A randomized trial of Chinese herbal medicines for the treatment of symptomatic hepatitis C

BACKGROUND: Many patients with the hepatitis C virus (HCV) cannot be successfully treated with interferon-based regimens. Chinese herbal medicines have been widely prescribed for HCV in Asia, and many infected patients in the United States have used these agents. However, data to support the efficacy of these medications are limited and, to our knowledge, no published trials have been conducted in a US population. METHODS: In a double-blinded design, 45 patients with HCV and fatigue were randomized to receive a combination of Chinese herbal medications or a matched placebo for 12 weeks. The main outcome measures were changes in health-related quality of life using the role physical and vitality scale scores from the validated Hepatitis Quality of Life Questionnaire and alanine aminotransferase levels. In addition, other Hepatitis Quality of Life Questionnaire variables, HCV load, and adverse effects were monitored. RESULTS: In patients with HCV, the herbal medications had no effect on any quality-of-life variables, as measured by the Hepatitis Quality of Life Questionnaire. In addition, no significant changes in alanine aminotransferase or serum HCV RNA levels were noted. No significant adverse effects were observed. CONCLUSIONS: In this study, a regimen of Chinese herbal medicines did not improve quality of life, liver chemistry results, or viral load in a cohort of patients with HCV. Patients and practitioners should remain cautious about the use of herbal medicines for HCV, because studies have not shown a clear benefit of these agents.     

Vertebral fractures following stereotactic body radiotherapy for spine metastases

Stereotactic body radiotherapy has emerged as one of the preferred treatments for patients with spine metastases, with the potential for long‐term control from lesion irradiation. Post‐treatment vertebral compression fractures are a known complication of this therapy, contributing to worsening pain and reduced quality of life, sometimes requiring surgical intervention. This review explores the current knowledge of post‐radiotherapy fractures, in terms of the rates and associated predictive factors. A search of databases including Medline, Embase and the Cochrane Library was conducted using keywords such as ‘vertebral compression fracture’, ‘stereotactic body radiotherapy’ and ‘spine metastases’. The search was limited to published studies up to March 2019, reporting clinical outcomes including both the post‐treatment fracture rate and statistical identification of associated risk factors. Rates of post‐treatment fractures ranged from 4 to 39%. A variety of factors were found to increase the risk, including the appearance of lytic vertebral disease, degree of pre‐existing compression, spinal malalignment, increased dose per fraction and a Spinal Instability Neoplastic Score >6. This knowledge can enable clinicians to counsel patients when considering management options for spine metastases, maintaining the balance between local tumour control and the risk of subsequent fracture.     

α-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer’s disease

The gene encoding α-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer’s disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that α-T-catenin is expressed in human brain, and like other α-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Aβ deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n>700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.     

Toxicity study of an antidipsotropic Chinese herbal mixture in rats: NPI-028

OBJECTIVES: To determine the potential toxicity and safety of the Chinese herbal medicine NPI-028 in rats following subchronic (3-month) exposure via daily oral consumption. DESIGN: Subchronic toxicity was evaluated in four groups of rats (n = 10 per group) receiving NPI-028 orally at a dose of either 0.0 (normal diet control), 0.5, 1.0, or 2.0 g/kg, ingested as part of their daily diet for 3 months. NPI-028 was incorporated into powdered rat chow diet as a specific percent of the total diet provided each day. The primary active isoflavone content of NPI-028 (puerarin) used in the rat diet was also determined. OUTCOME MEASURES: Subchronic toxicity was assessed over a 3-month period by biweekly measurement of water and food intake, weight gain, and visual inspection for maintenance of grooming and normal behavior. At the end of the study period rats were euthanized and blood was obtained for hematologic and chemical analysis. Organs were removed for histopathologic examination. RESULTS: Rats in all three NPI-028 dose groups were similar to the control group in weight gain, food intake, and water intake over the study period. Hematology, blood chemistries, and organ histology in rats at all three NPI-028 doses did not significantly differ from control rats. Minor exceptions were elevated urea nitrogen values at all NPI-028 doses, and increased triglyceride and thyroid-stimulating hormone values in the lowest NPI-028 dose-treated group. Puerarin (used as a dietary isoflavone marker) content of NPI-028 was 26 mg/g dry weight. CONCLUSIONS: NPI-028 ingested orally at doses up to 2.0 g/kg per day in the rat diet for up to 3 months resulted in normal growth with no changes in hematologic or hepatic parameters, and only minor alterations in renal and blood chemistry parameters. There was no evidence of abnormal histology. These data suggest the long-term daily oral consumption of NPI-028 as a part of the daily diet for 3 months, at the doses studied, is safe in rats. Thus, NPI-028 may potentially be safe for clinical use as an antidipsotropic agent.     

Bioelectrical impedance analysis revisited

Although total limb volume measurements are used to track the progress of lymphedema and its treatment, these measurements can be confounded by changes other than fluid excess namely muscle or fat gain. Bioelectrical impedance analysis (BIA) is a technique that specifically quantifies both total body fluid and extracellular fluid in extremities. Whereas BIA has potential as a quick, inexpensive, and quantitative technique to measure directly fluid gain or loss from lymphedema, it also has certain shortcomings that must be addressed before it can be validated. this paper examines the back-ground that explains why measuring total limb volume is insufficient to quantify the extent of peripheral lymphedema and explores the advantages and drawbacks of using BIA for this purpose.     

Association of methamphetamine use and restrictive interventions in an acute adult inpatient mental health unit: A retrospective cohort study

The aim of the present study was to describe incidences of restrictive interventions and the association of methamphetamine use at an acute adult inpatient mental health unit in metropolitan Melbourne, Victoria, Australia. A total of 232 consecutive consumer admissions to the inpatient unit across a 3‐month period were described for illicit substance use and the use of restrictive interventions (seclusion, mechanical restraint, and physical restraint) prior to and during admission. Of all admissions, 25 (10.8%) involved consumers subjected to a restrictive intervention. Methamphetamine use was either self‐reported or detected by saliva test for 71 (30.6%) consumers. Following multivariate analyses, methamphetamine use (odds ratio (OR): 7.83, 95% confidence interval (CI): 2.33–26.31) and restrictive intervention in the emergency department prior to admission (OR: 8.85, 95% CI: 2.83–27.70) were significant independent predictors of the use of restrictive interventions after inpatient admission. Anecdotal observations provided by clinical mental health staff that consumers intoxicated with methamphetamine appear to require restrictive intervention more frequently than other consumers was confirmed with the results of the current study. As the state of Victoria in Australia is on a pathway to the elimination of the use of restrictive interventions in mental health services, clinicians need to develop management strategies that provide specialist mental health care using the least‐restrictive interventions. Although 26.8% of methamphetamine users were secluded after admission, restrictive interventions should not be the default management strategy for consumers who present with self‐report or positive screen for methamphetamine use.     

When reduction strategies are put in place and mental health consumers are still secluded: An analysis of clinical and sociodemographic characteristics

Internationally, seclusion practices continue to be the subject of intense clinical health service and academic scrutiny. Despite extensive efforts to reduce and eliminate this controversial practice, seclusion remains a clinical intervention widely used in contemporary mental health service settings. Early identification of people who are at risk for seclusion and the timely application of alternative evidence‐based interventions are critical for reducing incidents of seclusion in real‐world practice settings. This retrospective study aimed to determine the relationship between sociodemographic and clinical characteristics, and the use of seclusion for those mental health consumers for whom evidence‐based seclusion‐reduction initiatives had little impact. A 12‐month centred moving average was fitted to seclusion data from a psychiatric inpatient unit over 2 years to determine stabilization in seclusion reduction. The number of consumers admitted was calculated from the point of stabilization for 1 year (n = 469). In this cohort, univariate analysis sought to compare the characteristics of those who were secluded and those who were not. A multivariate logistic regression model was undertaken to associate future seclusion based on significant independent variables. Of those people admitted, 88 (19%) were secluded. The majority of seclusions occurred in the first 5 days (70/88, 79%). Multivariate logistic regression indicated that three variables maintained their independent associative risk of seclusion: (i) age less than 35 years; (ii) assessment of risk of violence to others; and (iii) a history of seclusion. The implications of these findings for nursing practice are discussed.