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Data extraction is a crucial, yet labor-intensive and error-prone part of evidence synthesis. To date, efforts to harness machine learning for enhancing efficiency of the data extraction process have fallen short of achieving sufficient accuracy and usability. With the release of large language models (LLMs), new possibilities have emerged to increase efficiency and accuracy of data extraction for evidence synthesis. The objective of this proof-of-concept study was to assess the performance of an LLM (Claude 2) in extracting data elements from published studies, compared with human data extraction as employed in systematic reviews. Our analysis utilized a convenience sample of 10 English-language, open-access publications of randomized controlled trials included in a single systematic review. We selected 16 distinct types of data, posing varying degrees of difficulty (160 data elements across 10 studies). We used the browser version of Claude 2 to upload the portable document format of each publication and then prompted the model for each data element. Across 160 data elements, Claude 2 demonstrated an overall accuracy of 96.3% with a high test-retest reliability (replication 1: 96.9%; replication 2: 95.0% accuracy). Overall, Claude 2 made 6 errors on 160 data items. The most common errors (n = 4) were missed data items. Importantly, Claude 2's ease of use was high; it required no technical expertise or labeled training data for effective operation (i.e., zero-shot learning). Based on findings of our proof-of-concept study, leveraging LLMs has the potential to substantially enhance the efficiency and accuracy of data extraction for evidence syntheses.

Abstract Background Promoting the use of insecticide-treated mosquito nets (ITNs) is one of the main strategies for reducing malaria-related morbidity. An innovative activity-based contracting (ABC) approach has been implemented in Kwilu Province, Democratic Republic of Congo to optimize ITN mass distribution campaigns, with payments based on contractually defined programmatic outcomes for key campaign activities following independent verification of results. Methods This internal evaluation was carried out using a mixed methods approach combining qualitative and quantitative document and content analysis from a series of three workshops: validation workshops for campaign results at provincial level for the 2021 and 2022 campaigns; internal evaluation workshop for the Kwilu campaign as part of the ABC approach organized by “Santé pour tous en milieu rural” (SANRU) with its sub-contractors; and national campaign evaluation workshop organized by the National Malaria Control Program. Results The pilot campaign with the ABC approach in Kwilu has demonstrated better results than campaigns conducted using the standard, non-ABC, approach: better household coverage (99.9% vs. 97.3%) and improved compliance with ITN allocation to households based on the household size (98. 9% vs. 84.7%); lower loss of ITNs (0.3% vs. 0.5%) with immediate penalties for lost ITNs in the province under the ABC approach; shorter campaign lead times (14 vs. 28 weeks from the start of training to the launch of distribution). This last point is crucial, as it is likely to generate efficiencies and contribute to ensuring timely ITN replacement campaigns. Conclusion The challenges encountered and the lessons learned in the implementation of the pilot ABC approach in Kwilu could guide future distribution campaigns in the DRC and other African countries that would like to engage in distribution campaigns based on performance-based incentive contracts.

Abstract Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux in NPC1 cells resulted in mitochondrial dysfunction due to impairment of mitophagy, leading to the depletion of both the reduced and oxidised forms of NAD as identified via metabolic profiling. Consequently, exhaustion of the NAD pools triggered mitochondrial depolarisation and apoptotic cell death. Our chemical screening identified two FDA-approved drugs, celecoxib and memantine, as autophagy activators which effectively restored autophagic flux, NAD levels, and cell viability of NPC1 cells. Of biomedical relevance, either pharmacological rescue of the autophagy deficiency or NAD precursor supplementation restored NAD levels and improved the viability of NPC1 patient fibroblasts and induced pluripotent stem cell (iPSC)-derived cortical neurons. Together, our findings identify the autophagy-NAD axis as a mechanism of cell death and a target for therapeutic interventions in NPC1 disease, with a potential relevance to other neurodegenerative disorders.

Young children with visual impairment and their families often require specialized assistance through early intervention to develop adaptive routines, cues, and environmental settings during mealtimes and other daily tasks. There is little empirical data in the area of mealtime routines available to support families of young children with visual impairment, and the need for research-based interventions is great. The purpose of this initial needs assessment survey was to gather information as little is already known about what teachers of students with visual impairment trained in early intervention (TSVI-EIs) and other early interventionists who work with infants and toddlers with visual impairment already know about the development of independent mealtime skills. The results of this survey indicate that early intervention professionals would like additional opportunities to learn about mealtime routine strategies for young children with visual impairment, confirm their current experiences and knowledge, and identify additional training and resources.

Objectives The use of digital technology in surgery is increasing rapidly, with a wide array of new applications from presurgical planning to postsurgical performance assessment. Understanding the clinical and economic value of these technologies is vital for making appropriate health policy and purchasing decisions. We explore the potential value of digital technologies in surgery and produce expert consensus on how to assess this value.Design A modified Delphi and consensus conference approach was adopted. Delphi rounds were used to generate priority topics and consensus statements for discussion.Setting and participants An international panel of 14 experts was assembled, representing relevant stakeholder groups: clinicians, health economists, health technology assessment experts, policy-makers and industry.Primary and secondary outcome measures A scoping questionnaire was used to generate research questions to be answered. A second questionnaire was used to rate the importance of these research questions. A final questionnaire was used to generate statements for discussion during three consensus conferences. After discussion, the panel voted on their level of agreement from 1 to 9; where 1=strongly disagree and 9=strongly agree. Consensus was defined as a mean level of agreement of >7.Results Four priority topics were identified: (1) how data are used in digital surgery, (2) the existing evidence base for digital surgical technologies, (3) how digital technologies may assist surgical training and education and (4) methods for the assessment of these technologies. Seven consensus statements were generated and refined, with the final level of consensus ranging from 7.1 to 8.6.Conclusion Potential benefits of digital technologies in surgery include reducing unwarranted variation in surgical practice, increasing access to surgery and reducing health inequalities. Assessments to consider the value of the entire surgical ecosystem holistically are critical, especially as many digital technologies are likely to interact simultaneously in the operating theatre.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

The current study aims to provide an in-depth analysis and extension of the Environmental Stress Hypothesis (ESH) framework, focusing on the complex interplay between poor motor skills and internalising problems like anxiety and depression. Using an integrative research review methodology, this study synthesises findings from 38 articles, both empirical and theoretical, building upon previous foundational works. The hypothesis posits that poor motor skills serve as a primary stressor, leading to internalising problems through various secondary stressors. A rigorous comparison of data was conducted, considering study design, findings, and methodologies—while exploring variables such as age, sex, and comorbidities. The study also enhances the ESH framework by including intrapersonal stressors and introducing resource buffers, including optimism and familial support as additional influencing factors. This multi-level approach yields a more nuanced and comprehensive ESH framework, highlighting the need for future studies to consider variables that intersect across multiple domains and how the relationship between poor motor skills and internalising problems may vary across different life stages.

Candida auris is an emerging fungal pathogen that typically affects patients in healthcare settings. Data on C. auris cases in correctional facilities are limited but are needed to guide public health recommendations. We describe cases and challenges of providing care for 13 patients who were transferred to correctional facilities during January 2020–December 2022 after having a positive C. auris specimen. All patients had positive specimens identified while receiving inpatient care at healthcare facilities in geographic areas with high C. auris prevalence. Correctional facilities reported challenges managing patients and implementing prevention measures; those challenges varied by whether patients were housed in prison medical units or general population units. Although rarely reported, C. auris cases in persons who are incarcerated may occur, particularly in persons with known risk factors. Measures to manage cases and prevent C. auris spread in correctional facilities should address setting-specific challenges in healthcare and nonhealthcare correctional environments.

Abstract Introduction The efficacy of intravenous cerebral Cone Beam Computed Tomography (IV CBCT) is well established; however, image quality has only ever been authenticated by subjective evaluation. The aim of this study was to quantify the factors pertinent to achieving consistent and optimal image quality when performing IV CBCT. Methods Between 1 March 2021 and 30 October 2022, 79 patients received IV CBCT. These candidates were divided into three main acquisition field size categories (22/32, 42 and 48 cm) according to the clinical indication. The images were analysed using both a quantitative assessment and a subjective evaluation. Here, a comparison of Hounsfield units (HUs), signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR) and noise index was conducted for each study and compared relative to the acquisition field size. The subjective analysis was performed in a non‐blinded fashion where the diagnostic value (DV) of the exam was determined according to a graded scale. A phantom analysis for each of the acquisition field sizes was conducted and modulation transfer function (MTF) graphed. Results Significantly higher HU, SNR, CNR and lower noise indices were achieved with the 42‐cm protocol than the 22/32 and 48‐cm protocols. Here a greater DV was also reported. The MTF demonstrates marginally improved spatial resolution for the 22‐cm protocol, but this is near equivocal for the 32‐, 42 and 48‐cm protocols. Conclusion The use of larger acquisition field sizes provides improved image quality when performing IV CBCT as an alternative to intra‐arterial (IA) CBCT.

Abstract Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).

ABSTRACTBackground: Governmental and non-governmental organizations across medical, legal, and psychosocial sectors providing care to survivors of gender-based violence (GBV) and their families rapidly digitalized services during the COVID-19 pandemic. GBV prevention/response services working with women and children who are forcibly displaced and/or living in low-and-middle income countries (LMIC) were no exception to the rapid digitalization trend. Literature is lacking a critical synthesis of best practices and lessons learned since digitalization replaced major operations involved in GBV prevention/response.Objective: This research qualitatively investigated how GBV service providers, located in a range of socio-political settings, navigated the process of digitalizing GBV prevention/response during the COVID-19 crisis.Method: Semi-structured key informant interviews (KII) with GBV service providers in varied sectors were implemented virtually (2020–2021) in Brazil, Guatemala, Iraq, and Italy (regarding forcibly displaced women/girls for the latter). Participants were recruited using purposive and snowball sampling. Interview guides covered a range of topics: perceived changes in violence and service provision, experiences with virtual services, system coordination, and challenges. The KIIs were conducted in Portuguese, Spanish, Arabic, and Italian. Interviews were audio-recorded, transcribed, and translated into English. The research team conducted thematic analysis within and between countries using a structured codebook of data driven and theory driven codes.Results: Major themes concerned the: (1) spectrum of services that were digitalized during the COVID-19 crisis; (2) gender digital divide as a barrier to equitable, safe, and effective service digitalization; (3) digital violence as an unintended consequence of increased digitalization across social/public services.Conclusion: Digitalization is a balancing act with respect to (1) the variety of remotely-delivered services that are possible and (2) the access/safety considerations related to the gender digital divide and digital violence.

Purpose: Many studies have found a correlation between overall usage rates of nonmainstream forms and reading scores, but less is known about which dialect differences are most predictive. Here, we consider different methods of characterizing African American English use from existing assessments and examine which methods best predict literacy achievement. Method: Kindergarten and first-grade students who speak African American English received two assessments of dialect use and two assessments of decoding at the beginning and end of the school year. Item-level analyses of the dialect-use assessments were used to compute measures of dialect usage: (a) an overall feature rate measure based on the Diagnostic Evaluation of Language Variation-Screening Test, (b) a subscore analysis of the Diagnostic Evaluation of Language Variation-Screening Test based on items that pattern together, (c) an alternative assessment where children repeat and translate sentences, and (d) "repertoire" measures based on a categorical distinction of whether a child used a particular feature of mainstream American English. Results: Models using feature rate measures provided better data--model fit than those with repertoire measures, and baseline performance on a sentence repetition task was a positive predictor of reading score at the end of the school year. For phonological subscores, change from the beginning to end of the school year predicted reading at the end of the school year, whereas baseline scores were most predictive for grammatical subscores. Conclusions: The addition of a sentence imitation task is useful for understanding a child's dialect and anticipating potential areas for support in early literacy. We observed some support for the idea that morphological dialect differences (i.e., irregular verb morphology) have a particularly close tie to later literacy, but future work will be necessary to confirm this finding.