Early life exposure to antibiotics and the risk of mood and anxiety disorders in children and adolescents: A population-based cohort study.

OBJECTIVE: Mood and anxiety disorders (MADs) are common conditions with multiple aetiologies. Exposure to antibiotics has been proposed as a possible risk factor in animal studies. We aimed to assess maternal antibiotic use in pregnancy and child antibiotic use in the first three years of life, collectively called early life, as potential risk factors for subsequent development of MADs during childhood and adolescence. METHODS: A population-based retrospective cohort study was conducted including 221,139 children born in Manitoba, Canada between 1996 and 2012. Exposure was defined as having filled one or more antibiotic prescriptions during early life. Children were followed until the earliest MADs diagnoses, 19th birthday, migration, death, or end of the study period. We computed crude and adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals (CIs) using Cox proportional hazard regression. RESULTS: Children born to mothers who received one or more antibiotic courses in pregnancy had significantly higher rates of MADs compared with non-exposed children (aHR 1.08, 95% CI 1.03,1.13). Overall antibiotic exposure during the first three years of life was not significantly associated with MADs (aHR 1.00, 95% CI 0.94,1.07). A significantly increased risk of MADs was observed after postnatal exposure to tetracyclines, aminoglycosides, quinolones (33%) or sulfonamides and trimethoprim (28%). Postnatal exposure to macrolides, lincosamides, and streptogramins significantly reduced the risk of MADs by 16%. CONCLUSION: Early life exposure to antibiotics is associated with different risk effects on MADs in children. The apparent associations may have been confounded by indication and may not be clinically meaningful.

Adverse drug reactions in a primary care population prescribed non-steroidal anti-inflammatory drugs.

OBJECTIVE: To determine how often patients with musculoskeletal (MSK) complaints prescribed a non-steroidal anti-inflammatory drug (NSAID) subsequently consult their general practitioner (GP) with a non-serious adverse drug reaction (ADR). DESIGN: Cohort study. SETTING: A healthcare database containing the electronic GP medical records of over 1.5 million patients throughout the Netherlands. PATIENTS: A total of 16 626 adult patients with MSK complaints prescribed an NSAID. MAIN OUTCOME MEASURES: The patients' medical records were manually assessed for the duration of NSAID use for a maximum of two months, and consultations for complaints predefined as potential ADRs were identified. Subsequently, the likelihood of an association with the NSAID use was assessed and these potential ADRs were categorized as likely, possible, or unlikely ADRs. RESULTS: In total, 961 patients (6%) consulted their GP with 1227 non-serious potential ADRs. In 174 patients (1%) at least one of these was categorized as a likely ADR, and in a further 408 patients (2.5%) at least one was categorized as a possible ADR. Dyspepsia was the most frequent likely ADR, followed by diarrhoea and dyspnoea (respectively 34%, 8%, and 8% of all likely ADRs). CONCLUSION: Of the patients with MSK complaints prescribed an NSAID, almost one in 30 patients re-consulted their GP with a complaint likely or possibly associated with the use of this drug. The burden of such consultations for non-serious ADRs should be taken into account by GPs when deciding whether treatment with an NSAID is appropriate.

Ischaemic cardiovascular risk and prescription of non-steroidal anti-inflammatory drugs for musculoskeletal complaints.

OBJECTIVE: To determine the influence of ischaemic cardiovascular (CV) risk on prescription of non-steroidal anti-inflammatory drugs (NSAIDs) by general practitioners (GPs) in patients with musculoskeletal complaints. DESIGN: Cohort study. SETTING: A healthcare database containing the electronic GP medical records of over one million patients throughout the Netherlands. PATIENTS: A total of 474 201 adults consulting their GP with a new musculoskeletal complaint between 2000 and 2010. Patients were considered at high CV risk if they had a history of myocardial infarction, angina pectoris, stroke, transient ischaemic attack, or peripheral arterial disease, and at low CV risk if they had no CV risk factors. MAIN OUTCOME MEASURES: Frequency of prescription of non-selective (ns)NSAIDs and selective cyclooxygenase-2 inhibitors (coxibs). RESULTS: Overall, 24.4% of patients were prescribed an nsNSAID and 1.4% a coxib. Of the 41,483 patients with a high CV risk, 19.9% received an nsNSAID and 2.2% a coxib. These patients were more likely to be prescribed a coxib than patients with a low CV risk (OR 1.9, 95% CI 1.8-2.0). Prescription of nsNSAIDs decreased over time in all risk groups and was lower in patients with a high CV risk than in patients with a low CV risk (OR 0.8, 95% CI 0.7-0.8). CONCLUSION: Overall, patients with a high CV risk were less likely to be prescribed an NSAID for musculoskeletal complaints than patients with a low CV risk. Nevertheless, one in five high CV risk patients received an NSAID, indicating that there is still room for improvement.

Inappropriate drug prescribing in older adults: the updated 2002 Beers criteria--a population-based cohort study.

BACKGROUND: In 1997, Beers and colleagues developed explicit criteria for potentially inappropriate drug prescribing in ambulatory older adults aged 65 years and over. Several studies have been performed to estimate the prevalence of inappropriate drug prescribing based on these criteria. In 2002, the criteria were updated. AIMS: To examine the extent and trend of inappropriate drug prescribing to ambulatory older adults in the Netherlands between 1997 and 2001, according to the 1997 and the updated Beers criteria. METHODS: Data were retrieved from the Integrated Primary Care Information (IPCI) project, a general practice research database with data from computer-based patient records of a group of 150 general practitioners in the Netherlands. All subjects aged 65 and over were included. Prescriptions were classified as inappropriate if they fulfilled the Beers criteria of prescriptions that generally should be avoided in older adults because of a high risk of adverse effects, while also considering dose and comorbidity. RESULTS: Between 1997 and 2001, the 1-year risk of receiving at least one inappropriate drug prescription for older adults ranged between 16.8% (95% CI: 16.3-17.3%) and 18.5% (18.3-18.7%) according to the 1997 criteria and between 19.1% (18.6-19.6%) and 20.0% (19.5-20.5%) according to the updated Beers criteria. According to the updated criteria, the most frequently prescribed inappropriate drugs were nitrofurantoin, long-acting benzodiazepines, amitriptyline, promethazine and cimetidine. Temazepam and zolpidem were mostly prescribed in supratherapeutic dose. Conventional NSAIDs in persons with a history of gastric/duodenal ulcer were the most frequently prescribed contra-indicated drugs. CONCLUSIONS: Prescribing potentially inappropriate prescriptions to ambulatory older people in the Netherlands is substantial. Compared with other studies using the 1997 Beers criteria, inappropriate prescribing to the elderly is lower than in the USA but similar to Finland. Despite a restrictive medication policy and a growing attention for medication surveillance in Europe, inappropriate drug prescribing is still a substantial problem.