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34 result(s) for "Rudd, Kristina E."
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The global burden of sepsis: barriers and potential solutions
Sepsis is a major contributor to the global burden of disease. The majority of sepsis cases and deaths are estimated to occur in low and middle-income countries. Barriers to reducing the global burden of sepsis include difficulty quantifying attributable morbidity and mortality, low awareness, poverty and health inequity, and under-resourced and low-resilience public health and acute health care delivery systems. Important differences in the populations at risk, infecting pathogens, and clinical capacity to manage sepsis in high and low-resource settings necessitate context-specific approaches to this significant problem. We review these challenges and propose strategies to overcome them. These strategies include strengthening health systems, accurately identifying and quantifying sepsis cases, conducting inclusive research, establishing data-driven and context-specific management guidelines, promoting creative clinical interventions, and advocacy.
Comparative prognostic accuracy of sepsis scores for hospital mortality in adults with suspected infection in non-ICU and ICU at an academic public hospital
Sepsis is a global healthcare challenge and reliable tools are needed to identify patients and stratify their risk. Here we compare the prognostic accuracy of the sepsis-related organ failure assessment (SOFA), quick SOFA (qSOFA), systemic inflammatory response syndrome (SIRS), and national early warning system (NEWS) scores for hospital mortality and other outcomes amongst patients with suspected infection at an academic public hospital. 10,981 adult patients with suspected infection hospitalized at a U.S. academic public hospital between 2011-2017 were retrospectively identified. Primary exposures were the maximum SIRS, qSOFA, SOFA, and NEWS scores upon inclusion. Comparative prognostic accuracy for the primary outcome of hospital mortality was assessed using the area under the receiver operating characteristic curve (AUROC). Secondary outcomes included mortality in ICU versus non-ICU settings, ICU transfer, ICU length of stay (LOS) >3 days, and hospital LOS >7 days. Adjusted analyses were performed using a model of baseline risk for hospital mortality. 774 patients (7.1%) died in hospital. Discrimination for hospital mortality was highest for SOFA (AUROC 0.90 [95% CI, 0.89-0.91]), followed by NEWS (AUROC 0.85 [95% CI, 0.84-0.86]), qSOFA (AUROC 0.84 [95% CI, 0.83-0.85]), and SIRS (AUROC 0.79 [95% CI, 0.78-0.81]; p<0.001 for all comparisons). NEWS (AUROC 0.94 [95% CI, 0.93-0.95]) outperformed other scores in predicting ICU transfer (qSOFA AUROC 0.89 [95% CI, 0.87-0.91]; SOFA AUROC, 0.84 [95% CI, 0.82-0.87]; SIRS AUROC 0.81 [95% CI, 0.79-0.83]; p<0.001 for all comparisons). NEWS (AUROC 0.86 [95% CI, 0.85-0.86]) was also superior to other scores in predicting ICU LOS >3 days (SOFA AUROC 0.84 [95% CI, 0.83-0.85; qSOFA AUROC, 0.83 [95% CI, 0.83-0.84]; SIRS AUROC, 0.75 [95% CI, 0.74-0.76]; p<0.002 for all comparisons). Multivariate prediction scores, such as SOFA and NEWS, had greater prognostic accuracy than qSOFA or SIRS for hospital mortality, ICU transfer, and ICU length of stay. Complex sepsis scores may offer enhanced prognostic performance as compared to simple sepsis scores in inpatient hospital settings where more complex scores can be readily calculated.
sTREM-1 predicts mortality in hospitalized patients with infection in a tropical, middle-income country
Background Few studies of biomarkers as predictors of outcome in infection have been performed in tropical, low- and middle-income countries where the burden of sepsis is highest. We evaluated whether selected biomarkers could predict 28-day mortality in infected patients in rural Thailand. Methods Four thousand nine hundred eighty-nine adult patients admitted with suspected infection to a referral hospital in northeast Thailand were prospectively enrolled within 24 h of admission. In a secondary analysis of 760 patients, interleukin-8 (IL-8), soluble tumor necrosis factor receptor 1 (sTNFR-1), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and soluble triggering receptor expressed by myeloid cells 1 (sTREM-1) were measured in the plasma. Association with 28-day mortality was evaluated using regression; a parsimonious biomarker model was selected using the least absolute shrinkage and selection operator (LASSO) method. Discrimination of mortality was assessed by receiver operating characteristic curve analysis and verified by multiple methods. Results IL-8, sTNFR-1, Ang-2, and sTREM-1 concentrations were strongly associated with death. LASSO identified a three-biomarker model of sTREM-1, Ang-2, and IL-8, but sTREM-1 alone provided comparable mortality discrimination ( p  = 0.07). sTREM-1 alone was comparable to a model of clinical variables (area under receiver operating characteristic curve [AUC] 0.81, 95% confidence interval [CI] 0.77–0.85 vs AUC 0.79, 95% CI 0.74–0.84; p  = 0.43). The combination of sTREM-1 and clinical variables yielded greater mortality discrimination than clinical variables alone (AUC 0.83, 95% CI 0.79–0.87; p  = 0.004). Conclusions sTREM-1 predicts mortality from infection in a tropical, middle-income country comparably to a model derived from clinical variables and, when combined with clinical variables, can further augment mortality prediction. Trial registration The Ubon-sepsis study was registered on ClinicalTrials.gov ( NCT02217592 ), 2014.
Comparative clinical characteristics and outcomes of patients with community acquired bacteremia caused by Escherichia coli, Burkholderia pseudomallei and Staphylococcus aureus: A prospective observational study (Ubon-sepsis)
Community acquired bacteremia (CAB) is a common cause of sepsis in low and middle-income countries (LMICs). However, knowledge about factors associated with outcomes of CAB in LMICs is limited. A prospective observational study (Ubon-sepsis) of adults admitted to a referral hospital with community-acquired infection in Northeastern Thailand was conducted between March 1, 2013 and February 1, 2017. In the present analysis, patients with a blood culture collected within 24 hours of admission that was positive for one of the three most common pathogens were studied. Clinical features, management, and outcomes of patients with each cause of CAB were compared. Of 3,806 patients presenting with community-acquired sepsis, 155, 131 and 37 patients had a blood culture positive for Escherichia coli, Burkholderia pseudomallei and Staphylococcus aureus, respectively. Of these 323 CAB patients, 284 (89%) were transferred from other hospitals. 28-day mortality was highest in patients with B. pseudomallei bactaeremia (66%), followed by those with S. aureus bacteraemia (43%) and E. coli (19%) bacteraemia. In the multivariable Cox proportional hazards model adjusted for age, sex, transfer from another hospital, empirical antibiotics prior to or during the transfer, and presence of organ dysfunction on admission, B. pseudomallei (aHR 3.78; 95%CI 2.31-6.21) and S. aureus (aHR 2.72; 95%CI 1.40-5.28) bacteraemias were associated with higher mortality compared to E. coli bacteraemia. Receiving empirical antibiotics recommended for CAB caused by the etiologic organism prior to or during transfer was associated with survival (aHR 0.58; 95%CI 0.38-0.88). Mortality of patients with CAB caused by B. pseudomallei was higher than those caused by S. aureus and E. coli, even after adjusting for presence of organ dysfunction on admission and effectiveness of empirical antibiotics received. Improving algorithms or rapid diagnostic tests to guide early empirical antibiotic may be key to improving CAB outcomes in LMICs.
Presentation, management, and outcomes of sepsis in adults and children admitted to a rural Ugandan hospital: A prospective observational cohort study
Limited data are available on sepsis in low-resource settings, particularly outside of urban referral centers. We conducted a prospective observational single-center cohort study in May 2013 to assess the presentation, management and outcomes of adult and pediatric patients admitted with sepsis to a community hospital in rural Uganda. We consecutively screened all patients admitted to medical wards who met sepsis criteria. We evaluated eligible patients within 24 hours of presentation and 24-48 hours after admission, and followed them until hospital discharge. In addition to chart review, mental status evaluation, peripheral capillary oxygen saturation, and point-of-care venous whole blood lactate and glucose testing were performed. Of 56 eligible patients, we analyzed data on 51 (20 adults and 31 children). Median age was 8 years (IQR 2-23 years). Sepsis accounted for a quarter of all adult and pediatric medical ward admissions during the study period. HIV prevalence among adults was 30%. On enrollment, over half of patients had elevated point-of-care whole blood lactate, few were hypoglycemic or had altered mental status, and one third were hypoxic. Over 80% of patients received at least one antibiotic, all severely hypoxic patients received supplemental oxygen, and half of patients with elevated lactate received fluid resuscitation. The most common causes of sepsis were malaria and pneumonia. In-hospital mortality was 3.9%. This study highlights the importance of sepsis among adult and pediatric patients admitted to a rural Ugandan hospital and underscores the need for continued research on sepsis in low resource settings.
Protocol: identifying policy, system, and environment change interventions to enhance availability of blood for transfusion in Kenya, a mixed-methods study
Background Safe blood is essential for the care of patients with life-threatening anemia and hemorrhage. Low blood donation rates, inefficient testing procedures, and other supply chain disruptions in blood administration affect patients in low-resource settings across Sub-Saharan countries, including Kenya. Most efforts to improve access to transfusion have been unidimensional, usually focusing on only point along the blood system continuum, and have excluded community stakeholders from early stages of intervention development. Context-appropriate interventions to improve the availability of safe blood at the point of use in low-resource settings are of paramount importance. Thus, this protocol proposes a multifaceted approach to characterize the Kenyan blood supply chain through quantitative and qualitative analyses as well as an industrial engineering approach. Methods This study will use a mixed-methods approach in addition to engineering process mapping, modeling and simulation of blood availability in Kenya. It will be guided by a multidimensional three-by-three-by-three matrix: three socioeconomic settings, three components of the blood system continuum, and three levels of urgency of blood transfusion. Qualitative data collection includes one-on-one interviews and focus group discussions with stakeholders across the continuum to characterize ground-level deficits and potential policy, systems, and environment (PSE) interventions. Prospectively-collected quantitative data will be used to estimate blood collection and transfusion of blood. We will create a process map of the blood system continuum to model the response to PSE changes proposed by stakeholders. Lastly, we will identify those PSE changes that may have the greatest impact on blood transfusion availability, accounting for differences across socioeconomic settings and levels of urgency. Discussion Identifying and prioritizing community-driven interventions to improve blood supply in low-resource settings are of utmost importance. Varied constraints in blood collection, processing, delivery, and use make each socioeconomic setting unique. Using a multifaceted approach to understand the Kenyan blood supply and model the response to stakeholder-proposed PSE changes may lead to identification of contextually appropriate intervention targets to meet the transfusion needs of the population.
Association of clinical prediction scores with hospital mortality in an adult medical and surgical intensive care unit in Kenya
Mortality prediction among critically ill patients in resource limited settings is difficult. Identifying the best mortality prediction tool is important for counseling patients and families, benchmarking quality improvement efforts, and defining severity of illness for clinical research studies. Compare predictive capacity of the Modified Early Warning Score (MEWS), Universal Vital Assessment (UVA), Tropical Intensive Care Score (TropICS), Rwanda Mortality Probability Model (R-MPM), and quick Sequential Organ Failure Assessment (qSOFA) for hospital mortality among adults admitted to a medical-surgical intensive care unit (ICU) in rural Kenya. We performed a pre-planned subgroup analysis among ICU patients with suspected infection. Prospective single-center cohort study at a tertiary care, academic hospital in Kenya. All adults 18 years and older admitted to the ICU January 2018-June 2019 were included. The primary outcome was association of clinical prediction tool score with hospital mortality, as defined by area under the receiver operating characteristic curve (AUROC). Demographic, physiologic, laboratory, therapeutic, and mortality data were collected. 338 patients were included, none were excluded. Median age was 42 years (IQR 33-62) and 61% ( = 207) were male. Fifty-nine percent ( = 199) required mechanical ventilation and 35% ( = 118) received vasopressors upon ICU admission. Overall hospital mortality was 31% ( = 104). 323 patients had all component variables recorded for R-MPM, 261 for MEWS, and 253 for UVA. The AUROC was highest for MEWS (0.76), followed by R-MPM (0.75), qSOFA (0.70), and UVA (0.69) ( < 0.001). Predictive capacity was similar among patients with suspected infection. All tools had acceptable predictive capacity for hospital mortality, with variable observed availability of the component data. R-MPM and MEWS had high rates of variable availability as well as good AUROC, suggesting these tools may prove useful in low resource ICUs.
Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study
Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.
Safety of Administration of Vasopressors Through Peripheral Compared to Central Venous Catheters in a Rural Kenyan Hospital: Protocol for a Prospective Observational Cohort Study
The infusion of vasopressors is a standard treatment for shock, and international guidelines recommend administering these medications through central venous catheters (CVCs) due to concerns about potential extravasation and local tissue injury with peripheral intravenous (PIV) administration. However, CVCs are often unavailable in resource-variable settings due to lack of human and material resources. Previous studies have assessed the safety of vasopressor infusion through PIV catheters but have considered only limited patient populations or a short infusion time or have used retrospective designs that may have failed to capture mild complications. The primary objective of this study is to observe and describe the incidence of complications among patients receiving vasopressor infusion via PIV administration. The secondary objective is to assess whether the safety of PIV vasopressor administration is noninferior to the safety of administration via CVC. This prospective observational study is being conducted at African Inland Church (AIC) Kijabe Hospital, a 360-bed tertiary care teaching hospital in rural Kenya. All patients (adult, obstetric, and pediatric) receiving intravenous vasopressor infusions who are admitted to the intensive care unit or high-dependency unit will be included. Patients will be followed up on twice daily from the start of vasopressor infusion to 72 hours after vasopressor discontinuation or death, whichever occurs first. Demographic, physiological, laboratory, therapeutic, and outcome data will be collected. Consecutive enrollment began in October 2023 and is ongoing. As of July 2025, we have enrolled 190 patients. We anticipate that the time to enroll the number of patients required to reach our power goal will be 24 months. This study in a resource-variable setting will allow for more accurate and comprehensive data collection on vasopressor administration and potential complications as they arise, whereas most previous studies have been retrospective in nature. In addition, this is the first study of its kind to include both adult and pediatric patients within a mixed intensive care unit population with broad etiologies of shock, which could improve generalizability.