Digital technologies for health financing in low-income and middle-income countries: a scoping review protocol.

INTRODUCTION: Universal health coverage (UHC) is a global priority, ensuring equitable access to quality healthcare services without financial hardship. Many countries face challenges in progressing towards UHC. Health financing is pivotal for advancing UHC by raising revenues, enabling risk-sharing through pooling of funds and allocating resources. Digital technologies in the healthcare sector offer promising opportunities for health systems. In low-income and middle-income countries (LMICs), digital technologies for health financing (DTHF) have gained traction, supporting these three main functions of health financing for UHC. As existing information on DTHF in LMICs is limited, our scoping review aims to provide a comprehensive overview of DTHF in LMICs. Our objectives include identifying and describing existing DTHF, exploring evaluation approaches, examining their positive and negative effects, and investigating facilitating factors and barriers to implementation at the national level. METHODS AND ANALYSIS: Our scoping review follows the six stages proposed by Arksey and O'Malley, further developed by Levac et al and the Joanna Briggs Institute. The reporting adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews framework. Eligibility criteria for studies reflect the three core elements of the search: (1) health financing, (2) digital technologies and (3) LMICs. We search multiple databases, including Medline via PubMed, EMBASE via Ovid, the Web of Science Core Collection, CENTRAL via Cochrane and the Global Index Medicus by the WHO. The extracted information is synthesised from both quantitative and qualitative studies. ETHICS AND DISSEMINATION: As our scoping review is based solely on information gathered from previously published studies, documents and publicly available scientific literature, ethical clearance is not required for its conduct. The findings are presented and discussed in a peer-reviewed article, as well as shared at conferences relevant to the topic.

Inter-facility transfers for emergency obstetrical and neonatal care in rural Madagascar: a cost-effectiveness analysis.

CONTEXT: There is a substantial lack of inter-facility referral systems for emergency obstetrical and neonatal care in rural areas of sub-Saharan Africa. Data on the costs and cost-effectiveness of such systems that reduce preventable maternal and neonatal deaths are scarce. SETTING: We aimed to determine the cost-effectiveness of a non-governmental organisation (NGO)-run inter-facility referral system for emergency obstetrical and neonatal care in rural Southern Madagascar by analysing the characteristics of cases referred through the intervention as well as its costs. DESIGN: We used secondary NGO data, drawn from an NGO's monitoring and financial administration database, including medical and financial records. OUTCOME MEASURES: We performed a descriptive and a cost-effectiveness analysis, including a one-way deterministic sensitivity analysis. RESULTS: 1172 cases were referred over a period of 4 years. The most common referral reasons were obstructed labour, ineffective labour and eclampsia. In total, 48 neonates were referred through the referral system over the study period. Estimated cost per referral was US$336 and the incremental cost-effectiveness ratio (ICER) was US$70 per additional life-year saved (undiscounted, discounted US$137). The sensitivity analysis showed that the intervention was cost-effective for all scenarios with the lowest ICER at US$99 and the highest ICER at US$205 per additional life-year saved. When extrapolated to the population living in the study area, the investment costs of the programme were US$0.13 per person and annual running costs US$0.06 per person. CONCLUSIONS: In our study, the inter-facility referral system was a very cost-effective intervention. Our findings may inform policies, decision-making and implementation strategies for emergency obstetrical and neonatal care referral systems in similar resource-constrained settings.

A cross-sectional analysis of the effectiveness of a nutritional support programme for people with tuberculosis in Southern Madagascar using secondary data from a non-governmental organisation.

BACKGROUND: There is a strong, bi-directional link between tuberculosis (TB) and undernutrition: TB often causes undernutrition, and undernourished people are more likely to contract TB and experience worse outcomes. Globally, several TB nutritional support programmes exist; however, evidence on their effectiveness is limited and contested. This study evaluates the effect of a nutritional support programme implemented for people with TB in the Atsimo-Andrefana region, Madagascar in 2022. Within this programme, undernourished people with TB [with a body mass index (BMI) of < 18.5 kg/m2] receive 0.6 L of vegetable oil and 6.0 kg of a soy-wheat blend per month throughout their TB treatment. METHODS: We analysed secondary non-governmental organisation data collected between January and November 2022 in the Atsimo-Andrefana region, Southern Madagascar, including information on an individual's medical conditions (e.g., type of TB, treatment outcomes) and nutritional status measured prior to, during, and after completion of treatment (e.g., height, weight, mid-upper arm circumference). We conducted descriptive analyses of patient baseline characteristics and outcomes to assess the impact of the provided nutritional support on the BMI of people with TB. RESULTS: A total of 1310 people with TB were included in the study [9.9% (130) children under the age of 5, 32.1% (420) children between 5 and 18 years, 58.0% (760) adults]. 55.4% of children under 5, 28.1% of children between ages 5 and 18, and 81.3% of adults were undernourished at treatment initiation. 42.3% (55/130) of children under 5 experienced severe acute malnutrition at treatment uptake. While the average BMI of adults with TB receiving food support increased over time, from 17.1 kg/m2 (interquartile range: 15.8-18.3, range: 10.3-22.5) to 17.9 kg/m2 (interquartile range: 16.6-19.1, range: 11.9-24.1), most adults remained undernourished even after completing TB treatment. CONCLUSIONS: The current TB nutritional support programme falls short of sufficiently increasing the BMI of people with TB to overcome malnutrition. There is an urgent need to revise the nutritional support available for people with TB, particularly for children under 5.

Design Research to Embed mHealth into a Community-Led Blood Pressure Management System in Uganda: Protocol for a Mixed Methods Study.

BACKGROUND: Uncontrolled hypertension is a leading risk factor for cardiovascular diseases. In Uganda, such diseases account for approximately 10% of all deaths, with 1 in 5 adults having hypertension (>90% of the hypertensive cases are uncontrolled). Although basic health care in the country is available free of cost at government facilities, regularly accessing medication to control hypertension is difficult because supply chain challenges impede availability. Clients therefore frequently suspend treatment or buy medication individually at private facilities or pharmacies (incurring significant costs). In recent years, mobile health (mHealth) interventions have shown increasing potential in addressing health system challenges in sub-Saharan Africa, but the acceptability, feasibility, and uptake conditions of mobile money approaches to chronic disease management remain understudied. OBJECTIVE: This study aims to design and pilot-test a mobile money-based intervention to increase the availability of antihypertensive medication and lower clients' out-of-pocket payments. We will build on existing local approaches and assess the acceptability, feasibility, and uptake of the designed intervention. Furthermore, rather than entering the study setting with a ready-made intervention, this research will place emphasis on gathering applied ethnographic insights early, which can then inform the parameters of the intervention prototype and concurrent trial. METHODS: We will conduct a mixed methods study following a human-centered design approach. We will begin by conducting extensive qualitative research with a range of stakeholders (clients; health care providers; religious, cultural, and community leaders; academics; and policy makers at district and national levels) on their perceptions of hypertension management, money-saving systems, and mobile money in the context of health care. Our results will inform the design, iterative adaptation, and implementation of an mHealth-facilitated pooled financing intervention prototype. At study conclusion, the finalized prototype will be evaluated quantitatively via a randomized controlled trial. RESULTS: As of August 2023, qualitative data collection, which started in November 2022, is ongoing, with data analysis of the first qualitative interviews underway to inform platform and implementation design. Recruitment for the quantitative part of this study began in August 2023. CONCLUSIONS: Our results aim to inform the ongoing discourse on novel and sustainable pathways to facilitate access to medication for the management of hypertension in resource-constrained settings. TRIAL REGISTRATION: German registry of clinical trials DRKS00030922; https://drks.de/search/en/trial/DRKS00030922. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46614.

Usability and acceptance of a mobile health wallet for pregnancy-related healthcare: A mixed methods study on stakeholders' perceptions in central Madagascar.

BACKGROUND: Several sub-Saharan African countries use digital financial services to improve health financing, especially for maternal and child health. In cooperation with the Malagasy Ministry of Health, the NGO Doctors for Madagascar is implementing a mobile health wallet for maternal health care in public-sector health facilities in Madagascar. Our aim was to explore the enabling and limiting factors related to the usability and acceptance of the Mobile Maternal Health Wallet (MMHW) intervention during its implementation. METHODS: We conducted a cross-sectional, mixed methods study with mothers and pregnant women and facility- (FBHWs) and community-based (CHWs) health workers from public-sector health facilities in three districts of the Analamanga region in Madagascar. We used a convergent design in collecting and analyzing quantitative and qualitative data. We performed one-stage proportional sampling of women who had signed up for the MMHW. All FBHWs and CHWs at primary care facilities in the intervention area were eligible to participate. RESULTS AND SIGNIFICANCE: 314 women, 76 FBHWs, and 52 CHWs were included in the quantitative survey. Qualitative data were extracted from in-depth interviews with 12 women and 12 FBHWs and from six focus group discussions with 39 CHWSs. The MMHW intervention was accepted and used by health workers and women from different socioeconomic backgrounds. Main motivations for women to enroll in the intervention were the opportunity to save money for health (30.6%), electronic vouchers for antenatal ultrasound (30.2%), and bonus payments upon reaching a savings goal (27.9%). Main motivation for health workers was enabling pregnant women to save for health, thus encouraging facility-based deliveries (57.9%). Performance-based payments had low motivational value for health workers. Key facilitators were community sensitization, strong women-health worker relationship, decision making at the household level, and repetitive training on the use of the MMHW. Key barriers included limited phone ownership, low level of digital literacy, disinformation concerning the effects of the intervention, and technical problems like slow payout processes.

Assessing spatial learning and memory in mice: Classic radial maze versus a new animal-friendly automated radial maze allowing free access and not requiring food deprivation.

The radial arm maze (RAM) is a common behavioral test to quantify spatial learning and memory in rodents. Prior attempts to refine the standard experimental setup have been insufficient. Previously, we demonstrated the feasibility of a fully automated, voluntary, and stress-free eight-arm RAM not requiring food or water deprivation. Here, we compared this newly developed refined RAM to a classic manual experimental setup using 24 female 10-12 weeks old C57BL/6J mice. We used a lipopolysaccharide (LPS)-induced model of systemic inflammation to examine long-term cognitive impairment for up to 13 weeks following LPS injection. Both mazes demonstrated robust spatial learning performance during the working memory paradigm. The refined RAM detected spatial learning and memory deficits among LPS-treated mice in the working memory paradigm, whereas the classic RAM detected spatial learning and memory deficits only in the combined working/reference memory paradigm. In addition, the refined RAM allowed for quantification of an animal's overall exploratory behavior and day/night activity pattern. While our study highlights important aspects of refinement of the new setup, our comparison of methods suggests that both RAMs have their respective merits depending on experimental requirements.

Proportion of stroke types in Madagascar: A tertiary-level hospital-based case series.

BACKGROUND: Like other countries in sub-Saharan Africa, Madagascar has a high burden of stroke. The Malagasy population is unique in sharing both African and Asian ancestry. The proportion of ischemic and hemorrhagic stroke types is unknown for this population. AIM: Our aim was to establish the proportion of stroke types and known risk factors for the Malagasy population. METHODS: We conducted a single-center, tertiary-level hospital-based case series. We included all patients with a CT-imaging confirmed stroke who presented at the emergency ward of the study hospital between January 1, 2017, and November 20, 2018. RESULTS: Of 223 patients with CT-confirmed stroke, 57.4% (128/223, 95% CI: 51-64%) had an ischemic stroke and 42.6% (95/223, 95% CI: 36-49%) had an intracranial hemorrhage. The majority (89.5%; 85/95, 95% CI: 83-96%) of intracranial hemorrhages were intracerebral; 4.2% (4/95, 95% CI: 0-8%) had a subdural hematoma, 5.3% (5/95, 95% CI: 1-10%) had a subarachnoid hemorrhage, there was one isolated intraventricular hemorrhage (1.1%; 1/95, 95% CI: -1-3%). The prevalence of hypertension among stroke patients was high (86.6%; 187/216, 95% CI: 82-91%). CONCLUSIONS: Our study is the first to report the proportion of stroke types and known risk factors in Madagascar. We find that the proportion of hemorrhagic strokes was unexpectedly higher than that reported from other countries in sub-Saharan Africa. Our findings highlight the need for a country-specific approach to stroke prevention, treatment, and rehabilitation and provide guidance on public health resource allocation in Madagascar.

Crossing the Last Mile of TB Care in Rural Southern Madagascar: A Multistakeholder Initiative.

Despite a free TB care policy, access to TB care in rural Madagascar is limited due to a markedly underfunded health care system. The World Health Organization estimated the yearly TB incidence in Madagascar at 238 cases per 100,000 people in 2020; only half of the patients with TB are being notified and treated. We describe the development, implementation, and lessons learned of an intervention to improve TB care services in a remote, rural district in southern Madagascar. We involved national, regional, and local stakeholders in assessing the multifaceted challenges in a remote, rural area and codesigning activities to address them. The overarching principles of the intervention were to (1) promote national TB guidelines, (2) build on best practices, and (3) prioritize low-cost activities to enable scale-up. An in-depth assessment of challenges in accessing and delivering TB care resulted in the following prioritization of activities: (1) fostering community engagement, (2) decentralizing service provision, (3) improving quality of care, (4) providing nutritional support, and (5) ensuring staff support and supervision. The intervention was launched in September 2019 and is ongoing as of October 2022. During mobile TB clinics conducted between September 2019 and December 2020, 4,982 presumptive patients were screened and 1,706 (34.2%) have been diagnosed with TB. Based on 2010-2020 official TB notification data, we calculated trend-adjusted additional TB notifications during the intervention, resulting in a 2.6-fold increase in cases in 2019-2020. The intervention district's TB notification rate increased from 178 cases per 100,000 people in 2018 to 424 cases per 100,000 people in 2020. Involving stakeholders from all levels of care was perceived as a key to success. The unexpected increase in the number of patients with TB in the intervention district overburdened the current paper-based TB notification system and emphasized the need for expanded diagnostics and social support services.

Direct patient costs of maternal care and birth-related complications at faith-based hospitals in Madagascar: a secondary analysis of programme data using patient invoices.

OBJECTIVES: We aimed to determine the rate of catastrophic health expenditure incurred by women using maternal healthcare services at faith-based hospitals in Madagascar. DESIGN: This was a secondary analysis of programmatic data obtained from a non-governmental organisation. SETTING: Two faith-based, secondary-level hospitals located in rural communities in southern Madagascar. PARTICIPANTS: All women using maternal healthcare services at the study hospitals between 1 March 2019 and 7 September 2020 were included (n=957 women). MEASURES: We collected patient invoices and medical records of all participants. We then calculated the rate of catastrophic health expenditure relative to 10% and 25% of average annual household consumption in the study region. RESULTS: Overall, we found a high rate of catastrophic health expenditure (10% threshold: 486/890, 54.6%; 25% threshold: 366/890, 41.1%). Almost all women who required surgical care, most commonly a caesarean section, incurred catastrophic health expenditure (10% threshold: 279/280, 99.6%; 25% threshold: 279/280, 99.6%). The rate of catastrophic health expenditure among women delivering spontaneously was 5.7% (14/247; 10% threshold). CONCLUSIONS: Our findings suggest that direct patient costs of managing pregnancy and birth-related complications at faith-based hospitals are likely to cause catastrophic health expenditure. Financial risk protection strategies for reducing out-of-pocket payments for maternal healthcare should include faith-based hospitals to improve health-seeking behaviour and ultimately achieve universal health coverage in Madagascar.

The 4MOTHERS trial of the impact of a mobile money-based intervention on maternal and neonatal health outcomes in Madagascar: study protocol of a cluster-randomized hybrid effectiveness-implementation trial.

BACKGROUND: Mobile money-a service enabling users to receive, store, and send electronic money using mobile phones-has been widely adopted across low- and middle-income economies to pay for a variety of services, including healthcare. However, evidence on its effects on healthcare access and health outcomes are scarce and the possible implications of using mobile money for financing and payment of maternal healthcare services-which generally require large one-time out-of-pocket payments-have not yet been systematically assessed in low-resource settings. The aim of this study is to determine the impact on health outcomes, cost-effectiveness, feasibility, acceptability, and usefulness of mobile phone-based savings and payment service, the Mobile Maternal Health Wallet (MMHW), for skilled healthcare during pregnancy and delivery among women in Madagascar. METHODS: This is a hybrid effectiveness-implementation type-1 trial, determining the effectiveness of the intervention while evaluating the context of its implementation in Madagascar's Analamanga region, containing the capital, Antananarivo. Using a stratified cluster randomized design, 61 public-sector primary-care health facilities were randomized within 6 strata to either receive the intervention or not (29 intervention vs. 32 control facilities). The strata were defined by a health facility's antenatal care visit volume and its capacity to offer facility-based deliveries. The registered pre-specified primary outcomes are (i) delivery at a health facility, (ii) antenatal care visits, and (iii) total healthcare expenditure during pregnancy, delivery, and neonatal period. The registered pre-specified secondary outcomes include additional health outcomes, economic outcomes, and measurements of user experience and satisfaction. Our estimated enrolment number is 4600 women, who completed their pregnancy between July 1, 2020, and December 31, 2021. A series of nested mixed-methods studies will elucidate client and provider perceptions on feasibility, acceptability, and usefulness of the intervention to inform future implementation efforts. DISCUSSION: A cluster-randomized, hybrid effectiveness-implementation design allows for a robust approach to determine whether the MMHW is a feasible and beneficial intervention in a resource-restricted public healthcare environment. We expect the results of our study to guide future initiatives and health policy decisions related to maternal and neonatal health and universal healthcare coverage through technology in Madagascar and other countries in sub-Saharan Africa. TRIAL REGISTRATION: This trial was registered on March 12, 2021: Deutsches Register Klinischer Studien (German Clinical Trials Register), identifier: DRKS00014928 . For World Health Organization Trial Registration Data Set see Additional file 1.

Systemic inflammation induced the delayed reduction of excitatory synapses in the CA3 during ageing.

Sepsis-associated encephalopathy (SAE) represents diverse cerebral dysfunctions in response to pathogen-induced systemic inflammation. Peripheral exposure to lipopolysaccharide (LPS), a component of the gram-negative bacterial cell wall, has been extensively used to model systemic inflammation. Our previous studies suggested that LPS led to hippocampal neuron death and synaptic destruction in vivo. However, the underlying roles of activated microglia in these neuronal changes remained unclear. Here, LPS from two different bacterial strains (Salmonella enterica or E. coli) were compared and injected in 14- to 16-month-old mice and evaluated for neuroinflammation and neuronal integrity in the hippocampus at 7 or 63 days post-injection (dpi). LPS injection resulted in persistent neuroinflammation lasting for seven days and a subsequent normalisation by 63 dpi. Of note, increases in proinflammatory cytokines, microglial morphology and microglial mean lysosome volume were more pronounced after E. coli LPS injection than Salmonella LPS at 7 dpi. While inhibitory synaptic puncta density remained normal, excitatory synaptic puncta were locally reduced in the CA3 region of the hippocampus at 63 dpi. Finally, we provide evidence that excitatory synapses coated with complement factor 3 (C3) decreased between 7 dpi and 63 dpi. Although we did not find an increase of synaptic pruning by microglia, it is plausible that microglia recognised and eliminated these C3-tagged synapses between the two time points of investigation. Since a region-specific decline of CA3 synapses has previously been reported during normal ageing, we postulate that systemic inflammation may have accelerated or worsened the CA3 synaptic changes in the ageing brain.

Facilitators and barriers to the implementation of a Mobile Health Wallet for pregnancy-related health care: A qualitative study of stakeholders' perceptions in Madagascar.

Financial barriers are a major obstacle to accessing maternal health care services in low-resource settings. In Madagascar, less than half of live births are attended by skilled health staff. Although mobile money-based savings and payment systems are often used to pay for a variety of services, including health care, data on the implications of a dedicated mobile money wallet restricted to health-related spending during pregnancy-a mobile health wallet (MHW)-are not well understood. In cooperation with the Madagascan Ministry of Health, this study aims to elicit the perceptions, experiences, and recommendations of key stakeholders in relation to a MHW amid a pilot study in 31 state-funded health care facilities. We conducted a two-stage qualitative study using semi-structured in-depth interviews with stakeholders (N = 21) representing the following groups: community representatives, health care providers, health officials and representatives from phone provider companies. Interviews were conducted in Atsimondrano and Renivohitra districts, between November and December of 2017. Data was coded thematically using inductive and deductive approaches, and found to align with a social ecological model. Key facilitators for successful implementation of the MHW, include (i) close collaboration with existing communal structures and (ii) creation of an incentive scheme to reward pregnant women to save. Key barriers to the application of the MHW in the study zone include (i) disruption of informal benefits for health care providers related to the current cash-based payment system, (ii) low mobile phone ownership, (iii) illiteracy among the target population, and (iv) failure of the MHW to overcome essential access barriers towards institutional health care services such as fear of unpredictable expenses. The MHW was perceived as a potential solution to reduce disparities in access to maternal health care. To ensure success of the MHW, direct demand-side and provider-side financial incentives merit consideration.

Automated radial 8-arm maze: A voluntary and stress-free behavior test to assess spatial learning and memory in mice.

The radial arm maze (RAM) is a common behavioral test to assess spatial working and reference memory in mice. However, conventional RAM experiments require a substantial degree of manual handling and animals are usually subjected to prolonged periods of food or water deprivation to achieve sufficient learning motivation resulting in stress-induced confounding effects and unwanted intra- and inter-subject variation. In a proof-of-concept approach to improve reliability and repeatability of results by refining the conventional maze methodology, we developed a voluntary, fully automated 8-arm RAM and tested its feasibility and usability using both spatial working and combined working/reference memory paradigms in ten female C57BL/6J mice. We demonstrate that experimental procedures of up to 7 days duration could be conducted without any manual animal handling and that mice up to 18 months of age showed robust spatial learning performance without any food or water restrictions being applied. Therefore, a voluntary, automated 8-arm RAM can serve to minimize variation in experimental results by reducing an animal's distress, suffering, and pain, which, in turn, contributes to the comprehensive application of 3R principles.

Cognitive Deficits Following Intensive Care.

BACKGROUND: Illnesses that necessitate intensive care can impair cognitive function severely over the long term, leaving patients less able to cope with the demands of everyday living and markedly lowering their quality of life. There has not yet been any comprehensive study of the cognitive sequelae of critical illness among non- surgical patients treated in intensive care. The purpose of this review is to present the available study findings on cognitive deficits in such patients, with particular at- tention to prevalence, types of deficit, clinical course, risk factors, prevention, and treatment. METHODS: This review is based on pertinent publications retrieved by a selective search in MEDLINE. RESULTS: The literature search yielded 3360 hits, among which there were 14 studies that met our inclusion criteria. 17-78% of patients had cognitive deficits after dis- charge from the intensive care unit; most had never had a cognitive deficit before. Cognitive impairment often persisted for up to several years after discharge (0.5 to 9 years) and tended to improve over time. The only definite risk factor is delirium. CONCLUSION: Cognitive dysfunction is a common sequela of the treatment of non-surgical patients in intensive care units. It is a serious problem for the affected persons and an increasingly important socio-economic problem as well. The effective management of delirium is very important. General conclusions are hard to draw from the available data because of heterogeneous study designs, varying methods of measurement, and differences among patient cohorts. Further studies are needed so that study designs and clinical testing procedures can be standard- ized and effective measures for prevention and treatment can be identified.

Assessing the Effects of Cytoprotectants on Selective Neuronal Loss, Sensorimotor Deficit and Microglial Activation after Temporary Middle Cerebral Occlusion.

Although early reperfusion after stroke salvages the still-viable ischemic tissue, peri-infarct selective neuronal loss (SNL) can cause sensorimotor deficits (SMD). We designed a longitudinal protocol to assess the effects of cytoprotectants on SMD, microglial activation (MA) and SNL, and specifically tested whether the KCa3.1-blocker TRAM-34 would prevent SNL. Spontaneously hypertensive rats underwent 15 min middle-cerebral artery occlusion and were randomized into control or treatment group, which received TRAM-34 intraperitoneally for 4 weeks starting 12 h after reperfusion. SMD was assessed longitudinally using the sticky-label test. MA was quantified at day 14 using in vivo [11C]-PK111195 positron emission tomography (PET), and again across the same regions-of-interest template by immunofluorescence together with SNL at day 28. SMD recovered significantly faster in the treated group (p = 0.004). On PET, MA was present in 5/6 rats in each group, with no significant between-group difference. On immunofluorescence, both SNL and MA were present in 5/6 control rats and 4/6 TRAM-34 rats, with a non-significantly lower degree of MA but a significantly (p = 0.009) lower degree of SNL in the treated group. These findings document the utility of our longitudinal protocol and suggest that TRAM-34 reduces SNL and hastens behavioural recovery without marked MA blocking at the assessed time-points.

Metadata Correction: A Mobile Health Wallet for Pregnancy-Related Health Care in Madagascar: Mixed-Methods Study on Opportunities and Challenges.

[This corrects the article DOI: 10.2196/11420.].

Refining humane endpoints in mouse models of disease by systematic review and machine learning-based endpoint definition.

Ideally, humane endpoints allow for early termination of experiments by minimizing an animal's discomfort, distress and pain, while ensuring that scientific objectives are reached. Yet, lack of commonly agreed methodology and heterogeneity of cut-off values published in the literature remain a challenge to the accurate determination and application of humane endpoints. With the aim to synthesize and appraise existing humane endpoint definitions for commonly used physiological parameters, we conducted a systematic review of mouse studies of acute and chronic disease models, which used body weight, temperature and/or sickness scores for endpoint definition. In the second part of the study, we used previously published and unpublished data on weight, temperature and sickness scores from mouse models of sepsis and stroke and applied machine learning algorithms to assess the usefulness of this method for parameter selection and endpoint definition across models. Studies were searched for in two electronic databases (MEDLINE/Pubmed and Embase). Out of 110 retrieved full-text manuscripts, 34 studies were included. We found large intra- and inter-model variance in humane endpoint determination and application due to varying animal models, lack of standardized experimental protocols and heterogeneity of performance metrics (part 1). Machine learning models trained with physiological data and sickness severity score or modified DeSimoni neuroscore identified animals with a high risk of death at an early time point in both mouse models of stroke (male: 93.2% at 72h post-treatment; female: 93.0% at 48h post-treatment) and sepsis (96.2% at 24h post-treatment), thus demonstrating generalizability in endpoint determination across models (part 2).