Perioperative Care Pathways in Low- and Lower-Middle-Income Countries: Systematic Review and Narrative Synthesis

BACKGROUND: Safe and effective care for surgical patients requires high-quality perioperative care. In high-income countries (HICs), care pathways have been shown to be effective in standardizing clinical practice to optimize patient outcomes. Little is known about their use in low- and middle-income countries (LMICs) where perioperative mortality is substantially higher. METHODS: Systematic review and narrative synthesis to identify and describe studies in peer-reviewed journals on the implementation or evaluation of perioperative care pathways in LMICs. Searches were conducted in MEDLINE, EMBASE, CINAHL Plus, WHO Global Index, Web of Science, Scopus, Global Health and SciELO alongside citation searching. Descriptive statistics, taxonomy classifications and framework analyses were used to summarize the setting, outcome measures, implementation strategies, and facilitators and barriers to implementation. RESULTS: Twenty-seven studies were included. The majority of pathways were set in tertiary hospitals in lower-middle-income countries and were focused on elective surgery. Only six studies were assessed as high quality. Most pathways were adapted from international guidance and had been implemented in a single hospital. The most commonly reported barriers to implementation were cost of interventions and lack of available resources. CONCLUSIONS: Studies from a geographically diverse set of low and lower-middle-income countries demonstrate increasing use of perioperative pathways adapted to resource-poor settings, though there is sparsity of literature from low-income countries, first-level hospitals and emergency surgery. As in HICs, addressing patient and clinician beliefs is a major challenge in improving care. Context-relevant and patient-centered research, including qualitative and implementation studies, would make a valuable contribution to existing knowledge. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00268-022-06621-x

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Parent and staff attitudes towards in-hospital opportunistic vaccination

Objectives Recent trends of ‘vaccine hesitancy’ have resulted in calls for public health campaigns to improve immunisation uptake to World Health Organisation (WHO) targets. One potential strategy to improve uptake is to offer opportunistic vaccination to those hospital in-patients who have missed them. We aimed to evaluate parental and staff attitudes about introducing such a service for hospitalised children. Study design Cross sectional questionnaire-based design. Methods We developed and distributed a questionnaire for parents/guardians of paediatric inpatients aged 5 years and under, and a questionnaire for frontline paediatric staff (including medical, nursing and allied health professionals). Vaccination rates were assessed through discussion with parents and by reviewing the personal child health record. Results One-hundred families and 100 paediatric staff participated. Local vaccination rates were significantly below the WHO target (P < 0.001), particularly for the Bacille Calmette-Guerine (BCG) vaccination (P = 0.001). Both parents (89/100, 89%) and staff (87/100, 87%) regarded inpatient opportunistic vaccination acceptable. Parents of children with chronic disease reported a potentially higher rate of missed vaccinations, stating reasons of frequent illness and inpatient stays. The majority of staff (81/95, 85.3%) would be willing to support inpatient vaccination if appropriately trained. A significant minority had reservations. Conclusions Opportunistic vaccination is a strategy deemed acceptable by the majority of parents and staff. Children with chronic disease would especially benefit from opportunistic inpatient immunisation. In order to facilitate this, improved digital access to primary care vaccination records and investment in staff training, education and support would be required

Barriers to Quality Perioperative Care Delivery in Low- and Middle-Income Countries: A Qualitative Rapid Appraisal Study.

BACKGROUND: Provision of timely, safe, and affordable surgical care is an essential component of any high-quality health system. Increasingly, it is recognized that poor quality of care in the perioperative period (before, during, and after surgery) may contribute to significant excess mortality and morbidity. Therefore, improving access to surgical procedures alone will not address the disparities in surgical outcomes globally until the quality of perioperative care is addressed. We aimed to identify key barriers to quality perioperative care delivery for 3 "Bellwether" procedures (cesarean delivery, emergency laparotomy, and long-bone fracture fixation) in 5 low- and middle-income countries (LMICs). METHODS: Ten hospitals representing secondary and tertiary facilities from 5 LMICs were purposefully selected: 2 upper-middle income (Colombia and South Africa); 2 lower-middle income (Sri Lanka and Tanzania); and 1 lower income (Uganda). We used a rapid appraisal design (pathway mapping, ethnography, and interviews) to map out and explore the complexities of the perioperative pathway and care delivery for the Bellwether procedures. The framework approach was used for data analysis, with triangulation across different data sources to identify barriers in the country and pattern matching to identify common barriers across the 5 LMICs. RESULTS: We developed 25 pathway maps, undertook >30 periods of observation, and held >40 interviews with patients and clinical staff. Although the extent and impact of the barriers varied across the LMIC settings, 4 key common barriers to safe and effective perioperative care were identified: (1) the fragmented nature of the care pathways, (2) the limited human and structural resources available for the provision of care, (3) the direct and indirect costs of care for patients (even in health systems for which care is ostensibly free of charge), and (4) patients' low expectations of care. CONCLUSIONS: We identified key barriers to effective perioperative care in LMICs. Addressing these barriers is important if LMIC health systems are to provide safe, timely, and affordable provision of the Bellwether procedures

Operationalisation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 trials in a low and lower-middle income critical care learning health system

The Randomized Embedded Multifactorial Adaptive Platform (REMAP-CAP) adapted for COVID-19) trial is a global adaptive platform trial of hospitalised patients with COVID-19. We describe implementation in three countries under the umbrella of the Wellcome supported Low and Middle Income Country (LMIC) critical care network: Collaboration for Research, Implementation and Training in Asia (CCA). The collaboration sought to overcome known barriers to multi centre-clinical trials in resource-limited settings. Methods described focused on six aspects of implementation: i, Strengthening an existing community of practice; ii, Remote study site recruitment, training and support; iii, Harmonising the REMAP CAP- COVID trial with existing care processes; iv, Embedding REMAP CAP- COVID case report form into the existing CCA registry platform, v, Context specific adaptation and data management; vi, Alignment with existing pandemic and critical care research in the CCA. Methods described here may enable other LMIC sites to participate as equal partners in international critical care trials of urgent public health importance, both during this pandemic and beyond

Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%. Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). CONCLUSIONS AND RELEVANCE: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707