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- Association between oral fluoroquinolone use and the development of retinal detachment: a systematic review and meta-analysis of observational studies. [JOURNAL ARTICLE]
- J Antimicrob Chemother 2014 Dec 18.
Several observational studies have been published investigating the association between oral fluoroquinolone use and the development of retinal detachment; however, the findings are not concordant. This study is a meta-analysis of the existing literature and estimates the overall absolute risk of such an event.Electronic databases were searched for observational studies on the association between oral fluoroquinolone and retinal detachment up to August 2014. Studies that did not meet the criteria for meta-analysis were narratively reviewed. Cases of retinal detachment during current fluoroquinolone use were also extracted for absolute risk calculation.Seven observational studies were included. Three (case-control and self-controlled case series studies) were eligible for meta-analysis and four (cohort studies) were narratively reviewed. The rate ratio of the case-control studies was 1.82 (95% CI 0.67-4.93), I(2) = 96% and the incidence rate ratio of the self-controlled case series was 1.03 (95% CI 0.84-1.27), I(2) = 36%. Three of the four cohort studies found no significant association between oral fluoroquinolone use and the development of retinal detachment. The pooled absolute risk of retinal detachment whilst on current oral fluoroquinolone treatment is estimated to be 4.85 per 1 000 000 prescriptions (95% CI 0.78-8.91).The findings of this systematic review and meta-analysis do not support an association between oral fluoroquinolone use and the development of retinal detachment. Given the low absolute risk, such an event would be rare if there were an association. The current prescribing practice for fluoroquinolones should not be altered because of a previously suggested potential risk of retinal detachment.
- Prescription Drug Insurance Coverage and Patient Health Outcomes: A Systematic Review. [JOURNAL ARTICLE]
- Am J Public Health 2014 Dec 18.:e1-e14.
Previous reviews have shown that changes in prescription drug insurance benefits can affect medication use and adherence. We conducted a systematic review of the literature to identify studies addressing the association between prescription drug coverage and health outcomes. Studies were included if they collected empirical data on expansions or restrictions of prescription drug coverage and if they reported clinical outcomes. We found 23 studies demonstrating that broader prescription drug insurance reduces use of other health care services and has a positive impact on patient outcomes. Coverage gaps or caps on drug insurance generally led to worse outcomes. States should consider implementing the Affordable Care Act expansions in drug coverage to improve the health of low-income patients receiving state-based health insurance. (Am J Public Health. Published online ahead of print December 18, 2014: e1-e14. doi:10.2105/AJPH.2014.302240).
- Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. [Journal Article]
- Pharmaceutics 2014; 6(4):632-50.
Dovitinib (TKI-258) is under development for the treatment of diverse cancer entities. No published information on its pharmacokinetic drug interaction potential is available. Thus, we assessed its interaction with important drug metabolising enzymes and drug transporters and its efficacy in multidrug resistant cells in vitro. P-glycoprotein (P-gp, MDR1, ABCB1) inhibition was evaluated by calcein assay, inhibition of breast cancer resistance protein (BCRP, ABCG2) by pheophorbide A efflux, and inhibition of organic anion transporting polypeptides (OATPs) by 8-fluorescein-cAMP uptake. Inhibition of cytochrome P450 3A4, 2C19, and 2D6 was assessed by using commercial kits. Induction of transporters and enzymes was quantified by real-time RT-PCR. Possible aryl hydrocarbon receptor (AhR) activating properties were assessed by a reporter gene assay. Substrate characteristics were evaluated by growth inhibition assays in cells over-expressing P-gp or BCRP. Dovitinib weakly inhibited CYP2C19, CYP3A4, P-gp and OATPs. The strongest inhibition was observed for BCRP (IC50 = 10.3 ± 4.5 μM). Among the genes investigated, dovitinib only induced mRNA expression of CYP1A1, CYP1A2, ABCC3 (coding for multidrug resistance-associated protein 3), and ABCG2 and suppressed mRNA expression of some transporters and drug metabolising enzymes. AhR reporter gene assay demonstrated that dovitinib is an activator of this nuclear receptor. Dovitinib retained its efficacy in cell lines over-expressing P-gp or BCRP. Our analysis indicates that dovitinib will most likely retain its efficacy in tumours over-expressing P-gp or BCRP and gives first evidence that dovitinib might act as a perpetrator drug in pharmacokinetic drug-drug interactions.
- Previously diagnosed influenza infections and the risk of developing epilepsy. [JOURNAL ARTICLE]
- Epidemiol Infect 2014 Dec 18.:1-8.
SUMMARY Several epidemiological studies suggest a possible involvement of viral infection in the development of epilepsy. While recent research from in vitro studies increasingly supports the role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of epilepsy, little is known about the role of other viral infections such as influenza. Using data from the Clinical Practice Research Datalink (CPRD), we conducted a matched case-control analysis to assess the association between GP-diagnosed influenza infections and the risk of developing an incident diagnosis of epilepsy. During the study period 11 244 incident epilepsy cases and 44 976 matched control patients were identified. Prior exposure to influenza was reported in 7·5% of epilepsy cases and 6·7% of controls [adjusted odds ratio (aOR) 1·12, 95% confidence interval (CI) 1·03-1·22]. Prior history of 'complicated influenza', i.e. influenza associated with a possible super-infection, was associated with a slightly increased epilepsy risk (aOR 1·64, 95% CI 1·10-2·46), particularly if recorded within the 2 months preceding the epilepsy diagnosis (aOR 6·03, 95% CI 1·10-33·2). Our findings suggest that prior influenza exposure does not appear to materially alter the risk of developing epilepsy. By contrast, influenza episodes accompanied by complications were associated with a slightly increased epilepsy risk.
- Regional Variation in Use of a New Class of Antidiabetic Medication Among Medicare Beneficiaries: The Case of Incretin Mimetics. [JOURNAL ARTICLE]
- Ann Pharmacother 2014 Dec 16.
When incretin mimetic (IM) medications were introduced in 2005, their effectiveness compared with other less-expensive second-line diabetes therapies was unknown, especially for older adults. Physicians likely had some uncertainty about the role of IMs in the diabetes treatment armamentarium. Regional variation in uptake of IMs may be a marker of such uncertainty.To investigate the extent of regional variation in the use of IMs among beneficiaries and estimate the cost implications for Medicare.This was a cross-sectional analysis of 2009-2010 claims data from a nationally representative sample of 238 499 Medicare Part D beneficiaries aged ≥65 years, who were continuously enrolled in fee-for-service Medicare and Part D and filled ≥1 antidiabetic prescription. Beneficiaries were assigned to 1 of 306 hospital-referral regions (HRRs) using ZIP codes. The main outcome was adjusted proportion of antidiabetic users in an HRR receiving an IM.Overall, 29 933 beneficiaries (12.6%) filled an IM prescription, including 26 939 (11.3%) for sitagliptin or saxagliptin and 3718 (1.6%) for exenatide or liraglutide. The adjusted proportion of beneficiaries using IMs varied more than 3-fold across HRRs, from 5th and 95th percentiles of 5.2% to 17.0%. Compared with non-IM users, IM users faced a 155% higher annual Part D plan ($1067 vs $418) and 144% higher patient ($369 vs $151) costs for antidiabetic prescriptions.Among older Part D beneficiaries using antidiabetic drugs, substantial regional variation exists in the use of IMs, not accounted for by sociodemographics and health status. IM use was associated with substantially greater costs for Part D plans and beneficiaries.
- The Quasi-cohort Approach in Pharmacoepidemiology: Upgrading the Nested Case-Control. [JOURNAL ARTICLE]
- Epidemiology 2014 Dec 15.
Observational studies of drug effects conducted using health care mega-databases often involve large cohorts with multiple time-varying exposures and covariates. These present formidable technical challenges in data analysis, necessitating sampling approaches such as nested case-control designs. The nested case-control approach is, however, baffling to medical journal readers, particularly the comparisons involving "cases" versus "controls" and the convoluted way in which forward-looking relations from exposure to outcome are extracted from backward-looking data. I propose a "quasi-cohort" approach involving alternative ways of data presentation and analysis that are more in line with the underlying cohort design, including the computation of quasi-rates, rate ratios, and quasi-rate differences. I illustrate the quasi-cohort approach using data from a study of pneumonia risk associated with inhaled corticosteroid use in a cohort of 163,514 patients with chronic obstructive pulmonary disease, including 20,344 who had the outcome event of pneumonia hospitalization during more than 304 million person-days of follow-up.
- [Abstracts of the 6th Scientific Forum of Pharmacoepidemiology, June 27-28, 2013, Paris, France]. [Congresses, Overall]
- Rev Epidemiol Sante Publique 2014 Feb.:S3-30.
- Comment on: "Desideratum for Evidence-Based Epidemiology" [JOURNAL ARTICLE]
- Drug Saf 2014 Dec 16.
- Anticipated and unanticipated consequences of abuse deterrent formulations of opioid analgesics. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Dec 16.
- Potential Drug-Drug Interactions in Infant, Child, and Adolescent Patients in Children's Hospitals. [JOURNAL ARTICLE]
- Pediatrics 2014 Dec 15.
Hospitalized infants, children, and adolescents are typically exposed to numerous distinct medications during inpatient admissions, increasing their risk of potential drug-drug interactions (PDDIs). We assessed the prevalence and characteristics of PDDI exposure of pediatric patients treated in children's hospitals.This retrospective cohort study included patients <21 years old hospitalized in children's hospitals throughout the United States. PDDIs were identified by using the MicroMedex DRUG-REAX system. We calculated the patients exposed to PDDIs, stratified according to the seriousness of the interaction; daily and cumulative counts of PDDI exposures; and characterization of the cited potential adverse effects.Of 498 956 hospitalizations in 2011, 49% were associated with ≥1 PDDI, with a "contraindicated" PDDI occurring in 5% of all hospitalizations, a "major" PDDI present in 41%, a "moderate" PDDI in 28%, and a "minor" PDDI in 11%. Opioids were involved in 25% of all PDDIs, followed by antiinfective agents (17%), neurologic agents (15%), gastrointestinal agents (13%), and cardiovascular agents (13%). One-half of all PDDI exposures were due to specific drug pairs occurring in ≤3% of patients per hospital day. The most common potential adverse drug events included additive respiratory depression (in 21% of PDDIs), bleeding risk (5%), QT interval prolongation (4%), reduced iron absorption/availability (4%), central nervous system depression (4%), hyperkalemia (3%), and altered diuretic effectiveness (3%).Exposure to PDDIs is common among hospitalized children. Empirical data are needed to determine the probability and magnitude of the actual harm for each specific PDDI, particularly for less common drug pairs.