bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing thresholds for important benefits considering the harms of screening interventions
Authors: Helsingen Lise Mørkved , Zeng Linan , Siemieniuk Reed Alexander , Lytvyn Lyubov , Vandvik Per Olav , Agoritsas Thomas , Bretthauer Michael , Guyatt Gordon 
Published: December 2020

Context and objectiveStandards for clinical practice guidelines require explicit statements regarding how values and preferences influence recommendations. However, no cancer screening guideline has addressed the key question of what magnitude of benefit people require to undergo screening, given its harms and burdens. This article describes the development of a new method for guideline developers to address this key question in the absence of high-quality evidence from published literature.Summary of methodThe new method was developed and applied in the context of a recent BMJ Rapid Recommendation clinical practice guideline for colorectal cancer (CRC) screening. First, we presented the guideline panel with harms and burdens (derived from a systematic review) associated with the CRC screening tests under consideration. Second, each panel member completed surveys documenting their views of expected benefits on CRC incidence and mortality that people would require to accept the harms and burdens of screening. Third, the panel discussed results of the surveys and agreed on thresholds for benefits at which the majority of people would choose screening. During these three steps, the panel had no access to the actual benefits of the screening tests. In step four, the panel was presented with screening test benefits derived from a systematic review of clinical trials and microsimulation modelling. The thresholds derived through steps one to three were applied to these benefits, and directly informed the panel’s recommendations.ConclusionWe present the development and application of a new, four-step method enabling incorporation of explicit and transparent judgements of values and preferences in a screening guideline. Guideline panels should establish their view regarding the magnitude of required benefit, given burdens and harms, before they review screening benefits and make their recommendations accordingly. Making informed screening decisions requires transparency in values and preferences judgements that our new method greatly facilitates.
Methods for estimating economic benefits of surgical interventions in low-income and middle-income countries: a scoping review
Authors: Hilla Amy , Reese Victoria , Nonvignon Justice , Dolan Carrie B. 
Published: December 2020

ObjectivesStudies indicate that many types of surgical care are cost-effective compared with other health interventions in low-income and middle-income countries (LMICs). However, global health investments to support these interventions remain limited. This study undertakes a scoping review of research on the economic impact of surgical interventions in LMICs to determine the methodologies used in measuring economic benefits.DesignThe Arksey and O’Malley methodological framework for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist were used to review the data systematically. Online databases were used to identify papers published between 2005 and 2020, from which we selected 19 publications that quantitatively examined the economic benefits of surgical interventions in LMICs.ResultsMajority of publications (79%) reported the use of disability-adjusted life-years (DALYs) to assess economic impact. In comparison, 21% used other measures, such as the value of statistical life or cost-effectiveness ratios, or no measure at all. 31% were systematic or retrospective reviews of the literature on surgical procedures in LMICs, while 69% either directly assessed economic impact in a specific area or evaluated the need for surgical procedures in LMICs. All studies reviewed related to the economic impact of surgical procedures in LMICs, with most about paediatric surgical procedures or a specific surgical specialty.ConclusionTo make informed policy decisions regarding global health investments, the economic impact must be accurately measured. Researchers employ a range of techniques to quantify the economic benefit of surgeries in LMICs, which limits understanding of overall economic value. We conclude that the literature would benefit from a careful selection of methods, incorporating age and disability weights based on the Global Burden of Disease weights, and converting DALYs to dollars using the value of statistical life approach and the human capital approach, reporting both estimates.
Effects of a peer co-facilitated educational programme for parents of children with ADHD: a feasibility randomised controlled trial protocol
Authors: Mundal Ingunn , Gråwe Rolf W , Hafstad Hege , Cuevas Carlos De las , Lara-Cabrera Mariela Loreto 
Published: December 2020

IntroductionSignificant numbers of children with attention deficit hyperactivity disorder (ADHD) display problems that cause multiple disabilities, deficits and handicaps that interfere with social relationships, development and school achievement. They may have multiple problems, which strain family dynamics and influence the child’s treatment. Parent activation, described as parents’ knowledge, skills and confidence in dealing with their child’s health and healthcare, has been shown to be an important factor in improving health outcomes. Research suggests that parents need edification to learn skills crucial to the treatment and management of their children’s healthcare. Promoting positive parenting techniques may reduce negative parenting factors in families. This study aims to assess the acceptability, feasibility and estimated sample size of a randomised controlled trial (RCT) comparing an ADHD peer co-led educational programme added to treatment as usual (TAU).Methods and analysisUsing a randomised waitlist controlled trial, parents of children aged 6–12 years newly diagnosed with ADHD, and referred to a child mental health outpatient clinic in Mid-Norway, will receive TAU concomitant with a peer co-facilitated parental engagement educational programme (n=25). Parents in the control group will receive TAU, and the educational programme treatment within a waitlist period of 3–6 months (n=25). Parent activation, satisfaction, well-being, quality of life and treatment adherence, will be assessed at baseline (T0), 2 weeks (T1) pre–post intervention (T2, T3) and at 3 months follow-up (T4). Shared decision making, parents preferred role in health-related decisions and involvement, parent-reported symptoms of ADHD and child’s overall level of functioning will be assessed at T0 and T4. Such data will be used to calculate the required sample size for a full-scale RCT.Ethics and disseminationApproval was obtained from the Regional Committee for Medicine and Health Research Ethics in Mid-Norway (ref: 2018/1196). The findings of this study are expected to provide valuable knowledge about how to optimise family education and management of ADHD and will be disseminated through presentations at conferences and publication in peer-reviewed journals.Trial registration numberNCT04010851.
Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a community-based individually randomised controlled trial in Kasaï, Democratic Republic of Congo
Authors: Cazes Cécile , Phelan Kevin , Hubert Victoire , Alitanou Rodrigue , Boubacar Harouna , Izie Bozama Liévin , Tshibangu Sakubu Gilbert , Beuscart Aurélie , Yao Cyrille , Gabillard Delphine , Kinda Moumouni , Augier Augustin , Anglaret Xavier , Shepherd Susan , Becquet Renaud 
Published: December 2020

IntroductionAcute malnutrition (AM) is a continuum condition, arbitrarily divided into moderate and severe AM (SAM) categories, funded and managed in separate programmes under different protocols. Optimising acute MAlnutrition (OptiMA) treatment aims to simplify and optimise AM management by treating children with mid-upper arm circumference (MUAC) <125 mm or oedema with one product—ready-to-use therapeutic food—at a gradually tapered dose. Our main objective was to compare the OptiMA strategy with the standard nutritional protocol in children 6–59 months presenting with MUAC <125 mm or oedema without additional complications, as well as in children classified as uncomplicated SAM (ie, MUAC <115 mm or weight-for-height Z-score (WHZ) <−3 or with oedema).Methods and analysisThis study was a non-inferiority, individually randomised controlled clinical trial conducted at community level in the Democratic Republic of Congo. Children 6–59 months presenting with MUAC <125 mm or WHZ <−3 or with bipedal oedema and without medical complication were included after signed informed consent in outpatient health facilities. All participants were followed for 6 months. Success in both arms was defined at 6 months post inclusion as being alive, not acutely malnourished per the definition applied at inclusion and without an additional episode of AM throughout the 6-month observation period. Recovery among children with uncomplicated SAM was the main secondary outcome. For the primary objective, 890 participants were needed, and 480 children with SAM were needed for the main secondary objective. We will perform non-inferiority analyses in per-protocol and intention-to-treat basis for both outcomes.Ethics and disseminationEthics approvals were obtained from the National Health Ethics Committee of the Democratic Republic of Congo and from the Ethics Evaluation Committee of Inserm, the French National Institute for Health and Medical Research (Paris, France). We will submit results for publication to a peer-reviewed journal and disseminate findings in international and national conferences and meetings.Trial registration numberNCT03751475. Registered 19 September 2018, https://clinicaltrials.gov/ct2/show/NCT03751475.
Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study
Authors: Hodges Gethin , Pallisgaard Jannik , Schjerning Olsen Anne-Marie , McGettigan Patricia , Andersen Mikkel , Krogager Maria , Kragholm Kristian , Køber Lars , Gislason Gunnar Hilmar , Torp-Pedersen Christian , Bang Casper N 
Published: December 2020

ObjectiveTo evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19.DesignRetrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender.SettingAll hospitals in Denmark.Participants1310 patients aged ≥18 years admitted to hospital with COVID-19 from 27th of February to 1st of May 2020, with available biochemistry data.Main outcome measuresA composite of death/ICU admission occurring within 30 days.ResultsOf the 1310 patients admitted to hospital (54.6% men; median age 73.6 years), 352 (26.9%) experienced the composite endpoint and 263 (20.1%) died. For the composite endpoint, the absolute risks for moderately and severely elevated C reactive protein (CRP) were significantly higher, 21.5% and 39.2%, respectively, compared with 5.0% for those with normal CRP. Moderately and severely elevated leucocytes were significantly higher, 34.5% and 46.6% risk, respectively, compared with 23.2% for those with normal leucocytes. Moderately and severely decreased estimated glomerular filtration rates (eGFR) were significantly higher, 41.5% and 45.9% risk, respectively, compared with 30.4% for those with normal/mildly decreased eGFR. Normal and elevated ureas were significantly higher, 22.3% and 40.6% risk, respectively, compared with 7.3% for those with low urea. Elevated D-dimer was significantly higher, 31.8% risk, compared with 17.5% for those with normal D-dimer. Moderately and severely elevated troponins were significantly higher, 27.7% and 57.3% risk, respectively, compared with 9.4% for those with normal troponin. Elevated procalcitonin was significantly higher, 52.1% risk, compared with 28.0% for those with normal procalcitonin.ConclusionIn this nationwide study of patients admitted with COVID-19, elevated levels of CRP, leucocytes, procalcitonin, urea, troponins and D-dimer, and low levels of eGFR were associated with higher standardised absolute risk of death/ICU admission within 30 days.
The DemWG study: reducing the risk of hospitalisation through a complex intervention for people with dementia and mild cognitive impairment (MCI) in German shared-housing arrangements: study protocol of a prospective, mixed-methods, multicentre, cluster-randomised controlled trial
Authors: Kratzer André , Scheel Jennifer , Wolf-Ostermann Karin , Schmidt Annika , Ratz Katrin , Donath Carolin , Graessel Elmar 
Published: December 2020

IntroductionShared-housing arrangements (SHAs) are small, home-like care environments in Germany. Residents are predominantly people with dementia. The risk for all-cause hospitalisation is consistently higher for people with dementia compared with people without dementia and there is currently no evidence-based intervention to reduce the risk of hospitalisation. Thus, the DemWG study investigates whether a complex intervention is effective in reducing hospitalisation (primary outcome), behavioural and psychological symptoms of dementia and falls and for stabilising cognitive functioning and quality of life in people with dementia and mild cognitive impairment (MCI) in German SHAs.Methods and analysisBased on the UK Medical Research Council framework ‘Developing and evaluating complex interventions’, a prospective, mixed-methods, multicentre, cluster-randomised controlled trial combining primary and secondary data analyses as well as quantitative and qualitative research methods is being conducted. The intervention consists of three parts: (A) education of nursing staff in SHAs; (B) awareness raising and continuing medical education (CME) of general practitioners; (C) multicomponent non-pharmacological group intervention MAKS-mk+ (‘m’=motor training; ‘k’=cognitive training; ‘+’=fall prevention) for people with dementia and MCI. Randomisation is stratified by the German federal states and type of setting (rural vs urban). Neither the trained professionals nor the participants are blinded. Data are collected at baseline and after 6, 12 and 18 months with standardised instruments. Quantitative data will be analysed by multivariate analyses according to the general linear model, qualitative data using qualitative content analysis. Recruitment is still ongoing until 31 December 2020.Ethics and disseminationAll procedures were approved by the Ethics Committee of the University of Bremen (Ref. 2019-18-06-3). Informed consent will be obtained before enrolment of participants. Due to findings of previous randomised controlled trials, serious adverse events are not expected. Results will be disseminated in peer-reviewed journal publications and conference presentations.Trial registration numberISRCTN89825211.
Clinical effectiveness and cost effectiveness of individual mental health workers colocated within primary care practices: a systematic literature review
Authors: Woods Jean-Baptiste , Greenfield Geva , Majeed Azeem , Hayhoe Benedict 
Published: December 2020

ObjectivesMental health disorders contribute significantly to the global burden of disease and lead to extensive strain on health systems. The integration of mental health workers into primary care has been proposed as one possible solution, but evidence of clinical and cost effectiveness of this approach is unclear. We reviewed the clinical and cost effectiveness of mental health workers colocated within primary care practices.DesignSystematic literature review.Data sourcesWe searched the Medline, Embase, PsycINFO, Healthcare Management Information Consortium (HMIC) and Global Health databases.Eligibility criteriaAll quantitative studies published before July 2019 were eligible for the review; participants of any age and gender were included. Studies did not need to report a certain outcome measure or comparator in order to be eligible.Data extraction and synthesisData were extracted using a standardised table; however, pooled analysis proved unfeasible. Studies were assessed for risk of bias using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool and the Cochrane collaboration’s tool for assessing risk of bias in randomised trials.ResultsFifteen studies from four countries were included. Mental health worker integration was associated with mental health benefits to varied populations, including minority groups and those with comorbid chronic diseases. Furthermore, the interventions were correlated with high patient satisfaction and increases in specialist mental health referrals among minority populations. However, there was insufficient evidence to suggest clinical outcomes were significantly different from usual general practitioner care.ConclusionsWhile there appear to be some benefits associated with mental health worker integration in primary care practices, we found insufficient evidence to conclude that an onsite primary care mental health worker is significantly more clinically or cost effective when compared with usual general practitioner care. There should therefore be an increased emphasis on generating new evidence from clinical trials to better understand the benefits and effectiveness of mental health workers colocated within primary care practices.
Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review
Authors: Patel Roshni , Naqvi Sumrah A , Griffiths Chris , Bloom Chloe I 
Published: December 2020

BackgroundOral corticosteroid use increases the risk of systemic adverse effects including osteoporosis, bone fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if inhaled corticosteroid (ICS) use in asthma is also associated with increased risk of systemic effects.MethodsMEDLINE and Embase databases were searched to identify studies that were designed to investigate ICS-related systemic adverse effects in people with asthma. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia or mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and Risk of Bias In Non-randomised Studies of Interventions-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies reporting each outcome.ResultsThirteen studies met the inclusion criteria, 2 trials and 11 observational studies. Study numbers by outcome were: six BMD, six respiratory infections (four pneumonia, one tuberculosis (TB), one non-TB mycobacteria), one ocular disorder (cataracts) and no diabetes. BMD studies found conflicting results (three found loss of BMD and three found no loss), but were limited by study size, short follow-up and lack of generalisability. Studies addressing infection risk generally found positive associations but suffered from a lack of power, misclassification and selection bias. The one study which assessed ocular disorders found an increased risk of cataracts. Most studies were not able to fully adjust for known confounders, including oral corticosteroids.ConclusionThere is a paucity of studies assessing systemic adverse effects associated with ICS use in asthma. Those studies that have been carried out present conflicting findings and are limited by multiple biases and residual confounding. Further appropriately designed studies are needed to quantify the magnitude of the risk for ICS-related systemic effects in people with asthma.
Workload of learners during simulated paediatric cardiopulmonary resuscitation
Authors: Young Ann L , Doughty Cara B , Williamson Kaitlin C , Won Sharon K , Rus Marideth C , Villarreal Nadia N , Camp Elizabeth A , Lemke Daniel S 
Published: December 2020

IntroductionLearner workload during simulated team-based resuscitations is not well understood. In this descriptive study, we measured the workload of learners in different team roles during simulated paediatric cardiopulmonary resuscitation.MethodsPaediatric emergency nurses and paediatric and emergency medicine residents formed teams of four to eight and randomised into roles to participate in simulation-based, paediatric resuscitation. Participant workload was measured using the NASA Task Load Index, which provides an average workload score (from 0 to 100) across six subscores: mental demand, physical demand, temporal demand, performance, frustration and mental effort. Workload is considered low if less than 40, moderate if between 40 and 60 and high if greater than 60.ResultsThere were 210 participants representing 40 simulation teams. 138 residents (66%) and 72 nurses (34%) participated. Team lead reported the highest workload at 65.2±10.0 (p=0.001), while the airway reported the lowest at 53.9±10.8 (p=0.001); team lead had higher scores for all subscores except physical demand. Team lead reported the highest mental demand (p<0.001), while airway reported the lowest. Cardiopulmonary resuscitation coach and first responder reported the highest physical demands (p<0.001), while team lead and nurse recorder reported the lowest (p<0.001).ConclusionsWorkload for learners in paediatric simulated resuscitation teams was moderate to high and varied significantly based on team role. Composition of workload varied significantly by team role. Measuring learner workload during simulated resuscitations allows improved processes and choreography to optimise workload distribution.
Mitochondrial Lon-induced mtDNA leakage contributes to PD-L1–mediated immunoescape via STING-IFN signaling and extracellular vesicles
Authors: Cheng An Ning , Cheng Li-Chun , Kuo Cheng-Liang , Lo Yu Kang , Chou Han-Yu , Chen Chung-Hsing , Wang Yi-Hao , Chuang Tsung-Hsien , Cheng Shih-Jung , Lee Alan Yueh-Luen 
Published: December 2020

BackgroundMitochondrial Lon is a chaperone and DNA-binding protein that functions in protein quality control and stress response pathways. The level of Lon regulates mitochondrial DNA (mtDNA) metabolism and the production of mitochondrial reactive oxygen species (ROS). However, there is little information in detail on how mitochondrial Lon regulates ROS-dependent cancer immunoescape through mtDNA metabolism in the tumor microenvironment (TME).MethodsWe explored the understanding of the intricate interplay between mitochondria and the innate immune response in the inflammatory TME.ResultsWe found that oxidized mtDNA is released into the cytosol when Lon is overexpressed and then it induces interferon (IFN) signaling via cGAS-STING-TBK1, which upregulates PD-L1 and IDO-1 expression to inhibit T-cell activation. Unexpectedly, upregulation of Lon also induces the secretion of extracellular vehicles (EVs), which carry mtDNA and PD-L1. Lon-induced EVs further induce the production of IFN and IL-6 from macrophages, which attenuates T-cell immunity in the TME.ConclusionsThe levels of mtDNA and PD-L1 in EVs in patients with oral cancer function as a potential diagnostic biomarker for anti-PD-L1 immunotherapy. Our studies provide an insight into the immunosuppression on mitochondrial stress and suggest a therapeutic synergy between anti-inflammation therapy and immunotherapy in cancer.