Hirschsprung disease: a cost analysis study of the direct, indirect costs and financial coping strategies for the surgical management in Western Uganda.

BACKGROUND: Surgical management of Hirschsprung disease (HD) in low- and middle-income countries is typically a staged procedure, necessitating multiple hospitalizations and clinic visits increasing family financial burden. Currently, there is limited information on the costs borne by caretakers of children with Hirschsprung disease seeking surgical intervention. This study seeks to measure the costs and economic burden of surgical treatment for Hirschsprung disease in western Uganda. METHODS: A cross-sectional study using cost analysis was conducted among caretakers of patients who completed surgical treatment of HD between January 2017 and December 2021 at two hospitals in western Uganda. The average direct and indirect costs incurred by caretakers presenting at a public and private hospital were computed. RESULTS: A total of 69 patients (M: F = 7:1) were enrolled in the study. The median age at diagnosis was 60.5 (IQR 3-151.25) days for children and two-staged pull-through procedure was the common surgery performed. The mean overall cost for treatment was US $960 (SD = $720), with the majority of costs coming from direct medical costs. Nearly half (48%) of participants resorted to distress financing to finance their child's surgical care. The overwhelming majority of patients (n = 64, 93%) incurred catastrophic expenditure from the total costs of surgery for HD, and 97% of participants fell below the international poverty line at the time treatment was completed. CONCLUSION: Despite the availability of 'free care' from government hospital and non-profit services, this study found that surgical management of Hirschsprung disease imposed substantial cost burden on families with Hirschsprung disease patients.

Improving Surgical Research Capacity in Low- and Middle-Income Countries: Can Episodic Data Collection Reliably Estimate Perioperative Mortality?

OBJECTIVE: The aim of this study was to empirically determine the optimal sample size needed to reliably estimate perioperative mortality (POMR) in different contexts. SUMMARY BACKGROUND DATA: POMR is a key metric for measuring the quality and safety of surgical systems and will need to be tracked as surgical care is scaled up globally. Continuous collection of outcomes for all surgical cases is not the standard in high-income countries and may not be necessary in low- and middle-income countries. METHODS: We created simulated datasets to determine the sampling frame needed to reach a given precision. We validated our findings using data collected at Mulago National Referral Hospital in Kampala, Uganda. We used these data to create a tool that can be used to determine the optimal sampling frame for a population based on POMR rate and target POMR improvement goal. RESULTS: Precision improved as the sampling frame increased. However, as POMR increased, lower sampling percentages were needed to achieve a given precision. A total of 357 eligible cases were identified in the Mulago database with an overall POMR rate of 14%. Precision of ±10% was achieved with 34% sampling, and precision of ±25% was obtained at 9% sampling. Using simulated datasets, a tool was created to determine the minimum sample percentage needed to detect a given mortality improvement goal. CONCLUSIONS: Reliably tracking POMR does not require continuous data collection. Data driven sampling strategies can be used to decrease the burden of data collection to track POMR in resource-constrained settings.

Clinical Practices Following Train-The-Trainer Trauma Course Completion in Uganda: A Parallel-Convergent Mixed-Methods Study.

BACKGROUND: Despite the growth of trauma training courses worldwide, evidence for their impact on clinical practice in low- and middle-income countries (LMICs) is sparse. We investigated trauma practices by trained providers in Uganda using clinical observation, surveys, and interviews. METHODS: Ugandan providers participated in the Kampala Advanced Trauma Course (KATC) from 2018 to 2019. Between July and September of 2019, we directly evaluated guideline-concordant behaviors in KATC-exposed facilities using a structured real-time observation tool. We conducted 27 semi-structured interviews with course-trained providers to elucidate experiences of trauma care and factors that impact adoption of guideline-concordant behaviors. We assessed perceptions of trauma resource availability through a validated survey. RESULTS: Of 23 resuscitations, 83% were managed without course-trained providers. Frontline providers inconsistently performed universally applicable assessments: pulse checks (61%), pulse oximetry (39%), lung auscultation (52%), blood pressure (65%), pupil examination (52%). We did not observe skill transference between trained and untrained providers. In interviews, respondents found KATC personally transformative but not sufficient for facility-wide improvement due to issues with retention, lack of trained peers, and resource shortages. Resource perception surveys similarly demonstrated profound resource shortages and variation across facilities. CONCLUSIONS: Trained providers view short-term trauma training interventions positively, but these courses may lack long-term impact due to barriers to adopting best practices. Trauma courses should include more frontline providers, target skill transference and retention, and increase the proportion of trained providers at each facility to promote communities of practice. Essential supplies and infrastructure in facilities must be consistent for providers to practice what they have learned.

Financing Pediatric Surgery: A Provider's Perspective from the Global Initiative for Children's Surgery.

BACKGROUND: Half the world's population is at risk of catastrophic health expenditure (CHE, out-of-pocket spending of more than 10% of annual expenditure) should they require surgery. Protection against CHE is a key indicator of successful health care delivery and has been identified as a priority area by the Global Initiative for Children's Surgery (GICS). Data specific to pediatric surgical patients is limited. This study examines the financial risks for pediatric surgical patients and their families from a provider's perspective. METHODS: We surveyed GICS members about the existing financial protection mechanisms and estimated expenditures for their patients. Questions were structured based on the National Surgical, Obstetric and Anesthesia Planning Surgical Indicators and finalized based on multi-institutional consensus between high-income country and low-and middle-income country (LMIC) providers. Chi-squared test, Fisher's exact test and student's t-test were used as appropriate. RESULTS: Among 107 respondents, 72.4% were from low income or lower-middle income (LIC/LMIC) countries, and 55.1% were attending or consultant physicians. Families were most likely to decline surgery in LIC/LMIC due to inability to afford treatment (mean Likert = 3.77 ± 1.06). The odds of incurring CHE after children's surgery are up to 17 times greater in LIC/LMIC (P = 0.001, unadjusted OR 17.28, 95%CI 2.13-140.02). Over 50% of families of children undergoing major surgery in these settings face CHE. An estimated 5.1% of providers in LIC/LMIC and 56.2% (P < 0.001) of providers in UMIC/HIC reported that families are able to pay for their direct medical costs with the assistance available to them and were more likely to sell assets (74.4% vs. 33.3%, P = 0.005). CONCLUSION: Patients in LMICs are at greater risk for CHE and have less financial risk protection than their HIC counterparts. Given this disparity, intervention is needed to make safe surgery affordable for children worldwide.

Stance leg and surface stability modulate cortical activity during human single leg stance.

Mobile Electroencephalography (EEG) provides insights into cortical contributions to postural control. Although changes in theta (4-8 Hz) and alpha frequency power (8-12 Hz) were shown to reflect attentional and sensorimotor processing during balance tasks, information about the effect of stance leg on cortical processing related to postural control is lacking. Therefore, the aim was to examine patterns of cortical activity during single-leg stance with varying surface stability. EEG and force plate data from 21 healthy males (22.43 ± 2.23 years) was recorded during unipedal stance (left/right) on a stable and unstable surface. Using source-space analysis, power spectral density was analyzed in the theta, alpha-1 (8-10 Hz) and alpha-2 (10-12 Hz) frequency bands. Repeated measures ANOVA with the factors leg and surface stability revealed significant interaction effects in the left (p = 0.045, ηp2 = 0.13) and right motor clusters (F = 16.156; p = 0.001, ηp2 = 0.41). Furthermore, significant main effects for surface stability were observed for the fronto-central cluster (theta), left and right motor (alpha-1), as well as for the right parieto-occipital cluster (alpha-1/alpha-2). Leg dependent changes in alpha-2 power may indicate lateralized patterns of cortical processing in motor areas during single-leg stance. Future studies may therefore consider lateralized patterns of cortical activity for the interpretation of postural deficiencies in unilateral lower limb injuries.

Pulmonary Metastasis of Low-risk Perinatal Neuroblastoma After Resection: Implications for Surveillance.

In the wake of the Children's Oncology Group (COG) ANBL00P2 trial and the ongoing ANBL1232 trial, an increasing number of children with neonatal neuroblastoma are being managed nonoperatively. We report the case of a patient with low-risk, non-MYCN amplified, neuroblastoma that was diagnosed and resected in the neonatal period but subsequently developed pulmonary metastases by the age of 7 months. Though rare, the possibility of low-risk disease metastasizing during surveillance should be recognized and may not be identified by current protocols.

Burden and Outcomes of Neonatal Surgery in Uganda: Results of a Five-Year Prospective Study.

BACKGROUND: Ninety-four percent of congenital anomalies occur in low- and middle-income countries. In Uganda, only three pediatric surgeons and three pediatric anesthesiologists serve more than 20 million children. This study estimates burden, outcomes, coverage, and economic benefit of neonatal surgical conditions in Uganda. METHODS: A prospectively collected database was reviewed for neonatal surgical admissions from January 1, 2012, to December 31, 2017, at the only two sites with specialist pediatric surgical coverage. Outcomes were compared with high-income countries. Met and unmet need were estimated using disability-adjusted life years. Economic benefit was estimated using a value of statistical life-year approach. RESULTS: For 1313 neonatal admissions, the median age of presentation was 3 d, overall mortality was 36%, and median distance traveled was 40 km. Anorectal malformations were most common (18%). Postoperative mortality was 24%. Mortality was significantly associated with surgical intervention (P < 0.0001). Met need was 4181 disability-adjusted life years per year, which corresponds to a $3.5 million net economic benefit to Uganda, with a potential additional benefit of $153 million if unmet need were fully addressed. Approximately 2% of the total need is met by the health care system. CONCLUSIONS: Neonatal surgery is associated with improved survival for most conditions. Despite increases in workforce and infrastructure, a limited proportion of the need for neonatal surgery is currently being met. This is multifactorial, including lack of access to surgical care and severe shortages of workforce and infrastructure. Current and potential economic benefit to Uganda appears substantial.

Development of an Operative Trauma Course in Uganda-A Report of a Three-Year Experience.

BACKGROUND: Trauma is a leading cause of morbidity and mortality in low-income countries. Improved health care systems and training are potential avenues to combat this burden. We detail a collaborative and context-specific operative trauma course taught to postgraduate surgical trainees practicing in a low-resource setting and examine its effect on resident practice. METHOD: Three classes of second year surgical residents participated in trainings from 2017 to 2019. The course was developed and taught in conjunction with local faculty. The most recent cohort logged cases before and after the course to assess resources used during initial patient evaluation and operative techniques used if the patient was taken to theater. RESULTS: Over the study period, 52 residents participated in the course. Eighteen participated in the case log study and logged 117 cases. There was no statistically significant difference in patient demographics or injury severity precourse and postcourse. Postcourse, penetrating injuries were reported less frequently (40 to 21% P < 0.05) and road traffic crashes were reported more frequently (39 to 60%, P < 0.05). There was no change in the use of bedside interventions or diagnostic imaging, besides head CT. Of patients taken for a laparotomy, there was a nonstatistically significant increase in the use of four-quadrant packing 3.4 to 21.7%) and a decrease in liver repair (20.7 to 4.3%). CONCLUSIONS: The course did not change resource utilization; however, it did influence clinical decision-making and operative techniques used during laparotomy. Additional research is indicated to evaluate sustained changes in practice patterns and clinical outcomes after operative skills training.

Global children's surgery: recent advances and future directions.

PURPOSE OF REVIEW: Two-thirds of the world's population lacks access to surgical care, many of them being children. This review provides an update on recent advances in global children's surgery. RECENT FINDINGS: Surgery is being increasingly recognized as an essential component of global and child health. There is a greater focus on sustainable collaborations between high-income countries (HICs) and low-and-middle-income countries (HICs and LMICs). Recent work provides greater insight into the global disease burden, perioperative outcomes and effective context-specific solutions. Surgery has continued to be identified as a cost-effective intervention in LMICs. There have also been substantial advances in research and advocacy for a number of childhood surgical conditions. SUMMARY: Substantial global disparities persist in the care of childhood surgical conditions. Recent work has provided greater visibility to the challenges and solutions for children's surgery in LMICs. Capacity-building and scale up of children's surgical care, more robust implementation research and ongoing advocacy are needed to increase access to children's surgical care worldwide.

Correction to: Epidemiology and mortality of pediatric surgical conditions: insights from a tertiary center in Uganda.

In the original publication, the family name of one of the authors was spelt incorrectly. The correct name should read as Nensi Ruzgar.

Epidemiology and mortality of pediatric surgical conditions: insights from a tertiary center in Uganda.

INTRODUCTION/PURPOSE: The burden of pediatric surgical disease is largely unknown in low- and middle-income countries such as Uganda where access to care is limited. METHODS: Implementation of a locally led database in January 2012 at a Ugandan tertiary referral hospital, and review of 3465 prospectively collected pediatric surgical admissions from January 2012 to August 2016. RESULTS: 2090 children (60.3%) underwent surgery during admission. 59% were male and 41% female. 28.6% of admissions were in neonates and 50.4% were in children less than 1 year old. Congenital anomalies including Hirschsprung's, anorectal malformations, intestinal atresias, omphalocele, and gastroschisis were the most common diagnoses (38.6%) followed by infections (15.0%) and tumors (8.6%). Mortality rates were substantially higher than those of high-income countries; for example, gastroschisis and intussusception had mortality rates of 90.1% and 19.7%, respectively. Post-operative mortality was highest in the congenital anomalies group (15.0%). CONCLUSION: There is a high burden of infant congenital anomalies with higher mortality rates compared to high-income countries. The unit performs primarily specialized procedures appropriate for a tertiary center. We hope that these data will facilitate evaluation of ongoing quality improvement and capacity-building initiatives.

Surgical management of complicated Crohn's disease.

Surgical management of pediatric Crohn's disease is fundamentally palliative, aiming to treat the sequalae of complicated disease while preserving intestinal length. Multidisciplinary discussion of risk factors and quality of life should take place prior to operative intervention. Though the surgical management of pediatric Crohn's disease is largely based on the adult literature, there are considerations specific to the pediatric population - notably disease and treatment effects on growth and development. Intrabdominal abscess is approached with percutaneous drainage when feasible, reserving surgical intervention for the patient who is unstable or failing medical therapy. Pediatric patients with fibrostenotic disease should be considered for strictureplasty when possible, for maximum preservation of bowel length. Patients with medically refractory Crohn's proctocolitis should be treated initially with fecal diversion without proctocolectomy.

Identification of urological anomalies associated with anorectal malformation in southwestern Uganda: Limitations and opportunities.

INTRODUCTION: Anorectal malformations (ARMs) may be associated with congenital anomalies affecting other body parts namely vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb (VACTERL) with varying incidences of 7%-60% . Genitourinary defects might occur approximately in 50% of all patients with anorectal malformations hence patients should be evaluated from birth to rule out these defects. OBJECTIVE: To identify urological anomalies associated with anorectal malformation in southwestern Uganda. STUDY DESIGN: This was a descriptive retrospective cohort study conducted at our regional referral hospital in Southwestern Uganda involving patients who have undergone surgical correction of ARMs between June 2021 and July 2023. RESULTS: The overall prevalence of renal anomalies in our study patient population was 18.05%. Of those with ARM-associated renal anomalies, Specific anomalies included; renal agenesis (6.8%), hydronephrosis, (4.5%), duplex collecting system (3.8%), crossed fused kidney (1.5%), and ectopic kidney (0.75%). (Table) DISCUSSION: We found that the prevalence of ARM-associated renal anomalies was 18.05%, and the commonest anomaly was unilateral agenesis (6.8%) similar to other studies. Previous data have shown renal anomalies are common anomalies in ARM. While the exact values vary across studies, they all concluded that the rate of associated anomalies is extremely high in ARMs and warrants a thorough preoperative investigation once the ARMs are detected. This finding therefore underscores the importance of thorough evaluation and a multidisciplinary approach of care and follow-up system for ARM management including urologists even when the children are asymptomatic now. The main limitation of our study was missing information on patients' charts, we were not able to get the diagnosis since most patients didn't have their discharge forms at the time of evaluation. CONCLUSION: ARM associated with renal anomalies may remain undiagnosed and asymptomatic. Those identified as asymptomatic need to be followed in a multidisciplinary fashion including pediatric urologists.

Does Length of Extended Resection Beyond Transition Zone Change Clinical Outcome for Hirschsprung Pull-Through?

INTRODUCTION: A proximal resection margin greater than 5 cm from the intra-operative histologically determined transition zone has been deemed necessary to minimize the risk of transition zone pull-through. This extended resection may require the sacrifice of vascular supply and even further bowel resection. The impact of extended proximal resection margin on post-operative complications and functional outcomes is unclear. METHODS: A retrospective chart review of patients who underwent primary pull-through for Hirschsprung disease at a single institution between January 2008 and December 2022 was performed. An adequate proximal margin was defined by a circumferential normally ganglionated ring and absence of hypertrophic nerves. The extended margin was defined as the total length of proximal colon with normal ganglion cells and without hypertrophic nerves. Fecal incontinence severity was assessed with the Pediatric Fecal Incontinence Severity Score (PFISS). RESULTS: Eighty seven patients met criteria for inclusion. Median age at primary pull-through was 17 days (IQR 10-92 days), 55% (n = 48) of patients had an extended proximal margin (EPM) ≤ 5 cm, and 45% (n = 39) had an EPM > 5 cm. An EPM ≤5 cm was not associated with increased rates of Hirschsprung associated enterocolitis (≤5 cm 43%, >5 cm 39%, P = 0.701), diversion post pull-through (≤5 cm 10%, >5 cm 5%, P = 0.367) or reoperation for transition zone pull-through (≤5 cm 3%, >5 cm 0%, P = 0.112). EPM ≤5 cm had more frequent involuntary daytime bowel movements (P = 0.041) and more frequent voluntary bowel movements (P = 0.035). There were no differences in other measures of fecal incontinence severity. CONCLUSIONS: Shorter proximal extended margins beyond the adequate ganglionated margin do not significantly impact post-operative complication rates and have an unclear effect on fecal incontinence. TYPE OF STUDY: Case Control. LEVEL OF EVIDENCE: Level III.

The Pediatric Emergency Surgery Course: Impact on Provider Practice in Rural Uganda.

PURPOSE: The Pediatric Emergency Surgery Course (PESC) trains rural Ugandan providers to recognize and manage critical pediatric surgical conditions. 45 providers took PESC between 2018 and 2019. We sought to assess the impact of the course at three regional hospitals: Fort Portal, Kabale, and Kiwoko. METHODS: We conducted a retrospective cohort study. Diagnosis, procedure, and patient outcome data were collected twelve months before and after PESC from admission and theater logbooks. We also assessed referrals from these institutions to Uganda's two pediatric surgery hubs: Mulago and Mbarara Hospitals. Wilcoxon rank-sum and Pearson's chi-squared tests compared pre- and post-PESC measures. Interrupted time-series-analysis assessed referral volume before and after PESC. RESULTS: 1534 admissions and 2148 cases were documented across the three regional hospitals. Kiwoko made 539 referrals, while pediatric surgery hubs received 116 referrals. There was a statistically significant immediate increase in the number of referrals from Fort Portal, from 0.5 patients/month pre-PESC to 0.8 post-PESC (95 % CI 0.03-1.51). Moving averages of the combined number of pyloromyotomy, intussusception reductions, and hernia repairs at the rural hospitals also increased post-course. Neonatal time to referral and referred patient age were significantly lower after PESC delivery. CONCLUSION: Our data suggest that PESC increased referrals to tertiary centers and operative volume of selected cases at rural hospitals and shortened time to presentation at sites receiving referrals. PESC is a locally-driven, validated, clinical education intervention that improves timely care of pediatric surgical emergencies and merits further support and dissemination. TYPE OF STUDY: Retrospective Cohort Study. LEVEL OF EVIDENCE: III.

Does Delayed Diagnosis of Hirschsprung Disease Impact Post-operative and Functional Outcomes? A Multi-Center Review From the Pediatric Colorectal and Pelvic Learning Consortium.

BACKGROUND: Hirschsprung Disease (HD) is a rare cause of functional bowel obstruction in children. Patients are typically diagnosed in the neonatal period and undergo pull-through (PT) soon after diagnosis. The optimal management and post-operative outcomes of children who present in a delayed fashion are unknown. METHODS: A multi-center retrospective review of children with HD was performed at participating Pediatric Colorectal and Pelvic Learning Consortium sites. Children were stratified by age at diagnosis (neonates <29 days; infants 29 days-12 months; toddler 1 year-5 years and child >5 years). RESULTS: 679 patients with HD from 14 sites were included; Most (69%) were diagnosed in the neonatal period. Age at diagnosis was not associated with differences in 30-day complication rates or need for PT revision. Older age at diagnosis was associated with a greater likelihood of undergoing fecal diversion after PT (neonate 10%, infant 12%, toddler 26%, child 28%, P < 0.001) and a greater need for intervention for constipation or incontinence postoperatively (neonate 56%, infant 62%, toddler 78%, child 69%, P < 0.001). CONCLUSION: Delayed diagnosis of HD does not impact 30-day post-operative outcomes or need for revision surgery but, delayed diagnosis is associated with increased need for fecal diversion after pull-through. LEVEL OF EVIDENCE: III.

In utero delivery of miRNA induces epigenetic alterations and corrects pulmonary pathology in congenital diaphragmatic hernia.

Structural fetal diseases, such as congenital diaphragmatic hernia (CDH) can be diagnosed prenatally. Neonates with CDH are healthy in utero as gas exchange is managed by the placenta, but impaired lung function results in critical illness from the time a baby takes its first breath. MicroRNA (miR) 200b and its downstream targets in the TGF-ß pathway are critically involved in lung branching morphogenesis. Here, we characterize the expression of miR200b and the TGF-ß pathway at different gestational times using a rat model of CDH. Fetal rats with CDH are deficient in miR200b at gestational day 18. We demonstrate that novel polymeric nanoparticles loaded with miR200b, delivered in utero via vitelline vein injection to fetal rats with CDH results in changes in the TGF-ß pathway as measured by qRT-PCR; these epigenetic changes improve lung size and lung morphology, and lead to favorable pulmonary vascular remodeling on histology. This is the first demonstration of in utero epigenetic therapy to improve lung growth and development in a pre-clinical model. With refinement, this technique could be applied to fetal cases of CDH or other forms of impaired lung development in a minimally invasive fashion.

Cryptogenic acute lower extremities and multiorgan ischemia in an 8-year-old girl.

Pediatric acute limb ischemia is rare but can have devastating effects on children. The most common causes of acute limb ischemia in the pediatric age group are iatrogenic injury during cardiac catheterization and traumatic vessel injury. Embolic events have been described less often. We present the case of an 8-year-old girl with cryptogenic extensive bilateral lower extremity ischemia and embolization to multiple visceral organs. Our findings have highlighted the importance of interdisciplinary workup, timely intervention, and the advantage of intraoperative imaging for revascularization.

Relevance and Regulation of Alternative Splicing in Plant Heat Stress Response: Current Understanding and Future Directions.

Alternative splicing (AS) is a major mechanism for gene expression in eukaryotes, increasing proteome diversity but also regulating transcriptome abundance. High temperatures have a strong impact on the splicing profile of many genes and therefore AS is considered as an integral part of heat stress response. While many studies have established a detailed description of the diversity of the RNAome under heat stress in different plant species and stress regimes, little is known on the underlying mechanisms that control this temperature-sensitive process. AS is mainly regulated by the activity of splicing regulators. Changes in the abundance of these proteins through transcription and AS, post-translational modifications and interactions with exonic and intronic cis-elements and core elements of the spliceosomes modulate the outcome of pre-mRNA splicing. As a major part of pre-mRNAs are spliced co-transcriptionally, the chromatin environment along with the RNA polymerase II elongation play a major role in the regulation of pre-mRNA splicing under heat stress conditions. Despite its importance, our understanding on the regulation of heat stress sensitive AS in plants is scarce. In this review, we summarize the current status of knowledge on the regulation of AS in plants under heat stress conditions. We discuss possible implications of different pathways based on results from non-plant systems to provide a perspective for researchers who aim to elucidate the molecular basis of AS under high temperatures.