Pharmacoepidemiology and Drug Safety via MedWorm.com

Issues in multiple imputation of missing data for large general practice clinical databases

Pharmacoepidemiology and Drug Safety — Sat, 20 Mar 2010 00:00:00 +0100

Missing data are a substantial problem in clinical databases. This paper aims to examine patterns of missing data in a primary care database, compare this to nationally representative datasets and explore the use of multiple imputation (MI) for these data.The patterns and extent of missing health indicators in a UK primary care database (THIN) were quantified using 488 384 patients aged 16 or over in their first year after registration with a GP from 354 General Practices. MI models were developed and the resulting data compared to that from nationally representative datasets (14 142 participants aged 16 or over from the Health Survey for England 2006 (HSE) and 4 252 men from the British Regional Heart Study (BRHS)).Between 22% (smoking) and 38% (height) of health indicator data were missi...

Neuroleptic malignant syndrome and its controversies

Pharmacoepidemiology and Drug Safety — Fri, 19 Mar 2010 00:00:00 +0100

Neuroleptic malignant syndrome (NMS) is a rare and life threatening condition usually defined as a complication of treatment with antipsychotics characterized by severe rigidity, tremor, fever, altered mental status, autonomic dysfunction, and elevated serum creatine phosphokinase and white blood cell count. The literature on this topic is rather extensive, but many aspects related to the syndrome are thought to be controversial. The aim of this paper, written with the clinician in mind, is to summarize some of the most prominent controversies that may have importance in usual clinical practice.The literature was searched for reviews, reports on the series of cases, individual case reports of NMS, and other clinically and theoretically important information.There are controversies associat...

Laboratory monitoring and adverse patient outcomes with antihypertensive therapy in primary care

Pharmacoepidemiology and Drug Safety — Fri, 19 Mar 2010 00:00:00 +0100

The monitoring of serum electrolyte and creatinine concentrations in patients treated with antihypertensive therapy is recommended. We wished to examine the relationship between laboratory monitoring and adverse patient outcomes.We carried out a retrospective cohort study using the General Practice Research Database (GPRD). Patients aged 18 years or older with newly diagnosed hypertension and prescribed a single antihypertensive agent were included. Monitoring was defined as any laboratory test for serum electrolyte and creatinine (or urea) concentrations within 6 months of starting treatment.We identified 74 096 patients who were newly diagnosed with hypertension and prescribed a single antihypertensive agent. Twenty six thousand nine hundred forty six (36.4%) patients had any biochemical...

Estimating the prevalence of inflammatory bowel disease in Portugal using a pharmaco-epidemiological approach

Pharmacoepidemiology and Drug Safety — Thu, 18 Mar 2010 00:00:00 +0100

To estimate inflammatory bowel disease (IBD) prevalence in Portugal from 2003 to 2007, and to obtain disease, sex and age specific estimates.A pharmaco-epidemiological approach based on intestinal anti-inflammatory (IAI) drugs consumption was used. Proportion of patients taking IAI drugs and mean prescribed daily dose (PDD) were estimated from a sample of 513 IBD patients. Assumptions were made about unknown parameters and sensitivity analysis performed: drug compliance (80% in base case; range 70-85%) and proportion of sulphasalazine used in IBD (52%; range 40-80%). Sex and age specific estimates were based on a proposed methodological extension and results from a nationwide (n = 5893) cross-sectional study.IBD prevalence increased from 86 patients per 100 000 in 2003 to 146 in 2007. Regi...

Pre-existing cardiovascular conditions and pharmacological treatment of adult ADHD

Pharmacoepidemiology and Drug Safety — Tue, 16 Mar 2010 00:00:00 +0100

Stimulants and atomoxetine should generally not be used or used only with caution in adults with pre-existing cardiovascular conditions. The extent to which pre-existing cardiovascular conditions influence initiation of these ADHD medications in adults is not known.We performed a retrospective cohort study of privately insured adults with new ADHD treatment episodes. Pre-existing cardiovascular conditions were assessed by the presence of ICD-9-CM codes for congenital abnormalities, atherosclerosis, cardiac disease, and cerebrovascular disease in the 12 months before the index ADHD diagnosis. The primary outcome was new initiation of a stimulant or atomoxetine in the 3 months after the index date. Multivariate logistic regression was used to predict the likelihood of treatment initiation wi...

Antiepileptic drugs and risk of suicide: a nationwide study

Pharmacoepidemiology and Drug Safety — Tue, 16 Mar 2010 00:00:00 +0100

This study investigated possible differences in suicide risk associated with different AEDs.The use of AEDs in the Danish population from 1997 to 2006 was determined by prescription claims. The risk of suicide associated with use of AEDs was estimated by case-crossover analyses, where each case serves at its own control during different periods. For sensitivity, the risk of suicide was estimated by a time-dependent Cox proportional-hazard analysis in AED treatment-naïve patients.There were 6780 cases committing suicide in the 10-year study period, of which 422 received AED treatment at the time of suicide. The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36-2.49). Clonazepam (OR: 2.01, CI...

Assessment of regional variation in polypharmacy

Pharmacoepidemiology and Drug Safety — Fri, 26 Feb 2010 00:00:00 +0100

To assess polypharmacy in a population with emphasis on regions.We studied the individual-based data of all dispensed prescription drugs (DP) during a 3-month study period in Sweden 2006. As an indicator of polypharmacy, five or more (DP [ge] 5) different drugs (substances) dispensed were applied. For analysis, we used comparisons of prevalence, correlation of prevalence of polypharmacy with different socioeconomic variables, and a novel weighted polypharmacy index.The national prevalence of polypharmacy, DP [ge] 5, was 10.5% (inter-regional variation 9.1-12.1%). The regional variation in the prevalence of polypharmacy was largest for the age groups [ge]90 (45.6-59.1%), 80-89 (46.1-53.4%) and 70-79 years (33.1-38.0%). The national prevalence of excessive polypharmacy, DP [ge] 10, was 2.2% ...

Increased risk of abdominal wall hernia associated with combination anti-retroviral therapy in HIV-infected patients - results from a Swedish cohort-study

Pharmacoepidemiology and Drug Safety — Wed, 24 Feb 2010 00:00:00 +0100

To determine if anti-retroviral therapy (ART) in HIV-infected patients is associated with an increased risk for development of abdominal wall hernia.A cohort study of 1072 HIV-infected patients in Sweden. Information was collected by questionnaires to patients and treating physicians, chart reviews by study physicians and regular blood tests for metabolic disorders. Adjusted relative risks were estimated by Cox proportional hazards models.Sixty-three patients (5.9%) developed abdominal wall hernia during the study period, 34 inguinal and 29 midline. Compared to the male general population, inguinal hernia was twice as common in the male study population, standardized incidence ratio (SIR) 2.0 (95% confidence interval (CI) 1.4-2.8). An increased incidence rate of abdominal wall hernia was f...

Multivariate-adjusted pharmacoepidemiologic analyses of confidential information pooled from multiple health care utilization databases

Pharmacoepidemiology and Drug Safety — Wed, 17 Feb 2010 00:00:00 +0100

Mandated post-marketing drug safety studies require vast databases pooled from multiple administrative data sources which can contain private and proprietary information. We sought to create a method to conduct pooled analyses while keeping information private and allowing for full confounder adjustment.We propose a method based on propensity score (PS) techniques. A set of propensity scores are computed in each data-contributing center and a PS-adjusted analysis is then carried out on a pooled basis. The method is demonstrated in a study of the potentially negative effects of concurrent initiation of clopidogrel and proton pump inhibitors (PPIs) in four cohorts of patients assembled from North American claims data sources. Clinical outcomes were myocardial infarction (MI) hospitalization ...

Adverse drug reactions induced by cardiovascular drugs in cardiovascular care unit patients

Pharmacoepidemiology and Drug Safety — Wed, 10 Feb 2010 00:00:00 +0100

Factors associated with psychoactive drug initiation in a sample of workers in France: results of the VISAT cohort study

Pharmacoepidemiology and Drug Safety — Mon, 08 Feb 2010 00:00:00 +0100

This study used data collected from the VISAT ('Vieillissement, Santé, Travail') cohort which included workers aged 32, 42, 52 and 62 years in 1996 with follow-ups conducted over the following 5 years. Data were collected through interviews and five standardized questionnaires in annual occupational medical examinations in 1996, 1999 and 2001. We defined new consumers of psychoactive drugs according to their answers during the follow-ups and compared their psychosocial and working characteristics to non-consumers. A multivariate logistic regression analysis was performed to investigate factors related to a psychoactive drug initiation.Among 1533 subjects, 5.4% began consuming psychoactive drugs during the follow-up with a twofold rate for women than for men. Factors related to psychoactiv...

Validation of claims-based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially-insured population

Pharmacoepidemiology and Drug Safety — Fri, 05 Feb 2010 00:00:00 +0100

To validate administrative claims codes with medical chart review for myocardial infarction (MI), ischemic stroke, and severe upper gastrointestinal (UGI) bleed events in a large, commercially-insured US population.These validation studies were part of a larger study examining the risk of MI, ischemic stroke, and severe UGI bleeds in patients receiving a new prescription of selective cyclooxygenase (COX)-2 inhibitors (coxibs) and non-over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs), between 1 July 2002 and 30 September 2004. Patients from the study cohort and other health plan members from the HealthCore Integrated Research DatabaseSM (HIRD) experiencing these events were selected for these studies. The positive predictive value (PPV) of each of the claims code algorit...

General exposures to prescription medications by race/ethnicity in a population-based sample: results from the Boston Area Community Health Survey

Pharmacoepidemiology and Drug Safety — Fri, 05 Feb 2010 00:00:00 +0100

Few recent U.S. studies have examined population-based patterns in prescription drug use and even fewer have considered detailed patterns by race/ethnicity. In a representative community sample, our objectives were to determine the most commonly used prescription drug classes, and to describe their use by age, gender, and race/ethnicity.Cross-sectional epidemiologic study of 5503 (1767 black, 1877 Hispanic, 1859 white) community-dwelling participants aged 30-79 in the Boston Area Community Health (BACH) Survey (2002-2005). Using medication information collected from an in-home interview and medication inventory, the prevalence of use of a therapeutic class (95% confidence interval (95%CI)) in the past month was estimated by gender, age group, and race/ethnicity. Estimates were weighted inv...

Pharmacoepidemiological research using French reimbursement databases: yes we can!

Pharmacoepidemiology and Drug Safety — Wed, 03 Feb 2010 00:00:00 +0100

To describe the reimbursement databases available in France for pharmacoepidemiological research and their use.France has a publicly funded health system that systematically covers the population. Within this system, three main insurance schemes provide health services to citizens in France and each have their own reimbursement database. Together these three databases cover almost 97% of the French population (respectively for 54.5, 3.6, and 3.3 million individuals, and a total of 61.4 million individuals). Data in these concern patients, prescribers, all the medical acts reimbursed, prescription and undertaking of laboratory tests (but without results), private hospital data, partial public hospital data and vital status. Their use is regulated but access is free and the data are anonymou...

Validation of ischemic cerebrovascular diagnoses in the health improvement network (THIN)

Pharmacoepidemiology and Drug Safety — Wed, 03 Feb 2010 00:00:00 +0100

To evaluate the validity of recorded diagnoses of ischemic cerebrovascular events requiring hospitalization within The Health Improvement Network (THIN) UK primary care database.We identified 15 397 individuals aged 40-84 years with a first recorded ischemic event in 2000-2004. Of these, 4239 had a code suggestive of a hospitalization within 2 weeks of the event. A three-step strategy was used to validate the records of these patients: manual review of computerized medical records excluding free-text comments; manual review including free-text comments (which include information gained from specialists, hospital discharge letters and results of diagnostic tests) of a random sample of possible cases (n = 300) and non-cases (n = 100); and review of full medical records of this random sample ...

Prevalence and predictors of anti-infective use during pregnancy

Pharmacoepidemiology and Drug Safety — Sat, 30 Jan 2010 00:00:00 +0100

(1) Measure the prevalence and trends of anti-infective drug use before, during, and after pregnancy; (2) to list the doses, classes, types, and indications for anti-infective use during pregnancy; and (3) to identify predictors associated with anti-infective drug use during pregnancy.Retrospective cohort study within the Quebec Pregnancy Registry, which was created by the linkage of three administrative databases: RAMQ, Méd-Echo, and ISQ. Women were eligible if they were (1) continuously insured by the RAMQ drug plan for at least 12 months before the first day of gestation, during pregnancy and 12 months after the end of the pregnancy and (2) if they gave birth to a live born between January 1998 and December 2003. Ninety-seven thousand six hundred and eighty pregnant women met the eligi...

Predicting the risk of hyperkalemia in patients with chronic kidney disease starting lisinopril

Pharmacoepidemiology and Drug Safety — Fri, 29 Jan 2010 00:00:00 +0100

Angiotensin-converting enzyme (ACE) inhibitors are recommended for patients with chronic kidney disease (CKD) because they slow disease progression. But physicians' concerns about the risk of hyperkalemia (elevated serum potassium level), a potentially fatal adverse effect, may limit optimal management with ACE-inhibitors. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia.We assembled a retrospective cohort of adult patients with possible CKD (at least one estimated glomerular filtration rate (eGFR) value less than 60 ml/min/1.73 m2) who started an ACE-inhibitor (i.e., incident users) between 1998 and 2006 at a health maintenance organization. We followed patients for hyperkalemia: (1) potassium value >5.5 mmol/L; or (2) diagno...

Medication use in early pregnancy-prevalence and determinants of use in a prospective cohort of women

Pharmacoepidemiology and Drug Safety — Sat, 23 Jan 2010 00:00:00 +0100

To examine the extent, nature and determinants of medication use in early pregnancy.We reviewed early pregnancy medication use, as reported to a midwife at the booking interview, in women delivering between 2000 and 2007 in a large maternity hospital in Dublin, Ireland (n = 61 252).Excluding folic acid, at least one medication was reported in 23 989 (39.2%) pregnancies. Over the counter (OTC) medications were reported in 11 970 (19.5%) pregnancies, illicit drugs or methadone in 545 (0.9%) and herbal medicines/supplements in 352 (0.58%). FDA category D and X medications were reported by 1532 (2.5%) and 1987 (3.2%) women. Asthma, depression and hypertension were among the most commonly reported chronic medical disorders. Medications with potential for foetal harm were reported by 86 (15.7%) ...

Commentary on the validation studies of sudden cardiac death and ventricular arrhythmia by Hennessy et al. and Chung et al.

Pharmacoepidemiology and Drug Safety — Wed, 20 Jan 2010 00:00:00 +0100

No Abstract. (Source: Pharmacoepidemiology and Drug Safety)

Socioeconomic position and secondary preventive therapy after an AMI

Pharmacoepidemiology and Drug Safety — Tue, 19 Jan 2010 00:00:00 +0100

To investigate the association between socioeconomic position and use of lipid-lowering drugs and ACE-inhibitors after an acute myocardial infarction (AMI) when simultaneously considering participation in the national quality register RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive care Admissions), age, sex and previous hospitalizations of the patients.Population-based prospective cohort study included all 1346 AMI patients cared in the county of Scania, Sweden during 2006 of whom 1061 were register at the RIKS-HIA. Treatment with lipid-lowering and ACE-inhibiting therapy in relation to income was investigated with Cox and logistic regression modelling.In the whole population of AMI patients, high income patients had a higher adherence to guidelines for pharm...

Safety assessment of recalled Haemophilus influenzae type b (Hib) conjugate vaccines - United States, 2007-2008

Pharmacoepidemiology and Drug Safety — Mon, 18 Jan 2010 00:00:00 +0100

On 13 December 2007, Merck & Co., Inc. voluntarily recalled 1.2 million doses of Haemophilus influenzae type b (Hib) vaccines that had been distributed since April 2007 for concerns regarding potential Bacillus cereus contamination. Enhanced postrecall surveillance was conducted to detect vaccine-associated B. cereus infections.We reviewed reports involving recalled Hib vaccines received by the Vaccine Adverse Event Reporting System (VAERS) during 1 April 2007-29 February 2008. For each reported death, autopsy review sought evidence of B. cereus infections. For each specified outcome, the proportional reporting ratios (PRRs) were calculated to compare the recalled Hib vaccines with the manufacturer's nonrecalled Hib vaccines in the VAERS databases. On 20 December 2007, we used the Epidemic...

Exploring differential prescribing between anti-epileptic drugs in epilepsy patients with a history of mood disorders

Pharmacoepidemiology and Drug Safety — Fri, 15 Jan 2010 00:00:00 +0100

To explore differential prescribing of anti-epileptic drugs (AEDs) to patients with epilepsy by history of mood disorder.Epilepsy was defined as at least one diagnosis code and one AED prescription, and all patients must have been on the database 182 days before and after their first AED prescription. The Integrated HealthCare Information Services (IHCIS) insurance claims database included 44 557 patients with epilepsy between January 1997 and March 2007. The General Practice Research Database (GPRD) included 16 904 patients with epilepsy up to March 2007. Patients were categorized by their first use of specified AEDs. Mood disorders were defined as diagnosis codes for depression and bipolar disorder, or anti-depressant use. The unadjusted odds ratios and 95% confidence intervals for a his...

Surveillance of methadone-related poisonings in Kentucky using multiple data sources

Pharmacoepidemiology and Drug Safety — Thu, 14 Jan 2010 00:00:00 +0100

The methadone poisoning death rate for Kentucky in the year 2005 was the sixth highest in the US and increased 17-fold from 1999 to 2005. The purpose of this study was to identify and characterize methadone related poisonings in Kentucky using multiple data sources: inpatient hospitalization discharge data, poison control center data, vital statistics mortality data, and Kentucky All Schedule Prescription Electronic Reporting (KASPER) data.A descriptive analysis study was performed on Kentucky inpatient hospitalization discharge data, Kentucky Regional Poison Center (KRPC) data, Kentucky vital statistics mortality data, and KASPER data.While methadone prescription rates decreased from a peak of 27 prescriptions per 1000 population in the year 2003 to 21 in 2007, there was a statistically s...

Anxiolytic, hypnotic and sedative medication use in Australia

Pharmacoepidemiology and Drug Safety — Wed, 13 Jan 2010 00:00:00 +0100

We examined the trends in the prescribing of subsidised anxiolytic, hypnotic and sedative (AHS) medication use in the Australian population from 2002 to 2007.We analysed the Medicare Australia and Drug Utilisation Sub-Committee databases for AHS script data from 2002 to 2007 by source, class of prescriber, gender and 5-year age groups. Scripts were converted to defined daily dose per 1000 population per day (DDD/1000 population/day) using Australian Bureau of Statistics population data.Overall use of AHS increased from 23.76 to 24.11 DDD/1000 population/day between 2002 and 2007. Anxiolytic medication utilisation increased as hypnotic medication utilisation decreased. Diazepam was the most widely used anxiolytic followed by alprazolam and oxazepam. Temazepam was the most widely used hypnot...

Adverse drug reactions to antiretroviral therapy (ART): an experience of spontaneous reporting and intensive monitoring from ART centre in India

Pharmacoepidemiology and Drug Safety — Tue, 12 Jan 2010 00:00:00 +0100

To assess the nature, severity, predictability and preventability of adverse drug reactions (ADRs) and to identify risk factors for antiretroviral ADRs.Enrolled ambulatory patients were intensively monitored for ADRs. Spontaneously reported ADRs by clinicians were also included. Predictability was assessed based on history of previous exposure to the drug or literature incidence of ADRs. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using modified Hartwig and Siegel scale. Bivariate analysis and subsequently multivariate logistic regression were used to identify the risk factors for ADRs. Data from spontaneous reporting was assessed using Bayesian neural network method for possible ADR signals.Monitoring by active surveillance indentified 159 (5...

Combination therapy with sulfonylureas and metformin and the prevention of death in type 2 diabetes: a nested case-control study

Pharmacoepidemiology and Drug Safety — Tue, 05 Jan 2010 00:00:00 +0100

To determine whether combination of sulfonylureas and metformin increases the risk of death from any cause in patients with type 2 diabetes.A nested case-control study was conducted within a population-based cohort from the UK General Practice Research Database (GPRD). The cohort included patients over the age of 40 who were prescribed a first oral hypoglycaemic agent between 1 January 1988 and 30 June 2008. Cases included all patients who deceased during follow-up. Up to 10 controls were matched to each case on year of birth, date of cohort entry (±1 year) and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RRs) of death from any cause associated with the use of combination of sulfonylureas and metformin, relative to sulfonylurea monotherapy.The c...

Changes in US antidepressant and antipsychotic prescription patterns during a period of FDA actions

Pharmacoepidemiology and Drug Safety — Mon, 04 Jan 2010 00:00:00 +0100

To determine if paroxetine versus non-paroxetine selective serotonin reuptake inhibitors (SSRIs) prescribing changed after the June 2003 FDA Paroxetine Public Health Advisory (PPHA) and if antidepressant and antipsychotic prescribing changed after the February 2004 FDA Advisory Committee Meeting (FDACM).Ecologic analysis using estimates of patients dispensed antidepressants and antipsychotics, census data, and promotional spending data. Data sources were SDI: Vector One®, US Census, and IMS Health®. Measures were monthly use levels (number of patients dispensed antidepressants, antipsychotics, paroxetine, and non-paroxetine SSRIs prescriptions by age group per population count). Percent changes pre- to post-PPHA were used to assess changes in paroxetine versus non-paroxetine SSRIs prescr...

Potential bias caused by control selection in secondary data analysis: Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke

Pharmacoepidemiology and Drug Safety — Mon, 04 Jan 2010 00:00:00 +0100

This study investigated the potential for bias introduction when selecting controls for secondary analysis of case-control study data.We used a data set previously collected for an acute brain bleeding analysis (ABBA) study, which was designed to investigate the risk of hemorrhagic stroke (HS) resulting from the use of phenylpropanolamine in Korea. Cases in that study had experienced an HS. Each HS case was matched with age- and gender-based hospital and community controls. Information was obtained on drug exposures including nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs). Odds ratios (OR) for, and 95% confidence intervals (CI) of, experiencing an HS were calculated using conditional logistic regressions for each control group.A total of 940 patients were matched with 1880 cont...

Signal detection of rosuvastatin compared to other statins: data-mining study using national health insurance claims database

Pharmacoepidemiology and Drug Safety — Mon, 04 Jan 2010 00:00:00 +0100

To detect adverse drug reaction (ADR) signals of rosuvastatin compared to other statins with a novel data-mining approach based on relative risk (RR) using the national health insurance claims database, and to evaluate the usefulness of this method as a tool for signal detection.We used the Health Insurance Review & Assessment Service (HIRA) claims database (Seoul, Korea). Serious adverse events (SAE) were defined as any diagnostic code at the time of hospitalization within 12 weeks from a statin prescription date, regardless of causality. Among statin users, RRs were calculated to compare the proportion of rosuvastatin-specific SAE pairs for rosuvastatin users with the corresponding proportion of drug-SAE pairs for users of other statins. Any SAE for which the lower limit of the RR's 95% ...

Hospital pharmacists' knowledge and opinions regarding adverse drug reaction reporting in Northern China

Pharmacoepidemiology and Drug Safety — Thu, 24 Dec 2009 00:00:00 +0100

This study was designed to investigate the knowledge and opinions of hospital pharmacists about the spontaneous reporting of adverse drug reactions (ADRs) in Inner Mongolia, a northern region of China.A face-to-face questionnaire survey of hospital pharmacists was conducted in five tertiary general hospitals in Inner Mongolia between July and December 2007. The structured questionnaire consisted of questions about the demographic details of the pharmacists, their knowledge of pharmacovigilance and their opinions on pharmacists' involvement in ADR reporting.Of the 288 pharmacists visited, 246 responded giving a total response rate of 85.4%. An amount of 70% of the pharmacists could define ADR correctly and 78.0% knew how to report ADRs. However, only one-third were clear as to what should b...

Adverse drug events among children presenting to a hospital emergency department in Newfoundland and Labrador, Canada

Pharmacoepidemiology and Drug Safety — Wed, 23 Dec 2009 00:00:00 +0100

This study was conducted in three phases and included an ED chart review of visits to the Janeway Hospital in St. John's, NL, between 27th April 2006 and 26th April 2007. The first phase narrowed the sampling frame by excluding visits highly unlikely to be drug-related. In the second phase, a random sample of ED charts was selected for review by two research nurses using a Trigger Assessment Tool that classified ED visits according to their likelihood of being drug related ('high', 'moderate', 'low', 'very low', or 'no' probability). The third phase included a full chart review of all 'high', 'moderate', 'low', and 'very low' probability ADE charts, carried out independently by two ED pediatricians and two clinical pharmacists. Each ADE was also scored for severity and preventability, and ...

Early communication of drug safety concerns: a feasibility study on enhancing interaction between the pharmaceutical industry and regulators

Pharmacoepidemiology and Drug Safety — Wed, 23 Dec 2009 00:00:00 +0100

The responsibility for monitoring the safety of marketed medicines is shared between regulatory authorities and the pharmaceutical industry and is underpinned by legal obligations on both sides. Both marketing authorisation holders (MAHs) and regulators initially evaluate and investigate potential safety concerns, and then work together on further review as appropriate. We wanted to test the feasibility of enhanced interaction between MAH and regulator via a regular monthly, two-way communication of potential safety concerns between the MAHs and the Medicines and Healthcare Products Regulatory Agency (MHRA). It was envisaged that such a process would aid prioritisation and planning by both parties, avoid duplication of effort and support a collaborative approach for decision making.Four MA...

A computer case definition for sudden cardiac death

Pharmacoepidemiology and Drug Safety — Tue, 22 Dec 2009 00:00:00 +0100

To facilitate studies of medications and sudden cardiac death, we developed and validated a computer case definition for these deaths. The study of community dwelling Tennessee Medicaid enrollees 30-74 years of age utilized a linked database with Medicaid inpatient/outpatient files, state death certificate files, and a state 'all-payers' hospital discharge file.The computerized case definition was developed from a retrospective cohort study of sudden cardiac deaths occurring between 1990 and 1993. Medical records for 926 potential cases had been adjudicated for this study to determine if they met the clinical definition for sudden cardiac death occurring in the community and were likely to be due to ventricular tachyarrhythmias. The computerized case definition included deaths with (1) no ...

A drug utilization study to provide background data for bringing amendments in the drug dispensing policy of a pediatric referral center

Pharmacoepidemiology and Drug Safety — Thu, 17 Dec 2009 00:00:00 +0100

The purpose of this study was to generate data regarding the drug utilization pattern in pediatric population of our tertiary care hospital so that we could generate an essential medicine list (EML).Drug therapy accounts for a major portion of expenditure toward health care. Reduction in health care cost for an individual can be achieved by lowering the cost of drug treatment.This was an observational study conducted in the Advanced Pediatric Centre of our hospital, during which prescriptions and case records were reviewed.During the study a total of 891 prescriptions were reviewed. Antibiotics and nutritional supplements were the major drugs prescribed. A large percentage of drugs were prescribed as trade names. Eighty three per cent of the drugs were prescribed from the National List Of ...

Extent of pharmacovigilance among resident doctors in Edo and Lagos states of Nigeria

Pharmacoepidemiology and Drug Safety — Wed, 16 Dec 2009 00:00:00 +0100

Systematic attention to adverse drug reactions (ADRs) started with the thalidomide disaster in the early 60s of the 20th century. In 1968 ten countries supported a spontaneous reporting system for ADR and collaborated with the WHO pilot research project for international drug monitoring. This survey was conducted to determine the level of awareness of resident doctors about ADRs reporting, the extent of their involvement in pharmacovigilance activities and to build a useful data base that will improve the quality of health care in Nigeria.This cross-sectional observational survey was conducted in University of Benin Teaching Hospital (UBTH) and Irrua Specialist Teaching Hospital (ISTH), Lagos University Teaching Hospital (LUTH) and Lagos State University Teaching Hospital (LASUTH) in Edo a...

Use of over-the-counter analgesics and perceived stress among 25-44-year olds

Pharmacoepidemiology and Drug Safety — Tue, 15 Dec 2009 00:00:00 +0100

To examine the association between perceived stress and use of over-the-counter analgesics in a representative sample of 25-44-year old adults, and to examine the association across various socio-demographic strata. Furthermore, to examine whether an association between perceived stress and use of over-the-counter analgesics attenuates when controlled by potential stress-related pain and discomfort.National representative cross-sectional study in Denmark. The study population consisted of men and women aged 25-44 years, n = 4739. The survey was conducted by face-to-face interviews. The outcome measure was use of over-the-counter analgesics (OTCA). The independent variable was perceived stress. Demographic variables and pain and discomfort symptoms were included as covariates.Analyses strat...

Patient focused drug surveillance of elderly patients in nursing homes

Pharmacoepidemiology and Drug Safety — Tue, 15 Dec 2009 00:00:00 +0100

To examine whether patient focused drug surveillance was associated with a higher quality of drug treatment at nursing homes.An intervention study in four nursing homes in Sweden and four other nursing homes served as controls. At the intervention nursing homes physicians focused on patients' health status as a baseline for further ongoing medication. The outcomes were mortality, health care consumption, and number of drugs, health status and evaluations as parameters for "quality of drug treatment".There were no significant differences in mortality rates. Health care consumption and polypharmacy were extensive in both groups. There was a significant reduction of number of drugs used per patient at the intervention homes during the study (p < 0.05). Monitoring and evaluation of the effects...

Muscle toxicity with statins

Pharmacoepidemiology and Drug Safety — Mon, 14 Dec 2009 00:00:00 +0100

Statins rarely cause serious muscle toxicity and rhabdomyolysis. The aim of our investigation was to identify and quantify potential risk factors for statin-induced rhabdomyolysis.All cases of suspected adverse reactions to statins reported to the Swedish Adverse Drug Reactions Advisory Committee until 15 September 2006 containing the codes myalgia, myopathy, increased serum creatine kinase (CK), myoglobinuria or rhabdomyolysis were included in the study. Cases were classified into different CK categories, where cases with CK levels >10 times the upper limit of normal (ULN) laboratory range were compared with cases with normal CK levels (in some analyses cases with CK not measured were also included as controls). Fisher's test and multiple logistic regression were used to test the degree o...

Trends in the non-steroidal anti-inflammatory drug market in six Central-Eastern European countries based on retail information

Pharmacoepidemiology and Drug Safety — Mon, 14 Dec 2009 00:00:00 +0100

The objective of this study was to evaluate the non-steroidal anti-inflammatory drug market of six Central and Eastern European countries. Trends and similarities were compared across the examined countries.The Intercontinental Marketing Service Health database was used to determine consumption data between the years 2000 and 2007. We applied the anatomical therapeutical chemical-defined daily dose method, focussing on three major non-steroidal anti-inflammatory drug groups: conventional non-steroidal anti-inflammatory drugs, 'stronger cyclooxygenase 2 inhibitors' (all together as: non-cyclooxygenase 2 selective non-steroidal anti-inflammatory drugs) and selective cyclooxygenase 2 inhibitors. The main outcome measure was defined daily dose/1000 inhabitants/day. Different active agents have...

Signal detection for vaccine side effects that have not been specified in advance

Pharmacoepidemiology and Drug Safety — Mon, 14 Dec 2009 00:00:00 +0100

An information-theoretic definition of similarity proposed by Dekang Lin in 1998 appears to have attractive properties for identifying medically similar cases in a large database. Examination of similar cases that appear following vaccination may provide a way of detecting previously unexpected associations. A key element here is the inclusion of shared time-since-vaccination as a dimension of similarity while considering concordance on many other features. The system is potentially much more sensitive to patterns with multiple features than are very large, high-dimension contingency tables. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)

Measuring exacerbations in obstructive lung disease

Pharmacoepidemiology and Drug Safety — Mon, 14 Dec 2009 00:00:00 +0100

Using hospitalization always has been seen as a solid measurement for exacerbation in pharmacoepidemiology, but might lead to an underestimation of disease exacerbation because of a trend towards outpatient care. The aim of this study was to quantify the incidence of different exacerbation markers in obstructive lung disease and to identify predictors for these exacerbation markers.We conducted a cohort study using the PHARMO record linkage system, including demographic details and complete medication histories of more than two million community-dwelling residents in the Netherlands from 1985 onwards. Eligible patients were adult users of inhaled corticosteroids (ICS). Outcome parameters were hospitalization and short courses of systemic corticosteroids. Patients were allowed to have multi...

Usefulness of prescription monitoring programs for surveillance - analysis of Schedule II opioid prescription data in Massachusetts, 1996-2006

Pharmacoepidemiology and Drug Safety — Mon, 14 Dec 2009 00:00:00 +0100

Electronic prescription monitoring programs (PMPs) have been developed in many states as a public health surveillance tool. We analyze herein 11 years of Massachusetts PMP data to evaluate trends in opioid prescribing, dispensing, and usage.Prescription records from the Massachusetts PMP for Schedule II opioids from fiscal year 1996 to 2006 were analyzed. 'Questionable activity' (potential 'doctor shopping') estimates were based on individual use of multiple prescribers and pharmacies, and early refills.The number of prescriptions, doses prescribed, and individuals receiving Schedule II prescription opioids steadily increased from 1996 to 2006. Most individuals (87.5%) used 1-2 prescribers, 1-2 pharmacies, and had no early refills (2006). The greater the number of prescribers used, the gre...

Topical bovine thrombin: a 21-year review of topical bovine thrombin spontaneous case safety reports submitted to FDA's Adverse Event Reporting System

Pharmacoepidemiology and Drug Safety — Sat, 12 Dec 2009 00:00:00 +0100

To review topical bovine thrombin spontaneous adverse event (AE) reports that were forwarded to the US Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS) between January 1986 and December 2006.Forty-one spontaneous AE reports were summarized for reported AE profile and chronological reporting patterns. Each AE report was adjudicated by a hematologist for the topical bovine thrombin product that was given and the AE(s) that were reported. AEs were grouped as allergic, coagulopathy/bleeding, and all other AEs combined. Grouped AE serial analyses were carried out using successive 3-year time increments between 1986 (the year an AE report was first noted for a bovine thrombin product) and 2006 (the first full year that was available at the time of initiation of the data...

Use of psychotropic drugs and analgesics among users of antiobesity drugs - a population based study

Pharmacoepidemiology and Drug Safety — Fri, 11 Dec 2009 00:00:00 +0100

The aim of the present study was to investigate to what extent patients using prescription antiobesity drugs (orlistat, sibutramine and rimonabant) concomitantly or concurrently used psychotropic drugs and analgesics and the association between this drug use and the patients' gender and age. An additional aim was to investigate the sequence of drug therapy among users of both antiobesity drugs and antidepressants or antipsychotics, respectively.Data were retrieved from the Norwegian Prescription Database (NorPD). All patients who had an antiobesity drug (ATC code A08A) dispensed from a Norwegian pharmacy between January 2004 and December 2007 were included in the study.One in four patients using antiobesity drugs had at least on one occasion used a psychotropic drug concomitantly. The most...

Prescription refill records as a screening tool to identify antidepressant non-adherence

Pharmacoepidemiology and Drug Safety — Tue, 08 Dec 2009 00:00:00 +0100

Non-adherence is a significant problem with antidepressants. Identifying patients at highest risk for discontinuing antidepressant treatment can be used to target clinical management. Accordingly, our purpose was to determine the shortest gap in medication supply that is predictive of discontinuation, while minimizing false positive results.A retrospective cohort study of medical and prescription claims from a national health plan affiliated with i3 Innovus. Sensitivities, specificities, and positive and negative predictive values were calculated for gap lengths to assess how well they predicted discontinuation. Continuously insured individuals aged 18-65 with newly diagnosed major depression and an antidepressant prescription within 45 days of diagnosis were included. Gap length was defin...

Congenital abnormalities in children of 43 pregnant women who attempted suicide with large doses of nitrazepam

Pharmacoepidemiology and Drug Safety — Tue, 08 Dec 2009 00:00:00 +0100

To evaluate the teratogenic effect of very large doses of nitrazepam in children born to pregnant women who attempted suicide and to check the feasibility of self-poisoning pregnant women model.Comparative analysis of exposed children and their unexposed sibs born to the same mothers who attempted suicide during the study pregnancy and admitted to the toxicological inpatients clinic, Budapest, 1960-1993.Of 1044 pregnant women who attempted suicide, 107 (10.3%) used large doses of nitrazepam alone or combination with other drugs, and 43 delivered live-born babies, these exposed children were evaluated.Structural birth defects, i.e., congenital abnormalities (CAs), pregnancy age at delivery, and birth weight.The mean dose of nitrazepam used for suicide attempt was 204 mg. Of 43 exposed child...

Thiazolidinediones and the risk of incident strokes in patients with type 2 diabetes: a nested case-control study

Pharmacoepidemiology and Drug Safety — Tue, 08 Dec 2009 00:00:00 +0100

To determine whether the use of thiazolidinediones (TZDs) decreases the risk of incident strokes in patients with type 2 diabetes.We conducted a nested case-control study within a population-based cohort from the UK General Practice Research Database (GPRD). The cohort comprised patients over the age of 40 who were prescribed a first oral hypoglycemic agent between 1 January 1988 and 30 June 2008. Cases included all subjects who experienced a first stroke during follow-up. Up to 10 controls were matched to each case on age (±2 years), sex, date of cohort entry (±1 year), and duration of follow-up. Rate ratios (RRs) of stroke associated with TZD use, including rosiglitazone and pioglitazone, relative to combinations of other oral hypoglycemic agents, were estimated using conditional logis...

Preventable drug related mortality in a Swedish population

Pharmacoepidemiology and Drug Safety — Tue, 08 Dec 2009 00:00:00 +0100

In this study, the preventability of all these identified FADRs and FDPs was evaluated by clinical experts in a stepwise manner, applying a set of predefined and well established preventability criteria. Only cases for which consensus was achieved were included in the study.Of 49 FADRs, 14% (seven fatalities) was considered definitely or possibly preventable and four of these were due to the presence of a contraindication for the drug. All nine FDPs were considered possibly preventable. As one subject had a combination of an FADR and an FDP, a total of 15 persons (26%) were considered having a definitely or possibly preventable FADR or FDP, corresponding to 0.95% of all deceased subjects in Sweden.The results of this study indicate that approximately one fourth of FADRs and FDPs could be p...

Mefloquine prescriptions in the presence of contraindications: prevalence among US military personnel deployed to Afghanistan, 2007

Pharmacoepidemiology and Drug Safety — Mon, 07 Dec 2009 00:00:00 +0100

Contraindications to mefloquine use include a history of certain prevalent neuropsychiatric disorders, which are thought to increase the risk of severe adverse events including anxiety, paranoia, depression, hallucinations, psychosis, and possibly suicide. Within the US military, the continued availability and use of mefloquine is subject to administrative policies dating to 2002 that require clinicians to exercise added caution during prescribing. This analysis was performed to quantify the effectiveness of these policies in ensuring health care provider compliance with package insert prescribing guidance.A previously identified cohort consisting of 11 725 active duty US military personnel, among whom 1127 (9.6%) had contraindications to mefloquine use identified through medical surveilla...

A systematic literature review: prescribing indicators related to type 2 diabetes mellitus and cardiovascular risk management

Pharmacoepidemiology and Drug Safety — Fri, 04 Dec 2009 00:00:00 +0100

Valid prescribing indicators (PI) are needed for reliable assessment of prescribing quality. The purpose of this study is to describe the validity of existing PI for type 2 diabetes mellitus and cardiovascular risk management.We conducted a systematic literature search for studies describing the development and assessment of relevant PIs between January 1990 and January 2009. We grouped identified PI as drug- or disease-oriented, and according to the aspects of prescribing addressed and the additional clinical information included. We reviewed the clinimetric characteristics of the different types of PI.We identified 59 documents describing the clinimetrics of 16 types of PI covering relevant prescribing aspects, including first-choice treatment, safety issues, dosing, costs, sufficient an...

Media attention and the influence on the reporting odds ratio in disproportionality analysis: an example of patient reporting of statins

Pharmacoepidemiology and Drug Safety — Tue, 01 Dec 2009 00:00:00 +0100

To study the influence of media attention about statins and ADRs on the level of disproportionality, expressed as the reporting odds ratio (ROR) for statins in the Lareb database, based on patients' reports.Patient reports about statins, before and after the broadcast of a consumer programme about statins, were compared. In order to calculate the correlation between the ROR for patient-statin reports between the period before and after the broadcast a Pearson correlation-coefficient (r) was calculated. The type of reported ADRs associated with statins before and after the broadcast was compared both on the level of system organ class (SOC) and preferred terms (PT).Pearson's Correlation-coefficient for the comparison of RORs before and after the broadcast was 0.83. In respect to specific AD...

Increasingly restrictive definitions of hyperkalemia outcomes in a database study: effect on incidence estimates

Pharmacoepidemiology and Drug Safety — Thu, 26 Nov 2009 00:00:00 +0100

To determine the incidence of hyperkalemia-associated adverse outcomes among ambulatory patients with diabetes newly initiating renin-angiotensin-aldosterone system (RAAS) inhibitor therapy and to examine to what extent increasingly restrictive definitions of hyperkalemia-associated outcomes influenced incidence estimates.Retrospective cohort study of 27 355 individuals with diabetes who were new users of RAAS inhibitors at three integrated healthcare systems.Using the least restrictive definition of hyperkalemia-associated outcome, an ambulatory visit (AV), inpatient hospitalization (IP), or emergency department (ED) visit co-occurring within 7 days of coded hyperkalemia diagnosis and/or potassium concentration of [ge]5.5 mmol/L, the incidence rate of hyperkalemia was 30.1 per 1000 person...

Factors associated with medicine use among children aged under 12 years - a population survey in Finland

Pharmacoepidemiology and Drug Safety — Tue, 24 Nov 2009 00:00:00 +0100

The goal was to determine the prevalence of medicine use and to provide population-based information on factors associated with medicine use, including prescribed and over-the-counter (OTC) medicines, in children aged under 12 years.A cross-sectional population survey of a random sample of children aged under 12 years (n = 6000) was carried out in Finland in spring 2007, with a response rate of 67%. A questionnaire was sent to their parents. Current use of medicines prescribed by a physician and use of OTC medicines during the preceding two days were the main outcome measures.The prevalence of current prescribed medicine use was 17%, and the 2-day prevalence of OTC medicine use 17% (vitamins excluded). The use of prescribed medicines was higher among children with illnesses diagnosed by a ...

Pravastatin use and cancer risk: a meta-analysis of individual patient data from long-term prospective controlled trials in Japan

Pharmacoepidemiology and Drug Safety — Mon, 26 Oct 2009 00:00:00 +0100

To assess the influence of pravastatin therapy on cancer morbidity and mortality by a meta-analysis of individual patient data (IPD) from three independent Japanese large-scale clinical trials.We conducted a meta-analysis of IPD collected from three large-scale prospective studies, the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study, Kyushu Lipid Intervention Study (KLIS), and Hokuriku Lipid Coronary Heart Disease Study-Pravastatin Atherosclerosis Trial (Holicos-PAT), which compared cardiovascular outcomes with pravastatin therapy and non-statin therapy in Japanese patients with hypercholesterolemia over a follow-up period of [ge]4 years. The incidence of cancer or cancer death in the pravastatin and non-statin therapy groups was compared b...

NSAID switching and short-term gastrointestinal outcome rates after the withdrawal of rofecoxib

Pharmacoepidemiology and Drug Safety — Tue, 20 Oct 2009 23:00:00 +0100

The consequences of the rofecoxib withdrawal on upper GI toxicity are largely unknown. We sought to estimate the effect of switching from selective Cox-2 inhibitors to non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) on the incidence of upper GI adverse events following the withdrawal of rofecoxib on 30 September 2004.We identified a cohort of 33 045 patients with arthritis and chronic use of any selective Cox-2 inhibitor during the 6 months before the withdrawal of rofecoxib in claims data from several US health plans. We calculated monthly rates of hospitalization for upper GI adverse events or upper GI endoscopy for the 6 months before and 3 months after the switching and compared the time trends in outcomes.In the subgroup of 15 916 patients using rofecoxib immediately be...

Validation of diagnostic codes for outpatient-originating sudden cardiac death and ventricular arrhythmia in Medicaid and Medicare claims data

Pharmacoepidemiology and Drug Safety — Mon, 19 Oct 2009 23:00:00 +0100

This study examined the positive predictive value (PPV) of hospitalization and emergency department encounter diagnoses in identifying SD/VA events originating in the outpatient setting.We selected random samples of hospitalizations and emergency department claims with principal or first-listed discharge diagnosis codes indicative of SD/VA in individuals contributing at least 6 months of baseline time within 1999-2002 Medicaid and Medicare data from five large states. We then obtained and reviewed medical records corresponding to these events to serve as the reference standard.We identified 5239 inpatient and 29 135 emergency department events, randomly selected 100 of each, and obtained 119 medical records, 116 of which were for the requested courses of care. The PPVs for an outpatient-or...

Commentary on 'case series of liver failure associated with rosiglitazone and pioglitazone' by James Floyd et al

Pharmacoepidemiology and Drug Safety — Sun, 18 Oct 2009 23:00:00 +0100

No Abstract. (Source: Pharmacoepidemiology and Drug Safety)

Self-medication with antibiotics: questionnaire survey among primary care center attendants

Pharmacoepidemiology and Drug Safety — Tue, 13 Oct 2009 23:00:00 +0100

The aim of this study was to determine the frequency and reasons for self-medication with antibiotics within the last 12 months among primary healthcare center attendants aged 18 or over, in Ankara.A questionnaire was applied by face to face interview technique to 2696 subjects attending at five primary healthcare centers. Information on demographic characteristics, intention to self-medication with antibiotics and self-medication within last 12 months were collected.It was found that 28% of the subjects were storing antibiotics at home. The percentage of self-administering antibiotics was 19.1% in the last 12 months. The most common reasons for self-administration of antibiotics were sore throat (59.6%), fever (46.2%), and cough (40.0%). Other reasons were dental infection, rheumatism, an...

Tramadol dependence: a survey of spontaneously reported cases in Sweden

Pharmacoepidemiology and Drug Safety — Mon, 12 Oct 2009 23:00:00 +0100

Tramadol is a weak opioid analgesic, which is generally considered to be safe. However, conflicting data exist on the dependence potential of tramadol.The aim of this study was to investigate occurrence of tramadol dependence and associated risk factors using spontaneously reported adverse drug reactions.The Swedish database for spontaneously reported adverse drug reactions, Swedish Drug Information System (SweDIS), was searched for reports on tramadol dependence from 1 January 1995 until 31 December 2006. Selection was conducted based on the DSM-IV definition of dependence. Available information was scrutinised and registered and then presented descriptively.A total of 104 reports of tramadol dependence were identified, of which 60 (58%) concerned women. The median age (range) was 45 (15-...

The identification of pregnancies within the general practice research database

Pharmacoepidemiology and Drug Safety — Mon, 12 Oct 2009 23:00:00 +0100

The United States is moving toward active drug safety surveillance using sources such as administrative claims and electronic medical records, but use of these data for studying teratogenicity has been challenging, as they typically do not allow for the easy identification of pregnancies. Our goal was to develop and validate an algorithm for the identification of pregnancies in the general practice research database (GPRD) that could be used to study pregnancy outcomes.The algorithm identified pregnancies in women 15-45-year-old that were pregnant between 1 January 1987 and 31 December 2006. We identified live births, stillbirths, and spontaneous and elective terminations within a woman's record. We validated the algorithm using the additional clinical details maternity (ACDM) file and de-...

Influence of genetic variation in CYP3A4 and ABCB1 on dose decrease or switching during simvastatin and atorvastatin therapy

Pharmacoepidemiology and Drug Safety — Fri, 02 Oct 2009 23:00:00 +0100

Simvastatin and atorvastatin are metabolized by the CYP3A4 enzyme and transported by the ABCB1 transporter. We studied whether the polymorphism CYP3A4*1B and the polymorphisms C1236T, G2677A/T and C3435T in the ABCB1 gene were associated with a decrease of the prescribed dose or a switch to another cholesterol lowering drug during simvastatin and atorvastatin therapy. These events may indicate that statin plasma levels were too high and resulted in an adverse drug reaction or a too strong reduction in cholesterol level.We identified 1239 incident simvastatin and atorvastatin users in the Rotterdam Study, a population-based cohort study. Associations between the polymorphisms in the CYP3A4 and ABCB1 gene and the time to a decrease in dose or a switch to another cholesterol lowering drug wer...

Antiepileptic drugs in Australia: 2002-2007

Pharmacoepidemiology and Drug Safety — Thu, 01 Oct 2009 23:00:00 +0100

We examined the trends in the prescribing of subsidised AEDs in the Australian population from 2002 to 2007.We analysed the Medicare Australia and Drug Utilisation Sub-Committee databases for script data for AEDs from 2002 to 2007 in 5-year age groups by gender and by class of prescriber. Scripts were converted to defined daily doses (DDDs)/1000/day using Australian Bureau of Statistics population data.Overall AED use (mainly valproate, lamotrigine and levetiracetam) increased progressively in 2002-2007 from 9.33 to 10.12 DDD/1000 population/day. Sodium valproate was the most widely used agent followed by carbamazepine then phenytoin. Amount of AED used increased in those aged in their 20s and 30s to plateau between 40 and 90 years. Use peaked in those aged 80-84 years and was slightly hig...

Should response rules be used to decide continued subsidy of very expensive drugs? A checklist for decision makers

Pharmacoepidemiology and Drug Safety — Thu, 01 Oct 2009 23:00:00 +0100

We present a four-item checklist that may be used to help decision makers identify when a response rule is appropriate. As an example, we apply our checklist to the response rules used for tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis. On the basis of the checklist we find that the response rules in both countries are inadequate and may cause therapy to be inappropriately ceased in some and continued in others. Careful assessment is needed before decision makers adopt a response rule as a way of increasing the cost effectiveness of therapy. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)

Trends of the potentially inappropriate medication consumption over 10 years in older adults in the East of France

Pharmacoepidemiology and Drug Safety — Wed, 30 Sep 2009 23:00:00 +0100

This study shows a decrease in PIM consumption. Despite an increase of drug use in the elderly, an improving of the quality of this consumption remains possible. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)

An application of propensity score methods to estimate the treatment effect of corticosteroids in patients with severe cutaneous adverse reactions

Pharmacoepidemiology and Drug Safety — Tue, 29 Sep 2009 23:00:00 +0100

To investigate whether propensity score (ps) methods could reasonably be applied to estimate the treatment effect on mortality, based on a comparatively small sample of patients with severe cutaneous adverse reactions (SCAR) and who come from different countries where physicians prefer different treatment schemes.Ps methods were applied to cope with confounding due to non-randomized treatment assignment for the analysis of the treatment data obtained in the case-control study EuroSCAR. For the study's purpose, the analysis focused on the comparison of the treatments: corticosteroids (STER) and supportive care only (SUPP).206 French and German patients were treated either with SUPP or STER. Imbalances between treatment groups as well as between the countries were recognized. Concerning the ...

Polypharmacy in primary care practices: an analysis using a large health insurance database

Pharmacoepidemiology and Drug Safety — Tue, 29 Sep 2009 23:00:00 +0100

To ascertain the rate and range of continuous polypharmacy in German general practices and compare practice characteristics and prescribing profiles in practices with a high rate of polypharmacy patients (HPP) and a low rate of polypharmacy patients (LPP), respectively.This observational study used a database composed of prescription data from a large German statutory health insurance. We defined polypharmacy as the continuous prescription of five or more drugs and calculated the percentage of polypharmacy patients for each practice to identify HPP and LPP.A total of 136 521 patients in 730 general practices received continuous medication. About 10% of these patients (14 293/136 521) received five or more different drugs. HPP had, on average, 15.1% polypharmacy patients compared to 4.2% in...

Compliance with dosing recommendations from common references in prescribing antibiotics for preterm neonates

Pharmacoepidemiology and Drug Safety — Thu, 24 Sep 2009 23:00:00 +0100

This study assesses the compliance rate with the common reference sources in antibiotic dosage prescribed for preterm infants in a neonatal intensive care unit (NICU).A retrospective study using chart review was conducted at a tertiary care medical center with university affiliation in Taiwan. Study subjects were preterm neonates admitted to the NICU of the medical center between 2000 and 2002 and prescribed at least one antibiotic during the stay. Recommendations from three commonly used reference sources (Pediatric Dosage Handbook, Neonatal Drug Formulary, and Neofax) were employed to evaluate the dosage compliance of the antibiotic prescriptions.A total of 433 preterm infants and 3459 prescriptions were included. Depending on the reference source used, the percentages of antibiotic pres...

Effectiveness of rosuvastatin compared to other statins for the prevention of cardiovascular events - a cohort study in 395 039 patients from clinical practice

Pharmacoepidemiology and Drug Safety — Wed, 23 Sep 2009 23:00:00 +0100

This study compared the effectiveness of rosuvastatin (RSV) to other statins prescribed in clinical practice in prevention of cardiovascular (CV) events.This longitudinal inception cohort study, using Thomson Healthcare's MarketScan databases, included patients aged [ge] 18 starting statin therapy during August 2003-December 2005. Patients were followed until 90 days after index statin monotherapy exposure, start of another lipid-lowering therapy, an event, end of eligibility, or end of study. The primary endpoint was a composite of CV death (in-hospital only), myocardial infarction, unstable angina, coronary revascularization, stroke, and carotid revascularization. Adjusted time-to-event analyses incorporating a propensity score covariate were used, and analyses were stratified by duratio...

Prevalence and safety-relevance of drug-related problems in German community pharmacies

Pharmacoepidemiology and Drug Safety — Tue, 22 Sep 2009 23:00:00 +0100

The purpose of this study was to assess prevalence and characteristics, including safety-relevance, of drug-related problems (DRPs) detectable in community pharmacy routine service, and to investigate the influence of relevant risk factors.Patients in 69 community pharmacies in Berlin were surveyed using a checklist for quality assurance of DRP detection in order to enable quantitative detection. An expert committee assessed the safety-relevance of detected DRPs by use of an algorithm. Logistic regression analysis was applied to investigate the influence of different risk factors.Of the 3040 surveyed patients, 638 (21.0%) were affected by DRPs. Among these, 455 (71.3%) had problems of low, 170 (26.6%) of significant and 13 (2.0%) of high safety-relevance. Significant risk factors identifie...

Phynx: an open source software solution supporting data management and web-based patient-level data review for drug safety studies in the general practice research database and other health care databases

Pharmacoepidemiology and Drug Safety — Tue, 22 Sep 2009 23:00:00 +0100

To develop a software solution that supports management and clinical review of patient data from electronic medical records databases or claims databases for pharmacoepidemiological drug safety studies.We used open source software to build a data management system and an internet application with a Flex client on a Java application server with a MySQL database backend. The application is hosted on Amazon Elastic Compute Cloud. This solution named Phynx supports data management, Web-based display of electronic patient information, and interactive review of patient-level information in the individual clinical context. This system was applied to a dataset from the UK General Practice Research Database (GPRD).Our solution can be setup and customized with limited programming resources, and ther...

Factors associated with a continuous regular analgesic use - a population-based study of more than 45 000 Danish women and men 18-45 years of age

Pharmacoepidemiology and Drug Safety — Mon, 14 Sep 2009 23:00:00 +0100

The objective of this study was to describe continuous regular analgesics use and examine factors associated with a continuous regular analgesic use.The study was based on data from two surveys and included a random sample of women and men aged 18-45 years from the general Danish population. Information on analgesics use, self-rated health, demographic and lifestyle factors was collected using a self-administered questionnaire. A total of 28 000 women and 33 000 men were invited to participate and 22 199 women (response-rate 81.4%) and 23 080 men (response-rate 71.0%), respectively, were included in the study. Data were analyzed using multivariate logistic regression.We found that 27% of the women and 18% of the men reported a regular monthly use of at least seven analgesic tablets during ...

Calcium supplementation, cardiovascular disease and mortality in older women

Pharmacoepidemiology and Drug Safety — Mon, 14 Sep 2009 23:00:00 +0100

To investigate the long-term cumulative effect of calcium and vitamin D supplementation on cardiovascular outcomes and death in older women.We undertook an observational cohort study using UK electronic primary care records in the Doctor's Independent Network (DIN-LINK) database; 9910 women aged 60-89 who started calcium and vitamin D supplementation between 2000 and 2005, with no heart disease or stroke history and who survived disease free for 2 years after supplement initiation were studied. The main outcome was first occurrence of myocardial infarction (MI), stroke or death more than 2 years after initiation.In the period from 2 years after supplement initiation, women who had received >600 days supplementation in these first 2 years were no more at risk of MI, stroke or death (hazard ...

Confounder summary scores when comparing the effects of multiple drug exposures

Pharmacoepidemiology and Drug Safety — Mon, 14 Sep 2009 23:00:00 +0100

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS).Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard mod...

Systematic reviews of adverse effects of drug interventions: a survey of their conduct and reporting quality

Pharmacoepidemiology and Drug Safety — Mon, 14 Sep 2009 23:00:00 +0100

There is a need for high quality evidence on the adverse effects of medical interventions to inform policy, practice and research. Methods to systematically review adverse effects have not been fully developed. We aimed to assess the current methods and reporting used by such reviews.Survey of general medical, drug safety and pharmacology journals published in 2006. Methods including: searching, inclusion criteria, quality assessment and meta-analysis were assessed.Forty three systematic reviews from 2704 abstracts in 16 journals were included. The search strategy was not reported by 10 (23%) of reviews. The collection and reporting of the adverse effects from primary studies was described by 4/37 (12%) reviews and the quality of included studies was assessed by 15 (35%) of reviews. Meta-a...

Data mining on electronic health record databases for signal detection in pharmacovigilance: which events to monitor?

Pharmacoepidemiology and Drug Safety — Mon, 14 Sep 2009 23:00:00 +0100

Data mining on electronic health records (EHRs) has emerged as a promising complementary method for post-marketing drug safety surveillance. The EU-ADR project, funded by the European Commission, is developing techniques that allow mining of EHRs for adverse drug events across different countries in Europe. Since mining on all possible events was considered to unduly increase the number of spurious signals, we wanted to create a ranked list of high-priority events.Scientific literature, medical textbooks, and websites of regulatory agencies were reviewed to create a preliminary list of events that are deemed important in pharmacovigilance. Two teams of pharmacovigilance experts independently rated each event on five criteria: 'trigger for drug withdrawal', 'trigger for black box warning', ...

Evaluating the positive predictive values of antidote signals to detect potential adverse drug reactions (ADRs) in the medical intensive care unit (ICU)

Pharmacoepidemiology and Drug Safety — Tue, 01 Sep 2009 23:00:00 +0100

Signals are used to alert clinicians of potential ADRs. Positive predictive values (PPVs) of antidote signals in ICUs are unknown. The primary purpose was to determine PPVs of six signals. The secondary objective was to determine the sensitivity of various ADR detection strategies including manual chart review, administrative data review, and voluntary reporting at identifying the same ADRs discovered using antidotes as a signal.Adult patients admitted to a medical ICU from July 1, 2005 to June 30, 2006 who were prescribed select signals were eligible. Evaluated antidote signals included injectable diphenhydramine, protamine, phytonadione, dextrose 50%, injectable methylprednisolone, and sodium polystyrene. For each signal, a random sample of 50 patients was evaluated for the presence of a...

Using health information technology to improve drug monitoring: a systematic review

Pharmacoepidemiology and Drug Safety — Mon, 31 Aug 2009 23:00:00 +0100

To conduct a systematic review of current evidence regarding the use of health information technology (HIT) interventions to improve drug monitoring in ambulatory care.We searched PubMed, CINAHL, the Cochrane Library, and other computerized databases from 1 January 1998 to 30 June 2008 using the key words "drug monitoring," "medical records systems, computerized," "ambulatory care," and "outpatients." We manually reviewed reference lists of articles identified through computer searches and asked experts in the field to review our search strategy and results for completeness.Seven relevant studies were identified. Four of these studies assessed real-time interventions that used alerts to physicians at the time of medication ordering to ensure adequate monitoring, only one of which showed an...

The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada

Pharmacoepidemiology and Drug Safety — Fri, 28 Aug 2009 23:00:00 +0100

This study showed a modest increased risk of AMI/CHD with various traditional NSAIDs and COX-2 inhibitors. Confidence intervals of estimated ORs included the null value for most comparisons. The study confirmed that the differentiation between traditional NSAIDs and COX-2 inhibitors is not a reliable tool for predicting cardiovascular risk associated with NSAIDs. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)

The effect of selected patient's characteristics on the choice of antihypertensive medication in the elderly in Slovakia

Pharmacoepidemiology and Drug Safety — Thu, 27 Aug 2009 23:00:00 +0100

The aim of the present study was to determine which patient-related characteristics influence the selection of the antihypertensive drug class in elderly patients in Slovakia.The sample for our study (n = 401) was selected from 1045 patients admitted to the Department of Internal Medicine of a general hospital during the period of 1 December 2003 - 31 March 2005. Patients aged 65 or more with documented arterial hypertension and treated with at least one antihypertensive drug were enrolled in our retrospective study. Specific socio-demographic and clinical characteristics as well as cardiovascular comorbid conditions were evaluated as potential factors that could have influenced the choice of antihypertensive drug class.The most frequently prescribed antihypertensive drugs were angiotensin...

Trends in long-term opioid therapy for chronic non-cancer pain

Pharmacoepidemiology and Drug Safety — Thu, 27 Aug 2009 23:00:00 +0100

To report trends and characteristics of long-term opioid use for non-cancer pain.CONSORT (CONsortium to Study Opioid Risks and Trends) includes adult enrollees of two health plans serving over 1 per cent of the US population. Using automated data, we constructed episodes of opioid use between 1997 and 2005. We estimated age-sex standardized rates of opioid use episodes beginning in each year (incident) and on-going in each year (prevalent), and the per cent change in rates annualized (PCA) over the 9-year period. Long-term episodes were defined as > 90 days with 120+ days supply or 10+ opioid prescriptions in a given year.Over the study period, incident long-term use increased from 8.5 to 12.1 per 1000 at Group Health (GH) (6.0% PCA), and 6.3 to 8.6 per 1000 at Kaiser Permanente of Norther...

An algorithm to identify incident myocardial infarction using Medicaid data

Pharmacoepidemiology and Drug Safety — Thu, 27 Aug 2009 23:00:00 +0100

Studies of non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events using administrative data require identification of incident acute myocardial infarctions (AMIs) and information on whether confounders differ by NSAID status.We identified patients with a first AMI hospitalization from Tennessee Medicaid files as those with primary ICD-9 discharge diagnosis 410.x and hospitalization stay of > 2 calendar days. Eligible persons were non-institutionalized, aged 50-84 years between 1999-2004, had continuous enrollment and no AMI, stroke, or non-cardiovascular serious medical illness in the prior year. Of 5524 patients with a potential first AMI, a systematic sample (n = 350) was selected for review. Using defined criteria, we classified events using chest pain history, EKG, an...

Gender differences in the use of anxiolytics and antidepressants: a population based study

Pharmacoepidemiology and Drug Safety — Mon, 17 Aug 2009 23:00:00 +0100

In the majority of studies on determinants of use of anxiolytics and antidepressants a substantially higher consumption is observed among women than among men. We investigated gender differences in the association between the use of anxiolytics and antidepressants and mental health and explored if there are indications of gender differences in inappropriate use of these medicines.Data were from the 2004 Belgian Health Interview Survey, a nationally representative sample of the Belgian population. The analysis was restricted to the population of 15 years and older (n = 11,220). The probability of use of anxiolytics and antidepressants was assessed through logistic regression models by gender and through models including the interaction between gender and mental health.The association betwee...

U.S. physician knowledge of the FDA-approved indications and evidence base for commonly prescribed drugs: results of a national survey

Pharmacoepidemiology and Drug Safety — Thu, 13 Aug 2009 23:00:00 +0100

The Food and Drug Administration (FDA) regulates prescription drug marketing, not prescribing. However, off-label use is common, often lacks supporting evidence, and may expose patients to unwarranted risk. We sought to determine physicians' knowledge of the FDA-approved indications of commonly prescribed drugs, and to assess whether physicians' belief that an indication is FDA-approved increases with level of evidence supporting such use.We conducted a national random sample mail survey of 599 primary care physicians and 600 psychiatrists from November 2007 to August 2008. Physicians were presented with 14 drug-indication pairs (e.g., gabapentin [Neurontin®] for diabetic neuropathy) that varied in their FDA-approval status and levels of supporting evidence.The adjusted response rate was ...

Out-of-hospital medication errors: a 6-year analysis of the national poison data system

Pharmacoepidemiology and Drug Safety — Thu, 13 Aug 2009 23:00:00 +0100

Previous research and reporting has focused on the incidence and prevention of medication errors in the hospital setting; however, no previous study has reported the frequencies, characteristics and outcomes of out-of-hospital medication (OHME) errors.Data from the National Poison Data System (NPDS) was collected for 2000-2005 and information regarding out-of-hospital medication errors reported to Poison Control Centers (PCC) was collected by a trained investigator.From 2000-2005 there were 1,166,116 OHME reported to PCC. Of these patients, 88,451 (7.5%) received medical evaluation by a healthcare provided and 229 (0.01%) deaths reported. The most common drug classes involved included cough/cold medications, analgesics, cardiovascular agents, antihistamines, antidepressants and antimicrobi...

Validity of computerized diagnoses, procedures, and drugs for inflammatory bowel disease in a northern California managed care organization

Pharmacoepidemiology and Drug Safety — Tue, 11 Aug 2009 23:00:00 +0100

Resources for studying inflammatory bowel disease (IBD) are needed in evaluations of drug safety including traditional drugs and new biologics agents. We developed an IBD registry, with ascertainment from computerized visit information.We sought to characterize the positive predictive value (PPV) of IBD case-finding using computerized data compared with chart review.We identified 2906 persons aged 89 years or younger with one or more IBD diagnoses in computerized visit data during the period of 1996-2002. The diagnosis of IBD was confirmed through chart review. Adopting chart review as the gold standard, the validity of computerized encounter data to determine IBD was estimated.Among the 2906 study subjects with one or more ICD-9 diagnosis codes of 555 or 556 in computerized data, 81% were...

Aspirin increases mortality in diabetic patients without cardiovascular disease: a Swedish record linkage study

Pharmacoepidemiology and Drug Safety — Mon, 10 Aug 2009 23:00:00 +0100

Aspirin is effective in secondary prevention of cardiovascular disease. The results are less convincing when aspirin is used for primary prevention even in high-risk patients (i.e., patients with diabetes). We therefore analyzed the effect of aspirin on mortality and serious bleeding in diabetic patients with and without cardiovascular disease.We performed a record linkage study of the patient registry of the Västra Götaland region in south-western Sweden, the Swedish mortality register and the Swedish register of dispensed drugs. All diabetic patients (n = 58 465) from 1 July 2005 to 30 June 2006 were followed up with respect to bleeding until 31 October 2006, and mortality until 31 December 2006.When 19 confounding factors (diseases and interventions) were assessed, aspirin significant...

Prescription quality in an acute medical ward

Pharmacoepidemiology and Drug Safety — Sun, 09 Aug 2009 23:00:00 +0100

This study demonstrates a relatively acceptable level of prescription quality compared to the published literature. However, the number of DDIs and level of allergy documentation are of concern emphasising the need for continued education in this field. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)

Global benefit-risk analysis of adjunctive aripiprazole in the treatment of patients with major depressive disorder

Pharmacoepidemiology and Drug Safety — Wed, 05 Aug 2009 23:00:00 +0100

This study quantified the overall merit of adjunctive aripiprazole in major depressive disorder (MDD).Global benefit-risk (GBR) analysis quantified the benefit and risk differences between adjunctive aripiprazole and antidepressant (ADT) monotherapy. Three hundred and fifty six patients receiving ADT monotherapy and 366 patients receiving ADT and adjunctive aripiprazole (2-20 mg/day) were included. Efficacy measures included the Montgomery-Åsberg depression rating scale (MADRS) Total score response ([ge]50% reduction) and remission (response plus Total score [le] 10). Treatment-emergent adverse events were classified by severity. GBR ratio measures evaluated the relative benefit of adjunctive aripiprazole. Logistic regression models tested the effect of adjunctive aripiprazole on GBR and ...

Monitoring of drug-associated electrolyte disturbances in a hospital

Pharmacoepidemiology and Drug Safety — Tue, 04 Aug 2009 23:00:00 +0100

The aim of our study was to find drug-associated changes in serum levels of major electrolytes using clinical-event monitoring method.During 1-year period, electrolyte disturbances in serum samples from patients of Clinical Center Kragujevac, Serbia, were monitored in central biochemical facility. A sample of 982 patients was randomly selected from total population of 43 120 patients whose electrolyte serum levels were measured in the facility during the study period.Clinically important drug-associated electrolyte disturbances were detected in 181 patient. There were 25 significant associations between the drugs and electrolyte values outside the reference range. However, only four causal connections were established: use of normal saline infusion with hypernatremia (OR 6.97, 95%CI 2.24-2...

Temporal trends in anti-diabetes drug use in tricare following safety warnings in 2007 about rosiglitazone

Pharmacoepidemiology and Drug Safety — Mon, 03 Aug 2009 23:00:00 +0100

To describe utilization patterns for anti-diabetes medications among a cohort of diabetes patients in the Military Health System (MHS) before and after warnings about rosiglitazone issued in May 2007.We used segmented regression analysis to compare changes in the level and trend of rosiglitazone utilization and use of other anti-diabetes therapies in the period prior to the drug warnings (between April 2006 and May 2007) and the period after the warnings were issued (between October 2007 and May 2008).The level and trend of rosiglitazone use changed after the highly publicized warnings. The number of prescriptions filled fell by almost 7000 after the warning (p < 0.001). The number of prescriptions filled for pioglitazone, sulfonylureas, and other diabetes drugs increased significantly aft...

Commentary on 'case series of liver failure associated with rosiglitazone and pioglitazone' by Floyd et al.

Pharmacoepidemiology and Drug Safety — Mon, 03 Aug 2009 23:00:00 +0100

No Abstract. (Source: Pharmacoepidemiology and Drug Safety)

Access to linked administrative healthcare utilization data for pharmacoepidemiology and pharmacoeconomics research in Canada: anti-viral drugs as an example

Pharmacoepidemiology and Drug Safety — Sun, 02 Aug 2009 23:00:00 +0100

Administrative healthcare utilization data from Canadian provinces have been used for pharmacoepidemiology and pharmacoeconomics research, but limited transparency exists about opportunities for data access, who can access them, and processes to obtain data. An attempt was made to obtain data from all 10 provinces to evaluate access and its complexity.An initial enquiry about the process and requirements to obtain data on individual, anonymized patients dispensed any of four anti-viral drugs in the ambulatory setting, linked with data from hospital and physician service claims, was sent to each province. Where a response was encouraging, a technical description of the data of interest was submitted.Data were unavailable from the provinces of New Brunswick, Newfoundland and Labrador, and Pr...

Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden

Pharmacoepidemiology and Drug Safety — Sun, 02 Aug 2009 23:00:00 +0100

We describe the pattern of spontaneously reported CAM related adverse reactions submitted to the Swedish Medical Products Agency (MPA) and highlight areas of safety concern.All adverse reactions spontaneously reported to MPA between 1987 and 2006, where at least one CAM substance was a suspected agent, were scrutinised. From each report information about the patient, adverse reaction/s, drug treatment/s, dosage, time relationship and outcome was retrieved.Among a total of 64 493 reports, 778 reports concerned 967 suspected adverse reactions related to 175 different CAM products. The main distribution of suspected adverse reactions was: urticaria (8.3%), exanthema (7.4%) and contact dermatitis (5.7%). The most reported CAM substances were purple coneflower (Echinacea purpurea) (8.1%), purpl...

Highly active antiretroviral therapy adherence and its determinants in selected hospitals from south and central Ethiopia

Pharmacoepidemiology and Drug Safety — Sun, 02 Aug 2009 23:00:00 +0100

To determine the adherence rate and its determinants among people living with HIV/AIDS on highly active antiretroviral therapy (HAART) in selected governmental hospitals from central and south Ethiopia.A cross-sectional study involving both qualitative and quantitative methods was conducted between August and October 2007 in Yirgalem, Hawassa, and Shashemene Hospitals. Quantitative data collection techniques include patient self-report and unannounced pill count and the qualitative methods employed were focus group discussions (FGDs), semi-structured interviews, and observations of health facilities.Whereas females accounted for 56.4% (238), male participants were 43.6% (184) of the total participants. Adherence rate was 93.1% using 15-days self-report, but the rate came down to 88.1% when...

Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials

Pharmacoepidemiology and Drug Safety — Sun, 02 Aug 2009 23:00:00 +0100

Some clinicians may favor a strategy of early switch to oral antimicrobial therapy for patients responding to initial intravenous therapy. An important relevant consideration refers to the comparative safety and tolerability between oral and intravenous antimicrobial therapy.We sought to evaluate the above-mentioned issue by performing a systematic review of randomized studies comparing the occurrence of adverse events between oral and intravenous antimicrobial therapy with the same agents.Ten relevant studies (five randomized controlled trials, three randomized cross-over studies, and two randomized, placebo-controlled, parallel-design studies) were included. Seven of the studies evaluated antibacterials (fluoroquinolones in four, and telithromycin, amoxicillin-clavulanic acid, and linezo...

Non-aspirin NSAIDs, cyclooxygenase-2 inhibitors and risk for cardiovascular events-stroke, acute myocardial infarction, and death from coronary heart disease

Pharmacoepidemiology and Drug Safety — Mon, 27 Jul 2009 23:00:00 +0100

To determine if certain non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of cardiovascular events: acute myocardial infarction (AMI), stroke, and death from coronary heart disease (CHD).We conducted a retrospective cohort study of Tennessee Medicaid enrollees aged 35-94 years between 1 January 1999 and 31 December 2005. Eligible persons were non-institutionalized, had continuous enrollment, and had no serious illness prior to cohort entry. Exposure to celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin was studied. The outcome was hospitalization for AMI, stroke, or death from CHD among those with and without a history of cardiovascular disease (CVD). Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) are repo...

What do pregnant women know about non-steroidal anti-inflammatory drugs?

Pharmacoepidemiology and Drug Safety — Thu, 23 Jul 2009 23:00:00 +0100

Non-steroidal anti-inflammatory drug (NSAID) use on late pregnancy can be associated with severe adverse neonatal outcomes. Some NSAIDs, available over the counter, can be purchased easily by pregnant women. The present study evaluates pregnant womens' knowledge about NSAID use in pregnancy.The survey includes 250 pregnant women in South-west France. Women have been interviewed about their knowledge on analgesic and NSAID use in pregnancy.A total of 2% pregnant women use aspirin or ibuprofen as self-medication. More than 10% of the women think that it is safe to take NSAIDs on late pregnancy. A majority of them thought that aspirin and ibuprofen are not NSAIDs.NSAID risks in pregnancy are insufficiently known. Adequate information must be provided not only to medical practitioners and phar...

Methodological variability in detecting prescribing errors and consequences for the evaluation of interventions

Pharmacoepidemiology and Drug Safety — Thu, 23 Jul 2009 23:00:00 +0100

In this study, each method predominantly identified different PE. A combination of methods may be required to understand the true effectiveness of different interventions. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)

Increase in lipid-lowering treatment rates among TRICARE beneficiaries: a population-based study

Pharmacoepidemiology and Drug Safety — Thu, 23 Jul 2009 23:00:00 +0100

To evaluate the use of lipid-lowering treatment (LLT) among patients at risk for cardiovascular disease (CVD) in the US Military Health System (MHS).The study examined healthcare service and prescription records among beneficiaries [ge]18 years for calendar years 2002, 2004, and 2006. Patients were categorized based on cardiovascular (CV) risk, with exposure to LLT defined as one or more prescriptions for lipid-lowering medication. Logistic regression models estimated odds of treatment in 2004 and 2006 relative to 2002 after adjustment for age, gender, and CV risk.The yearly unadjusted population prevalence of LLT increased from 9.3% in 2002 to 14.7% in 2006. Among subjects with the highest CV risk, established coronary artery disease (CAD) or peripheral vascular disease (PVD), those recei...

Case series of liver failure associated with rosiglitazone and pioglitazone

Pharmacoepidemiology and Drug Safety — Tue, 21 Jul 2009 23:00:00 +0100

The thiazolidinedione drugs rosiglitazone and pioglitazone are not widely known to be hepatotoxic. We evaluated the FDA Adverse Event Reporting System (AERS) to determine the number of reported cases of liver failure associated with rosiglitazone and pioglitazone between 1997 and 2006, and described their clinical characteristics.Adverse event reports spontaneously submitted to the FDA AERS from 1997 to 2006 were examined. Liver failure associated with rosiglitazone or pioglitazone was defined as liver injury accompanied by hepatic encephalopathy, liver transplantation, placement on a liver transplant list, or death in which all other likely etiologies were excluded. Using prescribing data, the number of reported cases of liver failure per million patient-years of exposure was calculated f...

Positive predictive value of computerized medical records for uncomplicated and complicated upper gastrointestinal ulcer

Pharmacoepidemiology and Drug Safety — Tue, 21 Jul 2009 23:00:00 +0100

Computerized databases can be an efficient resource to study the epidemiology of peptic ulcer (PU) and upper gastrointestinal complications (UGIC) if we achieve a high positive predictive value (PPV) of outcome definitions. We assessed the PPV of diagnosis codes in THIN, a primary-care medical-record database, to ascertain individuals with uncomplicated PU, and to identify UGIC and Helicobacter pylori infection status (HPIS) among these patients.We identified: (1) patients with codes suggesting a first episode of uncomplicated PU; (2) episodes of UGIC among them. The computerized profiles with free-text comments of these individuals were reviewed and classified as definite, possible, or excluded cases. Dates and HPIS were also ascertained. For a sample of definite and possible PU, and for ...

Local anaesthetic drugs: adverse effects as reported through the ADROIT system in the UK

Pharmacoepidemiology and Drug Safety — Mon, 20 Jul 2009 23:00:00 +0100

Adverse drug reactions (ADRs) to local anaesthetic drugs are reported voluntarily through the Adverse Drug Reporting On Line Tracking system (ADROIT). We aimed to determine hazards associated with drugs commonly used in anaesthesia including ropivacaine and levobupivacaine.The ADROIT database was queried for all ADRs to local anaesthetics used in anaesthesia and surgery between 1967 and 2005. Details of age, sex, suspect drug, date and reaction details were analysed.There were 985 reports analysed, 797 for lidocaine, 160 for bupivacaine, 16 for ropivacaine and 12 for levobupivacaine. The female to male ratio was 1.6:1 and age was not a factor determining the frequency of reactions. A vasoconstrictor was included in the lidocaine formulation in 27% of reports. When methylprednisolone (Depo-...

Comparison of sales and reimbursement data regarding outpatient antibiotic use in a northern Italian Region

Pharmacoepidemiology and Drug Safety — Mon, 20 Jul 2009 23:00:00 +0100

To evaluate the accuracy of systemic antibiotic use statistics, based on the reimbursement data of the Emilia-Romagna Region (Italy), focusing on agents prescribed for urinary tract infections.Reimbursement data were obtained from the drug prescription database that includes all outpatient drug prescriptions reimbursed by the Regional Health Service in 2007. Reimbursements were compared to sales data, provided by International Medical Statistics (IMS) Health.The reimbursement data of the Emilia-Romagna Region significantly underestimates the actual use of systemic antibiotics when compared to sales. The overall underestimation of antibiotic use is 19%, ranging from 7% for second-third-generation cephalosporins to 98% for nitrofurantoin. Considering agents prescribed for urinary tract infec...

Refill adherence and polypharmacy among patients with type 2 diabetes in general practice

Pharmacoepidemiology and Drug Safety — Mon, 20 Jul 2009 23:00:00 +0100

This study aims to investigate the occurrence of polypharmacy and non-adherence in general practice, their mutual relationship and the association between adherence and the intermediate outcomes of diabetes care.We used the baseline and follow-up data of a randomised controlled trial (RCT) that compared usual care with care in accordance with a locally adapted national guideline. This study took place in the Netherlands and involved 30 general practices and 1283 patients. We obtained a complete medication profile of all participants and calculated the number of prescribed drugs and the adherence indices (AI) for oral blood glucose, blood pressure and cholesterol lowering drugs. Patients with an adherence index < 0.8 were considered non-adherent. Clustering at practice level and case-mix we...

Antidepressant use and colorectal cancer risk

Pharmacoepidemiology and Drug Safety — Mon, 20 Jul 2009 23:00:00 +0100

A previous epidemiologic study reported a 30% reduced risk of colorectal cancer among users of high doses of selective serotonin reuptake inhibitors (SSRIs). We assessed the association of colorectal cancer risk with SSRI and tricyclic antidepressant use in our hospital-based Case Control Surveillance Study.For the SSRI analyses, we used data collected on 529 colorectal cancer cases and 1955 hospitalized controls collected from 1995 to 2008. For the tricyclic antidepressant analyses, we used data on 2889 cases and 7122 controls collected from 1976 to 2008. We used multivariable logistic regression analysis to evaluate the association of regular SSRI use and regular tricyclic antidepressant use (daily use for at least 3 continuous months) with colorectal cancer risk.The odds ratio for regul...

Overdose of methyldopa, indapamide and theophylline resulting in prolonged hypotension, marked diuresis and hypokalaemia in an elderly patient

Pharmacoepidemiology and Drug Safety — Mon, 20 Jul 2009 23:00:00 +0100

An 89-year-old man with a history of hypertension, chronic obstructive pulmonary disease, personality disorder and previous attempts of self-poisoning attempted suicide by swallowing two mouthfuls of tablets (methyldopa 250 mg, theophylline SR 200 mg, indapamide 2.5 mg and paracetamol 500 mg). He had prolonged, severe hypotension, necessitating the use of 3000 ml of Gelofusine® and almost 2 days of intravenous norepinephrine infusion. He had marked diuresis for 4.5 days, requiring continuous and bolus infusions of intravenous fluids. He had marked renal potassium loss, requiring vigorous potassium replacement therapy. Multiple-dose activated charcoal was used to enhance theophylline elimination. The plasma paracetamol level was below the treatment line. Methyldopa via its metabolite stimu...

Trends in the prescription of anti-diabetic medications in the United Kingdom: a population-based analysis

Pharmacoepidemiology and Drug Safety — Sun, 19 Jul 2009 23:00:00 +0100

The objective of this study was to describe trends in the prescription of anti-diabetic medications among patients with type 2 diabetes in the United Kingdom (UK).Using the General Practice Research Database, we constructed a cohort of patients with type 2 diabetes. Diabetes was defined as the presence of a diagnosis of diabetes, HbA1c [ge] 7%, or [ge] 2 prescriptions for anti-diabetic medications. Analyses were conducted for the full cohort as well as a sub-cohort with incident diabetes.Our full cohort involved 67 981 patients and a total of 320 089 patient-years, and our sub-cohort involved 30 234 patients with incident diabetes and 111 890 patient-years. From 2000 to 2006, there was a substantial increase in the prescription rate of anti-diabetic medications. Overall, there were 9.6 pre...

Spontaneous reporting of adverse drug events by Korean regional pharmacovigilance centers

Pharmacoepidemiology and Drug Safety — Sun, 19 Jul 2009 23:00:00 +0100

In this study, we analyzed the causative drugs and clinical manifestations of spontaneously reported ADRs in Korea.Six Korean Regional Pharmacovigilance Centers collected 1418 cases of spontaneously reported adverse drug events (ADEs) by doctors, pharmacists, and nurses, and the clinical features and causative drugs were evaluated. The data were collected from general hospitals (76.5%), primary clinics, and pharmacies (23.5%).Based upon the World Health Organization (WHO)-Uppsala Monitoring Center criteria (certain - 13.7%, probable - 46.1%, possible - 32.1%), 91.9% of the collected events were suspected to be ADRs and 15.8% of patients experienced serious ADRs. The most prevalent causative drugs were antibiotics (31.6%), followed by contrast dyes (14.0%), non-steroidal anti-inflammatory d...

What can primary care prescribing data tell us about individual adherence to long-term medication? - comparison to pharmacy dispensing data

Pharmacoepidemiology and Drug Safety — Thu, 16 Jul 2009 23:00:00 +0100

To assess the predictive value of general practice electronic prescribing records with respect to adherence to long-term medications as compared to claims-based pharmacy dispensing data.A total of 29772 electronic prescribing records relating to 2713 patients attending a New Zealand general medical practice were linked by national health identifier to 63 833 dispensing records used for community pharmacy reimbursement. Individual possession ratios - prescription possession ratio (PPR) for prescribing and medication possession ratio (MPR) for dispensing - were calculated for the 15-month period from 1 January 2006 to 30 March 2007 based on each data source for the common long-term medications simvastatin, metoprolol succinate, bendrofluazide, felodipine, cilazapril and metformin.Out of 646 ...

COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors

Pharmacoepidemiology and Drug Safety — Thu, 09 Jul 2009 23:00:00 +0100

To compare hospitalization rates for serious upper and lower gastrointestinal (GI) events between chronic and acute users of a traditional non-steroidal anti-inflammatory drugs (tNSAID) + proton pump inhibitor (PPI) and users of a COX-2 selective inhibitor (Coxib).The PHARMO Record Linkage System, including linked drug-dispensing and hospital records of approximately 3 million individuals in the Netherlands was used. We selected new Coxib or tNSAID users (01/01/2000-31/12/2004) with [ge]1 year history before the first NSAID dispensing and [ge]1 year follow-up ending at the first hospitalization for GI event (the outcome), last dispensing, or end of the study period. Chronic users were patients who used any NSAIDs for [ge]60 days during the first year (n = 58 770); others were acute users (...

Central nervous system medication use and incident mobility limitation in community elders: the health, aging, and body composition study

Pharmacoepidemiology and Drug Safety — Tue, 07 Jul 2009 23:00:00 +0100

To evaluate whether CNS medication use in older adults was associated with a higher risk of future incident mobility limitation.This 5-year longitudinal cohort study included 3055 participants from the health, aging and body composition (Health ABC) study who were well-functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and antidepressants) was determined yearly (except year 4) during in-home or in-clinic interviews. Summated standardized daily doses (low, medium, and high) and duration of CNS drug use were computed. Incident mobility limitation was operationalized as two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting every 6 months after baseline. Multivariable Cox proportional h...

Selective and non-selective non-steroidal anti-inflammatory drugs and the risk of acute kidney injury

Pharmacoepidemiology and Drug Safety — Mon, 06 Jul 2009 23:00:00 +0100

This study provides evidence that risk of AKI may be lower with more selective agents than with naproxen or other non-selective NSAIDs. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)

Drug safety alert generation and overriding in a large Dutch university medical centre

Pharmacoepidemiology and Drug Safety — Sat, 04 Jul 2009 23:00:00 +0100

To evaluate numbers and types of drug safety alerts generated and overridden in a large Dutch university medical centre.A disguised observation study lasting 25 days on two internal medicine wards evaluating alert generation and handling of alerts. A retrospective analysis was also performed of all drug safety alerts overridden in the hospital using pharmacy log files over 24 months.In the disguised observation study 34% of the orders generated a drug safety alert of which 91% were overridden. The majority of alerts generated (56%) concerned drug-drug interactions (DDIs) and these were overridden more often (98%) than overdoses (89%) or duplicate orders (80%). All drug safety alerts concerning admission medicines were overridden.Retrospective analysis of pharmacy log files for all wards re...

Antipsychotics-induced ischaemic colitis and gastrointestinal necrosis: a review of the French pharmacovigilance database

Pharmacoepidemiology and Drug Safety — Tue, 30 Jun 2009 23:00:00 +0100

First- and second-generation antipsychotics commonly cause mild gastrointestinal hypomotility. Intestinal necrosis may be a consequence of such gastrointestinal perturbations.We reviewed all the observations of ischaemic colitis and gastrointestinal necrosis notified to the French Pharmacovigilance database (FPD) between 1997 and the end of 2006.Thirty-eight cases of ischaemic colitis and gastrointestinal necrosis associated with antipsychotics were analysed. The average age of the patients was 42.7 ± 14.7 years (15-77 years). The digestive complication was an intestinal necrosis in 27 cases, an ischaemic colitis in 10 cases (with perforation in three cases), and one perforation. Surgical procedure (partial or total resection of the colon and/or small intestine) was performed in 24 patien...

Greater Epoetin alfa (EPO) doses and short-term mortality risk among hemodialysis patients with hemoglobin levels less than 11 g/dL

Pharmacoepidemiology and Drug Safety — Tue, 30 Jun 2009 23:00:00 +0100

We examined the association between high doses of Epoetin alfa (EPO), which are used to raise and maintain hemoglobin (Hb) levels within target ranges for hemodialysis patients, and short-term mortality risk using multivariable regression and an instrumental variable (IV) analysis.We identified 32 734 patients receiving hemodialysis in 786 facilities from a large US dialysis provider between July 2000 and March 2002 who received care for >4 consecutive months, and had an Hb < 11 g/dL in the third month. We assessed dose titrations following the Hb < 11 g/dL and characterized facilities based on the percentage of patients with dose titrations >25% (instrument). We assessed deaths during the subsequent 90 days and evaluated the EPO dose-mortality association using conventional linear and IV ...

Trends and determinants of adequate gastroprotection in patients chronically using NSAIDs

Pharmacoepidemiology and Drug Safety — Tue, 30 Jun 2009 23:00:00 +0100

To identify determinants and trends of gastroprotection in patients chronically using NSAIDs.Design: retrospective cohort study. Data source: Agis Health Database (AHD) containing annual prescription records of approximately 1.5 million patients. Patients: All patients using more than 180 daily defined doses (DDD) annually, of any NSAID from 2001 to 2007. Main outcome measures: prevalence of NSAID use, adequate prescription of gastroprotective drugs (PPI, misoprostol or COX-2 inhibitor use), determinants of adequate gastroprotection.The percentage of patients chronically using NSAIDs rose from 7.3% of the total NSAIDs users in 2001 to 7.5% in 2007. The percentage of patients on NSAIDs receiving adequate gastroprotective medication in line with actual guidelines increased from 39.6% in 2001...

Current awareness: Pharmacoepidemiology and drug safety

Pharmacoepidemiology and Drug Safety — Thu, 25 Jun 2009 23:00:00 +0100

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 23 sections: 1 Reviews; 2 General; 3 Anti-infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non-steroidal Anti-inflammatory Agents; 7 CNS Agents; 8 Anti-neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator-Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti-inflammatory Agents - ...

Uses of proton pump inhibitors and serum potassium levels

Pharmacoepidemiology and Drug Safety — Thu, 25 Jun 2009 23:00:00 +0100

The objective of this study was to examine the association between serum potassium (K+) level and PPI use.A retrospective data analysis of hospitalized adults aged [ge]65 years during 2006, including PPI users (N = 257) and PPI non-users (N = 388), was conducted. Multiple linear and logistic regression analyses were used to assess the association between PPI use and serum K+ level.PPI users [mean age (SD):79.7 (8.0) years; 70% female] had significantly higher serum K+ levels than PPI non-users [80.2 (8.8) years; 64% female] on admission [4.13 (0.62) vs. 3.97 (0.57) mmol/L; p < 0.001]. The linear regression model revealed that [ge]2 defined daily dose (DDD) units of PPI use were a significantly positive contributor to serum K+ levels (p = 0.021) after adjusting for age, serum creatinine lev...

Congenital abnormalities of 88 children born to mothers who attempted suicide with phenobarbital during pregnany: the use of a disaster epidemiological model for the evaluation of drug teratogenicity

Pharmacoepidemiology and Drug Safety — Wed, 24 Jun 2009 23:00:00 +0100

To study the effect of large doses of phenobarbital used for a suicide attempt during pregnancy for fetuses to estimate the teratogenic potential of phenobarbital.Comparative analysis of exposed children and their unexposed sibs born to pregnant patients who attempted suicide during pregnancy and admitted to the toxicological inpatient clinic, Budapest, 1960-1993.Of 1044 self-poisoned pregnant women, 88 used phenobarbital for suicide attempt and delivered newborn babies.Structural birth detects, i.e., congenital abnormalities (CAs).Doses ranged between 400 and 3000 mg of phenobarbital in 88 pregnant women who attempted suicide with this drug during pregnancy and later delivered live-born babies. Twelve (13.6%) of 88 exposed children and eight (10.3%) of 78 sibs were affected with CAs (odds...

Montelukast and psychiatric disorders in children