Association of freeze-dried plasma with 24-h mortality among trauma patients at risk for hemorrhage.

BACKGROUND: Blood products form the cornerstone of contemporary hemorrhage control but are limited resources. Freeze-dried plasma (FDP), which contains coagulation factors, is a promising adjunct in hemostatic resuscitation. We explore the association between FDP alone or in combination with other blood products on 24-h mortality. STUDY DESIGN AND METHODS: This is a secondary data analysis from a cross-sectional prospective observational multicenter study of adult trauma patients in the Western Cape of South Africa. We compare mortality among trauma patients at risk of hemorrhage in three treatment groups: Blood Products only, FDP + Blood Products, and FDP only. We apply inverse probability of treatment weighting and fit a multivariable Cox proportional hazards model to assess the hazard of 24-h mortality. RESULTS: Four hundred and forty-eight patients were included, and 55 (12.2%) died within 24 h of hospital arrival. Compared to the Blood Products only group, we found no difference in 24-h mortality for the FDP + Blood Product group (p = .40) and a lower hazard of death for the FDP only group (hazard = 0.38; 95% CI, 0.15-1.00; p = .05). However, sensitivity analyses showed no difference in 24-h mortality across treatments in subgroups with moderate and severe shock, early blood product administration, and accounting for immortal time bias. CONCLUSION: We found insufficient evidence to conclude there is a difference in relative 24-h mortality among trauma patients at risk for hemorrhage who received FDP alone, blood products alone, or blood products with FDP. There may be an adjunctive role for FDP in hemorrhagic shock resuscitation in settings with significantly restricted access to blood products.

Patterns of on-scene and healthcare system trauma deaths in the Western Cape of South Africa.

BACKGROUND: Injuries account for 8% or 4.4 million deaths annually worldwide, with 90% of injury deaths occurring in low- and middle-income countries. Inter-personal violence and road traffic injuries account for most injury deaths in South Africa, with rates among the highest globally. Understanding the location, timing, and factors of trauma deaths can identify opportunities to strengthen care. METHODS: This is a retrospective cross-sectional secondary analysis of trauma deaths from 2021 to 2022 in the Western Cape of South Africa. Healthcare system trauma deaths were identified from a multicenter study paired with a dataset for on-scene (i.e., prior to ambulance or hospital) trauma deaths in the same jurisdictions. We describe locations, timing, injury factors, and cause of death. We assess associations between those factors. RESULTS: There were 2418 deaths, predominantly young men, with most (2274, 94.0%) occurring on-scene. The most frequent mechanism of injury for all deaths was firearms (32.6%), followed by road traffic collisions (17.8%). On-scene deaths (33.2%) were significantly more likely to be injured by firearms compared to healthcare system deaths (23.6%) (p-value <0.01). Most healthcare system deaths within 4-24 h of injury occurred in a hospital emergency center. Among healthcare system decedents, half died in the emergency unit. CONCLUSIONS: We identified a large burden of deaths from interpersonal violence and road traffic collisions, mostly on-scene. In addition to primary prevention, shortening delays to care can improve mortality outcomes especially for deaths occurring within 4-24 h in emergency centers.

Feasibility of conducting a military-relevant multicenter cohort study to assess outcomes of early trauma resuscitative interventions in a prolonged care civilian setting.

BACKGROUND: The Epidemiology and Outcomes of Prolonged Trauma Care (EpiC) study is a 4-year, prospective, observational, large-scale epidemiologic study in South Africa. It will provide novel evidence on how early resuscitation impacts postinjury mortality and morbidity in patients experiencing prolonged care. A pilot study was performed to inform the main EpiC study. We assess outcomes and experiences from the pilot to evaluate overall feasibility of conducting the main EpiC study. METHODS: The pilot was a prospective, multicenter, cohort study at four ambulance bases, four hospitals, and two mortuaries from March 25 to August 27, 2021. Trauma patients 18 years or older were included. Data were manually collected via chart review and abstraction from clinical records at all research sites and inputted into Research Electronic Data Capture. Feasibility metrics calculated were as follows: screening efficiency, adequate enrollment, availability of key exposure and outcome data, and availability of injury event date/time. RESULTS: A total of 2,303 patients were screened. Of the 981 included, 70% were male, and the median age was 31.4 years. Six percent had one or more trauma relevant comorbidity. Fifty-five percent arrived by ambulance. Forty percent had penetrating injuries. Fifty-three percent were critically injured. Thirty-three percent had one or more critical interventions performed. Mortality was 5%. Four of the eight feasibility metrics exceed the predetermined threshold: screening ratio, monthly enrollment, percentage with significant organ failure, and missing injury date/time for emergency medical services patients. Two feasibility metrics were borderline: key exposure and primary outcome. Two feasibility metrics fell below the feasibility threshold, which necessitate changes to the main EpiC study: percentage with infections and missing injury date/time for walk-in patients. CONCLUSION: The EpiC pilot study suggests that the main EpiC study is overall feasible. Improved data collection for infections and methods for missing data will be developed for the main study. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level V.

Tranexamic Acid Improves Survival in the Setting of Severe Head Injury in Combat Casualties.

INTRODUCTION: Approximately 1.7 million people sustain traumatic brain injuries (TBI) annually in the US. To reduce morbidity and mortality, management strategies aim to control progressive intracranial bleeding. This study analyzes the association between Tranexamic Acid (TXA) administration and mortality among casualties within the Department of Defense Trauma Registry, specifically focusing on subsets of patients with varying degree of head injury severities. METHODS: Besides descriptive statistics, we used inverse probability weighted (for age, military service category, mechanism of injury, total units of blood units administered), and injury severity (ISS) and Abbreviated Injury Scale (AIS) head score adjusted generalized linear models to analyze the association between TXA and mortality. Specific subgroups of interest were increasing severities of head injury and further stratifying these by Glasgow Coma Score of 3-8 and severe overall bodily injuries (ISS>=15). RESULTS: 25,866 patients were included in the analysis. 2,352 (9.1%) received TXA and 23,514 (90.9%) did not receive TXA. Among those with ISS>=15 (n=6,420), 21.2% received TXA. Among those with any head injury (AIS head injury severity score>=1; n=9,153), 7.2% received TXA. The median ISS scores were greater in the TXA versus no-TXA group (17 versus 6). Weighted and adjusted models showed overall, there was 25% lower mortality risk between those who received TXA at any point and those who did not (OR:0.75, 95% CI: 0.59, 0.95). Further, as the AIS severity score increased from >=1 (1.08; 0.80, 1.47) to >=5 (0.56; 0.33, 0.97), the odds of mortality decreased. CONCLUSIONS: TXA may potentially be beneficial in patients with severe head injuries, especially those with severe overall injury profiles. There is a need of definitive studies to confirm this association.

The epidemiology and outcomes of prolonged trauma care (EpiC) study: methodology of a prospective multicenter observational study in the Western Cape of South Africa.

BACKGROUND: Deaths due to injuries exceed 4.4 million annually, with over 90% occurring in low-and middle-income countries. A key contributor to high trauma mortality is prolonged trauma-to-treatment time. Earlier receipt of medical care following an injury is critical to better patient outcomes. Trauma epidemiological studies can identify gaps and opportunities to help strengthen emergency care systems globally, especially in lower income countries, and among military personnel wounded in combat. This paper describes the methodology of the "Epidemiology and Outcomes of Prolonged Trauma Care (EpiC)" study, which aims to investigate how the delivery of resuscitative interventions and their timeliness impacts the morbidity and mortality outcomes of patients with critical injuries in South Africa. METHODS: The EpiC study is a prospective, multicenter cohort study that will be implemented over a 6-year period in the Western Cape, South Africa. Data collected will link pre- and in-hospital care with mortuary reports through standardized clinical chart abstraction and will provide longitudinal documentation of the patient's clinical course after injury. The study will enroll an anticipated sample of 14,400 injured adults. Survival and regression analysis will be used to assess the effects of critical early resuscitative interventions (airway, breathing, circulatory, and neurologic) and trauma-to-treatment time on the primary 7-day mortality outcome and secondary mortality (24-h, 30-day) and morbidity outcomes (need for operative interventions, secondary infections, and organ failure). DISCUSSION: This study is the first effort in the Western Cape of South Africa to build a standardized, high-quality, multicenter epidemiologic trauma dataset that links pre- and in-hospital care with mortuary data. In high-income countries and the U.S. military, the introduction of trauma databases and registries has led to interventions that significantly reduce post-injury death and disability. The EpiC study will describe epidemiology trends over time, and it will enable assessments of how trauma care and system processes directly impact trauma outcomes to ultimately improve the overall emergency care system. TRIAL REGISTRATION: Not applicable as this study is not a clinical trial.

Prolonged casualty care: Extrapolating civilian data to the military context.

BACKGROUND: Civilian and military populations alike are increasingly faced with undesirable situations in which prehospital and definitive care times will be delayed. The Western Cape of South Africa has some similarities in capabilities, injury profiles, resource limitations, and system configuration to US military prolonged casualty care (PCC) settings. This study provides an initial description of civilians in the Western Cape who experience PCC and compares the PCC and non-PCC populations. METHODS: We conducted a 6-month analysis of an ongoing, prospective, large-scale epidemiologic study of prolonged trauma care in the Western Cape (Epidemiology and Outcomes of Prolonged Trauma Care [EpiC]). We define PCC as ≥10 hours from injury to arrival at definitive care. We describe patient characteristics, critical interventions, key times, and outcomes as they may relate to military PCC and compare these using χ 2 and Wilcoxon tests. We estimated the associations between PCC status and the primary and secondary outcomes using logistic regression models. RESULTS: Of 995 patients, 146 experienced PCC. The PCC group, compared with non-PCC, were more critically injured (66% vs. 51%), received more critical interventions (36% vs. 29%), and had a greater proportionate mortality (5% vs. 3%), longer hospital stays (3 vs. 1 day), and higher Sequential Organ Failure Assessment scores (5 vs. 3). The odds of 7-day mortality and a Sequential Organ Failure Assessment score of ≥5 were 1.6 (odds ratio, 1.59; 95% confidence interval, 0.68-3.74) and 3.6 (odds ratio, 3.69; 95% confidence interval, 2.11-6.42) times higher, respectively, in PCC versus non-PCC patients. CONCLUSION: The EpiC study enrolled critically injured patients with PCC who received resuscitative interventions. Prolonged casualty care patients had worse outcomes than non-PCC. The EpiC study will be a useful platform to provide ongoing data for PCC relevant analyses, for future PCC-focused interventional studies, and to develop PCC protocols and algorithms. Findings will be relevant to the Western Cape, South Africa, other LMICs, and military populations experiencing prolonged care. LEVEL OF EVIDENCE: Therapeutic/care management; Level IV.

Clinical impact of a prehospital trauma shock bundle of care in South Africa.

INTRODUCTION: Patients experiencing traumatic shock are at a higher risk for death and complications. We previously designed a bundle of emergency medical services traumatic shock care ("EMS-TruShoC") for prehospital providers in resource-limited settings. We assess how EMS-TruShoC changes clinical outcomes of critically injured prehospital patients. METHODS: This is a quasi-experimental educational implementation of a simplified bundle of care using a pre-post design with a control group. The intervention was delivered to EMS providers in Western Cape, South Africa. Delta shock index (heart rate divided by systolic blood pressure, reported as change from the scene to facility arrival) from the 13 months preceding intervention were compared to the 13 months post-implementation. A difference-in-differences analysis examined the difference in mean shock index change between the groups. RESULTS: Data were collected from 198 providers who treated 770 severe trauma patients. The patient groups had similar demographic and clinical characteristics at baseline. Over all time-points, both groups had an increase in mean delta shock index (worsening shock), with the largest difference occurring 4-months post-implementation (0.047 change in control arm, 0.004 change in intervention arm; -0.043 difference-in-differences, P = 0.27). In pre-specified subgroup analyses, there was a statistically significant improvement in delta shock index in the intervention arm in patients with penetrating trauma cared for by basic providers immediately post-implementation (-0.372 difference-in-differences, P = 0.02). DISCUSSION: Overall, there was no significant difference in delta shock index between the EMS-TruShoC intervention versus control groups. However, significant improvement in shock index in one subgroup suggests the intervention may be more likely to benefit penetrating trauma patients and basic providers.

Validity and reliability of the South African Triage Scale in prehospital providers.

BACKGROUND: The South African Triage Scale (SATS) is a validated in-hospital triage tool that has been innovatively adopted for use in the prehospital setting by Western Cape Government (WCG) Emergency Medical Services (EMS) in South Africa. The performance of SATS by EMS providers has not been formally assessed. The study sought to assess the validity and reliability of SATS when used by WCG EMS prehospital providers for single-patient triage. METHODS: This is a prospective, assessment-based validation study among WCG EMS providers from March to September 2017 in Cape Town, South Africa. Participants completed an assessment containing 50 clinical vignettes by calculating the three components - triage early warning score (TEWS), discriminators (pre-defined clinical conditions), and a final SATS triage color. Responses were scored against gold standard answers. Validity was assessed by calculating over- and under-triage rates compared to gold standard. Inter-rater reliability was assessed by calculating agreement among EMS providers' responses. RESULTS: A total of 102 EMS providers completed the assessment. The final SATS triage color was accurately determined in 56.5%, under-triaged in 29.5%, and over-triaged in 13.1% of vignette responses. TEWS was calculated correctly in 42.6% of vignettes, under-calculated in 45.0% and over-calculated in 10.9%. Discriminators were correctly identified in only 58.8% of vignettes. There was substantial inter-rater and gold standard agreement for both the TEWS component and final SATS color, but there was lower inter-rater agreement for clinical discriminators. CONCLUSION: This is the first assessment of SATS as used by EMS providers for prehospital triage. We found that SATS generally under-performed as a triage tool, mainly due to the clinical discriminators. We found good inter-rater reliability, but poor validity. The under-triage rate of 30% was higher than previous reports from the in-hospital setting. The over-triage rate of 13% was acceptable. Further clinically-based and qualitative studies are needed. TRIAL REGISTRATION: Not applicable.

The State of Emergency Medical Services (EMS) Systems in Africa.

Introduction Little is known about the existence, distribution, and characteristics of Emergency Medical Services (EMS) systems in Africa, or the corresponding epidemiology of prehospital illness and injury. METHODS: A survey was conducted between 2013 and 2014 by distributing a detailed EMS system questionnaire to experts in paper and electronic versions. The questionnaire ascertained EMS systems' jurisdiction, operations, finance, clinical care, resources, and regulatory environment. The discovery of respondents with requisite expertise occurred in multiple phases, including snowball sampling, a review of published scientific literature, and a rigorous search of the Internet. RESULTS: The survey response rate was 46%, and data represented 49 of 54 (91%) African countries. Twenty-five EMS systems were identified and distributed among 16 countries (30% of African countries). There was no evidence of EMS systems in 33 (61%) countries. A total of 98,574,731 (8.7%) of the African population were serviced by at least one EMS system in 2012. The leading causes of EMS transport were (in order of decreasing frequency): injury, obstetric, respiratory, cardiovascular, and gastrointestinal complaints. Nineteen percent of African countries had government-financed EMS systems and 26% had a toll-free public access telephone number. Basic emergency medical technicians (EMTs) and Basic Life Support (BLS)-equipped ambulances were the most common cadre of provider and ambulance level, respectively (84% each). CONCLUSION: Emergency Medical Services systems exist in one-third of African countries. Injury and obstetric complaints are the leading African prehospital conditions. Only a minority (<9.0%) of Africans have coverage by an EMS system. Most systems were predominantly BLS, government operated, and fee-for-service. Mould-Millman NK , Dixon JM , Sefa N , Yancey A , Hollong BG , Hagahmed M , Ginde AA , Wallis LA . The state of Emergency Medical Services (EMS) systems in Africa. Prehosp Disaster Med. 2017;32(3):273-283.

Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis.

CONTEXT: Low testosterone levels have been associated with outcomes that reduce survival in men. OBJECTIVE: Our objective was to perform a systematic review and meta-analysis of published studies to evaluate the association between endogenous testosterone and mortality. DATA SOURCES: Data sources included MEDLINE (1966 to December 2010), EMBASE (1988 to December 2010), and reference lists. STUDY SELECTION: Eligible studies were published English-language observational studies of men that reported the association between endogenous testosterone and all-cause or cardiovascular disease (CVD) mortality. A two-stage process was used for study selection. 1) Working independently and in duplicate, reviewers screened a subset (10%) of abstracts. Results indicated 96% agreement, and thereafter, abstract screening was conducted in singlicate. 2) All full-text publications were reviewed independently and in duplicate for eligibility. DATA EXTRACTION: Reviewers working independently and in duplicate determined methodological quality of studies and extracted descriptive, quality, and outcome data. DATA SYNTHESIS: Of 820 studies identified, 21 were included in the systematic review, and 12 were eligible for meta-analysis [n = 11 studies of all-cause mortality (16,184 subjects); n = 7 studies of CVD mortality (11,831 subjects)]. Subject mean age and testosterone level were 61 yr and 487 ng/dl, respectively, and mean follow-up time was 9.7 yr. Between-study heterogeneity was observed among studies of all-cause (P < .001) and CVD mortality (P = 0.06), limiting the ability to provide valid summary estimates. Heterogeneity in all-cause mortality (higher relative risks) was observed in studies that included older subjects (P = 0.020), reported lower testosterone levels (P = 0.018), followed subjects for a shorter time period (P = 0.010), and sampled blood throughout the day (P = 0.030). CONCLUSION: Low endogenous testosterone levels are associated with increased risk of all-cause and CVD death in community-based studies of men, but considerable between-study heterogeneity, which was related to study and subject characteristics, suggests that effects are driven by differences between cohorts (e.g. in underlying health status).

Do differing types of victimization and coping strategies influence the type of social reactions experienced by current victims of intimate partner violence?

This study examines whether differing types of victimization and coping strategies influence the type of social reactions experienced by 173 current victims of intimate partner violence (IPV). Results of path analyses showed that psychological and sexual IPV victimization were related to positive social reactions, whereas physical, psychological, and sexual IPV victimization were related to negative social reactions. Indirect relationships between victimization and social reactions differed by types of coping strategies (social support, problem solving, and avoidance) examined. Implications are discussed regarding the development of interventions with women's support networks and the augmentation of services to help victims modify their coping strategies.

Review of the economic and quality-of-life burden of cervical human papillomavirus disease.

OBJECTIVE: The purpose of this study was to conduct a systematic literature review on the economic burden and health-related quality-of-life impact of cervical human papillomavirus disease. STUDY DESIGN: A systematic review of cost-of-illness studies and health-related quality-of-life studies was conducted. PubMed, Embase, and PsycINFO databases were searched with the use of predefined terms. RESULTS: Nine economic and 24 quality-of-life studies were identified. The annual health care costs of human papillomavirus-related conditions in the United States range from 2.25-4.6 billion dollars (2005 US dollars). The burden of human papillomavirus is second only to human immunodeficiency virus among sexually transmitted diseases. Health-related quality-of-life areas that are impacted substantially by human papillomavirus include emotional, social, and sexual functioning. CONCLUSION: The economic and quality-of-life burden of cervical human papillomavirus disease is significant and highlights the need for treatment and prevention options for this condition.

Economic outcomes associated with atypical antipsychotics in bipolar disorder: a systematic review.

OBJECTIVE: Bipolar disorder is a serious condition that is costly to the health care system. Atypical antipsychotics are more expensive than conventional treatments. From a policy-making perspective, the additional cost must be justified by improved outcomes. The objective of this study was to conduct a systematic review to determine the relative costs and cost-effectiveness associated with atypical antipsychotics in bipolar disorder. DATA SOURCES: We conducted a systematic review of the literature in PubMed and EMBASE from January 1985 through October 2005, including published studies and conference proceedings. Databases were searched using predefined terms. STUDY SELECTION: Studies were included if they were claims data analyses, trial-based economic evaluations, or cost-effectiveness analyses using models. Data were extracted using predefined tables. DATA SYNTHESIS: Fourteen studies were identified. Seven were medical claims database analyses, 4 were trial-based economic evaluations, and 3 were cost-effectiveness models. Eight of these studies were conference proceedings. The studies did not provide sufficient information to determine any ranking of interventions in terms of least to most costly in overall resource consumption or in terms of their relative cost-effectiveness. Where comparable, results tended to be inconsistent. CONCLUSION: There is a scarcity of economic studies in this field. A reference case outlining how to address the complex interplay between effectiveness, safety, adherence, and quality of life and their impact on resource use and costs is needed to contribute to improving the treatment of patients with bipolar disorder while making the best use of scarce health resources.

Economics of atypical antipsychotics in bipolar disorder: a review of the literature.

Economic evaluations are increasingly being used by policy makers to evaluate the relative costs and benefits of healthcare interventions. These analyses provide economic and clinical evidence to decision makers seeking to make recommendations on treatment alternatives for patients. This article describes the economic evidence on the atypical antipsychotics currently approved for the treatment of bipolar disorder. This area remains under-researched. A literature search identified only six relevant studies of atypical antipsychotics in bipolar disorder: two retrospective database analyses, three economic analyses alongside clinical trials and one cost-effectiveness analysis. Based on the limited available studies, there appears to be no significant difference in healthcare resource use between olanzapine, quetiapine, risperidone and valproate semisodium (divalproex sodium; an antiepileptic drug and a standard treatment for mania associated with bipolar disorder). While a cost-effectiveness study for the UK found haloperidol (a conventional antipsychotic) to be more cost effective than atypical antipsychotics, these results must be considered with caution because of the non-inclusion of adverse effects in the model. No economic data are available for aripiprazole, clozapine or ziprasidone in bipolar disorder. Until more economic evidence becomes available, the economic implications of atypical antipsychotic treatment in patients with bipolar disorder are unlikely to significantly impact on prescribing and treatment patterns. Future economic studies evaluating atypical antipsychotics in bipolar disorder should address the issue of long-term costs and effectiveness to reflect the chronic nature of the disease, the variety of health states that patients may experience and the range of treatments they may receive. A better understanding of the complex interplay between effectiveness, safety, quality of life, adherence and resource use should ultimately contribute to improving the treatment of bipolar disorder.