Sexual uses of alcohol and drugs and the associated health risks: A cross sectional study of young people in nine European cities

<p>Abstract</p> <p>Background</p> <p>Young people in European countries are experiencing high levels of alcohol and drug use and escalating levels of sexually transmitted infections. Individually these represent major public health priorities. Understanding of the association between sex and substance use, and specifically the strategic roles for which young people utilise substances to facilitate sexual activity, remains limited.</p> <p>Methods</p> <p>Respondent driven sampling methodology was used in nine European cities to survey 1,341 16–35 year olds representing youth and younger adults who routinely engage in nightlife. Participants self-completed questionnaires, designed to gather demographic, social, and behavioural data on historic and current substance use and sexual behaviour.</p> <p>Results</p> <p>Respondents reported strategic use of specific substances for different sexual purposes. Substances differed significantly in the purposes for which each was deployed (e.g. 28.6% of alcohol users use it to facilitate sexual encounters; 26.2% of cocaine users use it to prolong sex) with user demographics also relating to levels of sexual use (e.g. higher levels of: ecstasy use by males to prolong sex; cocaine use by single individuals to enhance sensation and arousal). Associations between substance use and sex started at a young age, with alcohol, cannabis, cocaine or ecstasy use before age 16 all being associated with having had sex before the age of 16 (odds ratios, 3.47, 4.19, 5.73, 9.35 respectively). However, sexes differed and substance use under 16 years was associated with a proportionately greater increase in early sex amongst girls. Respondents' current drug use was associated with having multiple sexual partners. Thus, for instance, regular cocaine users (c.f. never users) were over five times more likely to have had five or more sexual partners in the last 12 months or have paid for sex.</p> <p>Conclusion</p> <p>An epidemic of recreational drug use and binge drinking exposes millions of young Europeans to routine consumption of substances which alter their sexual decisions and increase their chances of unsafe and regretted sex. For many, substance use has become an integral part of their strategic approach to sex, locking them into continued use. Tackling substances with both physiological and psychological links to sex requires approaching substance use and sexual behaviour in the same way that individuals experience them; as part of the same social process.</p

Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial (RACER-knee) : a study protocol

Introduction Robotic-assisted knee replacement systems have been introduced to healthcare services worldwide in an effort to improve clinical outcomes for people, although high-quality evidence that they are clinically, or cost-effective remains sparse. Robotic-arm systems may improve surgical accuracy and could contribute to reduced pain, improved function and lower overall cost of total knee replacement (TKR) surgery. However, TKR with conventional instruments may be just as effective and may be quicker and cheaper. There is a need for a robust evaluation of this technology, including cost-effectiveness analyses using both within-trial and modelling approaches. This trial will compare robotic-assisted against conventional TKR to provide high-quality evidence on whether robotic-assisted knee replacement is beneficial to patients and cost-effective for healthcare systems. Methods and analysis The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial-Knee is a multicentre, participant-assessor blinded, randomised controlled trial to evaluate the clinical and cost-effectiveness of robotic-assisted TKR compared with TKR using conventional instruments. A total of 332 participants will be randomised (1:1) to provide 90% power for a 12-point difference in the primary outcome measure; the Forgotten Joint Score at 12 months postrandomisation. Allocation concealment will be achieved using computer-based randomisation performed on the day of surgery and methods for blinding will include sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will be reported in line with the Consolidated Standards of Reporting Trials statement. A parallel study will collect data on the learning effects associated with robotic-arm systems. Ethics and dissemination The trial has been approved by an ethics committee for patient participation (East Midlands—Nottingham 2 Research Ethics Committee, 29 July 2020. NRES number: 20/EM/0159). All results from the study will be disseminated using peer-reviewed publications, presentations at international conferences, lay summaries and social media as appropriate. Trial registration number ISRCTN27624068

A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease

Abstract Background Late-onset Pompe disease is a rare genetic neuromuscular disorder caused by lysosomal acid alpha-glucosidase (GAA) deficiency that ultimately results in mobility loss and respiratory failure. Current enzyme replacement therapy with recombinant human (rh)GAA has demonstrated efficacy in subjects with late-onset Pompe disease. However, long-term effects of rhGAA on pulmonary function have not been observed, likely related to inefficient delivery of rhGAA to skeletal muscle lysosomes and associated deficits in the central nervous system. To address this limitation, reveglucosidase alfa, a novel insulin-like growth factor 2 (IGF2)-tagged GAA analogue with improved lysosomal uptake, was developed. This study evaluated the pharmacokinetics, safety, and exploratory efficacy of reveglucosidase alfa in 22 subjects with late-onset Pompe disease who were previously untreated with rhGAA. Results Reveglucosidase alfa plasma concentrations increased linearly with dose, and the elimination half-life was <1.2 h. Eighteen of 22 subjects completed 72 weeks of treatment. The most common adverse events were hypoglycemia (63%), dizziness, fall, headache, and nausea (55% for each). Serious adverse events included hypersensitivity (n = 1), symptomatic hypoglycemia (n = 2), presyncope (n = 1), and acute cardiac failure (n = 1). In the dose-escalation study, all treated subjects tested positive for anti-reveglucosidase alfa, anti-rhGAA, anti-IGF1, and anti-IGF2 antibodies at least once. Subjects receiving 20 mg/kg of reveglucosidase alfa demonstrated increases in predicted maximum inspiratory pressure (13.9%), predicted maximum expiratory pressure (8.0%), forced vital capacity (−0.4%), maximum voluntary ventilation (7.4 L/min), and mean absolute walking distance (22.3 m on the 6-min walk test) at 72 weeks. Conclusions Additional studies are needed to further assess the safety and efficacy of this approach. Improvements in respiratory muscle strength, lung function, and walking endurance in subjects with LOPD may make up for the risk of hypersensitivity reactions and hypoglycemia. Reveglucosidase alfa may provide a new treatment option for patients with late-onset Pompe disease. Trial registration ISRCTN01435772 and ISRCTN01230801 , registered 27 October 2011

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field