The mechanism of Bacillus anthracis intracellular germination requires multiple and highly diverse genetic loci.

In an effort to better understand the mechanisms by which Bacillus anthracis establishes disease, experiments were undertaken to identify the genes essential for intracellular germination. Eighteen diverse genetic loci were identified via an enrichment protocol using a transposon-mutated library of B. anthracis spores, which was screened for mutants delayed in intracellular germination.

Prescriber adoption of newly approved selective COX-2 inhibitors.

Introduction: There is no consistent definition of prescribers who adopt new drug treatments early. This study examines if COX-2 inhibitors (coxibs) were prescribed by subsets of practitioners and describes GP adoption patterns of coxibs and existing NSAIDs over time.

Methods: A population-based drug utilisation study using a Dutch medication claims database.

Monitoring the safety of pioglitazone : results of a prescription-event monitoring study of 12,772 patients in England.

Background: Pioglitazone is an antidiabetic drug that targets insulin resistance in patients with type 2 diabetes mellitus by stimulating the peroxisome proliferator-activated receptor (PPAR)-gamma. Pioglitazone belongs to a class of drugs called thiazolidinediones (TZDs) and was launched in the UK in November 2000.

Objective: To monitor, using prescription-event monitoring, the post-marketing safety of pioglitazone, which is prescribed in primary care in England.

Job satisfaction among doctors working at teaching hospital of Bahawalpur, Pakistan.

Background: Doctor's profession has long been among one of the most attractive professions in Pakistani society, but doctors are increasingly getting dissatisfied with their jobs. The focus of this study is to point out the most prominent factors of job dissatisfaction among doctors working at Bahawal-Victoria Hospital / Quaid-e-Azam Medical College, Bahawalpur.

Methods: A questionnaire was mailed to a random sample of 60 out of 244 doctors working at Bahawal-Victoria Hospital / Quaid-e-Azam Medical College, Bahawalpur.

Developing tools for the safety specification in risk management plans: lessons learned from a pilot project.

Purpose: Following the adoption of the ICH E2E guideline, risk management plans (RMP) defining the cumulative safety experience and identifying limitations in safety information are now required for marketing authorisation applications (MAA). A collaborative research project was conducted to gain experience with tools for presenting and evaluating data in the safety specification. This paper presents those tools found to be useful and the lessons learned from their use.

Safety profile of esomeprazole: results of a prescription-event monitoring study of 11 595 patients in England.

Objective: Esomeprazole, the S-isomer of omeprazole, was launched in the UK in September 2000. The first proton pump inhibitor, omeprazole, has been marketed in the UK for over 10 years. However, the adverse event database of newly marketed drugs is limited, and it is only after widespread clinical use that the adverse effect profile of a drug is ascertained more comprehensively.

Evaluation of risk profiles for gastrointestinal and cardiovascular adverse effects in nonselective NSAID and COX-2 inhibitor users: a cohort study using pharmacy dispensing data in The Netherlands.

Background: Newly approved drugs, in comparison with older drugs, are more often prescribed to patients who have not responded satisfactorily to established related drugs or as first-line therapy to patients with a high baseline risk for adverse outcomes (i.e. channelling).

The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England.

Introduction: Observational cohort studies were conducted using prescription-event monitoring (PEM) to examine the safety profiles of the anti-obesity agents orlistat and sibutramine. Adverse events reported as case reports were also evaluated to determine whether these events were also identified by PEM.

Research Methods And Procedures: Patients were identified from dispensed prescriptions written by general practitioners (GPs) in England for orlistat or sibutramine.

Effects of endogenous D-alanine synthesis and autoinhibition of Bacillus anthracis germination on in vitro and in vivo infections.

Bacillus anthracis transitions from a dormant spore to a vegetative bacillus through a series of structural and biochemical changes collectively referred to as germination. The timing of germination is important during early steps in infection and may determine if B. anthracis survives or succumbs to responsive macrophages.

Safety of nateglinide as used in general practice in England: results of a prescription-event monitoring study.

Nateglinide (Starlix((R))) is licensed for the treatment of Type 2 diabetes in patients inadequately controlled with metformin. The study objective was to monitor the safety and use of nateglinide prescribed by primary care physicians (GPs) in England, using the observational cohort technique, Prescription-Event Monitoring. Exposure data were derived from dispensed nateglinide prescriptions issued October 2001-June 2004; demographic and outcome data, from questionnaires sent to patients' GPs at least 6 months after patients' first prescription.

A modified prescription-event monitoring study to assess the introduction of Seretide Evohaler in England: an example of studying risk monitoring in pharmacovigilance.

Introduction: Monitoring was required for the introduction of non-chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDIs) to ensure that there were no unexpected adverse events due to the new products. A postmarketing surveillance study has been conducted to evaluate the introduction of the MDI Seretide Evohaler (hydrofluoroalkane-134a inhaler containing salmeterol and fluticasone propionate).

Objectives: To summarise the modified prescription-event monitoring (PEM) study conducted to evaluate the introduction of Seretide Evohaler and discuss the relevance of this type of study towards pharmacovigilance risk-management planning.

The safety of quetiapine: results of a post-marketing surveillance study on 1728 patients in England.

The safety of the atypical antipsychotic quetiapine as used in general practice in England was examined by prescription-event monitoring (PEM). Patients were identified from dispensed National Health Service (NHS) prescriptions issued by general practitioners (GPs) for quetiapine between October 1997 and July 1999. The outcome data were event reports obtained by sending questionnaires ('green forms') to the prescribing doctor at Least 6 months after the first prescription for an individual patient.

Reactive oxygen species mediate a cellular 'memory' of high glucose stress signalling.

Aims/hypothesis: A long-term 'memory' of hyperglycaemic stress, even when glycaemia is normalised, has been previously reported in endothelial cells. In this report we sought to duplicate and extend this finding.

Materials And Methods: HUVECs and ARPE-19 retinal cells were incubated in 5 or in 30 mmol/l glucose for 3 weeks or subjected to 1 week of normal glucose after being exposed for 2 weeks to continuous high glucose.

A modified prescription-event monitoring study to assess the introduction of Flixotide Evohaler into general practice in England: an example of pharmacovigilance planning and risk monitoring.

Introduction: A modified prescription-event monitoring (PEM) study was conducted to examine the safety of the introduction of the metered dose inhaler (MDI) Flixotide Evohaler (fluticasone with the propellant HFA 134a).

Methods: Patients were identified from the first NHS prescriptions dispensed in England for Flixotide Evohaler. Postal questionnaires were sent to the prescribing doctor, requesting information including: demographic characteristics, severity of indication, concomitant medication, event data 3 months prior to and 3 months after the first prescription, and any reasons for stopping Flixotide.

Safety of zafirlukast: results of a postmarketing surveillance study on 7976 patients in England.

Objectives: A prescription event monitoring (PEM) postmarketing surveillance study was carried out to examine the safety of zafirlukast as used in general practice in England.

Methods: Exposure data were obtained from the first National Health Service (NHS) prescription dispensed for patients whose prescription details were processed by the Prescription Pricing Authority between August 1998 and December 2000. Outcome data were obtained from 'green form' questionnaires sent to general practitioners (GPs) at least 6 months following the first prescription issued.

Application of the bradford hill criteria to assess the causality of cisapride-induced arrhythmia: a model for assessing causal association in pharmacovigilance.

Introduction: The Bradford Hill criteria are a widely used, useful tool for the assessment of biomedical causation. We have examined their application to pharmacovigilance using the example of cisapride-induced QTc interval prolongation/arrhythmia.

Methods: A literature search was conducted using MEDLINE, EMBASE, Reactions Weekly and regulatory websites to identify evidence for the association between cisapride and QTc interval prolongation/arrhythmia that had been published in the English language.

An observational cohort study investigating the cardiovascular safety of tadalafil when prescribed in primary care in England: mortality due to ischaemic heart disease.

Objective: To examine the cardiovascular safety of tadalafil, a phosphodiesterase type-5 inhibitor used for treating erectile dysfunction in patients prescribed this drug by general practitioners (GPs) in England in 2003, focusing on mortality due to ischaemic heart disease (IHD).

Patients And Methods: Patients in this observational cohort study were identified from dispensed prescriptions for tadalafil issued by GPs from February to November 2003. Demographic and outcome data were requested from patients' GPs using a postal questionnaire.

Safety profile of rosuvastatin: results of a prescription-event monitoring study of 11,680 patients.

Background And Objective: Rosuvastatin is a lipid-lowering drug, the newest of a class of drugs called HMG-CoA reductase inhibitors, or 'statins', launched in the UK in March 2003. Our objective was to monitor the post-marketing safety of this drug, prescribed in primary care in England, using prescription-event monitoring.

Methods: An observational cohort study in which patients were identified from dispensed prescriptions issued by primary care physicians/general practitioners (GPs) between August and December 2003.

Comparison of the risk of drowsiness and sedation between levocetirizine and desloratadine: a prescription-event monitoring study in England.

Background And Objectives: Desloratadine and levocetirizine are histamine H(1) receptor antagonists (antihistamines) that were launched in the UK in 2001. Our objective was to compare the frequency with which drowsiness and sedation were reported for desloratadine and levocetirizine within the first 30 days of observation, as monitored using the observational cohort technique of prescription-event monitoring (PEM).

Methods: Exposure data were derived from dispensed prescriptions written by primary care physicians and outcome data were derived from questionnaires that were posted to prescribers at least 6 months after the date of the first prescription for each patient.

Exposure to mirtazapine during pregnancy: a prospective, comparative study of birth outcomes.

Background: Mirtazapine is a novel piperazinoazepine antidepressant, unrelated to any known class of antidepressants. Currently, apart from a few case reports and case series in the literature, there are no studies evaluating the safety of this drug during pregnancy.

Objective: To determine whether mirtazapine increases the risk for major malformations in newborns when used by pregnant women.

Serious skin reactions and selective COX-2 inhibitors: a case series from prescription-event monitoring in England.

Background: The erythema multiforme (EM) spectrum of bullous eruptions (toxic epidermal necrolysis [TEN] and Stevens-Johnson syndrome [SJS]) are rare and serious skin reactions that have been reported for cyclo-oxygenase (COX)-2 selective inhibitors. Our objectives were to identify and describe cases of serious skin reactions reported during postmarketing studies of COX-2 selective inhibitors.

Methods: A retrospective review of information from reports of serious skin reactions reported during prescription-event monitoring (PEM) studies of rofecoxib, celecoxib, etoricoxib and valdecoxib conducted in England since 1999.

Examination of the safety and use of apomorphine prescribed in general practice in England as a treatment for erectile dysfunction.

Objective: To examine the safety and use of apomorphine as prescribed in general medical practice in England as a treatment for erectile dysfunction (ED).

Patients And Methods: Apomorphine hydrochloride (marketed as Uprima, Abbott Laboratories Ltd, UK) is licensed in the UK as a sublingual therapy for ED. It is the first treatment for ED with a central mode of action.

An analysis of the exclusion criteria used in observational pharmacoepidemiological studies.

Purpose: The application of exclusion criteria in pharmacoepidemiological studies could have a major impact on the findings but there appears to have been no previous research to examine the types of exclusion criteria applied.

Methods: We searched the literature and identified 10 senior pharmacoepidemiologists who had published five or more relevant papers between 1999 and 2004. All their published drug safety studies during this period were reviewed.