Distinct Patterns of Liver Chemistry Changes in Pediatric Acute Hepatitis of Unknown Origin and COVID-19 Patients: A Systematic Review.

In 2021 and 2022, there were noted to be clusters of pediatric acute hepatitis of unknown origin (AHUO) occurring across the globe. While there was not necessarily a global increase in cases, understanding the pattern of liver injury in AHUO is crucial to properly identify cases of this unexplained phenomenon, especially since it occurred simultaneously with a global resurgence of COVID-19. The objective of this study was to contrast the patterns in liver-relevant biochemical data from COVID-19 patients and AHUO. Studies reporting liver chemistries for cases of AHUO and COVID-19 were identified by a systematic review and search of the literature. For each case, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, and international normalized ratio (INR) levels were extracted as available. These were normalized to multiples of the upper limit of normal by patient age. There were statistically significant greater elevations of ALT and AST in patients with AHUO than in those with COVID-19. Only a subset of patients with COVID-19 had an AST or ALT greater than the normal range. INR elevation could be substantial for both conditions but was also statistically higher in the AHUO group. Liver chemistry changes were not statistically correlated with age. The pattern of liver chemistry changes between AHUO and COVID-19 have some distinctions, which suggests that AHUO is not a phenomenon driven primarily by SARS-CoV-2 infection alone. Differentiating AHUO and COVID-19 would be challenging based on patterns of liver chemistry changes alone.

Application of microphysiological systems for nonclinical evaluation of cell therapies.

Microphysiological systems (MPS) are gaining broader application in the pharmaceutical industry but have primarily been leveraged in early discovery toxicology and pharmacology studies with small molecules. The adoption of MPS offers a promising avenue to reduce animal use, improve in-vitro-to-in-vivo translation of pharmacokinetics/pharmacodynamics and toxicity correlation, and provide mechanistic understanding of model species suitability. While MPS have demonstrated utility in these areas with small molecules and biologics, cell therapeutic MPS models in drug development have not been fully explored, let alone validated. Distinguishing features of MPS, including long-term viability and physiologically relevant expression of functional enzymes, receptors, and pharmacological targets make them attractive tools for nonclinical characterization. However, there is currently limited published evidence of MPS being utilized to study the disposition, metabolism, pharmacology, and toxicity profiles of cell therapies. This review provides an industry perspective on the nonclinical application of MPS on cell therapies, first with a focus on oncology applications followed by examples in regenerative medicine.

Microphysiological systems (MPS) are advanced cell models, applied in the pharmaceutical industry to characterize novel therapies. While their application in studies of small molecule therapies has been very successful, the use of these models to study cell therapies has been limited. Cell therapies consist of cells and are living drugs, often with complex biological mechanisms of action, which can be very challenging to study. However, MPS have several features that make them attractive for studying cell therapies, including possibilities for longer-term studies and the ability to mimic physiologically relevant biological functions. MPS can mimic complex biological systems and processes, as such, the adoption of MPS offers a promising avenue to reduce the use of animals in the characterization of novel therapies. This review provides an industry perspective on current challenges and highlights opportunities for using MPS in the development of cell therapies.

The Influence of Talar Displacement on Articular Contact Mechanics: A 3D Finite Element Analysis Study Using Weightbearing Computed Tomography.

BACKGROUND: Talar displacement is considered the main predictive factor for poor outcomes and the development of post-traumatic osteoarthritis after ankle fractures. Isolated lateral talar translation, as previously studied by Ramsey and Hamilton using carbon powder imprinting, does not fully replicate the multidirectional joint subluxations seen in ankle fractures. The purpose of this study was to analyze the influence of multiple uniplanar talar displacements on tibiotalar contact mechanics utilizing weightbearing computed tomography (WBCT) and finite element analysis (FEA). METHODS: Nineteen subjects (mean age = 37.6 years) with no history of ankle surgery or injury having undergone WBCT arthrogram (n = 1) and WBCT without arthrogram (n = 18) were included. Segmentation of the WBCT images into 3D simulated models of bone and cartilage was performed. Three-dimensional (3D) multiple uniplanar talar displacements were simulated to investigate the respective influence of various uniaxial displacements (including lateral translation, anteroposterior translation, varus-valgus angulation, and external rotation) on the tibiotalar contact mechanics using FEA. Tibiotalar peak contact stress and contact area were modeled for each displacement and its gradations. RESULTS: Our modeling demonstrated that peak contact stress of the talus and tibia increased, whereas contact area decreased, with incremental displacement in all tested directions. Contact stress maps of the talus and tibia were computed for each displacement demonstrating unique patterns of pressure derangement. One millimeter of lateral translation resulted in 14% increase of peak talar contact pressure and a 3% decrease in contact area. CONCLUSION: Our model predicted that with lateral talar translation, there is less noticeable change in tibiotalar contact area compared with prior studies whereas external rotation greater than 12 degrees had the largest effect on peak contact stress predictions. LEVEL OF EVIDENCE: Level V, computational simulation study.

Hallux Valgus Bunion Splint: Surgical Dressing Technique.

BACKGROUND: Hallux valgus is a common condition with a complex etiology resulting in numerous treatment options. Recurrence of the deformity can occur following correction. Surgical technique and possibly also postoperative care play a role in reducing recurrence rates. This article highlights a postoperative surgical dressing technique which allows for semirigid support during the immediate postoperative period. METHODS: A wooden tongue depressor placed along the medial border of the hallux comprises the primary support for the dressing. The rigidity of the tongue depressor allows for the hallux to be drawn toward the depressor, encouraging neutral alignment of the hallux. Dressings are removed 2 weeks postoperatively, with new dressings applied in similar fashion and maintained in place until 6 weeks postoperatively. RESULTS: Based upon our observations, our surgical dressing technique provides sufficient support following hallux valgus correction surgery while being straightforward to replicate without the need for frequent dressing changes. The dressing materials are of negligible cost and are typically readily available. No associated wound complications have been observed. CONCLUSIONS: We present an easily replicable and affordable option for postoperative hallux valgus correction surgical dressings. LEVELS OF EVIDENCE: Level V: Expert Opinion.

A systematic review of the proposed etiologies of the 2021-2022 outbreaks of pediatric acute hepatitis of unknown etiology.

In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for which various etiologies have been proposed by the literature. This study examines primary reports of pediatric AHUE cases and summarizes the proposed etiologies. This systematic review collected and evaluated published peer-reviewed articles, official data, and clinical reports of AHUE cases that met the WHO working case definition. 19 hypothesized etiologies for AHUE were identified from 36 sources, which fell into eight categories. While human adenovirus (HAdV) infection, viral infection, and immune-mediated responses were commonly suspected as causes of AHUE, no definitive etiology or epidemiological link has been established. However, recent evidence implicates adeno-associated virus-2 (AAV2) as a likely significant contributor. Conducting a comprehensive literature review following outbreaks is necessary for developing responsive strategies and protocols.

Experiences of engaging a death doula: qualitative interviews with bereaved family members.

Background: There has been an emerging trend of adopting a death doula, a non-medical advocate and guide for people at the end of life and their families. While there has been growing empirical research regarding the work of death doulas, no studies have been undertaken with the families who have engaged them. Objectives: To understand the experiences of families who used a death doula in terms of what they did for the patient and family; to understand the benefits and drawbacks of using a death doula; and to use family insight to determine cultural shifts towards death and dying, and what the death doula phenomenon tells us around our attitudes towards death and dying. Methods: We recruited and interviewed 10 bereaved family members to learn about their experiences using a death doula. This qualitative research took an interpretive phenomenological approach, and thematic analysis was used to analyse the data. Results: The most valuable attribute the families gained from death doulas was an increase in death literacy resulting in personal empowerment. Empowerment enabled positive end-of-life experiences for the family and personalised deaths for the patient. A novel finding was that the connections and knowledge shared between the death doula and family had a resonant effect, resulting in families being more comfortable with death and keen to share their knowledge with others. Therefore, family engagement of a death doula led to an increase in community awareness around death and dying. Conclusion: Family members' experience with a death doula was overwhelmingly positive, empowering them practically and emotionally to deliver the best end-of-life care. Empathy and sharing of knowledge by death doulas were valued by families and resulted in an increase in death literacy which provided families with opportunities to 'pay it forward'. Furthermore, the relationships formed between doulas and families have the potential for a lasting, resonant effect.

What are bereaved family members experience of using a death doula? To date, there are no research studies with a focus on family experiences using death doulas for end-of-life care. We interviewed 10 family members from Australia and the United States to understand what benefits death doulas provided, what complicating factors might be involved when engaging them and what value and impact they had on end-of-life care for families. The most valuable attribute the families' gained from death doulas was an increase in death literacy. There was a direct connection between this and a sense of empowerment for patients and families. Empowerment enabled positive end of life experiences for the family and personalised deaths for the patient.

Perceptions of Addiction Medications Within Collegiate Recovery Communities.

OBJECTIVES: Addiction medications (AM) are effective in improving recovery outcomes, but many barriers still exist that reduce their implementation among young adults. While the perception of AM has been explored within clinicians and counselors in many settings, it has not yet been documented within collegiate recovery communities (CRC). The aim of this brief report is to assess the acceptability and intent to use AM among students in recovery, and to evaluate the effect of attitudes, perceived AM effectiveness, and social norms on these outcomes. METHODS: Using the Theory of Planned Behavior, CRC students (N = 162; 44% female) within the United States completed an online survey. RESULTS: Results from a hierarchical linear model indicated that the perceived acceptance of AM use by important others was significantly related to the intent to use AM ( ß = 0.47, P < 0.01) and encourage others to use AM ( ß = 0.16, P < 0.05). Positive attitudes about AM predicted acceptability of AM use ( ß = 0.42, P < 0.01) and encouraging other CRC students to use AM ( ß = 0.38, P < 0.01). Perceived AM effectiveness was positively associated with acceptability ( ß = 0.36, P < 0.01) and encouragement of others ( ß = 0.27, P < 0.01). CONCLUSIONS: Results highlight the importance of promoting effectiveness, improving attitudes, and tapping social networks to increase AM use and acceptability among CRC students. Implications for CRC policy and programming are discussed.

Death doula working practices and models of care: the views of death doula training organisations.

BACKGROUND: The role of death doula has emerged in recent years, arguably as a result of overwhelming demands on carers, healthcare professionals and service providers in end-of-life care. Death doulas work independently without governing oversight and enact the role in various ways. The main driver of this evolving role is the organisations that train them. The aim of this study was to examine death doula training organisations' views with regard to DD business models, incorporating the death doula role into other existing models of care, and role enactment. METHODS: An electronic survey was administered to 15 death doula training organisations in 5 countries asking additionally that they disseminate the survey. Responses were received from 13 organisations, based in Australia (n = 4), the US (n = 4), Canada (n = 2), the UK (n = 1), Sweden (n = 1) and New Zealand (n = 1). This paper provides the qualitative findings from four open-text questions posed within the survey related to models of care. RESULTS: Qualitative data analysis was inductive, themes were determined in relation to: (1) standardised business model for death doulas, (2) death doulas incorporated into existing models of care or existing funding options, (3) death doulas who volunteer their services rather than charge money, and (4) role specialisation such as has occurred with birth doulas. CONCLUSIONS: The death doula role has the potential to be formally recognised in the future under national registration schemes, accompanied by death doula training required via certification. Until such time the death doula role will continue to evolve much as the birth doula role has, organically and unstructured. How and if death doulas are incorporated into existing models of health or social care remains to be seen as the organisations that train them push for independence, flexibility and fiscal independence.

Five-Factor Modified Frailty Index as a Predictor of Complications Following Total Ankle Arthroplasty.

INTRODUCTION: Ankle arthritis adversely affects patients' function and quality of life. Treatment options for end-stage ankle arthritis include total ankle arthroplasty (TAA). A 5-item modified frailty index (mFI-5) has predicted adverse outcomes following multiple orthopaedic procedures; this study evaluated its suitability as a risk-stratification tool in patients undergoing TAA. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed for patients undergoing TAA between 2011 and 2017. Bivariate and multivariate statistical analyses were performed to investigate frailty as a possible predictor of postoperative complications. RESULTS: In total, 1035 patients were identified. When comparing patients with an mFI-5 score of 0 versus ≥2, overall complication rates significantly increased from 5.24% to 19.38%, 30-day readmission rate increased from 0.24% to 3.1%, adverse discharge rate increased from 3.81% to 15.5%, and wound complications increased from 0.24% to 1.55%. After multivariate analysis, mFI-5 score remained significantly associated with patients' risk of developing any complication (P = .03) and 30-day readmission rate (P = .005). CONCLUSIONS: Frailty is associated with adverse outcomes following TAA. The mFI-5 can help identify patients who are at an elevated risk of sustaining a complication, allowing for improved decision-making and perioperative care when considering TAA. LEVELS OF EVIDENCE: III, Prognostic.

Learning Designers as Expert Evaluators of Usability: Understanding Their Potential Contribution to Improving the Universality of Interface Design for Health Resources.

User-based evaluation by end users is an essential step in designing useful interfaces. Inspection methods can offer an alternate approach when end-user recruitment is problematic. A Learning Designers' usability scholarship could offer usability evaluation expertise adjunct to multidisciplinary teams in academic settings. The feasibility of Learning Designers as 'expert evaluators' is assessed within this study. Two groups, healthcare professionals and Learning Designers, applied a hybrid evaluation method to generate usability feedback from a palliative care toolkit prototype. Expert data were compared to end-user errors detected from usability testing. Interface errors were categorised, meta-aggregated and severity calculated. The analysis found that reviewers detected N = 333 errors, with N = 167 uniquely occurring within the interface. Learning Designers identified errors at greater frequencies (60.66% total interface errors, mean (M) = 28.86 per expert) than other evaluator groups (healthcare professionals 23.12%, M = 19.25 and end users 16.22%, M = 9.0). Patterns in severity and error types were also observed between reviewer groups. The findings suggest that Learning Designers are skilled in detecting interface errors, which benefits developers assessing usability when access to end users is limited. Whilst not offering rich narrative feedback generated by user-based evaluations, Learning Designers complement healthcare professionals' content-specific knowledge as a 'composite expert reviewer' with the ability to generate meaningful feedback to shape digital health interfaces.

Assessing the current and desired levels of training and applied experiences in chronic disease prevention of students during medical school.

INTRODUCTION: Chronic diseases account for approximately 70% of deaths in the U.S. annually. Though physicians are uniquely positioned to provide behavior change counseling for chronic disease prevention, they often lack the necessary training and self-efficacy. This study examined medical student interest in receiving chronic disease prevention training as a formal part of their education as part of an effort to enhance their ability to provide guidance to patients in the future. METHODS: A 23-question, online survey was sent to all undergraduate medical students enrolled in a large medical education program. The survey assessed medical student interest in receiving training related to chronic disease prevention. Survey topics included student awareness of primary prevention programs, perceived importance of receiving training and applied experience in chronic disease prevention, and preferences for how and when to receive this training. RESULTS: Of 793 eligible medical students, 432 completed the survey (54.5%). Overall, 92.4% of students reported receiving formal training in physical activity, public health, nutrition, obesity, smoking cessation, and chronic diseases was of "very high" or "high" importance. Despite this level of importance, students most frequently reported receiving no or 1-5 h of formal training in a number of topics, including physical activity (35.4% and 47.0%, respectively) and nutrition (16.9% and 56.3%, respectively). The level of importance given to public health training was significantly greater across degree type (p = 0.0001) and future specialty (p = 0.03) for MD/MPH students and those interested in primary care, respectively. CONCLUSIONS: While medical students perceive chronic disease prevention as an important topic, most reported receiving little to no formal training. To address the growing prevalence of chronic disease across our society, programs schools should place greater emphasis on integrating training in physical activity, nutrition, and obesity-related content into the medical education curriculum.

Natural Death Versus Known Date-Of-Death: A Qualitative Study of Views on Voluntary Assisted Dying in an Online Course About Death.

The study aimed to describe views on Voluntary Assisted Dying (VAD), gleaned through qualitative analysis of participant responses to a set activity, run during the 2018 'Dying2Learn' Massive Open Online Course (MOOC). Data from 508 participants, most of whom identified as health professionals, were analysed using thematic content analysis, and themes generated. A large proportion of participants discussed their personal views related to VAD, specifically around choice, control, dignity, palliative care and dying at home, medical intervention, societal factors, the impact on those left behind, laws and regulations, dying 'naturally', advance care directives, and being in pain. In this study, participants had many different views on the act itself, often divisive, but also with common concepts such as respecting the choices and decisions of others.

An international survey of Death Doula training organizations: the views of those driving Death Doula training and role enactment.

Context: Death Doulas are working globally to provide non-medical end-of-life care. They have different training experiences and views on the role and whether it should be standardised. Objective: To seek the views of organisations responsible for training Death Doulas in order to determine what the drivers are behind this emerging role. Methods: We conducted an online survey with Death Doula training organisations in five countries utilising both a targeted and snowball approach. Qualitative analysis was undertaken with themes pre-determined (apriori) due to the nature of the survey categories. Results: In total, representatives from 13 organisations in Australia, New Zealand, Sweden, Canada, United Kingdom, and United States responded. The organisations had provided training for 0 to 20 years, with one just starting and another training birth doulas and now expanding. Owners and trainers hold an array of qualifications such as academic, medical, non-medical, and life experience. Curricula have usually been developed locally, and not always included pedagogical consideration, a strategic business model, nor mapping processes such as gap analysis. The organisations are run similarly, and curricula have several consistent topics but with distinctly different approaches. Trainers' views are also mixed about the way to proceed with registration of the Death Doula role. Conclusion: The contrasting views of training organisations explain much of the ambiguity of Death Doulas themselves regarding standardisation of registration, education and role enactment. If heading towards the ultimate goal of professionalisation of the role then a challenging path lies ahead with little in the way of agreement in what this would require.

Assessment of a 3D neural spheroid model to detect pharmaceutical-induced neurotoxicity.

Drug-induced neurotoxicity is a leading cause of safety-related attrition for therapeutics in clinical trials, often driven by poor predictivity of preclinical in vitro and in vivo models of neurotoxicity. Over a dozen different iPSC-derived 3D spheroids have been described in recent years, but their ability to predict neurotoxicity in patients has not been evaluated nor compared with the predictive power of nonclinical species. To assess the predictive capabilities of human iPSC-derived neural spheroids (microBrains), we used 84 structurally diverse pharmaceuticals with robust clinical and pre-clinical datasets with varying degrees of seizurogenic and neurodegenerative liability. Drug-induced changes in neural viability and phenotypic calcium bursts were assessed using 7 endpoints based on calcium oscillation profiles and cel-lular ATP levels. These endpoints, normalized by therapeutic exposure, were used to build logistic regression models to establish endpoint cutoffs and evaluate probability for clinical neurotoxicity. The neurotoxicity score calculated from the logistic regression model could distinguish neurotoxic from non-neurotoxic clinical molecules with a specificity as high as 93.33% and a sensitivity of 53.49%, demonstrating a very low false positive rate for the prediction of seizures, convulsions, and neurodegeneration. In contrast, nonclinical species showed a higher sensitivity (75%) but much lower specificity (30.4%). The neural spheroids demonstrated higher likelihood ratio positive and inverse likelihood ratio neg-ative values compared with nonclinical safety studies. This assay has the potential to be used as a predictive assay to detect neurotoxicity in early drug discovery, aiding in the early identification of compounds that eventually may fail due to neurotoxicity.

Current Therapeutic Landscape and Safety Roadmap for Targeting the Aryl Hydrocarbon Receptor in Inflammatory Gastrointestinal Indications.

Target modulation of the AhR for inflammatory gastrointestinal (GI) conditions holds great promise but also the potential for safety liabilities both within and beyond the GI tract. The ubiquitous expression of the AhR across mammalian tissues coupled with its role in diverse signaling pathways makes development of a "clean" AhR therapeutically challenging. Ligand promiscuity and diversity in context-specific AhR activation further complicates targeting the AhR for drug development due to limitations surrounding clinical translatability. Despite these concerns, several approaches to target the AhR have been explored such as small molecules, microbials, PROTACs, and oligonucleotide-based approaches. These various chemical modalities are not without safety liabilities and require unique de-risking strategies to parse out toxicities. Collectively, these programs can benefit from in silico and in vitro methodologies that investigate specific AhR pathway activation and have the potential to implement thresholding parameters to categorize AhR ligands as "high" or "low" risk for sustained AhR activation. Exploration into transcriptomic signatures for AhR safety assessment, incorporation of physiologically-relevant in vitro model systems, and investigation into chronic activation of the AhR by structurally diverse ligands will help address gaps in our understanding regarding AhR-dependent toxicities. Here, we review the role of the AhR within the GI tract, novel therapeutic modality approaches to target the AhR, key AhR-dependent safety liabilities, and relevant strategies that can be implemented to address drug safety concerns. Together, this review discusses the emerging therapeutic landscape of modalities targeting the AhR for inflammatory GI indications and offers a safety roadmap for AhR drug development.

Impact of the COVID-19 Pandemic on Funerals: Experiences of Participants in the 2020 Dying2Learn Massive Open Online Course.

A Massive-Open-Online-Course (MOOC) on death and dying (Dying2Learn) was offered in 2020, designed to build conversations about death as a natural part of life. In week 1, the content focused on how today's society engages with death through the language we use, humour, public mourning and funerals. This study investigated 2020 MOOC participants' responses to an online activity reflecting on funerals and memorials during the time of COVID-19. From this activity, n = 204 responses were analysed qualitatively. Themes included the positives and negatives of virtual funeral attendance (e.g. opportunity to have a way to participate when travel barriers existed, versus a sense of impersonal voyeurism); and the challenges related to the inability to physically comfort the bereaved due to physical distancing requirements. Comments made as part of this MOOC activity provide a unique insight into the community's experience of funeral changes necessitated by COVID-19, with important implications for the grieving process.

Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons.

Elucidation of predictive fluidic biochemical markers to detect and monitor chemical-induced neurodegeneration has been a major challenge due to a lack of understanding of molecular mechanisms driving altered neuronal morphology and function, as well as poor sensitivity in methods to quantify low-level biomarkers in bodily fluids. Here, we evaluated 5 neurotoxicants (acetaminophen [negative control], bisindolylmaleimide-1, colchicine, doxorubicin, paclitaxel, and rotenone) in human-induced pluripotent stem cell-derived neurons to profile secreted microRNAs (miRNAs) at early and late stages of decline in neuronal cell morphology and viability. Based on evaluation of these morphological (neurite outgrowth parameters) and viability (adenosine triphosphate) changes, 2 concentrations of each chemical were selected for analysis in a human 754 miRNA panel: a low concentration with no/minimal effect on cell viability but a significant decrease in neurite outgrowth, and a high concentration with a significant decrease in both endpoints. A total of 39 miRNAs demonstrated significant changes (fold-change ≥ 1.5 or ≤ 0.67, p value < .01) with at least 1 exposure. Further analyses of targets modulated by these miRNAs revealed 38 key messenger RNA targets with roles in neurological dysfunctions, and identified transforming growth factor-beta (TGF-ß) signaling as a commonly enriched pathway. Of the 39 miRNAs, 5 miRNAs, 3 downregulated (miR-20a, miR-30b, and miR-30d) and 3 upregulated (miR-1243 and miR-1305), correlated well with morphological changes induced by multiple neurotoxicants and were notable based on their relationship to various neurodegenerative conditions and/or key pathways, such as TGF-ß signaling. These datasets reveal miRNA candidates that warrant further evaluation as potential safety biomarkers of chemical-induced neurodegeneration.

Prolonged Perioperative Antibiotics: A Hidden Problem.

OBJECTIVES: National guidelines generally recommend 24 hours or less of surgical antibiotic prophylaxis. In a freestanding, regional children's hospital, we evaluated the duration of antibiotic surgical prophylaxis to identify targets for standardization of practice. METHODS: All procedures performed in 2017 were extracted from our local data warehouse; those involving an incision were considered a surgical procedure and correlated to antibiotic data. Antibiotic courses were reviewed if administered for >24 hours, or if the duration or indication for prophylaxis was uncertain. Total duration of prophylaxis (including discharge prescriptions) was calculated in hours for all procedures and categorized by department and by the quantity of prophylaxis received: none, single dose, multiple doses within 24 hours, and >24 hours. Percentage of procedures and total days of potential excess were calculated. RESULTS: A total of 15 651 procedures were included; 5009 met criteria for chart review, and after further exclusions, 12 895 procedures were included in the analysis. In total, 55% of all 12 895 procedures received prophylaxis. A single dose was given in 30%. Over 24 hours was administered in 11%, and 14% received multiple doses <24 hours (both potential excess). Results were evaluated by surgical subspecialty and procedure type. There were 5733 cumulative days of surgical prophylaxis administered after 24 hours (potential excess). CONCLUSION: In 2017, up to 25% of procedures received potentially unnecessary perioperative prophylaxis, indicating that national guidance specific to pediatrics would have high impact on antibiotic overuse in the pediatric surgical population.

Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages.

BACKGROUND: Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours. METHODS: Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns. RESULTS: Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5-29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5-14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5-14-year-olds reported fever in the two weeks prior to survey (p = 0.044). CONCLUSIONS: The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.