Efficacy of teriparatide compared with risedronate on FRAX-defined major osteoporotic fractures: results of the VERO clinical trial.

Unlabelled: FRAX calculates the 10-year probability of major osteoporotic fractures (MOF), which are considered to have a greater clinical impact than other fractures. Our results suggest that, in postmenopausal women with severe osteoporosis, those treated with teriparatide had a 60% lower risk of FRAX-defined MOF compared with those treated with risedronate.

Introduction: The VERO trial was an active-controlled fracture endpoint clinical trial that enrolled postmenopausal women with severe osteoporosis.

Serum 25-hydroxy-vitamin D and the risk of fractures in the teriparatide versus risedronate VERO clinical trial.

Purpose: Using data from the 2-year, randomized, double-dummy VERO trial, we examined the changes in 25-hydroxy-vitamin D (25[OH]D) concentrations over time, and whether the fracture risk reduction of teriparatide versus risedronate varies by baseline 25(OH)D sufficiency category.

Methods: Postmenopausal women with established osteoporosis received subcutaneous daily teriparatide 20 μg or oral weekly risedronate 35 mg, with concomitant 500-1000 mg of elemental calcium and 400-800 IU/day of vitamin D supplements. Fracture endpoints were analyzed by predefined subgroups of 25(OH)D insufficient and sufficient patients.

Study description and baseline characteristics of the population enrolled in a multinational, observational study of teriparatide in postmenopausal women with osteoporosis: the Asia and Latin America Fracture Observational Study (ALAFOS).

Objective: To describe the study design and baseline patient characteristics of the Asia and Latin America Fracture Observational Study (ALAFOS) to better understand the profile of patients receiving teriparatide during the course of routine clinical practice in Asia, Latin America, the Middle East and Russia.

Methods: Prospective, observational, non-interventional study in postmenopausal women with osteoporosis who are prescribed teriparatide for up to 24 months, according to local medical standards, with a 12 month post-treatment follow-up.

Measures: Demographics, risk factors for osteoporosis and fractures, history of fracture, prior osteoporosis medications, comorbidities, physical function, back pain and quality of life (QoL).

Effects of teriparatide on hip and upper limb fractures in patients with osteoporosis: A systematic review and meta-analysis.

In randomized clinical trials (RCTs) with teriparatide, the number of patients with incident hip fractures was small and insufficiently powered to show statistically significant differences between groups. We, therefore, conducted a systematic review and meta-analysis of the efficacy of teriparatide in the reduction of hip and upper limb fractures in women and men with osteoporosis. A comprehensive search of databases until 22 November 2017 was conducted for RCTs of at least 6-month duration that reported non-spine fractures (hip, humerus, forearm, wrist), either as an efficacy or safety endpoint.

Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations.

Background: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP.

Objectives: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS.

Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial.

The 2-year, randomized, double-blind, active-controlled fracture endpoint VERO study included postmenopausal women with established osteoporosis, who had at least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral density (BMD) T-score ≤-1.5. Patients were treated with either s.

Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.

Background: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis.

Methods: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50.

Long-Term, Open-Label, Safety Study of Edivoxetine Monotherapy in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

Objective: The purpose of this study was to assess the long-term safety and tolerability of edivoxetine, a selective norepinephrine reuptake inhibitor, which was being developed as monotherapy in pediatric attention-deficit/hyperactivity disorder (ADHD).

Methods: This was an open-label study of edivoxetine once daily dosing (0.1-0.

Is the current standard of care leading to cost-effective outcomes for patients with type 2 diabetes requiring insulin? A long-term health economic analysis for the UK.

Aims: The aim of the analysis was to investigate whether insulin intensification, based on the use of intensive insulin regimens as recommended by the current standard of care in routine clinical practice, would be cost-effective for patients with type 2 diabetes in the UK.

Methods: Clinical data were derived from a retrospective analysis of 3185 patients with type 2 diabetes on basal insulin in The Health Improvement Network (THIN) general practice database. In total, 48% (614 patients) intensified insulin therapy, defined by adding bolus or premix insulin to a basal regimen, which was associated with a reduction in HbA1c and an increase in body mass index.

Recommendations of the Alzheimer's disease-related dementias conference.

The National Alzheimer's Project Act, signed into law in 2011, mandates a National Plan to Address Alzheimer's Disease that is updated annually. In the Plan, the term Alzheimer disease includes not only Alzheimer disease (AD) proper, but also several specified related dementias, namely, frontotemporal, Lewy body, vascular, and mixed dementia. In response to a specific action item in the 2012 National Plan, the National Institute of Neurological Disorders and Stroke, in collaboration with the National Institute on Aging, convened panels of experts and conducted a 2-day public conference to develop research priorities and timelines for addressing Alzheimer disease-related dementias (ADRD) in 5 topic areas: multiple etiology dementias, health disparities, Lewy body dementias including dementia with Lewy bodies and Parkinson disease dementia, frontotemporal dementia and related tauopathies, and vascular contributions to ADRD.

The effect of exenatide on lisinopril pharmacodynamics and pharmacokinetics in patients with hypertension.

Objectives: This study evaluated the potential effect of exenatide on the pharmacokinetics and pharmacodynamics of lisinopril in patients with mild-to-moderate hypertension.

Methods: 22 patients with mild-to-moderate primary hypertension participated in a double-blind, randomized, placebo-controlled, 2-period, 2-sequence crossover study. Patients on stable lisinopril therapy were randomly assigned to receive subcutaneous exenatide (10 microg b.

Effect of renal impairment on the pharmacokinetics of exenatide.

Aims: To evaluate the pharmacokinetics (PK), safety and tolerability of a single exenatide dose in patients with renal impairment (RI).

Methods: Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function [Cockcroft-Gault creatinine clearance (CrCL), number of subjects]: normal (>80 ml min(-1), n = 8), mild RI (51-80 ml min(-1), n = 8), moderate RI (31-50 ml min(-1), n = 7) or end-stage renal disease (ESRD) requiring haemodialysis (n = 8). PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL.

Relationship between bone quantitative ultrasound and fractures: a meta-analysis.

Unlabelled: The relationship between bone QUS and fracture risk was estimated in a systematic review of data from 14 prospective studies of 47,300 individuals and 2350 incident fractures. In older women, low QUS values were associated with overall fracture risk, low-trauma fractures, and with hip, forearm, and humerus fractures separately.

Introduction: Bone quantitative ultrasound (QUS) has emerged as a promising technique to evaluate bone status.

Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial.

Objective: Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder (MDD).

Methods: In this randomized, double-blind trial, patients age > or =18 meeting DSM-IV criteria for MDD were randomized to placebo (N=99), duloxetine 80 mg/day (N=93), duloxetine 120 mg/day (N=103), or paroxetine 20 mg/day (N=97). The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression (HAMD(17)) total score after 8 weeks of treatment; a number of secondary efficacy measures also were assessed.

Duloxetine Treatment of Stress Urinary Incontinence in Women Does Not Induce Mania or Hypomania.

BACKGROUND: Mania is a rare but unwelcome side effect of treating depressed patients with antidepressants. This research sought to determine the risk of treatment-emergent mania or hypomania in women with stress urinary incontinence treated with duloxetine, a balanced dual serotonin-norepinephrine reuptake inhibitor currently under investigation for the treatment of both stress urinary incontinence and major depressive disorder. METHOD: Data were obtained from 4 double-blind, randomized, placebo-controlled studies involving 1913 women aged 22 to 83 years and 4 ongoing uncontrolled longer-term studies involving 1877 women aged 20 to 87 years.

Population dose-response model for tadalafil in the treatment of male erectile dysfunction.

Purpose: To determine the population dose-response relationship for tadalafil during on-demand (as-needed) administration for treatment of erectile dysfunction (ED).

Methods: A total of 212 male patients with mild, moderate, or severe ED participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive placebo or 2, 5, 10, or 25 mg tadalafil, taken on demand over an 8-week period.

Involvement of sigma receptors in the modulation of the glutamatergic/NMDA neurotransmission in the dopaminergic systems.

Extracellular single-unit recordings and iontophoresis were used to examine the effects of different selective sigma receptor ligands on dopaminergic and glutamatergic N-methyl-D-aspartate (NMDA) neurotransmissions both in origin (A10 and A9 areas) and terminal (nucleus accumbens and caudate nucleus) regions of the rat mesolimbic and nigrostriatal dopaminergic systems. The selective sigma1 receptor ligands 2-[4-(4-methoxy-benzyl)piperazin-1-yl-methyl]4-oxo[4H]-benzo-th iazolin-2-one (S-21377), systemically administered (1.2 mg/kg, i.

Phase I studies of gemcitabine combined with carboplatin or paclitaxel.

Gemcitabine is a novel nucleoside analogue with a unique mechanism of action. In light of its good single-agent activity in several solid tumors, generally mild toxicity profile, and potential for synergy, combination phase I studies with other active chemotherapeutic agents have been conducted. In two studies the combination of gemcitabine and carboplatin was used to treat patients with non-small cell lung cancer.

Behavioral pharmacology of olanzapine: a novel antipsychotic drug.

Background: In this paper, we review the behavioral pharmacology of olanzapine and compare it to its in vitro profile and to clozapine and a number of other antipsychotic agents, and we estimate the likelihood that olanzapine will be an effective and safe antipsychotic with fewer side effects.

Method: Since there is no model of schizophrenia, per se, a battery of behavioral assays was used.

Results: Behavioral assays confirmed the in vitro results that olanzapine interacts with dopamine, serotonin, and muscarinic receptor subtypes.

Indium-111-radiolabeled guinea pig peripheral leukocytes. In vivo distribution and response to leukotriene B4.

The preparation of indium-111 tropolonate-radiolabeled guinea pig peripheral mixed white cells (greater than 80% neutrophils) is described. Autologous rather than homologous cells are required to provide a population of labeled, functional cells on reintroduction to the animals. Surgery has been shown to result in a profound neutropenia from which the animals must recover before removal of blood for cell preparation.