bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining decision thresholds for judgments on health benefits and harms using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks: a protocol for a randomised methodological study (GRADE-THRESHOLD)
Authors: Morgano Gian Paolo , Mbuagbaw Lawrence , Santesso Nancy , Xie Feng , Brozek Jan L , Siebert Uwe , Bognanni Antonio , Wiercioch Wojtek , Piggott Thomas , Darzi Andrea J , Akl Elie A , Verstijnen Ilse M , Parmelli Elena , Saz-Parkinson Zuleika , Alonso-Coello Pablo , Schünemann Holger J 
Published: March 2022

IntroductionThe Grading of Recommendations Assessment, Development and Evaluation (GRADE) and similar Evidence to Decision (EtD) frameworks require its users to judge how substantial the effects of interventions are on desirable and undesirable people-important health outcomes. However, decision thresholds (DTs) that could help understand the magnitude of intervention effects and serve as reference for interpretation of findings are not yet available.The objective of this study is an approach to derive and use DTs for EtD judgments about the magnitude of health benefits and harms. We hypothesise that approximate DTs could have the ability to discriminate between the existing four categories of EtD judgments (Trivial, Small, Moderate, Large), support panels of decision-makers in their work, and promote consistency and transparency in judgments.Methods and analysisWe will conduct a methodological randomised controlled trial to collect the data that allow deriving the DTs. We will invite clinicians, epidemiologists, decision scientists, health research methodologists, experts in Health Technology Assessment (HTA), members of guideline development groups and the public to participate in the trial. Then, we will investigate the validity of our DTs by measuring the agreement between judgments that were made in the past by guideline panels and the judgments that our DTs approach would suggest if applied on the same guideline data.Ethics and disseminationThe Hamilton Integrated Research Ethics Board reviewed this study as a quality improvement study and determined that it requires no further consent. Survey participants will be required to read a consent statement in order to participate in this study at the beginning of the trial. This statement reads: You are being invited to participate in a research project which aims to identify indicative DTs that could assist users of the GRADE EtD frameworks in making judgments. Your input will be used in determining these indicative thresholds. By completing this survey, you provide consent that the anonymised data collected will be used for the research study and to be summarised in aggregate in publication and electronic tools.PROTOCOL registration numberNCT05237635.
Burden of whooping cough in China (PertussisChina): study protocol of a prospective, population-based case–control study
Authors: Yu Jianxing , He Hanqing , Zhang Yanyang , Gao Yuan , Chen Chuanwei , Xu Juan , Xu Li , Zhang Xiaoxiao , Zhou Qianqian , Zhu Yao , Tang Xuewen , Guo Yonghao , Chen Zhiping , Shao Zhujun 
Published: March 2022

IntroductionPertussis is one of the top 10 diseases of children under 10 years of age, and the few vaccine-preventable diseases who is on a rise in China in recent years; however, the true burden of pertussis, including age-stratified incidence and risk factors of severe sequelae, are under-recognised. We aim to estimate the health burden of laboratory-confirmed pertussis by age groups, considering the setting of illness onset (ie, in community, outpatient and inpatient), in a Chinese population (~2.23 million in total) at two sites.Methods and analysisThis paper describes the study design of a 1-year, prospective, age-stratified and population-based case–control study, including site selection, study population, case registry, ascertainment and enrolment, control recruitment, follow-up of case, microbiological methods, data collection, quality control activities and statistical methods used to generate incidence estimates. During June 2021 through May 2022, registry of suspected pertussis cases (namely chronic/persistent cough) will be conducted in several participating hospitals (SHs) at the two sites, which are selected based on Healthcare Utilisation and Attitudes Surveys (HUAS) carried out before study initiation. A case–control study will be conducted in the SHs and we aim to enrol a total of 1000 suspected pertussis cases (ie, all hospital admissions and the first 1–3 outpatient visits each week each hospital) and 2000 frequency matched healthy controls in community. Our primary study outcome, the laboratory-confirmed Bordetella pertussis infection, will be determined by a comprehensive laboratory methods and procedures (ie, culture, PCR and serological tests) in both cases and controls at enrolment and during 60-day’s follow-up visits. Finally, data from HUAS (ie, population size), case registry (ie, the total number of suspected pertussis cases) and case–control study (ie, the prevalence or population attributable fraction of Bordetella pertussis) will be combined to calculate incidence and its 95% CI through bootstrap method. Epidemiological analyses will be conducted to determine the risk factors associated with severe sequelae of pertussis.Ethics and disseminationThis study has been approved by Chinese Centre for Disease Control and Prevention’s Institutional Review Board (no. ICDC-202110). Results will be disseminated via academic presentations and publication in peer-reviewed journals, and will provide valuable scientific data and some new insights into the incidence, aetiology and risk factors for severe sequelae of pertussis to academic societies and the public health authorities who is currently struggling and fighting against this burdensome disease worldwide.
Safety and pharmacokinetics-pharmacodynamics of a shorter tuberculosis treatment with high-dose pyrazinamide and rifampicin: a study protocol of a phase II clinical trial (HighShort-RP)
Authors: Ekqvist David , Bornefall Anna , Augustinsson Daniel , Sönnerbrandt Martina , Nordvall Michaela Jonsson , Fredrikson Mats , Carlsson Björn , Sandstedt Mårten , Simonsson Ulrika S H , Alffenaar Jan-Willem C , Paues Jakob , Niward Katarina 
Published: March 2022

IntroductionIncreased dosing of rifampicin and pyrazinamide seems a viable strategy to shorten treatment and prevent relapse of drug-susceptible tuberculosis (TB), but safety and efficacy remains to be confirmed. This clinical trial aims to explore safety and pharmacokinetics-pharmacodynamics of a high-dose pyrazinamide-rifampicin regimen.Methods and analysisAdult patients with pulmonary TB admitted to six hospitals in Sweden and subjected to receive first-line treatment are included. Patients are randomised (1:3) to either 6-month standardised TB treatment or a 4-month regimen based on high-dose pyrazinamide (40 mg/kg) and rifampicin (35 mg/kg) along with standard doses of isoniazid and ethambutol. Plasma samples for measurement of drug exposure determined by liquid chromatography tandem-mass spectrometry are obtained at 0, 1, 2, 4, 6, 8, 12 and 24 hours, at day 1 and 14. Maximal drug concentration (Cmax) and area under the concentration-time curve (AUC0-24h) are estimated by non-compartmental analysis. Conditions for early model-informed precision dosing of high-dose pyrazinamide-rifampicin are pharmacometrically explored. Adverse drug effects are monitored throughout the study and graded according to Common Terminology Criteria for Adverse Events V.5.0. Early bactericidal activity is assessed by time to positivity in BACTEC MGIT 960 of induced sputum collected at day 0, 5, 8, 15 and week 8. Minimum inhibitory concentrations of first-line drugs are determined using broth microdilution. Disease severity is assessed with X-ray grading and a validated clinical scoring tool (TBscore II). Clinical outcome is registered according to WHO definitions (2020) in addition to occurrence of relapse after end of treatment. Primary endpoint is pyrazinamide AUC0-24h and main secondary endpoint is safety.Ethics and disseminationThe study is approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. Informed written consent is collected before study enrolment. The study results will be submitted to a peer-reviewed journal.Trial registration numberNCT04694586.
Peripheral intravenous cannulation decision-making in emergency settings: a qualitative descriptive study
Authors: Evison Hugo , Carrington Mercedes , Keijzers Gerben , Marsh Nicole M , Sweeny Amy Lynn , Byrnes Joshua , Rickard Claire M , Carr Peter J , Ranse Jamie 
Published: March 2022

ObjectivesRates of unused (‘idle’) peripheral intravenous catheters (PIVCs) are high but can vary per setting. Understanding factors that influence the decision-making of doctors, nurses and paramedics in the emergency setting regarding PIVC insertion, and what factors may modify their decision is essential to identify opportunities to reduce unnecessary cannulations and improve patient-centred outcomes. This study aimed to understand factors associated with clinicians’ decision-making on whether to insert or use a PIVC in the emergency care setting.DesignA qualitative descriptive study using in-depth semistructured interviews and thematic analysis.SettingGold Coast, Queensland, Australia, in a large tertiary level emergency department (ED) and local government ambulance service.ParticipantsParticipants recruited were ED clinicians (doctors, nurses) and paramedics who regularly insert PIVCs.ResultsFrom the 15 clinicians interviewed 4 key themes:knowledge and experience, complicated and multifactorial,convenience, anticipated patient clinical course,and several subthemes emerged relating to clinician decision-making across all disciplines. The first two themes focused on decision-making to gather data and evidence, such asknowledge and experience, and decisions beingcomplicated and multifactorial. The remaining two themes related to the actions clinicians took such asconvenienceandanticipated patient clinical course.ConclusionThe decision to insert a PIVC is more complicated than clinicians, administrators and policy-makers may realise. When explored, clinician decisions were multifaceted with many factors influencing the decision to insert a PIVC. In actual practice, clinicians routinely insert PIVCs in most patients as a learnt reflex with little cognitive input. When considering PIVC insertion, more time needs to be devoted to the awareness of: (1) decision-making in the context of the clinician’s own experience, (2) cognitive biases and (3) patient-centred factors. Such awareness will support an appropriate risk assessment which will benefit the patient, clinician and healthcare system.
Uptake of the multi-arm multi-stage (MAMS) adaptive platform approach: a trial-registry review of late-phase randomised clinical trials
Authors: Noor Nurulamin M , Love Sharon B , Isaacs Talia , Kaplan Richard , Parmar Mahesh K B , Sydes Matthew R 
Published: March 2022

BackgroundFor medical conditions with numerous interventions worthy of investigation, there are many advantages of a multi-arm multi-stage (MAMS) platform trial approach. However, there is currently limited knowledge on uptake of the MAMS design, especially in the late-phase setting. We sought to examine uptake and characteristics of late-phase MAMS platform trials, to enable better planning for teams considering future use of this approach.DesignWe examined uptake of registered, late-phase MAMS platforms in the EU clinical trials register, Australian New Zealand Clinical Trials Registry, International Standard Randomised Controlled Trial Number registry, Pan African Clinical Trials Registry, WHO International Clinical Trial Registry Platform and databases: PubMed, Medline, Cochrane Library, Global Health Library and EMBASE. Searching was performed and review data frozen on 1 April 2021. MAMS platforms were defined as requiring two or more comparison arms, with two or more trial stages, with an interim analysis allowing for stopping of recruitment to arms and typically the ability to add new intervention arms.Results62 late-phase clinical trials using an MAMS approach were included. Overall, the number of late-phase trials using the MAMS design has been increasing since 2001 and been accelerated by COVID-19. The majority of current MAMS platforms were either targeting infectious diseases (52%) or cancers (29%) and all identified trials were for treatment interventions. 89% (55/62) of MAMS platforms were evaluating medications, with 45% (28/62) of the MAMS platforms having at least one or more repurposed medication as a comparison arm.ConclusionsHistorically, late-phase trials have adhered to long-established standard (two-arm) designs. However, the number of late-phase MAMS platform trials is increasing, across a range of different disease areas. This study highlights the potential scope of MAMS platform trials and may assist research teams considering use of this approach in the late-phase randomised clinical trial setting.PROSPERO registration numberCRD42019153910.
Analysis of the relationship between sex and prescriptions for guideline-recommended therapy in peripheral arterial disease, in relation to 1-year all-cause mortality: a primary care cohort study
Authors: Benson Ruth A , Okoth Kelvin , Keerthy Deepiksana , Gokhale Krishna , Adderley Nicola J , Nirantharakumar Krishnarajah , Lasserson Daniel S 
Published: March 2022

ObjectivesTo explore population patterns of sex-based incidence and prevalence of peripheral arterial disease (PAD), guideline-directed best medical therapy prescriptions and its relationship with all-cause mortality at 1 year.DesignA retrospective cohort study.SettingAnonymised electronic primary care from 787 practices in the UK, or approximately 6.2% of the UK population.ParticipantsAll registered patients over 40 with a documented diagnosis of peripheral arterial disease.Outcome measurePopulation incidence and prevalence of PAD by sex. Patterns of guideline-directed therapy, and correlation with all-cause mortality at 1 year (defined as death due to any outcome) in patients with and without an existing diagnosis of cardiovascular disease. Covariates included Charlson comorbidity, sex, age, body mass index, Townsend score of deprivation, smoking status, diabetes, hypertension, statin and antiplatelet prescription.ResultsSequential cross-sectional studies from 2010 to 2017 found annual PAD prevalence (12.7–14.3 vs 25.6 per 1000 in men) and incidence were lower in women (11.6–12.4 vs 22.7–26.8 per 10 000 person years in men). Cox proportional hazards models created for PAD patients with and without cardiovascular disease over one full year analysed 25 121 men and 13 480 women, finding that following adjustment for age, women were still less likely to be on a statin (OR 0.69; 95% CI 0.66 to 0.72; p<0.001) or antiplatelet (OR: 0.87; 95% CI 0.83 to 0.90; p<0.001). Once fully adjusted for guideline recommended medical therapy, all-cause mortality was similar between women and men (adjusted HR (aHR) 0.95, 95% CI 0.87 to 1.03, p=0.198 for all patients, aHR 1.01, 95% CI 0.88 to 1.16, p=0.860 for those with cardiovascular disease).ConclusionsWomen with a new diagnosis of PAD were not prescribed guideline-directed therapy at the same rate as men. However once adjusted for factors including age, all-cause mortality in men and women was similar.
Short-term effectiveness of nutrition therapy to treat type 2 diabetes in low-income and middle-income countries: systematic review and meta-analysis of randomised controlled trials
Authors: Guilbert Elizabeth , Perry Rachel , Whitmarsh Alex , Sauchelli Sarah 
Published: March 2022

ObjectivesThis review examined the evidence arising from randomised controlled trials regarding the impact of nutrition therapy on glycaemic control in people living with type 2 diabetes mellitus (T2DM) in low/middle-income countries (LMICs).DesignSystematic review and meta-analysis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Approach.Data sourcesMEDLINE, EMBASE, Web of Science, OpenGrey and the International Clinical Trials Registry were searched (up to July 3 2020).Eligibility criteriaTrials were included if they evaluated nutrition therapy in adults diagnosed with T2DM, were conducted in LMICs, measured glycaemic control and the trial included a 3-month post-intervention assessment. Nutrition therapy was defined according to American Diabetes Association recommendations.Data extraction and synthesisTwo independent reviewers screened the database. Study characteristics and outcome data were extracted using a data collection form. Meta-analyses were conducted for glycated haemoglobin (HbA1c) and fasting blood glucose. Trials were assessed for risk of bias (Cochrane Risk-of-Bias, Version 2.0) and overall certainty of evidence (GRADE).ResultsFour trials met inclusion criteria (total n=463), conducted in Malaysia, Iran and South Africa. All trials focused on nutrition education with no direct prescription or manipulation of diet. Mean differences between intervention and standard care were −0.63% (95% CI −1.47% to 0.21%) for HbA1c and −13.63 mg/dL (95% CI −37.61 to 10.34) for fasting blood glucose in favour of the intervention. Given the small number of eligible trials, moderate to high risk of publication bias and serious concerns regarding consistency and precision of the evidence, certainty of evidence was deemed to be very low.ConclusionsThere is a lack of well-conducted randomised controlled trials that examine the long-term impact of nutrition therapy in LMICs, preventing firm conclusions to be made on their effectiveness. Further research is essential to discover realistic, evidence-based solutions.PROSPERO registration numberCRD42020188435.
Relationships between overwork, burnout and suicidal ideation among resident physicians in hospitals in Japan with medical residency programmes: a nationwide questionnaire-based survey
Authors: Ishikawa Masatoshi 
Published: March 2022

ObjectivesThis study examined the relationships between overwork, burnout and suicidal ideation among resident physicians working in hospitals throughout Japan.DesignA nationwide, questionnaire-based survey.SettingParticipating hospitals (n=416) were accredited by the Japanese Medical Specialty Board to offer medical residency programmes in 19 core specialties. Surveys were conducted in October 2020.ParticipantsValid responses were obtained from 4306 physicians (response rate: 49%).Outcome measuresItems pertaining to the Japanese Burnout Scale, depressive tendencies and suicidal ideation were included in questionnaires. Multiple regression analyses were performed: suicidal ideation was the response variable; sex, age, core specialty, marital status, income, weekly working hours and workplace (ownership, number of beds, number of full-time physicians and regional classification) were explanatory variables.ResultsRegarding the Japanese Burnout Scale, the highest score was recorded for ‘sense of personal accomplishment’, followed by ‘emotional exhaustion’ and ‘depersonalization’. Increased emotional exhaustion and depersonalisation were associated with longer working hours, but there was no such trend for sense of personal accomplishment. Depressive tendencies and suicidal ideation were noted in 24.1% and 5.6% of respondents, respectively. These percentages tended to increase when respondents worked longer hours. Several factors were significantly associated with suicidal ideation: female sex (reference: male, OR: 2.08, 95% CI: 1.56 to 2.77), ≥12 million yen income (reference: <2 million yen, OR: 0.21, 95% CI: 0.05 to 0.79), ≥100 working hours/week (reference:<40 hours/week, OR: 3.64, 95% CI: 1.88 to 7.04) and 600–799 hospital beds (reference: <200 beds, OR: 0.23, 95% CI: 0.07 to 0.82).ConclusionsMany Japanese residents demonstrated a tendency to experience burnout and suicidal ideation. Female sex, low income, long working hours and insufficient hospital beds were associated with suicidal ideation. To ensure physicians’ health and patients’ safety, it is necessary to advance workstyle reform for physicians.
Aetiology of lobar pneumonia determined by multiplex molecular analyses of lung and pleural aspirate specimens in the Gambia: findings from population-based pneumonia surveillance
Authors: Mackenzie Grant Austin , McLellan Jessica , Machuka Eunice , Ndiaye Malick , Pathirana Jayani , Fombah Augustin , Abatan Baderinwa , Hossain Ilias , Manjang Ahmed , Greenwood Brian , Hill Philip 
Published: March 2022

ObjectivesTo determine the causes of lobar pneumonia in rural Gambia.Design and settingPopulation-based pneumonia surveillance at seven peripheral health facilities and two regional hospitals in rural Gambia. 7-valent pneumococcal conjugate vaccine (PCV7) was introduced routinely in August 2009 and replaced by PCV13 from May 2011.MethodsProspective pneumonia surveillance was undertaken among all ages with referral of suspected pneumonia cases to the regional hospitals. Blood culture and chest radiographs were performed routinely while lung or pleural aspirates were collected from selected, clinically stable patients with pleural effusion on radiograph and/or large, dense, peripheral consolidation. We used conventional microbiology, and from 8 April 2011 to 17 July 2012, used a multiplex PCR assay on lung and pleural aspirates. We calculated proportions with pathogens, associations between coinfecting pathogens and PCV effectiveness.Participants2550 patients were admitted with clinical pneumonia; 741 with lobar pneumonia or pleural effusion. We performed 181 lung or pleural aspirates and multiplex PCR on 156 lung and 4 pleural aspirates.ResultsPathogens were detected in 116/160 specimens, the most common being Streptococcus pneumoniae(n=68), Staphylococcus aureus (n=26) and Haemophilus influenzae type b (n=11). Bacteria (n=97) were more common than viruses (n=49). Common viruses were bocavirus (n=11) and influenza (n=11). Coinfections were frequent (n=55). Moraxella catarrhalis was detected in eight patients and in every case there was coinfection with S. pneumoniae. The odds ratio of vaccine-type pneumococcal pneumonia in patients with two or three compared with zero doses of PCV was 0.17 (95% CI 0.06 to 0.51).ConclusionsLobar pneumonia in rural Gambia was caused primarily by bacteria, particularly S. pneumoniae and S. aureus. Coinfection was common and M. catarrhalis always coinfected with S. pneumoniae. PCV was highly efficacious against vaccine-type pneumococcal pneumonia.