Low adipocyte hepatocellular carcinoma is associated with aggressive cancer biology and with worse survival.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and non-alcoholic fatty liver disease is strongly associated with its development. To explore the role of adipocytes in HCC, we investigated intratumoral adipocytes, also known as cancer-associated adipocytes (CAA). Based on our prior breast cancer findings, we hypothesized that low intratumoral adipocytes would be associated with aggressive cancer biology, worse tumor microenvironment (TME), and clinical outcomes. The Cancer Genome Atlas (TCGA) was used and validated by the Gene Expression Omnibus (GEO) cohort. xCell algorithm was used to quantify intratumoral adipocytes and top 90% were defined as adipocyte high (AH) and bottom 10% as adipocyte low (AL). We found that AL-HCC was significantly associated with worse disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). AL-HCC were higher-grade, had high MKI67 expression, enriched cell proliferation-related gene sets, and had increased altered fraction, aneuploidy, and homologous recombination defects. Also, anti-cancer immune cells, CD8, Th1, and M1 cells, as well as pro-cancer Th2 cells were increased in AL-HCC. Micro-RNAs miR-122 (associated with cholesterol metabolism) and miR-885 (associated with liver pathologies) were significantly increased in the AL TME. In conclusion, we found that AL-HCC has worse patient outcomes and is biologically more aggressive with enhanced cell proliferation. Our findings take initial steps to clarify the role of adipocytes in HCC.

Octogenarians' Breast Cancer Is Associated with an Unfavorable Tumor Immune Microenvironment and Worse Disease-Free Survival.

Elderly patients are known to have a worse prognosis for breast cancer. This is commonly blamed on their medical comorbidities and access to care. However, in addition to these social issues, we hypothesized that the extreme elderly (octogenarians-patients over 80 years old) have biologically worse cancer with unfavorable tumor immune microenvironment. The Cancer Genomic Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were analyzed. The control (aged 40-65) and octogenarians numbered 668 and 53 in TCGA and 979 and 118 in METABRIC, respectively. Octogenarians had significantly worse breast cancer-specific survival in both cohorts (p < 0.01). Octogenarians had a higher ER-positive subtype rate than controls in both cohorts. Regarding PAM50 classification, luminal-A and -B subtypes were significantly higher in octogenarians, whereas basal and claudin-low subtypes were significantly lower (p < 0.05) in octogenarians. There was no difference in tumor mutation load, intratumor heterogeneity, or cytolytic activity by age. However, the octogenarian cohort was significantly associated with high infiltration of pro-cancer immune cells, M2 macrophage, and regulatory T cells in both cohorts (p < 0.05). Our results demonstrate that octogenarians' breast cancer is associated with worse survival and with an unfavorable tumor immune microenvironment.

Annexin A1 Expression Is Associated with Epithelial-Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer.

Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein overexpressed in pancreatic cancer (PC). ANXA1 expression has been shown to take part in a wide variety of cancer biology, including carcinogenesis, cell proliferation, invasion, apoptosis, and metastasis, in addition to the initially identified anti-inflammatory effect in experimental settings. We hypothesized that ANXA1 expression is associated with cell proliferation and survival in PC patients. To test this hypothesis, we analyzed 239 PC patients in The Cancer Genome Atlas (TCGA) and GSE57495 cohorts. ANXA1 expression correlated with epithelial-mesenchymal transition (EMT) but weakly with angiogenesis in PC patients. ANXA1-high PC was significantly associated with a high fraction of fibroblasts and keratinocytes in the tumor microenvironment. ANXA1 high PC enriched multiple malignant gene sets, including hypoxia, tumor necrosis factor (TNF)-α signaling via nuclear factor-kappa B (NF-kB), and MTORC1, as well as apoptosis, protein secretion, glycolysis, and the androgen response gene sets consistently in both cohorts. ANXA1 expression was associated with TP53 mutation alone but associated with all KRAS, p53, E2F, and transforming growth factor (TGF)-ß signaling pathways and also associated with homologous recombination deficiency in the TCGA cohort. ANXA1 high PC was associated with a high infiltration of T-helper type 2 cells in the TME, with advanced histological grade and MKI67 expression, as well as with a worse prognosis regardless of the grade. ANXA1 expression correlated with a sensitivity to gemcitabine, doxorubicin, and 5-fluorouracil in PC cell lines. In conclusion, ANXA1 expression is associated with EMT, cell proliferation, survival, and the drug response in PC.

Identifying essential components of surgical care delivery through quality improvement: An updated surgical assessment tool.

BACKGROUND: Surgical care is a cost-effective intervention with major public health impact. Yet, five billion people do not have access to surgical and anesthesia care. This overwhelming unmet need has generated a rising interest in scale-up of these services globally. The purpose of this research was to aggregate available guidelines and create a synthesized tool that could provide valuable information at the local, national, and international health system levels. METHODS: A systematic review identified current documents cataloging elements for surgical care provision. Items with a reported frequency of >30% were included in the initial draft of the Surgical Assessment Tool. This underwent two cycles of Delphi-method expert opinion elicitation from providers working in low- and middle-income settings. Finally, the tool underwent vetting by the World Health Organization to create an expert-endorsed survey. RESULTS: Fifteen surgical tools were identified, containing a total of 216 unique elements in the following domains: infrastructure (n = 152), service delivery (n = 49), and workforce (n = 15). The final tool consisted of 169 items in the following domains: infrastructure (n = 35), service delivery (n = 92), workforce (n = 20), information management (n = 10), and financing (n = 12). CONCLUSION: Informed planning is critical to ensure successful expansion of surgical services. Our analysis of current tools shows varying agreement on the essential components of surgical care delivery. This updated tool serves as a crucial method to systematically assess surgical systems as well as monitor, modify, and strengthen in a scalable fashion. Importantly, it has the potential to be used in all settings after adaptation to local context.

Self-Diagnosis of Surgical Site Infections: Lessons from a tertiary care centre in Karachi, Pakistan.

BACKGROUND AND OBJECTIVE: Surgical site infections (SSIs) usually manifest post-discharge, rendering accurate diagnosis and treatment challenging, thereby catalyzing the development of alternate strategies like self-monitored SSI surveillance. This study aimed to evaluate the diagnostic accuracy of patients and Infection Control Monitors (ICMs) to develop a replicable method of SSI-detection. METHODS: A two-year prospective diagnostic accuracy study was conducted in Karachi, Pakistan between 2015 and 2017. Patients were educated about SSIs and provided with questionnaires to elicit symptoms of SSI during post-discharge self-screening. Results of patient's self-screening and ICM evaluation at follow-ups were compared to surgeon evaluation. RESULTS: A total of 348 patients completed the study, among whom 18 (5.5%) developed a SSI. Patient self-screening had a sensitivity of 39%, specificity of 95%, positive predictive value (PPV) of 28%, and negative predictive value (NPV) of 97%. ICM evaluation had a sensitivity of 82%, specificity of 99%, PPV of 82%, and NPV of 99%. CONCLUSION: Patients cannot self-diagnose a SSI reliably. However, diagnostic accuracy of ICMs is significantly higher and they may serve as a proxy for surgeons, thereby reducing the burden on specialized surgical workforce in LMICs. Regardless, supplementing post-discharge follow-up with patient self-screening could increase SSI-detection and reduce burden on health systems.

Towards equitable surgical systems: development and outcomes of a national surgical, obstetric and anaesthesia plan in Tanzania.

Despite emergency and essential surgery and anaesthesia care being recognised as a part of Universal Health Coverage, 5 billion people worldwide lack access to safe, timely and affordable surgery and anaesthesia care. In Tanzania, 19% of all deaths and 17 % of disability-adjusted life years are attributable to conditions amenable to surgery. It is recommended that countries develop and implement National Surgical, Obstetric and Anesthesia Plans (NSOAPs) to systematically improve quality and access to surgical, obstetric and anaesthesia (SOA) care across six domains of the health system including (1) service delivery, (2) infrastructure, including equipment and supplies, (3) workforce, (4) information management, (5) finance and (6) Governance. This paper describes the NSOAP development, recommendations and lessons learnt from undertaking NSOAP development in Tanzania. The NSOAP development driven by the Ministry of Health Community Development Gender Elderly and Children involved broad consultation with over 200 stakeholders from across government, professional associations, clinicians, ancillary staff, civil society and patient organisations. The NSOAP describes time-bound, costed strategic objectives, outputs, activities and targets to improve each domain of the SOA system. The final NSOAP is ambitious but attainable, reflects on-the-ground priorities, aligns with existing health policy and costs an additional 3% of current healthcare expenditure. Tanzania is the third country to complete such a plan and the first to report on the NSOAP development in such detail. The NSOAP development in Tanzania provides a roadmap for other countries wishing to undertake a similar NSOAP development to strengthen their SOA system.

Time-driven activity-based costing of total knee replacements in Karachi, Pakistan.

INTRODUCTION: Osteoarthritis of the knee has been identified as the most common disability in Pakistan. Total knee replacement (TKR) surgery is the curative treatment for advanced osteoarthritis of the knee; however, cost remains one of the barriers to effective and timely service delivery. OBJECTIVE: We conducted a time-driven activity-based costing (TDABC) analysis of TKR to identify major cost drivers and areas for process improvement. METHODS AND ANALYSIS: We performed a prospective TDABC analysis of patients who underwent bilateral TKR at The Indus Hospital (TIH) during a 14-month period from October 2015 to December 2016. Detailed process maps were developed for each phase of the care cycle. Time durations and costs were allocated to each resource utilised and aggregated across the care cycle, including personnel, direct and indirect costs. RESULTS: We identified seven care phases for a complete TKR care cycle and created their detailed process maps. Major time contributors were ward stay and discharge (20 160 min), TKR surgery (563 min) and surgical admission (333 min). Overall, 92.10% of time is spent during the ward stay and discharge phase of care. Patients remain hospitalised for an average of 14 days postoperatively. Overall institutional cost of a TKR at TIH was US$4360.51 (Pakistani rupees 456 981.17) per bilateral TKR surgery. The overall primary cost drivers for the full bundle of care were consumables used during TKR surgery itself, consumables utilised in the wards and personnel costs contributing 57.64%, 27.45% and 12.03% of total costs, respectively. CONCLUSION: Utilising TDABC allowed us to obtain a granular analysis of time and cost that was subsequently used to inform quality process improvement initiatives. In low-resource settings, such as Pakistan, TDABC has the potential to be a useful tool to guide resource allocation and process improvement.

The global neurosurgical workforce: a mixed-methods assessment of density and growth.

OBJECTIVE: In 2000, the global density of neurosurgeons was estimated at 1 per 230,000 population, which remains the most recent estimate of the global neurosurgeon workforce density. In 2004, the World Health Organization (WHO) estimated that there were 33,193 neurosurgeons worldwide, including trainees. There have been no updates to this estimate in the past decade. Moreover, only WHO region-level granularity regarding neurosurgeon distribution exists; country-level estimates are limited. The neurosurgery workforce is a crucial component to meeting the growing burden of neurosurgical diseases, which not only represent high absolute incidences and prevalences, but also represent correspondingly high disability-adjusted life years affecting hundreds of millions of people worldwide. Combining the lack of knowledge about the availability of the neurosurgical workforce and the increasing demand for neurosurgical services underscores the need for a system of neurosurgical workforce density surveillance. METHODS: This study involved 3 key steps: 1) global survey/literature review to obtain the number of working neurosurgeons per WHO-recognized country, 2) regression to interpolate any missing data, and 3) calculation of workforce densities and comparison to available historical data by WHO region. RESULTS: Data for 198 countries were collected (158) or interpolated (40). The global total number of neurosurgeons was estimated at 49,940. Overall, neurosurgeon density ranged from 0 to 58.95 (standardized to per 1,000,000 population) with a median of 3.56 (IQR 0.29-8.26). Thirty-three countries were found to have no neurosurgeons (zero). The highest density, 58.95, was in Japan, where 7495 neurosurgeons are taking care of a population of 127,131,800. CONCLUSIONS: In 2015, the Lancet Commission on Global Surgery estimated that 143 million additional surgical procedures are needed in low- and middle-income countries each year, and a subsequent study revealed that approximately 15% of those surgical procedures are neurosurgical. Based on our results, we can conclude that there are approximately 49,940 neurosurgeons currently, worldwide. The availability of neurosurgeons appears to have increased in all geographic regions over the past decade, with Southeast Asia experiencing the greatest growth. Such remarkable expansion should be assessed to determine factors that could play a role in other regions where the acceleration of growth would be beneficial.

Quality of essential surgical care in low- and middle-income countries: a systematic review of the literature.

PURPOSE: Quality of care is an emerging area of focus in the surgical disciplines. However, much of the emphasis on quality is limited to high-income countries. To address this gap, we conducted a systematic review of the literature on the quality of essential surgical care in low- and middle- income countries (LMIC). DATA SOURCES: We searched PubMed, Cinahl, Embase and CAB Abstracts using three domains: quality of care, surgery and LMIC. STUDY SELECTION: We limited our review to studies of essential surgeries that pertained to all three search domains. DATA EXTRACTION: We extracted data on study characteristics, type of surgery and the way in which quality was studied. RESULTS OF DATA SYNTHESIS: 354 studies were included. 281 (79.4%) were single-center studies and nearly half (n = 169, 46.9%) did not specify the level of facility. 207 studies reported on mortality (58.47%) and 325 reported on a morbidity (91.81%), most commonly surgical site infection (n = 190, 53.67%). Of the Institute of Medicine domains of quality, studies were most commonly of safety (n = 310, 87.57%) and effectiveness (n = 180, 50.85%) and least commonly of equity (n = 21, 5.93%). CONCLUSION: We find that while there are numerous studies that report on some aspects of quality of care, much of the data is single center and observational. Additionally, there is variability on which outcomes are reported both within and across specialties. Finally, we find under-reporting of parameters of equity and timeliness, which may be critical areas for research moving forward.

Global surgical, obstetric, and anesthetic task shifting: A systematic literature review.

BACKGROUND: Five billion people lack access to safe, affordable, and timely surgical care; this is in part driven by severe shortages in the global surgical workforce. Task shifting is commonly implemented to expand the surgical workforce. A more complete understanding of the global distribution and use of surgical, obstetric, and anesthetic task shifting is lacking in the literature. We aimed to document the use of task shifting worldwide with a systematic review of the literature. METHODS: We performed a systematic review of 10 health literature databases. We included journal articles published between January 1, 1995, and February 17, 2017, documenting the provision of surgical or anesthetic care by associate clinicians (any non-physician clinician). We extracted data for health cadres performing task shifting, types of tasks performed, training programs, and levels of supervision, and compared these across regions and income groups. RESULTS: We identified 55 relevant studies, with data for 52 countries for surgery and 147 countries for anesthesia. Surgical task shifting was documented in 19 of 52 countries and anesthetic task shifting in 119 of 147. Task shifting was documented across all World Bank income groups. No associate clinicians were found to perform surgical procedures unsupervised in high-income countries (0 of 3 countries with data). Independent anesthesia care by associate clinicians was noted in 3 of 19 countries with data. In low-income countries, associate clinicians performed surgical procedures independently in 2 of 3 countries and independent anesthesia care in 17 of 17 countries with data. CONCLUSION: Task shifting is used to augment the global surgical, obstetric, and anesthetic workforce across all geographic regions and income groups. Associate clinicians are ubiquitous among the global surgical workforce and should be considered in plans to scale up the surgical workforce. Further research is required to assess outcomes, especially in low-income and middle-income countries where documented supervision is less robust.

Health-system-adapted data envelopment analysis for decision-making in universal health coverage.

OBJECTIVE: To develop and test a method that allows an objective assessment of the value of any health policy in multiple domains. METHODS: We developed a method to assist decision-makers with constrained resources and insufficient knowledge about a society's preferences to choose between policies with unequal, and at times opposing, effects on multiple outcomes. Our method extends standard data envelopment analysis to address the realities of health policy, such as multiple and adverse outcomes and a lack of information about the population's preferences over those outcomes. We made four modifications to the standard analysis: (i) treating the policy itself as the object of analysis, (ii) allowing the method to produce a rank-ordering of policies; (iii) allowing any outcome to serve as both an output and input; and (iv) allowing variable return to scale. We tested the method against three previously published analyses of health policies in low-income settings. RESULTS: When applied to previous analyses, our new method performed better than traditional cost-effectiveness analysis and standard data envelopment analysis. The adapted analysis could identify the most efficient policy interventions from among any set of evaluated policies and was able to provide a rank ordering of all interventions. CONCLUSION: Health-system-adapted data envelopment analysis allows any quantifiable attribute or determinant of health to be included in a calculation. It is easy to perform and, in the absence of evidence about a society's preferences among multiple policy outcomes, can provide a comprehensive method for health-policy decision-making in the era of sustainable development.

Reducing road traffic deaths: where should we focus global health initiatives?

BACKGROUND: Current global surgery initiatives focus on increasing surgical workforce; however, it is unclear whether this approach would be helpful globally, as patients in low-resource countries may not be able to reach hospitals in a timely fashion without formal Emergency Medical Services (EMS). We hypothesize that increased surgical workforce correlates with decreased road traffic deaths (RTDs) only in countries with EMS. METHODS: Estimated RTDs were obtained from the Global Status Report on Road Safety 2013, which estimated the RTD rate in 2010 (RTD 2010). The classification of EMS was defined by the Global Status Report on Road Safety 2009. The density of surgeons, anesthesiologists, and obstetricians (SAO density) and 2010 income classification were accessed from the World Bank. Multivariable regression analysis was performed adjusting for different countries, income levels, and trauma system characteristics. Sensitivity analysis was performed. RESULTS: One-fourth of the countries reported not having formal EMS (n = 41, 23.4%). On adjusted analysis, SAO density was not associated with changes in RTD 2010 in countries without EMS (n = 25, P = 0.50). However, in countries with EMS, each increase in SAO density per 100,000 population decreased RTDs by 0.079 per 100,000 population (n = 97, P <0.001). Income was the only other factor resulting in reduced mortality rates (P = 0.004). Sensitivity analysis confirmed these findings. CONCLUSIONS: Increases in surgical workforce reduce RTDs only when EMS exist. Surgical workforce and EMS must be seen as part of the same system and developed together to maximize their effect in reducing RTDs. Global health initiatives should be tailored to individual country need. LEVEL OF EVIDENCE: Level II (Ecological study).

Neurosurgical Care: Availability and Access in Low-Income and Middle-Income Countries.

BACKGROUND: An estimated 5 billion people worldwide lack access to basic surgical care. In particular, the vast majority of low-income and middle-income countries (LMICs) currently struggle to provide adequate neurosurgical services. Significant barriers exist, including limited access to trained medical, nursing, and allied health staff; lack of equipment; and availability of services at reasonable distance and at reasonable cost to patients. An accurate assessment of current neurosurgical capacity in LIMCs is an essential first step in tackling this deficit. OBJECTIVE: To quantify the neurosurgical operational capacity and assess access to neurosurgical services in LMICs, by taking into account the location of workforce and services. METHODS: A total of 141 LMICs were contacted and asked to report the number of currently practicing neurosurgeons, access to computed tomographic and magnetic resonance imaging, and availability of neurosurgical equipment (microscope, endoscope, bipolar diathermy, high-speed neurosurgical drill). A proposed World Federation of Neurosurgeons classification was used to stratify cities based on the level of neurosurgical care that could be provided. The data were geocoded and analyzed in Redivis (Redivis Inc.) to assess the percentage of the population covered within a 2-hour travel time of a city offering differing levels of neurosurgical care. RESULTS: 68 countries provided complete data (response rate, 48.2%). Eleven countries reported having no practicing neurosurgeons. The average percentage of the population with access to neurosurgical services within a 2-hour window is 25.26% in sub-Saharan Africa, 62.3% in Latin America and the Caribbean, 29.64% in East Asia and the Pacific, 52.83% in South Asia, 79.65% in the Middle East and North Africa, and 93.3% in Eastern Europe and Central Asia. CONCLUSIONS: There are several challenges to the provision of adequate neurosurgical services in low-resource settings. This study used mapping techniques to determine the current global neurosurgical workforce capacity and distribution. We have used our findings to identify areas for improvement. These include increasing and improving neurosurgical training programs worldwide, recruiting students and young physicians into the field, and retaining existing neurosurgeons within their home countries.

The Colorado Humanitarian Surgical Skills Workshop: A Cadaver-Based Workshop to Prepare Residents for Surgery in Austere Settings.

OBJECTIVE: Interest in humanitarian surgery is high among surgical and obstetric residents. The Colorado Humanitarian Surgical Skills Workshop is an annual 2-day course exposing senior residents to surgical techniques essential in low- and middle-income countries but not traditionally taught in US residencies. We evaluated the course's ability to foster resident comfort, knowledge, and competence in these skills. DESIGN: The cohort of course participants was studied prospectively. Participants attended didactic sessions followed by skills sessions using cadavers. Sample areas of focus included general surgery (mesh-free hernia repair), orthopedics (powerless external fixation), and neurosurgery (powerless craniotomy). Before and after the course, participants answered a questionnaire assessing confidence with taught skills; took a knowledge-based test composed of multiple choice and open-ended questions; and participated in a manual skills test of tibial external fixation. SETTING: The Center for Surgical Innovation, University of Colorado School of Medicine. PARTICIPANTS: A total of 12 residents (11 general surgical and 1 obstetric) from ten US institutions. RESULTS: After the course, participants perceived increased confidence in performing all 27 taught procedures and ability to practice in low- and middle-income countries. In knowledge-based testing, 10 of 12 residents demonstrated improvement on multiple choice questioning and 9 of 12 residents demonstrated improvement on open-ended questioning with structured scoring. In manual skills testing, all external fixator constructs demonstrated objective improvement on structured scoring and subjective improvement on stability assessment. CONCLUSIONS: For senior residents interested in humanitarian surgery, a combination of skills-focused teaching and manual practice led to self-perceived and objective improvement in relevant surgical knowledge and skills. The Colorado Humanitarian Surgical Skills Workshop represents an effective model for transmitting essential surgical principles and techniques of value in low-resource settings.

Guide to research in academic global surgery: A statement of the Society of University Surgeons Global Academic Surgery Committee.

Global surgery is an emerging academic discipline that is developing in tandem with numerous policy and advocacy initiatives. In this regard, academic global surgery will be crucial for measuring the progress toward improving surgical care worldwide. However, as a nascent academic discipline, there must be rigorous standards for the quality of work that emerges from this field. In this white paper, which reflects the opinion of the Global Academic Surgery Committee of the Society for University Surgeons, we discuss the importance of research in global surgery, the methodologies that can be used in such research, and the challenges and benefits associated with carrying out this research. In each of these topics, we draw on existing examples from the literature to demonstrate our points. We conclude with a call for continued, high-quality research that will strengthen the discipline's academic standing and help us move toward improved access to and quality of surgical care worldwide.

Using the Consolidated Framework for Implementation Research to implement and evaluate national surgical planning.

The Lancet Commission on Global Surgery defined six surgical indicators and a framework for a national surgical plan that aimed to incorporate surgical care as a part of global public health. Multiple countries have since begun national surgical planning; each faces unique challenges in doing so. Implementation science can be used to more systematically explain this heterogeneous process, guide implementation efforts and ultimately evaluate progress. We describe our intervention using the Consolidated Framework for Implementation Research. This framework requires identifying characteristics of the intervention, the individuals involved, the inner and outer setting of the intervention, and finally describing implementation processes. By hosting a consultative symposium with clinicians and policy makers from around the world, we are able to specify key aspects of each element of this framework. We define our intervention as the incorporation of surgical care into public health planning, identify local champions as the key individuals involved, and describe elements of the inner and outer settings. Ultimately we describe top-down and bottom-up models that are distinct implementation processes. With the Consolidated Framework for Implementation Research, we are able to identify specific strategic models that can be used by implementers in various settings. While the integration of surgical care into public health throughout the world may seem like an insurmountable challenge, this work adds to a growing effort that seeks to find a way forward.

Effect of removing the barrier of transportation costs on surgical utilisation in Guinea, Madagascar and the Republic of Congo.

BACKGROUND: 81 million people face impoverishment from surgical costs every year. The majority of this impoverishment is attributable to the non-medical costs of care-for transportation, for food and for lodging. Of these, transportation is the largest, but because it is not viewed as an actual medical cost, it is frequently unaddressed. This paper examines the effect on surgical utilisation of paying for transportation. METHODS: A hierarchical logistic regression was performed on 2692 patients presenting for surgical care to a non-governmental organisation operating in the Republic of the Congo, Guinea and Madagascar. Controlling for distance from the hospital, age, gender, the need for air travel and time between appointments, the effect of payment for transportation on the surgical no-show rate was evaluated. RESULTS: After adjustment for observed confounders, paying for transportation drops the surgical no-show rate by 45% (OR 0.55; 95% CI 0.40 to 0.77; p<0.001). Age, delay between appointments and the number of hours travelled for surgery also predict surgical no-show. For 28% of no-show patients, the cost of transportation from their homes to a nearby predetermined pick-up point remained a barrier, even when transportation from the pick-up point to the hospital was free. CONCLUSION: Transportation costs are a significant barrier to surgical care in low-resource settings, and paying for it halves the no-show rate. This finding highlights that decreasing demand-side barriers to surgical care cannot be limited only to the removal of user fees.