Metformin and risk of adverse pregnancy outcomes among pregnant women with gestational diabetes in the United Kingdom: A population-based cohort study.

Aims: Metformin is increasingly used off-label as the treatment of gestational diabetes (GDM). Our objective was to determine if metformin versus insulin initiation is associated with the adverse pregnancy outcomes.

Materials And Methods: We conducted a retrospective cohort study using data from the Clinical Practice Research Datalink, its pregnancy register, and Hospital Episode Statistics from 1998 to 2018.

Modern Sources of Controls in Case-Control Studies.

In 1992, Wacholder and colleagues developed a theoretical framework for case-control studies to minimize bias in control selection. They described three comparability principles (study base, deconfounding, and comparable accuracy) to reduce the potential for selection bias, confounding, and information bias in case-control studies. Wacholder et al.

Development of a Canadian Guidance for reporting real-world evidence for regulatory and health-technology assessment (HTA) decision-making.

Background And Objective: Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making.

Exposure to Valsartan Products Containing Nitrosamine Impurities in the United States, Canada, and Denmark.

Background: Following the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the United States, Canada, and Denmark.

Methods: We conducted a retrospective cohort study using administrative healthcare data from the US FDA Sentinel System, four Canadian provinces that contribute to the Canadian Network for Observational Drug Effect Studies (CNODES), and the Danish National Prescription Registry.

Levothyroxine Treatment of Subclinical Hypothyroidism and the Risk of Adverse Cardiovascular Events.

There is uncertainty as to whether treatment of subclinical hypothyroidism (SCH) is associated with cardiovascular outcomes. To determine whether levothyroxine replacement therapy decreases the risk of major adverse cardiovascular events (MACE) among individuals with SCH defined as having a thyrotropin (TSH) level between 5 and 10 mU/L. We conducted a population-based cohort study using a prevalent new-user design.

Structured learning in time-dependent Cox models.

Cox models with time-dependent coefficients and covariates are widely used in survival analysis. In high-dimensional settings, sparse regularization techniques are employed for variable selection, but existing methods for time-dependent Cox models lack flexibility in enforcing specific sparsity patterns (ie, covariate structures). We propose a flexible framework for variable selection in time-dependent Cox models, accommodating complex selection rules.

Fluoroquinolones and the risk of severe hypoglycaemia among sulphonylurea users: Population-based cohort study.

Aim: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas.

Materials And Methods: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020).

What is the ideal time to begin tapering opioid agonist treatment? A protocol for a retrospective population-based comparative effectiveness study in British Columbia, Canada.

Introduction: Opioid agonist treatment (OAT) tapering involves a gradual reduction in daily medication dose to ultimately reach a state of opioid abstinence. Due to the high risk of relapse and overdose after tapering, this practice is not recommended by clinical guidelines, however, clients may still request to taper off medication. The ideal time to initiate an OAT taper is not known.

Variable selection when estimating effects in external target populations.

External validity is an important part of epidemiologic research. To validly estimate effects in specific external target populations using a chosen effect measure (ie, "transport"), some methods require that one account for all effect measure modifiers (EMMs). However, little is known about how including other variables that are not EMMs (ie, non-EMMs) in adjustment sets affects estimates.

Effectiveness and safety of direct oral anticoagulants among patients with non-valvular atrial fibrillation and liver disease: A multinational cohort study.

Background And Aims: The effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population.

Methods: We assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020.

Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding.

Importance: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized.

Objectives: To assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk.

Standardizing to specific target populations in distributed networks and multisite pharmacoepidemiologic studies.

Distributed network studies and multisite studies assess drug safety and effectiveness in diverse populations by pooling information. Targeting groups of clinical or policy interest (including specific sites or site combinations) and applying weights based on effect measure modifiers (EMMs) prior to pooling estimates within multisite studies may increase interpretability and improve precision. We simulated a 4-site study, standardized each site using inverse odds weights (IOWs) to resemble the 3 smallest sites or the smallest site, estimated IOW-weighted risk differences (RDs), and combined estimates with inverse variance weights (IVWs).

Prescribing trends of proton pump inhibitors and histamine blockers among children in the United Kingdom (1998-2019): A population-based assessment.

Purpose: To describe the prescribing trends of proton pump inhibitors (PPIs) and H receptor antagonists (H RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019.

Methods: We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all children aged ≤18 years with a first ever diagnosis of gastroesophageal reflux between 1998 and 2019. Using negative binomial regression, we estimated crude and adjusted annual prescription rates per 1000 person-years and corresponding 95% confidence intervals (CIs) for PPIs and H RAs.

Comparative Analysis of Instrumental Variables on the Assignment of Buprenorphine/Naloxone or Methadone for the Treatment of Opioid Use Disorder.

Background: Instrumental variable (IV) analysis provides an alternative set of identification assumptions in the presence of uncontrolled confounding when attempting to estimate causal effects. Our objective was to evaluate the suitability of measures of prescriber preference and calendar time as potential IVs to evaluate the comparative effectiveness of buprenorphine/naloxone versus methadone for treatment of opioid use disorder (OUD).

Methods: Using linked population-level health administrative data, we constructed five IVs: prescribing preference at the individual, facility, and region levels (continuous and categorical variables), calendar time, and a binary prescriber's preference IV in analyzing the treatment assignment-treatment discontinuation association using both incident-user and prevalent-new-user designs.

The International Working Group on New Developments in Pharmacovigilance: Advancing Methods and Communication in Pharmacovigilance.

Purpose: In 2019, the International Working Group (IWG), focusing on New Developments in Pharmacovigilance, was established. This group is coordinated by the Drug Safety Research Unit in the United Kingdom, and the mission of the IWG is to progress pharmacovigilance methodologies and promote the safe and effective use of medicines and vaccines, thereby further protecting patients. Novel therapeutics are continuously being developed to alleviate medical conditions, but with advancing technologies, innovative pharmacovigilance methodologies need to be developed to effectively monitor the use and safety of these products.

Impact of COVID-19 Pandemic on Dispensing of Cardiovascular Drugs in Norway: An Interrupted Time Series Study.

Introduction: The COVID-19 pandemic resulted in changes in prescription patterns and fillings for certain medications, but little is known about its impact on the dispensing of cardiovascular drugs.

Methods: Trends in dispensing of cardiovascular drugs before and during the pandemic were examined using a population-based cohort in Norway. Using interrupted time series analyses and considering March 1, 2020 as the interruption point, the impact of the pandemic on defined daily dose dispensing of prescribed cardiovascular drugs was estimated in a population of adults with and without pre-existing cardiovascular disease from January 2018 to December 2021.

Dipeptidyl peptidase-4 inhibitors and the risk of skin cancer among patients with type 2 diabetes: a UK population-based cohort study.

Introduction: The dipeptidyl peptidase-4 (DPP-4) enzyme significantly influences carcinogenic pathways in the skin. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas.

Research Design And Methods: Using the United Kingdom Clinical Practice Research Datalink, we assembled two new-user active comparator cohorts for each skin cancer outcome from 2007 to 2019.

Levothyroxine initiation and the risk of pregnancy loss among pregnant women with subclinical hypothyroidism: An observational study emulating a target trial.

Background: While the benefits of levothyroxine are well-established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women.

Objective: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data.

Methods: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care.

Glucagon like peptide-1 receptor agonists and the risk of skin cancer among patients with type 2 diabetes: Population-based cohort study.

Aims: The objective of this study was to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is associated with an increased risk of melanoma and nonmelanoma skin cancer, separately, compared with the use of sulfonylureas among patients with type 2 diabetes.

Methods: Using the United Kingdom Clinical Practice Research Datalink (2007-2019), we assembled two new-user active comparator cohorts. In the first cohort assessing melanoma as the outcome, 11,786 new users of GLP-1 RAs were compared with 208,519 new users of sulfonylureas.

Type of infertility and prevalence of congenital malformations.

Background: Children conceived with assisted reproductive technologies (ART) or after a long waiting time have a higher prevalence of congenital malformations, but few studies have examined the contribution of type of infertility.

Objectives: To quantify the association between causes of infertility and prevalence of malformations.

Methods: We compared the prevalence at birth of all and severe malformations diagnosed up to age 2 between 6656 children born in 1996-2017 to parents who had previously been assessed for infertility a an academic fertility clinic ("exposed") and 10,382 children born in the same period to parents with no recent medical history of infertility ("reference").