Vasopeptidase inhibition with omapatrilat in chronic heart failure: acute and long-term hemodynamic and neurohumoral effects

OBJECTIVES: We investigated the acute and long-term hemodynamic and neurohumoral effects of the vasopeptidase inhibitor omapatrilat in human heart failure. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition constitutes a major advance in the treatment of chronic heart failure (CHF). Simultaneous inhibition of both neutral endopeptidase and ACE with omapatrilat may represent a new treatment strategy in CHF. METHODS: Three hundred and sixty-nine patients with symptomatic heart failure were randomized to double-blind treatment with omapatrilat (first 190 patients: 2.5 mg, 5 mg or 10 mg; last 179 patients: 2.5 mg, 20 mg or 40 mg once daily) for 12 weeks. RESULTS: Acutely, the 10 mg, 20 mg and 40 mg doses of omapatrilat produced greater reductions in pulmonary capillary wedge pressure (PCWP), systolic blood pressure (SBP) and systemic vascular resistance compared with 2.5 mg. Higher doses were associated with greater increases in vasodilator and natriuretic peptides, in addition to ACE inhibition. After 12 weeks, omapatrilat 20 mg and 40 mg showed greater falls from baseline in PCWP (40 mg: 0 h to 12 h average change -7.3 +/- 0.8 mm Hg) and SBP (40 mg: -11.7 +/- 1.7 mm Hg) than 2.5 mg (both p < 0.01 vs. 2.5 mg). The incidence of adverse experiences and patient withdrawal were similar in all groups. CONCLUSIONS: In CHF, the acute hemodynamic benefit seen with higher doses of omapatrilat was associated with increases in plasma vasodilator and natriuretic peptide levels in addition to ACE inhibition. After 12 weeks, the hemodynamic benefit was maintained. Omapatrilat may be a promising new agent in CHF.     

Biomechanical evaluation and comparison of polyetheretherketone rod system to traditional titanium rod fixation on adjacent levels

PurposeAdjacent segment degeneration or fracture of the vertebral body was commonly reported in rigid fusion. Use of semirigid instruments such as PEEK rod system could be an alternative treatment. However, the biomechanical implications of using PEEK rod systems are not well understood. Purpose of this study was to compare a PEEK rod fixation system to traditional titanium rod fixation via a finite element analysis.MethodsA lumbar spine model from L2–L5 vertebral bodies was constructed. A fusion model, created by modifying the intact lumbar model, was used to simulate anterior interbody and posterolateral lumbar fusion. Loading was applied through flexion, extension, lateral bending, torsion.ResultsThe greatest increase in stress was estimated at the upper disc adjacent to the titanium rod with interbody fusion. The lower increase in stress on adjacent segments occurred with PEEK rod fixation without fusion and noninstrumented posterolateral lumbar fusion models. With the same fusion or nonfusion procedures, the stress on discs and facet joints of adjacent segments in the PEEK rod group decreased by 5–25% of that in the titanium rod group for all loading conditions.ConclusionIn comparison with rigid fixation, some potential advantages of using PEEK rod systems include a reduced stress on adjacent segment disc and facet joint, and the elastic ability of PEEK rod fixation allows for a greater range of motion, which may reduce the incidence of clinical complications seen with rigid fusion devices.     

A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A Hoosier Oncology Group study

In a previous phase I study, olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of chemotherapy-induced nausea and vomiting in chemotherapy-naïve patients. The regimen was 5 mg/day of oral olanzapine on the 2 days prior to chemotherapy, 10 mg on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg and dexamethasone 20 mg), and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25–84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2–5 postchemotherapy), and 80% for the overall period (0–120 h postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin 70 mg/m²). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin 50 mg/m²). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea [0 on scale of 0–10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or restlessness experienced by the patients. Complete response and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Olanzapine is safe and highly effective in controlling acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly and moderately emetogenic chemotherapy.     

Low lung volume alters contractile properties of airway smooth muscle in sheep.

Breathing at volumes lower than functional residual capacity (FRC) can induce changes in nonasthmatic airways consistent with the behaviour of asthmatic airways. This study investigated the chronic effect of breathing at volumes lower than FRC on the contractility of airway smooth muscle and myosin light chain kinase (MLCK) content and activity. Sheep of three age groups (neonate, adolescent and adult) had their FRC reduced by approximately 25%, for 4 weeks using a leather corset. Contractile responses to carbachol were then recorded in isolated tracheal strips and bronchial rings. MLCK content and activity were assessed by immunoblotting. The rate of stress generation increased in the bronchial smooth muscle of both adult and adolescent but not neonatal corseted sheep: adolescent corseted versus control, 65.0 +/- 4.1 versus 103.4 +/- 7.0 s (to reach 50% maximum stress), respectively; and adult corseted versus control, 57.0 +/- 6.4 versus 93.4 +/- 8.2 s, respectively. This was not due to increases in either bronchial or tracheal smooth muscle amount or MLCK content and activity. The present results indicate that chronic breathing at low lung volumes increases the rate of stress generation in airway smooth muscle.     

A multidistrict audit of the management of chlamydial PID in genitourinary medicine clinics in Yorkshire

In response to recent reviews of practice of pelvic inflammatory disease (PID) management, a multidistrict audit involving eight genitourinary clinics within the Yorkshire region was carried out. This audit reports the referral patterns of patients, physical signs and microscopy findings at the first genitourinary medicine (GUM) clinic attendance, antibiotic treatment and follow-up data as well as health adviser involvement and partner participation for 68 patients diagnosed with chlamydial PID. Twenty-eight (41.2%) patients presented with symptoms of less than or equal to four weeks duration, partner notification was recorded as being carried out for all patients and at least one partner was documented as having been treated in 57 (83.8%) patients. There is, however, a wide variation in the antibiotic regimens used for treatment and their duration.     

UK National Audit of chlamydial infection management in sexual health clinics. clinic policies audit

There was a wide range of activity and chlamydial diagnoses between the 177 clinics that responded. Most (92%) clinics have nucleic acid tests for chlamydial diagnosis. Different practitioners largely share roles in providing advice to patients about partner notification, treatment adherence, safer sex advice and abstinence. Most (97%) clinics have information leaflets about chlamydia, although about 30% of clinics lack leaflets containing information about antibiotics and hormonal contraception. About two-third clinics follow the National Guideline recommended interval for providing a test of cure where this is indicated. Only 18% of clinics routinely ask patients to reattend, with 40% having a policy of no routine follow-up and 62% using telephone or text follow-up. These categories were not mutually exclusive. Most (86%) of the 146 English clinics had a local Chlamydia Screening Programme coordinator for their Primary Care Trust area, although cooperation varies, with cooperation over treatment of 70% and Programme policy of 62%.     

Diagnostic Accuracy of Coronary CT Angiography for the Evaluation of Bioresorbable Vascular Scaffolds

Objectives

The purpose of this study was to assess the diagnostic accuracy of coronary computed tomography angiography (CTA) for bioresorbable vascular scaffold (BVS) evaluation.