Alcohol abuse associated with poor response to systemic therapies for psoriasis: findings from a prospective multicentre cohort study

Background Factors that might influence response to systemic treatment for moderate-to-severe psoriasis are varied, and generally, are poorly understood, aside from high body weight, suggesting that other unidentified factors may be relevant in determining response to treatment. The impact of alcohol abuse on treatment response has not been previously investigated. Objective To investigate whether alcohol abuse is associated with poor response to treatment for psoriasis. Methods Prospective cohort study in which response to systemic therapies was assessed using the Psoriasis Area and Severity Index (PASI). The CAGE questionnaire was used to screen for alcohol abuse. A multivariable factional polynomial linear regression model was used to examine factors associated with change in PASI between baseline and follow-up. Results The cohort comprised of 266 patients (biologic cohort, n=134; conventional systemic cohort, n=132). For the entire cohort, the median (interquartile range) PASI improved from 13[10-18.3] at baseline to 3[1-7.5] during follow-up. A higher CAGE score (regression co-efficient: 1.40; 95% CIs: 0.04-2.77); obesity (1.84; 0.48-3.20); and receiving a conventional systemic rather than a biologic therapy (4.39; 2.84-5.95) were significantly associated with poor response to treatment; whereas a higher baseline PASI (-0.83; -0.92,-0.74) was associated with better response to treatment. Conclusion The poor response to therapy associated with alcohol abuse and obesity found in people with psoriasis calls for lifestyle behaviour change interventions and support as part of routine clinical care. Targeting interventions to prevent, detect and manage alcohol abuse among people with psoriasis is needed to minimise adverse health consequences and improve treatment response

Fear of hypoglycaemia: defining a minimum clinically important difference in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>To explore the concept of the Minimum Clinically Important Difference (MID) of the Worry Scale of the Hypoglycaemia Fear Survey (HFS-II) and to quantify the clinical importance of different types of patient-reported hypoglycaemia.</p> <p>Methods</p> <p>An observational study was conducted in Germany with 392 patients with type 2 diabetes mellitus treated with combinations of oral anti-hyperglycaemic agents. Patients completed the HFS-II, the Treatment Satisfaction Questionnaire for Medication (TSQM), and reported on severity of hypoglycaemia. Distribution- and anchor-based methods were used to determine MID. In turn, MID was used to determine if hypoglycaemia with or without need for assistance was clinically meaningful compared to having had no hypoglycaemia.</p> <p>Results</p> <p>112 patients (28.6%) reported hypoglycaemic episodes, with 15 patients (3.8%) reporting episodes that required assistance from others. Distribution- and anchor-based methods resulted in MID between 2.0 and 5.8 and 3.6 and 3.9 for the HFS-II, respectively. Patients who reported hypoglycaemia with (21.6) and without (12.1) need for assistance scored higher on the HFS-II (range 0 to 72) than patients who did not report hypoglycaemia (6.0).</p> <p>Conclusion</p> <p>We provide MID for HFS-II. Our findings indicate that the differences between having reported no hypoglycaemia, hypoglycaemia without need for assistance, and hypoglycaemia with need for assistance appear to be clinically important in patients with type 2 diabetes mellitus treated with oral anti-hyperglycaemic agents.</p

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis

Background Naltrexone is an opioid antagonist used in many different conditions, both licensed and unlicensed. It is used at widely varying doses from 3 - 250 mg. The aim of this review was to evaluate the safety of oral naltrexone by examining the risk of serious adverse events (SAEs) in randomised controlled trials (RCTs) of naltrexone compared to placebo. Methods A systematic search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, other databases and clinical trials registries was undertaken up to March 2018. Parallel placebo-controlled RCTs longer than 4 weeks published after 1/1/2001, of oral naltrexone at any dose were selected. Any condition and age group were included, excluding only studies for opioid or ex-opioid users, due to possible opioid/opioid antagonist interactions. The systematic review used the guidance of the Cochrane Handbook throughout. Numerical data was independently extracted by two people and cross-checked. Risk of bias was assessed with the Cochrane Risk of Bias Tool. Meta-analyses were performed using Stata 15 and R, using random and fixed effects models throughout. Results Eighty-nine RCTs with 11194 participants were found, studying alcohol use disorders, various psychiatric disorders, impulse control disorders, other addictions, obesity, Crohn’s disease, fibromyalgia and cancers. Twenty-six studies (4,960 participants) recorded SAEs occurring by arm of study. There was no evidence of increased risk of SAEs for naltrexone compared to placebo, relative risk (RR) 0.84 (95% CI: 0.66 to 1.06). Sensitivity analyses pooling risk differences supported this conclusion (RD = -0.01 (-0.02, 0.00)) and subgroup analyses showed that results were consistent across different doses and disease groups. The quality of evidence for this outcome was judged high using the GRADE criteria. Conclusions Naltrexone does not appear to increase the risk of SAEs over placebo. These findings confirm the safety of naltrexone when used in licensed indications and encourage investments to undertake efficacy studies in unlicensed indications

Environmental Geotechnics: Challenges and Opportunities in the Post COVID-19 World

The outbreak of the COVID-19 pandemic not only created a health crisis across the world but is expected to negatively impact the global economy and societies at a scale that maybe larger than the 2008 financial crisis. Simultaneously, it has inevitably exerted many negative consequences on the geoenvironment upon which human beings depend. The current article articulates the role of environmental geotechnics to elucidate and mitigate the effects of the current pandemic. It is the belief of all authors that the COVID-19 pandemic presents significant challenges, but also opportunities for the development of our field. Our discipline should make full use of our professional skills and expertise to look for development opportunities from this crisis, to highlight our discipline’s irreplaceable position in the global fight against pandemics, and to contribute to the health and prosperity of our communities, so as to better serve humankind. In order to reach this goal, while taking into account the specificity of the SARS-CoV-2 and the uncertainty of its environmental effects, it is believed that more emphasis should be placed on the following research directions: pathogen-soil interactions, isolation and remediation technologies for pathogen-contaminated sites, new materials for pathogen-contaminated soil, recycling and safe disposal of medical wastes, quantification of uncertainty in geoenvironmental and epidemiological problems, emerging technologies and adaptation strategies in civil, geotechnical, and geoenvironmental infrastructure, pandemic-induced environmental risk management, and model pathogen transport and fate in geoenvironment, among others. Moreover, COVID-19 has made it clear to the environmental geotechnics community the importance of urgent international cooperation and of multidisciplinary research actions that must extend to a broad range of scientific fields, including medical and public health disciplines, in order to meet the complexities posed by the COVID-19 pandemic

Rapid Production of Clinical-Grade Gammaretroviral Vectors in Expanded Surface Roller Bottles Using a “Modified” Step-Filtration Process for Clearance of Packaging Cells

Production of clinical-grade gammaretroviral vectors for ex vivo gene delivery requires a scalable process that can rapidly generate large amounts of vector supernatant, clear large numbers of residual packaging cells with minimal decreases in vector titer, and satisfy all current regulatory guidelines regarding product biosafety. To that end, we have developed a simplified method that is compliant with current good manufacturing practices for the production of clinical-grade gammaretroviral vectors in a clinical research environment. We validated a large-scale production platform utilizing 1,700-cm2 expanded surface roller bottles and a “modified” step-filtration process consisting of a 40/150-μm dual-screen filter for aggregate removal followed by a Sepacell 500II leukocyte reduction filter for removal of residual packaging cells. This clarification process can clear at least 2 × 109 viable producer cells using a single filter set-up without any significant loss of titer post-filtration. This platform typically generates 18 liters of vector supernatant to support small-scale clinical trials, but can easily be scaled up to 70 liters during a single manufacturing run. To date, this platform has generated five clinical-grade gammaretroviral vector products, four of which are now being used in adoptive cell therapy clinical trials for the treatment of a variety of solid cancers