bluuebunny/crossref_metadata_2025_split huggingface dataset:
The economic burden of ischaemic heart diseases on health systems: a systematic review
Authors: Rittiphairoj Thanitsara , Bulstra Caroline , Ruampatana Chochat , Stavridou Maria , Grewal Sagar , Reddy Che L , Atun Rifat 
Published: February 2025

IntroductionThere is a dearth of evidence regarding the global economic burden of ischaemic heart diseases (IHDs). This systematic review aims to synthesise national-level studies worldwide quantifying the economic burden of IHDs from a provider’s perspective.MethodsWe searched PubMed, Embase, Cochrane, DARE and EconLit databases from 1 January 2000 to 29 June 2022. We included observational, cost-of-illness and economic modelling studies reporting direct healthcare cost data for IHDs at the national level. At least two reviewers independently screened titles and abstracts and full texts, extracted data and assessed quality using a seven-question assessment tool. We synthesised findings by country, focusing on three key economic estimates: total annual costs of IHDs, costs of managing acute IHD episodes and chronic IHD care. We correlated these costs with country-specific macroeconomic measures and disease burden.ResultsWe included 65 national-level studies conducted in 21 countries worldwide, with a majority in high-income countries. The median direct healthcare cost per episode of IHDs was 8062 Int$ 2019 (IQR: 5770–9580), and the median direct healthcare cost of IHDs per patient-year was 10 064 Int$ 2019 (IQR: 7619–14 818). These estimates positively correlated with country-specific macroeconomic and DALY measures.ConclusionIHDs impose a substantial economic burden on health systems globally. Economic costs in countries exceed per capita public health expenditure, primarily driven by acute episodes. National-level data were available for only 21 countries, and none from low-middle-income and low-income countries. Economic costs of IHDs need to be quantified to inform resource allocation decisions at national and global levels.CRD42022337577.
Immunoglobulin unresponsive Guillain-Barré syndrome: rinse or repeat? A systematic review
Authors: Roe Thomas , Gordon Alex , Gourd Nicholas , Thomas Charlotte , Ward James , Osman Chinar , Dushianthan Ahilanandan 
Published: February 2025

IntroductionSevere Guillain-Barré syndrome (GBS) patients may not show improvement after a single course of intravenous immunoglobulin (IVIg) therapy. Current treatment options include either a second course of IVIg or therapeutic plasma exchange (TPE). This systematic review aims to evaluate the current literature on the use of a second course of IVIg or TPE in patients who fail to show clinical improvement after the first IVIg course.MethodsWe searched PubMed, Embase and Medline databases up until 26 October 2023. Studies that evaluated adult patients with confirmed GBS who have failed one full course of IVIg and subsequently received either repeat IVIg or TPE were included. Risk of bias was performed using study-specific checklists. A narrative synthesis of results is presented.ResultsA total of 37 articles were identified (1 randomised controlled trial (RCT), 3 observational and 33 case reports/series), consisting of 422 patients in total. 12 studies evaluated repeat IVIg and 24 studies evaluated TPE after IVIg. There was no superiority of a repeat course of IVIg or TPE in all clinical outcome measures.ConclusionsThe evidence suggests with a low degree of certainty that there is no beneficial effect of further IVIg in unresponsive GBS. The quality of evidence regarding TPE after IVIg is insufficient to suggest any efficacy due to a lack of RCTs. We recommend standardised case reporting with consideration for a multinational case registry and RCTs to determine the efficacy of TPE after initial IVIg unresponsiveness.
Exploring the levels of variation, inequality and use of physical activity intervention referrals in England primary care from 2017–2020: a retrospective cohort study
Authors: Jani Anant , Liyanage Harshana , Okusi Cecilia , Sherlock Julian , Hoang Uy , McGagh Dylan , Williams John , Ferreira Filipa , Yonova Ivelina , de Lusignan Simon 
Published: February 2025

ObjectivesIn this study, we explore the use of physical activity intervention referrals in primary care in England and compare their use with the rate of cardiovascular disease (CVD) risk factors in England from 2017 to 2020. We also explore variation and inequalities in referrals to these interventions in England across the study period.DesignRetrospective cohort study.SettingEngland primary care via the Royal College of General Practitioners Research Surveillance Centre.ParticipantsThe Royal College of General Practitioners Research Surveillance Centre, a sentinel network across England covering a population of over 15 000 000 registered patients, was used for data analyses covering the 2017–2020 financial years and including patients with long-term conditions indicating CVD risk factors.Outcome measuresAn existing ontology of primary care codes was used to capture physical activity interventions and a new ontology was designed to cover long-term conditions indicating CVD risk factors. Single factor analysis of variance, paired samples t-test and two-tailed, one proportion z-tests were used to determine the significance of our findings.ResultsWe observed statistically significant variation in physical activity intervention referrals for people with CVD risk factors from different ethnic groups and age groups across different regions of England as well as a marked decrease during the COVID-19 pandemic. Interestingly, a significant difference was not seen for different socioeconomic groups or sexes. Across all attributes and time periods (with the exception of the 18–39 group, 2017–2019), we observed a statistically significant underuse of physical activity intervention referrals.ConclusionsOur findings identified statistically significant variation and underuse of physical activity referrals in primary care in England for individuals at risk of CVD for different population subgroups, especially different ethnicities and age groups, across different regions of England and across time, with the COVID-19 pandemic exerting a significant negative impact on referral rates.
Implementing Guidelines for hypothermia prevention with Local adaptation to keep periOperative patients Warm (GLOW): protocol of a stepped-wedge cluster randomised hybrid type II effectiveness-implementation study
Authors: Munday Judy , Duff Jed , Wood Fiona M , Sturgess David , Keogh Samantha , Ralph Nicholas , White Nicole M , Carter Hannah , Graham Ian D 
Published: February 2025

IntroductionPerioperative hypothermia is a common and preventable complication of surgery. Systems level change that enables perioperative teams to integrate hypothermia prevention into practice in ways that are contextually appropriate is needed. The purpose of this trial is to evaluate the effectiveness and implementation of perioperative hypothermia prevention guidance with local adaptation on clinical, implementation and economic outcomes. Our objective is to decrease the risk of patients developing perioperative hypothermia.Methods and analysisA hybrid type II effectiveness-implementation study. An incomplete stepped-wedge cluster randomised controlled trial design will be used, with a 6-month transition period for implementation. Perioperative departments from five major public hospitals in South East Queensland, Australia, will participate over 27 months. The co-primary outcomes are (effectiveness) hypothermia on arrival to the post anaesthetic care unit (PACU) and (implementation) extent of temperature monitoring and active warming. Secondary clinical effectiveness outcomes include hypothermia at any perioperative time point, PACU and hospital length of stay, intraoperative or post-anaesthetic adverse events, blood transfusions and surgical site infection. Secondary implementation outcomes include pre-transition measures of adoptability and implementability, and post-transition measures of adoption, fidelity of implementation strategy and site team learning. Cost-effectiveness will evaluate implementation costs and quality-adjusted life years. Based on the number and unequal sizes of clusters, we used a constrained randomisation approach for sample size determination to minimise the imbalance between control and intervention period sample sizes. Generalised linear mixed models will be used to analyse primary and secondary outcomes.Ethics and disseminationEthical approval was obtained with a waiver of consent to access clinical records (reference: HREC/2023/MNHB/94571). Informed consent will be sought from patients completing surveys. Consent will be implied from clinicians participating in implementation evaluation. Findings will be disseminated through journal publications and conference presentations. Practice and policy recommendations will be collaboratively developed with partner organisations.Trial registration numberProspective registration of the trial was obtained on 28 July 2023 on the Australia and New Zealand Clinical Trials Registry Network: ACTRN12623000814673.
Association between the COVID-19 vaccination campaign and fertility trends: a population-level time series analysis for 22 countries
Authors: Jasilioniene Aiva , Jasilionis Domantas , Jdanov Dmitri , Myrskylä Mikko 
Published: February 2025

IntroductionAt the turn of 2021–2022, monthly birth rates declined in many higher-income countries. We explore how the rollout of COVID-19 vaccination was associated with this decline.MethodsUsing an interrupted time series design, we evaluate the impact of the onset of the COVID-19 pandemic and the start of COVID-19 vaccination on seasonally adjusted monthly total fertility rates in 22 high-income countries. We study the associations between COVID-19 vaccination and fertility by additionally controlling for youth unemployment, stringency index and vaccination coverage. Fertility data come from the Short-Term Fertility Fluctuations data series under the Human Fertility Database. Indicators used as control variables originate from Eurostat and OECD databases, Oxford COVID-19 Government Response Tracker and Our World in Data.ResultsThe start of the pandemic had an immediate effect on fertility in most countries, although the size and direction of level changes considerably varied across them. The impact of COVID-19 vaccination was likewise extensive. While a relatively pronounced negative association between the COVID-19 vaccine rollout and fertility 9 months later was found only for 10 out of 22 countries, indications of a negative fertility response were detected in the vast majority of countries. For several countries, the decline was preceded by fertility increase that took place after the onset of the pandemic. Only 4 out of 22 countries had post-vaccination fertility declines that resulted in fertility being on lower level than what the pre-pandemic trend predicted. Additional control variables changed the associations only a little.ConclusionsThe COVID-19 vaccination campaign contributed to the variation in short-term fertility trends. Several countries experienced declines following the campaign, which often returned fertility closer to the pre-pandemic trend. Fertility appears to have responded in short run to vaccination, but only in few cases such that the long-term trajectory is below the pre-pandemic trend.
Understanding patient experiences during gynaecological procedures: a qualitative exploratory study
Authors: Gopisetty Deepti Divya , Rogers-Shepp India , Padron Elisa , Shankar Megha , Shaw Kate A 
Published: February 2025

BackgroundPain with gynaecological clinic-based procedures is common and undertreated. Prior research has focused on interventions for reducing pain and anxiety with analgesics, yet there remain gaps in understanding the myriad of facilitators and barriers to a person’s positive experience. We aimed to start to address these gaps by exploring factors that influence a person’s experience during gynaecological procedures beyond quantitative measures of pain.MethodsA qualitative thematic analysis approach was used for this exploratory study. Through convenience sampling, we recruited 15 participants with gynaecological procedural experience with intrauterine device (IUD) insertions, surgical abortions, colposcopies and/or endometrial biopsies. We conducted in-depth, semi-structured 1:1 interviews that explored participants' experience of the procedure. We then used a mixed inductive and deductive approach for development of a codebook and thematic analysis based on the Person-Centered Care Framework for Reproductive Health Equity (PCFRHE).ResultsFour themes fundamental to understanding how patients process procedural experiences were identified: (1) Balancing preparation and anxiety, (2) Variable rapport with clinicians, (3) Self-advocacy and autonomy and (4) Clinician responsiveness to pain.ConclusionsPerson-centred care in an inclusive, trauma-responsive environment is essential for improving gynaecological procedural experience. Ensuring patient access to pre- and post-visit information and offering multiple options to increase comfort are tangible actions clinicians can take to improve patient experience. This study underscores the importance of person-centred care in gynaecological procedures, emphasising better preprocedural education and support.
Efficacy and safety of nivolumab plus ipilimumab in patients with metastatic variant histology (non-clear cell) renal cell carcinoma
Authors: Moussa Mohammad Jad , Khandelwal Jaanki , Wilson Nathaniel R , Malikayil Kiran L , Surasi Devaki Shilpa , Bathala Tharakeswara K , Lin Yiyun , Rao Priya , Tamboli Pheroze , Sircar Kanishka , Ajufo Helen , Elsayes Khaled M , Shah Amishi , Johns Andrew C , Goswami Sangeeta , Hasanov Elshad , Jonasch Eric , Msaouel Pavlos , Campbell Matthew T , Alhalabi Omar , Tannir Nizar M 
Published: February 2025

BackgroundNivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC.MethodsBetween November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed on available tumor specimens.ResultsTwenty-five (45.5%) patients had papillary histology (pRCC), 12 (21.8%) patients had chromophobe (chRCC), and 18 (32.7%) patients had unclassified RCC (uRCC). Fifty-two (94.5%) patients received nivo/ipi in 1 L. Sarcomatoid features (SF) were found in 20 (36.4%) cases. ORR was 48% (12/25) in pRCC, 25% (3/12) in chRCC (all 3 cases had SF), 27.8% (5/18) in uRCC, and 55% (11/20) across histologies with SF.The median PFS was 10.6 months (95% CI: 2.8 to 22.8) in pRCC, 3.6 months (95% CI: 0.9 – NE) in chRCC, and 3 months (95% CI: 2.1 to 7) in uRCC; 6-month milestone PFS was 56% (95% CI: 36.3 to 75.7), 41.7% (95% CI: 22 to 61.3), and 38.9% (95% CI: 21.7 to 56.1) in pRCC, chRCC, and uRCC, respectively. The median DoR for the entire cohort was 8.5 months (95% CI: 8 – NE). The median OS was 36.7 months (95% CI: 11.5 to 54.8) in pRCC, 25.7 months (95% CI: 0.9 – NE) in chRCC, and 11.1 months (95% CI: 6.5 – NE) in uRCC.Ten (18.2%) patients discontinued treatment due to treatment-related adverse events (AEs). Grade 3/4 immune-mediated AEs were noted in 17 (30.9%) patients. We performed NGS on 26 cases:TP53(42%),PTEN(23%), andTERT(23%) alterations were most frequently found, withTERTandTP53mutations enriched in pRCC and chRCC, respectively.ConclusionNivo/ipi produced favorable outcomes in patients with pRCC supporting its use as 1 L therapy. Responses in patients with chRCC were noted exclusively with SF. Despite achieving an ORR of 27.8% with nivo/ipi, patients with uRCC had short PFS and inferior OS.
Opioid use among injured workers: pain and the return-to-work experience
Authors: Nadalin Victoria , Carnide Nancy , Mustard Cameron , Severin Colette N , Furlan Andrea D , Smith Peter M 
Published: February 2025

ObjectiveIn this cross-sectional analysis, we explored how return-to-work (RTW) experiences and postinjury pain are associated with opioid use after a workplace injury/illness.MethodsWorkers with accepted lost-time claims, compensated by the workers’ compensation board in Ontario, Canada were interviewed by telephone 18 months following a work-related physical injury/illness. Participants were asked about their past-year opioid use, current pain, RTW timing and workplace accommodations. Separate logistic regression analyses were conducted to estimate the association between two independent variables and opioid use: one combining the presence of pain with workplace accommodation and a second combining the presence of pain with RTW timing, adjusted for sociodemographic, work, injury and health covariates.ResultsOf 1793 participants included in the analysis, 35.6% used opioids more than once in the past 12 months. Compared with those who did not return to work too soon and had no/mild pain, odds of opioid use were higher among those with severe pain, both those who returned too soon (OR 2.90, 95% CI 2.11 to 3.99) and those who did not return too soon (OR 3.01, 95% CI 2.16 to 4.19). Compared with those who had an offer of accommodation and no/mild pain, workers with severe pain and an accommodation offer (OR 2.78, 95% CI 2.16 to 3.57) or without an offer (OR 2.69, 95% CI 1.90 to 3.81) had increased odds of reporting use of opioids.ConclusionsFindings suggest pain is the main factor associated with opioid use after a work-related injury, irrespective of RTW experiences. However, due to the limitations of this exploratory analysis, longitudinal research examining this issue is warranted.
Does selenium offset methylmercury toxicity across trophic levels in a primary producer, Auxenochlorella pyrenoidosa, and a detritovore, Aeolosoma variegatum?
Authors: Azmi Husnah , Melles Stephanie J. , Laursen Andrew E. 
Published: February 2025

Methylmercury ([CH3Hg]+ or MeHg) is a potent neurotoxin that impairs functioning of the nervous system, and selenium (Se) is known to provide a protective effect against MeHg. Experiments were run to investigate the expected offsetting of MeHg toxicity by Se across trophic levels at the base of the aquatic food chain. An algal primary producer, Auxenochlorella pyrenoidosa, was exposed to MeHg (2 µg L−1) in the presence or absence of varying levels of Se (0 µg L−1, 2 µg L−1, and 5 µg L−1). Results showed that MeHg decreased the maximum density of Auxenochlorella, which Se did not offset. Equal amounts (8 mg) of the algal biomass produced under exposure conditions were subsequently fed to a detritovore, Aeolosoma variegatum (a small freshwater annelid worm). When consuming dietary Se in MeHg contaminated water, or when consuming dietary Se with dietary MeHg, Aeolosoma populations experienced a rescue effect against MeHg, i.e., they achieved greater final population density. Understanding safe levels of dietary Se that provide population level protection against MeHg is a critical step towards managing mercury in contaminated ecosystems.
A Case of Sarcoid Uveitis Diagnosed With Mammography Two Months After Normal Chest Imaging
Authors: Riccardi Madison , Contento Robert , Christensen Cory , Brady Amy , Swan Rebecca L. , Swan Robert T. 
Published: February 2025

Purpose: Sarcoidosis is a systemic inflammatory disease associated with ocular involvement in 20%–30% of cases. The current gold standard for detecting sarcoidosis is computed tomography of the thorax, which is 73% sensitive. Definitive diagnosis necessitates biopsy, with Schaumann bodies and non‐necrotizing granulomas serving as key pathological hallmarks.Observations: Our patient, a 44‐year‐old White female, presented for a second opinion on her bilateral chronic intermediate uveitis with intractable chronic cystoid macular edema of the left eye. Our clinical suspicion for sarcoidosis was high, but the computed tomography thorax scan did not show any abnormal findings. A routine mammogram completed 4 weeks prior to our initial evaluation showed axillary lymph node enlargement with calcifications. Subsequent biopsy was consistent with sarcoidosis. Treatment with mycophenolate mofetil resolved the uveitis and macular edema.Conclusions and Importance: The diagnosis of sarcoidosis can be challenging due to nonspecific ocular signs and the potential for falsely negative findings on imaging. This case highlights the importance of patient education and self‐surveillance regarding the characteristic systemic symptoms of sarcoidosis, which commonly involve the lungs, eyes, skin, joints, etc. Our report demonstrates the significance of maintaining a high level of suspicion for sarcoidosis in patients with characteristic ocular findings, even when initial imaging results are negative or inconclusive.
Genetic Predictive Association Between Inflammatory Cytokines and Vitiligo: A Bidirectional Mendelian Randomization Study
Authors: Lei Tianbing , Ni Yao 
Published: February 2025

Background: Previous studies have indicated a close association between vitiligo and inflammatory cytokines, yet the genetic predictive association remains unclear. The study aimed to predict the relationship between vitiligo and inflammatory cytokines in genetics.Methods: A bidirectional analysis was conducted by the two‐sample MR. We selected independent genetic tools for significant levels associated with inflammatory cytokines and vitiligo from corresponding meta‐analyses of genome‐wide association study (GWAS). The summary data for inflammatory cytokines were derived from a GWAS meta‐analysis conducted on three separate Finnish population cohorts, comprising a total of 8293 individuals (N = 8293). The vitiligo data, on the other hand, were extracted from a GWAS meta‐analysis conducted on individuals of European ancestry, totaling 44,266 individuals (N = 44,266). As the primary analytical approach, we employed the inverse variance weighted (IVW) method, and to ensure the reliability of our main findings, we also performed sensitivity analysis to evaluate the robustness.Results: Compelling evidence indicated a causal association between genetically predicted IL‐18 and IL‐8 with vitiligo (odds ratio, OR: 1.162, 95% CI: 1.043–1.295, p = 0.006, and pfdr = 0.020 and OR: 0.726, 95% CI: 0.602–0.876, p = 0.001, and pfdr = 0.004). In addition, cytokines including stromal cell‐derived factor‐1 alpha (SDF1a) (Beta: 0.032, p = 0.016, and pfdr = 0.039), IL‐17 (Beta: 0.038, p = 0.005, and pfdr = 0.027), basic fibroblast growth factor (FGFBasic) (Beta: 0.028, p = 0.034, and pfdr = 0.170), monocyte chemoattractant protein‐1(MCP1) (Beta: 0.026, p = 0.046, and pfdr = 0.189), and platelet‐derived growth factor BB (PDGFbb) (Beta: 0.026, p = 0.040, and pfdr = 0.198) were suggested to be the consequences of vitiligo.Conclusions: According to this investigation, it has been proposed that the etiology of vitiligo is likely associated with IL‐18 and IL‐8, whereas the downstream progression of vitiligo can be attributed to several inflammatory cytokines such as IL‐17, SDF1a, PDGFbb, MCP1, and FGFBasic.