Access to mifepristone, misoprostol, and contraceptive medicines in eight countries in the Eastern Mediterranean Region: descriptive analyses of country-level assessments.

BACKGROUND: Despite their importance in reducing maternal mortality, information on access to Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region is limited. METHODS: A standardized assessment tool measuring access to Mifepristone, Misoprostol, and contraceptive medicines included in the WHO essential medicines list (EML) was implemented in eight countries in the Eastern Mediterranean Region (Afghanistan, Iraq, Lebanon, Libya, Morocco, Palestine, Pakistan, and Somalia) between 2020-2021. The assessment focused on five access measures: 1) the inclusion of medicines in national family planning guidelines; 2) inclusion of medicines in comprehensive abortion care guidelines; 3) inclusion of medicines on national essential medicines lists; 4) medicines registration; and 5) procurement and forecasting of Mifepristone, Misoprostol, and contraceptive medicines. A descriptive analysis of findings from these eight national assessments was conducted. RESULTS: Only Lebanon and Pakistan included all 12 contraceptives that are enlisted in the WHO-EML within their national family planning guidelines. Only Afghanistan and Lebanon included mifepristone and mifepristone-misoprostol combination in post-abortion care guidelines, but these medicines were not included in their national EMLs. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs-and registered-in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan). However, only three countries procured misoprostol (Iraq, Morocco, and Somalia). CONCLUSION: These findings can guide efforts aimed at improving the availability of Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region. Opportunities include expanding national EMLs to include more options for Mifepristone, Misoprostol, and contraceptive medicines and strengthening the registration and procurement systems to ensure these medicines' availability were permitted under national law and where culturally acceptable.

Ensuring access to Mifepristone, Misoprostol, and contraceptive medicines is critical to improving women's health, and more specifically reducing maternal mortality and improving women's sexual and reproductive health in the Eastern Mediterranean Region.The aim of this study was to analyse findings from national assessments to capture information on the implementation of relevant policies and procedures. Those were the policies that ensure access to Mifepristone, Misoprostol, and contraceptive medicines in the public sector for the eight Eastern Mediterranean Region countries included in the study (Afghanistan, Iraq, Libya, Lebanon, Morocco, Palestine, Pakistan, and Somalia). The assessments were completed between 2020 and 2021.We found that most countries did not include all twelve contraceptives enlisted in the WHO essential medicines list (EML) in their national family planning guidelines. No country had developed a national abortion care guidelines nor included mifepristone (alone or in combination with misoprostol) on national EML. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs­and registered­in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan) yet, only three countries procured misoprostol (Iraq, Morocco, and Somalia).Our findings provide evidence on system-level barriers to availability of Mifepristone, Misoprostol, and contraceptive medicines (e.g., lack of guidelines or inclusion on EML, lack of registration and procurement) that can support policy and advocacy efforts to strengthen the pharmaceutical sector to better ensure availability of Mifepristone, Misoprostol, and contraceptive medicines to women in reproductive age at the country-level in accordance with the national law and prevailing culture.

The Use of Evidence to Design an Essential Package of Health Services in Pakistan: A Review and Analysis of Prioritisation Decisions at Different Stages of the Appraisal Process.

BACKGROUND: Pakistan embarked on a process of designing an essential package of health services (EPHS) as a pathway towards universal health coverage (UHC). The EPHS design followed an evidence-informed deliberative process; evidence on 170 interventions was introduced along multiple stages of appraisal engaging different stakeholders tasked with prioritising interventions for inclusion. We report on the composition of the package at different stages, analyse trends of prioritised and deprioritised interventions and reflect on the trade-offs made. METHODS: Quantitative evidence on cost-effectiveness, budget impact, and avoidable burden of disease was presented to stakeholders in stages. We recorded which interventions were prioritised and deprioritised at each stage and carried out three analyses: (1) a review of total number of interventions prioritised at each stage, along with associated costs per capita and disability-adjusted life years (DALYs) averted, to understand changes in affordability and efficiency in the package, (2) an analysis of interventions broken down by decision criteria and intervention characteristics to analyse prioritisation trends across different stages, and (3) a description of the trajectory of interventions broken down by current coverage and cost-effectiveness. RESULTS: Value for money generally increased throughout the process, although not uniformly. Stakeholders largely prioritised interventions with low budget impact and those preventing a high burden of disease. Highly cost-effective interventions were also prioritised, but less consistently throughout the stages of the process. Interventions with high current coverage were overwhelmingly prioritised for inclusion. CONCLUSION: Evidence-informed deliberative processes can produce actionable and affordable health benefit packages. While cost-effective interventions are generally preferred, other factors play a role and limit efficiency.

Costing Interventions for Developing an Essential Package of Health Services: Application of a Rapid Method and Results From Pakistan.

BACKGROUND: The Federal Ministry of National Health Services, Regulations and Coordination (MNHSR&C) in Pakistan has committed to progress towards universal health coverage (UHC) by 2030 by providing an Essential Package of Health Services (EPHS). Starting in 2019, the Disease Control Priorities 3rd edition (DCP3) evidence framework was used to guide the development of Pakistan's EPHS. In this paper, we describe the methods and results of a rapid costing approach used to inform the EPHS design process. METHODS: A total of 167 unit costs were calculated through a context-specific, normative, ingredients-based, and bottom-up economic costing approach. Costs were constructed by determining resource use from descriptions provided by MNHSR&C and validated by technical experts. Price data from publicly available sources were used. Deterministic univariate sensitivity analyses were carried out. RESULTS: Unit costs ranged from 2019 US$ 0.27 to 2019 US$ 1478. Interventions in the cancer package of services had the highest average cost (2019 US$ 837) while interventions in the environmental package of services had the lowest (2019 US$ 0.68). Cost drivers varied by platform; the two largest drivers were drug regimens and surgery-related costs. Sensitivity analyses suggest our results are not sensitive to changes in staff salary but are sensitive to changes in medicine pricing. CONCLUSION: We estimated a large number of context-specific unit costs, over a six-month period, demonstrating a rapid costing method suitable for EPHS design.

Country readiness and prerequisites for successful design and transition to implementation of essential packages of health services: experience from six countries.

This paper reviews the experience of six low-income and lower middle-income countries in setting their own essential packages of health services (EPHS), with the purpose of identifying the key requirements for the successful design and transition to implementation of the packages in the context of accelerating progress towards universal health coverage (UHC). The analysis is based on input from three meetings of a knowledge network established by the Disease Control Priorities 3 Country Translation Project and working groups, supplemented by a survey of participating countries.All countries endorsed the Sustainable Development Goals target 3.8 on UHC for achievement by 2030. The assessment of country experiences found that health system strengthening and mobilising and sustaining health financing are major challenges. EPHS implementation is more likely when health system gaps are addressed and when there are realistic and sustainable financing prospects. However, health system assessments were inadequate and the government planning and finance sectors were not consistently engaged in setting the EPHS in most of the countries studied. There was also a need for greater engagement with community and civil society representatives, academia and the private sector in package design. Leadership and reinforcement of technical and managerial capacity are critical in the transition from EPHS design to sustained implementation, as are strong human resources and country ownership of the process. Political commitment beyond the health sector is key, particularly commitment from parliamentarians and policymakers in the planning and finance sectors. National ownership, institutionalisation of technical and managerial capacity and reinforcing human resources are critical for success.The review concludes that four prerequisites are crucial for a successful EPHS: (1) sustained high-level commitment, (2) sustainable financing, (3) health system readiness, and (4) institutionalisation.

Meningothelial Hamartoma Overlying a Prior Craniotomy: A Case Report and Review of Literature.

Meningothelial hamartomas are benign lesions of the scalp with a handful of case reports published. Usually thought to be congenital lesions, they have, on occasion, been seen in older adults. In this report, we describe the first ever reported case of a patient diagnosed with a meningothelial hamartoma overlying a prior craniotomy performed two decades prior. We also briefly describe the literature surrounding these rare lesions, as well as their management and differential diagnosis.

Indirect effects of COVID-19 pandemic on reproductive, maternal, newborn and child health services in Pakistan.

Background: COVID-19 is having many impacts on health, economy and social life; some due to the indirect effects of closure of health facilities to curb the spread. Closures were implemented in Pakistan from March 2020, affecting provision of reproductive, maternal, newborn and child health (RMNCH) services. Aims: To appraise the effects of containment and lockdown policies on RMNCH service utilization in order to develop an early response to avoid the catastrophic impact of COVID-19 on RMNCH in Pakistan. Methods: Routine monitoring data were analysed for indicators utilization of RMNCH care. The analysis was based on Period 1 (January-May 2020, first wave of COVID-19); Period 2 (June-September 2020, declining number of cases of COVID-19); and Period 3 (October-December 2020, second wave of COVID-19). We also compared data from May and December 2020 with corresponding months in 2019, to ascertain whether changes were due to COVID-19. Results: Reduced utilization was noted for all RMNCH indicators during Periods 1 and 3. There was a greater decline in service utilization during the first wave, and the highest reduction (~82%) was among children aged < 5 years, who were treated for pneumonia. The number of caesarean sections dropped by 57%, followed by institutional deliveries and first postnatal visit (37% each). Service utilization increased from June to September, but the second wave of COVID-19 led to another decrease. Conclusion: To reinstate routine services, priority actions and key areas include continued provision of family planning services along with uninterrupted immunization campaigns and routine maternal and child services.

Carcinomas assemble a filamentous CXCL12-keratin-19 coating that suppresses T cell-mediated immune attack.

Cancer immunotherapy frequently fails because most carcinomas have few T cells, suggesting that cancers can suppress T cell infiltration. Here, we show that cancer cells of human pancreatic ductal adenocarcinoma (PDA), colorectal cancer, and breast cancer are coated with transglutaminase-2 (TGM2)-dependent covalent CXCL12-keratin-19 (KRT19) heterodimers that are organized as filamentous networks. Since a dimeric form of CXCL12 suppresses the motility of human T cells, we determined whether this polymeric CXCL12-KRT19 coating mediated T cell exclusion. Mouse tumors containing control PDA cells exhibited the CXCL12-KRT19 coating, excluded T cells, and did not respond to treatment with anti-PD-1 antibody. Tumors containing PDA cells not expressing either KRT19 or TGM2 lacked the CXCL12-KRT19 coating, were infiltrated with activated CD8+ T cells, and growth was suppressed with anti-PD-1 antibody treatment. Thus, carcinomas assemble a CXCL12-KRT19 coating to evade cancer immune attack.

Benefit-risk analysis of maintaining essential Reproductive, Maternal, Newborn, and Child Health (RMNCH) services against risk of COVID-19 infection.

With the COVID-19 pandemic spreading across the world, its disruptive effect on the provision and utilization of non- COVID related health services have become well-documented. As countries developed mitigation strategies to help continue the delivery of essential health services through the pandemic, they needed to carefully weigh the benefits and risks of pursuing these strategies. In an attempt to assist countries in their mitigation efforts, a Benefit-Risk model was designed to provide guidance on how to compare the health benefits of sustained essential reproductive, maternal, newborn and child (RMNCH) services against the risk of SARS-CoV-2 infections incurred by the countries' populations when accessing these services. This article describes how two existing models were combined to create this model, the field-testing process carried out from November 2020 through March 2021 in six countries and the findings. The overall Benefit-Risk Ratio in the 6 countries analyzed was found to be between 13.7 and 79.2, which means that for every 13.7 to 79.2 lives gained due to increased RMNCH service coverage, there was one loss of a life related to COVID-19. In all cases and for all services, the benefit of maintaining essential health services far exceeded the risks associated with additional COVID-19 infections and deaths. This modelling process illustrated how essential health services can continue to operate during a pandemic and how mitigation measures can reduce COVID-19 infections and restore or increase coverage of essential health services. Overall, this Benefit-Risk analysis underscored the importance and value of maintaining coverage of essential health services even during public health emergencies, including the recent COVID-19 pandemic.

Resuscitative Endovascular Balloon Occlusion of the Aorta in Hemodynamically Unstable Patients With Pelvic Ring Injuries.

OBJECTIVE: To evaluate the outcomes of patients with pelvic ring injuries managed with resuscitative endovascular balloon occlusion of the aorta (REBOA). DESIGN: Retrospective case series. SETTING: Academic, Level 1 trauma center in North America. PATIENTS: Twenty-five patients with disruption of the pelvic ring and hemodynamic instability. INTERVENTION: Placement of a REBOA device as an adjuvant treatment to trauma resuscitation. MAIN OUTCOME MEASURE: Death and ischemic-related complications. RESULTS: The average age of patients was 43 years (range: 17-85). Patients presented with a median lactate of 6.3 mmol/L, systolic blood pressure of 116 mm Hg, heart rate of 121 beats/minute, and injury severity score of 34. The median unit of packed red blood cells received through transfusion in the first 24 hours of hospital admission was 13 (interquartile range: 8-28). Young-Burgess injury patterns included fractures of the following types: 5 lateral compression (LC)-1, 1 LC-2, 8 LC-3, 4 anteroposterior compression-2, and 7 anteroposterior compression-3. Angiography and embolization were performed in 24 (96%) patients. Selective embolization occurred in 18 (72%) patients, with nonselective angiography of the iliac system occurring in 7 (24%) patients. There were 12 (48%) deaths, 7 (28%) patients requiring lower extremity fasciotomy, and 5 (20%) patients requiring lower extremity amputations, and there was 1 (4%) patient requiring thrombectomy. CONCLUSIONS: REBOA use in pelvic ring injuries is rare and most frequently used in critically ill patients with polytrauma. Successful pelvic embolization can occur in concert with REBOA use; however, the severity of injury is associated with a high complication profile. In this series of 25 patients, in-hospital mortality was 48%. For those patients who survived, 54% experienced a major complication (fasciotomy, amputation, and deep infection). Further investigation is required to evaluate the role REBOA may play in managing these patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Stark choices: exploring health sector costs of policy responses to COVID-19 in low-income and middle-income countries.

OBJECTIVES: COVID-19 has altered health sector capacity in low-income and middle-income countries (LMICs). Cost data to inform evidence-based priority setting are urgently needed. Consequently, in this paper, we calculate the full economic health sector costs of COVID-19 clinical management in 79 LMICs under different epidemiological scenarios. METHODS: We used country-specific epidemiological projections from a dynamic transmission model to determine number of cases, hospitalisations and deaths over 1 year under four mitigation scenarios. We defined the health sector response for three base LMICs through guidelines and expert opinion. We calculated costs through local resource use and price data and extrapolated costs across 79 LMICs. Lastly, we compared cost estimates against gross domestic product (GDP) and total annual health expenditure in 76 LMICs. RESULTS: COVID-19 clinical management costs vary greatly by country, ranging between <0.1%-12% of GDP and 0.4%-223% of total annual health expenditure (excluding out-of-pocket payments). Without mitigation policies, COVID-19 clinical management costs per capita range from US$43.39 to US$75.57; in 22 of 76 LMICs, these costs would surpass total annual health expenditure. In a scenario of stringent social distancing, costs per capita fall to US$1.10-US$1.32. CONCLUSIONS: We present the first dataset of COVID-19 clinical management costs across LMICs. These costs can be used to inform decision-making on priority setting. Our results show that COVID-19 clinical management costs in LMICs are substantial, even in scenarios of moderate social distancing. Low-income countries are particularly vulnerable and some will struggle to cope with almost any epidemiological scenario. The choices facing LMICs are likely to remain stark and emergency financial support will be needed.

Religious Perspectives on Precision Medicine in Singapore.

Precision medicine (PM) aims to revolutionise healthcare, but little is known about the role religion and spirituality might play in the ethical discourse about PM. This Perspective reports the outcomes of a knowledge exchange fora with religious authorities in Singapore about data sharing for PM. While the exchange did not identify any foundational religious objections to PM, ethical concerns were raised about the possibility for private industry to profiteer from social resources and the potential for genetic discrimination by private health insurers. According to religious authorities in Singapore, sharing PM data with private industry will require a clear public benefit and robust data governance that incorporates principles of transparency, accountability and oversight. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41649-021-00180-4.

Enhanced postoperative recovery with minimally invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies of gastrointestinal origin.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are the treatment of choice for select patients with peritoneal surface malignancies; however, the traditional open approach may be associated with significant morbidity. We evaluated postoperative outcomes with minimally invasive (MI) CRS and HIPEC. METHODS: Review of our institutional database identified 47 patients who underwent optimal cytoreduction (CC0 or CC1). Those with a PCI ≤ 15 and primary malignancy of gastrointestinal origin were then selected for subgroup analysis. Multivariable regression was performed to identify factors impacting postoperative outcomes. RESULTS: Demographic data did not significantly differ between open (n = 24) and minimally invasive (n = 9) groups. The MI group had a mean age of 57.34 ± 14.92, BMI of 27.03 ± 4.27, Charlson comorbidity score of 1.78 ± 1.72, and PCI of 5.56 ± 5.08. Mean time to flatus (days) was 2.78 in the MI group and 5.04 in the open group (p < 0.001), and mean length of IV analgesic use (days) was 3.11 in the MI group compared to 6.00 in the open group (p = 0.006). Mean length of stay (days) was 5.11 in the MI group and 8.67 in the open group (p = 0.033). Surgical approach (p = 0.037) and BMI (p = 0.039) were the only factors impacting length of stay. CONCLUSIONS: Minimally invasive CRS and HIPEC is an excellent option for low volume peritoneal disease of gastrointestinal origin. A minimally invasive approach yields faster return of bowel function, reduced postoperative analgesia requirements, and shorter hospital stay.

Patients' response to an emergency department-based HIV testing program and perception of their friends' attitudes on HIV testing among patients seeking care at an urban emergency department in Baltimore, Maryland, USA.

BACKGROUND: Little is known regarding the possible role of social network members and peer attitudes on emergency department (ED) patients' willingness to be tested for HIV. METHODS: We conducted mixed methods in-depth interview and quantitative survey with ED patients from November 2013 to June 2014 to assess peer and personal perceptions of ED-based HIV testing. Patients enrolled were asked about their own attitudes toward HIV testing as well as those of their friends. Interviews were transcribed and categories that captured free responses in the verbatim were independently coded by two reviewers. RESULTS: Overall, 86 patients were enrolled including 22 HIV known positive. Among 64 HIV-negative participants, 50 were tested during the past 12 months and 4 had never been tested. The majority (82.5%) of participants thought that their friends were likely to accept HIV testing in EDs. Participants discussed their perceptions of friends' attitudes toward HIV testing: the majority (60%) believed their friends held positive attitudes about HIV testing. The majority of participants believed that their friends had positive feelings about HIV testing and were likely to accept testing in ED settings. CONCLUSIONS: Interventions utilizing peer networks to promote HIV testing and increase testing acceptance could be designed and explored.

Improved outcomes with surgery compared to radiofrequency ablation in the treatment of resectable hepatocellular carcinoma.

BACKGROUND: While overall cancer incidence and mortality have decreased over the last decade, hepatocellular carcinoma (HCC) cases have increased sharply. OBJECTIVE: This study set out to evaluate the utility of surgery for resectable single tumor HCC in this setting. PATIENTS AND METHODS: This study analyzed the National Cancer Database, selecting all patients with a histological diagnosis of HCC and an isolated tumor (≤5 cm) treated with radiofrequency ablation (RFA) or surgical resection. RESULTS: A total of 7821 patients were identified for this study. In the patients with a single tumor up to 3 cm, 40% had a surgical resection and 60% had RFA. In the group with a tumor 3.01-5 cm, 62% had a surgical resection and 38% had RFA. Patients with a single tumor up to 5 cm had a 3-year survival of 60% after resection compared to 42% with RFA. When the patients were split into those with a tumor up to 3 cm or a tumor 3.01-5 cm, there was a survival benefit in the surgical resection cohort. CONCLUSION: Surgical resection may be underutilized in the USA for resectable HCC, especially in patients with a tumor up to 3 cm.

Venous thromboembolism in patients with cancer undergoing surgical exploration.

Malignancy and surgery are both independent risk factors for venous thromboembolism (VTE) events. The current NCCN guidelines recommend VTE prophylaxis for up to 28 days after major abdominal or pelvic surgery for malignancy. We set out to evaluate the rate and timing of VTEs among patients with gastric, pancreatic, colorectal, and gynecologic malignancies who underwent surgery. We performed a retrospective review of the NSQIP database (2005-2013) focusing on patients with gastric, colorectal, pancreatic, and gynecologic malignancies. Our primary endpoint was a diagnosis of VTE within 30 days of surgery. We analyzed 128,864 patients in this study. On multivariable analysis, patients with pre-operative sepsis (OR 2.36, CI 2.04-2.76, p < 0.001), disseminated cancer (OR 1.73, CI 1.55-1.92, p < 0.001), congestive heart failure (OR 1.69, CI 1.25-2.28, p = 0.001), gastric cancer (OR 1.3, CI 1.09-1.56, p = 0.004), and pancreatic cancer (OR 1.2, CI 1.03-1.30, p = 0.021) were more likely to have a VTE. Of patients who had a VTE event, 34% occurred after discharge from surgery (gastric: 25%, colorectal 34%, pancreatic 31%, gynecologic malignancy 42%). Our study demonstrates that patients who undergo an operation for malignancy with pre-operative sepsis, disseminated cancer, congestive heart failure, gastric cancer, or pancreatic cancer are more likely to develop a VTE within 30 days of their operation. Of those patients who developed a VTE, approximately one-third occurred after discharge during a 30 day post-operative period. This data supports that further studies are needed to determine the appropriate length of post-operative VTE chemoprophylaxis in patients with cancer.

Comparison of ketorolac and low-dose ketamine in preventing tourniquet-induced increase in arterial pressure.

BACKGROUND AND AIMS: Application of tourniquet during orthopaedic procedures causes pain and increase in blood pressure despite adequate anaesthesia and analgesia. In this study, we compared ketorolac with ketamine in patients undergoing elective lower limb surgery with tourniquet in order to discover if ketorolac was equally effective or better than ketamine in preventing tourniquet-induced hypertension. METHODS: Approval was granted by the Institutional Ethics Review Committee and informed consent was obtained from all participants. A randomised double-blinded controlled trial with 38 patients each in the ketamine and ketorolac groups undergoing elective knee surgery for anterior cruciate ligament repair or reconstruction was conducted. Induction and maintenance of anaesthesia were standardised in all patients, and the minimum alveolar concentration of isoflurane was maintained at 1.2 throughout the study period. One group received ketamine in a dose of 0.25 mg/kg and the other group received 30 mg ketorolac 10 min before tourniquet inflation. Blood pressure was recorded before induction of anaesthesia (baseline) and at 0, 10, 20, 30, 40, 50, and 60 min after tourniquet inflation. RESULTS: The demographic and anaesthetic characteristics were similar in the two groups. At 0 and 10 min, tourniquet-induced rise in blood pressure was not observed in both groups. From 20 min onward, both systolic and diastolic blood pressures were significantly higher in ketorolac group compared to ketamine group. CONCLUSION: We conclude that ketamine is superior to ketorolac in preventing tourniquet-induced increases in blood pressure.

Urethrocutaneous fistula following hypospadias repair: regional anesthesia and other factors.

BACKGROUND: Urethrocutaneous fistula is a well-known complication of hypospadias surgery. A recent prospective study by Kundra et al. (Pediatr Anesth 2012) has suggested that caudal anesthesia may increase the risk of fistula formation. We sought to evaluate this possible association and determine if any other novel factors may be associated with fistula formation. METHODS: Children who underwent primary hypospadias repair between January 1, 1994 and March 31, 2013 at our tertiary care center were included in this study. Reviewed surgical data included repair type, duration of procedure, use of local anesthetic infiltration, and subcutaneous epinephrine. Analgesic factors included use of caudal and/or penile block, opioid usage, postoperative pain scores, and nausea/vomiting. Postoperative surgical complications and estimates of family household median income by zip code were also reviewed. RESULTS: Fistula occurrence was not associated with caudal or penile block, severity of postoperative pain, or surgeon experience. A more proximal location of the urethral meatus, longer operating time, and use of subcutaneous epinephrine were significantly more common in patients who developed fistula. As assessed by home address zip code, distance of more than 100 miles and median household income in the bottom 25th percentile of our study population were not associated with fistula, as compared to closer distance or higher income. CONCLUSION: In this series, we found no association between the use of caudal regional anesthesia and fistula formation. Location of the starting urethral meatus, prolonged surgical duration, and subcutaneous epinephrine use were associated with fistula formation. Our findings call into question the routine use of epinephrine in hypospadias repair.