Critical care delivery across health care systems in low-income and low-middle-income country settings: A systematic review.

Background: Prior research has demonstrated that low- and low-middle-income countries (LLMICs) bear a higher burden of critical illness and have a higher rate of mortality from critical illness than high-income countries (HICs). There is a pressing need for improved critical care delivery in LLMICs to reduce this inequity. This systematic review aimed to characterise the range of critical care interventions and services delivered within LLMIC health care systems as reported in the literature. Methods: A search strategy using terms related to critical care in LLMICs was implemented in multiple databases. We included English language articles with human subjects describing at least one critical care intervention or service in an LLMIC setting published between 1 January 2008 and 1 January 2020. Results: A total of 1620 studies met the inclusion criteria. Among the included studies, 45% of studies reported on pediatric patients, 43% on adults, 23% on infants, 8.9% on geriatric patients and 4.2% on maternal patients. Most of the care described (94%) was delivered in-hospital, with the remainder (6.2%) taking place in out-of-hospital care settings. Overall, 49% of critical care described was delivered outside of a designated intensive care unit. Specialist physicians delivered critical care in 60% of the included studies. Additional critical care was delivered by general physicians (40%), as well as specialist physician trainees (22%), pharmacists (16%), advanced nursing or midlevel practitioners (8.9%), ambulance providers (3.3%) and respiratory therapists (3.1%). Conclusions: This review represents a comprehensive synthesis of critical care delivery in LLMIC settings. Approximately 50% of critical care interventions and services were delivered outside of a designated intensive care unit. Specialist physicians were the most common health care professionals involved in care delivery in the included studies, however generalist physicians were commonly reported to provide critical care interventions and services. This study additionally characterised the quality of the published evidence guiding critical care practice in LLMICs, demonstrating a paucity of interventional and cost-effectiveness studies. Future research is needed to understand better how to optimise critical care interventions, services, care delivery and costs in these settings. Registration: PROSPERO CRD42019146802.

Implementation and outcomes of a comprehensive emergency care curriculum at a low-resource referral hospital in Liberia: A novel approach to application of the WHO Basic Emergency Care toolkit.

BACKGROUND: Emergency care is vital in low- and middle-income countries (LMICs) but many frontline healthcare workers in low-resource settings have no formal training in emergency care. To address this gap, the World Health Organization (WHO) developed Basic Emergency Care (BEC): Approach to the acutely ill and injured, a multi-day, open-source course for healthcare workers in low-resource settings. Building on the BEC foundation, this study uses an implementation science (IS) lens to develop, implement, and evaluate a comprehensive emergency care curriculum in a single emergency facility in Liberia. METHODS: A six-month emergency care curriculum consisting of BEC content, standardized WHO clinical documentation forms, African Federation of Emergency Medicine (AFEM) didactics, and clinical mentorship by visiting emergency medicine (EM) faculty was designed and implemented using IS frameworks at Redemption Hospital, a low-resource public referral hospital in Monrovia, the capital of Liberia. Healthcare worker performance on validated knowledge-based exams during pre- and post-intervention testing, post-course surveys, and patient outcomes were used to evaluate the program. RESULTS: Nine visiting EM physicians provided 1400 hours of clinical mentorship and 560 hours of didactic training to fifty-six Redemption Hospital staff over six-months. Median test scores improved 20.0% (p<0.001) among the forty-three healthcare workers who took both the pre- and post-intervention tests. Participants reported increased confidence in caring for medical and trauma patients and comfort performing emergency care tasks on post-course surveys. Emergency unit (EU)/Isolation unit (IU) mortality decreased during the six-month implementation period, albeit non-significantly. Course satisfaction was high across multiple domains. DISCUSSION: This study builds on prior research supporting WHO efforts to improve emergency care globally. BEC implementation over a six-month timeframe using IS principles is an effective alternative strategy for facilities in resource-constrained environments wishing to strengthen emergency care delivery.

Emergency department antimicrobial use in a low-resource setting: results from a retrospective observational study at a referral hospital in Liberia.

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators. DESIGN: Retrospective observational study. SETTING: An adult ED of a large public hospital in Monrovia, Liberia. PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January to 30 June 2019. MAIN OUTCOME MEASURES: Number, type and name of antimicrobials ordered per patient were presented as number and percentages, with comparison to known WHO prescribing indicators. Pearson χ2 tests were used to assess patient variables and trends in medication use. RESULTS: Of the total patients, 44.0% (n=476) were female and the mean age was 40.2 years (SD=17.4). An average of 2.78 (SD=2.02) medicines were prescribed per patient encounter. At least one antimicrobial was ordered for 64.5% encounters (n=713) and two or more antimicrobials for 35.7% (n=386). All antimicrobial orders in our sample used the generic name. Ceftriaxone, metronidazole and ampicillin were the most common and accounted for 61.2% (n=743) of antimicrobial prescriptions. The majority (99.9%, n=1211) of antimicrobials prescribed were from the WHO Essential Drugs List. CONCLUSION: This study is one of the first on ED-specific antimicrobial use in LMICs. We revealed a high rate of antimicrobial prescription, regardless of patient demographic or diagnosis. While empiric antimicrobial use is justified in certain acute clinical scenarios, the high rate from this setting warrants further investigation. The results of this study underscore the importance of ED surveillance to develop targeted antimicrobial stewardship interventions and improve patient care.

Patient-Centered Outcomes of an Emergency Department Social and Medical Resource Intervention.

INTRODUCTION: Few studies have examined the impact of emergency department (ED) social interventions on patient outcomes and revisits, especially in underserved populations. Our objective in this study was to characterize a volunteer initiative that provided community medical and social resources at ED discharge and its effect on ED revisit rates and adherence to follow-up appointments at a large, county hospital ED. METHODS: We performed a cross-sectional analysis of ED patients who received medical and social resources and an educational intervention at discharge between September 2017-June 2018. Demographic information, the number of ED return visits, and outpatient follow-up appointment adherence within 30 and 90 days of ED discharge were obtained from electronic health records. We obtained data regarding patient utilization of resources via telephone follow-up communication. We used logistic regression analyses to evaluate associations between patient characteristics, reported resource utilization, and revisit outcomes. RESULTS: Most patients (55.3% of 494 participants) identified as Latino/Hispanic, and 49.4% received healthcare assistance through a local governmental program. A majority of patients (83.6%) received at least one medical or social resource, with most requesting more than one. Patients provided with a medical or social resource were associated with a higher 90-day follow-up appointment adherence (odds ratio [OR] 2.56; 95% confidence interval [CI] 1.05-6.25, and OR 4.75; 95% CI 1.49-15.20], respectively), and the provision of both resources was associated with lower odds of ED revisit within 30 days (OR 0.50; 95% CI 0.27-0.95). Males and those enrolled in the healthcare assistance program had higher odds of ED revisits, while Hispanic/Latino and Spanish-speaking patients had lower odds of revisits. CONCLUSION: An ED discharge intervention providing medical and social resources may be associated with improved follow-up adherence and reduced ED revisit rates in underserved populations.

White Paper on Early Critical Care Services in Low Resource Settings.

This White Paper has been formally accepted for support by the International Federation for Emergency Medicine (IFEM) and by the World Federation of Intensive and Critical Care (WFICC), put forth by a multi-specialty group of intensivists and emergency medicine providers from low- and low-middle-income countries (LMICs) and high-income countries (HiCs) with the aim of 1) defining the current state of caring for the critically ill in low-resource settings (LRS) within LMICs and 2) highlighting policy options and recommendations for improving the system-level delivery of early critical care services in LRS. LMICs have a high burden of critical illness and worse patient outcomes than HICs, hence, the focus of this White Paper is on the care of critically ill patients in the early stages of presentation in LMIC settings. In such settings, the provision of early critical care is challenged by a fragmented health system, costs, a health care workforce with limited training, and competing healthcare priorities. Early critical care services are defined as the early interventions that support vital organ function during the initial care provided to the critically ill patient-these interventions can be performed at any point of patient contact and can be delivered across diverse settings in the healthcare system and do not necessitate specialty personnel. Currently, a single "best" care delivery model likely does not exist in LMICs given the heterogeneity in local context; therefore, objective comparisons of quality, efficiency, and cost-effectiveness between varying models are difficult to establish. While limited, there is data to suggest that caring for the critically ill may be cost effective in LMICs, contrary to a widely held belief. Drawing from locally available resources and context, strengthening early critical care services in LRS will require a multi-faceted approach, including three core pillars: education, research, and policy. Education initiatives for physicians, nurses, and allied health staff that focus on protocolized emergency response training can bridge the workforce gap in the short-term; however, each country's current human resources must be evaluated to decide on the duration of training, who should be trained, and using what curriculum. Understanding the burden of critical Illness, best practices for resuscitation, and appropriate quality metrics for different early critical care services implementation models in LMICs are reliant upon strengthening the regional research capacity, therefore, standard documentation systems should be implemented to allow for registry use and quality improvement. Policy efforts at a local, national and international level to strengthen early critical care services should focus on funding the building blocks of early critical care services systems and promoting the right to access early critical care regardless of the patient's geographic or financial barriers. Additionally, national and local policies describing ethical dilemmas involving the withdrawal of life-sustaining care should be developed with broad stakeholder representation based on local cultural beliefs as well as the optimization of limited resources.

Critical care service delivery across healthcare systems in low-income and low-middle-income countries: protocol for a systematic review.

INTRODUCTION: Critical care in low-income and low-middle income countries (LLMICs) is an underdeveloped component of the healthcare system. Given the increasing growth in demand for critical care services in LLMICs, understanding the current capacity to provide critical care is imperative to inform policy on service expansion. Thus, our aim is to describe the provision of critical care in LLMICs with respect to patients, providers, location of care and services and interventions delivered. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, Web of Science and EMBASE for full-text original research articles available in English describing critical care services that specify the location of service delivery and describe patients and interventions. We will restrict our review to populations from LLMICs (using 2016 World Bank classifications) and published from 1 January 2008 to 1 January 2020. Two-reviewer agreement will be required for both title/abstract and full text review stages, and rate of agreement will be calculated for each stage. We will extract data regarding the location of critical care service delivery, the training of the healthcare professionals providing services, and the illnesses treated according to classification by the WHO Universal Health Coverage Compendium. ETHICS AND DISSEMINATION: Reviewed and exempted by the Stanford University Office for Human Subjects Research and IRB on 20 May 2020. The results of this review will be disseminated through scholarly publication and presentation at regional and international conferences. This review is designed to inform broader WHO, International Federation for Emergency Medicine and partner efforts to strengthen critical care globally. PROSPERO REGISTRATION NUMBER: CRD42019146802.

Models of care for patients with hypertension and diabetes in humanitarian crises: a systematic review.

Care for non-communicable diseases, including hypertension and diabetes (HTN/DM), is recognized as a growing challenge in humanitarian crises, particularly in low- and middle-income countries (LMICs) where most crises occur. There is little evidence to support humanitarian actors and governments in designing efficient, effective, and context-adapted models of care for HTN/DM in such settings. This article aimed to systematically review the evidence on models of care targeting people with HTN/DM affected by humanitarian crises in LMICs. A search of the MEDLINE, Embase, Global Health, Global Indexus Medicus, Web of Science, and EconLit bibliographic databases and grey literature sources was performed. Studies were selected that described models of care for HTN/DM in humanitarian crises in LMICs. We descriptively analysed and compared models of care using a conceptual framework and evaluated study quality using the Mixed Methods Appraisal Tool. We report our findings according to PRISMA guidelines. The search yielded 10 645 citations, of which 45 were eligible for this review. Quantitative methods were most commonly used (n = 34), with four qualitative, three mixed methods, and four descriptive reviews of specific care models were also included. Most studies detailed primary care facility-based services for HTN/DM, focusing on health system inputs. More limited references were made to community-based services. Health care workforce and treatment protocols were commonly described framework components, whereas few studies described patient centredness, quality of care, financing and governance, broader health policy, and sociocultural contexts. There were few programme evaluations or effectiveness studies, and only one study reported costs. Most studies were of low quality. We concluded that an increasing body of literature describing models of care for patients with HTN/DM in humanitarian crises demonstrated the development of context-adapted services but showed little evidence of impact. Our conceptual framework could be used for further research and development of NCD models of care.

International Emergency Psychiatry Challenges: Disaster Medicine, War, Human Trafficking, Displaced Persons.

Mental health disorders are a major cause of morbidity and a growing burden in low-income and middle-income countries; but there is little existing literature on the detailed epidemiology, diagnosis, and treatment in low-resource settings. Special situations with vulnerable populations, such as those created by international humanitarian emergencies, refugees or internally displaced people, and victims of human trafficking, are increasing in prevalence. These victims are often resettled in developed countries and come to the emergency department seeking care. To better care for these populations, knowledge of specialized psychosocial and cultural considerations should inform the comprehensive psychiatric assessment and treatment plan.

Road traffic injuries among middle school students in a rural area of China.

OBJECTIVE: Injuries resulting from road traffic crashes are a major and growing public health problem worldwide, disproportionately affecting vulnerable road users in developing countries. However, research on road traffic injuries in developing countries has been limited. We studied road traffic injuries among middle school students in a rural area of China. METHODS: We surveyed 1551 students in Hunan province using a hard-copy survey questionnaire. The survey was conducted at two middle schools with the cooperation of teachers and school officials. The questionnaire gathered data including sociodemographics, school activities, and sleep patterns along with road traffic injuries among middle students during a 3-month recall period in 2006. Road traffic injuries were defined as injuries incurred as a result of a road traffic collision involving at least one vehicle in motion on a public or private road that resulted in at least one person being injured. RESULTS: There were 56 road traffic injuries reported by the surveyed students yielding a rate of 3.6 percent over the 3-month period. The greatest percentage of those injuries involved a motorcycle (80%). Nearly two fifths of injuries resulted in a period of activity restriction lasting one day or more (39%). The multivariable logistic regression analysis indicated that there were statistically significant associations between the assignment of extra homework by parents (odds ratio [OR] = 3.78, 95% confidence intervals [CI] = 1.49-9.60, p-value < 0.01) and parents' treatment for poor academic performance (OR = 2.18, 95% CI = 1.18-4.02, p-value < 0.05) with road traffic injuries and difficulty falling asleep was a marginally a significant risk factor (OR = 2.03, 95% CI = 0.78-5.28, p-value = 0.06). CONCLUSION: School-related stress and sleep disturbance were identified as possible risk factors for road traffic injuries among students in a rural area of China. Further research is warranted in order to develop prevention strategies to address these preventable injuries.

Child drowning deaths in Xiamen city and suburbs, People's Republic of China, 2001 5.

BACKGROUND: Risk-factor research and prevention programs targeting drowning deaths in children have been well developed in industrialized countries, but little research has been undertaken in developing countries where the majority of drowning deaths occur. We conducted an epidemiological study to describe the sociodemographic characteristics, drowning circumstances, and medical service in drowning deaths of children in Xiamen city and suburbs, People's Republic of China. MATERIAL AND METHODS: Drowning deaths in 1-14-year-old children between 2001 and 2005 were identified using death certificates. Parents of each case were interviewed face to face about the sociodemographics of the family and child, the drowning event, and medical care received. Mortalities were calculated using census data for urban and rural areas, and Poisson regression was used to evaluate confounding effects and interactions of several major risk factors for drowning death. RESULTS: Of 67 drowning deaths identified, 52 (77.6%) were males. A higher proportion of deaths were in children aged 5-9 years (40.3%) and 10-14 years (40.3%). The drowning mortality per 100 000 population was 5.84 in rural areas and 0.75 in urban areas. Drowning events occurred most commonly during the summer months (56.7% from June to August), during the hours of 13:00-17:59 (62.7%), and in natural or man-made bodies of water (eg, ponds, ditches, construction sites, and wells). None of the children were proficient swimmers, the majority of drowning events (88.1%) occurred in the absence of adult supervision, and 86.6% children died at the scene without any medical care. Results from muiltivariable Poisson regression analysis indicated that 10-14-year-old boys were at the highest risk of drowning deaths in this area. DISCUSSION AND CONCLUSIONS: Drowning deaths in children in Xiamen city and suburbs follow trends that are markedly different from patterns observed in other countries. Different prevention strategies may be required for preventing child drowning deaths in Xiamen and other developing regions.

Transcriptional control of human T-BET expression: the role of Sp1.

Murine T-bet (T-box expressed in T cells) is a master regulator of IFN-gamma gene expression in NK and T cells. T-bet also plays a critical role in autoimmunity, asthma and other diseases. However, cis elements or trans factors responsible for regulating T-bet expression remain largely unknown. Here, we report on our discovery of six Sp1-binding sites within the proximal human T-BET promoter that are highly conserved among mammalian species. Electrophoretic mobility shift assays demonstrate a physical association between Sp1 and the proximal T-BET promoter with a direct dose response between Sp1 expression and T-BET promoter activity. Ectopic overexpression of Sp1 also enhanced T-BET expression and cytokine-induced IFN-gamma secretion in NK cells and T cells. Mithramycin A, which blocks the binding of Sp1 to the T-BET promoter, diminished both T-BET expression and IFN-gamma protein production in monokine-stimulated primary human NK cells. Collectively, our results suggest that Sp1 is a positive transcriptional regulator of T-BET. As T-BET and IFN-gamma are critically important in inflammation, infection, and cancer, targeting Sp1, possibly with mithramycin A, may be useful for preventing and/or treating diseases associated with aberrant T-BET or IFN-gamma expression.

Pro- and antiinflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells.

Activated monocytes produce proinflammatory cytokines (monokines) such as interleukin (IL)-12, IL-15, and IL-18 for induction of interferon-gamma (IFN-gamma) by natural killer (NK) cells. NK cells provide the antiinflammatory cytokine transforming growth factor (TGF)-beta, an autocrine/negative regulator of IFN-gamma. The ability of one signaling pathway to prevail over the other is likely important in controlling IFN-gamma for the purposes of infection and autoimmunity, but the molecular mechanism(s) of how this counterregulation occurs is unknown. Here we show that in isolated human NK cells, proinflammatory monokines antagonize antiinflammatory TGF-beta signaling by downregulating the expression of the TGF-beta type II receptor, and its signaling intermediates SMAD2 and SMAD3. In contrast, TGF-beta utilizes SMAD2, SMAD3, and SMAD4 to suppress IFN-gamma and T-BET, a positive regulator of IFN-gamma. Indeed, activated NK cells from Smad3(-/-) mice produce more IFN-gamma in vivo than NK cells from wild-type mice. Collectively, our data suggest that pro- and antiinflammatory cytokine signaling reciprocally antagonize each other in an effort to prevail in the regulation of NK cell IFN-gamma production.