Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26-41) versus 29% (IQR: 17-38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14-1.90 versus 1.00 (95% CI: 0.87-1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08-1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09-1.93] vs. 1.09 [95% CI: 0.93-1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.

Does the implementation of a trauma system affect injury-related morbidity and economic outcomes? A systematic review.

BACKGROUND: Trauma accounts for a huge burden of disease worldwide. Trauma systems have been implemented in multiple countries across the globe, aiming to link and optimise multiple aspects of the trauma care pathway, and while they have been shown to reduce overall mortality, much less is known about their cost-effectiveness and impact on morbidity. METHODS: We performed a systematic review to explore the impact the implementation of a trauma system has on morbidity, quality of life and economic outcomes, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All comparator study types published since 2000 were included, both retrospective and prospective in nature, and no limits were placed on language. Data were reported as a narrative review. RESULTS: Seven articles were identified that met the inclusion criteria, all of which reported a pre-trauma and post-trauma system implementation comparison in high-income settings. The overall study quality was poor, with all studies demonstrating a severe risk of bias. Five studies reported across multiple types of trauma patients, the majority describing a positive impact across a variety of morbidity and health economic outcomes following trauma system implementation. Two studies focused specifically on traumatic brain injury and did not demonstrate any impact on morbidity outcomes. DISCUSSION: There is currently limited and poor quality evidence that assesses the impact that trauma systems have on morbidity, quality of life and economic outcomes. While trauma systems have a fundamental role to play in high-quality trauma care, morbidity and disability data can have large economic and cultural consequences, even if mortality rates have improved. The sociocultural and political context of the surrounding healthcare infrastructure must be better understood before implementing any trauma system, particularly in resource-poor and fragile settings. PROSPERO REGISTRATION NUMBER: CRD42022348529 LEVEL OF EVIDENCE: Level III.

A Research Agenda for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome: An Official American Thoracic Society Research Statement.

Background: Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. The recent success of precision medicine in non-critical care settings has resulted from the confluence of large clinical and biospecimen repositories, innovative bioinformatics, and novel trial designs. Similar advances for precision medicine in sepsis and in the acute respiratory distress syndrome (ARDS) are possible but will require further investigation and significant investment in infrastructure. Methods: This project was funded by the American Thoracic Society Board of Directors. A multidisciplinary and diverse working group reviewed the available literature, established a conceptual framework, and iteratively developed recommendations for the Precision Medicine Research Agenda for Sepsis and ARDS. Results: The following six priority recommendations were developed by the working group: 1) the creation of large richly phenotyped and harmonized knowledge networks of clinical, imaging, and multianalyte molecular data for sepsis and ARDS; 2) the implementation of novel trial designs, including adaptive designs, and embedding trial procedures in the electronic health record; 3) continued innovation in the data science and engineering methods required to identify heterogeneity of treatment effect; 4) further development of the tools necessary for the real-time application of precision medicine approaches; 5) work to ensure that precision medicine strategies are applicable and available to a broad range of patients varying across differing racial, ethnic, socioeconomic, and demographic groups; and 6) the securement and maintenance of adequate and sustainable funding for precision medicine efforts. Conclusions: Precision medicine approaches that incorporate variability in genomic, biologic, and environmental factors may provide a path forward for better individualizing the delivery of therapies and improving care for patients with sepsis and ARDS.

Safety and efficacy of hydroxychloroquine for treatment of non-severe COVID-19 among adults in Uganda: a randomized open label phase II clinical trial.

BACKGROUND: Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. DESIGN: We conducted a randomized open label Phase II clinical trial from October-December 2020. METHODS: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. RESULTS: Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. CONCLUSION: Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. TRIAL REGISTRATION:  NCT04860284.

A Machine Learning-Based Triage Tool for Children With Acute Infection in a Low Resource Setting.

OBJECTIVES: To deploy machine learning tools (random forests) to develop a model that reliably predicts hospital mortality in children with acute infections residing in low- and middle-income countries, using age and other variables collected at hospital admission. DESIGN: Post hoc analysis of a single-center, prospective, before-and-after feasibility trial. SETTING: Rural district hospital in Rwanda, a low-income country in Sub-Sahara Africa. PATIENTS: Infants and children greater than 28 days and less than 18 years of life hospitalized because of an acute infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age, vital signs (heart rate, respiratory rate, and temperature) capillary refill time, altered mental state collected at hospital admission, as well as survival status at hospital discharge were extracted from the trial database. This information was collected for 1,579 adult and pediatric patients admitted to a regional referral hospital with an acute infection in rural Rwanda. Nine-hundred forty-nine children were included in this analysis. We predicted survival in study subjects using random forests, a machine learning algorithm. Five prediction models, all including age plus two to five other variables, were tested. Three distinct optimization criteria of the algorithm were then compared. The in-hospital mortality was 1.5% (n = 14). All five models could predict in-hospital mortality with an area under the receiver operating characteristic curve ranging between 0.69 and 0.8. The model including age, respiratory rate, capillary refill time, altered mental state exhibited the highest predictive value area under the receiver operating characteristic curve 0.8 (95% CI, 0.78-0.8) with the lowest possible number of variables. CONCLUSIONS: A machine learning-based algorithm could reliably predict hospital mortality in a Sub-Sahara African population of 949 children with an acute infection using easily collected information at admission which includes age, respiratory rate, capillary refill time, and altered mental state. Future studies need to evaluate and strengthen this algorithm in larger pediatric populations, both in high- and low-/middle-income countries.

Increasing Evidence-Based Interventions in Patients with Acute Infections in a Resource-Limited Setting: A Before-and-After Feasibility Trial in Gitwe, Rwanda.

OBJECTIVE: To evaluate whether a focused education program and implementation of a treatment bundle increases the rate of early evidence-based interventions in patients with acute infections. DESIGN: Single-center, prospective, before-and-after feasibility trial. SETTING: Emergency department of a sub-Saharan African district hospital. PATIENTS: Patients > 28 days of life admitted to the study hospital for an acute infection. INTERVENTIONS: The trial had three phases (each of four months). Interventions took place during the second (educational program followed by implementation of the treatment bundle) and third (provision of resources to implement treatment bundle) phases. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were collected at study enrollment; 24, 48, and 72 hours after hospital admission; and at discharge. A total of 1,594 patients were enrolled (pre-intervention, n = 661; intervention I, n = 531; intervention II, n = 402). The rate of early evidence-based interventions per patient during Intervention Phase I was greater than during the pre-intervention phase (74 ± 17 vs. 79 ± 15%, p < 0.001). No difference was detected when data were compared between Intervention Phases I and II (79 ± 15 vs. 80 ± 15%, p = 0.58). No differences in the incidence of blood transfusion (pre-intervention, 6%; intervention I, 7%; intervention II, 7%) or severe adverse events in the first 24 hours (allergic reactions: pre-intervention, 0.2%; intervention I, 0%; intervention II, 0%; respiratory failure: pre-intervention, 2%; intervention I, 2%; intervention II, 2%; acute renal failure: pre-intervention, 2%; intervention I, 2%; intervention II, 1%) were observed. CONCLUSIONS: Our results indicate that a focused education program and implementation of an infection treatment bundle in clinical practice increased the rate of early evidence-based interventions in patients with acute infections (mostly malaria) admitted to a sub-Saharan African district hospital. Provision of material resources did not further increase this rate. While no safety issues were detected, this could be related to the very low disease severity of the enrolled patient population (www.clinicaltrials.gov: NCT02697513).

World Health Organization Surgical Safety Checklist: Compliance and Associated Surgical Outcomes in Uganda's Referral Hospitals.

BACKGROUND: A pilot study on the World Health Organization (WHO) Surgical Safety Checklist (SSC) showed a reduction in both major complications and mortality of surgical patients. Compliance with this checklist varies around the world. We aimed to determine the extent of compliance with the WHO SSC and its association with surgical outcomes in 5 of Uganda's referral hospitals. METHODS: A multicentre prospective cohort study was conducted in 5 referral hospitals in Uganda. Using a questionnaire based on the WHO SSC, patients undergoing surgical operations were systematically recruited into the study from April 2016 to July 2016. The patients were followed up daily for 30 days or until discharge for the purpose of documentation of complications. Logistic regression and linear regression were used to assess for association between compliance and perioperative surgical outcomes. RESULTS: We recruited 859 patients into the study. Overall compliance with the WHO SSC was 41.7% (95% confidence interval [CI], 39.7-43.8) ranging from 11.9% to 89.8% across the different hospitals. Overall compliance with "sign in" was 44.7% (95% CI, 43-45.6), with "time out" was 42.0% (95% CI, 39.4-44.6), and with "sign out" was 33.3% (95% CI, 30.7-35.9). There was no association between compliance and perioperative surgical outcomes: length of hospital stay, adverse events, and mortality. CONCLUSIONS: This study revealed low levels of compliance with the WHO SSC. There was a statistically significant association between this level of compliance and the incidence of pain and loss of consciousness postoperatively.

Gender Parity in Critical Care Medicine.

Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. These documents inform and shape patient care around the world. In this Perspective we discuss the importance of diversity on guideline panels, the disproportionately low representation of women on critical care guideline panels, and existing initiatives to increase the representation of women in corporations, universities, and government. We propose five strategies to ensure gender parity within critical care medicine.

Ringer's Lactate Versus Normal Saline in Urgent Cesarean Delivery in a Resource-Limited Setting: A Pragmatic Clinical Trial.

BACKGROUND: Crystalloids are used routinely for perioperative fluid management in cesarean delivery. Few studies have determined the crystalloid of choice in obstetric anesthesia. We compared the effects of Ringer's lactate (RL) versus 0.9% normal saline (NS) on maternal and neonatal blood pH and 24-hour postoperative morbidity in urgent cesarean delivery in a low-resource setting. Our hypothesis was that RL would result in 30% less acidosis than NS. METHODS: This was a pragmatic prospective double-blind randomized controlled trial in the Mulago National Referral Hospital Labor Ward Theater from September 2011 to May 2012. Five hundred parturients were studied; 252 were randomly assigned to NS and 248 to RL groups. Preoperative and postoperative maternal venous blood gases and placental umbilical arterial cord blood gases were analyzed. The primary outcome was incidence of maternal acidosis, as defined by a postoperative drop in venous pH below 7.32 or reduction in base excess below -3 in a previously normal parturient. Maternal 24-hour postoperative morbidity, neonatal pH, and neonatal base excess were the main secondary outcomes. The study was registered in ClinicalTrials.gov as NCT01585740. RESULTS: The overall incidence of maternal acidosis was 38% in NS and 29% in RL (relative risk, 1.29; 95% confidence interval, 1.01-1.66; P = .04). Thirty-two percent of parturients in NS experienced a drop in venous pH below 7.32 postoperatively, compared with 19% in RL (relative risk, 1.65; 95% confidence interval, 1.18-2.31; P = .003). The comparative drop in base excess postoperatively below -3 between the 2 groups was not statistically significant. There were no significant differences in the incidence of maternal 24-hour postoperative morbidity events and neonatal outcomes between the 2 groups. CONCLUSIONS: NS may be a safe choice for intraoperative fluid therapy in urgent cesarean delivery as RL, albeit with an increased incidence of metabolic acidosis.

Feasibility of the modified sequential organ function assessment score in a resource-constrained setting: a prospective observational study.

BACKGROUND: Sub-Saharan Africa has a great burden of critical illness with limited health care resources. We evaluated the feasibility and utility of the modified Sequential Organ Function Assessment (mSOFA) score in assessing morbidity and mortality in the National Referral Hospital's intensive care unit (ICU) for one year. METHODS: We conducted a prospective, observational cohort study on patients above 12 years of age admitted to the ICU at Mulago Hospital (Kampala, Uganda). All SOFA scores were determined at admission and at 48 h. We modified the SOFA score by replacing the PaO2/FiO2 ratio with SPO2/FiO2. The primary outcome was ICU mortality. RESULTS: This ICU cohort of 118 patients had a mean age of 37 years and an ICU mortality rate of 46.6%. Non-survivors had higher initial (7.7 SD 3.8 vs. 5.5 SD 3.3; p = 0.007), mean (8.1 SD 3.9 vs 4.7 SD 2.6; p < 0.001) and highest mSOFA scores (9.4 SD 4.2 vs. 5.8 SD 3.2; p < 0.001), with an increase of 1.0 (SD 3.1) mSOFA on average after 48 h when compared to survivors (p < 0.001). The area under the receiver operating characteristic curves for each mSOFA category was: initial-0.68, mean-0.76, highest-0.76 and delta mSOFA-0.74. Multivariate logistic regression analysis showed no significant association between mSOFA scores and mortality. CONCLUSION: Our results confirm that calculation of the mSOFA score is feasible for an ICU population in a resource-limited country. More data are needed to test for an association between mSOFA and mortality.

Antibiotic prophylaxis for caesarean section at a Ugandan hospital: a randomised clinical trial evaluating the effect of administration time on the incidence of postoperative infections.

BACKGROUND: Prophylactic antibiotics are used to prevent postoperative infections after caesarean section. Studies have suggested that the timing of prophylaxis plays an important role. Over the years, the role of the anaesthesiologist in the administration of prophylactic antibiotics has become prominent. Therefore, there is an increasing need for anaesthesia providers to understand the rationale of antibiotic prophylaxis. We therefore sought to compare the effect of antibiotics prophylaxis within 1 hour before skin incision and after skin incision on the incidence of postoperative infections in patients undergoing caesarean section at Mulago Hospital. METHODS: We conducted a single-blind randomised clinical trial conducted at Mulago Hospital evaluating 464 patients undergoing emergency caesarean section. Patients were randomly assigned a group number that allocated them to either arm of the study. They received the same prophylactic antibiotic according to their allotment, that is, either within 1 hour before skin incision or after skin incision as per current standards of practice in Mulago Hospital. They were followed up to detect infection up to 10 days postoperatively. The primary outcome was postoperative infection. The data collected were analysed with STATA version 12 using univariate and bivariate analysis. RESULTS: The risk of overall postoperative infection was significantly lower when prophylaxis was given within an hour before incision (RR O.77, 95% CI 0.62-0.97). We also found endometritis to be significantly reduced in the pre-incision group (RR 0.62; 95% CI 0.39-0.99; P value 0.036). CONCLUSIONS: Giving prophylactic antibiotics before skin incision reduces risk of postoperative infection, in particular of endometritis. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR201311000610495. Date of trial registration: 12(th) August 2013.

Acute kidney injury among adult patients with sepsis in a low-income country: clinical patterns and short-term outcomes.

BACKGROUND: Acute kidney injury (AKI) is a common complication of sepsis. We determined the prevalence of AKI among adult patients with sepsis on the medical wards in a low-income country and described their clinical pattern and outcomes at discharge. METHODS: We conducted a cross-sectional study of sepsis-related AKI on the adult medical wards of Mulago National Referral Hospital between January and April 2013. All patients meeting the American College of Chest Physicians (ACP) sepsis criteria were recruited. Demographic, clinical, laboratory and ultrasonography data were recorded and all patients with AKI were followed up to a maximum of 2 weeks. Proportional analysis was carried out and odds ratios with 95% confidence intervals were calculated in the bivariate analysis. RESULTS: Of 387 patients recruited, 217 (55.6%) were male and the average age was 37 years (range18-90 years). The prevalence of sepsis-related AKI was 16.3%. Age >59 years (p = 0.023), a postural drop in systolic blood pressure of >9 mmHg (p = 0.015) and a white blood cell count >12,000 cells/mL (p = 0.003) were significantly associated with AKI. In-hospital mortality among patients with AKI was 21% (13/63). 59% (20/49) of patients who were discharged alive or were still on the wards after 2 weeks had persistent kidney injury. Acute Kidney Injury Network (AKIN) Stage 3 was significantly associated with persistence of kidney injury (p = 0.001). None of the patients requiring dialysis or ICU care received either because of limited access. CONCLUSIONS: The prevalence, morbidity and mortality due to AKI among sepsis patients in Uganda is very high and limited access to dialysis and ICU care is a major factor in poor outcomes for these patients.

Effects of propofol versus thiopental on Apgar scores in newborns and peri-operative outcomes of women undergoing emergency cesarean section: a randomized clinical trial.

BACKGROUND: General and regional anesthesia are the two main techniques used in cesarean section. Regional anesthesia is preferred, but under certain circumstances, such as by patient request and in patients with back deformities, general anesthesia is the only option. Commonly used induction agents include thiopental, ketamine, and propofol, depending on availability and the maternal clinical condition. The objective of this study was to investigate the effects of thiopental and propofol on the neonatal Apgar score and maternal recovery time following emergency cesarean section in order to determine the superior agent for mothers and neonates. METHODS: This single-blinded randomized clinical trial included 150 ASA I and II patients block-randomized equally between the two study arms. Pregnant women at term scheduled to undergo cesarean section and their neonates were enrolled. The primary outcomes were the Apgar scores through 10-min postpartum, resuscitation requirement, and admission to the neonatal intensive care unit. The secondary outcome was the maternal recovery times. RESULTS: At 0 min (umbilical cord clamp time), 43 (57.3%) neonates in the propofol group had an Apgar score < 7 compared with 31 (41.3%) neonates in the thiopental group (p = 0.05). The maternal recovery time was shorter in the propofol group than in the thiopental group (25 min vs. 31 min, respectively, p = 0.003). CONCLUSION: Apgar scores do not differ significantly whether thiopental or propofol is used for anesthetic induction in women undergoing general anesthesia for an emergency cesarean section. TRIAL REGISTRATION: Pan-African Clinical Trial Registry (#PACTR201306000536344) http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?_nfpb=true&_pageLabel=atm_portal_page_mytrials.

Knowledge, attitudes and use of labour analgesia among women at a low-income country antenatal clinic.

BACKGROUND: Childbirth is one of the most painful experiences of a woman's life. Authorities in the fields of obstetrics and anaesthesia encourage use of labour analgesia. Unlike in high-income countries, pain relief in labour in Africa is not a well established service, especially in the low-income countries like Uganda. Little is known about whether parturients would be amenable to labour analgesia. We sought to determine knowledge, attitudes and use of labour analgesia among women attending the antenatal clinic at Mulago National Referral Hospital. METHODS: Upon obtaining institutional approval, we conducted a cross-sectional descriptive study. Women were requested to complete the researcher-administered survey following informed consent. The study was conducted in the general antenatal clinic at the Mulago National Referral Hospital. RESULTS: Of 1293 participants interviewed, only 7 % of the participants had knowledge of labour analgesia. Of the multiparous mothers 87.9 % did not have labour analgesia in their previous deliveries, although 79.2 % of them had delivered in a national referral hospital. The commonest reason for refusal of labour analgesia was to experience natural childbirth. 87.7 % of the participants wanted labour analgesia for their next delivery. CONCLUSION: There is a wide gap between the desire for labour analgesia and its availability. Obstetricians and anaesthesiologists have a role to educate the women, and to provide this much desired service.

Prevalence, outcomes and factors associated with adult in hospital cardiac arrests in a low-income country tertiary hospital: a prospective observational study.

BACKGROUND: Research on cardiac arrest and cardiopulmonary resuscitation (CPR) has considerably increased in recent decades, and international guidelines for resuscitation have been implemented and have undergone several changes. Very little is known about the prevalence and management of in-hospital cardiac arrest in low-resource settings. We therefore sought to determine the prevalence, outcomes and associated factors of adult inpatients with cardiac arrest at a tertiary referral hospital in a low-income country. METHODS: Upon obtaining institutional approval, we conducted a prospective observational period prevalence study over a 2-month period. We recruited adult inpatients with cardiac arrest in the intensive care unit and emergency wards of Mulago Hospital, Uganda during the study period. We reviewed all files and monitoring charts, and also any postmortem findings. Data were analyzed with Stata 12 and statistical significance was set at p < 0.05. RESULTS: There was a cardiac arrest in 2.3% (190) of 8,131 hospital admissions; 34.5% occurred in the intensive care unit, 4.4% in emergency operating theaters, and 3.0% in emergency wards. A majority (63.2%) was unwitnessed, and only 35 patients (18.4%) received CPR. There was return of spontaneous circulation (ROSC) in 14 (7.4%) cardiac arrest patients. Survival to 24 h occurred in three ROSC patients, which was only 1.6% of all cardiac arrest patients during the study period. Trauma was the most common primary diagnosis and HIV infection was the most common co-morbidity. CONCLUSION: Our hospital has a high prevalence of cardiac arrest, and low rates of CPR performance, ROSC, and 24-hour survival. Single provider CPR; abnormal temperatures as well as after hours/weekend CAs were associated with lower survival rates.

Characteristics and outcomes of patients admitted to intensive care units in Uganda: a descriptive nationwide multicentre prospective study.

Intensive care unit (ICU) mortality rates have decreased over time. However, in low-and lower-middle income countries (LMICs), there remains an excess ICU mortality with limited understanding of patient characteristics, treatments, and outcomes from small single centre studies. We aimed therefore, to describe the characteristics, therapies and outcomes of patients admitted to all intensive care units in Uganda. A nationwide prospective observational study including all patients admitted Uganda's ICUs with available daily charts was conducted from 8th January 2018 to 1st April 2018. Socio-demographics and clinical characteristics including worst vital signs in the first 24 h of admission were recorded with calculation of the National Early Warning Score (NEWS-2) and quick Sequential Organ Function Assessment (qSOFA) score. ICU interventions were recorded during the ICU stay and patients were followed up to 28 days in ICU. The primary outcome was 28 day ICU mortality. Three-hundred fifty-one patients were analysed with mean age 39 (24.1) years, 205 (58.4%) males with 197 (56%) surgical admissions. The commonest indication for ICU admission was postoperative care (42.9%), 214 (61%) had at least one comorbidity, with hypertension 104 (48.6%) most prevalent and 35 (10%) HIV positive. The 28 day ICU mortality was 90/351 (25.6%) with a median ICU stay of 3 (1-7) days. The highest probability of death occurred during the first 10 days with more non-survivors receiving mechanical ventilation (80% vs 34%; p < 0.001), sedation/paralysis (70% vs 50%; p < 0.001), inotropic/vasopressor support (56.7% vs 22.2%; p < 0.001) and renal replacement therapy (14.4% vs 4.2%; p < 0.001). Independent predictors of ICU mortality included mechanical ventilation (HR 3.34, 95% CI 1.48-7.52), sedation/paralysis (HR 2.68, 95% CI 1.39-5.16), inotropes/vasopressor (HR 3.17,95% CI 1.89-5.29) and an HIV positive status (HR 2.28, 95% CI 1.14-4.56). This study provides a comprehensive description of ICU patient characteristics, treatment patterns, and outcomes in Uganda. It not only adds to the global body of knowledge on ICU care in resource-limited settings but also serves as a foundation for future research and policy initiatives aimed at optimizing ICU care in Sub-Saharan Africa.

Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial - the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study.

RATIONALE: Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting. METHODS: This is a prospective, multicentre, randomised, controlled, stepped wedge trial, in which patients presenting with AHRF in Uganda will be randomly assigned to standard oxygen therapy delivered through a face mask, HFNC oxygen or CPAP. The primary outcome is all-cause mortality at 28 days. Secondary outcomes include the number of patients with criteria for intubation at day 7, the number of patients intubated at day 28, ventilator-free days at day 28 and tolerance of each respiratory support. ETHICS AND DISSEMINATION: The study has obtained ethical approval from the Research and Ethics Committee, School of Biomedical Sciences, College of Health Sciences, Makerere University as well as the Uganda National Council for Science and Technology. Patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04693403. PROTOCOL VERSION: 8 September 2023; version 5.

Evaluating patient factors, operative management and postoperative outcomes in trauma laparotomy patients worldwide: a protocol for a global observational multicentre trauma study.

INTRODUCTION: Trauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed operation. Variation likely exists in how these patients are managed and their subsequent outcomes, yet very little global data on the topic currently exists. The objective of the GOAL-Trauma study is to evaluate both patient and injury factors for those undergoing trauma laparotomy, their clinical management and postoperative outcomes. METHODS: We describe a planned prospective multicentre observational cohort study of patients undergoing trauma laparotomy. We will include patients of all ages who present to hospital with a blunt or penetrating injury and undergo a trauma laparotomy within 5 days of presentation to the treating centre. The study will collect system, patient, process and outcome data, following patients up until 30 days postoperatively (or until discharge or death, whichever is first). Our sample size calculation suggests we will need to recruit 552 patients from approximately 150 recruiting centres. DISCUSSION: The GOAL-Trauma study will provide a global snapshot of the current management and outcomes for patients undergoing a trauma laparotomy. It will also provide insight into the variation seen in the time delays for receiving care, the disease and patient factors present, and patient outcomes. For current standards of trauma care to be improved worldwide, a greater understanding of the current state of trauma laparotomy care is paramount if appropriate interventions and targets are to be identified and implemented.