Beyond the Ivory Tower: Perception of academic global surgery by surgeons in low- and middle-income countries.

Interest in global surgery has surged amongst academics and practitioners in high-income countries (HICs), but it is unclear how frontline surgical practitioners in low-resource environments perceive the new field or its benefit. Our objective was to assess perceptions of academic global surgery amongst surgeons in low- and middle-income countries (LMICs). We conducted a cross-sectional e-survey among surgical trainees and consultants in 62 LMICs, as defined by the World Bank in 2020. This paper is a sub-analysis highlighting the perception of academic surgery and the association between practice setting and responses using Pearson's Chi-square test. Analyses were completed using Stata15. The survey received 416 responses, including 173 consultants (41.6%), 221 residents (53.1%), 8 medical graduates (1.9%), and 14 fellows (3.4%). Of these, 72 responses (17.3%) were from low-income countries, 137 (32.9%) from lower-middle-income countries, and 207 (49.8%) from upper-middle-income countries. 286 respondents (68.8%) practiced in urban areas, 34 (8.2%) in rural areas, and 84 (20.2%) in both rural and urban areas. Only 185 (44.58%) were familiar with the term "global surgery." However, 326 (79.3%) agreed that collaborating with HIC surgeons for research is beneficial to being a global surgeon, 323 (78.8%) agreed that having an HIC co-author improves likelihood of publication in a reputable journal, 337 (81.6%) agreed that securing research funding is difficult in their country, 195 (47.3%) agreed that their institutions consider research for promotion, 252 (61.0%) agreed that they can combine research and clinical practice, and 336 (82%) are willing to train HIC medical students and residents. A majority of these LMIC surgeons noted limited academic incentives to perform research in the field. The academic global surgery community should take note and foster equitable collaborations to ensure that this critical segment of stakeholders is engaged and has fewer barriers to participation.

Food Allergy Reaction Severity and Management in a Diverse Population.

BACKGROUND: Definitive treatment for food allergy reactions including anaphylaxis varies widely by reaction severity and socioeconomic status, but little data exist to characterize the relationship between severity, management, and race and ethnicity. OBJECTIVE: To analyze the differences in reaction severity, epinephrine use, and emergency room (ER) use by race and ethnicity in a large, diverse, food-allergic cohort. METHODS: We analyzed intake data from participants in the Food Allergy Outcomes Related to White and African-American Racial Differences cohort on the history of food allergy reactions, severity of the reactions, and management associated with each reaction. We used descriptive statistics as well as mixed-effects logistic and Poisson models to describe the differences in reaction severity, ER visits, and total lifetime epinephrine use by race and ethnicity. RESULTS: A total of 784 children were included in the analysis: 425 (54.2%) were non-Hispanic White, 282 (36.0%) were non-Hispanic Black, and 77 (9.8%) were Hispanic/Latino. Non-Hispanic Black children had increased odds of more severe reactions (odds ratio, 1.7; 95% CI, 1.2-2.3) and higher odds of going to the ER (odds ratio, 2.8; 95% CI, 1.4-5.4). Both non-Hispanic Black (incidence rate ratio, 0.4; 95% CI, 0.3-0.5) and Hispanic/Latino (incidence rate ratio, 0.3; 95% CI, 0.2-0.5) children had lower rates of total lifetime epinephrine use. CONCLUSIONS: There are significant disparities in the severity and treatment of food allergy reactions by race and ethnicity, resulting in increased ER use and decreased total lifetime epinephrine use. Equipping parents with resources and tools on management of food allergy reactions may result in decreased disparity in access to definitive care.

Natural Topical Treatment Contributes to a Reduction of Dry Scalp Symptoms in Children.

Background: Dry scalp conditions affect a significant portion of the population, including children. Emerging evidence indicates the potential for improvement of atopic symptoms through altering the skin microbiome. Therefore, a topical treatment consisting of probiotic extracts, honey, turmeric, and vitamin B12 was manufactured to improve dry scalp symptomology through sustained balance of the microbiome. Purpose: This interventional clinical study aims to determine the safety and efficacy of the topical treatment in reducing dry scalp symptomology in children 1-17 years old with dry scalp symptoms. Methods: Participants applied the topical dry scalp treatment 2-3 times per week for two weeks. Safety and efficacy of the topical treatment was determined through physician assessment using the validated Investigator's Global Assessment (IGA) scale and the Total Severity Scale (TSS) during pre- and post-treatment clinic visits as well as parent reports at baseline, 1-week midpoint, and 2-week exit. Results: Use of the topical treatment was associated with reduced symptoms of itchiness, dryness, irritation, and flakiness in children. The average IGA score was 3.0 at baseline and 2.0 after treatment, corresponding to a score difference of 1.0 (p < 0.001, 95% CI: 0.7, 1.2). The TSS score difference was 1.9 (p < 0.001, 95% CI: 1.4, 2.4). The total parent-reported scalp severity score decreased from 16.6 (95% CI: 14.8, 18.4) to 12.4 (p < 0.001, 95% CI: 11.0, 13.7) at 2-week exit. Discussion: Study results mirror those reported in a study conducted in adults and point to the safety and efficacy of this natural topical treatment in reducing dry scalp symptomology in children. Based on our data, the combination of probiotic extracts and other anti-inflammatory ingredients appears to improve overall scalp health and appearance, though further studies will need to be conducted to further elucidate the link between clinical improvement and a balanced scalp microbiome.

Gut microbiome is associated with asthma and race in children with food allergy.

BACKGROUND: The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children with FA have higher rate of asthma compared to their White counterparts. OBJECTIVE: We sought to investigate whether the diversity and relative abundance (RA) of gut microbiota is different between children with FA from different racial backgrounds living in the same cities. Furthermore, we aimed to understand whether the difference in the gut microbiota is associated with asthma in children with FA. METHODS: We analyzed and compared the stool microbiome of a cohort of Black and White children with FA by shotgun genomic sequencing. RESULTS: A total of 152 children with IgE-mediated FA enrolled onto FORWARD (Food Allergy Outcomes Related to White and African American Racial Differences); 30 Black and 122 White children were included. The RA of several bacteria was associated with race and asthma. Most notably the RA of Bacteroides thetaiotaomicron, Chlamydia thrachomatis, Parabacteroides goldsteinii, and Bacteroides eggerthii were significantly higher, while the RA of Bifidobacterium sp CAG:754, Parabacterium johnsonii, Bacteroides intestinalis, and Bifidobacterium breve were significantly lower in stool samples of Black children compared to White children. Asthma was associated with lower RA of B breve, Bifidobacterium catenulatum, Prevotella copri, Veilloella sp CAG:933, and Bacteroides plebius, and higher RA of 3 Bacteroides species. CONCLUSIONS: The observed variations in the gut microbiota of Black and White children such as differences in the Bacteroides and Bifidobacterium species along with their association to history of asthma in our cohort is indicative of their potential role in the higher rate of asthma observed among Black children with FA.

Geographic and socioeconomic inequities in cesarean delivery rates at the district level in Madhya Pradesh, India: A secondary analysis of the national family health survey-5.

BACKGROUND: In India, caesarean delivery (CD) accounts for 17% of the births, of which 41% occur in private facilities. However, areas to CD in rural areas are limited, particularly for the poor populations. Little information is available on state-wise district-level CD rates by geography and the population wealth quintiles, especially in Madhya Pradesh (MP), the fifth most populous and third poorest state. OBJECTIVE: Investigate geographic and socioeconomic inequities of CD across the 51 districts in MP and compare the contribution of public and private healthcare facilities to the overall state CD rate. METHODS: This cross-sectional study utilised the summary fact sheets of the National Family Health Survey (NFHS)-5 performed from January 2019 to April 2021. Women aged 15 to 49 years, with live births two years preceding the survey were included. District-level CD rates in MP were used to determine the inequalities in accessing CD in the poorer and poorest wealth quintiles. CD rates were stratified as <10%, 10-20% and >20% to measure equity of access. A linear regression model was used to examine the correlation between the fractions of the population in the two bottom wealth quintiles and CD rates. RESULTS: Eighteen districts had a CD rate below 10%, 32 districts were within the 10%-20% threshold and four had a rate of 20% or higher. Districts with a higher proportion of poorer population and were at a distance from the capital city Bhopal were associated with lower CD rates. However, this decline was steeper for private healthcare facilities (R2 = 0.382) revealing a possible dependency of the poor populations on public healthcare facilities (R2 = 0.009) for accessing CD. CONCLUSION: Although CD rates have increased across MP, inequities within districts and wealth quintiles exist, warranting closer attention to the outreach of government policies and the need to incentivise CDs where underuse is significant.

Bleeding, Hemorrhagic Shock, and the Global Blood Supply.

Hemorrhage is responsible for at least 40% of deaths after trauma and 27% of maternal deaths worldwide. Patients with hemorrhagic shock require attentive critical care and transfusion of blood products. Access to a safe and affordable blood supply is critical to providing safe surgical care. Traumatic injury, obstetric hemorrhage, and upper gastrointestinal bleed are the main causes of severe bleeding requiring transfusion. This article discusses the presentation and management of these causes across the world and provides a brief overview of the current challenges in maintaining a global blood supply.

Racial, ethnic, and socioeconomic disparities in COVID-19 and influenza vaccination in pediatric food allergy.

Background: Current COVID-19 and influenza vaccination-related knowledge, attitudes, and behaviors remain poorly understood among US children with food allergy-and particularly those from non-Hispanic Black, Latinx, and lower income backgrounds who bear a disproportionate burden by allergic disease. These data are especially relevant due to historical vaccine hesitancy in children with food allergy and an initial contraindication for those with severe allergic reactions to be vaccinated against COVID-19. Objective: We sought to characterize COVID-19 and influenza vaccination-related knowledge, attitudes, and behaviors in a racially, ethnically, and socioeconomically diverse longitudinal cohort of caregiver-child dyads with IgE-mediated food allergy. Methods: We leveraged the NIH-supported FORWARD cohort, consisting of non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx children diagnosed with food allergy to assess COVID-19 testing, vaccination, and influenza vaccine concern and utilization through administering a one-time IRB-approved survey. Results: Non-Hispanic Black participants were less likely than Non-Hispanic White participants to be vaccinated (OR=0.25, 95%CI:0.08-0.75) or tested (OR=0.33, 95%CI:0.13-0.85) for COVID-19 and have the intention to vaccinate their children for influenza (OR=0.42; 0.18-0.98). Over one third of participants reported that they believe their child is at greater risk of complications from COVID-19 vaccination due to food allergy. There were racial/ethnic disparities in the belief that COVID vaccines contain allergenic ingredients such that more Hispanic/Latinx (37%) and Black (37%) participants than White (22%) participants reported this belief (p=.02). Conclusion: The present findings of disparities in vaccination-related knowledge, attitudes, and behaviors across racial/ethnic, and household income strata suggest that initial reports of COVID-19 vaccination hesitancy within the population with food allergy may be further exacerbated by well-documented, racial, ethnic, and socioeconomic differences in vaccine hesitancy, potentially leading to a greater infectious disease burden in these vulnerable populations. This highlights a need for targeted education and outreach among members of these communities who are living with food allergy.

Assessing the Rates and Reasons of Elective Surgical Cancellations on the Day of Surgery: A Multicentre Study from Urban Indian Hospitals.

BACKGROUND: Cancellations of elective surgeries on the day of surgery (DOS) can lead to added financial burden and wastage of resources for healthcare facilities; as well as social and emotional problems to patients. These cancellations act as barriers to delivering efficient surgical services. Optimal utilisation of the available resources is necessary for resource-constrained low-and-middle-income countries (LMIC). This study investigates the rate and causes of cancellations of elective surgeries on the DOS in various surgical departments across ten hospitals in India. METHODS: A research consortium 'IndSurg' led by World Health Organisation Collaboration Centre (WHOCC) for Research in Surgical Care Delivery in LMICs, India conducted this multicentre retrospective cross-sectional study to analyse the cancellations of elective/planned surgical operations on DOS across urban secondary and tertiary level hospitals. We audited surgical records of a pre-decided period of six weeks for cancellations, documented relevant demographic information and reasons for cancellations. RESULTS: We analysed records from the participating hospitals, with an overall cancellation rate of 9.7% (508/5231) on the DOS for elective surgical operations. Of these, 74% were avoidable cancellations. A majority (30%) of these 508 cancellations were attributed to insufficient resources, 28% due to patient's refusal or failure to show-up, and 22% due to change in patient's medical status. CONCLUSION: We saw a preponderance of avoidable reasons for elective surgery cancellations. A multidisciplinary approach with adequate preoperative patient counselling, timely communication between the patients and caregivers, adequate preoperative anaesthetic assessment, and planning by the surgical team may help reduce the cancellation rate.

Associations of Food Allergy-Related Dietary Knowledge, Attitudes, and Behaviors Among Caregivers of Black and White Children With Food Allergy.

BACKGROUND: The increasing prevalence of pediatric food allergy (FA) in the United States has disproportionately affected non-Hispanic Black youth. However, racial and other socioeconomic disparities in FA management among caregivers of children with FA remain unclear. OBJECTIVE: To determine associations between socioeconomic, clinical, and health care factors and FA-related knowledge, attitudes, and behaviors among caregivers of Black and White children with FA. DESIGN: Cross-sectional survey analysis from the Food Allergy Outcomes Related to White and African American Racial Differences Study. PARTICIPANTS/SETTINGS: Longitudinal cohort of caregivers of 385 Black and White children with FA ages birth to 12 years residing in Chicago, Illinois, Cincinnati, Ohio, and Washington, DC from 2017 to March 2021. MAIN OUTCOME MEASURES: There were 3 primary outcomes of interest: (1) FA knowledge assessed by scores from the Knowledge Survey, (2) FA-related attitudes assessed by newly developed survey, and (3) food-related behaviors assessed by the FORWARD Diet and Purchasing Habit Surveys completed 6 months postenrollment. ANALYSES: Multivariable linear and logistic regression. RESULTS: The overall response rate to the 6-month postenrollment survey was 51.3% (385 of 751). White caregivers represented 69.4% of the participants. Black race was associated with a 1.5-point mean decrease in FA knowledge score (95% CI: -2.2 to -0.7) compared with White caregivers, and a graduate degree or bachelor's degree was associated with associated with a 1.7-point mean increase (95% CI: 0.8-2.7) and 1.1-point mean increase (95% CI: 0.2-2.0) in FA knowledge score, respectively, compared with caregivers who had less than a bachelor's degree. Multiple FAs and ever visited the emergency department for a food-related allergic reaction were also associated with higher levels of FA knowledge. Ever visited the emergency department for FA was also associated with higher odds of 2 measures of FA attitudes reflecting parental anxiety. Greater FA knowledge scores were consistently associated with lower odds of several FA-related food purchasing and eating behaviors assumed to have elevated risk of FA. Eating food prepared at school was the only FA behavior associated with race. Compared with White children, Black children were 2.5 times more likely to eat school-prepared foods (95% CI: 1.2-5.6). CONCLUSIONS: Findings from this study identified socioeconomic, racial, and clinical factors associated with caregivers' FA-related knowledge, attitudes, and behaviors, but further research is warranted to better understand these relationships.

Are morbidity and mortality estimates from randomized controlled trials externally valid? A comparison of outcomes among infants enrolled into an RCT or a cohort study in Botswana.

BACKGROUND: The external validity of the randomized controlled trial (RCT) refers to the extent to which the results of the RCT apply to the relevant, non-trial population and is impacted by its eligibility criteria, its organization, and its delivery of the intervention. Here, we compared the outcomes of mortality and hospitalization between an RCT and a cohort study that concurrently enrolled HIV-exposed uninfected (HEU) newborns in Botswana. METHODS: The Mpepu Study (the RCT) was a clinical trial which determined that co-trimoxazole (CTX) provided no survival benefit for HEUs, allowing both arms of the RCT to be used. The Maikaelelo study (the cohort study) was a prospective observational study that enrolled HEU newborns with telephone follow-up and no in-person visits. Rates of death and hospitalization in the pooled population, were modeled using cox-proportional hazards models for time to death or time to first hospitalization, with study setting (RCT vs. cohort study) as an independent variable. The causal effect of study setting on morbidity and mortality was obtained through a treatment effects approach. RESULTS: In total, 4,010 infants were included; 1,306 were enrolled into the cohort study and 2,704 were enrolled into the RCT. No significant differences in mortality were observed between the two study settings (HR: 1.28, 95% CI: 0.76, 2.13), but RCT participants had a lower risk of hospitalization (HR: 0.72, 95% CI: 0.58, 0.89) that decreased with age. However, RCT participants had a higher risk of hospitalization within the first six months of life. The causal risk difference in hospitalizations attributable to the RCT setting was -0.03 (95% CI: -0.05, -0.01). CONCLUSIONS: Children in an RCT with rigorous application of national standard of care guidelines experienced a significantly lower risk of hospitalization than children participating in a cohort study that did not alter clinical care. Future research is needed to further investigate outcome disparities when real-world results fail to mirror those achieved in a clinical trial. Trial registration The Mpepu Trial was funded by the U.S. National Institutes of Health (No. NCT01229761) and the Maikaelelo Study was funded primarily by the U.S. Centers for Disease Control and Prevention (32AI007433-21).

Transition to Dolutegravir Is Associated With an Increase in the Rate of Body Mass Index Change in a Cohort of Virally Suppressed Adolescents.

BACKGROUND: Antiretroviral therapy (ART) regimens that contain dolutegravir (DTG) have been associated with increases in body mass index (BMI) in adults. However, this relationship has not been well described in adolescents. METHODS: In a retrospective observational cohort of 460 virally suppressed (<200 copies/mL) adolescents living with human immunodeficiency virus at a clinical site in Eswatini, body mass index (BMI) measurements were analyzed between 1 year prior to the transition to DTG and up to 1 year after DTG transition. Random-effects linear spline models were used to describe the rate of change in BMI before and after the transition to DTG. RESULTS: In adolescents, BMI increased at a rate of 0.3 kg/m2 per year before DTG transition and increased to a rate of 1.2 kg/m2 per year after DTG transition. Sex of the adolescent modified the relationship between DTG and rate of BMI change: BMI rate of change after DTG transition was increased by 1.1 kg/m2 in females and 0.6 kg/m2 per year in males. CONCLUSIONS: Transition to DTG in virally suppressed adolescents (aged 10-19 years) is associated with an increase in the rate of BMI change. Female adolescents may experience a larger change than males. Further investigation is required to elucidate the mechanism that underlies these observations and to assess how DTG impacts BMI in adolescents following longer durations of treatment.

Predictors of suboptimal adherence to isoniazid preventive therapy among adolescents and children living with HIV.

This study identified factors associated with adherence to a 6-month isoniazid preventive therapy (IPT) course among adolescents and children living with HIV. Forty adolescents living with HIV and 48 primary caregivers of children living with HIV completed a Likert-based survey to measure respondent opinions regarding access to care, quality of care, preferred regimens, perceived stigma, and confidence in self-efficacy. Sociodemographic data were collected and adherence measured as the average of pill counts obtained while on IPT. The rates of suboptimal adherence (< 95% adherent) were 22.5% among adolescents and 37.5% among the children of primary caregivers. Univariate logistic regression was used to model the change in the odds of suboptimal adherence. Independent factors associated with suboptimal adherence among adolescents included age, education level, the cost of coming to clinic, stigma from community members, and two variables relating to self-efficacy. Among primary caregivers, child age, concerns about stigma, and location preference for meeting a community-health worker were associated with suboptimal adherence. To determine whether these combined factors contributed different information to the prediction of suboptimal adherence, a risk score containing these predictors was constructed for each group. The risk score had an AUC of 0.87 (95% CI: 0.76, 0.99) among adolescents and an AUC of 0.76 (95% CI: 0.62, 0.90), among primary caregivers suggesting that these variables may have complementary predictive utility. The heterogeneous scope and associations of these variables in different populations suggests that interventions aiming to increase optimal adherence will need to be tailored to specific populations and multifaceted in nature. Ideally interventions should address both long-established barriers to adherence such as cost of transportation to attend clinic and more nuanced psychosocial barriers such as perceived community stigma and confidence in self-efficacy.

Predicting Sexually Transmitted Infections Among HIV+ Adolescents and Young Adults: A Novel Risk Score to Augment Syndromic Management in Eswatini.

BACKGROUND: Despite poor predictive power, syndromic screening is standard of care for diagnosing sexually transmitted infections (STIs) in low-resource, high HIV-burden settings. Predictive models may augment syndromic screening when diagnostic testing is not universally available for screening high-risk patient populations such as adolescents and young adults living with HIV. SETTING: Four hundred fifteen adolescents and young adults living with HIV, age 15-24 years, participated from 3 clinical sites in Eswatini, provided urine, sexual and medical history, and completed physical examination. METHODS: STI cases were defined by a positive Xpert result for Chlamydia trachomatis, Neisseria gonorrhea, or Trichomonas vaginalis. Features predictive of an STI were selected through Least Absolute Shrinkage and Selection Operator (LASSO) with 5-fold cross validation. Various model strategies were compared with parametric area under the Receiver Operator Curve (AUC) estimation and inferences were made with bootstrapped standard errors. RESULTS: Syndromic screening poorly predicted STIs [AUC 0.640 95% Confidence Interval (95% CI): 0.577 to 0.703]. A model considering 5 predictors (age group, sex, any sexual activity, not always using condoms (either self or partner), a partner who was 25 years or older, and horizontal or unknown mode of HIV acquisition) predicted STIs better than syndromic screening [AUC: 0.829 (95% CI: 0.774 to 0.885)] and was improved when the risk score was supplemented with leukocyte esterase (LE) testing [AUC: 0.883 (95% CI: 0.806 to 0.961)]. CONCLUSIONS: This simple predictive model, with or without leukocyte esterase testing, could improve STI diagnosis in HIV-positive adolescents and young adults in high burden settings through complementary use with syndromic screening and to guide patient selection for molecular STI diagnostic tests.

Evaluating the Contribution of Transition-State Destabilization to Changes in the Residence Time of Triazole-Based InhA Inhibitors.

A critical goal of lead compound selection and optimization is to maximize target engagement while minimizing off-target binding. Since target engagement is a function of both the thermodynamics and kinetics of drug-target interactions, it follows that the structures of both the ground states and transition states on the binding reaction coordinate are needed to rationally modulate the lifetime of the drug-target complex. Previously, we predicted the structure of the rate-limiting transition state that controlled the time-dependent inhibition of the enoyl-ACP reductase InhA. This led to the discovery of a triazole-containing diphenyl ether with an increased residence time on InhA due to transition-state destabilization rather than ground-state stabilization. In the present work, we evaluate the inhibition of InhA by 14 triazole-based diphenyl ethers and use a combination of enzyme kinetics and X-ray crystallography to generate a structure-kinetic relationship for time-dependent binding. We show that the triazole motif slows the rate of formation for the final drug-target complex by up to 3 orders of magnitude. In addition, we identify a novel inhibitor with a residence time on InhA of 220 min, which is 3.5-fold longer than that of the INH-NAD adduct formed by the tuberculosis drug, isoniazid. This study provides a clear example in which the lifetime of the drug-target complex is controlled by interactions in the transition state for inhibitor binding rather than the ground state of the enzyme-inhibitor complex, and demonstrates the important role that on-rates can play in drug-target residence time.