Phase 1 pharmacokinetics and safety study of extended duration dapivirine vaginal rings in the United States.

Introduction: Vaginal rings are a promising approach to provide a woman-centred, long-acting HIV prevention strategy. Prior trials of a 25 mg dapivirine (DPV) ring have shown a favourable safety profile and approximately 30% risk reduction of HIV-1 infection. Extended duration rings replaced every three months may encourage user adherence, improve health service efficiency and reduce cost overall.

Prolonged combination lipid therapy is associated with reduced carotid intima-media thickness: a case-control study of the 20-year Familial Atherosclerosis Treatment - Observational Study (FATS-OS).

Background: Studies have documented the short-term vascular benefits of combination lipid therapy.

Objective: Our objective was to evaluate the long-term effects of combination lipid therapy on carotid intima-media thickness (CIMT) in patients with coronary artery disease.

Methods: We performed a case-control study in patients who had finished the Familial Atherosclerosis Treatment Study (FATS) and returned to usual care with statin therapy alone or had elected to participate in the 20-year FATS-Observational Study (FATS-OS) and received combination therapy with lovastatin (40 mg/day), niacin (2-3 g/day), and colestipol (20 gm/day) for 11 years, then continued with simvastatin (10-80 mg/day) or lovastatin (40-80 mg/day) plus niacin (2-4 g/day).

Evaluation of otoscope cone disinfection techniques and contamination level in small animal private practice.

The objective of this study was to evaluate the level of bacterial contamination of otoscope cones in veterinary private practice, and to determine the most effective method of disinfection. Fifty small animal practices participated in this study, which included a detailed survey regarding otoscope cleaning, storage and usage and quantitative culture of the cleaned and stored otoscope cones. Using sterile technique, two cones from each of the 50 hospitals were swabbed and submitted for quantitative culture.

Effects of combination lipid therapy on coronary stenosis progression and clinical cardiovascular events in coronary disease patients with metabolic syndrome: a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL-Atherosclerosis Treatment Study (HATS), and the Armed Forces Regression Study (AFREGS).

We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein (LDL) cholesterol lowering and LDL cholesterol lowering plus high-density lipoprotein (HDL) cholesterol increasing. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary end points were change in mean proximal coronary diameter stenosis (Delta%S(prox)) over 3 years and the frequency of the predefined composite of coronary artery disease death, nonfatal myocardial infarction, stroke, and revascularization due to worsening ischemia.

Hemorrhage and large lipid-rich necrotic cores are independently associated with thin or ruptured fibrous caps: an in vivo 3T MRI study.

Objective: Histological studies suggest associations between hemorrhage and large lipid-rich/necrotic cores with thin or ruptured fibrous caps in advanced atherosclerosis. We investigated these associations in carotid arteries with mild to severe stenosis by in vivo 3T MRI.

Methods And Results: Seventy-seven patients with >or=50% carotid stenosis in at least one side by duplex ultrasound underwent bilateral multi-contrast carotid MRI scans.

Regional lung blood flow and ventilation in upright humans studied with quantitative SPECT.

We used quantitative Single Photon Emission Computed Tomography (SPECT) to study the effect of the upright posture on regional lung blood flow and ventilation. Nine (upright) plus seven (prone and supine) healthy volunteers were studied awake, breathing spontaneously. Regional blood flow and ventilation were marked in sitting upright, supine and prone postures using (113m)In-labeled macroaggregates and inhaled Technegas ((99m)Tc); both remain fixed in the lung after administration.

Proximal humeral fracture as a risk factor for subsequent hip fractures.

Background: With the aging of the world's population, the social and economic implications of osteoporotic fractures are at epidemic proportions. This study was performed to test the hypothesis that a proximal humeral fracture is an independent risk factor for a subsequent hip fracture and that the risk of the subsequent hip fracture is highest within the first five years after the humeral fracture.

Methods: A cohort of 8049 older white women with no history of a hip or humeral fracture who were enrolled in the Study of Osteoporotic Fractures was followed for a mean of 9.

Impact of implementing the Washington State ergonomics rule on employer reported risk factors and hazard reduction activity.

Background: In Washington State an ergonomics rule was adopted in 2000 that focused on primary prevention. The implementation process followed a 6-year phase-in schedule where employers came into compliance based upon their size and industry. In late 2003 the rule was repealed by an industry-funded voter initiative.

Changes in arterial oxygenation and self-reported oxygen use after lung volume reduction surgery.

Rationale: Lung volume reduction surgery (LVRS) is inconsistently reported to improve arterial oxygenation in patients with chronic obstructive pulmonary disease.

Objectives: We studied the effects of surgery on oxygenation in a large cohort and identified predictors of postoperative oxygenation improvement.

Methods: We evaluated oxygenation in 1,078 subjects with chronic obstructive pulmonary disease enrolled in the National Emphysema Treatment Trial after LVRS compared with medical control subjects, including arterial blood gases, use of supplemental oxygen during treadmill walking, and self-reported use of oxygen during rest, exertion, and sleep.

Timing of surgery in cauda equina syndrome with urinary retention: meta-analysis of observational studies.

Object: The authors performed exploratory meta-analyses of observational cohort studies, evidence level III, examining whether earlier surgery makes a difference in outcome in terms of urinary function once cauda equina syndrome (CES) from a herniated lumbar disc has progressed to urinary retention (CESR).

Methods: Literature search identified 27 studies of CESR patients with clear definition of surgical timing. Relative risk (RR) could not be calculated in 11 studies, leaving 16 for meta-analysis.

Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial.

Background: Magnetic resonance imaging (MRI) can noninvasively assess changes in atherosclerotic plaque morphology and composition. The ORION trial assessed the effects of rosuvastatin on carotid plaque volume and composition.

Methods: The randomized, double-blind ORION trial used 1.

Hypoxia has a greater effect than exercise on the redistribution of pulmonary blood flow in swine.

Strenuous exercise combined with hypoxia is implicated in the development of high-altitude pulmonary edema (HAPE), which is believed to result from rupture of pulmonary capillaries secondary to high vascular pressures. The relative importance of hypoxia and exercise in altering the distribution of pulmonary blood flow (PBF) is unknown. Six chronically catheterized specific pathogen-free Yorkshire hybrid pigs (25.

Pulmonary response to 3 h of hypoxia in prone pigs.

Studies in whole animals, isolated lungs and pulmonary tissue strips have shown that the pulmonary vascular resistance (PVR) to hypoxia is temporally biphasic in nature. We studied the regional temporal response to hypoxia in prone pigs. The animals were ventilated with an FIO2 of 0.

Sporadic coordinated shifts of regional ventilation and perfusion in juvenile pigs with normal gas exchange.

Repeated high-resolution measurements of both regional pulmonary ventilation and regional blood flow (r ) have revealed that approximately 6 to 10% of the summed spatial and temporal heterogeneity can be attributed to spontaneous temporal variability. To test the hypothesis that the spontaneous temporal shifts of r and r are coordinated, 12 anaesthetized juvenile pigs had pairs of colours of aerosol and intravenous fluorescent microspheres (FMS) administered simultaneously at 20 min intervals to mark r and r . The animals were killed, the lungs inflated, air-dried and cut into approximately 2 cm(3) cubes.

The complex characteristics of 282 unsatisfactory shoulder arthroplasties.

The purpose of our study is to augment the knowledge of patient dissatisfaction after a shoulder arthroplasty. A total of 353 shoulders were prospectively enrolled into the Shoulder Arthroplasty Failure Experience (SAFE) project. Of these, 282 patients had complete data for the final analysis, including demographic information, medical history, physical examination, standard radiographs, and the Simple Shoulder Test (SST) scores.

Quantifying the genetic influence on mammalian vascular tree structure.

The ubiquity of fractal vascular trees throughout the plant and animal kingdoms is postulated to be due to evolutionary advantages conferred through efficient distribution of nutrients to multicellular organisms. The implicit, and untested, assertion in this theory is that the geometry of vascular trees is heritable. Because vascular trees are constructed through the iterative use of signaling pathways modified by local factors at each step of the branching process, we sought to investigate how genetic and nongenetic influences are balanced to create vascular trees and the regional distribution of nutrients through them.

Endovenous laser treatment of the small [corrected] saphenous vein: efficacy and complications.

Objective: The study was conducted to assess the efficacy and rate of complications of endovenous laser treatment (EVLT) of the short saphenous vein (SSV).

Methods: During a 17-month period, 210 (187 patients) with SSV incompetence documented by duplex ultrasound studies were treated with EVLT using a 980-nm diode laser. Duplex ultrasound examinations were performed on the day of the procedure, within the first week, and 2 to 11 months after the procedure (mean follow-up, 4 months).

Posture primarily affects lung tissue distribution with minor effect on blood flow and ventilation.

We used quantitative single photon emission computed tomography to estimate the proportion of the observed redistribution of blood flow and ventilation that is due to lung tissue shift with a change in posture. Seven healthy volunteers were studied awake, breathing spontaneously. Regional blood flow and ventilation were marked using radiotracers that remain fixed in the lung after administration.

The spatial-temporal redistribution of pulmonary blood flow with postnatal growth.

The pulmonary vascular tree undergoes remarkable postnatal development and remodeling. While a number of studies have characterized longitudinal changes in vascular function with growth, none have explored regional patterns of vascular remodeling. We therefore studied six neonatal pigs to see how regional blood flow changes with growth.

Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism.

We studied the roles of endothelins in determining ventilation (Va) and perfusion (Q) mismatch in a porcine model of acute pulmonary thromboembolism (APTE), using a nonspecific endothelin antagonist, tezosentan. Nine anesthetized piglets (approximately 23 kg) received autologous clots (approximately 20 g) via a central venous catheter at time = 0 min. The distribution of Va and Q at five different time points (-30, -5, 30, 60, 120 min) was mapped by fluorescent microspheres of 10 different colors.

Predictors of carotid atherosclerotic plaque progression as measured by noninvasive magnetic resonance imaging.

The purpose of this in vivo MRI study was to quantify changes in atherosclerotic plaque morphology prospectively and to identify factors that may alter the rate of progression in plaque burden. Sixty-eight asymptomatic subjects with >or=50% stenosis, underwent serial carotid MRI examinations over an 18-month period. Clinical risk factors for atherosclerosis, and medications were documented prospectively.

Sample size calculation for clinical trials using magnetic resonance imaging for the quantitative assessment of carotid atherosclerosis.

Purpose: To provide sample size calculation for the quantitative assessment of carotid atherosclerotic plaque using non-invasive magnetic resonance imaging in multi-center clinical trials. METHODS. As part of a broader double-blind randomized trial of an experimental pharmaceutical agent, 20 asymptomatic placebo-control subjects were recruited from 5 clinical sites for a multi-center study.

Hypoxic pulmonary vasoconstriction is heterogeneously distributed in the prone dog.

Hypoxic pulmonary vasoconstriction (HPV) is thought to protect gas exchange by decreasing perfusion to hypoxic regions. However, with global hypoxia, non-uniformity in HPV may cause over-perfusion to some regions, leading to high-altitude pulmonary edema. To quantify the spatial distribution of HPV and regional PO2 (PRO2) among small lung regions (approximately 2.