Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial.

Background & Aims: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients.

Methods: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015.

Once daily ledipasvir/sofosbuvir fixed-dose combination with ribavirin in patients with inherited bleeding disorders and hepatitis C genotype 1 infection.

Aim: People with inherited bleeding disorders have been disproportionally affected by HCV. We assessed the fixed-dose combination of the NS5A inhibitor ledipasvir (LDV) with the NS5B polymerase inhibitor sofosbuvir (SOF) with ribavirin (RBV) in patients with genotype 1 HCV and inherited bleeding disorders.

Methods: To be eligible, patients had to be over 18 years of age and have an inherited bleeding disorder.

Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection.

Background & Aims: We performed a phase 2 clinical trial to evaluate the efficacy and safety of ledipasvir and sofosbuvir, with or without ribavirin, in patients infected with hepatitis C virus (HCV) genotype 3 or 6.

Methods: We performed an open-label study of 126 patients with HCV genotype 3 or 6 infections at 2 centers in New Zealand from April 2013 through October 2014. Subjects were assigned 1 of 4 groups that received 12 weeks of treatment.

Simplification of a scoring system maintained overall accuracy but decreased the proportion classified as low risk.

Objectives: Scoring systems are developed to assist clinicians in making a diagnosis. However, their uptake is often limited because they are cumbersome to use, requiring information on many predictors, or complicated calculations. We examined whether, and how, simplifications affected the performance of a validated score for identifying adults with chest pain in an emergency department who have low risk of major adverse cardiac events.

Acute colonic pseudo-obstruction in pregnancy.

Background: Acute colonic pseudo-obstruction is an uncommon but potentially morbid complication of pregnancy. The aim of the study was to review a single institution's experience with acute colonic pseudo-obstruction in post-partum patients and develop an algorithm for management based on a literature review.

Methods: This is a retrospective study where patients were identified over a 2-year period (1 December 2012 to 31 November 2014) by checking all deliveries in Christchurch Women's Hospital against diagnosis codes for bowel obstruction and ileus.

Management of hypertension and heart failure in patients with Addison's disease.

Addison's disease may be complicated by hypertension and less commonly by heart failure. We review the pathophysiology of the renin-angiotensin-aldosterone axis in Addison's disease and how this is altered in the setting of hypertension and heart failure. An essential first step in management in both conditions is optimizing glucocorticoid replacement and considering dose reduction if excessive.

Gentamicin and renal function: lessons from 15 years' experience of a pharmacokinetic service for extended interval dosing of gentamicin.

Background: Extended interval dosing (EID) of gentamicin most commonly involves dosing every 24 hours, but patients with impaired renal function may require a longer dose interval. This study examines a large database of patients treated with gentamicin from 1996 to 2010 to see how many patients with renal impairment would have benefited from dose intervals >24 hours and to define the incidence of nephrotoxicity.

Methods: All patients aged ≥ 16 years who had received gentamicin by EID over the 14-year period and had concentration data available were examined.

Fecal biomarkers in the diagnosis and monitoring of Crohn's disease.

The diagnosis and monitoring of Crohn's disease has traditionally relied on clinical assessment, serum markers of inflammation, and endoscopic examination. Fecal biomarkers such as calprotectin, lactoferrin, and S100A12 are predominantly derived from neutrophils, are easily detectable in the feces, and are emerging as valuable markers of intestinal inflammation. This review focuses on the role of fecal biomarkers in the diagnosis and monitoring of Crohn's disease, in particular how these biomarkers change with disease activity and remission, how they can be used to monitor the response to medical therapy, their value in predicting clinical relapse, and their role in monitoring the postoperative state.

Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection.

Background & Aims: We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibitor ledipasvir (LDV) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection.

Methods: A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and LDV (90 mg once daily) plus ribavirin (RBV) were given for 12 weeks to treatment-naïve (TN) patients (n = 25) and those who did not respond to previous therapy (prior null responders, n = 9).

Skin closure after laparotomy with staples or sutures: a study of the mature scar.

Background: Surgeons are divided in their method of choice for skin closure following laparotomy. We suggest that the most important determinant should be the resulting scar. This study aims to compare both patients' and independent observers' assessment of mature laparotomy scars that had been closed with either subcuticular sutures or external staples.

Integrated microscopy techniques for comprehensive pathology evaluation of an implantable left atrial pressure sensor.

The safety and efficacy of an implantable left atrial pressure (LAP) monitoring system is being evaluated in a clinical trial setting. Because the number of available specimens from the clinical trial for histopathology analysis is limited, it is beneficial to maximize the usage of each available specimen by relying on integrated microscopy techniques. The aim of this study is to demonstrate how a comprehensive pathology analysis of a single specimen may be reliably achieved using integrated microscopy techniques.

Impact of obesity on the cost of major colorectal surgery.

Background: The incidence of obesity is increasing in New Zealand. The aim of the study was to determine whether obesity impacts on the cost of treating patients undergoing major colorectal surgery.

Methods: Between 1 February 2008 and 31 July 2009, consecutive patients undergoing major colorectal surgery at Christchurch Hospital, New Zealand, were enrolled in the study.

The effect of a graphical interpretation of a statistic trend indicator (Trigg's Tracking Variable) on the detection of simulated changes.

Anaesthesia involves processing large amounts of information over time. One task of the anaesthetist is to detect substantive changes in physiological variables promptly and reliably. It has been previously demonstrated that a graphical trend display of historical data leads to more rapid detection of such changes.

Changing patterns in anesthetic fresh gas flow rates over 5 years in a teaching hospital.

Background: Reducing anesthetic fresh gas flows can reduce volatile anesthetic consumption without affecting drug delivery to the patient. Delivery systems with electronic flow transducers permit the simple and accurate collection of fresh gas flow information. In a 2001 audit of fresh gas flow, we found little response to interventions designed to foster more efficient use of fresh gas.

Effect-site half-time for burst suppression is longer than for hypnosis during anaesthesia with sevoflurane.

Background: The relationship between measures of drug effect such as bispectral index (BIS) and end-tidal (ET) levels of anaesthetic agents is described by the 'effect site equilibrium half-time', t(1/2)(ke0). There are limited data available on sevoflurane t(1/2)(ke0) during routine anaesthesia and surgery. Preliminary observations suggested t(1/2)(ke0) for the degree of hypnosis as estimated by BIS is different from that for burst suppression of the electroencephalograph, occurring at 'deep' levels of anaesthesia.