based on a review of appropriate LOT determination. These resulting rules were then applied to an independent cohort of patients with EGFR+ mNSCLC to illustrate their use.

Results: Six rules for determining LOTs were developed. Among 1133 patients with EGFR mutations and mNSCLC, a total of 3168 regimens were recorded with a median of 2 regimens per patient (IQR, 1-4; range, 1-13). After applying our rules, there were 2834 total LOTs with a median of 2 LOTs per patient (IQR, 1-3; range, 1-11). Rules 1-3 kept 11% of regimen changes from advancing the LOT. When compared to previously published rules, LOT assignments differed 5.7% of the time, mostly in LOTs with targeted therapy.

Conclusion: These rules provide an updated framework to evaluate current treatment patterns, accounting for the increased use of targeted therapies in patients with mNSCLC, and promote standardization of methods for determining LOT from real-world data.

Background: Determining a therapeutic window for maintaining antiretroviral drug concentrations within an appropriate range is required for identifying effective dosing regimens. The limits of this window are typically calculated using predictive models. We propose that target concentrations should instead be calculated based on counterfactual probabilities of relevant outcomes and describe a counterfactual framework for this.

Methods: The proposed framework is applied in an analysis including longitudinal observational data from 125 HIV-positive children treated with efavirenz-based regimens within the CHAPAS-3 trial, which enrolled children < 13 years in Zambia/Uganda. A directed acyclic graph was developed to visualize the mechanisms affecting antiretroviral concentrations. Causal concentration-response curves, adjusted for measured time-varying confounding of weight and adherence, are calculated using g-computation.

Results: The estimated curves show that higher concentrations during follow-up, 12/24 h after dose, lead to lower probabilities of viral failure (> 100 c/mL) at 96 weeks of follow-up. Estimated counterfactual failure probabilities under the current target range of 1-4 mg/L range from 24% to about 2%. The curves are almost identical for slow, intermediate and extensive metabolizers and show that a mid-dose concentration level of ≥ 3.5 mg/L would be required to achieve a failure probability of < 5%.

Conclusions: Our analyses demonstrate that a causal approach may lead to different minimum concentration limits than analyses that are based on purely predictive models. Moreover, the approach highlights that indirect causes of failure, such as patients' metabolizing status, may predict patients' failure risk, but do not alter the threshold at which antiviral activity of efavirenz is severely reduced.