Long-term effectiveness of a cognitive behavioural therapy (CBT) in the management of fatigue in patients with relapsing remitting multiple sclerosis (RRMS): a multicentre, randomised, open-label, controlled trial versus standard care.

BACKGROUND: Fatigue is a disabling symptom of multiple sclerosis (MS). The lack of effective therapeutics has promoted the development of cognitive behavioural therapy (CBT)-based fatigue management programmes. However, their efficacy does not sustain over time. We proposed to test the long-term effectiveness of a 6-week fatigue programme supplemented with four booster sessions ('FACETS+') in patients with relapsing remitting MS (RRMS) and fatigue. METHODS: This multicentre, randomised, controlled, open-label, parallel-group trial versus standard care enrolled patients with RRMS and fatigue. Participants were randomised to either FACETS+ plus standard care or standard care alone. The primary outcome measure was fatigue impact (Modified Fatigue Impact Scale (MFIS) at 12 months) based on intention-to-treat analyses. RESULTS: From May 2017 to September 2020, 162 patients were screened; 105 were randomly assigned to FACETS+ (n=57) or standard care (n=48) and 88 completed the primary outcome assessment for the MFIS. At month 12, participants showed improved MFIS compared with baseline in the intervention group (mean difference (MD)=14.0 points; (95% CI 6.45 to 21.5)) and the control group (MD=6.1 points; (95% CI -0.30 to 12.5)) with a significant between-group difference in favour of the intervention group (adjusted MD=7.89 points; (95% CI 1.26 to 14.52), standardised effect size=0.52, p=0.021). No trial-related serious adverse events were reported. CONCLUSIONS: A 6-week CBT-based programme with four booster sessions is superior to standard care alone to treat MS-related fatigue in the long term (12 months follow-up). The results support the use of the FACETS+ programme for the treatment of MS-related fatigue. TRIAL REGISTRATION NUMBER: NCT03758820.

Impact of Long-Term Dietary High Fat and Eicosapentaenoic Acid on Behavior and Hypothalamic-Pituitary-Adrenal Axis Activity in Amyloidogenic APPswe/PSEN1dE9 Mice.

INTRODUCTION: Alzheimer's disease (AD) alters neurocognitive and emotional function and causes dysregulation of multiple homeostatic processes. The leading AD framework pins amyloid beta plaques and tau tangles as primary drivers of dysfunction. However, many additional variables, including diet, stress, sex, age, and pain tolerance, interact in ways that are not fully understood to impact the onset and progression of AD pathophysiology. We asked: (1) does high-fat diet, compared to low-fat diet, exacerbate AD pathophysiology and behavioral decline? And, (2) can supplementation with eicosapentaenoic (EPA)-enriched fish oil prevent high-fat-diet-induced changes? METHODS: Male and female APPswePSdE9 mice, and their non-transgenic littermates, were randomly assigned to a diet condition (low-fat, high-fat, high-fat with EPA) and followed from 2 to 10 months of age. We assessed baseline corticosterone concentration during aging, pain tolerance, cognitive function, stress coping, and corticosterone response to a stressor. RESULTS: Transgenic mice were consistently more active than non-transgenic mice but did not perform worse on either cognitive task, even though we recently reported that these same transgenic mice exhibited metabolic changes and had increased amyloid beta. Mice fed high-fat diet had higher baseline and post-stressor corticosterone, but diet did not impact cognition or pain tolerance. Sex had the biggest influence, as female mice were consistently more active and had higher corticosterone than males. CONCLUSION: Overall, diet, genotype, and sex did not have consistent impacts on outcomes. We found little support for predicted interactions and correlations, suggesting diet impacts metabolic function and amyloid beta levels, but these outcomes do not translate to changes in behaviors measured here.

The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers.

OBJECTIVES: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2). SUBJECTS AND METHODS: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years. The questionnaire included questions on sociodemographics and the following measures: Hospital Anxiety and Depression Scale, Impact of Event Scale, 36-item Short-Form Health Survey, Memorial Anxiety Scale for PrCa, Cancer Worry Scale, risk perception and knowledge. RESULTS: A total of 760 participants completed questionnaires: 207 participants with GPV in BRCA1, 265 with GPV in BRCA2 and 288 controls (non-carriers from families with a known GPV). We found no evidence of clinically concerning levels of general or cancer-specific distress or poor health-related quality of life in the cohort as a whole. Individuals in the control group had significantly less worry about PrCa compared with the carriers; however, all mean scores were low and within reported general population norms, where available. BRCA2 carriers with previously high prostate-specific antigen (PSA) levels experience a small but significant increase in PrCa anxiety (P = 0.01) and PSA-specific anxiety (P < 0.001). Cancer risk perceptions reflected information provided during genetic counselling and participants had good levels of knowledge, although this declined over time. CONCLUSION: This is the first study to report the longitudinal psychosocial impact of a targeted PrCa screening programme for BRCA1 and BRCA2 carriers. The results reassure that an annual PSA-based screening programme does not have an adverse impact on psychosocial health or health-related quality of life in these higher-risk individuals. These results are important as more PrCa screening is targeted to higher-risk groups.

Correlates of Menarcheal Age in a Psychiatric Sample of Adolescents.

ABSTRACT: Early pubertal timing is associated with more adverse childhood experiences (ACEs) and increased risk for psychopathology during adolescence. However, most work to date has used community or epidemiological samples, and it remains unclear whether these associations persist in acute clinical samples. The present study examined associations between age at menarche and ACEs, psychiatric symptoms, and emotion regulation difficulties in a sample of N = 140 adolescents on a psychiatric inpatient unit. Youth with early menarche reported higher levels of depressive symptoms, more severe suicidal ideation, and greater difficulty with emotion regulation than youth with normative age at menarche. There was a marginal effect of youth with early menarche reporting more ACEs and more anxiety symptoms. These results suggest menarcheal age, and ACEs may be useful risk factors to assess in inpatient settings to predict risk for more severe outcomes, and future research on pubertal timing in high acuity settings is warranted.

Virtual reality used to distract children and young people with long-term conditions from pain or pruritus: A scoping review using PAGER.

AIMS AND OBJECTIVES: To map out the primary research studies relating to how virtual reality (VR) has been used to distract children and young people with long-term conditions from pain or pruritus. BACKGROUND: Pharmacologic treatment of chronic pain and pruritus may have side effects; hence, non-invasive non-pharmacological treatments are being sought. DESIGN: The scoping review followed the methodology recommended by the Joanna Briggs Institute, PAGER framework and PRISMA-ScR checklist. The protocol was registered with the Open Science Registration on 14 February 2022 https//doi.org/10.17605/OSF.IO/K2R93. METHODS: Five databases (Medline, CINAHL, PsycINFO, Web of Science and Scopus) were searched. Data were extracted from primary research studies published between 2000 and 2022 involving children and adolescent populations (<21 years) with a long-term condition that had an element of enduring pruritus and/or pain. RESULTS: Of 464 abstracts screened, 35 full-text papers were assessed with 5 studies meeting the eligibility criteria. Three main themes emerged from the included studies: (1) Improvements in pain and daily functioning; (2) positive perceptions of VR and (3) accessibility and feasibility of VR. No papers were found on the effect of VR on alleviating pruritus. CONCLUSION: VR is feasible, acceptable, and safe for children and adolescents with chronic pain in a range of long-term conditions and offers promise as an adjunctive treatment for improving chronic pain and quality of life. No studies were identified that targeted pruritis or measured pruritis outcomes; thus, the effects of VR for pruritis are unknown. There is a need for rigorously designed, randomised controlled trials to test the clinical and cost-effectiveness of VR interventions for chronic pain and pruritis in children and adolescents. The use of the PAGER (Patterns, Advances, Gaps, Evidence for Practice and Research Recommendations) framework for scoping reviews helped to structure analysis and findings and identify research gaps. RELEVANCE TO CLINICAL PRACTICE: VR interventions offer promise in improving chronic pain related to long-term conditions.

Investigating Substance Use as a Coping Strategy Among Adolescent Psychiatric Inpatients: A Comparative Analysis Before and During the COVID-19 Pandemic.

The COVID-19 pandemic resulted in significant changes in daily life, potentially impacting mental health and substance use behavior. Research on COVID-related changes in adolescent substance use have yielded mixed findings. The current cross-sectional chart review study compared rates of past-year substance use before and during COVID-19 among adolescent psychiatric inpatients, and investigated how motives for coping with COVID-19 changes were related to psychiatric acuity, and past-year substance use. Count models assessed if the number of past-year days of alcohol and cannabis use was higher among adolescents (n = 491, 11-18 years, 61% female) hospitalized during COVID-19 (3/14/20 to 4/5/21) versus adolescents hospitalized before COVID-19 (8/30/2019 to 3/13/20). For a subsample of COVID-19 inpatients (n = 124; 75% female), we evaluated psychiatric correlates of endorsing substances to cope with COVID-19 changes/rules. Results indicated adolescents admitted during COVID-19 reported significantly more past-year alcohol and cannabis use days than adolescents admitted before COVID-19. Adolescents endorsed using alcohol (19%), cannabis (33%), and e-cigarettes/vaping (25%) to cope with COVID-19. E-cigarette/vaping to cope with COVID-19 was significantly related to lifetime suicide attempt. Endorsing alcohol or cannabis to cope with COVID-19 was associated with a significantly greater number of past-year use days for each respective substance. Adolescent psychiatric inpatients admitted during COVID-19 reported more substance use days than adolescents admitted before COVID-19. Using substances to cope was linked to psychiatric correlates (e.g., suicidality). Assessing the presence and function of substance use in this population may be important to identify, treat, and prevent compounding negative outcomes during times of community stress.

Management Considerations for Air Medical Transport Programs Transfusing RhD-Positive Red Blood Cell-Containing Products to Females of Childbearing Potential.

Recent years have seen increased discussion surrounding the benefits of damage control resuscitation, prehospital transfusion (PHT) of blood products, and the use of whole blood over component therapy. Concurrent shortages of blood products with the desire to provide PHT during air medical transport have prompted reconsideration of the traditional approach of administering RhD-negative red cell-containing blood products first-line to females of childbearing potential (FCPs). Given that only 7% of the US population has blood type O negative and 38% has O positive, some programs may be limited to offering RhD-positive blood products to FCPs. Adopting the practice of giving RhD-positive blood products first-line to FCPs extends the benefits of PHT to such patients, but this practice does incur the risk of future hemolytic disease of the fetus and newborn (HDFN). Although the risk of future fetal mortality after an RhD-incompatible transfusion is estimated to be low in the setting of acute hemorrhage, the number of FCPs who are affected by this disease will increase as more air medical transport programs adopt this practice. The process of monitoring and managing HDFN can also be time intensive and costly regardless of the rates of fetal mortality. Air medical transport programs planning on performing PHT of RhD-positive red cell-containing products to FCPs should have a basic understanding of the pathophysiology, prevention, and management of hemolytic disease of the newborn before introducing this practice. Programs should additionally ensure there is a reliable process to notify receiving centers of potentially RhD-incompatible PHT because alloimmunization prophylaxis is time sensitive. Facilities receiving patients who have had PHT must be prepared to identify, counsel, and offer alloimmunization prophylaxis to these patients. This review aims to provide air medical transport professionals with an understanding of the pathophysiology and management of HDFN and provide a template for the early management of FCPs who have received an RhD-positive red cell-containing PHT. This review also covers the initial workup and long-term anticipatory guidance that receiving trauma centers must provide to FCPs who have received RhD-positive red cell-containing PHT.

A Faster Prostate MRI: Comparing a Novel Denoised, Single-Average T2 Sequence to the Conventional Multiaverage T2 Sequence Regarding Lesion Detection and PI-RADS Score Assessment.

BACKGROUND: The T2 w sequence is a standard component of a prostate MRI examination; however, it is time-consuming, requiring multiple signal averages to achieve acceptable image quality. PURPOSE/HYPOTHESIS: To determine whether a denoised, single-average T2 sequence (T2 -R) is noninferior to the standard multiaverage T2 sequence (T2 -S) in terms of lesion detection and PI-RADS score assessment. STUDY TYPE: Retrospective. POPULATION: A total of 45 males (age range 60-75 years) who underwent clinically indicated prostate MRI examinations, 21 of whom had pathologically proven prostate cancer. FIELD STRENGTH/SEQUENCE: A 3 T; T2 w FSE, DWI with ADC maps, and dynamic contrast-enhanced images with color-coded perfusion maps. T2 -R images were created from the raw data utilizing a single "average" with iterative denoising. ASSESSMENT: Nine readers randomly assessed complete exams including T2 -R and T2 -S images in separate sessions. PI-RADS version 2.1 was used. All readers then compared the T2 -R and T2 -S images side by side to evaluate subjective preference. An additional detailed image quality assessment was performed by three senior level readers. STATISTICAL TESTS: Generalized linear mixed effects models for differences in lesion detection, image quality features, and overall preference between T2 -R and T2 -S sequences. Intraclass correlation coefficients (ICC) were used to assess reader agreement for all comparisons. A significance threshold of P = 0.05 was used for all statistical tests. RESULTS: There was no significant difference between sequences regarding identification of lesions with PI-RADS ≥3 (P = 0.10) or PI-RADS score (P = 0.77). Reader agreement was excellent for lesion identification (ICC = 0.84). There was no significant overall preference between the two sequences regarding image quality (P = 0.07, 95% CI: [-0.23, 0.01]). Reader agreement was good regarding sequence preference (ICC = 0.62). DATA CONCLUSION: Use of single-average, denoised T2 -weighted images was noninferior in prostate lesion detection or PI-RADS scoring when compared to standard multiaverage T2 -weighted images. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Evaluation of the impact of a novel denoising algorithm on image quality in dual-energy abdominal CT of obese patients.

OBJECTIVES: Evaluate a novel algorithm for noise reduction in obese patients using dual-source dual-energy (DE) CT imaging. METHODS: Seventy-nine patients with contrast-enhanced abdominal imaging (54 women; age: 58 ± 14 years; BMI: 39 ± 5 kg/m2, range: 35-62 kg/m2) from seven DECT (SOMATOM Flash or Force) were retrospectively included (01/2019-12/2020). Image domain data were reconstructed with the standard clinical algorithm (ADMIRE/SAFIRE 2), and denoised with a comparison (ME-NLM) and a test algorithm (rank-sparse kernel regression). Contrast-to-noise ratio (CNR) was calculated. Four blinded readers evaluated the same original and denoised images (0 (worst)-100 (best)) in randomized order for perceived image noise, quality, and their comfort making a diagnosis from a table of 80 options. Comparisons between algorithms were performed using paired t-tests and mixed-effects linear modeling. RESULTS: Average CNR was 5.0 ± 1.9 (original), 31.1 ± 10.3 (comparison; p < 0.001), and 8.9 ± 2.9 (test; p < 0.001). Readers were in good to moderate agreement over perceived image noise (ICC: 0.83), image quality (ICC: 0.71), and diagnostic comfort (ICC: 0.6). Diagnostic accuracy was low across algorithms (accuracy: 66, 63, and 67% (original, comparison, test)). The noise received a mean score of 54, 84, and 66 (p < 0.05); image quality 59, 61, and 65; and the diagnostic comfort 63, 68, and 68, respectively. Quality and comfort scores were not statistically significantly different between algorithms. CONCLUSIONS: The test algorithm produces quantitatively higher image quality than current standard and existing denoising algorithms in obese patients imaged with DECT and readers show a preference for it. CLINICAL RELEVANCE STATEMENT: Accurate diagnosis on CT imaging of obese patients is challenging and denoising algorithms can increase the diagnostic comfort and quantitative image quality. This could lead to better clinical reads. KEY POINTS: • Improving image quality in DECT imaging of obese patients is important for accurate and confident clinical reads, which may be aided by novel denoising algorithms using image domain data. • Accurate diagnosis on CT imaging of obese patients is especially challenging and denoising algorithms can increase quantitative and qualitative image quality. • Image domain algorithms can generalize well and can be implemented at other institutions.

The quality of paediatric asthma guidelines: evidence underpinning diagnostic test recommendations from a meta-epidemiological study.

BACKGROUND: Asthma is one of the most frequent reasons children visit a general practitioner (GP). The diagnosis of childhood asthma is challenging, and a variety of diagnostic tests for asthma exist. GPs may refer to clinical practice guidelines when deciding which tests, if any, are appropriate, but the quality of these guidelines is unknown. OBJECTIVES: To determine (i) the methodological quality and reporting of paediatric guidelines for the diagnosis of childhood asthma in primary care, and (ii) the strength of evidence supporting diagnostic test recommendations. DESIGN: Meta-epidemiological study of English-language guidelines from the United Kingdom and other high-income countries with comparable primary care systems including diagnostic testing recommendations for childhood asthma in primary care. The AGREE-II tool was used to assess the quality and reporting of the guidelines. The quality of the evidence was assessed using GRADE. RESULTS: Eleven guidelines met the eligibility criteria. The methodology and reporting quality varied across the AGREE II domains (median score 4.5 out of 7, range 2-6). The quality of evidence supporting diagnostic recommendations was generally of very low quality. All guidelines recommended the use of spirometry and reversibility testing for children aged ≥5 years, however, the recommended spirometry thresholds for diagnosis differed across guidelines. There were disagreements in testing recommendations for 3 of the 7 included tests. CONCLUSIONS: The variable quality of guidelines, lack of good quality evidence, and inconsistent recommendations for diagnostic tests may contribute to poor clinician adherence to guidelines and variation in testing for diagnosing childhood asthma.

Survival Benefit of Helicopter Scene Response for Patients with an Injury Severity Score of at Least Nine: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Helicopter EMS (HEMS) is a well-established mode of rapid transportation for patients with need for time-sensitive interventions, especially in patients with significant traumatic injuries. Traditionally in the setting of trauma, HEMS is often considered appropriate when used for patients with "severe" injury as defined by Injury Severity Score (ISS) >15. This may be overly conservative, and patients with a lower ISS may benefit from HEMS-associated speed or care quality. Our objective was to perform a meta-analysis of trauma HEMS transports to evaluate for possible mortality benefit in injured cases defined by an ISS score >8, lower than the customary ISS cutoff of >15. METHODS: A broad search of the literature was performed including PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Google Scholar from the years 1970 to 2022. The gray literature and reference lists of included publications were also examined. We included studies with the outcome of mortality in HEMS vs control in trauma transports from scene of injury for patients (adult or pediatric) with ISS > 8. RESULTS: Nine eligible studies were used in the final analysis: six in the primary analysis and three in sensitivity analysis due to patient overlap. All studies reported statistically significant survival benefit in HEMS compared to control group. The minimum survival odds ratio (OR) benefit observed was OR 1.15 (95% CI 1.06-1.25) and maximum was OR 2.04 (95% CI 1.18-3.57). Risk of bias tool (ROBINS-I) application yielded moderate to low risk of bias, mainly due to the observational nature of the studies included. CONCLUSIONS: There was a statistically significant survival benefit in patients with ISS > 8 when HEMS was used over traditional ground ambulance transportation, although novel and more inclusive trauma triage criteria may be more appropriate in the future to guide HEMS utilization decision-making. Restricting HEMS to trauma patients with ISS >15 likely misses survival benefit that could be afforded to the subset of trauma patients with serious injury.

The quality of diagnostic guidelines for children in primary care: A meta-epidemiological study.

AIM: To determine the quality of paediatric guidelines relevant to diagnosis of three of the most common conditions in primary care: fever, gastroenteritis and constipation. METHODS: We undertook a meta-epidemiological study of paediatric guidelines for fever, gastroenteritis and gastroenteritis. We systematically searched MEDLINE, Embase, Trip Database, Guidelines International Network, the National Guideline Clearinghouse and WHO from February 2011 to September 2022 for guidelines from high-income settings containing diagnostic recommendations. We assessed the quality of guideline reporting for included guidelines using the AGREE II tool. RESULTS: We included 16 guidelines: fever (n = 7); constipation (n = 4) and gastroenteritis (n = 5). The overall quality across the three conditions was graded moderate (median AGREE II score 4.5/7, range 2.5-6.5) with constipation guidelines rated the highest (median 6/7), and fever rated the lowest (median 3.8/7). Major methodological weaknesses included consideration of guideline applicability. Half of the guidelines did not report involving parent representatives, and 56% did not adequately declare or address their competing interests. CONCLUSIONS: Substantial variations exist in the quality of paediatric guidelines related to the diagnosis of primary care presentations. Better quality guidance is needed for general practitioners to improve diagnosis for children in primary care.

A Statewide Randomized Controlled Trial to Compare Three Models for Implementing Parent Child Interaction Therapy.

OBJECTIVE: This study (NIMH RO1 MH095750; ClinicalTrials.gov Identifier: NCT02543359) evaluated the effectiveness of three training models to implement a well-established evidence-based treatment, Parent-Child Interaction Therapy (PCIT). METHOD: Fifty licensed outpatient clinics, including 100 clinicians, 50 supervisors, and 50 administrators were randomized to one of three training conditions: 1) Learning Collaborative (LC), 2) Cascading Model (CM) or 3) Distance Education (DE). Data to assess training and implementation outcomes were collected at 4 time points coinciding with the training period: baseline, 6- (mid), 12- (post), and 24-months (1-year follow-up). RESULTS: Multi-level hierarchical linear growth modeling was used to examine changes over time in training outcomes. Results indicate that clinicians in CM were more likely to complete training, reported high levels of training satisfaction and better learning experiences compared to the other training conditions. However, supervisors in the LC condition reported greater learning experiences, higher levels of knowledge, understanding of treatment, and satisfaction compared to supervisors in other conditions. Although clinicians and supervisors in the DE condition did not outperform their counterparts on any outcomes, their performance was comparable to both LC and CM in terms of PCIT use, supervisor perceived acceptability, feasibility, system support, and clinician satisfaction. CONCLUSIONS: Through the use of a randomized controlled design and community implementation, this study contributes to the current understanding of the impact of training design on implementation of PCIT. Results also indicate that although in-person training methods may produce more positive clinician and supervisor outcomes, training is not a one-size-fits-all model, with DE producing comparable results on some variables.

Reverse Coding of a Common-Sense Physical Activity Intervention for Older Adults Using Elements of the Behaviour Change Wheel Framework.

"Common-sense" physical activity (PA) interventions for older adults may be more effective if developed in accordance with behavior change theory. One way to achieve this is through retrospectively applying a theoretical behavior change framework to "reverse code" an existing intervention and guide its ongoing development. This study aimed to detail a clear and systematic procedure that applied elements of the Behaviour Change Wheel (BCW) framework to reverse code the Active Ageing Pathway (AAP) intervention. The objectives of the procedure were to characterize the content of the AAP and its links to behavior change theory. The content of the AAP was first deconstructed through the examination of "standard operating procedures" documents, in-person observation, and a series of face-to-face discussions with AAP management. Then, the behavior change techniques (BCT) and BCW intervention functions associated with the AAP's content were identified and coded using the BCT Taxonomy version 1. Forty-one active components were identified within the AAP, which involved numerous professionals, and pertained to a diverse and interlinked range of factors, across various modes of delivery. The components were classified under 20 separate BCT labels, which related to eight of the nine BCW intervention functions. These outcomes were demonstrated to have practical applications for identifying gaps in intervention content as well as for guiding future intervention evaluation. This study supports previous work detailing the usefulness of reverse coding procedures as a tool for developing common-sense interventions, and is the first to do so in the context of a PA intervention for older adults.

Helicopter Emergency Medical Services Outcomes Research 1983 to 2022: Evidence Overview and Longitudinal Trends.

OBJECTIVE: Helicopter emergency medical services (HEMS) literature has been assessed in reviews focusing on various diagnoses, but there are few, if any, summaries of the entire body of HEMS outcomes evidence. Our goal was to summarize the existing research addressing patient-centered outcomes potentially accrued with HEMS. METHODS: As part of the Critical Care Transport Collaborative Outcomes Research Effort, we generated the HEMS Outcomes Assessment Research Database and executed descriptive analyses of longitudinal trends from 1983 to 2022. Both indexed and gray literature sources were incorporated in the HEMS Outcomes Assessment Research Database. Studies were reviewed by at least 2 authors to select those that addressed a patient-centered outcome. Studies addressing solely HEMS logistics were excluded. Categoric analyses were executed with the Fisher exact test, and continuous variables were evaluated for normality with normal quantile plotting and a comparison of medians and 95% confidence intervals. RESULTS: We found that HEMS outcomes study sample sizes increased steadily from 1983 to 2012, with the most recent decade demonstrating a marked increase in the rate of publication of HEMS outcomes studies. Most research (70.6%) addressed trauma patient outcomes, but recent decades have seen a significant increase in non-trauma studies. Recent decades have also been characterized by an increase in the production of HEMS outcomes research outside of North America and Europe. CONCLUSION: This study summarizes the current state of the HEMS outcome literature. We highlight increasing contributions from worldwide researchers and increasing focus on HEMS benefits in non-trauma cases, particularly time-critical cases such as cardiac or stroke diagnoses. This provides a basis for further investigations into patient-oriented benefits potentially accrued with HEMS.

Measuring the cost-effectiveness of treatments for people with multiple sclerosis: Beyond quality-adjusted life-years.

BACKGROUND: It is a familiar story. A promising multiple sclerosis (MS) treatment clears the three regulatory hurdles of safety, quality and efficacy, only to fall at the fourth: cost-effectiveness. This has led to concerns about the validity of the measures typically used to quantify treatment effects in cost-effectiveness analyses and in 2012, in the United Kingdom, the National Institute for Health and Care Excellence called for an improvement in the cost-effectiveness framework for assessing MS treatments. OBJECTIVE AND METHODS: This review describes what is meant by cost-effectiveness in health/social care funding decision-making, and usual practice for assessing treatment benefits. RESULTS: We detail the use of the quality-adjusted life-year (QALY) in resource allocation decisions, and set out limitations of this approach in the context of MS. CONCLUSION: We conclude by highlighting methodological and policy developments which should aid addressing these limitations.

Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Examining bidirectional associations between perceived social support and psychological symptoms in the context of stressful event exposure: a prospective, longitudinal study.

BACKGROUND: After stressful event exposure, higher perceived social support is a well-established correlate of decreased risk for psychological symptoms, including depressive, anxiety and posttraumatic stress (PTS) symptoms. However, longitudinal data on the direction of this association and the stability of perceived social support are scarce and have yielded mixed results, with a particular lack of prospective studies. We aimed to investigate changes in perceived social support and bidirectional associations between perceived social support and psychological symptoms in a prospective, longitudinal study. METHODS: A sample of German soldiers was assessed before and after deployment to Afghanistan. Group-based trajectory modelling was used to investigate the stability of perceived social support and to identify possible distinguishable trajectories of perceived social support. Bidirectional associations between perceived social support (general and workplace) and psychological symptoms (depressive, anxiety and PTS) were examined using gamma regressions. RESULTS: Average levels of perceived general social support did not change, while perceived workplace social support increased slightly (t(344) = 5.51, p < .001). There were no distinguishable trajectories of perceived social support. Higher perceived general (Mean ratio (MR) = 0.84, 95% CI = [0.74, 0.95]) and workplace social support (MR = 0.82, 95% CI = [0.72, 0.92]) predicted lower depressive symptoms, but not anxiety or PTS symptoms. Only higher PTS (MR = 0.95, 95% CI = [0.91, 0.99]) and higher depressive symptoms (MR = 0.96, 95% CI = [0.93, 0.99]) predicted lower perceived general social support. CONCLUSIONS: Perceived social support can remain relatively stable under exposure to environmental stressors such as military deployment. Higher perceived social support could protect against depressive symptoms via a stress-buffering mechanism, while support may need to be more tailored to individual needs for a protection against PTS symptoms. Individuals with elevated depressive and PTS symptoms might have impaired abilities or opportunities to access social support after stressful event exposure. Future studies could investigate distressing social emotions and associated maladaptive social cognitions as possible mechanisms in the association between symptoms and lower perceived social support. Especially with respect to PTS symptoms, future studies could focus on conditions that enable individuals to benefit from social support.

Adjunct Use of Continuous Renal Replacement Therapy with Extracorporeal Membrane Oxygenation Achieves Negative Fluid Balance and Enhances Oxygenation Which Improves Survival in Critically Ill Patients without Kidney Failure.

INTRODUCTION: Fluid overload in extracorporeal membrane oxygenation (ECMO) patients has been associated with increased mortality. Patients receiving ECMO and continuous renal replacement therapy (CRRT) who achieve a negative fluid balance have improved survival. Limited data exist on the use of CRRT solely for fluid management in ECMO patients. METHODS: We performed a single-center retrospective review of 19 adult ECMO patients without significant renal dysfunction who received CRRT for fluid management. These patients were compared to a cohort of propensity-matched controls. RESULTS: After 72 h, the treatment group had a fluid balance of -3840 mL versus + 425 mL (p ≤ 0.05). This lower fluid balance correlated with survival to discharge (odds ratio 2.54, 95% confidence interval 1.10-5.87). Improvement in the ratio of arterial oxygen content to fraction of inspired oxygen was also significantly higher in the CRRT group (102.4 vs. 0.7, p ≤ 0.05). We did not observe any significant difference in renal outcomes. CONCLUSIONS: The use of CRRT for fluid management is effective and, when resulting in negative fluid balance, improves survival in adult ECMO patients without significant renal dysfunction.

Hydrophobic gasket mutation produces gating pore currents in closed human voltage-gated proton channels.

The hydrophobic gasket (HG), a ring of hydrophobic amino acids in the voltage-sensing domain of most voltage-gated ion channels, forms a constriction between internal and external aqueous vestibules. Cationic Arg or Lys side chains lining the S4 helix move through this "gating pore" when the channel opens. S4 movement may occur during gating of the human voltage-gated proton channel, hHV1, but proton current flows through the same pore in open channels. Here, we replaced putative HG residues with less hydrophobic residues or acidic Asp. Substitution of individuals, pairs, or all 3 HG positions did not impair proton selectivity. Evidently, the HG does not act as a secondary selectivity filter. However, 2 unexpected functions of the HG in HV1 were discovered. Mutating HG residues independently accelerated channel opening and compromised the closed state. Mutants exhibited open-closed gating, but strikingly, at negative voltages where "normal" gating produces a nonconducting closed state, the channel leaked protons. Closed-channel proton current was smaller than open-channel current and was inhibited by 10 µM Zn2+ Extreme hyperpolarization produced a deeper closed state through a weakly voltage-dependent transition. We functionally identify the HG as Val109, Phe150, Val177, and Val178, which play a critical and exclusive role in preventing H+ influx through closed channels. Molecular dynamics simulations revealed enhanced mobility of Arg208 in mutants exhibiting H+ leak. Mutation of HG residues produces gating pore currents reminiscent of several channelopathies.