Artificial intelligence and medical education: application in classroom instruction and student assessment using a pharmacology & therapeutics case study.

BACKGROUND: Artificial intelligence (AI) tools are designed to create or generate content from their trained parameters using an online conversational interface. AI has opened new avenues in redefining the role boundaries of teachers and learners and has the potential to impact the teaching-learning process. METHODS: In this descriptive proof-of- concept cross-sectional study we have explored the application of three generative AI tools on drug treatment of hypertension theme to generate: (1) specific learning outcomes (SLOs); (2) test items (MCQs- A type and case cluster; SAQs; OSPE); (3) test standard-setting parameters for medical students. RESULTS: Analysis of AI-generated output showed profound homology but divergence in quality and responsiveness to refining search queries. The SLOs identified key domains of antihypertensive pharmacology and therapeutics relevant to stages of the medical program, stated with appropriate action verbs as per Bloom's taxonomy. Test items often had clinical vignettes aligned with the key domain stated in search queries. Some test items related to A-type MCQs had construction defects, multiple correct answers, and dubious appropriateness to the learner's stage. ChatGPT generated explanations for test items, this enhancing usefulness to support self-study by learners. Integrated case-cluster items had focused clinical case description vignettes, integration across disciplines, and targeted higher levels of competencies. The response of AI tools on standard-setting varied. Individual questions for each SAQ clinical scenario were mostly open-ended. The AI-generated OSPE test items were appropriate for the learner's stage and identified relevant pharmacotherapeutic issues. The model answers supplied for both SAQs and OSPEs can aid course instructors in planning classroom lessons, identifying suitable instructional methods, establishing rubrics for grading, and for learners as a study guide. Key lessons learnt for improving AI-generated test item quality are outlined. CONCLUSIONS: AI tools are useful adjuncts to plan instructional methods, identify themes for test blueprinting, generate test items, and guide test standard-setting appropriate to learners' stage in the medical program. However, experts need to review the content validity of AI-generated output. We expect AIs to influence the medical education landscape to empower learners, and to align competencies with curriculum implementation. AI literacy is an essential competency for health professionals.

Ultrasound assessment of humeral shaft nonunion risk: a feasibility and proof of concept study.

PURPOSE: To determine the feasibility and reliability of ultrasound in the assessment of humeral shaft fracture healing and estimate the accuracy of 6wk ultrasound in predicting nonunion. METHODS: Twelve adults with a non-operatively managed humeral shaft fracture were prospectively recruited and underwent ultrasound scanning at 6wks and 12wks post-injury. Seven blinded observers evaluated sonographic callus appearance to determine intra- and inter-observer reliability. Nonunion prediction accuracy was estimated by comparing images for patients that united (n = 10/12) with those that developed a nonunion (n = 2/12). RESULTS: The mean scan duration was 8 min (5-12) and all patients tolerated the procedure. At 6wks and 12wks, sonographic callus (SC) was present in 11 patients (10 united, one nonunion) and sonographic bridging callus (SBC) in seven (all united). Ultrasound had substantial intra- (weighted kappa: 6wk 0.75; 12wk 0.75) and inter-observer reliability (intraclass correlation coefficient: 6wk 0.60; 12wk 0.76). At 6wks, the absence of SC demonstrated sensitivity 50%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91% in nonunion prediction (overall accuracy 92%). The absence of SBC demonstrated sensitivity 100%, specificity 70%, PPV 40% and NPV 100% in nonunion prediction (overall accuracy 75%). Of three patients at risk of nonunion (Radiographic Union Score for HUmeral fractures < 8), one had SBC on 6wk ultrasound (that subsequently united) and the others had non-bridging/absent SC (both developed nonunion). CONCLUSIONS: Ultrasound assessment of humeral shaft fracture healing was feasible, reliable and may predict nonunion. Ultrasound could be useful in defining nonunion risk among patients with reduced radiographic callus formation.

Comparative Evaluation of a Lower-Dose CBCT Acquisition Protocol for Preoperative Implant Site Assessment in Dry Human Skulls: A Proof-of-Concept Study.

Restoration of edentulous sites with dental implants is increasingly becoming a popular choice. Cross-sectional 3-dimensional imaging using cone-beam computed tomography (CBCT) provides a better depiction of the implant site to help the clinician plan the procedure better. In spite of the advantages, radiation dose will always remain a concern. The evolution of lower-dose protocols is ongoing, but whether those acquisition protocols yield comparable diagnostic information is still not well established. The objective of this study was to evaluate the diagnostic efficacy of a low-dose, 180° rotational CBCT acquisition protocol for evaluating a potential implant site in comparison with a conventional 360° rotational acquisition. Ten dentate and partially edentulous dry human skulls providing 82 randomized implant sites-40 in the maxilla and 42 in the mandible-were chosen for this study. Each skull was imaged using a 360° and a 180° rotational acquisition on a J. Morita Accuitomo CBCT scanner. Evaluation of cortical and trabecular bone, height, width, and proximity to critical structures, such as the inferior alveolar nerve canal and the maxillary sinus, were measured. An oral surgeon and an oral radiologist rated the diagnostic efficacy of the scans by evaluating the above characteristics. Statistical evaluation of the data with linear regression showed significant agreement between both protocol measurements. Kappa analyses yielded a good interobserver agreement. In this proof-of-concept study, CBCT imaging using the lower-dose, modified arc, and 180° acquisition protocol shows comparable results to the conventional 360° protocol for preoperative implant assessment.

A proof of concept study of promotive, mixed, and risk effects using the SAVRY assessment tool items with youth with sexual offenses.

There is currently a lack of consensus about the nature of strengths in forensic assessments. With 273 justice-involved male youth and a fixed 3-year follow-up, this study adopted the approach of Farrington and colleagues to investigating the nature of associations between trichotomized variables, representing risks and strengths, and outcomes using pairs of odds ratios (ORs) and percentage point changes from base rates. Items from the Structured Assessment of Violence Risk in Youth (SAVRY), a structured professional judgment tool used to assess risk and protective factors in justice-involved youth, were employed for this purpose. In the literature, the accuracy of SAVRY summed totals for its Risk Factor item sets (each item rated using a trichotomy) has been generally in the moderate range in predicting future violence. But the total for its summed Protective Factor items (each rated using a dichotomy) has been less consistently encouraging. In this study, contrary to their labels, the majority of SAVRY Risk and Protective Factors (rated using trichotomies) exerted a risk effect at one end of their trichotomy (risk item ratings of 2, protective item ratings of 0) and a promotive effect at the other end (risk item ratings of 0, protective factor ratings of 2) for a new violent (including sexual) offense and any new offense. Subsets of items conservatively weighted using ORs (capturing risk and strength) were statistically significantly more accurate in predicting outcomes than their originally rated counterpart subsets. Implications for understanding the nature of strengths and for applied assessment practices are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept study.

BACKGROUND: Coronary microvascular obstruction also known as no-reflow phenomenon is a major issue during myocardial infarction that bears important prognostic implications. Alterations of the microvascular network remains however challenging to assess as there is no imaging modality in the clinics that can image directly the coronary microvascular vessels. Ultrasound Localization Microscopy (ULM) imaging was recently introduced to map microvascular flows at high spatial resolution (∼10 µm). In this study, we developed an approach to image alterations of the microvascular coronary flow in ex vivo perfused swine hearts. METHODS: A porcine model of myocardial ischemia-reperfusion was used to obtain microvascular coronary alterations and no-reflow. Four female hearts with myocardial infarction in addition to 6 controls were explanted and placed immediately in a dedicated preservation and perfusion box manufactured for ultrasound imaging. Microbubbles (MB) were injected into the vasculature to perform Ultrasound Localization Microscopy (ULM) imaging and a linear ultrasound probe mounted on a motorized device was used to scan the heart on multiple slices. The coronary microvascular anatomy and flow velocity was reconstructed using dedicated ULM algorithms and analyzed quantitatively. FINDINGS: We were able to image the coronary microcirculation of ex vivo swine hearts at a resolution of tens of microns and measure flow velocities ranging from 10 mm/s in arterioles up to more than 200 mm/s in epicardial arteries. Under different aortic perfusion pressures, we measured in large arteries of a subset of control hearts an increase of flow velocity from 31 ± 11 mm/s at 87 mmHg to 47 ± 17 mm/s at 132 mmHg (N = 3 hearts, P < 0.05). This increase was compared with a control measurement with a flowmeter in the aorta. We also compared 6 control hearts to 4 hearts in which no-reflow was induced by the occlusion and reperfusion of a coronary artery. Using average MB velocity and average density of MB per unit of surface as two ULM quantitative markers of perfusion, we were able to detect areas of coronary no-reflow in good agreement with a control anatomical pathology analysis of the cardiac tissue. In the no-reflow zone, we measured an average perfusion of 204 ± 305 MB/mm2 compared to 3182 ± 1302 MB/mm2 in the surrounding re-perfused area. INTERPRETATION: We demonstrated this approach can directly image and quantify coronary microvascular obstruction and no-reflow on large mammal perfused hearts. This is a first step for noninvasive, quantitative and affordable assessment of the coronary microcirculation function and particularly coronary microvascular anatomy in the infarcted heart. This approach has the potential to be extended to other clinical situations characterized by microvascular dysfunction. FUNDING: This study was supported by the French National Research Agency (ANR) under ANR-21-CE19-0002 grant agreement.

Monte Carlo based continuous aperture optimization for VMAT on conventional and MR-linacs: A proof of concept.

BACKGROUND: Currently, the commercial treatment planning systems for magnetic-resonance guided linear accelerators (MR-linacs) only support step-and-shoot intensity-modulated radiation therapy (IMRT). However, recent studies have shown the feasibility of delivering arc therapy on MR-linacs, which is expected to improve dose distributions and delivery speed. By accurately accounting for the electron return effect in the presence of a magnetic field, a Monte Carlo (MC) algorithm is ideally suited for the inverse treatment planning of this technique. PURPOSE: We propose a novel MC-based continuous aperture optimization (MCCAO) algorithm for volumetric modulated arc therapy (VMAT), including applications to VMAT on MR-linacs and trajectory-based VMAT. A unique feature of MCCAO is that the continuous character of gantry rotation and multileaf collimator (MLC) motion is accounted for at every stage of the optimization. METHODS: The optimization process uses a multistage simulation of 4D dose distribution. A phase space is scored at the top surface of the MLC and the energy deposition of each particle history is mapped to its position in this phase space. A progressive sampling method is used, where both MLC leaf positions and monitor unit (MU) weights are randomly changed, while respecting the linac mechanical limits. Due to the continuous nature of the leaf motion, such changes affect not only a single control point, but propagate to the adjacent ones as well, and the corresponding dose distribution changes are accounted for. A dose-volume cost function is used, which includes the MC statistical uncertainty. RESULTS: We applied our optimization technique to various treatment sites, using standard and flattening-filter-free (FFF) 6 MV beam models, with and without a 1.5 T magnetic field. MCCAO generates deliverable plans, whose dose distributions are in good agreement with measurements on ArcCHECK and stereotactic radiosurgery End-To-End Phantom. CONCLUSIONS: We show that the novel MCCAO method generates VMAT plans that meet clinical objectives for both conventional and MR-linacs.

Promoting health and social equity through family navigation to prevention and early intervention services: a proof of concept study.

BACKGROUND: Health and social inequality are associated with multiple adverse childhood experiences including poverty, mental illness, and child maltreatment. While effective interventions currently exist for many health and social problems, large segments of the population experience barriers accessing needed services. In alignment with broader public health efforts to reduce health and social inequality in one state in the U.S.A., the current study describes the development and formative evaluation of a brief, low cost, portable model of prevention-oriented family service navigation called Navigate Your Way. METHODS: Caregivers of children experiencing significant unmet health or social service needs were recruited to the study. Participants completed an initial and closing telephone interview which included measures of past and current family health and social service utilization, service barriers, parenting stress, and child internalizing/externalizing behaviors. Between interviews participants created a family service plan and received 10 weeks of telephone and web-mediated family navigation, at which time process and fidelity of implementation data were collected. Frequency and descriptive statistics are provided for participant demographic characteristics, service barriers, intervention engagement, and primary and secondary study outcomes. Paired samples t-tests examined changes in study outcomes between initial and closing telephone interviews. RESULTS: Thirty two caregivers enrolled, twenty-nine completed the study. The age range was 20-59 (M = 39.5, SD = 10.0). The majority identified as female (96.9%, n = 31), racial/ethnic minority (56.2%, n = 18), and reported an average 10 barriers to care (M = 10.4, SD = 4.1). The most frequently reported service needs were mental health care, housing, food security, transportation, and health insurance. The mean duration of intervention delivery was 83 days. Most participants (82.8%, n = 24) were connected to one or more health or social services. Caregivers reported significant improvements to youth internalizing behaviors (d = 2.5, p = .05) and high levels of overall satisfaction with the navigation approach. CONCLUSION: Telephone and web-mediated service navigation is a feasible and practical approach to supporting families in rapidly connecting to health and social care. Future research investigating the efficacy and implementation of Navigate Your Way in routine settings is indicated.

Psycho-cognitive assessment and quality of life in older adults with chronic obstructive pulmonary disease-carrying the rs4713916 gene polymorphism (G/A) of gene FKBP5 and response to pulmonary rehabilitation: a proof of concept study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extra-pulmonary multi-morbidity including depression, anxiety and cognitive disorders. Several studies investigated the association of the FKBP5 gene polymorphisms with susceptibility to anxiety, depression, and behavioral disorders. The FKBP5 gene codifies the FKBP51 protein which modulates the glucocorticoid receptor in the adaptive stress response. Genetic variants of the FKBP5 gene have been associated to a higher risk of developing mental disorders. We analyzed the association of genetic variants and stress exposure investigating the susceptibility to psychological distress and the impact on cognitive balance and quality of life (QoL) of COPD patients carrying the rs4713916 polymorphism (G/A) and we examined its association, with COPD rehabilitative outcomes. MATERIALS AND METHODS: A pilot study evaluated cognitive, psychological, clinical alterations/disorders, QoL, and coping strategies in 70 older adults with COPD, undergoing pulmonary rehabilitation, stratified according to the FKBP5 rs4713916 genotype (GG or GA). RESULTS: Carriers of rs4713916 polymorphisms (G/A) show better cognitive performances, a higher degree of independence in the daily living activities, better QoL, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorders, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant, anti-psychotic, hypnotic-sedative drugs. No difference was found in the number of comorbidities. CONCLUSION: These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical, psychological and behavioral features of COPD patients.

Temporomandibular disorders cases with high-impact pain are more likely to experience short-term pain fluctuations.

Temporomandibular disorders (TMD) patients can present clinically significant jaw pain fluctuations which can be debilitating and lead to poor global health. The Graded Chronic Pain Scale evaluates pain-related disability and its dichotomous grading (high/low impact pain) can determine patient care pathways and in general high-impact pain patients have worse treatment outcomes. Individuals with low-impact TMD pain are thought to have better psychosocial functioning, more favorable disease course, and better ability to control pain, while individuals with high-impact pain can present with higher levels of physical and psychological symptoms. Thereby, there is reason to believe that individuals with low- and high-impact TMD pain could experience different pain trajectories over time. Our primary objective was to determine if short-term jaw pain fluctuations serve as a clinical marker for the impact status of TMD pain. To this end, we estimated the association between high/low impact pain status and jaw pain fluctuations over three visits (≤ 21-day-period) in 30 TMD cases. Secondarily, we measured the association between jaw pain intensity and pressure pain thresholds (PPT) over the face and hand, the latter measurements compared to matched pain-free controls (n = 17). Jaw pain fluctuations were more frequent among high-impact pain cases (n = 15) than low-impact pain cases (n = 15) (OR 5.5; 95% CI 1.2, 26.4; p value = 0.033). Jaw pain ratings were not associated with PPT ratings (p value > 0.220), suggesting different mechanisms for clinical versus experimental pain. Results from this proof-of-concept study suggest that targeted treatments to reduce short-term pain fluctuations in high-impact TMD pain is a potential strategy to achieve improved patient perception of clinical pain management outcomes.

Telementoring Feasibility Using a Novel Low-cost Lazy Glass Microsurgical Simulator: A "Proof of Concept" Experimental Study.

BACKGROUND: In order to mitigate the challenges in microsurgical skill acquisition and training, especially in the COVID-19 era, we devised a novel microsurgical telementoring protocol for imparting microsurgical skill training in a socially distanced setting. We objectively analyzed its feasibility among neurosurgical trainees. METHODS: In a controlled experimental design, 8 residents at different stages of their tenure participated in a lazy glass microsurgical simulator-based telementoring exercise. Microsuturing with 4-0 silk, 10-0 nylon on silastic sheets, and eggshell peeling tasks were performed by the residents prior to and after a telementoring session by a panel of 4 neurosurgical experts. Impact of telementoring was assessed in terms of surgical accuracy, efficiency, and dexterity by providing objective (Performance score [PS]), subjective (Neurosurgery Education and Training School [NETS] score), and cumulative scores (CS). Subgroup analysis was performed to assess the impact at different stages of residency. RESULTS: PS, NETS score, and CS were significantly improved by telementoring sessions for 10-0 nylon micro-suturing (P < 0.001), and egg-hell peeling tasks (P < 0.01). PS and CS improved significantly (P = 0.01) after telementoring sessions for 4-0 silk microsuturing. Both pre- and post-training CS were similar across the 2 subgroups PGY 1-4 and PGY 5-6 (P > 0.05). CONCLUSIONS: Telementoring is a viable alternative for neurosurgical resident training in the COVID-19 era, where reduction in elective surgeries and social distancing norms preclude conventional teaching. Lazy glass microsurgical simulator-based structured telementoring protocol is a cost-effective tool to augment surgical proficiency and finesse, irrespective of stage of residency.

Self-reporting data assets and their representation in the pharmaceutical industry.

Standardizing data is crucial for preserving and exchanging scientific information. In particular, recording the context in which data were created ensures that information remains findable, accessible, interoperable, and reusable. Here, we introduce the concept of self-reporting data assets (SRDAs), which preserve data and contextual information. SRDAs are an abstract concept, which requires a suitable data format for implementation. Four promising data formats or languages are popularly used to represent data in pharma: JCAMP-DX, JSON, AnIML, and, more recently, the Allotrope Data Format (ADF). Here, we evaluate these four options in common use cases within the pharmaceutical industry using multiple criteria. The evaluation shows that ADF is the most suitable format for the implementation of SRDAs.

Photo-aging evaluation - In vitro biological endpoints combined with collagen density assessment with multi-photon microscopy.

BACKGROUND: Ultraviolet exposure has profound effect on the dermal connective tissue of human skin. OBJECTIVE: We aimed to develop and validate an evaluation method/methodology using a full-thickness reconstructed skin model, to assess the anti-photoaging efficacy of cosmetic ingredients and sunscreen formulas by blending multi relevant biological endpoints including the newly developed dermal collagen quantification method with Multi-photon microscopy. METHODS: The response of ex vivo human skin to UVA exposure was first characterized with multiphoton microscopy. Reconstructed full-thickness skin models was then used to reproduce the data and to create a proof-of-concept study by treating the models with sunscreen prototypes A or B, which differ on their UVA absorption properties, and systemic Vitamin C (Vit C). After exposure to UVA, the collagen density was quantified via multiphoton microscopy with automatic imaging processing. Histology, fibroblasts number, metalloprotease 1 (MMP1) secretion were also assessed. RESULTS: UVA exposure induced pronounced reduction in collagen density and increased MMP1 secretion within both ex vivo human skin and reconstructed skin. Histological damage and fibroblast disappearance was observed with reconstructed skin. Within the proof-of-concept study prototype B, possessing higher UVA filtration, gave better protection than prototype A on the UV associated biological markers, and association with Vit C boosted sunscreen formula efficacy. CONCLUSIONS: The photoaging evaluation method, consists of multi biological markers as well as dermal collagen quantification, is a relevant mean to assess the pre-clinical efficacy of anti-photoaging ingredients and sunscreen products. This approach is also beneficial for evaluating the efficacy of sunscreens and photoprotective ingredients.

A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion.

No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = - 0.874, P < 0.001), AST (R = - 0.812, P = 0.004) and ALT (R = - 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.

Development and Preliminary Feasibility of iByte4Health: A Mobile Health (mHealth) Pediatric Obesity Prevention Intervention to Engage Parents with Low-Income of Children 2-9 Years.

This research describes the development and preliminary feasibility of iByte4Health, a mobile health (mHealth) obesity prevention intervention designed for parents with a low-income of children 2-9 years of age. Study 1 (n = 36) presents findings from formative work used to develop the program. Study 2 (n = 23) presents a 2-week proof-of-concept feasibility testing of iByte4Health, including participant acceptability, utilization, and engagement. Based on Study 1, iByte4Health was designed as a text-messaging program, targeting barriers and challenges identified by parents of young children for six key obesity prevention behaviors: (1) snacking; (2) physical activity; (3) sleep; (4) sugary drinks; (5) fruit and vegetable intake; and (6) healthy cooking at home. In Study 2, participants demonstrated high program retention (95.7% at follow-up) and acceptability (90.9% reported liking or loving the program). Users were engaged with the program; 87.0% responded to at least one self-monitoring text message; 90.9% found the videos and linked content to be helpful or extremely helpful; 86.4% found text messages helpful or extremely helpful. iByte4Health is a community-informed, evidenced-based program that holds promise for obesity prevention efforts, especially for those families at the increased risk of obesity and related disparities. Future work is warranted to test the efficacy of the program.

Mucosal-associated invariant T (MAIT) cells, a new source of universal immune cells for chimeric antigen receptor (CAR)-cell therapy.

Treatment of hematological malignancies by autologous T cells expressing a chimeric antigen receptor (CAR) is a breakthrough in the field of cancer immunotherapy. As CAR-T cells are entering advanced phases of clinical development, there is a need to develop universal, ready-to-use products using immune cells from healthy donors, to reduce time to treatment, improve response rate and finally reduce the cost of production. Mucosal-associated invariant T cells (MAIT) are unconventional T cells which recognize microbial-derived riboflavin derivatives presented by the conserved MR1 molecule and are endowed with potent effector functions. Because they are not selected by classical MHC/peptide complexes and express a semi-invariant T cell receptor, MAIT cells do not mediate alloreactivity, prompting their use as a new source of universal effector cells for allogeneic CAR-T cell therapy without the need to inactivate their endogenous TCR. We produced CD19-CAR MAIT cells as proof-of-concept allowing subsequent head-to-head comparison with currently used CD19-CAR T cells. We demonstrated their anti-tumor efficacy in vitro and their capacity to engraft without mediating GVHD in preclinical immunodeficient mouse models. Universal, off-the-shelf CAR-MAIT cells could provide a suitable alternative to current autologous CAR-T cells to treat patients regardless of HLA disparity, without production delay, enabling a cost-effective manufacturing model for large-scale clinical application.

Using allocative efficiency analysis to inform health benefits package design for progressing towards Universal Health Coverage: Proof-of-concept studies in countries seeking decision support.

BACKGROUND: Countries are increasingly defining health benefits packages (HBPs) as a way of progressing towards Universal Health Coverage (UHC). Resources for health are commonly constrained, so it is imperative to allocate funds as efficiently as possible. We conducted allocative efficiency analyses using the Health Interventions Prioritization tool (HIPtool) to estimate the cost and impact of potential HBPs in three countries. These analyses explore the usefulness of allocative efficiency analysis and HIPtool in particular, in contributing to priority setting discussions. METHODS AND FINDINGS: HIPtool is an open-access and open-source allocative efficiency modelling tool. It is preloaded with publicly available data, including data on the 218 cost-effective interventions comprising the Essential UHC package identified in the 3rd Edition of Disease Control Priorities, and global burden of disease data from the Institute for Health Metrics and Evaluation. For these analyses, the data were adapted to the health systems of Armenia, Côte d'Ivoire and Zimbabwe. Local data replaced global data where possible. Optimized resource allocations were then estimated using the optimization algorithm. In Armenia, optimized spending on UHC interventions could avert 26% more disability-adjusted life years (DALYs), but even highly cost-effective interventions are not funded without an increase in the current health budget. In Côte d'Ivoire, surgical interventions, maternal and child health and health promotion interventions are scaled up under optimized spending with an estimated 22% increase in DALYs averted-mostly at the primary care level. In Zimbabwe, the estimated gain was even higher at 49% of additional DALYs averted through optimized spending. CONCLUSIONS: HIPtool applications can assist discussions around spending prioritization, HBP design and primary health care transformation. The analyses provided actionable policy recommendations regarding spending allocations across specific delivery platforms, disease programs and interventions. Resource constraints exacerbated by the COVID-19 pandemic increase the need for formal planning of resource allocation to maximize health benefits.

High-throughput low-cost nl-qPCR for enteropathogen detection: A proof-of-concept among hospitalized patients in Bangladesh.

BACKGROUND: Diarrheal disease is a leading cause of morbidity and mortality globally, especially in low- and middle-income countries. High-throughput and low-cost approaches to identify etiologic agents are needed to guide public health mitigation. Nanoliter-qPCR (nl-qPCR) is an attractive alternative to more expensive methods yet is nascent in application and without a proof-of-concept among hospitalized patients. METHODS: A census-based study was conducted among diarrheal patients admitted at two government hospitals in rural Bangladesh during a diarrheal outbreak period. DNA was extracted from stool samples and assayed by nl-qPCR for common bacterial, protozoan, and helminth enteropathogens as the primary outcome. RESULTS: A total of 961 patients were enrolled; stool samples were collected from 827 patients. Enteropathogens were detected in 69% of patient samples; More than one enteropathogen was detected in 32%. Enteropathogens most commonly detected were enteroaggregative Escherichia coli (26.0%), Shiga toxin-producing E.coli (18.3%), enterotoxigenic E. coli (15.5% heat stable toxin positive, 2.2% heat labile toxin positive), Shigella spp. (14.8%), and Vibrio cholerae (9.0%). Geospatial analysis revealed that the median number of pathogens per patient and the proportion of cases presenting with severe dehydration were greatest amongst patients residing closest to the study hospitals." CONCLUSIONS: This study demonstrates a proof-of-concept for nl-qPCR as a high-throughput low-cost method for enteropathogen detection among hospitalized patients.