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- Outcomes of peptic ulcer bleeding following treatment with proton pump inhibitors in routine clinical practice: 935 patients with high- or low-risk stigmata. [JOURNAL ARTICLE]
- Scand J Gastroenterol 2014 Aug 21.:1-10.
Abstract Objective. To assess rates of further bleeding, surgery and mortality in patients hospitalized owing to peptic ulcer bleeding. Materials and methods. Consecutive patients hospitalized for peptic ulcer bleeding and treated with a proton pump inhibitor (PPI) (esomeprazole or pantoprazole) were identified retrospectively in 12 centers in Spain. Patients were included if they had high-risk stigmata (Forrest class Ia-IIb, underwent therapeutic endoscopy and received intravenous PPI ≥120 mg/day for ≥24 h) or low-risk stigmata (Forrest class IIc-III, underwent no therapeutic endoscopy and received intravenous or oral PPI [any dose]). Results. Of 935 identified patients, 58.3% had high-risk stigmata and 41.7% had low-risk stigmata. After endoscopy, 88.3% of high-risk patients and 22.1% of low-risk patients received intravenous PPI therapy at doses of at least 160 mg/day. Further bleeding within 72 h occurred in 9.4% and 2.1% of high- and low-risk patients, respectively (p < 0.001). Surgery to stop bleeding was required within 30 days in 3.5% and 0.8% of high- and low-risk patients, respectively (p = 0.007). Mortality at 30 days was similar in both groups (3.3% in high-risk and 2.3% in low-risk patients). Conclusion. Among patients hospitalized owing to peptic ulcer bleeding and treated with PPIs, patients with high-risk stigmata have a higher risk of further bleeding and surgery, but not of death, than those with low-risk stigmata.
- The Role of Prediction Modeling in Propensity Score Estimation: An Evaluation of Logistic Regression, bCART, and the Covariate-Balancing Propensity Score. [JOURNAL ARTICLE]
- Am J Epidemiol 2014 Aug 20.
The covariate-balancing propensity score (CBPS) extends logistic regression to simultaneously optimize covariate balance and treatment prediction. Although the CBPS has been shown to perform well in certain settings, its performance has not been evaluated in settings specific to pharmacoepidemiology and large database research. In this study, we use both simulations and empirical data to compare the performance of the CBPS with logistic regression and boosted classification and regression trees. We simulated various degrees of model misspecification to evaluate the robustness of each propensity score (PS) estimation method. We then applied these methods to compare the effect of initiating glucagonlike peptide-1 agonists versus sulfonylureas on cardiovascular events and all-cause mortality in the US Medicare population in 2007-2009. In simulations, the CBPS was generally more robust in terms of balancing covariates and reducing bias compared with misspecified logistic PS models and boosted classification and regression trees. All PS estimation methods performed similarly in the empirical example. For settings common to pharmacoepidemiology, logistic regression with balance checks to assess model specification is a valid method for PS estimation, but it can require refitting multiple models until covariate balance is achieved. The CBPS is a promising method to improve the robustness of PS models.
- Alzheimer's disease and cancer: the need of putting research into context with previous published systematic reviews. [JOURNAL ARTICLE]
- J Cancer Res Clin Oncol 2014 Aug 21.
- Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis. [JOURNAL ARTICLE]
- PLoS One 2014; 9(8):e105376.
Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs.Pubmed and Science Citation Index.Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a "new user" design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events.For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference-comparing FGAs to SGAs-mediated by their difference in risk for the medical event.We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference.The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.
- Systemic exposure of topical erythromycin in comparison to oral administration and the effect on CYP3A activity. [JOURNAL ARTICLE]
- Br J Clin Pharmacol 2014 Aug 19.
Erythromycin is a macrolide antibiotic, which is frequently used as a topical formulation for the treatment of acne. It is also known as an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. In this study the systemic availability of topical erythromycin and hence the influence on the activity of CYP3A is evaluated in comparison to orally administered erythromycin.Sixteen healthy volunteers received consecutively topical (2 x 800 mg) and oral erythromycin (two dose groups 250 and 1000 mg with n=8) to assess erythromycin pharmacokinetics. A microdose midazolam (3μg orally) was used to determine the effect on CYP3A activity.After topical administration, erythromycin was detected in the plasma of every participant without causing a statistically significant alteration of CYP3A activity. After oral administration dose normalised erythromycin exposure (AUC∞ ) was 1335 h*ng/mL after 250 mg and was 3-fold higher for the 1000 mg dose (4051 h*ng/mL; p<0.01) suggesting non-linear pharmacokinetics of erythromycin. Both oral doses inhibited CYP3A activity, midazolam clearance was decreased to 61 % (250 mg) and 21 % (1000 mg). The relationship between erythromycin exposure and CYP3A activity (Hill equation) revealed a 50% reduction of CYP3A activity by an erythromycin AUC∞ of 2106 h*ng/mL.Topical erythromycin did not cause clinically relevant CYP3A alterations although low systemic availability of erythromycin was observed. This supports the assumption that treatment with topical erythromycin is not critical in terms of CYP3A inhibition. Furthermore, substantial non-linearity of erythromycin pharmacokinetics after 2 different oral doses was observed possibly due to autoinhibition.
- Severe teenage acne and risk of endometriosis. [JOURNAL ARTICLE]
- Hum Reprod 2014 Aug 19.
Is there a relationship between severe teenage acne and endometriosis?Endometriosis is positively associated with severe teenage acne.No studies have specifically explored a possible association between severe acne in adolescence and risk of endometriosis.This prospective cohort study used data collected from 88 623 female nurses from September 1989 to June 2009 as part of the Nurses' Health Study II (NHS II) cohort.Regression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for endometriosis among women with and without severe teenage acne. Multivariate models were adjusted for established risk factors of endometriosis.A total of 4 382 laparoscopically confirmed endometriosis cases were documented during 1 132 272 woman-years of follow-up. Compared with women without a history of severe teenage acne, women who had severe teenage acne had a 20% increased risk of endometriosis (HR = 1.20, 95% CI: 1.08-1.32). The association was not affected by adjusting for use of tetracycline or isotretinoin.The HR is likely to be underestimated since we only included endometriosis cases confirmed by laparoscopy. Although geographically diverse, the NHS II cohort is primarily Caucasian, which may limit generalization to more ethnically diverse populations.The results of this study suggest that severe teenage acne is associated with an increased risk of endometriosis. As a visible and non-invasive clinical indicator, severe teenage acne may be useful for early detection of endometriosis. We bring this counter-intuitive association to the attention of clinicians for the benefit of the patient and an early diagnosis of endometriosis.This study was funded by research grant CA176726 from the National Institute of Health. M.K. is supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078). The funding agencies had no role in the design of the study, in the analysis and interpretation of the data, in the writing of the report or in the decision to submit the paper for publication.
- Long-term use of 5α-reductase inhibitors and the risk of male breast cancer. [JOURNAL ARTICLE]
- Cancer Causes Control 2014 Aug 19.
The 5α-reductase inhibitors (5-ARI) finasteride and dutasteride are indicated for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. Case reports have suggested that 5-ARIs increase the risk for male breast cancer, with no conclusive evidence. The objective of this study was to quantify the association between use of 5-ARIs and the risk for male breast cancer.A case-control study was conducted with data from the United Kingdom Clinical Practice Research Datalink database among all men aged 45 years and older in the period 1 January 1992 to 31 December 2011. Cases of men diagnosed with breast cancer were matched to up 10 controls on age and general practice. Crude and adjusted odds ratios were estimated for the risk of breast cancer associated with the use of 5-ARIs.Three hundred and ninety-eight cases were identified and matched to 3,930 controls. Ever use of 5-ARIs was associated with an adjusted odds ratio for breast cancer of 1.08 (95 % CI 0.62-1.87) compared to non-users. Increasing cumulative duration of treatment showed no increasing risks: adjusted odds ratios for use for less than 280, for 280 to 1,036 and for more than 1,036 days were 1.21 (95 % CI 0.47-3.10), 0.94 (95 % CI 0.36-2.41) and 1.29 (95 % CI 0.54-3.08), respectively.In this study, there was no evidence of an association between short- or long-term treatment with 5-ARIs and the risk for breast cancer in older men.
- The current state of ethnic and racial disparities in cardiovascular care: lessons from the past and opportunities for the future. [Journal Article]
- Curr Cardiol Rep 2014 Oct; 16(10):530.
Significant racial/ethnic disparities have been documented in cardiovascular care. Although health care quality is improving for many Americans, differences in clinical outcomes have persisted between racial/ethnic minority patients and non-minorities, even when income, education level, and site of care are taken into consideration. Potential causes of disparities are complex and are related to differences in risk factor prevalence and control, use of evidence-based procedures and medications, and social and environmental factors. Minority patients are more likely to receive care from lower-quality health care providers and institutions and experience more barriers to accessing care. Factors such as stereotyping and bias in medicine are hard to quantify, but likely contribute to differences in treatment. Recent trends suggest that some disparities are decreasing. Opportunities for change and improvement exist for patients, providers, and health care systems. Promising interventions, such as health policy changes, quality improvement programs, and culturally targeted community and clinic-based interventions offer hope that high-quality health care in the USA can be provided to all patients.
- Zonisamide: Pharmacokinetics, Efficacy, and Adverse Events in Children with Epilepsy. [JOURNAL ARTICLE]
- Neuropediatrics 2014 Aug 18.
Background Zonisamide is a new generation antiepileptic drug (AED) widely used in children with refractory epilepsy, although until recently, it was used to a large extent as off-label or unlicensed medication due to the lack of evidence-based studies. Children have a different pharmacokinetic profile than adults and an adult dose regimen cannot be directly translated into pediatric use. Patients and Methods In this retrospective noninterventional study of the medical records of 75 children with pharmacoresistant epilepsy, the pharmacokinetics, efficacy and safety of zonisamide were examined. The dose-to-concentration ratio, the daily weight-normalized dose of zonisamide divided by its plasma concentration, was used as a measure of clearance. In addition, data on the efficacy of zonisamide to reduce seizures and reported adverse events were extracted from the medical records and analyzed. Results Young children (range, 0-4 years) had a significantly increased zonisamide clearance compared with older ones (range, 5-17 years) and those with enzyme-inducing comedication (carbamazepine, phenobarbital, or phenytoin) had increased clearance compared with those on nonenzyme inducers; the increases were 1.7-fold and 1.8-fold, respectively. No significant difference in clearance was found between female and male subjects. The clearances of concomitant AEDs were not affected by zonisamide administration. The overall efficacy of zonisamide for reducing seizure frequency ≥50% was 35% and the most frequent adverse event was fatigue, reported in 23% of the patients. Conclusion Patients with enzyme-inducing comedication or of young age (range, 0-4 years) might need higher weight-normalized doses to achieve the same plasma levels as in patients with no enzyme-inducing comedication or patients of older age. Zonisamide was not found to influence the pharmacokinetics of concomitant AEDs. The shortage of pharmacokinetic studies of zonisamide in children highlights the need for research of this kind.
- Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease. Evidence from a large population -based study. [JOURNAL ARTICLE]
- Eur J Clin Invest 2014 Aug 16.
Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern.To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes.A population-based, nested case-control study was carried out by including the cohort of 78,520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2,206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents.There was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0.86; 95% CI 0.63 to 1.17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1.19; 95% CI 0.86 to 1.63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1.18 (0.96 to 1.47), 0.87 (0.63 to 1.21), and 1.08 (0.80 to 1.46).Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real world clinical practice. This article is protected by copyright. All rights reserved.