bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of adverse events after covid-19 in Danish children and adolescents and effectiveness of BNT162b2 in adolescents: cohort study
Authors: Kildegaard Helene , Lund Lars Christian , Højlund Mikkel , Stensballe Lone Graff , Pottegård Anton 
Published: April 2022

AbstractObjectivesTo assess the risk of acute and post-acute adverse events after SARS-CoV-2 infection in children and adolescents in Denmark and to evaluate the real world effectiveness of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) among adolescents.DesignCohort study.SettingNationwide Danish healthcare registers.ParticipantsAll Danish people younger than 18 years who were either tested for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) or vaccinated with BNT162b2 to 1 October 2021.Main outcome measuresRisk of hospital admissions (any hospital contact of ≥12 hours); intensive care unit (ICU) admissions; serious complications, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and neuroimmune disorders; and initiating drug treatment and health service use up to six months after being tested. Vaccine effectiveness in vaccine recipients compared with unvaccinated peers was evaluated as one minus the risk ratio at 20 days after the first dose and 60 days after the second dose.ResultsOf 991 682 children and adolescents tested for SARS-CoV-2 using RT-PCR in Denmark, 74 611 (7.5%) were positive. The risk of hospital admission with any variant for ≥12 hours was 0.49% (95% confidence interval 0.44% to 0.54%; 361/74 350), and 0.01% (0.01% to 0.03%; 10/73 187) of participants were admitted to an ICU within 30 days of testing positive. The risk of MIS-C within two months of SARS-CoV-2 infection was 0.05% (0.03% to 0.06%; 32/70 666), whereas no participants had myocarditis outside of MIS-C or encephalitis and fewer than five had Guillain-Barré syndrome. In the post-acute phase (1-6 months after infection), participants who tested positive for SARS-CoV-2 showed a 1.08-fold (95% confidence interval 1.06-fold to 1.10-fold) increase in rate of contacts with general practitioners compared with a reference cohort sampled among all children tested for SARS-CoV-2 during the study period. Overall, 278 649 adolescents received BNT162b2. Compared with unvaccinated adolescents, the estimated vaccine effectiveness among 229 799 adolescents vaccinated with one dose was 62% (95% confidence interval 59% to 65%) after 20 days, and among 175 176 vaccinated with two doses was 93% (92% to 94%) after 60 days during a period when delta was the dominant variant.ConclusionsThe absolute risks of adverse events after SARS-CoV-2 infection were generally low in Danish children and adolescents, although MIS-C occurred in 0.05% (32/70 666) of participants with RT-PCR confirmed SARS-CoV-2 infection. In adjusted analyses, rates of general practitioner visits were slightly increased in SARS-CoV-2 positive children and adolescents, which could indicate persisting symptoms. BNT162b2 appeared to be effective in reducing the risk of SARS-CoV-2 infection with the delta variant in adolescents.
Cohort profile: the South African HIV Cancer Match (SAM) Study, a national population-based cohort
Authors: Muchengeti Mazvita , Bartels Lina , Olago Victor , Dhokotera Tafadzwa , Chen Wenlong Carl , Spoerri Adrian , Rohner Eliane , Bütikofer Lukas , Ruffieux Yann , Singh Elvira , Egger Matthias , Bohlius Julia 
Published: April 2022

PurposeThe South African HIV Cancer Match (SAM) Study is a national cohort of people living with HIV (PLWH). It was created using probabilistic record linkages of routine laboratory records of PLWH retrieved by National Health Laboratory Services (NHLS) and cancer data from the National Cancer Registry. The SAM Study aims to assess the spectrum and risk of cancer in PLWH in the context of the evolving South African HIV epidemic. The SAM Study’s overarching goal is to inform cancer prevention and control programmes in PLWH in the era of antiretroviral treatment in South Africa.ParticipantsPLWH (both adults and children) who accessed HIV care in public sector facilities and had HIV diagnostic or monitoring laboratory tests from NHLS.Findings to dateThe SAM cohort currently includes 5 248 648 PLWH for the period 2004 to 2014; 69% of these are women. The median age at cohort entry was 33.0 years (IQR: 26.2–40.9). The overall cancer incidence in males and females was 235.9 (95% CI: 231.5 to 240.5) and 183.7 (181.2–186.2) per 100 000 person-years, respectively.Using data from the SAM Study, we examined national cancer incidence in PLWH and the association of different cancers with immunodeficiency. Cancers with the highest incidence rates were Kaposi sarcoma, cervix, breast, non-Hodgkin's lymphoma and eye cancer.Future plansThe SAM Study is a unique, evolving resource for research and surveillance of malignancies in PLWH. The SAM Study will be regularly updated. We plan to enrich the SAM Study through record linkages with other laboratory data within the NHLS (eg, tuberculosis, diabetes and lipid profile data), mortality data and socioeconomic data to facilitate comprehensive epidemiological research of comorbidities among PLWH.
Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study
Authors:   Global Health Research Group on Children’s Non-Communicable Diseases Collaborative
Published: April 2022

ObjectivesPaediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.DesignA multicentre, international, collaborative cohort study.Setting91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.ParticipantsPatients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measureAll-cause mortality at 30 days and 90 days.Results1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001).ConclusionsThe COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.
Neuromodulation through brain stimulation-assisted cognitive training in patients with post-COVID-19 cognitive impairment (Neuromod-COV): study protocol for a PROBE phase IIb trial
Authors: Thams Friederike , Antonenko Daria , Fleischmann Robert , Meinzer Marcus , Grittner Ulrike , Schmidt Sein , Brakemeier Eva-Lotta , Steinmetz Anke , Flöel Agnes 
Published: April 2022

IntroductionA substantial number of patients diagnosed with COVID-19 experience long-term persistent symptoms. First evidence suggests that long-term symptoms develop largely independently of disease severity and include, among others, cognitive impairment. For these symptoms, there are currently no validated therapeutic approaches available. Cognitive training interventions are a promising approach to counteract cognitive impairment. Combining training with concurrent transcranial direct current stimulation (tDCS) may further increase and sustain behavioural training effects. Here, we aim to examine the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with post-COVID-19 subjective or objective cognitive impairments.Methods and analysisThis study protocol describes a prospective randomised open endpoint-blinded trial. Patients with post-COVID-19 cognitive impairment will either participate in a 3-week cognitive training or in a defined muscle relaxation training (open-label interventions). Irrespective of their primary intervention, half of the cognitive training group will additionally receive anodal tDCS, all other patients will receive sham tDCS (double-blinded, secondary intervention). The primary outcome will be improvement of working memory performance, operationalised by an n-back task, at the postintervention assessment. Secondary outcomes will include performance on trained and untrained tasks and measures of health-related quality of life at postassessment and follow-up assessments (1 month after the end of the trainings).Ethics and disseminationEthical approval was granted by the Ethics Committee of the University Medicine Greifswald (number: BB 066/21). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.Trial registration numberNCT04944147.
Applying the health capability profile to empirically study chronic hepatitis B in rural Senegal: a social justice mixed-methods study protocol
Authors: Coste Marion , Badji Mouhamed Ahmed , Diallo Aldiouma , Mora Marion , Boyer Sylvie , Prah Jennifer J 
Published: April 2022

IntroductionDespite the early implementation of hepatitis B vaccination and the ongoing decentralisation of chronic hepatitis B (CHB) care, over 10% of the Senegalese adult population lives with CHB and liver cancer remains a main cause of death. Investigating factors associated with CHB infection, prevention of CHB-related morbidity, and prevention and treatment of mortality secondary to CHB calls for a holistic and multidimensional approach. This paper presents the adaptation of the health capability profile (HCP) to a specific epidemiological issue and empirical setting: it seeks to identify and analyse inter-related abilities and conditions (health capabilities) in relation to the CHB epidemic in the rural area of Niakhar, Senegal.Methods and analysisThis ongoing study relies on a sequential social justice mixed-methods design. The HCP is comprehensively adapted to CHB in rural Senegal and guides the design and conduct of the study. Objective and subjective data are collected at the individual level following a mixed-methods explanatory core design. The quantitative module, embedded in the ANRS12356 AmBASS cross-sectional survey (exhaustive sampling), is used to select a purposeful sampling of participants invited for one-on-one qualitative interviews. Additional data are collected at the institutional and community level through health facility surveys and an ethnography (in-depth interviews) of local and national CHB stakeholders. Data analysis adopts a synergistic approach to produce a multilayered analysis of individual HCPs and crosscutting analysis of the 15 health capabilities. The data integration strategy relies on a mixed-methods convergent core design, and will use 0–100 health capability scores as well as flow diagrams to measure and characterise levels of development and interactions among health capabilities, respectively.Ethics and disseminationThis study was approved by Senegalese and French authorities. Results dissemination through local workshops and scientific publications aim at fuelling effective policy change towards CHB-related health capability.
ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder–Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial
Authors: Zimmermann Sina , Thomas Bettina C , Krisam Johannes , Limprecht Ronald , Klose Christina , Stenger Manuel , Pourbaix Madeleine , Ries Marcel , Vollstaedt-Klein Sabine , Koopmann Anne , Lenz Bernd , Kiefer Falk , Bach Patrick 
Published: April 2022

IntroductionAlthough alcohol dependence (AD) is highly prevalent, only few medications are approved for its treatment. While currently approved medications, such as naltrexone (NTX), reduce craving and relapse risk to a certain extent, new approaches are needed to complement these pharmaca. One potential compound is oxytocin (OXY), which proved beneficial effects on alcohol craving and stress reactivity in preliminary clinical studies and synergism with NTX effects.Methods and analysisThis clinical phase II trial is a monocentre two-armed, placebo (PLC)-controlled, 1:1 randomised, double-blind, parallel-group study. 62 participants with AD will be randomised to receive either intranasal OXY spray (24 IU) or PLC spray plus oral NTX (50 mg) for 2 days, and alcohol craving will be assessed using a validated combined stress-exposure and cue-exposure experiments and MRI. The primary outcome will be the intensity of alcohol craving, assessed using the Alcohol Urge Questionnaire (AUQ), 60 min after OXY/PLC application, directly after the stress and cue exposures. Secondary outcomes include subjective stress, negative affect, cortisol and OXY plasma levels, and neural response to alcohol and emotional cues and natural rewards. Follow-up drinking data were collected over 90 days. The primary efficacy analysis will test the difference between the verum and the PLC group in the distribution of AUQ craving scores. Appropriate statistical analysis will be used for the evaluation of the secondary outcomes.Ethics and disseminationThis trial has been approved by the ethics committee of Heidelberg University and competent authority. All participants in the trial will provide written informed consent. The study will be conducted according to the principles of the Declaration of Helsinki and in accordance to the German Medicinal Products act. Results of this study will be disseminated in peer-reviewed scientific journals and deidentified data, and the statistical analysis plan will be made available via open-access online repositories.Trial registration numbersEudraCT 2021-003610-40 and NCT05093296.
Predicting outcome after cardiac resynchronisation therapy defibrillator implantation: the cardiac resynchronisation therapy defibrillator Futility score
Authors: Maille Baptiste , Bodin Alexandre , Bisson Arnaud , Herbert Julien , Pierre Bertrand , Clementy Nicolas , Klein Victor , Franceschi Frédéric , Deharo Jean-Claude , Fauchier Laurent 
Published: April 2022

BackgroundRisk-benefit for cardiac resynchronisation therapy (CRT) defibrillator (CRT-D) over CRT pacemaker remains a matter of debate. We aimed to identify patients with a poor outcome within 1 year of CRT-D implantation, and to develop a CRT-D Futility score.MethodsBased on an administrative hospital-discharge database, all consecutive patients treated with prophylactic CRT-D implantation in France (2010–2019) were included. A prediction model was derived and validated for 1-year all-cause death after CRT-D implantation (considered as futility) by using split-sample validation.ResultsAmong 23 029 patients (mean age 68±10 years; 4873 (21.2%) women), 7016 deaths were recorded (yearly incidence rate 7.2%), of which 1604 (22.8%) occurred within 1 year of CRT-D implantation. In the derivation cohort (n=11 514), the final logistic regression model included—as main predictors of futility—older age, diabetes, mitral regurgitation, aortic stenosis, history of hospitalisation with heart failure, history of pulmonary oedema, atrial fibrillation, renal disease, liver disease, undernutrition and anaemia. Area under the curve for the CRT-D Futility score was 0.716 (95% CI: 0.698 to 0.734) in the derivation cohort and 0.692 (0.673 to 0.710) in the validation cohort. The Hosmer-Lemeshow test had a p-value of 0.57 suggesting accurate calibration. The CRT-D Futility score outperformed the Goldenberg and EAARN scores for identifying futility. Based on the CRT-D Futility score, 15.9% of these patients were categorised at high risk (predicted futility of 16.6%).ConclusionsThe CRT-D Futility score, established from a large nationwide cohort of patients treated with CRT-D, may be a relevant tool for optimising healthcare decision-making.
Body iron stores had no impact on coronary heart disease outcomes: a middle-aged male cohort from the general population with 21-year follow-up
Authors: Barywani Salim Bary , Östgärd Thunström Erik , Mandalenakis Zacharias , Hansson Per-Olof 
Published: April 2022

BackgroundBody iron stores (BISs) have been proposed to be related to the development of cardiovascular diseases. However, results from epidemiological studies are conflicting. Knowledge on the long-term impact of BIS on cardiovascular outcomes in the general population is lacking.PurposeThe aim of this study was to explore the relationship between BIS and coronary heart disease (CHD) including death due to CHD.MethodsThis investigation is part of ‘The Study of Men Born in 1943’, a longitudinal prospective study of men living in the city of Gothenburg, Sweden. This random population sample was examined in 1993 (all at 50 years of age at baseline). A medical examination was performed, and questionnaires were used to evaluate lifestyle factors. Biomarkers for iron stores (serum ferritin and serum transferrin receptor) was analysed from frozen blood samples in 2014. All hospital admissions were registered through national registers during the entire follow-up from 1993 to 2014. HRs were estimated by Cox proportional-hazard regression analyses.ResultsDuring the 21 years follow-up period, 120 participants (15.2%) developed CHD and 16 patients (2%) died due to CHD. The all-cause mortality was 15.2% (n=120) including 40 cardiovascular deaths (5.1%). In a multivariable Cox regression analysis, the daily smoking, hypertension and the increased resting heart rate was independent predictors of CHD, while no significant association was found between BIS and risk of CHD.ConclusionsIn a cohort of middle-aged men from the general population with well validated and prospectively collected data, we did not find any association between serum ferritin or serum transferrin receptor as markers of BIS and CHD events after 21 years of follow-up.Trail registration numberNCT03138122.
Prognostic value of microvascular resistance and its association to fractional flow reserve: a DEFINE-FLOW substudy
Authors: Eftekhari Ashkan , Westra Jelmer , Stegehuis Valérie , Holm Niels Ramsing , van de Hoef Tim P , Kirkeeide Richard L , Piek Jan J , Lance Gould K , Johnson Nils P , Christiansen Evald Høj 
Published: April 2022

ObjectiveThis study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary artery disease.MethodsThis is a substudy of the DEFINE-FLOW cohort (NCT02328820), which evaluated the prognosis of lesions (n=456) after combined FFR and coronary flow reserve (CFR) assessment in a prospective, non-blinded, non-randomised, multicentre study in 12 centres in Europe and Japan. Participants (n=430) were evaluated by wire-based measurement of coronary pressure, flow and vascular resistance (ComboWire XT, Phillips Volcano, San Diego, California, USA).ResultsMean FFR and CFR were 0.82±0.10 and 2.2±0.6, respectively. When divided according to FFR and CFR thresholds (above and below 0.80 and 2.0, respectively), HMR was highest in lesions with FFR>0.80 and CFR<2.0 (n=99) compared with lesions with FFR≤0.80 and CFR≥2.0 (n=68) (2.92±1.2 vs 1.91±0.64 mm Hg/cm/s, p<0.001). The FFR value was proportional to the ratio between HMR and the HMR+HSR (total resistance), 95% limits of agreement (−0.032; 0.019), bias (−0.003±0.02) and correlation (r2=0.98, p<0.0001). Cox regression model using HMR as continuous parameter for target vessel failure showed an HR of 1.51, 95% CI (0.9 to 2.4), p=0.10.ConclusionsIncreased HMR was not associated with a higher rate of adverse clinical events, in this population of mainly stable patients. FFR can be equally well expressed as HMR/HMR+HSR, thereby providing an alternative conceptual formulation linking epicardial severity with microvascular resistance.Trial registration numberNCT02328820.
Delivering surgical education: a specialist surgical society and undergraduate student collaboration
Authors: Singh Shashwat , Thiagarajah Viswan , Banerjee Rishi , Iyenger Kartik , Garg Sunil , Singh Bijayendra , Ahluwalia Raju ,   BIOS Collaborative, Shah Nilesh , Koka Ravi , Sinha Amit , Khanduja Vikas , Kotwal Rahul , Anand Sanjeev , Gill Inder , Tolat Amat , Desai Aravind 
Published: April 2022

Abstract
Currently, the delivery of the undergraduate medical curriculum includes various teaching, learning and assessment strategies. Self-directed learning is an important aspect of this mix and includes the use of resources, sometimes not provided by the parent University, in the student’s own time to enhance the student’s knowledge, skills and professional practice. Societies aimed at a particular specialty contain a pool of professionals that can provide undergraduate students with opportunities for further self-directed learning, development of specialty-specific core skills and exploration of research interests. This may then enhance and enlighten the students’ approach to a particular orthopaedic problem and reinforce the curriculum they are studying while providing an understanding of current areas of debate that are not part of the curriculum at present. The collaboration of postgraduate societies with undergraduate students in developing and implementing undergraduate engagement strategies is of benefit to undergraduate education, the specialty society and the collaborating students. We explore the planning and implementation of an interactive webinar series run by the British Indian Orthopaedic Society in collaboration with undergraduate students. We provide a case study of a surgical specialty society engaging with undergraduate students with synergistic effect. We pay particular attention to the benefits accrued by the specialty society and the student collaborators by this joint effort.