Evaluating different physician's prescribing preference based instrumental variables in two primary care databases: a study of inhaled long-acting beta2-agonist use and the risk of myocardial infarction.

Purpose: Instrumental variable (IV) analysis with physician's prescribing preference (PPP) as IV is increasingly used in pharmacoepidemiology. However, it is unclear whether this IV performs consistently across databases. We aimed to evaluate the validity of different PPPs in a study of inhaled long-acting beta2-agonist (LABA) use and myocardial infarction (MI).

Instrumental variables analysis using multiple databases: an example of antidepressant use and risk of hip fracture.

Purpose: Instrumental variable (IV) analysis can control for unmeasured confounding, yet it has not been widely used in pharmacoepidemiology. We aimed to assess the performance of IV analysis using different IVs in multiple databases in a study of antidepressant use and hip fracture.

Methods: Information on adults with at least one prescription of a selective serotonin reuptake inhibitor (SSRI) or tricyclic antidepressant (TCA) during 2001-2009 was extracted from the THIN (UK), BIFAP (Spain), and Mondriaan (Netherlands) databases.

Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

Background: Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture.

Methods: A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009.

Case-only designs for studying the association of antidepressants and hip or femur fracture.

Purpose: The purpose of this study is to evaluate the performance and validity of the case-crossover (CCO) and self-controlled case-series (SCCS) designs when studying the association between hip/femur fracture (HF) and antidepressant (AD) use in general practitioner databases. In addition, comparability with cohort and case-control designs is discussed.

Methods: Adult patients with HF and who received an AD prescription during 2001-2009 were identified from UK's The Health Improvement Network (THIN) and the Dutch Mondriaan databases.

Understanding inconsistency in the results from observational pharmacoepidemiological studies: the case of antidepressant use and risk of hip/femur fractures.

Purpose: Results from observational studies on the same exposure-outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs.

Methods: Cohort and nested case control studies were conducted in three European primary care databases (Spanish BIFAP, Dutch Mondriaan and UK THIN) to assess the association between use of antidepressants and hip/femur fracture.

Single dose efficacy evaluation of two partial benzodiazepine receptor agonists in photosensitive epilepsy patients: A placebo-controlled pilot study.

Benzodiazepines (BZDs) are highly effective to suppress various types of seizures; however, their clinical use is limited due to adverse effects and tolerance and dependence liability. Drugs that act only as partial agonists at the BZD recognition site (initially termed "BZD receptor") of the GABAA receptor chloride ionophore complex or exhibit a GABAA receptor subtype-selectivity are thought to have advantages vs. full agonists such as diazepam and most other clinically used BZDs in that such compounds have less adverse effects and reduced or absent tolerance and dependence liability.

Tailoring treatments using treatment effect modification.

Background And Objective: Applying results from clinical studies to individual patients can be a difficult process. Using the concept of treatment effect modification (also referred to as interaction), defined as a difference in treatment response between patient groups, we discuss whether and how treatment effects can be tailored to better meet patients' needs.

Results: First we argue that contrary to how most studies are designed, treatment effect modification should be expected.

Do Self-Management Interventions Work in Patients With Heart Failure? An Individual Patient Data Meta-Analysis.

Background: Self-management interventions are widely implemented in the care for patients with heart failure (HF). However, trials show inconsistent results, and whether specific patient groups respond differently is unknown. This individual patient data meta-analysis assessed the effectiveness of self-management interventions in patients with HF and whether subgroups of patients respond differently.

Identifying components of self-management interventions that improve health-related quality of life in chronically ill patients: Systematic review and meta-regression analysis.

Objective: To quantify diversity in components of self-management interventions and explore which components are associated with improvement in health-related quality of life (HRQoL) in patients with chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), or type 2 diabetes mellitus (T2DM).

Methods: Systematic literature search was conducted from January 1985 through June 2013. Included studies were randomised trials in patients with CHF, COPD, or T2DM, comparing self-management interventions with usual care, and reporting data on disease-specific HRQoL.

Chemotherapy effectiveness and mortality prediction in surgically treated osteosarcoma dogs: A validation study.

Canine osteosarcoma is the most common bone cancer, and an important cause of mortality and morbidity, in large purebred dogs. Previously we constructed two multivariable models to predict a dog's 5-month or 1-year mortality risk after surgical treatment for osteosarcoma. According to the 5-month model, dogs with a relatively low risk of 5-month mortality benefited most from additional chemotherapy treatment.

The "Efficacy-Effectiveness Gap": Historical Background and Current Conceptualization.

Background: The concept of the "efficacy-effectiveness gap" (EEG) has started to challenge confidence in decisions made for drugs when based on randomized controlled trials alone. Launched by the Innovative Medicines Initiative, the GetReal project aims to improve understanding of how to reconcile evidence to support efficacy and effectiveness and at proposing operational solutions.

Objectives: The objectives of the present narrative review were 1) to understand the historical background in which the concept of the EEG has emerged and 2) to describe the conceptualization of EEG.

Which dogs with appendicular osteosarcoma benefit most from chemotherapy after surgery? Results from an individual patient data meta-analysis.

Osteosarcoma (OS) is a malignant tumor of mesenchymal origin that produces osteoid. Given that the prognosis can vary considerably between dogs, we aimed to explore whether treatment could be tailored towards patient subgroups, characterized by their predicted risk of mortality. For the current study, a subset of five nonrandomized studies (400 subjects of whom 88 were dead at 5 months follow-up) was used from a previously published 20 study individual patient data meta-analysis.

Pessary placement in the prevention of preterm birth in multiple pregnancies: a propensity score analysis.

Objective: In asymptomatic women with a multiple pregnancy and short cervix prophylactic use of a cervical pessary might reduce preterm birth. We assessed the possible treatment effects of pessary use in pregnancy duration and for poor perinatal outcome.

Study Design: This cohort study was performed between December 2012 and September 2014 in 44 hospitals in the Netherlands.

Risk indicators for referral during labor from community midwife to gynecologist: a prospective cohort study.

Objective: To identify risk indicators for referral during labor from community midwife to a gynecologist in a prospective cohort of women with a singleton term pregnancy, starting labor with a community midwife between 2000 and 2007, registered in the Dutch national perinatal registry.

Main Outcome Measures: Referral from community midwife to a gynecologist during labor, because of fetal distress, failure to progress in second stage of labor, meconium stained amniotic fluid, failure to progress in first stage of labor, wish for pain relief, a combination of other less urgent reasons or no referral (reference).

Results: A total of 241 595 (32%) were referred from community midwife to a gynecologist during labor, because of fetal distress (FD;5%), failure to progress in second stage of labor (FTP2;14%), meconium stained amniotic fluid (MSAF;24%), failure to progress in first stage of labor (FTP1;17%), wish for pain relief (WFPR;7%) or a combination of other less urgent reasons, for example, malpresentation (e.

Serum Magnesium and Sudden Death in European Hemodialysis Patients.

Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.

Adjusting for Confounding in Early Postlaunch Settings: Going Beyond Logistic Regression Models.

Background: Postlaunch data on medical treatments can be analyzed to explore adverse events or relative effectiveness in real-life settings. These analyses are often complicated by the number of potential confounders and the possibility of model misspecification.

Methods: We conducted a simulation study to compare the performance of logistic regression, propensity score, disease risk score, and stabilized inverse probability weighting methods to adjust for confounding.

Benzodiazepine-associated delirium in critically ill adults.

Purpose: The association between benzodiazepine use and delirium risk in the ICU remains unclear. Prior investigations have failed to account for disease severity prior to delirium onset, competing events that may preclude delirium detection, other important delirium risk factors, and an adequate number of patients receiving continuous midazolam. The aim of this study was to address these limitations and evaluate the association between benzodiazepine exposure and ICU delirium occurrence.

Quality of reporting of confounding remained suboptimal after the STROBE guideline.

Objectives: Poor quality of reporting of confounding has been observed in observational studies prior the STrenghtening the Reporting of Observational studies in Epidemiology (STROBE) statement, a reporting guideline for observational studies. We assessed whether the reporting of confounding improved after the STROBE statement.

Study Design And Setting: We searched MEDLINE for all articles about observational cohort and case-control studies on interventions with a hypothesized beneficial effect in five general medical and five epidemiologic journals published between January 2010 and December 2012.

Get real in individual participant data (IPD) meta-analysis: a review of the methodology.

Individual participant data (IPD) meta-analysis is an increasingly used approach for synthesizing and investigating treatment effect estimates. Over the past few years, numerous methods for conducting an IPD meta-analysis (IPD-MA) have been proposed, often making different assumptions and modeling choices while addressing a similar research question. We conducted a literature review to provide an overview of methods for performing an IPD-MA using evidence from clinical trials or non-randomized studies when investigating treatment efficacy.

Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable: an illustrative case study of cancer risk of patients on glucose-lowering therapies.

Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through substantially different risk levels between exposure groups at the start of follow-up when exposure is deemed too short to have any plausible biological effect of the drug.

[For the critical reader: questions to ask about randomised trials].

The aim of this article is to provide guidance for the assessment of articles on randomised trials. This guide is intended for those who may want to apply the published results of randomised trials in everyday medical practice. In order to be able to attribute the observed differences in health outcomes between treatment groups with due certainty to the treatment being evaluated, it is necessary that the groups are comparable at the start of the study, during the study, and at the end of the study, i.