Core sepsis-related competencies for medical students: an international consensus by Delphi technique.

BACKGROUND: Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. METHODS: Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13-18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. RESULTS: The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. CONCLUSION: Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.

Implementing health worker training on sepsis in South Eastern Nigeria using innovative digital strategies: an interventional study.

Background: Sepsis is a leading cause of morbidity and mortality especially in low- and middle-income countries such as Nigeria. Training of health workers using digital platforms may improve knowledge and lead to better patient outcomes. Objectives: To assess the effectiveness of a digital health educational module on sepsis in improving the knowledge of medical doctors in Cross River State Nigeria on the diagnosis and management of patients presenting with sepsis. Design: Quasi-experimental analytical study. Methods: We developed and deployed a sepsis module through an innovative application (Sepsis tutorial app) to doctors in Calabar, Nigeria. We assessed quantitative pre- and post-intervention knowledge scores for those completing the tutorial on sepsis between both assessments. A user satisfaction survey evaluated the content of the tutorial and the usability of the app. Results: One hundred and two doctors completed the course. There were more males than females (58.8% versus 41.2%). Over half (52%) were junior doctors, a minority were general practitioners and house officers (3% and 5%, respectively), and 72.6% had practiced for periods ranging from 1 to 15 years post-qualification. Gender and age appeared to have no significant association with pre- and post-test scores. The oldest age group (61-70) had the lowest mean pre- and post-test scores, while general practitioners had higher mean pre- and post-test scores than other cadres. The majority (95%) of participants recorded higher post-test than pre-test scores with a significant overall increase in mean scores (25.5 ± 14.7%, p < 0.0001). Participants were satisfied with the content and multimodal delivery of the material and found the app usable. Conclusion: Digital training using context-responsive platforms is feasible and may be used to close the critical knowledge gap required to respond effectively to medical emergencies such as sepsis in low- to middle-income settings.

Training health workers on sepsis using digital strategies Sepsis occurs when the body injures itself as it attempts to fight an infection. It is now recognized as a leading cause of death especially in low- and middle-income countries such as Nigeria. Training of health workers using digital platforms may improve knowledge and lead to better patient outcomes. We assessed the effectiveness of a digital health educational course on sepsis in improving the knowledge of medical doctors in Cross River State, Nigeria on the diagnosis and management of patients presenting with sepsis. One hundred and two doctors completed the course. Most participants recorded higher post-test than pre-test scores, were generally satisfied with the content and delivery of the material, and found the app usable. We conclude that digital training using digital platforms may be useful in bridging the critical knowledge gap required to respond effectively to sepsis in low- to middle-income settings.

Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Proposed Framework for Conducting Clinically Relevant Translational Biomarker Research for the Diagnosis, Prognosis and Management of Sepsis.

Although the diagnosis of sepsis requires the identification of the three components of infection, a systemic inflammation response, and organ dysfunction, there is currently no consensus on gold-standard criteria. There are however suggested tools and tests, which have been proposed in international guidelines, including those produced by the Surviving Sepsis Campaign. Biomarkers play an important role in these tools and tests, and numerous heterogeneous studies have been performed to evaluate their respective clinical utility. Our review of the current practice shows that no biomarkers of infection, systemic inflammation response, organ dysfunction and sepsis are currently specifically recommended, which is probably due to the lack of standardization of studies. We therefore propose to define a framework for conducting clinically relevant translational biomarker research and seek to establish ideal criteria that can be applied to an infection, systemic inflammation response, organ dysfunction and sepsis biomarkers, which can enable early screening of sepsis, diagnosis of sepsis at the time of clinical suspicion and monitoring of sepsis treatment efficacy.

Pediatric post-discharge mortality in resource-poor countries: a systematic review and meta-analysis.

Background: Under-five mortality remains concentrated in resource-poor countries. Post-discharge mortality is becoming increasingly recognized as a significant contributor to overall child mortality. With a substantial recent expansion of research and novel data synthesis methods, this study aims to update the current evidence base by providing a more nuanced understanding of the burden and associated risk factors of pediatric post-discharge mortality after acute illness. Methods: Eligible studies published between January 1, 2017 and January 31, 2023, were retrieved using MEDLINE, Embase, and CINAHL databases. Studies published before 2017 were identified in a previous review and added to the total pool of studies. Only studies from countries with low or low-middle Socio-Demographic Index with a post-discharge observation period greater than seven days were included. Risk of bias was assessed using a modified version of the Joanna Briggs Institute critical appraisal tool for prevalence studies. Studies were grouped by patient population, and 6-month post-discharge mortality rates were quantified by random-effects meta-analysis. Secondary outcomes included post-discharge mortality relative to in-hospital mortality, pooled risk factor estimates, and pooled post-discharge Kaplan-Meier survival curves. PROSPERO study registration: #CRD42022350975. Findings: Of 1963 articles screened, 42 eligible articles were identified and combined with 22 articles identified in the previous review, resulting in 64 total articles. These articles represented 46 unique patient cohorts and included a total of 105,560 children. For children admitted with a general acute illness, the pooled risk of mortality six months post-discharge was 4.4% (95% CI: 3.5%-5.4%, I2 = 94.2%, n = 11 studies, 34,457 children), and the pooled in-hospital mortality rate was 5.9% (95% CI: 4.2%-7.7%, I2 = 98.7%, n = 12 studies, 63,307 children). Among disease subgroups, severe malnutrition (12.2%, 95% CI: 6.2%-19.7%, I2 = 98.2%, n = 10 studies, 7760 children) and severe anemia (6.4%, 95% CI: 4.2%-9.1%, I2 = 93.3%, n = 9 studies, 7806 children) demonstrated the highest 6-month post-discharge mortality estimates. Diarrhea demonstrated the shortest median time to death (3.3 weeks) and anemia the longest (8.9 weeks). Most significant risk factors for post-discharge mortality included unplanned discharges, severe malnutrition, and HIV seropositivity. Interpretation: Pediatric post-discharge mortality rates remain high in resource-poor settings, especially among children admitted with malnutrition or anemia. Global health strategies must prioritize this health issue by dedicating resources to research and policy innovation. Funding: No specific funding was received.

Drivers of Resistance in Uganda and Malawi (DRUM): a protocol for the evaluation of One-Health drivers of Extended Spectrum Beta Lactamase (ESBL) resistance in Low-Middle Income Countries (LMICs).

In sub-Saharan Africa (sSA), there is high morbidity and mortality from severe bacterial infection and this is compounded by antimicrobial resistance, in particular, resistance to 3rd-generation cephalosporins. This resistance is typically mediated by extended-spectrum beta lactamases (ESBLs). To interrupt ESBL transmission it will be important to investigate how human behaviour, water, sanitation, and hygiene (WASH) practices, environmental contamination, and antibiotic usage in both urban and rural settings interact to contribute to transmission of ESBL E. coli and ESBL K. pneumoniae between humans, animals, and the environment. Here we present the protocol for the Drivers of Resistance in Uganda and Malawi (DRUM) Consortium, in which we will collect demographic, geospatial, clinical, animal husbandry and WASH data from a total of 400 households in Uganda and Malawi. Longitudinal human, animal and environmental sampling at each household will be used to isolate ESBL E. coli and ESBL K. pneumoniae. This will be complimented by a Risks, Attitudes, Norms, Abilities and Self-Regulation (RANAS) survey and structured observations to understand the contextual and psychosocial drivers of regional WASH practices. Bacterial isolates and plate sweeps will be further characterised using a mixture of short-,long-read and metagenomic whole-genome sequencing. These datasets will be integrated into agent-based models to describe the transmission of EBSL resistance in Uganda and Malawi and allow us to inform the design of interventions for interrupting transmission of ESBL-bacteria.

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS:We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per µL (the median for the cohort) was 45% (95% CI 38­52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63­87), increasing to 89% (80­94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05­3·08) but not after 30 days (1·25, 0·84­2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16­8·84). INTERPRETATION:In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients