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MORU’s Mo Yin and MOCRU’s Myo Maung Maung Swe were awarded a prize by the NDM’s Graduate Studies Committee. Very competitive awards, the prizes are given annually to current or recently graduated students of NDM supervisors on the basis of their publication record, the impact and novelty of their research, references, and research within their department.
Operational evaluation of the deployment of Malaria/CRP Duo and Dengue Duo rapid diagnostic tests for the management of febrile illness by village malaria workers in rural Cambodia
Abstract Introduction The decline in malaria cases in Cambodia has led to a relative increase in non-malarial febrile illness. In rural Cambodia, village malaria workers (VMWs) provide early diagnosis and treatment for malaria, but their role and relevance are diminishing as malaria cases decline. Expanding VMW roles would ensure continued utilisation of their services until malaria elimination is achieved and strengthen community health services. Methods A mixed methods operational research study was implemented to evaluate the use of two combination-RDTs (combo-RDTs) as an expansion of the VMW role, enabling VMWs in Cambodia to test for diseases other than malaria for the first time. VMWs in 78 villages in Battambang and Pailin Provinces were trained and provided with either a Malaria/CRP Duo or Dengue Duo RDT to assess febrile patients. Data were collected on VMW consultations, and combo-RDT usage and results. Focus group discussions (FGDs) and competency assessments of combo-RDT usage were conducted with VMWs. The main objectives were to determine whether VMWs could perform these combo-RDTs correctly and follow management algorithms, and whether deployment had an impact on VMW consultation rates. Perspectives concerning role expansion and the feasibility of conducting additional tests were also explored. Results Between June 2022, and May 2023, a total of 2,425 febrile patients were assessed with either a Malaria/CRP Duo or Dengue Duo RDT. Active dengue infection (NS1- and/or IgM-positive) was identified in 1.2% (11/915) of patients. Positive CRP results (> 20 mg/L) were found for 3.2% (48/1,510) of patients. Following deployment, there was an immediate mean increase of 4.4 VMW consultations per month, from 9.0 to 13.4 (p < 0.01). Competency assessments revealed that some VMWs had difficulty performing the Dengue Duo RDT, particularly in collecting the correct blood volume. This limitation may have led to false-negative dengue NS1 results. VMWs and community members were keen to broaden the skills and responsibilities of VMWs. Conclusions Deploying combo-RDTs to VMWs led to a higher utilization of their services. Difficulties performing some aspects of the Dengue Duo RDT, low positivity rates, and a lack of actionable outcomes within the existing context of VMW services suggest that alternative interventions may be better suited for VMW role expansion at this time. Overall, VMWs and community members were receptive to the expansion of the VMW role for a wider range of diseases other than malaria.
Understanding the primary healthcare context in rural South and Southeast Asia: a village profiling study
Abstract Background Understanding contextual factors is critical to the success of health service planning and implementation. However, few contextual data are available at the village level in rural South and Southeast Asia. This study addressed the gap by profiling representative villages across seven sites in Thailand (n=3), Cambodia, Laos, Myanmar and Bangladesh. Methods Key informant surveys supplemented by other information sources were used to collect data from 687 villages on four key indicators (literacy rate, and percentages of attended deliveries, fully immunised children and latrine coverage), as well as access to various services. Data were analysed descriptively. Results Sites varied considerably. Five were highly diverse ethno-culturally and linguistically, and all relied on primary health centres and village health/malaria workers as the main providers of primary healthcare. These were generally bypassed by severely ill patients for urban first-level referral hospitals and private sector facilities. While >75% of villages were near primary schools, educational attainment was generally low. Over 70% of villages at each site had mobile phone coverage and availability of electricity was high (≥65% at all sites bar Myanmar). Conclusion These results illustrate the similarities and differences of villages in this region that must be considered in public health research and policymaking.
The spectrum of health conditions in community-based cross-sectional surveys in Southeast Asia 2010-21: a scoping review
Abstract Background Southeast Asia is undergoing an epidemiological transition with non-communicable illnesses becoming increasingly important, yet infectious diseases (tuberculosis, HIV, hepatitis B, malaria) remain widely prevalent in some populations, while emerging and zoonotic diseases threaten. There are also limited population-level estimates of many important heath conditions. This restricts evidence-based decision-making for disease control and prevention priorities. Cross-sectional surveys can be efficient epidemiological tools to measure the prevalence of a wide range of diseases, but no systematic assessment of their coverage of different health conditions has been produced for the region. Methods We conducted a systematic search in Medline, Embase, Global Health, CINAHL, Scopus, Web of Science Core Collection, and Global Index Medicus, and additionally Google Scholar. Our inclusion criteria were cross-sectional surveys conducted with community-based recruitment, in Bangladesh, Cambodia, Laos, Myanmar, and Thailand, published between January 1, 2010 and January 27, 2021, and reporting the prevalence of any health condition. Results 542 publications from 337 surveys were included. Non-communicable conditions (n = 205) were reported by more surveys than infectious conditions (n = 124). Disability (n = 49), self-report history of any disease or symptoms (n = 35), and self-perceived health status (n = 34), which reflect a holistic picture of health, were studied by many fewer surveys. In addition, 45 surveys studied symptomatic conditions which overlap between non-communicable and infectious conditions. The most surveyed conditions were undernutrition, obesity, hypertension, diabetes, intestinal parasites, malaria, anemia, diarrhea, fever, and acute respiratory infections. These conditions overlap with the most important causes of death and disability in the Global Burden of Disease study. However, other high-burden conditions (e.g. hearing loss, headache disorder, low back pain, chronic liver and kidney diseases, and cancers) were rarely studied. Conclusion There were relatively few recent surveys from which to estimate representative prevalences and trends of health conditions beyond those known to be high burden. Expanding the spectrum of health conditions in cross-sectional surveys could improve understanding of evolving disease patterns in the region.
Evaluation of an electronic clinical decision support algorithm to improve primary care management of acute febrile illness in rural Cambodia: protocol for a cluster-randomised trial
IntroductionAcute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called ‘Electronic clinical Decision support for Acute fever Management (EDAM)’ has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan.Methods and analysisThis is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM.Ethics and disseminationResults will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR).Trial registration numberInternational Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).
Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria.
Although asymptomatic malaria was historically perceived as innocuous, emerging evidence revealed an immunosuppressive signature induced by asymptomatic Plasmodium falciparum infections. To examine if a similar process occurs in Plasmodium vivax malaria, we pursued a systems approach, integrating transcriptional profiling together with previously reported and novel mass cytometry phenotypes from individuals with symptomatic and asymptomatic P. vivax malaria. Symptomatic P. vivax malaria featured upregulation of anti-inflammatory pathways and checkpoint receptors. A profound downregulation of transcripts with roles in monocyte function was observed in symptomatic P. vivax malaria. This reduction in monocyte transcriptional activity was accompanied by a significant depletion of CCR2+CXCR4+ classical monocytes in symptomatic individuals. Despite allowing transcriptional profiles supporting T-cell differentiation, dysregulation of genes associated with monocyte activation and the inflammasome was also evident in individuals carrying P. vivax asymptomatic infections. Our results identify monocyte dysregulation as a key feature of the response to P. vivax malaria and support the concept that asymptomatic infection is not innocuous and might not support all immune processes required to eliminate parasitemia or efficiently respond to vaccination.
Sedation Practices in Mechanically Ventilated Neurocritical Care Patients from 19 Countries: An International Cohort Study.
BackgroundOur objective was to characterize the impact of common initial sedation practices on invasive mechanical ventilation (IMV) duration and in-hospital outcomes in patients with acute brain injury (ABI) and to elucidate variations in practices between high-income and middle-income countries.MethodsThis was a post hoc analysis of a prospective observational data registry of neurocritically ill patients requiring IMV. The setting included 73 intensive care units (ICUs) in 18 countries, with a total of 1,450 patients with ABI requiring IMV. There were no interventions.ResultsPatients were categorized into day 1 propofol, midazolam, propofol and midazolam, dexmedetomidine, or sodium thiopental. The primary outcome was duration of IMV. Secondary outcomes were ICU and hospital mortality, ICU length of stay, days to first extubation, extubation failure, and withdrawal of life-sustaining therapy. Multivariable analyses were adjusted for clinically preselected covariates. Of 1,450 included patients (median age 54 years, 66% male), 41.2% (n = 597) were started on propofol, 26.1% (n = 379) were started on midazolam, 19.9% were started on propofol and midazolam, 0.3% (n = 5) were started on sodium thiopental, 0.7% (n = 10) were started on dexmedetomidine, and 11.8% (n = 171) were treated without sedation. After adjustment, there was no significant difference in IMV duration between patients who received midazolam (aβ = 0.64, p = 0.43, 95% confidence interval [CI] - 0.96 to 2.24) or propofol and midazolam (aβ = 0.32, p = 0.46, 95% CI - 1.44 to 2.12) compared with patients who received propofol. Patients who were started on midazolam had an average length of ICU stay that was 2.78 days longer than patients started on propofol (p = 0.003, 95% CI 0.94-4.63). There were no differences in mortality, days to first extubation, extubation failure, or withdrawal of life-sustaining therapy. Patients from high-income countries (n = 1,125) were more likely to receive propofol on day 1 (45.7 vs. 25.5%), whereas patients from middle-income countries (n = 325) were more likely to receive midazolam (32.6 vs. 24.3%) (p ConclusionsIn an international registry of patients with ABI requiring IMV, IMV duration did not differ significantly relative to initial sedation strategy. However, patients started on midazolam had longer ICU stay.
Epidemiology, Ventilation Management, and Outcomes in Invasively Ventilated Coronavirus Disease 2019 Patients: An Analysis of Four Observational Studies in Four Countries on Two Continents.
Epidemiology, ventilator management, and outcomes in patients with acute respiratory distress syndrome (ARDS) because of coronavirus disease 2019 (COVID-19) have been described extensively but have never been compared between countries. We performed an individual patient data analysis of four observational studies to compare epidemiology, ventilator management, and outcomes. We used propensity score weighting to control for confounding factors. The analysis included 6,702 patients: 1,500 from Argentina, 844 from Brazil, 975 from the Netherlands, and 3,383 from Spain. There were substantial differences in baseline characteristics between countries. There were small differences in ventilation management. Intensive care unit mortality was higher in Argentina and Brazil compared with the Netherlands and Spain (59.6% and 56.6% versus 32.1% and 34.7%; P <0.001). The median number of days free from ventilation and alive at day 28 was equally low (0 [0-7], 0 [0-18], 1 [0-16], and 0 [0-16] days, respectively; P = 0.03), and the median number of days free from ventilation and alive at day 60 was higher in the Netherlands and Spain (0 [0-37], 0 [0-50], 33 [0-48], and 26 [0-48] days, respectively; P <0.001). Propensity score matching confirmed the outcome differences. Thus, the outcome of COVID-19 ARDS patients in Argentina and Brazil was substantially worse compared with that of patients in the Netherlands and Spain. It is unlikely that this results from differences in case mix or ventilation management.
Closed-loop ventilation in COVID-19 patients with acute hypoxemic respiratory failure-A case series.
BackgroundINTELLiVENT-adaptive support ventilation (ASV) is an automated closed-loop mode of invasive ventilation for use in critically ill patients. INTELLiVENT-ASV automatically adjusts, without the intervention of the caregiver, ventilator settings to achieve the lowest work and force of breathing.AimsThe aim of this case series is to describe the specific adjustments of INTELLiVENT-ASV in patients with acute hypoxemic respiratory failure, who were intubated for invasive ventilation.Study designWe describe three patients with severe acute respiratory distress syndrome (ARDS) because of COVID-19 who received invasive ventilation in our intensive care unit (ICU) in the first year of the COVID-19 pandemic.ResultsINTELLiVENT-ASV could be used successfully, but only after certain adjustments in the settings of the ventilator. Specifically, the high oxygen targets that are automatically chosen by INTELLiVENT-ASV when the lung condition 'ARDS' is ticked had to be lowered, and the titration ranges for positive end expiratory pressure (PEEP) and inspired oxygen fraction (FiO2 ) had to be narrowed.ConclusionsThe challenges taught us how to adjust the ventilator settings so that INTELLiVENT-ASV could be used in successive COVID-19 ARDS patients, and we experienced the benefits of this closed-loop ventilation in clinical practice.Relevance to clinical practiceINTELLiVENT-ASV is attractive to use in clinical practice. It is safe and effective in providing lung-protective ventilation. A closely observing user always remains needed. INTELLiVENT-ASV has a strong potential to reduce the workload associated with ventilation because of the automated adjustments.
Enhanced lupus progression in alcohol-administered Fc gamma receptor-IIb-deficiency lupus mice, partly through leaky gut-induced inflammation.
Alcohol can induce a leaky gut, with translocation of microbial molecules from the gut into the blood circulation. Although the contribution of inflammation to organ-mediated damage in lupus has been previously demonstrated, the mechanistic roles of alcohol consumption in lupus activation are not known. Herein, we tested the effects of 10-week lasting alcohol administration on organ damages and immune responses in 8-week-old lupus-prone Fc gamma receptor IIb-deficient (FcγRIIb-/- ) mice. Our study endpoints were evaluation of systemic inflammation and assessment of fecal dysbiosis along with endotoxemia. In comparison with alcohol-administered wild-type mice, FcγRIIb-/- mice demonstrated more prominent liver damage (enzyme, histological score, apoptosis, malondialdehyde oxidant) and serum interleukin(IL)-6 levels, despite a similarity in leaky gut (fluorescein isothiocyanate-dextran assay, endotoxemia and gut occludin-1 immunofluorescence), fecal dysbiosis (microbiome analysis) and endotoxemia. All alcohol-administered FcγRIIb-/- mice developed lupus-like characteristics (serum anti-dsDNA, proteinuria, serum creatinine and kidney injury score) with spleen apoptosis, whereas control FcγRIIb-/- mice showed only a subtle anti-dsDNA. Both alcohol and lipopolysaccharide (LPS) similarly impaired enterocyte integrity (transepithelial electrical resistance), and only LPS, but not alcohol, upregulated the IL-8 gene in Caco-2 cells. In macrophages, alcohol mildly activated supernatant cytokines (tumor necrosis factor-α and IL-6), but not M1 polarization-associated genes (IL-1β and iNOS), whereas LPS prominently induced both parameters (more prominent in FcγRIIb-/- macrophages than wild type). There was no synergy in LPS plus alcohol compared with LPS alone in both enterocytes and macrophages. In conclusion, alcohol might exacerbate lupus-like activity partly through a profound inflammation from the leaky gut in FcγRIIb-/- mice.
Early acute kidney injury is associated with in-hospital adverse outcomes in critically ill burn patients: an observational study.
BackgroundThere are no studies in large series of burn patients on the relationship between acute kidney injury (AKI) and adverse outcomes using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.MethodsWe retrospectively analysed data from a cohort of burn patients admitted to the intensive care unit (ICU) with the diagnosis of burn injury. The diagnosis of AKI over the first 7 days after injury was made according to the KDIGO guidelines. The primary outcome was ICU mortality. We used estimative models using univariable and multivariable logistic regression analyses.ResultsA total of 960 patients were studied and AKI was diagnosed in 50.5%. In multivariable analysis, AKI was associated, as compared with patients without AKI, with ICU mortality {adjusted odds ratio [aOR] 2.135 [95% confidence interval (CI) 1.384-3.293]} and secondary outcomes [kidney replacement therapy, aOR 4.030 (95% CI 1.838-8.835); infection, aOR 1.437 (95% CI 1.107-1.866); hospital mortality, aOR 1.652 (95% CI 1.139-2.697)]. AKI stage 1 was associated with a higher ICU [aOR 1.869 (95% CI 1.183-2.954)] and hospital mortality [aOR 1.552 (95% CI 1.050-2.296)] and infection [aOR 1.383 (95% CI 1.049-1.823)]. AKI meeting the urine output (UO) criterion alone was not associated with increased mortality. Ignoring the UO criterion would have missed 50 (10.3%) cases with AKI.ConclusionThe KDIGO guidelines are useful to diagnose AKI in burn patients. Even the mild form of AKI is independently associated with increased mortality. Considering the UO criterion is important to more accurately assess the incidence of AKI, but AKI meeting the UO criterion alone is not associated with increased mortality.
Hyperoxia-induced lung injury in acute respiratory distress syndrome: what is its relative impact?
Over the past decade, the interest in oxygen toxicity has led to various observational studies and randomized clinical trials in critically ill patients, assessing the association with outcomes and the potential benefit of restrictive oxygenation targets. Yet to date, no consensus has been reached regarding the clinical impact of hyperoxia and hyperoxemia. In this perspective article, we explore the experimental and clinical evidence on hyperoxia-induced lung injury (HILI) and assess its relative impact in current critical care practice, specifically in patients who require oxygen therapy due to acute respiratory distress syndrome (ARDS). Here, we suggest that in current clinical practice in the setting of ARDS HILI may actually be of less importance than other ventilator-related factors.
A closed-loop ventilation mode that targets the lowest work and force of breathing reduces the transpulmonary driving pressure in patients with moderate-to-severe ARDS.
IntroductionThe driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing.AimTo compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS.MethodsSingle-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation.ResultsThirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0-10.0] vs. 10.0 [8.0-11.0] cmH2O, mean difference - 2.5 [95% CI - 2.6 to - 2.1] cmH2O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients.ConclusionsIn this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation. Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1 .
ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.
PurposeSevere community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP.MethodsThe European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations.ResultsRecommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions.ConclusionsIn these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.