microRNA and Overcoming the Challenges of Their Use in the Diagnosis of Endometriosis

Endometriosis is a common estrogen dependent and inflammatory disease affecting approximately 176 million women worldwide. Currently, the time between onset of symptoms and a definitive diagnosis has been reported by several international studies to range from 6 to 12 years. Presently, laparoscopic surgery followed by histopathological confirmation of lesions remains the gold standard for diagnosis. In part because of cost and invasiveness, current trends favor reduced laparoscopic surgeries in preference of the non-surgical diagnosis of endometriosis. However, the search for a clinical marker or markers of endometriosis that provide equal or similar sensitivity and specificity to laparoscopy has remained elusive. Thus, the search for a diagnostic test for the diagnosis of endometriosis continues to be a high priority research and clinical issue. Recent studies have reported favorable results with microRNA; however, lack of replication and absence of validation suggest that circulating miRNA may not be reliable for clinical use. Use of different screening platforms together with divergent methods may account for some of the lack or reproducibility in the literature. Herein we critically assess the recent literature and explore sources for discrepant findings. We suggest that prospective studies using validated reference miRNA to normalize results together with improved study design may yet reveal a suitable diagnostic marker or panel of markers for the diagnosis of endometriosis

Relative age effect in handball players of Spain

This study analyzes the effect of relative age in the selection process of handball players for licensed club teams in the Murcia region and the Murcia Regional Handball teams. To this end we studied gender, date of birth and player category in a total of 846 handball players (762 of them in licensed clubs from the Murcia Regional Handball Federation, henceforth FBRM and 84 players in Murcia regional teams respectively) in the children’s, junior and youth categories. Comparisons were made and differences were analyzed with χ2 and Z tests and the Bonferroni correction. The analysis of results according to quarter and semester of birth revealed statistically significant differences both for licensed clubs and for Murcia Regional handball team players. The gender and player category analysis showed statistically significant results only in the case of category in regional teams. Thus RAE is confirmed in the samples analyzed, this effect being stronger amongst regional team players

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

The Relational Approach to Treating Self-Harm (RELATE):Study protocol for a Feasibility Randomised Controlled Trial Study of Cognitive Analytic Therapy for Adults who Self-Harm versus Treatment at Usual

Background: Self-harm is a prevalent behaviour that has a major detrimental impact on a person’s life. Psychological therapies have the potential to help, but evidence of effective interventions remains limited. Access and acceptability of interventions can also be a significant challenge, with individuals either being unable to access help, or having to endure long waiting-lists. Cognitive analytic therapy (CAT) is a time-limited and relationally-focused psychotherapy that may provide a valuable treatment option for people who self-harm. This protocol outlines the methodology for the first feasibility randomised controlled trial (RCT) of CAT for adults that self-harm. The trial will aim to determine the feasibility, acceptability and safety of undertaking larger-scale evaluations of CAT for self-harm within an RCT context. Method: An RCT design with 1:1 allocation to CAT plus treatment as usual (TAU) or TAU alone. Participants will be adult outpatients with three or more instances of self-harm in the past year (target sample of n = 60). CAT will be 8 one-to-one weekly 60-minute sessions plus a follow-up session up to 8 weeks after the last session. Assessments will occur at baseline, 12 weeks and 18 weeks after randomisation. Qualitive interviews with participants will gain insights into feasibility and acceptability of CAT. Feasibility outcomes will be judged against progression criteria.Discussion: CAT may be an effective and accessible treatment option for people who self-harm, providing a more relationally orientated alternative to more behavioural therapies. The proposed feasibility RCT is an important first step in evaluating CAT as a treatment for self-harm. Trial Registration: The trial was pre-registered (21/10/22) on ISR CTN (ISRCTN code: ISRCTN75661422) <br/

Caring for children with complex emotional and psychological disorders: experiences of nurses in a rural paediatric unit

Aims:\ud To explore the experiences of general nurses towards caring for children with mental health issues and to identify strategies to improve management of these children.\ud \ud Background:\ud There has been an increase of children and adolescents with complex emotional and psychological disorders being admitted to paediatric units of general hospitals due to a lack of specialist child and youth mental health facilities. The study is situated in a 16 bed paediatric unit of a rural public hospital. As the closest inpatient child mental health unit of this kind is more than 600 km away, the paediatric unit admits children and adolescents with a primary psychiatric diagnosis.\ud \ud Design:\ud A participatory action research approach guided this study.\ud \ud Methods:\ud Focus groups and individual interviews were conducted with a purposive convenience sample of all nursing staff (n = 20) working in the paediatric unit. Verbatim interview transcripts were analysed to identify the major themes.\ud \ud Results:\ud Two main themes emerged from data analysis: (1) role preparation and adequacy; (2) lack of support and resources. Participants suggested several strategies to address these concerns including: improving relationships with mental health services, professional development, and developing a greater appreciation for mental health interventions.\ud \ud Conclusions:\ud There is a clear need for an increased understanding of mental health practices, an improved relationship between general and mental health services and continuing professional development to ensure nurses possess the skills and confidence to provide quality care to children admitted to a paediatric unit with a mental health diagnosis.\ud \ud Relevance to clinical practice:\ud Few general nurses have mental health training and, through no fault of their own, may be providing less than optimal care to children who are admitted with a mental health diagnosis. Through a desire to improve care, the following participatory action research project was instigated

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial

IMPORTANCE: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES: Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P \u3c .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795859

Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study

International audienceBackgroundPatients with COVID-19 who develop severe acute respiratory distress syndrome (ARDS) can have symptoms that rapidly evolve to profound hypoxaemia and death. The efficacy of extracorporeal membrane oxygenation (ECMO) for patients with severe ARDS in the context of COVID-19 is unclear. We aimed to establish the clinical characteristics and outcomes of patients with respiratory failure and COVID-19 treated with ECMO.MethodsThis retrospective cohort study was done in the Paris–Sorbonne University Hospital Network, comprising five intensive care units (ICUs) and included patients who received ECMO for COVID-19 associated ARDS. Patient demographics and daily pre-ECMO and on-ECMO data and outcomes were collected. Possible outcomes over time were categorised into four different states (states 1–4): on ECMO, in the ICU and weaned off ECMO, alive and out of ICU, or death. Daily probabilities of occupation in each state and of transitions between these states until day 90 post-ECMO onset were estimated with use of a multi-state Cox model stratified for each possible transition. Follow-up was right-censored on July 10, 2020.FindingsFrom March 8 to May 2, 2020, 492 patients with COVID-19 were treated in our ICUs. Complete day-60 follow-up was available for 83 patients (median age 49 [IQR 41–56] years and 61 [73%] men) who received ECMO. Pre-ECMO, 78 (94%) patients had been prone-positioned; their median driving pressure was 18 (IQR 16–21) cm H2O and PaO2/FiO2 was 60 (54–68) mm Hg. At 60 days post-ECMO initiation, the estimated probabilities of occupation in each state were 6% (95% CI 3–14) for state 1, 18% (11–28) for state 2, 45% (35–56) for state 3, and 31% (22–42) for state 4. 35 (42%) patients had major bleeding and four (5%) had a haemorrhagic stroke. 30 patients died.InterpretationThe estimated 60-day survival of ECMO-rescued patients with COVID-19 was similar to that of studies published in the past 2 years on ECMO for severe ARDS. If another COVID-19 outbreak occurs, ECMO should be considered for patients developing refractory respiratory failure despite optimised care