Pharmacoepidemiology, Volume 2, Issue 2 (June 2023) – 6 articles

COVID-19 pandemic-related pressures on primary care may have driven the inappropriate continuation of antibiotic prescriptions. Yet, prescribing modality (repeat/non-repeat) has not previously been investigated in a pandemic context. With the approval of NHS England, we conducted a retrospective cohort study of >19 million English primary care patient records using the OpenSAFELY-TPP analytics platform. We analysed repeat/non-repeat prescribing frequency in monthly patient cohorts between January 2020 and 2022. In-depth analysis was conducted on January 2020 (“pre-pandemic”) and January 2021 (“pandemic”) cohorts (with a particular focus on repeat prescribing). Per-patient prescribing and clinical conditions were determined by searching primary care records using clinical codelists. Prescriptions in a 6-month lookback period were used to delineate repeat prescribing (≥3 prescriptions) and non-repeat prescribing (1–2 prescriptions). Associations between demographics (e.g., age, sex, ethnicity) and prescribing were explored using unadjusted risk ratios. The frequency of clinical conditions among prescribed patients was examined. Antibiotic prescribing declined from May 2020; non-repeat prescribing declined more strongly than repeat prescribing (maximum declines −26% vs. −11%, respectively). Older patients were at a higher risk of prescribing (especially repeat prescribing). Comorbidities were more common among repeat- vs. non-repeat-prescribed patients. In the pandemic cohort, the most common clinical conditions linked to repeat prescribing were COPD comorbidity and urinary tract infection. Our findings inform the ongoing development of stewardship interventions in England, targeting patient groups wherein there is a high prevalence of repeat prescribing. Full article

Late adverse events (LAEs) are an important cause of illness and disability in childhood cancer survivors (CCSs) and increase the risk of mortality. The aim of this cross-sectional study was to describe the frequency and severity of treatment-related LAEs in Mexican CCSs. The study period was between September 2018 and April 2019. We tested a sample of 82 CCSs at the Hospital Infantil de México Federico Gómez. We considered an LAE to be any medical effect related to treatment after ending cancer therapy. All LAEs were classified according to severity (using the grades of Common Terminology Criteria for Adverse Events v.5.0), diagnosis and time of occurrence after treatment. The treatment-related LAE frequency was 11.0% (95% CI; 4.2–17.8%). A total of 11 LAEs were identified in nine patients. Slightly over half of the patients were male (54.9%). The most frequent diagnosis was acute lymphoblastic leukemia (45.1%). The body systems involved in LAEs were the endocrine (55.6%), neurological (22.2%), auditory (11.1%) and renal (11.1%) systems. Obesity was the most frequent LAE (45.4%). Most LAEs were classified as grade 1 and 2 (60%). The median follow-up was 6.5 years. The odds ratio was used as a measure of association to identify characteristics associated with the LAEs. We identified that the age at diagnosis (OR = 0.71, 95% CI, 0.51–0.99; p = 0.046) and chemotherapy-only group (OR = 0.03, 95% CI, 0.00–0.86, p = 0.040) were associated with LAEs. This is the first study that describes the frequency and severity of LAEs in Mexican childhood cancer survivors. Full article

Background: The extensive use of antibiotics has contributed to the development of antibiotic resistance. Understanding the factors behind the attitude of physicians in prescribing antibiotics may be useful to address educational interventions to sensitize them to a more rational use of these drugs. This study aimed to evaluate the general practitioners’ (GPs) characteristics potentially associated with antibiotic prescription in community-dwelling adults from 2000 to 2019. Method: Multivariable linear regression models were performed to evaluate the association of GPs’ characteristics with the mean number of different antibiotics prescribed and the mean number of Defined Daily Doses (DDD) prescribed per patient. Results: We found that GPs older than 60 years prescribed a smaller number of different antibiotics per patient compared to 30–40 years old GPs (mean (standard error) 1.4 (0.5) vs. 1.8 (0.4)). In contrast older GPs prescribed more DDD compared to younger ones (28.9 (0.1) vs. 27.3 (0.3)). GPs prescribed 29 (0.1) DDD for >200 patients on polypharmacy vs. 28 (0.1) DDD for <100 patients on polypharmacy. The mean number of DDD prescribed increased by 5 units and by 16 units for each refill and switch, respectively. Conclusions: Age and number of patients in polypharmacy in charge were found to be associated with higher antibiotic prescriptions. The knowledge of the GPs-related factors could allow the stakeholders to design interventions to sensitize them to a more appropriate use of antibiotics in view of the increasing issue of antibiotic resistance. Full article

We examined eligibility criteria from recent oncology clinical trials to see whether real-world data (RWD) from electronic health records (EHRs) could be used to create external control groups for clinical trials. Trials were identified from the Aggregate Analysis of ClinicalTrials.gov database; the selected trials were for oncology drugs approved by the FDA in 2020. Verbatim text from trial inclusion and exclusion criteria was qualitatively assessed by an expert panel to determine if criteria could be ascertained from structured and unstructured EHR data. Identified criteria were categorized (cancer-related, comorbidity-related, demographic, functional status, and trial operations) and subcategorized. Among 53 identified trials, 20 met the requirements for study inclusion, which included 463 eligibility criteria. Percentages of criteria by category were as follows: cancer-related factors (46%), comorbidities (20%), functional status (18%), trial operations (14%), and demographics (2%). For 18 of the 20 trials, 80% of the eligibility criteria could be ascertained with RWD; for 4 of the 20, it was 100%. When trial operation-specific criteria were excluded, all 20 met the 100% threshold. Our study indicates that both structured and unstructured data from community-based oncology-specific EHRs can be used for determining patient eligibility for external control arms for clinical trials. Full article

This study aimed to systematically review and explore the impact of study methods on the cost of managing adverse drug reactions (ADRs) among hospitalized patients to guide policymakers and researchers. A literature search was conducted in MEDLINE, EMBASE, CINAHL, Cochrane Library, and Google Scholar. The search was restricted to studies from 2000 to 2017. Two authors independently reviewed the studies, assessed their risk of bias, and extracted information for analysis. Data abstraction was based on the study design, ADR reporting, and costing approaches. Of 677 studies identified, 12 were included for analysis. All studies defined ADR according to WHO classifications. The percentage of admission due to ADR ranged from 0.03% to 17.11%. All studies adopted a healthcare provider perspective, using either a micro-costing (n = 7), case-mix group costing (n = 3), or average-per-diem costing (n = 2) approach. The cost per ADR widely fluctuated from USD 65.00 to USD 12,129.90 based on various factors. The micro-costing approach generally had a lower cost compared to other approaches. The cost per ADR in high-income countries was also 10 times higher than in lower- or middle-income countries. This study evidenced that the methodological heterogeneity across studies has resulted in a wide range of cost estimations for ADR management. Full article

Propylene glycol (PG) and benzyl alcohol (BA) have been shown to inhibit the metabolizing enzyme for acetaminophen in the liver. Ethanol has unpredictable effects on acetaminophen metabolism. Critically ill neonates commonly receive drug formulations containing PG, BA, and ethanol as excipients. Until now, there have been no reports on the influence of BA, PG, and ethanol as excipients in patients undergoing concomitant acetaminophen therapy. We devised the present study to evaluate whether any significant differences in plasma acetaminophen concentrations, liver function tests, and serum creatinine exist between neonates receiving excipients containing drugs compared to those without. We included neonates that were administered intravenous acetaminophen with at least one concomitant drug containing either BA, PG, or ethanol as excipients. Plasma acetaminophen concentrations and levels of liver function were evaluated using tests. The doubling of alanine aminotransferase levels was considered to be a marker of hepatotoxicity. Elevation of serum creatinine >1.5 times higher than the baseline value was considered to be indicative of an acute kidney injury. Fifty-seven neonates were recruited in the study. No significant differences in the serum acetaminophen concentrations, liver and renal function tests, and rates of successful closure of ductus arteriosus were observed between the groups. No significant changes in the serum acetaminophen levels and the clinical outcomes were observed due to the presence of BA, PG, or ethanol in concomitant drugs as excipients. Probably, drugs containing these excipients can be safely administered, and even formulations containing these excipients with acetaminophen are likely to be safe for critically ill neonates. Full article