Shigella Detection and Molecular Serotyping With a Customized TaqMan Array Card in the Enterics for Global Health (EFGH): Shigella Surveillance Study.

Background: Quantitative polymerase chain reaction (qPCR) targeting ipaH has been proven to be highly efficient in detecting Shigella in clinical samples compared to culture-based methods, which underestimate Shigella burden by 2- to 3-fold. qPCR assays have also been developed for Shigella speciation and serotyping, which is critical for both vaccine development and evaluation. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will utilize a customized real-time PCR-based TaqMan Array Card (TAC) interrogating 82 targets, for the detection and differentiation of Shigella spp, Shigella sonnei, Shigella flexneri serotypes, other diarrhea-associated enteropathogens, and antimicrobial resistance (AMR) genes. Total nucleic acid will be extracted from rectal swabs or stool samples, and assayed on TAC. Quantitative analysis will be performed to determine the likely attribution of Shigella and other particular etiologies of diarrhea using the quantification cycle cutoffs derived from previous studies. The qPCR results will be compared to conventional culture, serotyping, and phenotypic susceptibility approaches in EFGH. Conclusions: TAC enables simultaneous detection of diarrheal etiologies, the principal pathogen subtypes, and AMR genes. The high sensitivity of the assay enables more accurate estimation of Shigella-attributed disease burden, which is critical to informing policy and in the design of future clinical trials.

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Bangladesh.

Background: Shigella is an important cause of diarrhea in Bangladeshi children <5 years of age, with an incidence rate of 4.6 per 100 person-years. However, the report was more than a decade old, and data on Shigella consequences are similarly outdated and heterogeneously collected. Methods: Facility-based disease surveillance is planned to be carried out under the Enterics for Global Health (EFGH) Shigella Surveillance Study consortium for 2 years with aims to optimize and standardize laboratory techniques and healthcare utilization and coverage survey, clinical and anthropometric data collection, safety monitoring and responsiveness, and other related activities. The EFGH is a cohesive network of multidisciplinary experts, capable of operating in concert to conduct the study to generate data that will pave the way for potential Shigella vaccine trials in settings with high disease burden. The study will be conducted within 7 country sites in Asia, Africa, and Latin America. Conclusions: We outline the features of the Bangladesh site as part of this multisite surveillance network to determine an updated incidence rate and document the consequences of Shigella diarrhea in children aged 6-35 months, which will help inform policymakers and to implement the future vaccine trials.

Worker and workplace determinants of employment exit: a register study.

BACKGROUND: Workers with chronic illness are in higher risk of unemployment. This article investigated the worker and workplace characteristics associated with labour market inclusion for workers with a diagnosed chronic illness. METHODS: Linked employer-employee register data covering all Norwegian employers and employees each month from February 2015 to December 2019 were merged with patient data from specialist healthcare (136 196 observations (job spells); 70 923 individual workers). Survival analysis was used to estimate the risk of employment exit, with age, gender, chronic illness, full-time/part-time employment, skill level, marital status, children in household, branch, share of chronically ill workers, firm size and unemployment rate as covariates. RESULTS: 85% of the study population was employed in December 2019; 58% remain employed throughout the follow-up period. Mental illness, male gender, young age, part-time employment and lower skill levels were the worker-level predictors of labour market exit. Employments in secondary industries, in firms with high shares of chronically ill workers and, to some extent, in larger firms were the significant workplace-level determinants. CONCLUSION: Only a minority of our sample of workers with chronic illness experienced labour market exclusion. Targeted measures should be considered towards workers with poor mental health and/or low formal skills. Chronically ill workers within public administration have the best labour market prospects, while workplaces within the education branch have an unfulfilled potential.

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach.

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Toll-like receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

Role of TaqMan array card in determining causative organisms of acute febrile illness in hospitalized patients.

BACKGROUND: Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients. METHODS: The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test. RESULTS: The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test. CONCLUSION: TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.

Derivation and External Validation of a Clinical Prediction Model for Viral Diarrhea Etiology in Bangladesh.

Background: Antibiotics are commonly overused for diarrheal illness in many low- and middle-income countries, partly due to a lack of diagnostics to identify viral cases, in which antibiotics are not beneficial. This study aimed to develop clinical prediction models to predict risk of viral-only diarrhea across all ages, using routinely collected demographic and clinical variables. Methods: We used a derivation dataset from 10 hospitals across Bangladesh and a separate validation dataset from the icddr,b Dhaka Hospital. The primary outcome was viral-only etiology determined by stool quantitative polymerase chain reaction. Multivariable logistic regression models were fit and externally validated; discrimination was quantified using area under the receiver operating characteristic curve (AUC) and calibration assessed using calibration plots. Results: Viral-only diarrhea was common in all age groups (<1 year, 41.4%; 18-55 years, 17.7%). A forward stepwise model had AUC of 0.82 (95% confidence interval [CI], .80-.84) while a simplified model with age, abdominal pain, and bloody stool had AUC of 0.81 (95% CI, .78-.82). In external validation, the models performed adequately although less robustly (AUC, 0.72 [95% CI, .70-.74]). Conclusions: Prediction models consisting of 3 routinely collected variables can accurately predict viral-only diarrhea in patients of all ages in Bangladesh and may help support efforts to reduce inappropriate antibiotic use.

Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry.

There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children can be problematic, but high level and durable responses can be induced by presenting polysaccharides conjugated to carrier proteins. An effective shigella vaccine will need to be multivalent, targeting the most common global species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. Here we report the development of shigella conjugate vaccines (SCV) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using squaric acid chemistry to result in single point sun-burst type display of OSP from carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. We confirmed structure and demonstrated that these conjugates were recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG responses, as well as rTTHc-specific IgG responses. Vaccination induced serotype-specific bactericidal antibody responses against S. flexneri, and vaccinated animals were protected against keratoconjunctivitis (Sereny test) and intraperitoneal challenge with virulent S. flexneri 2a and 3a, respectively. Our results support further development of this platform conjugation technology in the development of shigella conjugate vaccines for use in resource-limited settings.

Promoting labour market inclusion of the chronically ill: a scoping review of Scandinavian countries' efforts.

OBJECTIVES: This article is a scoping review of efforts in labour market inclusion of the chronically ill in the Scandinavian countries, a research area that has received much political as well as research attention in recent years. The aim of the review was to identify promising strategies and the need for further research. METHODS: Six electronic databases were searched for literature published between 2015 and 2020. We included peer-reviewed articles that studied the effect of measures, aimed at the workplace or at the individual, that are intended to increase participation. Our search resulted in 2718 articles; our screening procedures resulted in 47 included articles. RESULTS: Among the included studies, musculoskeletal problems (17 articles) and mental health problems (29 articles) were the most frequent chronic conditions. Multimodal occupational rehabilitation programmes directed towards the individual employee were the most frequent interventions (30 articles). Return to work (24 articles) and sickness absence (12 articles) were the most common outcomes. About half (25 articles) of the included studies reported a positive impact of the intervention on work inclusion of the chronically ill. CONCLUSIONS: Our review found little evidence of how government programmes directed towards the supply side of the labour market succeed in including the chronically ill. Our review further indicated that multidisciplinary workplace interventions have a substantial effect. We also identified a significant lack of research on the effect of various governmental policies and programmes, including local health, work and welfare services, and limited coordination and cooperation between health and work services professions.

A cross-sector systematic review and synthesis of knowledge on telemedicine interventions in chronic wound management-Implications from a system perspective.

Based on initially identified needs for further telemedicine (TM) and chronic wound management research, the objective of this article is twofold: to conduct a systematic review of existing knowledge on TM interventions in chronic wound management-including barriers and opportunities-across the specialist and primary care sectors, and to incorporate the review findings into a system framework that can be further developed and validated through empirical data. We conclude that there is a pressing need for broader and more comprehensive empirical explorations into quality improvement and integration of TM in chronic wound management, including using system frameworks that can capture cross-sector system perspectives and associated implications. Of practical consideration, we suggest that the design and execution of TM improvement interventions and associated research projects should be conducted in close cooperation with managers and practitioners knowledgeable about barriers and opportunities that can influence the implementation of important interventions within chronic wound management.

Improved survival of non-small cell lung cancer patients after introducing patient navigation: A retrospective cohort study with propensity score weighted historic control.

OnkoNetwork is a patient navigation program established in the Moritz Kaposi General Hospital to improve the timeliness and completeness of cancer investigations and treatment. The H2020 SELFIE consortium selected OnkoNetwork as a promising integrated care initiative in Hungary and conducted a multicriteria decision analysis based on health, patient experience, and cost outcomes. In this paper, a more detailed analysis of clinical impacts is provided in the largest subgroup, non-small cell lung cancer (NSCLC) patients. A retrospective cohort study was conducted, enrolling new cancer suspect patients with subsequently confirmed NSCLC in two annual periods, before and after OnkoNetwork implementation (control and intervention cohorts, respectively). To control for selection bias and confounding, baseline balance was improved via propensity score weighting. Overall survival was analyzed in univariate and multivariate weighted Cox regression models and the effect was further characterized in a counterfactual analysis. Our analysis included 123 intervention and 173 control NSCLC patients from early to advanced stage, with significant between-cohort baseline differences. The propensity score-based weighting resulted in good baseline balance. A large survival benefit was observed in the intervention cohort, and intervention was an independent predictor of longer survival in a multivariate analysis when all baseline characteristics were included (HR = 0.63, p = 0.039). When post-baseline variables were included in the model, belonging to the intervention cohort was not an independent predictor of survival, but the survival benefit was explained by slightly better stage distribution and ECOG status at treatment initiation, together with trends for broader use of PET-CT and higher resectability rate. In conclusion, patient navigation is a valuable tool to improve cancer outcomes by facilitating more timely and complete cancer diagnostics. Contradictory evidence in the literature may be explained by common sources of bias, including the wait-time paradox and adjustment to intermediate outcomes.

Pharmacodynamics of Piperacillin-Tazobactam/Amikacin Combination versus Meropenem against Extended-Spectrum ß-Lactamase-Producing Escherichia coli in a Hollow Fiber Infection Model.

Carbapenems are recommended for the treatment of urosepsis caused by extended-spectrum ß-lactamase (ESBL)-producing, multidrug-resistant Escherichia coli; however, due to selection of carbapenem resistance, there is an increasing interest in alternative treatment regimens including the use of ß-lactam-aminoglycoside combinations. We compared the pharmacodynamic activity of piperacillin-tazobactam and amikacin as mono and combination therapy versus meropenem monotherapy against extended-spectrum ß-lactamase (ESBL)-producing, piperacillin-tazobactam resistant E. coli using a dynamic hollow fiber infection model (HFIM) over 7 days. Broth-microdilution was performed to determine the MIC of E. coli isolates. Whole genome sequencing was conducted. Four E. coli isolates were tested in HFIM with an initial inoculum of ~107 CFU/mL. Dosing regimens tested were piperacillin-tazobactam 4.5 g, 6-hourly, plus amikacin 30 mg/kg, 24-hourly, as combination therapy, and piperacillin-tazobactam 4.5 g, 6-hourly, amikacin 30 mg/kg, 24-hourly, and meropenem 1 g, 8-hourly, each as monotherapy. We observed that piperacillin-tazobactam and amikacin monotherapy demonstrated initial rapid bacterial killing but then led to amplification of resistant subpopulations. The piperacillin-tazobactam/amikacin combination and meropenem experiments both attained a rapid bacterial killing (~4-5 log10) within 24 h and did not result in any emergence of resistant subpopulations. Genome sequencing demonstrated that all ESBL-producing E. coli clinical isolates carried multiple antibiotic resistance genes including blaCTX-M-15, blaOXA-1, blaEC, blaTEM-1, and aac(6')-Ib-cr. These results suggest that the combination of piperacillin-tazobactam/amikacin may have a potential role as a carbapenem-sparing regimen, which should be tested in future urosepsis clinical trials.

A review of the impact of environmental factors and pollutants on covid-19 transmission.

The coronavirus disease (COVID-19) caused an unprecedented loss of life with colossal social and economic fallout over 237 countries and territories worldwide. Environmental conditions played a significant role in spreading the virus. Despite the availability of literature, the consecutive waves of COVID-19 in all geographical conditions create the necessity of reviewing the impact of environmental factors on it. This study synthesized and reviewed the findings of 110 previously published articles on meteorological factors and COVID-19 transmission. This study aimed to identify the diversified impacts of meteorological factors on the spread of infection and suggests future research. Temperature, rainfall, air quality, sunshine, wind speed, air pollution, and humidity were found as investigated frequently. Correlation and regression analysis have been widely used in previous studies. Most of the literature showed that temperature and humidity have a favorable relationship with the spread of COVID-19. On the other hand, 20 articles stated no relationship with humidity, and nine were revealed the negative effect of temperature. The daily number of COVID-19 confirmed cases increased by 4.86% for every 1 °C increase in temperature. Sunlight was also found as a significant factor in 10 studies. Moreover, increasing COVID-19 incidence appeared to be associated with increased air pollution, particularly PM10, PM2.5, and O3 concentrations. Studies also indicated a negative relation between the air quality index and the COVID-19 cases. This review determined environmental variables' complex and contradictory effects on COVID-19 transmission. Hence it becomes essential to include environmental parameters into epidemiological models and controlled laboratory experiments to draw more precious results.

Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum ß-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model.

BACKGROUND: Urosepsis caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened. OBJECTIVES: This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates. METHODS: E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days. RESULTS: Piperacillin/tazobactam regimens attained ∼4-5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h. CONCLUSIONS: Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome.

Pharmacodynamic evaluation of piperacillin/tazobactam against extended-spectrum ß-lactamase (ESBL)-producing versus non-ESBL-producing Escherichia coli in a hollow-fibre infection model.

Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli are a global public-health concern. We evaluated the pharmacodynamic activity of piperacillin/tazobactam (TZP) dosing regimens against ESBL-producing versus non-ESBL-producing E. coli. Five E. coli clinical isolates were obtained from Bangladesh. Broth microdilution and whole-genome sequencing (WGS) were performed on the five studied isolates. Three TZP-susceptible ESBL-producing and two non-ESBL-producing E. coli were exposed to TZP regimens of 4.5 g every 6 h (q6h) and every 8 h (q8h) as a 30-min infusion in a dynamic hollow-fibre infection model over 7 days. The extent of bacterial killing was ∼4-5 log10 CFU/mL against ESBL-producing and non-ESBL-producing E. coli with TZP q6h and q8h regimens over the first 8 h. Bacterial killing was similar between two of three ESBL-producing (CTAP#168 and CTAP#169) and two non-ESBL-producing (CTAP#179 and CTAP#180) E. coli clinical isolates over the course of the experiment. ESBL-producing CTAP#173 E. coli was poorly killed (∼1 log) compared with two non-ESBL-producing E. coli over 168 h. WGS revealed that ESBL-producing E. coli isolates co-harboured multiple antimicrobial resistance genes such as blaCTX-M-15, blaEC, blaOXA-1, blaTEM-1 and aac(6')-Ib-cr5. Overall, TZP q6h and q8h dosing regimens attained >3 log bacterial kill against all ESBL-producing or non-ESBL-producing E. coli within 24 h and maintained and prevented the emergence of resistance through the end of the experiment. In conclusion, TZP standard regimens resulted in similar bacterial killing and prevented the emergence of resistance against CTX-M-15-type ESBL-producing and non-ESBL-producing E. coli clinical isolates.

Integrated Care for Multimorbidity Population in Asian Countries: A Scoping Review.

Background: The complex needs of patients with multiple chronic diseases call for integrated care (IC). This scoping review examines several published Asian IC programmes and their relevant components and elements in managing multimorbidity patients. Method: A scoping review was conducted by searching electronic databases encompassing Medline, Embase, Scopus, and Web of Science. Three key concepts - 1) integrated care, 2) multimorbidity, and 3) Asian countries - were used to define searching strategies. Studies were included if an IC programme in Asia for multimorbidity was described or evaluated. Data extraction for IC components and elements was carried out by adopting the SELFIE framework. Results: This review yielded 1,112 articles, of which 156 remained after the title and abstract screening and 27 studies after the full-text screening - with 23 IC programmes identified from seven Asian countries. The top 5 mentioned IC components were service delivery (n = 23), workforce (n = 23), leadership and governance (n = 23), monitoring (n = 15), and environment (n = 14); whist financing (n = 9) was least mentioned. Compared to EU/US countries, technology and medical products (Asia: 40%, EU/US: 43%-100%) and multidisciplinary teams (Asia: 26%, EU/US: 50%-81%) were reported less in Asia. Most programmes involved more micro-level elements that coordinate services at the individual level (n = 20) than meso- and macro-level elements, and programmes generally incorporated horizontal and vertical integration (n = 14). Conclusion: In the IC programmes for patients with multimorbidity in Asia, service delivery, leadership, and workforce were most frequently mentioned, while the financing component was least mentioned. There appears to be considerable scope for development. Highlights: First scoping review to synthesise the key components and elements of integrated care programmes for multimorbidity in Asia.All programmes emphasized 'distinctive service delivery', 'leadership', and 'workforce' components.'Financing' component was least mentioned in identified integrated care programmes.

Value-based person-centred integrated care for frail elderly living at home: a quasi-experimental evaluation using multicriteria decision analysis.

OBJECTIVE: To evaluate the value of the person-centred, integrated care programme Care Chain Frail Elderly (CCFE) compared with usual care, using multicriteria decision analysis (MCDA). DESIGN: In a 12-month quasi-experimental study, triple-aim outcomes were measured at 0, 6 and 12 months by trained interviewers during home-visits. SETTING: Primary care, community-based elderly care. PARTICIPANTS: 384 community-dwelling frail elderly were enrolled. The 12-month completion rate was 70% in both groups. Propensity score matching was used to balance age, gender, marital status, living situation, education, smoking status and 3 month costs prior to baseline between the two groups. INTERVENTION: The CCFE is an integrated care programme with unique features like the presence of the elderly and informal caregiver at the multidisciplinary team meetings, and a bundled payment. PRIMARY AND SECONDARY OUTCOMES MEASURES: The MCDA results in weighted overall value scores that combines the performance on physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person-centredness, continuity of care and costs, with importance weights of patients, informal caregivers, professionals, payers and policy-makers. RESULTS: At 6 months, the overall value scores of CCFE were higher in all stakeholder groups, driven by enjoyment of life (standardised performance scores 0.729 vs 0.685) and person-centredness (0.749 vs 0.663). At 12 months, the overall value scores in both groups were similar from a patient's perspective, slightly higher for CCFE from an informal caregiver's and professional's perspective, and lower for CCFE from a payer's and policy-maker's perspective. The latter was driven by a worse performance on physical functioning (0.682 vs 0.731) and higher costs (€22 816 vs €20 680). CONCLUSIONS: The MCDA indicated that the CCFE is the preferred way of delivering care to frail elderly at 6 months. However, at 12 months, MCDA results showed little difference from the perspective of patients, informal caregivers and professionals, while payers and policy-makers seemed to prefer usual care.

Interpretable Machine Learning Algorithms to Predict the Axial Capacity of FRP-Reinforced Concrete Columns.

Fiber-reinforced polymer (FRP) rebars are increasingly being used as an alternative to steel rebars in reinforced concrete (RC) members due to their excellent corrosion resistance capability and enhanced mechanical properties. Extensive research works have been performed in the last two decades to develop predictive models, codes, and guidelines to estimate the axial load-carrying capacity of FRP-RC columns. This study utilizes the power of artificial intelligence and develops an alternative approach to predict the axial capacity of FRP-RC columns more accurately using data-driven machine learning (ML) algorithms. A database of 117 tests of axially loaded FRP-RC columns is collected from the literature. The geometric and material properties, column shape and slenderness ratio, reinforcement details, and FRP types are used as the input variables, while the load-carrying capacity is used as the output response to develop the ML models. Furthermore, the input-output relationship of the ML model is explained through feature importance analysis and the SHapely Additive exPlanations (SHAP) approach. Eight ML models, namely, Kernel Ridge Regression, Lasso Regression, Support Vector Machine, Gradient Boosting Machine, Adaptive Boosting, Random Forest, Categorical Gradient Boosting, and Extreme Gradient Boosting, are used in this study for capacity prediction, and their relative performances are compared to identify the best-performing ML model. Finally, predictive equations are proposed using the harmony search optimization and the model interpretations obtained through the SHAP algorithm.

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.

BACKGROUND: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. METHODS: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. FINDINGS: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. INTERPRETATION: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. FUNDING: The study was funded by the Bill & Melinda Gates Foundation.

Evaluating Complex Health and Social Care Program Using Multi-Criteria Decision Analysis: A Case Study of "Better Together in Amsterdam North".

OBJECTIVES: Multi-criteria decision analysis (MCDA) has been recommended to support policy making in healthcare. However, practical applications of MCDA are sparse. One potential use for MCDA is for the evaluation of programs for complex and vulnerable patients. These complex patients benefit from integrated care programs that span healthcare and social care and aim to improve more than just health outcomes. MCDA can evaluate programs that aim to improve broader outcomes because it allows the evaluation of multiple outcomes alongside each other. In this study, we evaluate an innovative integrated care program in the Netherlands using MCDA. METHODS: We used an innovative MCDA framework with broad outcomes of health, well-being, and cost to evaluate the Better Together in Amsterdam North (BSiN) program using preferences of patients, partners, providers, payers, and policy makers in the Netherlands. BSiN provides case management support for a period of 6 months. Seven outcomes that previous research has deemed important to complex patients were measured, including physical functioning and social relationships and participation. RESULTS: We find that the program improved the overall MCDA score marginally, and, thus, after 6 and after 12 months, BSiN was preferred to usual care by all stakeholders. BSiN was preferred to usual care, mostly owing to improvements in psychological well-being and social relationships and participation. CONCLUSIONS: The integrated healthcare and social care program BSiN in the Netherlands was preferred to usual care according to an MCDA evaluation. MCDA seems a useful method to evaluate complex programs with benefits beyond health.

Epidemiology of extended-spectrum ß-lactamase and metallo-ß-lactamase-producing Escherichia coli in South Asia.

Aim: To determine the prevalence of extended-spectrum ß-lactamase (ESBL) and metallo-ß-lactamase (MBL)-producing Escherichia coli in South Asia. Methodology: A systematic review and meta-analysis of data published in PubMed, EMBASE, Web of Science and Scopus. Results: The pooled prevalence of ESBL and MBL-producing E. coli in South Asia were 33% (95% CI: 27-40%) and 17% (95% CI: 12-24%), respectively. The prevalence of blaCTX-M type was 58% (95% CI: 49-66%) with blaCTX-M-15 being the most prevalent (51%, 95% CI: 40-62%) variant. The most prevalent MBL variant was blaNDM-1 (33%, 95% CI: 20-50%). Conclusion: This study suggests a high prevalence of ESBLs and MBLs among E. coli clinical isolates. Comprehensive resistance surveillance is required to guide clinicians prescribing antibiotics in South Asia.