Implementation of a pediatric trauma registry at a national referral center in Kenya: Utility and concern for sustainability.

BACKGROUND: Pediatric trauma disproportionately affects low- and middle-income countries, particularly the pediatric trauma systems, are frequently limited. This study assessed the patterns of pediatric traumatic injuries and treatment at the only free-standing public children's hospital in East Africa as well as the implementation and sustainability of the trauma registry. METHODS: A prospective pediatric trauma registry was established at Shoe4Africa Children's Hospital (S4A) in Eldoret, Kenya. All trauma patients over a six-month period were enrolled. Descriptive analyses were completed via SAS 9.4 to uncover patterns of demographics, trauma mechanisms and injuries, as well as outcomes. Implementation was assessed using the RE-AIM framework. RESULTS: The 425 patients had a median age of 5.14 years (IQR 2.4, 8.7). Average time to care was 267.5 min (IQR 134.0, 625.0). The most common pediatric trauma mechanisms were falls (32.7 %) and burns (17.7 %), but when stratified by age group, toddlers had a higher risk of sustaining injuries from burns and poisonings. Over half (56.2 %) required an operation during the hospitalization. Overall, implementation of the registry was limited by the clinical burden and inadequate personnel. Sustainability of the registry was limited by finances. CONCLUSIONS: This is the first study to describe the trauma epidemiology from a Kenyan public pediatric hospital. Maintenance of the trauma registry failed due to cost. Streamlining global surgery efforts through implementation science may allow easier development of trauma registries to then identify modifiable risk factors to prevent trauma and long-term outcomes to understand associated disability.

Human iPSC-derived retinal organoids develop robust Alzheimer's disease neuropathology.

Alzheimer's disease (AD), characterized by memory loss and cognitive decline, affects nearly 50 million people worldwide. Amyloid beta (Aß) plaques and intracellular neurofibrillary tangles (NFTs) of phosphorylated Tau protein (pTau) are key histopathological features of the disease in the brain, and recent advances have also identified AD histopathology in the retina. Thus, the retina represents a central nervous system (CNS) tissue highly amenable to non-invasive diagnostic imaging that shows promise as a biomarker for early AD. Given the devastating effects of AD on patients, their families, and society, new treatment modalities that can significantly alter the disease course are urgently needed. In this study, we have developed and characterized a novel human retinal organoid (RO) model derived from induced pluripotent stem cells (iPSCs) from patients with familial AD due to mutations in the amyloid precursor protein gene (APP). Using immunofluorescence and histological staining, we evaluated the cellular composition and AD histopathological features of AD-ROs compared to control ROs from healthy individuals. We found that AD-ROs largely resemble their healthy control counterparts in cellular composition but display increased levels of Aß and pTau. We also present proof of principle of an assay to quantify amyloid levels in whole ROs. This in vitro model of the human AD retina constitutes a new tool for drug screening, biomarker discovery, and pathophysiological studies.

Demographics and medical school exposures to rural health influence future practice.

BACKGROUND: One-fifth of the US population lives in rural areas. A record number of rural hospitals have closed, creating increased burdens on regional centers and delays in care. This study aimed to assess medical student perceptions of rural surgery and health care, and to elucidate influential factors for future practice. METHODS: We administered a survey to medical schools throughout Indiana, Illinois, and Michigan. The survey was designed and evaluated by a survey content expert and piloted among a group of students. Student and faculty liaisons disseminated the survey between February and May 2021. Descriptive analysis of data was completed using Stata v.16.1 (StataCorp, LLC, College Station, TX). RESULTS: The respondents included 700 medical students; 59.5% were female, with an equal distribution across medical school classes. More than 98% of students believe we "lack" or "are in great need of" rural health care providers, as well as rural surgeons; however, more than half of the students did not agree that the rural workforce is declining. Only 15.7% of students reported an interest in "pursuing a future career in a rural setting." Students with exposure to rural health care, coming from a rural hometown, or having a dependent had a positive association with interest in pursuing rural practice. CONCLUSION: Although students are aware of the lack of rural surgeons and health care providers, there remains an educational deficit. Expanding exposure to rural health care and surgery while in medical school may increase the number of students interested in pursuing a career in a rural setting, potentially shrinking the rural workforce gap.

Uncovering the Overlap of Global and Domestic Rural Surgery for Medical Trainees.

INTRODUCTION: Medical trainees who participate in global rotations demonstrate improved cultural sensitivity, increased involvement in humanitarian efforts, and ability to adapt to limited resources. The global coronavirus pandemic halted global rotations for medical trainees. Domestic rural surgery (DRS) may offer a unique alternative. We aimed to understand medical students' perceptions of the similarities and differences between global surgery and DRS and how students' priorities impact career choices. METHODS: An electronic survey was administered at eleven medical training institutions in Indiana, Illinois, and Michigan in spring 2021. Mixed methods analysis was performed for students who reported an interest in global surgery. Quantitative analysis was completed using Stata 16.1. RESULTS: Of the 697 medical student respondents, 202 were interested in global surgery. Of those, only 18.3% were also interested in DRS. Students interested in DRS had more rural exposures. Rural exposures associated with DRS interest were pre-clinical courses (P = 0.002), clinical rotations (P = 0.045), and rural health interest groups (P < 0.001). Students interested in DRS and those unsure were less likely to prioritize careers involving teaching or research, program prestige, perceived career advancement, and well-equipped facilities. The students who were unsure were willing to utilize DRS exposures. CONCLUSIONS: Students interested in global surgery express a desire to practice in low-resource settings. Increased DRS exposures may help students to understand the overlap between global surgery and DRS when it comes to working with limited resources, achieving work-life balance and practice location.

Paracentral Acute Middle Maculopathy in Pregnancy.

ABSTRACT: A 31-year-old previously healthy, pregnant woman presented with acute, unilateral, painless paracentral vision loss in the left eye. The results of neuroimaging studies were normal. Hypercoagulable workup was negative, and fundus examination showed no retinal emboli and no retinal vascular abnormalities. The patient had well-controlled blood pressure and did not have eclampsia/preeclampsia. Although a presumptive referral diagnosis of "optic neuritis" was made, optical coherence tomography (OCT) of the macula showed a hyperreflective band involving the inner nuclear layer, consistent with paracentral acute middle maculopathy (PAMM). Furthermore, OCT angiography (OCT-A) showed flow attenuation of the outer retinal capillary plexus, further supporting a diagnosis of PAMM in pregnancy. Clinicians should be aware of the benefit of OCT-A as a complement to macular OCT in the evaluation of acute monocular vision loss mimicking retrobulbar optic neuropathy, particularly when signs and findings of other retinal vasculopathy are absent. PAMM should be considered in pregnant patients with acute visual changes.

Uncomplicated gastroschisis care in the US and Kenya: Treatment at two tertiary care centers.

BACKGROUND: Gastroschisis is a common birth defect with < 5% mortality in high income countries, but mortality in sub Saharan Africa remains high. We sought to compare gastroschisis management strategies and patient outcomes at tertiary pediatric referral centers in the United States and Kenya. METHODS: This retrospective chart review examined uncomplicated gastroschisis patients treated at Riley Hospital for Children in Indianapolis, USA (n = 110), and Shoe4Africa Children's Hospital in Eldoret, Kenya (n = 75), from 2010 to 2018. Analyzed were completed using Chi square, Fisher's exact, and independent samples t tests and medians tests at the 95% significance level. RESULTS: Survival in the American cohort was double that of the Kenyan cohort (99.1% vs 45.3%, p< 0.001). Sterile bag use for bowel containment was lower in Kenya (81.3% vs 98.1%, p< 0.001), but silo use was comparable at both institutions (p = 0.811). Kenyan patients had earlier median enteral feeding initiation (4vs 10 days, p< 0.001) and accelerated achievement of full enteral feeding (10vs 23 days, p< 0.001), but none received TPN. Despite earlier feeding, Kenyan patients displayed a higher prevalence of wound infections (70.8% vs 17.1%, p< 0.001) and sepsis (43.9% vs 4.8%, p< 0.001). In Kenya, survivors and non survivors displayed no difference in sterile bag use, hemodynamic stability, all cause infection rates, or antibiotic free hospital days. Defect closure (p< 0.001) and enteral feeding initiation (p< 0.001) were most predictive of survival. CONCLUSION: Improving immediate response strategies for gastroschisis in Kenya could improve survival and decrease infection rates. Care strategies in the US can center on earlier enteral feeding initiation to reduce time to full feeding. LEVEL OF EVIDENCE: Level III.

A population-specific reference panel for improved genotype imputation in African Americans.

There is currently a dearth of accessible whole genome sequencing (WGS) data for individuals residing in the Americas with Sub-Saharan African ancestry. We generated whole genome sequencing data at intermediate (15×) coverage for 2,294 individuals with large amounts of Sub-Saharan African ancestry, predominantly Atlantic African admixed with varying amounts of European and American ancestry. We performed extensive comparisons of variant callers, phasing algorithms, and variant filtration on these data to construct a high quality imputation panel containing data from 2,269 unrelated individuals. With the exception of the TOPMed imputation server (which notably cannot be downloaded), our panel substantially outperformed other available panels when imputing African American individuals. The raw sequencing data, variant calls and imputation panel for this cohort are all freely available via dbGaP and should prove an invaluable resource for further study of admixed African genetics.

The role of community health workers in the surgical cascade: a scoping review.

BACKGROUND: Community health workers (CHWs) can increase access to various primary healthcare services; however, their potential for improving surgical care is under-explored. We sought to assess the role of CHWs in the surgical cascade, defined as disease screening, linkage to operative care, and post-operative care. Given the well-described literature on CHWs and screening, we focused on the latter two steps of the surgical cascade. METHODS: We conducted a scoping review of the peer-reviewed literature. We searched for studies published in any language from January 1, 2000 to May 1, 2020 using electronic literature databases including Pubmed/MEDLINE, Web of Science, SCOPUS, and Google Scholar. We included articles on CHW involvement in linkage to operative care and/or post-operative surgical care. Narrative and descriptive methods were used to analyze the data. RESULTS: The initial search identified 145 articles relevant to steps in the surgical cascade. Ten studies met our inclusion criteria and were included for review. In linkage to care, CHWs helped increase surgical enrollment, provide resources for vulnerable patients, and build trust in healthcare services. Post-operatively, CHWs acted as effective monitors for surgical-site infections and provided socially isolated patients with support and linkage to additional services. The complex and wide-ranging needs of surgical patients illustrated the need to view surgical care as a continuum rather than a singular operative event. CONCLUSION: While the current literature is limited, CHWs were able to maneuver complex medical, cultural, and social barriers to surgical care by linking patients to counseling, education, and community resources, as well as post-operative infection prevention services. Future studies would benefit from more rigorous study designs and larger sample sizes to further elucidate the role CHWs can serve in the surgical cascade.

Gender Differences in Insurance, Surgical Admissions and Outcomes at a Kenyan Referral Hospital.

INTRODUCTION: Gender is an important factor in determining access to healthcare resources. Women face additional barriers, especially in low- and middle-income countries. Surgical costs can be devastating, which can exacerbate engendered disparities. Kenya's National Hospital Insurance Fund (NHIF) aims to achieve universal coverage and protect beneficiaries from catastrophic health expenditures. We examine gender differences in NHIF coverage, health-seeking behavior, and surgical outcomes at a tertiary care hospital in Eldoret, Kenya. MATERIALS AND METHODS: All patients ≥13 years admitted to the general surgery service at Moi Teaching and Referral Hospital from January 2018-July 2018 were enrolled. Health records were retrospectively reviewed for demographic data, clinical parameters, NHIF enrollment, and cost information. Descriptive analyses utilized Wilcoxon Rank Sum, Pearson's Chi-square, and Fisher's Exact tests. RESULTS: 366 patients were included for analysis. 48.6% were enrolled in NHIF with significant female predominance (64.8% versus 37.9%, P < 0.0001). Despite differing coverage rates, male and female patients underwent surgery and suffered in-hospital mortality at similar rates. However, women only comprised 39.6% of admissions and were significantly more likely to delay care (median 60 versus 7 days, P < 0.0001), be diagnosed with cancer (26.6% versus 13.2%, P = 0.0024), and require a palliative procedure for cancer (44.1% versus 13.0%, P = 0.013). CONCLUSION: Many financial and cultural barriers exist in Kenya that prevent women from accessing healthcare as readily as men, persisting despite higher rates of NHIF coverage amongst female patients. Investigation into extra-hospital costs and social disempowerment for women may elucidate key needs for achieving health equity.

The association between blood pressure variability and hip or vertebral fracture risk: A population-based study.

BACKGROUND: The present study evaluated the association between blood pressure variability and the risk of hip/vertebral fractures in middle aged and elderly patients. METHODS: This was a retrospective observational study of patients attending family medicine outpatient clinics, recruited from 1st January 2000 to 31st December 2003 and were followed up until 31st December 2019. Standard deviation (SD), root mean square (RMS), coefficient of variation (CV) and a variability score (defined as the number of changes in blood pressure (diastolic and systolic) of 5 mm Hg or more) were used as measures of blood pressure variability. The primary outcome was a composite of new onset hip or vertebral fractures. RESULTS: A total of 57,810 patients were included. Over a median follow-up of 5894 days (interquartile range: 3505-6487), 3285 patients (5.68%) developed new onset hip/vertebral fractures. The crude incidence rates were 4.95%, 5.31%, and 7.2% for diastolic blood pressure-CV and 5.0%, 5.28%, and 7.08% for systolic blood pressure-CV in the first, second, and third tertiles, respectively. Survival analysis demonstrated differences in hip/vertebral fracture amongst the tertiles of systolic and diastolic blood pressure variability (P < 0.0001). CONCLUSIONS: Measures of blood pressure variability were significantly associated with incident hip/vertebral fractures. They can be incorporated into existing clinical scores to improve risk stratification.

Use of a Novel Trigger Tool to Identify Palliative Care Needs in Surgical Patients at a National Referral Hospital in Kenya: A Pilot Study.

Background: Addressing unmet palliative care needs in high-risk surgical patients in low- and middle-income countries must include innovative approaches to limitations in personnel and culturally acceptable assessment modalities. Objectives: We assessed the utility of a novel seven-item "Step-1" trigger tool in identifying surgical patients who may benefit from palliative care. Design: All adult patients (≥18 years) on general surgery, neurosurgery, and orthopedic surgery wards were enrolled over a four-month period. Setting/Subjects: This study took place at Moi Teaching and Referral Hospital (MTRH), one of two Kenyan national referral hospitals. Measurements: The "Step-1" trigger tool was administered, capturing provider estimates of prognosis, cancer history, social barriers, admission frequency, hospice history, symptom burden, and functional decline/wasting. A cut-point of ≥3 positive factors was selected, indicating a patient may benefit from palliative care. Results: A total of 411 patients were included for analysis. Twenty-five percent (n = 102) of patients had scores ≥3. The cut-point of ≥3 was significantly associated with identifying high-risk patients (HRP; χ2 = 32.3, p < 0.01), defined as those who died or were palliatively discharged, with a sensitivity and specificity of 63.9% and 78.9%, respectively. Survey questions with the highest overall impact included: "Would you be not surprised if the patient died within 12 months?," "Are there uncontrolled symptoms?," and "Is there functional decline/wasting?" Conclusions: This pilot study demonstrates that the "Step-One" trigger tool is a simple and effective method to identify HRP in resource-limited settings. Although this study identified three highly effective questions, the seven-question assessment is flexible and can be adapted to different settings.

Overview of methods for enhancing bone regeneration in distraction osteogenesis: Potential roles of biometals.

BACKGROUND: Distraction osteogenesis (DO) is a functional tissue engineering approach that applies gradual mechanical traction on the bone tissues after osteotomy to stimulate bone regeneration. However, DO still has disadvantages that limit its clinical use, including long treatment duration. METHODS: Review the current methods of promoting bone formation and consolidation in DO with particular interest on biometal. RESULTS: Numerous approaches, including physical therapy, gene therapy, growth factor-based therapy, stem-cell-based therapy, and improved distraction devices, have been explored to reduce the DO treatment duration with some success. Nevertheless, no approach to date is widely accepted in clinical practice due to various reasons, such as high expense, short biologic half-life, and lack of effective delivery methods. Biometals, including calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), manganese (Mn), and cobalt (Co) have attracted attention in bone regeneration attributed to their biodegradability and bioactive components released during in vivo degradation. CONCLUSION: This review summarizes the current therapies accelerating bone formation in DO and the beneficial role of biometals in bone regeneration, particularly focusing on the use of biometal Mg and its alloy in promoting bone formation in DO. Translational potential: The potential clinical applications using Mg-based devices to accelerate DO are promising. Mg stimulates expression of multiple intrinsic biological factors and the development of Mg as an implantable component in DO may be used to argument bone formation and consolidation in DO.

Accurate, scalable cohort variant calls using DeepVariant and GLnexus.

MOTIVATION: Population-scale sequenced cohorts are foundational resources for genetic analyses, but processing raw reads into analysis-ready cohort-level variants remains challenging. RESULTS: We introduce an open-source cohort-calling method that uses the highly accurate caller DeepVariant and scalable merging tool GLnexus. Using callset quality metrics based on variant recall and precision in benchmark samples and Mendelian consistency in father-mother-child trios, we optimize the method across a range of cohort sizes, sequencing methods and sequencing depths. The resulting callsets show consistent quality improvements over those generated using existing best practices with reduced cost. We further evaluate our pipeline in the deeply sequenced 1000 Genomes Project (1KGP) samples and show superior callset quality metrics and imputation reference panel performance compared to an independently generated GATK Best Practices pipeline. AVAILABILITY AND IMPLEMENTATION: We publicly release the 1KGP individual-level variant calls and cohort callset (https://console.cloud.google.com/storage/browser/brain-genomics-public/research/cohort/1KGP) to foster additional development and evaluation of cohort merging methods as well as broad studies of genetic variation. Both DeepVariant (https://github.com/google/deepvariant) and GLnexus (https://github.com/dnanexus-rnd/GLnexus) are open-source, and the optimized GLnexus setup discovered in this study is also integrated into GLnexus public releases v1.2.2 and later. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Paracentral Acute Middle Maculopathy Mimicking Retrobulbar Optic Neuropathy.

ABSTRACT: A 70-year-old woman presented with acute awareness of decreased color vision in her right eye. Fundus examination and a flash electroretinography (ERG) were both normal. A multifocal ERG (mfERG) however revealed foveal depression, and thinning of inner nuclear layer was noted on macular optical coherence tomography (OCT), and a diagnosis of resolved paracentral acute middle maculopathy was made. Clinicians should be aware of the complementary role of OCT and mfERG in unexplained acute central visual loss to distinguish retinal from neuro-ophthalmic etiologies. Structural ocular imaging with OCT shows features of inner, middle, and outer retinal localizations to the visual loss.

Arteritic Orbital Ischemia Producing Afferent and Efferent Pupillary Defects.

A 67-year-old woman presented with acute loss of vision to no light perception (NLP), a right afferent pupillary defect, and anisocoria with a nonreactive and dilated pupil in the right eye. Fundus examination showed pallid optic disc edema and a central retinal artery occlusion (CRAO) in the right eye. A temporal artery biopsy showed giant cell arteritis (GCA). Orbital involvement in GCA has been reported previously. However the combination of an afferent and efferent pupillary defect, NLP vision, pallid disc edema, and a CRAO in an elderly patient is likely a unique clinical combination that should strongly suggest GCA. Clinicians should be aware of the myriad presentations of GCA, including orbital ischemia.

Transient vision loss after optic nerve sheath fenestration.

Optic nerve sheath fenestration (ONSF) is a well-known, relatively safe, and effective surgical treatment for visual loss related to papilledema. Visual loss following ONSF is uncommon but can occur from direct surgical trauma, ischemic optic neuropathy, orbital or intrasheath hemorrhage, or arterial occlusion. Transient severe (e.g., light perception (LP) or no light perception (NLP) visual loss) after ONSF is uncommon but has been reported. We describe a case of LP vision following uncomplicated ONSF with orbital imaging demonstrating significant postoperative inflammation and slow recovery after intravenous steroid treatment. We discuss the various mechanisms for this phenomenon after ONSF. To our knowledge, this is the first clinico-radiologic description with follow up and recovery of this postoperative complication of ONSF to be reported in the English language ophthalmic literature.