A clinical and cost-effectiveness trial of a parent group intervention to manage challenging restricted and repetitive behaviours in young children with autism spectrum disorder: study protocol for a randomised controlled trial

Background Restricted and repetitive behaviours vary greatly across the autism spectrum, and although not all are problematic some can cause distress and interfere with learning and social opportunities. We have, alongside parents, developed a parent group based intervention for families of young children with autism, which aims to offer support to parents and carers; helping them to recognise, understand and learn how to respond to their child’s challenging restricted repetitive behaviours. Methods The study is a clinical and cost-effectiveness, multi-site randomised controlled trial of the Managing Repetitive Behaviours (MRB) parent group intervention versus a psychoeducation parent group Learning About Autism (LAA) (n = 250; 125 intervention/125 psychoeducation; ~ 83/site) for parents of young children aged 3–9 years 11 months with a diagnosis of autism. All analyses will be done under intention-to-treat principle. The primary outcome at 24 weeks will use generalised estimating equation (GEE) to compare proportion of children with improved RRB between the MRB group and the LAA group. The GEE model will account for the clustering of children by parent groups using exchangeable working correlation. All secondary outcomes will be analysed in a similar way using appropriate distribution and link function. The economic evaluation will be conducted from the perspective of both NHS costs and family access to local community services. A ‘within trial’ cost-effectiveness analysis with results reported as the incremental cost per additional child achieving at least the target improvement in CGI-I scale at 24 weeks. Discussion This is an efficacy trial to investigate the clinical and cost-effectiveness of a parent group based intervention designed to help parents understand and manage their child’s challenging RRB. If found to be effective, this intervention has the potential to improve the well-being of children and their families, reduce parental stress, greatly enhance community participation and potential for learning, and improve longer-term outcomes

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes

The endocannabinoid system serves many physiological roles, including in the regulation of energy balance, food reward, and voluntary locomotion. Signaling at the cannabinoid type 1 receptor has been specifically implicated in motivation for rodent voluntary exercise on wheels. We studied four replicate lines of high runner (HR) mice that have been selectively bred for 81 generations based on average number of wheel revolutions on days five and six of a six-day period of wheel access. Four additional replicate lines are bred without regard to wheel running, and serve as controls (C) for random genetic effects that may cause divergence among lines. On average, mice from HR lines voluntarily run on wheels three times more than C mice on a daily basis. We tested the general hypothesis that circulating levels of endocannabinoids (i.e., 2-arachidonoylglycerol [2-AG] and anandamide [AEA]) differ between HR and C mice in a sex-specific manner. Fifty male and 50 female mice were allowed access to wheels for six days, while another 50 males and 50 females were kept without access to wheels (half HR, half C for all groups). Blood was collected by cardiac puncture during the time of peak running on the sixth night of wheel access or no wheel access, and later analyzed for 2-AG and AEA content by ultra-performance liquid chromatography coupled to tandem mass spectrometry. We observed a significant three-way interaction among sex, linetype, and wheel access for 2-AG concentrations, with females generally having lower levels than males and wheel access lowering 2-AG levels in some but not all subgroups. The number of wheel revolutions in the minutes or hours immediately prior to sampling did not quantitatively predict plasma 2-AG levels within groups. We also observed a trend for a linetype-by-wheel access interaction for AEA levels, with wheel access lowering plasma concentrations of AEA in HR mice, while raising them in C mice. In addition, females tended to have higher AEA concentrations than males. For mice housed with wheels, the amount of running during the 30min before sampling was a significant positive predictor of plasma AEA within groups, and HR mice had significantly lower levels of AEA than C mice. Our results suggest that voluntary exercise alters circulating levels of endocannabinoids, and further demonstrate that selective breeding for voluntary exercise is associated with evolutionary changes in the endocannabinoid system

Stress and the contemporary student

Is contemporary student life stressful? And if so, what factors are associated with stress among students? This paper attempts to provide answers to these questions in reporting a research project that explored physical and mental health among students studying at Newcastle University in 1995. Forty-nine per cent of a stratified random sample of students (956 students) completed a postal questionnaire which, as well as addressing questions of health, covered numerous aspects of student living conditions and lifestyle. Stress was measured by the 12-item General Health Questionnaire, which was converted into a 36-point scale. The analysis identifies various factors that were associated with stress, and culminates in the construction of a multi-variate model that explains 25 per cent of the variance in student stress. The findings are discussed within the context of the changing nature of higher education in Britain

Successful Kidney Transplantation in a Recipient Coinfected with Hepatitis C Genotype 2 and HIV from a Donor Infected with Hepatitis C Genotype 1 in the Direct-Acting Antiviral Era

Despite significant advances in transplantation of HIV-infected individuals, little is known about HIV coinfected patients with hepatitis C virus (HCV) genotypes other than genotype 1, especially when receiving HCV-infected organs with a different genotype. We describe the first case of kidney transplantation in a man coinfected with hepatitis C and HIV in our state. To our knowledge, this is also the first report of an HIV/HCV/HBV tri-infected patient with non-1 (2a) HCV genotype who received an HCV-infected kidney graft with the discordant genotype (1a), to which he converted after transplant. Our case study highlights the following: (1) transplant centers need to monitor wait times for an HCV-infected organ and regularly assess the risk of delaying HCV antiviral treatment for HCV-infected transplant candidates in anticipation of the transplant from an HCV-infected donor; (2) closer monitoring of tacrolimus levels during the early phases of anti-HCV protease inhibitor introduction and discontinuation may be indicated; (3) donor genotype transmission can occur; (4) HIV/HCV coinfected transplant candidates require a holistic approach with emphasis on the cardiovascular risk profile and low threshold for cardiac catheterization as part of their pretransplant evaluation

Effects of early-life exposure to Western diet and voluntary exercise on adult activity levels, exercise physiology, and associated traits in selectively bred High Runner mice.

Exercise behavior is under partial genetic control, but it is also affected by numerous environmental factors, potentially including early-life experiences whose effects persist into adulthood. We studied genetic and early-life environmental effects on wheel-running behavior in a mouse model that includes four replicate high runner (HR) lines selectively bred for increased voluntary wheel running as young adults and four non-selected control (C) lines. In a full factorial design, mice from each line were granted wheel access or not and administered either standard or Western diet (WD) from weaning (3 weeks old) to 6 weeks of age (sexual maturity). In addition to acute effects, after a washout period of 8 weeks (∼6 human years) in which all mice had standard diet and no wheel access, we found both beneficial and detrimental effects of these early-life exposures. During the first week of treatments, WD increased distance run by 29% in C mice and 48% in HR mice (significant Diet × Linetype interaction), but diet effects disappeared by the third week. Across the three weeks of juvenile treatment, WD significantly increased fat mass (with lean mass as a covariate). Tested as adults, early-life exercise increased wheel running of C mice but not HR mice in the first week. Early-life exercise also reduced adult anxiety-like behavior and increased adult fasted blood glucose levels, triceps surae mass, subdermal fat pad mass, and brain mass, but decreased heart ventricle mass. Using fat mass as a covariate, early-life exercise treatment increased adult leptin concentration. In contrast, early-life WD increased adult wheel running of HR mice but not C mice. Early-life WD also increased adult lean mass and adult preference for Western diet in all groups. Surprisingly, early-life treatment had no significant effect on adult body fat or maximal aerobic capacity (VO2max). No previous study has tested for combined or interactive effects of early-life WD and exercise. Our results demonstrate that both factors can have long-lasting effects on adult voluntary exercise and related phenotypes, and that these effects are modulated by genetic background. Overall, the long-lasting effects of early-life exercise were more pervasive than those of WD, suggesting critical opportunities for health intervention in childhood habits, as well as possible threats from modern challenges. These results may be relevant for understanding potential effects of activity reductions and dietary changes associated with the obesity epidemic and COVID-19 pandemic

Maternal exposure to Western diet affects adult body composition and voluntary wheel running in a genotype-specific manner in mice

Some human diseases, including obesity, Type II diabetes, and numerous cancers, are thought to be influenced by environments experienced in early life, including in utero. Maternal diet during the perinatal period may be especially important for adult offspring energy balance, potentially affecting both body composition and physical activity. This effect may be mediated by the genetic background of individuals, including, for example, potential "protective" mechanisms for individuals with inherently high levels of physical activity or high basal metabolic rates. To examine some of the genetic and environmental factors that influence adult activity levels, we used an ongoing selection experiment with 4 replicate lines of mice bred for high voluntary wheel running (HR) and 4 replicate, non-selected control lines (C). Dams (half HR and half C) were fed a "Western" diet (WD, high in fat and sucrose) or a standard diet (SD) from 2weeks prior to mating until their pups could feed on solid food (14days of age). We analyzed dam and litter characteristics from birth to weaning, and offspring mass and physical activity into adulthood. One male offspring from each litter received additional metabolic and behavioral tests. Maternal WD caused pups to eat solid food significantly earlier for C litters, but not for HR litters (interaction of maternal environment and genotype). With dam mass as a covariate, mean pup mass was increased by maternal WD but litter size was unaffected. HR dams had larger litters and tended to have smaller pups than C dams. Home-cage activity of juvenile focal males was increased by maternal WD. Juvenile lean mass, fat mass, and fat percent were also increased by maternal WD, but food consumption (with body mass as a covariate) was unaffected (measured only for focal males). Behavior in an elevated plus maze, often used to indicate anxiety, was unaffected by maternal WD. Maximal aerobic capacity (VO2max) was also unaffected by maternal WD, but HR had higher VO2max than C mice. Adult lean, fat, and total body masses were significantly increased by maternal WD, with greater increase for fat than for lean mass. Overall, no aspect of adult wheel running (total distance, duration, average running speed, maximum speed) or home-cage activity was statistically affected by maternal WD. However, analysis of the 8 individual lines revealed that maternal WD significantly increased wheel running in one of the 4 HR lines. On average, all groups lost fat mass after 6days of voluntary wheel running, but the absolute amount lost was greater for mice with maternal WD resulting in no effect of maternal WD on absolute or % body fat after wheel access. All groups gained lean and total body mass during wheel access, regardless of maternal WD or linetype. Measured after wheel access, circulating leptin, adiponectin, and corticosterone concentrations were unaffected by maternal WD and did not differ between HR and C mice. With body mass as a covariate, heart ventricle mass was increased by maternal WD in both HR and C mice, but fat pads, liver, spleen, and brain masses were unaffected. As found previously, HR mice had larger brains than C mice. Body mass of grand-offspring was unaffected by grand-maternal WD, but grand-offspring wheel running was significantly increased for one HR line and decreased for another HR line by grand-maternal WD. In summary, maternal Western diet had long-lasting and general effects on offspring adult morphology, but effects on adult behavior were limited and contingent on sex and genetic background

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

International audienceAbstract Background Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO 2 ) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO 2 with patients’ outcome. Methods Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO 2  300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO 2 -AUC), for hyperoxemia was significantly associated with mortality ( p = 0.003). Conclusions In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration : clinicaltrials.gov NCT02908308 , Registered September 20, 2016

Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial

International audienc