Objective: To examine the epidemiology of gout and gout treatment in the United Kingdom using a large national practice based population. Methods: Data from the UK General Practice Research Database ...from 1990 to 1999 were examined. Physician diagnoses and drug codes were used, and trends in gout incidence and treatment examined. Additionally, disease prevalence for the year 1999 was assessed. To examine the association of gout with comorbid disease, the prevalence of select health conditions and drug use was compared with the corresponding prevalences seen in osteoarthritis, adjusting for both age and sex. Results: From 1 January 1990 to 31 December 1999 overall gout incidence remained relatively stable, ranging from a low of 11.9 cases (95% confidence interval (CI) 11.5 to 12.3) in 1991 to a high of 18.0 cases (95% CI 17.6 to 18.4) per 10 000 patient-years in 1994. Gout prevalence in 1999 was 1.4% with rates approaching 7% in men over the age of 65. Drugs used for the treatment of gout remained constant in prevalent cases with the exception of a significant decline in non-steroidal anti-inflammatory drug use over the 10 year follow up. Compared with patients with osteoarthritis, patients with gout were significantly more likely to have cardiovascular disease, hypertension, diabetes, and chronic renal failure, and were more likely to have used diuretics or ciclosporin, or both. Conclusion: Although gout is common in the UK, particularly among older men, the incidence of the disease seems to have remained stable during the 1990s.
A drug‐drug interaction (DDI) occurs when one or more drugs affect the pharmacokinetics (the body's effect on the drug) and/or pharmacodynamics (the drug's effect on the body) of one or more other ...drugs. Pharmacoepidemiologic studies are the principal way of studying the health effects of potential DDIs. This article discusses aspects of pharmacoepidemiologic research designs that are particularly salient to the design and interpretation of pharmacoepidemiologic studies of DDIs.
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The aim of this study was to determine whether a potential pharmacokinetic interaction between warfarin and orally administered anti‐infectives increases the risk of hospitalization for ...gastrointestinal (GI) bleeding in warfarin users. We conducted a nested case–control and case–crossover study using US Medicaid data. Logistic regression was used to determine the association between GI bleeding and prior use of ciprofloxacin, levofloxacin, gatifloxacin, co‐trimoxazole, or fluconazole vs. no exposure and also vs. use of cephalexin, which would not be expected to interact with warfarin. All of the anti‐infectives examined were associated with elevated odds ratios (ORs) when compared to no exposure to these drugs. With cephalexin data as the reference, the ORs for co‐trimoxazole (OR: 1.68 (95% confidence interval (CI): 1.21–2.33) in the prior 6–10 days) and fluconazole (OR: 2.09 (95% CI: 1.34–3.26) in the prior 11–15 days) were significantly elevated. Warfarin users who had received an anti‐infective agent showed a substantially increased risk of GI bleeding. However, a drug–drug interaction with warfarin was evident only for co‐trimoxazole and fluconazole.
Clinical Pharmacology & Therapeutics (2008); 84, 5, 581–588 doi:10.1038/clpt.2008.150
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Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests primarily as flat affect. Studies have examined the perception, experience, and expression of emotions ...in schizophrenia and reported normal ratings of experience but impaired affect identification. However, the relation between flat affect and performance on facial affect identification and cognitive tasks has not been systematically examined in relation to premorbid adjustment and clinical outcome. We report a prospective study of 63 patients with at least moderate severity of flat affect and 99 patients without flat affect, who were compared on functional domains, emotion processing tasks, and neurocognitive measures. Flat affect was more common in men and was associated with poorer premorbid adjustment, worse current quality of life, and worse outcome at 1-year follow-up. Patients overall performed more poorly on emotion processing tasks, one that required identification of happy and sad emotions and one that required differentiating among intensities within these emotions. They responded inaccurately yet faster than controls for the intensity differentiation task, suggesting a decomposition of the normal relation between accuracy and speed. Flat affect ratings, compared with other negative symptoms, uniquely predicted performance on emotion processing tasks. Patients with flat affect showed greater impairment in both emotion processing tasks, with the most pronounced impairment for the intensity differentiation task. However, the 2 patient groups did not differ in the neurocognitive profile except for verbal memory. We conclude that flat affect is an important clinical feature of schizophrenia that exacerbates the course of illness.
To identify risk factors for infection with imipenem-resistant Pseudomonas aeruginosa and determine the impact of imipenem resistance on clinical and economic outcomes among patients infected with P. ...aeruginosa.
An ecologic study, a case-control study, and a retrospective cohort study.
A 625-bed tertiary care medical center.
All patients who had an inpatient clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000.
From 1991 through 2000, the annual prevalence of imipenem resistance among P. aeruginosa isolates increased significantly (P<.001 by the chi (2) test for trend). Among 879 patients infected with P. aeruginosa during 1999-2000, a total of 142 had imipenem-resistant P. aeruginosa infection (the case group), whereas 737 had imipenem-susceptible P. aeruginosa infection (the control group). The only independent risk factor for imipenem-resistant P. aeruginosa infection was prior fluoroquinolone use (adjusted odds ratio, 2.52 95% confidence interval {CI}, 1.61-3.92; P<.001). Compared with patients infected with imipenem-susceptible P. aeruginosa, patients infected with imipenem-resistant P. aeruginosa had longer subsequent hospitalization durations (15.5 days vs 9 days; P=.02) and greater hospital costs (81,330 dollars vs 48,381dollars ; P<.001). The mortality rate among patients infected with imipenem-resistant P. aeruginosa was 31.1%, compared with 16.7% for patients infected with imipenem-susceptible P. aeruginosa (relative risk, 1.86 95% CI, 1.38-2.51; P<.001). In multivariable analyses, there remained an independent association between infection with imipenem-resistant P. aeruginosa and mortality.
The prevalence of imipenem resistance among P. aeruginosa strains has increased markedly in recent years and has had a significant impact on both clinical and economic outcomes. Our results suggest that curtailing use of other antibiotics (particularly fluoroquinolones) may be important in attempts to curb further emergence of imipenem resistance.
The prevalence of antibiotic resistance among extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. Thirty-three patients ...with infection due to ESBL-producing E. coli or K. pneumoniae (case patients) were compared with 66 matched controls. Total prior antibiotic use was the only independent risk factor for ESBL-producing E. coli or K. pneumoniae infection (odds ratio, 1.10; 95% confidence interval, 1.03-1.18; P = .006). Case patients were treated with an effective antibiotic a median of 72 hours after infection was suspected, compared with a median of 11.5 hours after infection was suspected for controls (P < .001). ESBL-producing E. coli or K. pneumoniae infection was associated with a significantly longer duration of hospital stay and greater hospital charges (P = .01 and P < .001, respectively). Finally, many ESBL-producing E. coli and K. pneumoniae isolates were closely related. ESBL-producing E. coli and K. pneumoniae infections have a significant impact on several important clinical outcomes, and efforts to control outbreaks of infection with ESBL-producing E. coli and K. pneumoniae should emphasize judicious use of all antibiotics as well as barrier precautions to reduce spread.
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Statistical power in matched case-control studies depends on both the correlation coefficient between cases and their matched controls (phi) and the prevalence of exposure among controls (P0). To ...examine the hypothesis that the value of increasing the control-to-case ratio beyond 5 varies with both phi and P0, the authors estimated statistical power for a hypothetical case-control study under different assumptions. The effect of increasing the control-to-case ratio depended on phi and, to a lesser extent, on P0. The results suggest that investigators consider including more than five controls per case when either phi is greater than about 0.2 or P0 is less than about 0.15. Am J Epidemiol 1999;149:195–7.
Drug–drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was ...associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis‐based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person‐years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea‐specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24–1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11–1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29–2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia.
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The objective of this study was to evaluate whether orally administered anti‐infectives increase the risk of severe hypoglycemia in users of glipizide or glyburide. We performed two case–control ...studies and two case–crossover studies using US Medicaid data. All the anti‐infectives examined were associated with an elevated risk of severe hypoglycemia. Using cephalexin as the reference category, in glipizide users, statistically significant associations were found with co‐trimoxazole (odds ratio (OR) = 3.14; 95% confidence interval (CI): 1.83–5.37); clarithromycin (OR = 2.90; 95% CI: 1.69–4.98); fluconazole (OR = 2.53; 95% CI: 1.23–5.23); and levofloxacin (OR = 2.09; 95% CI: 1.35–3.25). In glyburide users, with cephalexin as the reference, statistically significant associations were found with clarithromycin (OR = 5.02; 95% CI: 3.35–7.54); levofloxacin (OR = 2.83; 95% CI: 1.73–4.62); co‐trimoxazole (OR = 2.68; 95% CI: 1.59–4.52); fluconazole (OR = 2.20; 95% CI: 1.04–4.68); and ciprofloxacin (OR = 2.08; 95% CI: 1.23–3.52). In conclusion, exposure to all studied anti‐infective agents were associated with subsequent severe hypoglycemia. Using cephalexin as the reference, drug–drug interactions were evident with ciprofloxacin (in glyburide users only), clarithromycin, co‐trimoxazole, fluconazole, and levofloxacin.
Clinical Pharmacology & Therapeutics (2010) 88 2, 214–222. doi: 10.1038/clpt.2010.74
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