bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated prevalence and treatment of sleep disorders from 2011 to 2020: a nationwide population-based retrospective cohort study in Korea
Authors: Ahn Eunkyoung , Baek Younghwa , Park Ji-Eun , Lee Siwoo , Jin Hee-Jeong 
Published: February 2024

ObjectivesThis study used National Health Insurance claims data from Korea to report the prevalence of sleep disorders and treatment status, including traditional Korean medicine, in the last 10 years.MethodsThis is a retrospective cohort study in Korea. All diagnosis and prescription data, including herbal medicine claims, from the Health Insurance Review and Assessment Service from 2011 to 2020 were reviewed. Prevalence estimation, direct medical expenses and prescribed amounts for sleep disorders were recorded.ResultsThe prevalence of sleep disorders increased from 3 867 975 (7.62%) in 2011 to 7 446 846 (14.41%) in 2020, nearly doubling over 10 years. Insomnia was observed in 91.44% (n=9 011 692) of the patients. The mean number of hospital visits per patient for sleep disorders was 11.5 (±26.62). Benzodiazepines are the most commonly prescribed medications for sleep disorders, and gamma-isoyosan is the most frequently prescribed herbal medicine.ConclusionsSleep disorders are continuously increasing, as is the use of medical services—personal and social medical expenses are also increasing accordingly. Sleep disorders should be recognised as a significant health problem that needs to be actively addressed to improve quality of life.
Perioperative treatment with tranexamic acid in melanoma (PRIME): protocol for a Danish multicentre randomised controlled trial investigating the prognostic and treatment-related impact of the plasminogen–plasmin pathway
Authors: Kristjansen Karoline Assifuah , Engel Krag Andreas , Schmidt Henrik , Hölmich Lisbet Rosenkrantz , Bønnelykke-Behrndtz Marie Louise 
Published: February 2024

IntroductionInflammation is a hallmark of cancer and is involved in tumour growth and dissemination. However, the hallmarks of cancer are also the hallmarks of wound healing, and modulating the wound inflammatory response and immune contexture in relation to cancer surgery may represent effective targets of therapies.Repurposing anti-inflammatory drugs in a cancer setting has gained increasing interest in recent years. Interestingly, the known and thoroughly tested antifibrinolytic drug tranexamic acid reduces the risk of bleeding, but it is also suggested to play important roles in anti-inflammatory pathways, improving wound healing and affecting anti-carcinogenic mechanisms.As a novel approach, we will conduct a randomised controlled trial using perioperative treatment with tranexamic acid, aiming to prevent early relapses by >10% for patients with melanoma.Methods and analysisDesign: investigator-initiated parallel, two-arm, randomised, blinded, Danish multicentre superiority trial.Patients: ≥T2 b melanoma and eligible for sentinel lymph node biopsy (n=1204).Project drug: tranexamic acid or placebo.Treatment: before surgery (intravenous 15 mg/kg) and daily (peroral 1000 mg x 3) through postoperative day 4.Primary outcome: relapse within 2 years after surgery.Primary analysis: risk difference between the treatment arms (χ2test).Secondary outcomes: postoperative complications, adverse events and survival.Inclusion period: summer 2023 to summer 2026.Ethics and disseminationThe trial will be initiated during the summer of 2023 and is approved by the National Committee on Health Research Ethics, the Danish Medicine Agency, and registered under the Data Protection Act. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Patients included in the study will adhere to normal Danish treatment protocols and standards of care, and we expect only mild and temporary side effects. Positive and negative results will be published in peer-reviewed journals, with authorships adhering to the Vancouver rules.Trial registration numberNCT05899465; ClinicalTrials.gov Identifier.
Early ICD implantation following out-of-hospital cardiac arrest: a retrospective cohort study from the Swedish Registry for Cardiopulmonary Resuscitation
Authors: Sultanian Pedram , Lundgren Peter , Rawshani Aidin , Möller Sebastian , Jafari Arash Hadi , David Laura , Yassinson Shavan , Myredal Anna , Rorsman Cecilia , Taha Amar , Ravn-Fischer Annica , Martinsson Andreas , Herlitz Johan , Rawshani Araz 
Published: February 2024

BackgroundIt is unclear whether an implantable cardioverter-defibrillator (ICD) is generally beneficial in survivors of out-of-hospital cardiac arrest (OHCA).ObjectiveWe studied the association between ICD implantation prior to discharge and survival in patients with cardiac aetiology or initial shockable rhythm in OHCA.DesignWe conducted a retrospective cohort study in the Swedish Registry for Cardiopulmonary Resuscitation. Treatment associations were estimated using propensity scores. We used gradient boosting, Bayesian additive regression trees, neural networks, extreme gradient boosting and logistic regression to generate multiple propensity scores. We selected the model yielding maximum covariate balance to obtain weights, which were used in a Cox regression to calculate HRs for death or recurrent cardiac arrest.ParticipantsAll cases discharged alive during 2010 to 2020 with a cardiac aetiology or initial shockable rhythm were included. A total of 959 individuals were discharged with an ICD, and 2046 were discharged without one.ResultsAmong those experiencing events, 25% did so within 90 days in the ICD group, compared with 52% in the other group. All HRs favoured ICD implantation. The overall HR (95% CI) for ICD versus no ICD was 0.38 (0.26 to 0.56). The HR was 0.42 (0.28 to 0.63) in cases with initial shockable rhythm; 0.18 (0.06 to 0.58) in non-shockable rhythm; 0.32 (0.20 to 0.53) in cases with a history of coronary artery disease; 0.36 (0.22 to 0.61) in heart failure and 0.30 (0.13 to 0.69) in those with diabetes. Similar associations were noted in all subgroups.ConclusionAmong survivors of OHCA, those discharged with an ICD had approximately 60% lower risk of death or recurrent cardiac arrest. A randomised trial is warranted to study this further.
Effectiveness of an adaptive, multifaceted intervention to enhance care for patients with complex multimorbidity in general practice: protocol for a pragmatic cluster randomised controlled trial (the MM600 trial)
Authors: Holm Anne , Lyhnebeck Anna Bernhardt , Rozing Maarten , Buhl Sussi Friis , Willadsen Tora Grauers , Prior Anders , Christiansen Ann-Kathrin Lindahl , Kristensen Jette , Andersen John Sahl , Waldorff Frans Boch , Siersma Volkert , Brodersen John Brandt , Reventlow Susanne 
Published: February 2024

IntroductionPatients with complex multimorbidity face a high treatment burden and frequently have low quality of life. General practice is the key organisational setting in terms of offering people with complex multimorbidity integrated, longitudinal, patient-centred care. This protocol describes a pragmatic cluster randomised controlled trial to evaluate the effectiveness of an adaptive, multifaceted intervention in general practice for patients with complex multimorbidity.Methods and analysisIn this study, 250 recruited general practices will be randomly assigned 1:1 to either the intervention or control group. The eligible population are adult patients with two or more chronic conditions, at least one contact with secondary care within the last year, taking at least five repeat prescription drugs, living independently, who experience significant problems with their life and health due to their multimorbidity. During 2023 and 2024, intervention practices are financially incentivised to provide an extended consultation based on a patient-centred framework to eligible patients. Control practices continue care as usual. The primary outcome is need-based quality of life. Outcomes will be evaluated using linear and logistic regression models, with clustering considered. The analysis will be performed as intention to treat. In addition, a process evaluation will be carried out and reported elsewhere.Ethics and disseminationThe trial will be conducted in compliance with the protocol, the Helsinki Declaration in its most recent form and good clinical practice recommendations, as well as the regulation for informed consent. The study was submitted to the Danish Capital Region Ethical Committee (ref: H-22041229). As defined by Section 2 of the Danish Act on Research Ethics in Research Projects, this project does not constitute a health research project but is considered a quality improvement project that does not require formal ethical approval. All results from the study (whether positive, negative or inconclusive) will be published in peer-reviewed journals.Trial registration numberNCT05676541.
Implementing adaptive e-learning for newborn care in Tanzania: an observational study of provider engagement and knowledge gains
Authors: Meaney Peter Andrew , Hokororo Adolfine , Ndosi Hanston , Dahlen Alex , Jacob Theopista , Mwanga Joseph R , Kalabamu Florence Salvatory , Joyce Christine Lynn , Mediratta Rishi , Rozenfeld Boris , Berg Marc , Smith Zachary Haines , Chami Neema , Mkopi Namala , Mwanga Castory , Diocles Enock , Agweyu Ambrose 
Published: February 2024

IntroductionTo improve healthcare provider knowledge of Tanzanian newborn care guidelines, we developed adaptive Essential and Sick Newborn Care (aESNC), an adaptive e-learning environment. The objectives of this study were to (1) assess implementation success with use of in-person support and nudging strategy and (2) describe baseline provider knowledge and metacognition.Methods6-month observational study at one zonal hospital and three health centres in Mwanza, Tanzania. To assess implementation success, we used the Reach, Efficacy, Adoption, Implementation and Maintenance framework and to describe baseline provider knowledge and metacognition we used Howell’s conscious-competence model. Additionally, we explored provider characteristics associated with initial learning completion or persistent activity.ResultsaESNC reached 85% (195/231) of providers: 75 medical, 53 nursing and 21 clinical officers; 110 (56%) were at the zonal hospital and 85 (44%) at health centres. Median clinical experience was 4 years (IQR 1–9) and 45 (23%) had previous in-service training for both newborn essential and sick newborn care. Efficacy was 42% (SD ±17%). Providers averaged 78% (SD ±31%) completion of initial learning and 7% (SD ±11%) of refresher assignments. 130 (67%) providers had ≥1 episode of inactivity >30 day, no episodes were due to lack of internet access. Baseline conscious-competence was 53% (IQR: 38%–63%), unconscious-incompetence 32% (IQR: 23%–42%), conscious-incompetence 7% (IQR: 2%–15%), and unconscious-competence 2% (IQR: 0%–3%). Higher baseline conscious-competence (OR 31.6 (95% CI 5.8 to 183.5)) and being a nursing officer (aOR: 5.6 (95% CI 1.8 to 18.1)), compared with medical officer, were associated with initial learning completion or persistent activity.ConclusionaESNC reach was high in a population of frontline providers across diverse levels of care in Tanzania. Use of in-person support and nudging increased reach, initial learning and refresher assignment completion, but refresher assignment completion remains low. Providers were often unaware of knowledge gaps, and lower baseline knowledge may decrease initial learning completion or activity. Further study to identify barriers to adaptive e-learning normalisation is needed.
Understanding and addressing femicide in Africa: a systematic review of empirical research
Authors: Variava Tarique , Dekel Bianca 
Published: February 2024

ContextAgainst the backdrop of a high prevalence rate of femicide across Africa, it is crucial to gain methodological insights into the existing research on femicide.ObjectiveTo develop evidence-based strategies to address the complex and multifaceted nature of femicide in Africa, ultimately contributing to its prevention and reduction.Data sourcesEmpirical research was searched for using four electronic research databases (ProQuest, Web of Science, EBSCO and PubMed).Eligibility criteriaFull-text empirical articles (ie, observational or retrospective studies) published in English between the period of 1 January 1992 and 30 July 2021, which sampled femicide victims and/or perpetrators in Africa, were included in the review.Data extractionData were extracted using predefined data fields, including study quality indicators.Data synthesisThomas and Harden’s (2008) thematic synthesis method was used to analyse 22 empirical articles that met the inclusion criteria in this study.ResultsThis review highlights the significant focus on femicide research in South Africa. Most studies of femicides have used cross-sectional research designs. This review also demonstrates that crime dockets have benefited significantly from forensic contributions and police investigations. Furthermore, research efforts have uncovered various contextual factors that contribute to femicide, such as the high prevalence of early childhood trauma and the loss of primary caregivers among femicide offenders.ConclusionThis systematic review offers a thorough synthesis of the current understanding of femicide in an African context, focusing on South Africa. Despite acknowledging the strengths and limitations of the existing knowledge, this review emphasises the urgency of addressing femicide and calls for international attention and action to effectively combat this pressing issue.
What works for whom and why? Treatment effects and their moderators among forcibly displaced people receiving psychological and psychosocial interventions: study protocol for an individual patient data meta-analysis
Authors: Kurath Jennifer , Akhtar Aemal , Karyotaki Eirini , Sijbrandij Marit , Cuijpers Pim , Bryant Richard , Morina Naser 
Published: February 2024

IntroductionForcibly displaced people (FDP) have a high risk of developing mental disorders such as post-traumatic stress (PTS) disorder. Providing adequate mental healthcare for FDP is crucial but despite overall efficacy of many existing interventions, a large proportion of FDP does not benefit from treatment, highlighting the necessity of further investigating factors contributing to individual differences in treatment outcome. Yet, the few studies that have explored moderators of treatment effects are often insufficiently powered. Therefore, the present Individual Patient Data meta-analysis (IPD-MA) will investigate treatment effects and their moderators—variables related to beneficiaries, providers, intervention and study characteristics in relation to PTS outcomes.Methods and analysisA systematic literature search will be conducted from database inception in the databases PsycINFO, Cochrane, Embase, PTSDpubs and Web of Science. Only studies published in English, German, French, Spanish, Portuguese, and Dutch will be considered. Retrieved records will be screened for eligibility. Randomised controlled trials on adult FDP receiving psychological and psychosocial interventions aimed at alleviating symptoms such as PTS compared with a control condition without intervention will be included in this IPD-MA. Subsequently, authors of eligible studies will be contacted to request individual patient data (IPD). All datasets obtained will be synthesised into one large dataset which will be analysed using a one-stage approach by conducting mixed-effects linear regression models (ie, primary analysis). Additionally, aggregate data meta-analyes will be run using a two-stage approach by conducting multivariate regression models including all IPD (transformed) and available meta-data from study reports (ie, secondary analysis). PTS will serve as primary outcome measure, while mental health outcomes other than PTS, attendance, attrition, treatment non-response and adverse outcomes will be examined as secondary outcomes.Ethics and disseminationThis IPD-MA does not require ethical approval. The results will be published in international peer-reviewed journals.PROSPERO registration numberCRD42022299510.
Study protocol of short-course radiotherapy combined with CAPOX and PD-1 inhibitor for locally advanced colon cancer: a randomised, prospective, multicentre, phase II trial (TORCH-C)
Authors: Zhang Hui , Li Yaqi , Xia Fan , Sun Yiqun , Shen Lijun , Wan Juefeng , Chen Yajie , Wang Yaqi , Zhou Menglong , Wu Ruiyan , Zhou Shujuan , Wang Yan , Liu Fangqi , Cai Sanjun , Zhang Zhen 
Published: February 2024

IntroductionThe preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC.Methods and analysisTORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer.Ethics and disseminationThis study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12).Trial registration numberNCT05732493
Excess winter mortality in Finland, 1971–2019: a register-based study on long-term trends and effect modification by sociodemographic characteristics and pre-existing health conditions
Authors: Suulamo Ulla , Remes Hanna , Tarkiainen Lasse , Murphy Michael , Martikainen Pekka 
Published: February 2024

ObjectivesExcess winter mortality is a well-established phenomenon across the developed world. However, whether individual-level factors increase vulnerability to the effects of winter remains inadequately examined. Our aim was to assess long-term trends in excess winter mortality in Finland and estimate the modifying effect of sociodemographic and health characteristics on the risk of winter death.DesignNationwide register study.SettingFinland.ParticipantsPopulation aged 60 years and over, resident in Finland, 1971–2019.Outcome measuresAge-adjusted winter and non-winter death rates, and winter-to-non-winter rate ratios and relative risks (multiplicative interaction effects between winter and modifying characteristics).ResultsWe found a decreasing trend in the relative winter excess mortality over five decades and a drop in the series around 2000. During 2000–2019, winter mortality rates for men and women were 11% and 14% higher than expected based on non-winter rates. The relative risk of winter death increased with age but did not vary by income. Compared with those living with at least one other person, individuals in institutions had a higher relative risk (1.07, 95% CI 1.05 to 1.08). Most pre-existing health conditions did not predict winter death, but persons with dementia emerged at greater relative risk (1.06, 95% CI 1.04 to 1.07).ConclusionsAlthough winter mortality seems to affect frail people more strongly—those of advanced age, living in institutions and with dementia—there is an increased risk even beyond the more vulnerable groups. Protection of high-risk groups should be complemented with population-level preventive measures.
Phase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors
Authors: Patel Sandip P , Alonso-Gordoa Teresa , Banerjee Susana , Wang Ding , Naidoo Jarushka , Standifer Nathan E , Palmer Doug C , Cheng Lin-Yang , Kourtesis Panagiotis , Ascierto Maria L , Das Mayukh , Diamond Jennifer R , Hellmann Matthew D , Carneiro Benedito A 
Published: February 2024

BackgroundThe combination of monalizumab (anti-NKG2A/CD94) and durvalumab (anti-programmed death ligand-1) may promote antitumor immunity by targeting innate and adaptive immunity. This phase 1/2 study of monalizumab and durvalumab evaluated safety, antitumor activity, and pharmacodynamics in patients with advanced solid tumors.Main bodyImmunotherapy-naïve patients aged ≥18 years with advanced disease, Eastern Cooperative Oncology Group performance status of 0–1, and 1–3 prior lines of systemic therapy in the recurrent/metastatic setting were enrolled. In part 1 (dose escalation), patients received durvalumab 1500 mg every 4 weeks (Q4W) with increasing doses of monalizumab Q2W/Q4W (n=15). Dose expansion in part 1 included patients with cervical cancer (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W) or metastatic microsatellite stable (MSS)-colorectal cancer (CRC) (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q4W). In part 2 (dose expansion), patients with MSS-CRC (n=40), non-small cell lung cancer (NSCLC; n=20), MSS-endometrial cancer (n=40), or ovarian cancer (n=40) received durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W. The primary endpoint was safety. Secondary endpoints included antitumor activity per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Exploratory analyses included assessment of T-cell and natural killer (NK) cell activation and proliferation in peripheral blood and the tumor microenvironment (TME). The study enrolled 185 patients (part 1, 45; part 2, 140). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. In part 2, the most common treatment-related adverse events were fatigue (12.1%), asthenia (9.3%), diarrhea (9.3%), pruritus (7.9%), and pyrexia (7.1%). In the expansion cohorts, response rates were 0% (cervical), 7.7% (MSS-CRC), 10% (NSCLC), 5.4% (ovarian), and 0% (MSS-endometrial). Sustained NK cell activation, CD8+T-cell proliferation, increased serum levels of CXCL10 (C-X-C motif chemokine ligand 10) and CXCL11, and increased tumor infiltration of CD8+and granzyme B+cells were observed.ConclusionsAlthough efficacy was modest, monalizumab plus durvalumab was well tolerated and encouraging immune activation was observed in the peripheral blood and TME.Trial registration numberNCT02671435.