Pilot study of interferon gamma for chronic hepatitis C

BACKGROUND/AIMS: Currently, there are no effective therapies available for patients with chronic hepatitis C who have failed to respond to optimal interferon alfa-based regimens. The aims of this pilot study were to assess the antiviral activity and safety of interferon gamma in chronic hepatitis C. METHODS: Patients with chronic hepatitis C, genotype 1, who had not responded to or who had relapsed after therapy with interferon alfa and ribavirin were enrolled in a trial of interferon gamma 1b given in doses of 100, 200 or 400 microg subcutaneously three times weekly for 4 weeks. Frequent blood samples were obtained for HCV RNA levels. RESULTS: Fourteen patients were enrolled. Geometric mean HCV RNA levels remained unchanged. Serum aminotransferase levels also did not change, while there were significant decreases in neutrophil counts (-41% from baseline) and hematocrit (-5%). Low grade fever and malaise were common with the first injection of interferon gamma, but no serious side effects were encountered. CONCLUSIONS: Although relatively well tolerated, interferon gamma in doses of 100-400 microg thrice weekly had no effect on HCV RNA levels in patients with chronic hepatitis C who had failed to achieve a sustained response to interferon alfa-based therapies.     

A randomized,double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design

Objectives: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.

Results: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS–placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo.

Conclusions: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD.

Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.     

Craniofacial superimposition: a review of focus distance estimation methods and an extension to profile view photographs

International Journal of Legal Medicine - Craniofacial superimposition concerns the photographic overlay of skulls and faces, for skeletal identification. As a phased method that depends on...     

Endoscopic implantation of a biopolymer in the lower esophageal sphincter for gastroesophageal reflux: a pilot study

BACKGROUND: GERD is the most frequent disorder of the esophagus. Endoscopic minimally invasive treatment is desirable. However, the results of injection techniques have been disappointing. METHODS: A pilot study was conducted in patients with GERD, who required continuous therapy with a proton pump inhibitor, in which ethylene-vinyl-alcohol was injected into the muscle of the gastric cardia. Primary endpoints were the safety of the procedure, the effect on lower esophageal sphincter pressure and the stability of the injected material. A secondary endpoint was the effect on heartburn score after discontinuation of treatment with a proton pump inhibitor. RESULTS: Ethylene-vinyl-alcohol injection into the cardia resulted in circular diffusion of the product in 10 of 15 cases, suggesting that implantation into the muscle is feasible. Lower esophageal sphincter pressure was increased in 13 of 15 cases at 1 month and was sustained at a median follow-up of 6 months (range 4-12 months). Mean plus minus SEM of lower esophageal sphincter pressures (15 patients) were 12.2 plus minus 0.9, 18.7 plus minus 1.5 (p = 0.001 at baseline), and 16.7 plus minus 1.3 mm Hg (p = 0.038 from baseline) at, respectively, baseline, 1 month follow-up, and final follow-up. There was also a sustained reduction in heartburn score (off proton pump inhibitor) (3.40 plus minus 0.13 vs. 1.53 plus minus 0.24 and 1.87 plus minus 0.26 at baseline vs. 1 month and final follow-up, respectively; p < 0.01). Nine of the 15 patients had more than 50% of the injected material in place at second follow-up (at 6 months for 8 patients; at 12 months for 1 patient). In only 2 patients was there loss of more than 75% of injected ethylene-vinyl-alcohol. Persistence of greater than 50% of the material was associated with achievement of a circular injection. Only 4 patients had to resume therapy with a proton pump inhibitor. Mild retrosternal discomfort was observed in 8 patients; this disappeared in all cases after a maximum of 3 days. CONCLUSIONS: Ethylene-vinyl-alcohol implantation in the muscle of the cardia is feasible and safe. It leads to a sustained increase in resting lower esophageal sphincter pressure. This is associated with a sustained improvement in heartburn score for patients who previously required continuous therapy with a proton pump inhibitor.     

Evaluation of a morphological filter in mean cardiac output determination: application to left ventricular assist devices

A morphological filter (MF) is presented for the determination of beat-to-beat mean rotary left ventricular assist device (LVAD) flow rate, measured using an implanted flow probe. The performance of this non-linear filter was assessed using LVAD flow rate (Q_LVAD) data sets obtained from in silico and in vivo sources. The MF was compared with a third-order Butterworth filter (BWF) and a 10-s moving average filter (MAF). Performance was assessed by calculating the response time and steady state error across a range of heart rates and levels of noise. The response time of the MF was 3.5 times faster than the MAF, 0.5 s slower than the BWF, and had a steady state error of 2.61 %. It completely removed pulsatile signal components caused by residual ventricular function, and tracked sharp transient changes in Q_LVAD better than the BWF. The use of a two-stage MF improved the noise immunity compared to the single-stage MF. This study showed that the good performance characteristics of the non-linear MF make it a more suitable candidate for embedded real-time processing of Q_LVAD than linear filters.     

Specificity of psychological treatments for bulimia nervosa and binge eating disorder? A meta-analysis of direct comparisons

Treatment guidelines state that cognitive–behavioral therapy (CBT) and interpersonal therapy are the best-supported psychotherapies for bulimia nervosa (BN) and that CBT is the preferred psychological treatment for binge eating disorder (BED). However, no meta-analysis which both examined direct comparisons between psychological treatments for BN and BED and considered the role of moderating variables, such as the degree to which psychotherapy was bona fide, has previously been conducted Thus, such an analysis was undertaken. We included 77 comparisons reported in 53 studies. The results indicated that: (a) bona fide therapies outperformed non-bona fide treatments, (b) bona fide CBT outperformed bona fide non-CBT interventions by a statistically significant margin (only approaching statistical significance for BN and BED when examined individually), but many of these trials had confounds which limited their internal validity, (c) full CBT treatments offered no benefit over their components, and (d) the distribution of effect size differences between bona fide CBT treatments was homogeneously distributed around zero. These findings provide little support for treatment specificity in psychotherapy for BN and BED.     

The heterogeneous Gleason 7 carcinoma of the prostate: Analyses of low and high grade (risk) carcinomas with criteria of the International Society of Urological Pathology (ISUP)

Prostate carcinoma (PCa) with Gleason score (GS) 7 has to be examined differentially regarding its prognosis. Using the criteria of ISUP and supplementations, we attempted to analyze the heterogeneity of PCa with GS 7 of biopsy and corresponding specimens of radical prostatectomies (RP).