Publications by authors named "Almut Winterstein"

Introduction: Preventing prenatal exposure to teratogenic medications is an important goal of regulatory risk mitigation efforts. In the USA, as of March 2024, 11 teratogenic medications have a required Risk Evaluation and Mitigation Strategy (REMS) program. It is unclear whether these programs target those medications with the most significant impact on public health and adverse pregnancy outcomes.

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Introduction: Medical cannabis (MC) is available upon certification for one of several qualifying conditions in Florida, USA. Previous studies suggested that some people seek cannabis for medical conditions/symptoms beyond those legally permitted. However, data remain limited on patient motives for seeking MC and their experiences around its impact on their health.

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Florida's medical cannabis (marijuana) program is among the largest in the United States. Smokable cannabis forms were not legally available in this program until 2019, and five years after other forms of cannabis were available. This study assessed changes in Δ-9 tetrahydrocannabinol (THC) dispensed per patient following legalization of smokable cannabis in Florida.

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Introduction: With Medicaid covering half of US pregnancies, Medicaid Analytic eXtract (MAX) provides a valuable data source to enrich understanding about stillbirth etiologies.

Objective: We developed and validated a claims-based algorithm to predict GA at stillbirth.

Method: We linked the stillbirths identified in MAX 1999-2013 to Florida Fetal Death Records (FDRs) to obtain clinical estimates of GA (N=825).

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Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events.

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Dual antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers.

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Real-world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE.

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Background: Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents.

Objective: To investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs).

Design: Retrospective cohort study using a target trial emulation framework.

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Background: Cannabis use is associated with higher intravenous anesthetic administration. Similar data regarding inhalational anesthetics are limited. With rising cannabis use prevalence, understanding any potential relationship with inhalational anesthetic dosing is crucial.

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Background: Hypertension among persons with childbearing potential is on the rise. Maintaining proper blood pressure during pregnancy is vital to prevent maternal and neonatal complications. Yet, limited evidence on the risk-benefit of various antihypertensives presents challenges for informed decision-making during this critical period.

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Background: The cost of medically attended RSV LRI (lower respiratory infection) is critical in determining the economic value of new RSV immunoprophylaxes. However, most studies have focused on intermittent RSV encounters, not the episode of care that captures the entirety of RSV illness.

Methods: We created age- and condition-specific cohorts of children under 5 years of age using MarketScan® data (2015-2019).

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Introduction: Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between cannabis use and postoperative pain levels and opioid doses within 24 hours of surgery.

Methods: We conducted a propensity score-matched retrospective cohort study using electronic health records data of 22 476 older surgical patients with at least 24-hour hospital stays at University of Florida Health between 2018 and 2020.

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There is a dearth of safety data on maternal outcomes after perinatal medication exposure. Data-mining for unexpected adverse event occurrence in existing datasets is a potentially useful approach. One method, the Poisson tree-based scan statistic (TBSS), assumes that the expected outcome counts, based on incidence of outcomes in the control group, are estimated without error.

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Article Synopsis
  • The study investigates the accuracy of claims data in identifying Respiratory Syncytial Virus (RSV) as a cause of lower respiratory tract infections (LRTIs) in children, finding that not all cases are properly coded or tested.
  • Researchers used claims data from 2011-2019, along with RSV positivity data, to model the relationship between LRTI rates and RSV, estimating that about 42% of RSV cases were recorded in claims.
  • The findings reveal that a significant percentage of LRTIs are attributed to RSV, but coding inconsistencies exist, prompting recommendations for data adjustments to improve accuracy in estimating RSV incidence.
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Background: Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of antibiotics versus watchful waiting have focused on symptom resolution and RCTs, limiting the assessment of serious, rare complications. We sought to evaluate these complications by including observational studies.

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Background: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.

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Article Synopsis
  • Teratogenic risks linked to valproic acid use are significant for women of childbearing age, prompting regulatory agencies to enhance warnings and risk reduction strategies for pregnant individuals.
  • The study aimed to assess the pregnancy rates of women using valproic acid alongside contraception, utilizing data from a comprehensive commercial claims database spanning from 2005 to 2020.
  • Findings revealed stable pregnancy rates during valproic acid treatment, with mood disorders as the most common indication for its use, while the overall incidence of pregnancy showed little change over the years.
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Purpose: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions.

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Background: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear.

Objectives: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI).

Methods: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y inhibitor treatment were included.

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Real-world data (RWD) and real-world evidence (RWE) are now being routinely used in epidemiology, clinical practice, and post-approval regulatory decisions. Despite the increasing utility of the methodology and new regulatory guidelines in recent years, there remains a lack of awareness of how this approach can be applied in clinical pharmacology and translational research settings. Therefore, the American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a workshop on March 21st, 2023 entitled "Advancing the Utilization of Real-World Data (RWD) and Real-World Evidence (RWE) in Clinical Pharmacology and Translational Research.

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Background: Limited evidence exists on the short- and long-term safety of discontinuing versus continuing chronic opioid therapy (COT) among patients with Alzheimer's disease and related dementias (ADRD).

Methods: This cohort study was conducted among 162,677 older residents with ADRD and receipt of COT using a 100% Medicare nursing home sample. Discontinuation of COT was defined as no opioid refills for ≥90 days.

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Background: There are limited population-based data on the role of mental disorders in adolescent pregnancy, despite the presence of mental disorders that may affect adolescents' desires and decisions to become pregnant.

Objective: This study aimed to examine the relationship between specific types of mental disorders and pregnancy rates and outcome types among adolescents aged 13-19 years, using single-year age groups.

Methods: We conducted a retrospective cohort study using data from the Merative™ MarketScan Research Databases.

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Article Synopsis
  • - The updated Reporting recommendations for pharmaceutical risk Minimization Evaluation Studies (RIMES) aims to enhance how evaluations of risk minimization programs are reported, addressing past inadequacies and high-profile failures in program implementation.
  • - The RIMES-StaRI Extension (RIMES-SE) was created by developing a study protocol, mapping existing RIMES items against a new checklist, and gathering expert feedback to identify key reporting elements.
  • - With 27 items, the RIMES-SE features a dual structure detailing both the risk minimization program and its implementation strategy, and is designed to improve reporting quality across various research methods to boost drug safety science.
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