Penicillin to prevent recurrent leg cellulitis Williams, Hywel C; Crook, Angela M; Mason, James M
New England journal of medicine/The New England journal of medicine,
08/2013, Letnik:
369, Številka:
9
Journal Article
PURPOSE: Although the short-term safety and tolerability of statins has been well established, their potential carcinogenicity in the long term is still debated. The goal of this study was to ...determine whether long-term treatment with statins is associated with an increased risk of fatal and nonfatal cancers.
METHODS: We searched the Medline database between January 1966 and December 1999 for randomized, controlled trials of human subjects in which monotherapy with a statin was compared with placebo. No language restrictions were applied. Only trials with a minimum treatment duration of 4 years and a minimum of 1,000 subjects were included. Studies that did not provide information on fatal or nonfatal cancers were excluded. Data on fatal and nonfatal cancers and all-cause mortality were extracted by a single nonblinded reviewer. Overall crude estimates of risk difference were computed by summing the numerators and denominators of trial-specific risk estimates.
RESULTS: Five trials met the inclusion criteria. The estimated differences in absolute risk between treatment and placebo were as follows (negative risks indicate that treatment was safer than placebo): all nonfatal cancers, 0.0% (95% confidence interval CI: –0.8% to 0.8%); all fatal cancers, –0.1% (95% CI: –0.7% to 0.4%); all fatal and nonfatal cancers combined, –0.1% (95% CI: –1.0% to 0.7%); and all-cause mortality, –1.5% (95% CI: 2.8% to 0.2%).
CONCLUSION: This study demonstrates no association between statin use over a 5-year period and the risk of fatal and nonfatal cancers. This conclusion is limited by the relatively short follow-up of the studies analyzed. Similar analyses of data from studies with longer follow-up periods would be valuable.
Background
The period of time during which a patient is exposed to a drug does not necessarily correspond to the period during which the drug produces the adverse effect under consideration. We ...propose the term Pharmacologically pertinent period of effect (PPPE) to address this time window. We explored the PPPE in light of the rofecoxib saga.
Methods
We identified the observational database studies of rofecoxib at doses 25 and 50 mg daily and thromboembolic events. We also obtained the Kaplan‐Meier curves of Vioxx Gastrointestinal Outcomes Research trial (VIGOR) and Adenomatous Polyp Prevention on Vioxx (APPROVE) trials.
Results
We found seven observational studies with nine analyses. All the studies only looked at current exposure. At the dose of 25 mg, only three of nine analyses were barely statistically significant. At the dose of 50 mg, the risk ratios were much higher. The visual inspection of the Kaplan‐Meier curves shows that in the APPROVE trial (25 mg), the placebo and rofecoxib curves start separating to become statistically significantly different only after 36 months. In contrast the VIGOR (50 mg), curves start separating very early and the divergence increases after 8 months.
Discussion
The 50 mg observational studies, looking at current exposure, correctively identified the almost immediate increase in risk evident in the VIGOR Kaplan‐Meier curves. The absence of an immediate increase in risk shown by the APPROVE trial was also correctively identified by most observational 25 mg studies. To our knowledge no observational study was done on the long‐term cardiac toxicity of the 25‐mg dose. It would thus appear that the two doses of rofecoxib have different PPPEs.
Hypertension is a leading mortality risk factor yet inadequately controlled in most affected subjects. Effective programs to address this problem are lacking. We hypothesized that an information ...technology-supported management program could help improve blood pressure (BP) control.
This randomized controlled trial included 223 primary care hypertensive subjects with mean 24-hour BP >130/80 and daytime BP >135/85 mm Hg measured with ambulatory monitoring (ABPM). Intervention subjects received a BP monitor and access to an information technology-supported adherence and BP monitoring system providing nurses, pharmacists, and physicians with monthly reports. Control subjects received usual care. The mean (+/-SD) follow-up was 348 (+/-78) and 349 (+/-84) days in the intervention and control group, respectively. The primary end point of the change in the mean 24-hour ambulatory BP was consistently greater in intervention subjects for both systolic (-11.9 versus -7.1 mm Hg; P<0.001) and diastolic BP (-6.6 versus -4.5 mm Hg; P=0.007). The proportion of subjects that achieved Canadian Guideline target BP (46.0% versus 28.6%) was also greater in the intervention group (P=0.006). We observed similar BP declines for ABPM and self-recorded home BP suggesting the latter could be an alternative for confirming BP control. The intervention was associated with more physician-driven antihypertensive dose adjustments or changes in agents (P=0.03), more antihypertensive classes at study end (P=0.007), and a trend toward improved adherence measured by prescription refills (P=0.07).
This multidisciplinary information technology-supported program that provided feedback to patients and healthcare providers significantly improved blood pressure levels in a primary care setting.
Background and Objective. Bacterial resistance to antibiotics traditionally used to treat uncomplicated urinary tract infections (uUTIs) is rising in Canada. We compared the cost-per-patient in ...Ontario of including fosfomycin (an antibiotic with a low resistance profile) as an option for first-line empirical treatment of uUTIs with current cost of treatment with sulfonamides, fluoroquinolones, and nitrofurantoin. Methods. A decision-tree model was used to perform a cost-minimization analysis. All possible outcomes of a uUTI caused by bacterial species treated with either sulfonamides, fluoroquinolones, nitrofurantoin, or fosfomycin were included. Results. In the base case analysis, the cost-per-patient for treating uUTI with fosfomycin was $105.12. This is similar to the cost-per-patient for each of the other currently reimbursed antibiotics (e.g., $96.19 for sulfonamides, $98.85 for fluoroquinolones, and $99.09 for nitrofurantoins). The weighted average cost-per-patient for treating uUTI was not substantially elevated with the inclusion of fosfomycin in the treatment landscape ($98.41 versus $98.29 with and without fosfomycin, resp.). The sensitivity analyses revealed that most (88.34%) of the potential variation in cost was associated with the probability of progressing to pyelonephritis and hospitalization for pyelonephritis. Conclusion. Fosfomycin in addition to being a safe and effective agent to treat uUTI has a low resistance profile, offers a single-dose treatment administration, and is similar in cost to other reimbursed antibiotics.
In Canada, access to clopidogrel is restricted by most provincial drug insurance plans in order to contain costs. Until April 2007, the Régie de l'assurance maladie du Québec (RAMQ) Prescription Drug ...Insurance Plan reviewed special access forms before approving reimbursement for clopidogrel prescriptions. We investigated the impact of this restrictive process on patient's filling of prescriptions and on all-cause mortality following coronary stenting.
We analyzed prescriptions filled and all-cause mortality in the year following a percutaneous coronary intervention among patients who underwent stent implantation between January 2000 and September 2004. We obtained administrative data from the RAMQ databases. We included patients who filled at least 1 prescription for a nonrestricted cardiovascular drug after hospital discharge. We used Cox proportional models to compare mortality rates as a function of delayed or absent outpatient clopidogrel therapy.
Of 13,663 patients, 1571 (11.5%) did not fill any clopidogrel prescription despite filling at least 1 nonrestricted cardiovascular drug prescription after a percutaneous coronary intervention, and 1174 (8.6%) patients filled their clopidogrel prescription with a delay of at least 1 day (median delay 5 days) after filling the nonrestricted cardiovascular drug prescription. After controlling for pertinent covariables, not filling a clopidogrel prescription (hazard ratio HR 1.70, 95% confidence interval CI 1.35-2.15) and filling with a delay (HR 1.34, 95% CI 1.01-1.80) were associated with a significant increase in all-cause mortality.
Restricted access to clopidogrel was associated with about 20% of patients either not receiving clopidogrel or receiving therapy after a delay. Delay or absence of clopidogrel therapy increased the risk of all-cause mortality after percutaneous coronary intervention with stenting.
The use of systemic corticosteroids is a known risk factor for the development of cataracts.
To determine whether treatment with inhaled corticosteroids is associated with cataract extraction in the ...elderly.
Case-control study.
Quebec universal health insurance program for all elderly (provincial health insurance plan database RAMQ database).
RAMQ enrollees 70 years and older. The 3677 cases were patients with a cataract extraction between 1992 and 1994. The 21868 controls were randomly selected from patients who did not have a diagnosis of cataract and matched to cases on the index date of the case.
Odds ratio of cataract extraction in patients with prolonged cumulative exposure to inhaled corticosteroids compared with nonusers.
Excluding patients with systemic steroid treatment and after adjusting for age, sex, diabetes, systemic hypertension, glaucoma, ophthalmic steroids, and the number of physician claims for services, use of inhaled corticosteroids for more than 3 years was associated with undergoing cataract extraction (odds ratio OR, 3.06; 95% confidence interval CI, 1.53-6.13). For high average daily doses of beclomethasone or budesonide (>1 mg), the OR was elevated after more than 2 years of treatment (OR, 3.40; 95% CI, 1.49-7.76), whereas for low to medium doses (< or =1 mg) of these drugs, the OR was 1.63 (95% CI, 0.85-3.13) after 2 years.
Prolonged administration of high doses of inhaled corticosteroids increases the likelihood of undergoing cataract extraction in elderly patients. Further studies are needed to investigate the risk of developing cataracts for low to medium doses over longer periods.
To assess the effectiveness of nifedipine treatment in elderly hypertensives.
A single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged ...60-79 years alternatively allocated to either nifedipine or placebo after a 4-week placebo run-in period between 1987 and 1990 with mean follow-up of 30 months. Clinical events and risk modification were analysed in collaboration with the University of Montreal. Seventy-four patients with severe hypertension were reallocated to active nifedipine treatment after placebo run-in.
Cox's proportional hazards model accounting for covariates demonstrated a highly significant decrease in the probability of events: 'original treatment assignment' analysis indicated that 77 events occurred in the placebo and 32 in the nifedipine group. Similar significances were achieved with 'actual treatment' or 'changes excluded' (excluding reallocated subjects) analyses. A significant reduction in relative risk was observed for strokes and severe arrhythmia with an overall decrease from 1.0 to 0.41 (95% confidence interval 0.27-0.61).
Nifedipine treatment diminished the number of severe clinical outcomes in elderly hypertensives significantly.
PDF
