Sales and regulatory status of fixed dose combination psychotropic drugs in India: a retrospective longitudinal study.

Background: There is limited evidence to support use of fixed dose combination (FDC) drugs in the treatment of psychiatric disorders. This study aimed to examine the sales and regulatory status of psychotropic FDCs in India, in the context of two government regulatory initiatives.

Methods: Official documents were searched to establish an account of the initiatives and measures targeting psychotropic FDCs.

Statistical methods leveraging the hierarchical structure of adverse events for signal detection in clinical trials: a scoping review of the methodological literature.

Background: In randomised controlled trials with efficacy-related primary outcomes, adverse events are collected to monitor potential intervention harms. The analysis of adverse event data is challenging, due to the complex nature of the data and the large number of unprespecified outcomes. This is compounded by a lack of guidance on best analysis approaches, resulting in widespread inadequate practices and the use of overly simplistic methods; leading to sub-optimal exploitation of these rich datasets.

Temporal Exploration of COPD Phenotypes: Insights from the COPDGene and SPIROMICS Cohorts.

Background: Chronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships.

Methods: Cross-sectional data from 8,972 tobacco-exposed COPDGene participants, with and without COPD, were used to train a model with EPGA, using thirty clinical, physiologic and CT features.

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

Background: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety.

Objectives: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes.

Methods: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified.

Temporal trend of first-line drug choice and treatment continuity for hypertension among citizens 75 years or over - a register-based, cohort study.

Background: Limited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021.

Methods: Using nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified.

Transcriptomics analysis of the bovine endometrium during the perioestrus period.

During the oestrous cycle, the bovine endometrium undergoes morphological and functional changes, which are regulated by alterations in the levels of oestrogen and progesterone and consequent changes in gene expression. To clarify these changes before and after oestrus, RNA-seq was used to profile the transcriptome of oestrus-synchronized beef heifers. Endometrial samples were collected from 29 animals, which were slaughtered in six groups beginning 12 h after the withdrawal of intravaginal progesterone releasing devices until seven days post-oestrus onset (luteal phase).

Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study.

Background And Aims: A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis.

Methods: Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018-21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication.

Regulatory enforcement of the marketing of fixed-dose combinations in India: a case study of systemic antibiotics.

Background: In India, states have licensed the manufacture of large numbers of fixed-dose combination (FDC) drugs without the required prior approval of the central regulator. This paper describes two major regulatory initiatives to address the problem, which began in 2007 and 2013, and examines whether they have been sufficient to remove centrally unapproved systemic antibiotic FDCs from the market.

Methods: Information was extracted from documents published by the central regulator and the ministry of health, including the National List of Essential Medicines (NLEM), and court judgments, and analysed alongside sales volume data for 2008-2020 using PharmaTrac market dataset.

Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus.

Background: Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy.

Objectives: The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM.

Methods: Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis.

Systemic antibiotic sales and WHO recommendations, India.

Objective: To analyse sales of fixed-dose combination and single antibiotics in India in relation to World Health Organization (WHO) recommendations and national regulatory efforts to control antibiotic sales.

Methods: We extracted data on sales volumes of systemic antibiotics in India from a market research company sales database. We compared the market share of antibiotic sales in 2020 by WHO AWaRe (Access, Watch and Reserve) category and for those under additional national regulatory controls.

Changing co-morbidity and increasing deprivation among people living with HIV: UK population-based cross-sectional study.

Background: The great success of HIV treatments means that, increasingly, people living with HIV (PLHIV) are growing old enough to develop age-associated comorbid conditions. We investigated the evolution of comorbid conditions and demographics among PLHIV in England.

Methods: In a cross-sectional study linking Clinical Practice Research Datalink (CPRD) primary care, hospitalization, death registry and Index of Multiple Deprivation data, we measured the prevalence of 304 individual health conditions, categorized into 47 condition groups (36 non-communicable, 11 communicable).

Prescribing direct-acting oral anticoagulants - Mind the evidence gap.

Direct-acting oral anticoagulants (DOACs) are licensed for the prevention of thromboembolism in non-valvular atrial fibrillation, amongst other indications. Prescribers use information derived from the summary of product characteristics which is based on the key trials supporting the DOAC's market authorisation. However, prescribers may not be aware of the limitations within these trials regarding underrepresentation of patient populations commonly encountered in clinical practice and how this may adversely impact them.

Health conditions in adults with HIV compared with the general population: A population-based cross-sectional analysis.

Background: Life expectancy in adults with human immunodeficiency virus (HIV) has increased and managing other health conditions is increasingly important for patients and healthcare planning. The aim of this study was to examine the prevalence and association between different health conditions and HIV status.

Methods: We performed a cross-sectional analysis of adult UK Clinical Practice Research Datalink primary care electronic medical records linked to hospital admissions as of Nov 30, 2015.

Adverse Events Associated With Coprescription of Phosphodiesterase Type 5 Inhibitors and Oral Organic Nitrates in Male Patients With Ischemic Heart Disease : A Case-Crossover Study.

Background: Concomitant use of oral organic nitrates (nitrates) and phosphodiesterase type 5 (PDE5) inhibitors is contraindicated.

Objective: To measure temporal trends in the coprescription of nitrates and PDE5 inhibitors and to measure the association between cardiovascular outcomes and the coprescription of nitrates with PDE5 inhibitors.

Design: Case-crossover design.

Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran.

Background: Bleeding safety in relation to use of systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban, or dabigatran is insufficiently explored, despite clinical relevance and several reports suggesting associations.

Methods: Using nationwide Danish registers, we identified patients with atrial fibrillation initiated on apixaban, rivaroxaban, or dabigatran from 2012-2018. We investigated associations between bleeding incidents and systemic fluconazole or topical azole treatment using a case-crossover design with 30-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI).

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants.

Objective: Gastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.

Methods: This is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012-2018.

Capturing Data in Rare Disease Registries to Support Regulatory Decision Making: A Survey Study Among Industry and Other Stakeholders.

Introduction: In rare diseases, registry-based studies can be used to provide natural history data pre-approval and complement drug efficacy and/or safety knowledge post-approval.

Objective: The objective of this study was to investigate the opinion of stakeholders about key aspects of rare disease registries that are used to support regulatory decision making and to compare the responses of employees from industry to other stakeholders.

Methods: A web-based survey was used to gauge the importance of (1) common data elements (including safety outcomes), (2) data quality and (3) governance aspects that are generic across different rare diseases.

Effect of long-term beta-blocker treatment following myocardial infarction among stable, optimally treated patients without heart failure in the reperfusion era: a Danish, nationwide cohort study.

Aims: We aimed to investigate the long-term cardio-protective effect associated with beta-blocker (BB) treatment in stable, optimally treated myocardial infarction (MI) patients without heart failure (HF).

Methods And Results: Using nationwide registries, we included patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated with both acetyl-salicylic acid and statins post-discharge between 2003 and 2018. Patients with prior history of MI, prior BB use, or any alternative indication or contraindication for BB treatment were excluded.

Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study.

Objective: To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19.

Design: Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender.

Pregnancy protection and pregnancies in women prescribed ACE inhibitors or ARBs: a cross-sectional study in primary care.

Background: The teratogenic risks of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are well documented, but prescribing these in younger women in primary care is becoming increasingly frequent.

Aim: To record how frequently women of childbearing age, who are prescribed an ACE inhibitor or ARB, receive preconception advice and/or are prescribed contraception, and how many pregnancies, terminations, and miscarriages occur in this population. Additionally, to ascertain whether patterns in the above differ across age groups.