Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

Background: The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets.

Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome.

Background: A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1-17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril.

Methods: Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years.

Comparison of the intrinsic vasorelaxant and inotropic effects of the antiarrhythmic agents vernakalant and flecainide in human isolated vascular and cardiac tissues.

This study explored the intrinsic vasorelaxant and inotropic effects of the mixed potassium and sodium channel blocker atrial antiarrhythmic vernakalant and the class IC antiarrhythmic agent flecainide in human isolated subcutaneous resistance artery and in ventricular trabecular muscle preparations. At test concentrations encompassing free plasma concentrations associated with clinical efficacy for conversion of atrial fibrillation, vernakalant (1-10 μM) displayed no significant direct effects on human resistance artery tone or ventricular contractility. In contrast, tested at equimolar concentrations, flecainide significantly reduced peak isometric contractile force (10 μM) and maximal rates of force development and decline (3 and 10 μM) in the human ventricular muscle preparation while displaying no significant effect on human resistance artery tone.

Losartan and enalapril are comparable in reducing proteinuria in children.

Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers delay progression of chronic kidney disease and have antiproteinuric effects beyond their effects on blood pressure. They are routinely used in adults; however, their efficacy and safety in children, in whom the causes of chronic kidney disease are significantly different relative to adults, is uncertain. Here we assessed an open-label extension of a previous 3-month blinded trial, in which the efficacy and tolerability of losartan was compared to placebo or amlodipine in 306 normotensive and hypertensive children with proteinuria.

Effects of coadministered extended-release niacin/laropiprant and simvastatin on lipoprotein subclasses in patients with dyslipidemia.

Background: The use of extended-release niacin and the prostaglandin D₂ receptor antagonist laropiprant (ERN/LRPT) reduces niacin-induced flushing in patients while preserving its lipid-modifying effects.

Objective: This predefined exploratory analysis examined the individual and combined effects of ERN/LRPT and simvastatin (SIM) on lipoprotein subclasses.

Methods: This double-blind study randomized 1398 dyslipidemic patients equally to ERN/LRPT 1 g/20 mg, SIM (10, 20, or 40 mg), or ERN/LRPT 1 g/20 mg + SIM (10, 20, or 40 mg) once daily for 4 weeks.

Efficacy and safety of losartan in children with Alport syndrome--results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial.

Background: No prospective, randomized, double-blind trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported in adults or children with proteinuria secondary to Alport syndrome.

Methods: This 12-week, double-blind multinational study investigated the effects of losartan 0.7-1.

Randomized, double-blind, controlled study of losartan in children with proteinuria.

Background And Objectives: No large, randomized, double-blind trials in children with proteinuria treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported.

Design, Setting, Participants, & Measurements: This 12-week, double-blind, multinational study investigated the effects of losartan 0.7 to 1.

Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial.

Albuminuria reduction could be renoprotective in hypertensive patients with diabetic nephropathy. However, the current use of renin-angiotensin-system intervention is targeted to BP only. Therefore, this study investigated the adequacy of this approach in 1428 patients with hypertension and diabetic nephropathy from the placebo-controlled Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study.

A multicenter, randomized, double-blind, parallel-group trial of the antihypertensive efficacy and tolerability of a combination of once-daily losartan 100 mg/hydrochlorothiazide 12.5 mg compared with losartan 100-mg monotherapy in the treatment of mild to severe essential hypertension.

Background: Because patients with hypertension may require >1 antihypertensive agent to control blood pressure (BP), physicians often prescribe a fixed combination of antihypertensive medications.

Objective: This study evaluated the effect of adding low-dose hydrochlorothiazide 12.5 mg (HCTZ12.

Problem-based learning of research skills.

Purpose: To determine whether a short-term, problem-based educational intervention leads to increased research activity among health care practitioners.

Subjects And Methods: Participant's success was evaluated as a composite of 2 outcomes. These were (1) reporting results for the project designed during the practicum and (2) conducting subsequent research activities.

The impact of morbid events on survival following hospitalization for complicated myocardial infarction.

Background: Little is known about the importance of morbid events with respect to longer term survival following MI hospital discharge.

Aims: Establish the risk of death associated with morbid events following initial discharge from MI hospitalization.

Methods: We examined the rates of morbid events (reinfarction, stroke/TIA, revascularization, heart failure (HF) hospitalization, cardiovascular hospitalization and all-cause hospitalization) and the relationships of these events to subsequent death in patients who survived the initial hospitalization for MI (n = 5301) in the OPTIMAAL trial.

Importance of baseline distribution of proteinuria in renal outcomes trials: lessons from the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) study.

A key issue in the analysis of outcome trials is the adjustment for baseline covariates that influence the primary outcome. Imbalance of an important covariate between treatment groups at baseline is of considerable concern if one treatment group is favored over another with respect to the hypothesis testing outcome. With the use of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study database as an example, the influence of baseline proteinuria on the primary composite endpoint, ESRD, and ESRD or death after adjusting for baseline proteinuria as a continuous covariate was examined.

A double-blind, dose-response study of losartan in hypertensive children.

Background: The aim of this study was to determine the dose-response relationship for losartan, 2.5 to 100 mg, and to assess the safety and tolerability of losartan in hypertensive children 6 to 16 years of age.

Methods: This was a multicenter, randomized, double-blind, dose-response study.

Use of losartan in diabetic patients in the primary care setting: review of the results in LIFE and RENAAL.

Objective: To review outcomes of diabetic patients treated with losartan in two recent randomized, double-blind, clinical trials and compare outcomes to similar studies in diabetics.

Methods: The Reduction in ENdpoints with the Angiotensin II Antagonist Losartan (RENAAL) study recruited 1513 patients with type 2 diabetes and nephropathy. The Losartan Intervention For Endpoint reduction (LIFE) study recruited 9193 hypertensive patients with left ventricular hypertrophy (LVH) including 1195 with diabetes mellitus.

Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide.

We discuss combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics in light of the independent actions of both types of agents, and the adverse effects of both agents independently and in the context of the physiologic synergy achieved in using these agents together. ARBs counteract many of the adverse events associated with the use of thiazide diuretics and have been shown to reduce the occurrence of new-onset diabetes mellitus. We also review outcome trials in patients with hypertension (such as LIFE [Losartan Intervention For Endpoint reduction in hypertension], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], and SCOPE [Study on COgnition and Prognosis in the Elderly]), in which losartan, valsartan, and candesartan cilexetil were used in combination with hydrochlorothiazide.

The JNC 7 approach compared to conventional treatment in diabetic patients with hypertension: a double-blind trial of initial monotherapy vs. combination therapy.

The JNC 7 states that persons with blood pressure (BP) more than 20/10 mm Hg above goal should be started on combination drug therapy. This criterion includes patients with BP >160/100 mm Hg and diabetics with hypertension. The goal BP for persons with diabetes mellitus is <130/80 mm Hg.

Changes in serum sodium, sodium balance, water balance, and plasma hormone levels as the result of pelvic surgery in women.

Postoperative hyponatremia in women has been associated with the development of serious neurological disorders and even death, with a predisposition for menstruant women. The objective of this study was to evaluate the immediate hormonal, water and electrolyte responses to pelvic surgery in both pre and postmenopausal women. Of the twenty-five consecutive women studied, twenty were premenopausal while five were postmenopausal.

Electromyographic predictors of residual quadriceps muscle weakness after anterior cruciate ligament reconstruction.

Background: Despite the high prevalence of residual quadriceps muscle weakness after anterior cruciate ligament reconstruction, specific predictive factors have not been identified.

Hypothesis: Electromyographic analysis is a better predictor of residual muscle weakness than is preoperative strength.

Study Design: Prospective cohort study.

Differences in activation patterns between eccentric and concentric quadriceps contractions.

Previous studies analysing electromyograms (EMGs) from indwelling electrodes have indicated that fast-twitch motor units are selectively recruited for low-intensity eccentric contractions. The aim of this study was to compare the frequency content of surface EMGs from quadriceps muscles during eccentric and concentric contractions at various contraction intensities. Electromyograms were recorded from the rectus femoris, vastus lateralis and vastus medialis muscles of 10 men during isokinetic (1.

Endurance Training.

To improve endurance athletes' performance, exercise physiologists and coaches often recommend over-distance training. Frequently, though, athletes misinterpret this recommendation and increase their risk of injury and staleness by training excessively.

Children's Sports Injuries: Are They Avoidable?

In this study of 51 children's sports injuries, 21 injuries occurred in a nonorganized setting and 32 were deemed avoidable. Preventive measures are discussed.