bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of active case detection to malaria elimination in Thailand
Authors: Kitchakarn Suravadee , Naowarat Sathapana , Sudathip Prayuth , Simpson Hope , Stelmach Rachel , Suttiwong Chalita , Puengkasem Sombat , Chanti Worawut , Gopinath Deyer , Kanjanasuwan Jerdsuda , Tipmontree Rungrawee , Pinyajeerapat Niparueradee , Sintasath David , Bisanzio Donal , Shah Jui A 
Published: November 2023

IntroductionThailand’s malaria surveillance system complements passive case detection with active case detection (ACD), comprising proactive ACD (PACD) methods and reactive ACD (RACD) methods that target community members near index cases. However, it is unclear if these resource-intensive surveillance strategies continue to provide useful yield. This study aimed to document the evolution of the ACD programme and to assess the potential to optimise PACD and RACD.MethodsThis study used routine data from all 6 292 302 patients tested for malaria from fiscal year 2015 (FY15) to FY21. To assess trends over time and geography, ACD yield was defined as the proportion of cases detected among total screenings. To investigate geographical variation in yield from FY17 to FY21, we used intercept-only generalised linear regression models (binomial distribution), allowing random intercepts at different geographical levels. A costing analysis gathered the incremental financial costs for one instance of ACD per focus.ResultsTest positivity for ACD was low (0.08%) and declined over time (from 0.14% to 0.03%), compared with 3.81% for passive case detection (5.62%–1.93%). Whereas PACD and RACD contributed nearly equal proportions of confirmed cases in FY15, by FY21 PACD represented just 32.37% of ACD cases, with 0.01% test positivity. Each geography showed different yields. We provide a calculator for PACD costs, which vary widely. RACD costs an expected US$226 per case investigation survey (US$1.62 per person tested) or US$461 per mass blood survey (US$1.10 per person tested).ConclusionACD yield, particularly for PACD, is waning alongside incidence, offering an opportunity to optimise. PACD may remain useful only in specific microcontexts with sharper targeting and implementation. RACD could be narrowed by defining demographic-based screening criteria rather than geographical based. Ultimately, ACD can continue to contribute to Thailand’s malaria elimination programme but with more deliberate targeting to balance operational costs.
‘We were treated like we are nobody’: a mixed-methods study of medical doctors’ internship experiences in Kenya and Uganda
Authors: Zhao Yingxi , Mbuthia Daniel , Gathara David , Nzinga Jacinta , Tweheyo Raymond , English Mike 
Published: November 2023

ObjectiveMedical interns are an important workforce providing first-line healthcare services in hospitals. The internship year is important for doctors as they transition from theoretical learning with minimal hands-on work under supervision to clinical practice roles with considerable responsibility. However, this transition is considered stressful and commonly leads to burn-out due to challenging working conditions and an ongoing need for learning and assessment, which is worse in countries with resource constraints. In this study, we provide an overview of medical doctors’ internship experiences in Kenya and Uganda.MethodsUsing a convergent mixed-methods approach, we collected data from a survey of 854 medical interns and junior doctors and semistructured interviews with 54 junior doctors and 14 consultants. Data collection and analysis were guided by major themes identified from a previous global scoping review (well-being, educational environment and working environment and condition), using descriptive analysis and thematic analysis respectively for quantitative and qualitative data.FindingsMost medical interns are satisfied with their job but many reported suffering from stress, depression and burn-out, and working unreasonable hours due to staff shortages. They are also being affected by the challenging working environment characterised by a lack of adequate resources and a poor safety climate. Although the survey data suggested that most interns were satisfied with the supervision received, interviews revealed nuances where many interns faced challenging scenarios, for example, poor supervision, insufficient support due to consultants not being available or being ‘treated like we are nobody’.ConclusionWe highlight challenges experienced by Kenyan and Ugandan medical interns spanning from burn-out, stress, challenging working environment, inadequate support and poor quality of supervision. We recommend that regulators, educators and hospital administrators should improve the resource availability and capacity of internship hospitals, prioritise individual doctors’ well-being and provide standardised supervision, support systems and conducive learning environments.
Promoting REproductive Planning And REadiness in Diabetes (PREPARED) Study protocol: a clinic-randomised controlled trial testing a technology-based strategy to promote preconception care for women with type 2 diabetes
Authors: Bailey Stacy C , Pack Allison P , Wismer Guisselle , Calderon Norma , Velazquez Evelyn , Batio Stephanie , Ekong Abbey , Eggleston Alice , Wallia Amisha , Wolf Michael S , Schauer Jacob M , Tenfelde Sandi , Liebovitz David M , Grobman William A 
Published: November 2023

IntroductionWomen with type 2 diabetes (T2DM) are more likely to experience adverse reproductive outcomes, yet preconception care can significantly reduce these risks. For women with T2DM, preconception care includes reproductive planning and patient education on: (1) the importance of achieving glycaemic control before pregnancy, (2) using effective contraception until pregnancy is desired, (3) discontinuing teratogenic medications if pregnancy could occur, (4) taking folic acid, and (5) managing cardiovascular and other risks. Despite its importance, few women with T2DM receive recommended preconception care.Methods and analysisWe are conducting a two-arm, clinic-randomised trial at 51 primary care practices in Chicago, Illinois to evaluate a technology-based strategy to ‘hardwire’ preconception care for women of reproductive age with T2DM (the PREPARED (Promoting REproductive Planning And REadiness in Diabetes) strategy) versus usual care. PREPARED leverages electronic health record (EHR) technology before and during primary care visits to: (1) promote medication safety, (2) prompt preconception counselling and reproductive planning, and (3) deliver patient-friendly educational tools to reinforce counselling. Post-visit, text messaging is used to: (4) encourage healthy lifestyle behaviours. English and Spanish-speaking women, aged 18–44 years, with T2DM will be enrolled (N=840; n=420 per arm) and will receive either PREPARED or usual care based on their clinic’s assignment. Data will be collected from patient interviews and the EHR. Outcomes include haemoglobin A1c (primary), reproductive knowledge and self-management behaviours. We will use generalised linear mixed-effects models (GLMMs) to evaluate the impact of PREPARED on these outcomes. GLMMs will include a fixed effect for treatment assignment (PREPARED vs usual care) and random clinic effects.Ethics and disseminationThis study was approved by the Northwestern University Institutional Review Board (STU00214604). Study results will be published in journals with summaries shared online and with participants upon request.Trial registration numberClinicalTrials.gov Registry (NCT04976881).
Telehealth-based transitional care management programme to improve access to care
Authors: Elsener Michelle , Santana Felipes Rachel C , Sege Jonathan , Harmon Priscilla , Jafri Farrukh N 
Published: November 2023

BackgroundThe transition from hospital to home is a vulnerable time for patients and families that can be improved through care coordination and structured discharge planning.Local problemOur organisation aimed to develop and expand a programme that could improve 30-day readmission rates on overall and disease-specific populations by assessing the impact of a telehealth outreach by a registered nurse (RN) after discharge from an acute care setting on 30-day hospital readmission.MethodsThis is a prospective observational design conducted from May 2021 to December 2022 with an urban, non-academic, acute care hospital in Westchester County, New York. Outcomes for patients discharged home following inpatient hospitalisation were analysed within this study. We analysed overall and disease-specific populations (congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and pneumonia (PNA)) as compared with a 40-month prestudy cohort.Intervention(s)Patients were identified in a non-random fashion meeting criterion of being discharged home after an inpatient admission. Participants received a telephonic outreach by an RN within 72 hours of discharge. Contacted patients were asked questions addressing discharge instructions, medication access, follow-up appointments and social needs. Patients were offered services and resources based on their individual needs in response to the survey.Results68.2% of the 24 808 patients were contacted to assess and offer services. Median readmission rates for these patients were 1.2% less than the prestudy cohort (11.0% to 9.8%). Decreases were also noted for disease-specific conditions (CHF (14.3% to 9.1%), COPD (20.0% to 13.4%) and PNA (14.9% to 14.0%)). Among those in the study period, those that were contacted between 24 and 48 hours after discharge were 1.2 times less likely to be readmitted than if unable to be contacted (254/3742 (6.8%) vs 647/7866 (8.2%); p=0.005).ConclusionsUsing a multifaceted telehealth approach to improve patient engagement and access reduced 30-day hospital readmission for patients discharged from the acute care setting.
Talking about falls: a qualitative exploration of spoken communication of patients’ fall risks in hospitals and implications for multifactorial approaches to fall prevention
Authors: McVey Lynn , Alvarado Natasha , Healey Frances , Montague Jane , Todd Chris , Zaman Hadar , Dowding Dawn , Lynch Alison , Issa Basma , Randell Rebecca 
Published: November 2023

BackgroundInpatient falls are the most common safety incident reported by hospitals worldwide. Traditionally, responses have been guided by categorising patients’ levels of fall risk, but multifactorial approaches are now recommended. These target individual, modifiable fall risk factors, requiring clear communication between multidisciplinary team members. Spoken communication is an important channel, but little is known about its form in this context. We aim to address this by exploring spoken communication between hospital staff about fall prevention and how this supports multifactorial fall prevention practice.MethodsData were collected through semistructured qualitative interviews with 50 staff and ethnographic observations of fall prevention practices (251.25 hours) on orthopaedic and older person wards in four English hospitals. Findings were analysed using a framework approach.FindingsWe observed staff engaging in ‘multifactorial talk’ to address patients’ modifiable risk factors, especially during multidisciplinary meetings which were patient focused rather than risk type focused. Such communication coexisted with ‘categorisation talk’, which focused on patients’ levels of fall risk and allocating nursing supervision to ‘high risk’ patients. Staff negotiated tensions between these different approaches through frequent ‘hybrid talk’, where, as well as categorising risks, they also discussed how to modify them.ConclusionTo support hospitals in implementing multifactorial, multidisciplinary fall prevention, we recommend: (1) focusing on patients’ individual risk factors and actions to address them (a ‘why?’ rather than a ‘who’ approach); (2) where not possible to avoid ‘high risk’ categorisations, employing ‘hybrid’ communication which emphasises actions to modify individual risk factors, as well as risk level; (3) challenging assumptions about generic interventions to identify what individual patients need; and (4) timing meetings to enable staff from different disciplines to participate.
Association between serum high-density lipoprotein cholesterol and lung function in adults: three cross-sectional studies from US and Korea National Health and Nutrition Examination Survey
Authors: Lee Chanho , Cha Youngjae , Bae Soo Han , Kim Young Sam 
Published: November 2023

IntroductionCholesterol is an irreplaceable nutrient in pulmonary metabolism; however, studies on high-density lipoprotein cholesterol (HDL-C) levels have shown conflicting results regarding lung function. Therefore, we investigated the association between lung function and HDL-C levels in three cross-sectional studies conducted in the USA and South Korea.MethodsUS National Health and Nutrition Examination Survey (NHANES) III, US NHANES 2007–2012, and Korea National Health and Nutrition Examination Survey (KNHANES) IV–VII performed spirometry and met the American Thoracic Society recommendations. Multiple linear regression models were used to determine the relationship between serum lipid levels and lung function. The models were adjusted for age, sex, household income, body mass index, smoking pack year, use of lipid-lowering medication and race. Serum HDL-C levels were classified into three groups to assess the dose–response relationship according to the guideline from the National Cholesterol Education Program-Adult Treatment Panel III.ResultsThe adult participants of the KNHANES (n=31 288), NHANES III (n=12 182) and NHANES 2007–2012 (n=9122) were analysed. Multivariate linear regression analysis of the serum cholesterol profiles revealed that only serum HDL-C was associated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in all three studies. A 1 SD increase in the HDL-C level increased the percent predicted FVC by 0.5%–1.5% p, and the per cent predicted FEV1by 0.5%–1.7% p. In terms of HDL-C levels, correlations between the HDL-C groups and the per cent predicted FVC and FEV1showed dose–response relationships. Compared with the normal group, high HDL-C levels increased FVC by 0.75%–1.79% p and FEV1by 0.55%–1.90% p, while low levels led to 0.74%–2.19% p and 0.86%–2.68% p reductions in FVC and FEV1, respectively. Subgroup analyses revealed weaker associations in females from KNHANES and NHANES III.ConclusionIn the three nationwide cross-sectional studies, high HDL-C levels were associated with improved FVC and FEV1. However, future studies are needed to confirm this correlation and elucidate the underlying mechanisms.
MDR1-expressing CD4+T cells with Th1.17 features resist to neoadjuvant chemotherapy and are associated with breast cancer clinical response
Authors: Di Roio Anthony , Hubert Margaux , Besson Laurie , Bossennec Marion , Rodriguez Céline , Grinberg-Bleyer Yenkel , Lalle Guilhem , Moudombi Lyvia , Schneider Raphael , Degletagne Cyril , Treilleux Isabelle , Campbell Daniel J , Metzger Séverine , Duhen Thomas , Trédan Olivier , Caux Christophe , Ménétrier-Caux Christine 
Published: November 2023

BackgroundMultidrug resistance-1 (MDR1) transporter limits the intracellular accumulation of chemotherapies (paclitaxel, anthracyclines) used in breast cancer (BC) treatment. In addition to tumor cells, MDR1 is expressed on immune cell subsets in which it confers chemoresistance. Among human T cells, MDR1 is expressed by most CD8+T cells, and a subset of CD4+T helper (Th) cells. Here we explored the expression, function and regulation of MDR1 on CD4+T cells and investigated the role of this population in response to neoadjuvant chemotherapy (NAC) in BC.MethodsPhenotypic and functional characteristics of MDR1+CD4 Th cells were assessed on blood from healthy donors and patients with BC by flow cytometry. These features were extended to CD4+Th cells from untreated breast tumor by flow cytometry and RNA-sequencing (RNA-seq). We performed in vitro polarization assays to decipher MDR1 regulation on CD4 Th cells. We evaluated in vitro the impact of chemotherapy agents on MDR1+CD4+Th cells. We analyzed the impact of NAC treatment on MDR1+CD4+Th cells from blood and tumors and their association with treatment efficacy in two independent BC cohorts and in a public RNA-seq data set of BC tumor biopsies before and after NAC. Finally, we performed single cell (sc) RNAseq of blood CD4+memory T cells from NAC-treated patients and combined them with an scRNAseq public data set.ResultsMDR1+CD4 Th cells were strongly enriched in Th1.17 polyfunctional cells but also in Th17 cells, both in blood and untreated breast tumor tissues. Mechanistically, Tumor growth factor (TGF)-β1 was required for MDR1 induction during in vitro Th17 or Th1.17 polarization. MDR1 expression conferred a selective advantage to Th1.17 and Th17 cells following paclitaxel treatment in vitro and in vivo in NAC-treated patients. scRNAseq demonstrated MDR1 association with tumor Th1.17 and Th with features of cytotoxic cells. Enrichment in MDR1+CD4+Th1.17 and Th17 cells, in blood and tumors positively correlated with pathological response. Absence of early modulation of Th1.17 and Th17 in NAC-resistant patients, argue for its use as a biomarker for chemotherapy regimen adjustment.ConclusionMDR1 favored the enrichment of Th1.17 and Th17 in blood and tumor after NAC that correlated to clinical response.
Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer
Authors: Boelaars Kelly , Goossens-Kruijssen Laura , Wang Di , de Winde Charlotte M , Rodriguez Ernesto , Lindijer Dimitri , Springer Babet , van der Haar Àvila Irene , de Haas Aram , Wehry Laetitia , Boon Louis , Mebius Reina E , van Montfoort Nadine , Wuhrer Manfred , den Haan Joke M M , van Vliet Sandra J , van Kooyk Yvette 
Published: November 2023

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC is characterized by a desmoplastic, hypoxic and highly immunosuppressive tumor microenvironment (TME), where T-cell infiltration is often lacking (immune desert), or where T cells are located distant from the tumor islands (immune excluded). Converting the TME to an immune-inflamed state, allowing T-cell infiltration, could increase the success of immunotherapy in PDAC.MethodIn this study, we use the KPC3 subcutaneous PDAC mouse model to investigate the role of tumor-derived sialic acids in shaping the tumor immune landscape. A sialic acid deficient KPC3 line was generated by genetic knock-out of the CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) enzyme, a critical enzyme in the synthesis of sialic acid-containing glycans. The effect of sialic acid-deficiency on immunotherapy efficacy was assessed by treatment with anti-programmed cell death protein 1 (PD-1) and agonistic CD40.ResultThe absence of sialic acids in KPC3 tumors resulted in increased numbers of CD4+and CD8+T cells in the TME, and reduced frequencies of CD4+regulatory T cells (Tregs) within the T-cell population. Importantly, CD8+T cells were able to infiltrate the tumor islands in sialic acid-deficient tumors. These favorable alterations in the immune landscape sensitized sialic acid-deficient tumors to immunotherapy, which was ineffective in sialic acid-expressing KPC3 tumors. In addition, high expression of sialylation-related genes in human pancreatic cancer correlated with decreased CD8+T-cell infiltration, increased presence of Tregs, and poorer survival probability.ConclusionOur results demonstrate that tumor-derived sialic acids mediate T-cell exclusion within the PDAC TME, thereby impairing immunotherapy efficacy. Targeting sialic acids represents a potential strategy to enhance T-cell infiltration and improve immunotherapy outcomes in PDAC.
Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study
Authors: Wallace Eric L , Goker-Alpan Ozlem , Wilcox William R , Holida Myrl , Bernat John , Longo Nicola , Linhart Aleš , Hughes Derralynn A , Hopkin Robert J , Tøndel Camilla , Langeveld Mirjam , Giraldo Pilar , Pisani Antonio , Germain Dominique Paul , Mehta Ankit , Deegan Patrick B , Molnar Maria Judit , Ortiz Damara , Jovanovic Ana , Muriello Michael , Barshop Bruce A , Kimonis Virginia , Vujkovac Bojan , Nowak Albina , Geberhiwot Tarekegn , Kantola Ilkka , Knoll Jasmine , Waldek Stephen , Nedd Khan , Karaa Amel , Brill-Almon Einat , Alon Sari , Chertkoff Raul , Rocco Rossana , Sakov Anat , Warnock David G 
Published: November 2023

BackgroundPegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than −2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year.MethodsPatients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms.ResultsSeventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18–60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2and median (range) eGFR slope was −7.3 (−30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was −0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths.ConclusionsBased on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions.Trial registration numberNCT02795676.