Search

Immunotherapy (IO)-based combinations used to treat metastatic clear cell renal cell carcinoma (ccRCC) include dual immune checkpoint inhibition with ipilimumab and nivolumab (IO/IO) and several combinations of vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors (TKIs) with an immune checkpoint inhibitor (TKI/IO). IO/IO and TKI/IO approaches have not been compared directly, and it is unknown whether patients who do not respond to first-line IO/IO can salvage long-term survival by receiving a second-line TKI. Progression-free survival after second-line therapy (PFS-2) evaluates the ability to be salvaged by second-line therapy. We retrospectively evaluated 173 patients treated with first-line IO/IO or TKI/IO for metastatic ccRCC at Memorial Sloan Kettering Cancer Center and report PFS-2, overall survival, and response to second line of therapy (ORR

Medical devices that suit the needs and challenges of low- and middle-income countries are desperately needed. To provide sustainable access to such devices, business approaches must be developed to meet the demands of individual economic, healthcare, and innovation ecosystems. Currently, there is a gap in the literature regarding business models for medical devices in low- and middle-income countries.A multimodal approach using literature review and key informant interviews was performed to determine critical components of business models for medical device organizations operating in LMICs, specifically focusing on models in emerging markets.The search resulted in 4,674 articles, of which 31 were determined to be relevant and were reviewed. Additional sources included 1 government website, 5 nongovernmental organization websites, 2 private enterprises, and 6 publicly available, non-peer reviewed websites and 1 video. From these sources, four major criteria were found to be necessary for successful development of medical device business models in emerging markets: value proposition, partnerships, strategic pricing, and funding models.Innovators must custom tailor their business model when implementing these elements to the regulatory, cultural, and economic landscapes of each setting. This will improve access to safer, affordable medical care and successfully bring innovative technologies to emerging markets.

Gastroschisis mortality in sub-Saharan Africa (SSA) remains high at 59-100%. Silo inaccessibility contributes to this disparity. Standard of care (SOC) silos cost $240, while median monthly incomes in SSA are $200. Our multidisciplinary American and Ugandan team designed and bench-tested a low-cost (LC) silo that costs $2 and is constructed from locally available materials. Here we describe in vivo LC silo testing.A piglet gastroschisis model was achieved by eviscerating intestines through a midline incision. Eight piglets were randomized to LC or SOC silos. Bowel was placed into the LC or SOC silo, maintained for 1-h, and reduced. Procedure times for placement, intestinal reduction, and silo removal were recorded. Tissue injury of the abdominal wall and intestine was assessed. Bacterial and fungal growth on silos was also compared.There were no gross injuries to abdominal wall or intestine in either group or difference in minor bleeding. Times for silo application, bowel reduction, and silo removal between groups were not statistically or clinically different, indicating similar ease of use. Microbiologic analysis revealed growth on all samples, but density was below the standard peritoneal inoculum of 10LC silos designed for manufacturing and clinical use in SSA demonstrated similar ease of use, absence of tissue injury, and acceptable microbiology profile, similar to SOC silos. The findings will allow our team to proceed with a pilot study in Uganda.

Barriers in access to pediatric surgical care are common in low- and middle-income countries (LMICs), but also exist in high-income countries, particularly in urban and rural areas.This article describes "Disparities in Access to Care"-held within the Social Injustice Symposium at the 2020 American Pediatric Surgical Association (APSA) Annual Meeting.This symposium outlined disparities in access to care, illustrated by examples from pediatric trauma and neonatal surgery in U.S. urban, U.S. rural, and non-U.S. global locations (LMICs). Geographic and financial challenges were common to families from the rural U.S. and LMICs. In contrast, families in U.S. urban settings generally do not face geographic barriers, but are often economically and racially diverse and many face complex societal factors leading to poor outcomes. Systemic processes must be changed to improve pediatric surgical health outcomes.A comprehensive health system with an equal emphasis on supportive care and surgery is required in all settings. Global collaboration and partnerships can provide an avenue for advocacy and strategic innovation to improve quality of care.Ⅴ.

Type-I Diabetes (T1D) is caused by defective immunotolerance mechanisms enabling autoreactive T cells to escape regulation in lymphoid organs and destroy insulin-producing β-cells in the pancreas, leading to insulin dependence. Strategies to promote β-cell tolerance could arrest T1D. We previously showed that secretion of secondary lymphoid chemokine CCL21 by CCL21 transgenic β-cells induced tolerance and protected non-obese diabetic (NOD) mice from T1D. T1D protection was associated with formation of lymph node-like stromal networks containing tolerogenic fibroblastic reticular cells (FRCs). Here, we developed a polyethylene glycol (PEG) hydrogel platform with hydrolytically degradable PEG-diester dithiol crosslinkers to provide controlled and sustained delivery of CCL21 and β-cell antigens for at least 28 days in vitro and recapitulate properties associated with the tolerogenic environment of CCL21 transgenic β-cells in our previous studies. CCL21 and MHC-II restricted antigens were tethered to gels via simple click-chemistry while MHC-I restricted antigens were loaded in PEG-based polymeric nanovesicles and incorporated in the gel networks. CCL21 and antigen release kinetics depended on the PEG gel tethering strategy and the linkers. Importantly, in vitro functionality, chemotaxis, and activation of antigen-specific T cells were preserved. Implantation of CCL21 and β-cell antigen gels under the kidney capsule of pre-diabetic NOD mice led to enrichment of adoptively transferred antigen-specific T cells, formation of gp38 + FRC-like stromal cell networks, and increased regulation of specific T cells with reduced accumulation within pancreatic islets. Thus, our platform for sustained release of β-cell antigens and CCL21 immunomodulatory molecule could enable the development of antigen-specific tolerance therapies for T1D.

Background Many surgeons in low- and middle-income countries have described performing surgery using gasless (lift) laparoscopy due to inaccessibility of carbon dioxide and reliable electricity, but the safety and feasibility of the technique has not been well documented. We describe preclinical testing of the in vivo safety and utility of KeyLoop, a laparoscopic retractor system to enable gasless laparoscopy. Methods Experienced laparoscopic surgeons completed a series of four laparoscopic tasks in a porcine model: laparoscopic exposure, small bowel resection, intracorporeal suturing with knot tying, and cholecystectomy. For each participating surgeon, the four tasks were completed in a practice animal using KeyLoop. Surgeons then completed these tasks using standard-of-care (SOC) gas laparoscopy and KeyLoop in block randomized order to minimize learning curve effect. Vital signs, task completion time, blood loss and surgical complications were compared between SOC and KeyLoop using paired nonparametric tests. Surgeons completed a survey on use of KeyLoop compared to gas laparoscopy. Abdominal wall tissue was evaluated for injury by a blinded pathologist. Results Five surgeons performed 60 tasks in 15 pigs. There were no significant differences in times to complete the tasks between KeyLoop and SOC. For all tasks, there was a learning curve with task completion times related to learning the porcine model. There were no significant differences in blood loss, vital signs or surgical complications between KeyLoop and SOC. Eleven surgeons from the United States and Singapore felt that KeyLoop could be used to safely perform several common surgical procedures. No abdominal wall tissue injury was observed for either KeyLoop or SOC. Conclusions Procedure times, blood loss, abdominal wall tissue injury and surgical complications were similar between KeyLoop and SOC gas laparoscopy for basic surgical procedures. This data supports KeyLoop as a useful tool to increase access to laparoscopy in low- and middle-income countries.

Most organisms experience ontogenescence (high and decreasing mortality from conception to the age of maturity) in spite of the clear evolutionary disadvantage of dying prior to reproducing. One hypothesis that may help to explain the prevalence and persistence of ontogenescence is the Transitional Timing Hypothesis, which states that developmental transitions are dangerous and concentrated in the earliest phases of life (e.g., hatching or birth). This study's goal was to examine the transitional dangers of early development and hatching in the barnacle Chthamalus fragilis. Barnacle egg lamellae were monitored for 2 weeks after extraction from their parents, and all hatching events were recorded along with whether each hatched larva was a successful swimmer or not. The total number of eggs that failed to hatch from each egg lamella was also determined. Results showed significant brood mortality prior to hatching as well as a large proportion of newly-hatched larvae that were unable to swim well. There was also a clear pattern in the timing of hatching events from egg lamellae. However, there was no effect of delayed hatching on either hatching success or swimming ability of larvae. The high proportion of non-hatching and poor-swimming larvae lend support to the Transitional Timing Hypothesis, suggesting that early developmental stages and hatching in barnacles (and probably other organisms, too) are potentially dangerous transitional events that cannot be avoided and should be taken into account when studying the population ecology of these species.

Faith-based missions have played a large role in surgical care delivery in low- and middle-income countries (LMIC). As global surgery is now an academic discipline, this pilot study sought to understand how different faith ideologies influence surgeon motivations and subsequent culture of the global surgery landscape. Interviews were conducted with North American surgeons who pursue global surgery significantly in their career. Points of discussion included early influences, obstacles, motivations, philosophy and approach to global surgery work, and experiences with faith-based (FBO) and non-faith-based organizations (NFBO). Notes were transcribed and thematic analysis performed. Sixteen surgeons were interviewed (11 men, 5 women, ages 39–75 years-old). Surgeons had worked in 32 countries with FBO and NFBO in intermittent or long-term capacity. Religious upbringing and current affiliations included Atheism, Protestant Christianity, Catholicism, Hinduism, Judaism, Mormonism, Islam, and nonreligious spirituality. Early influences included international upbringing (n = 7), emphasis on service (n = 9), and exposure to the religious mission concept (n = 6). The most common core motivation among all participants was addressing disparities (n = 10). Some believed that FBO and NFBO have different goals (n = 4), and only surgeons identifying with Christianity believed the goals are similar (n = 3). Participants expressed that FBO are exclusive (n = 4) and focused on proselytization (n = 6) while NFBO are humanitarian (n = 3) but less integrated into the community (n = 4). Global surgeons have shared early influences, obstacles, and desire to address disparities. Perceptions of FBO and NFBO differed based on religious background. This pilot study will inform future studies regarding the collaborations of FBO and NFBO to improve global surgical care.

Background. Despite favorable outcomes of laparoscopic surgery in high-income countries, its implementation in low- and middle-income countries (LMICs) is challenging given a shortage of consumable supplies, high cost, and risk of power outages. To overcome these barriers, we designed a mechanical retractor that provides vertical tension on the anterior abdominal wall. Methods. The retractor design is anatomically and mathematically optimized to provide exposure similar to traditional gas-based insufflation methods. Anatomical data from computed tomography scans were used to define retractor size. The retractor is constructed of biocompatible stainless steel rods and paired with a table-mounted lifting system to provide 5 degrees of freedom. Structural integrity was assessed through finite element analysis (FEA) and load testing. Functional testing was performed in a laparotomy model. Results. A user guide based on patient height and weight was created to customize retractor size, and 4 retractor sizes were constructed. FEA data using a 13.6 kg mass (15 mm Hg pneumoperitoneum) show a maximum of 30 mm displacement with no permanent deformation. Physical load testing with applied weight from 0 to 13.6 kg shows a maximum of 60 mm displacement, again without permanent deformation. Retraction achieved a 57% larger field of view compared to an unretracted state in a laparotomy model. Conclusions. The KeyLoop retractor maintains structural integrity, is easily sterilized, and can be readily manufactured, making it a viable alternative to traditional insufflation methods. For surgeons and patients in LMICs, the KeyLoop provides a means to increase access to laparoscopic surgery.

Introduction The American Pediatric Surgical Association (APSA) travel fellowship was established in 2013 to allow pediatric surgeons from low- and middle-income countries to attend the APSA annual meeting. Travel fellows also participated in various clinical and didactic learning experiences during their stay in North America. Methods Previous travel fellows completed a survey regarding their motivations for participation in the program, its impact on their practice in their home countries, and suggestions for improvement of the fellowship. Results Eleven surgeons participated in the travel fellowship and attended the annual APSA meetings in 2013–2018. The response rate for survey completion was 100%. Fellows originated from 9 countries and 3 continents and most fellows worked in government practice (n = 8, 73%). Nine fellows (82%) spent > 3 weeks participating in additional learning activities such as courses and clinical observerships. The most common reasons for participation were networking (n = 11, 100%), learning different ways of providing care (n = 10, 90.9%), new procedural techniques (n = 9, 81.8%), exposure to a different medical culture (n = 10, 90.9%), and engaging in research (n = 8, 72.7%). Most of the fellows participated in a structured course: colorectal (n = 6, 55%), laparoscopy (n = 2, 18%), oncology (n = 2, 18%), leadership skills (n = 1, 9%), and safety and quality initiatives (n = 1, 9%). Many fellows participated in focused clinical mentorships: general pediatric surgery (n = 9, 82%), oncology (n = 5, 45%), colorectal (n = 3, 27%), neonatal care (n = 2, 18%) and laparoscopy (n = 2, 18%). Upon return to their countries, fellows reported that they were able to improve a system within their hospital (n = 7, 63%), expand their research efforts (n = 6, 54%), or implement a quality improvement initiative (n = 6, 54%). Conclusions The APSA travel fellowship is a valuable resource for pediatric surgeons in low- and middle-income countries. After completion of these travel fellowships, the majority of these fellows have implemented important changes in their hospital’s health systems, including research and quality initiatives, to improve pediatric surgical care in their home countries. Level of evidence This is not a clinical study. Therefore, the table that lists levels of evidence for “treatment study”, “prognosis study”, “study of diagnostic test” and “cost effectiveness study” does not apply to this paper.

The coronavirus disease 2019 (COVID-19) poses a serious global health threat. Without a vaccine, behavior change is the most effective means of reducing disease transmission. Identifying psychological factors that may encourage engagement in preventative health behaviors is crucial. The behavioral immune system (BIS) represents a set of psychological processes thought to promote health by encouraging disease avoidance behaviors. This study examined whether individual differences in BIS reactivity (germ aversion, pathogen disgust sensitivity) were associated with concern about COVID-19 and engagement in recommended preventative health behaviors (social distancing, handwashing, cleaning/disinfecting, avoiding touching face, wearing facemasks). From March 20 to 23, 2020, a US national sample (N = 1019) completed an online survey. Germ aversion and pathogen disgust sensitivity were the two variables most consistently associated with COVID-19 concern and preventative health behaviors, while accounting for demographic, health, and psychosocial covariates. Findings have implications for the development of interventions intended to increase preventative health behaviors.

Most existing medical devices were not built for the challenges often present in many African countries. Regulatory systems for medical devices are essential to ensuring device safety and efficacy. Yet, currently, most African countries do not have a well-defined regulatory process. This discourages both innovators within Africa and companies outside of Africa from developing quality medical devices suitable for these challenges., Key Findings Although 11 of 14 member countries of the College of Surgeons of East, Central, and Southern Africa have legislation mandating the regulation of medical devices, only half are currently developing medical device regulatory processes and half do not have a formal process. A country's gross domestic product had a strong correlation to level of medical device regulation. The number of years that had elapsed from the country's independence to the present had a strong correlation to the status of the country's regulatory processes. Key Implications To expand regulatory capacity and minimize resource expenditure when developing or creating new medical device regulations, policy makers should facilitate adopting or amending existing harmonized regulations. Ministries of health should prioritize local capacity building in the form of well-trained personnel, tools, and facilities to improve regulatory standards. Medical technology companies with a charitable division should consider investment in capacity building and innovation to harmonize regulatory standards across African countries., Effective regulatory frameworks, harmonized to international standards, are critical to expanding access to quality medical devices in low- and middle-income countries. This review provides a summary of the state of medical device regulation in the 14 member countries of the College of Surgeons of East, Central, and Southern Africa (COSECSA) and South Africa. Countries were categorized according to level of regulatory establishment, which was found to be positively correlated to gross domestic product (GDP; rs=0.90) and years of freedom from colonization (rs=0.60), and less positively correlated to GDP per capita (rs=0.40). Although most countries mandate medical device regulation in national legislation, few employ all the guidelines set forth by the World Health Organization. A streamlined regulatory process across African nations would simplify this process for innovators seeking to bring medical devices to the African market, thereby increasing patient access to safe medical devices.

Laparoscopic surgery is the standard of care in high-income countries for many procedures in the chest and abdomen. It avoids large incisions by using a tiny camera and fine instruments manipulated through keyhole incisions, but it is generally unavailable in low- and middle-income countries (LMICs) due to the high cost of installment, lack of qualified maintenance personnel, unreliable electricity, and shortage of consumable items. Patients in LMICs would benefit from laparoscopic surgery, as advantages include decreased pain, improved recovery time, fewer wound infections, and shorter hospital stays. To address this need, we developed an accessible laparoscopic system, called the ReadyView laparoscope for use in LMICs. The device includes an integrated camera and LED light source that can be displayed on any monitor. The ReadyView laparoscope was evaluated with standard optical imaging targets to determine its performance against a state-of-the-art commercial laparoscope. The ReadyView laparoscope has a comparable resolving power, lens distortion, field of view, depth of field, and color reproduction accuracy to a commercially available endoscope, particularly at shorter, commonly-used working distances (3-5 cm). Additionally, the ReadyView has a cooler temperature profile, decreasing the risk for tissue injury and operating room fires. The ReadyView features a waterproof design, enabling sterilization by submersion, as commonly performed in LMICs. A custom desktop software was developed to view the video on a laptop computer with a frame rate greater than 30 frames per second and to white balance the image, which is critical for clinical use. The ReadyView laparoscope is capable of providing the image quality and overall performance needed for laparoscopic surgery. This portable low-cost system is well suited to increase access to laparoscopic surgery in LMICs.

The true incidence of congenital anomalies in sub-Saharan Africa is unknown. Owing to complex challenges associated with congenital anomalies, many affected babies may never present to a health facility, resulting in an underestimation of disease burden.Interviews were conducted with Ugandans between September 2018 and May 2019. Responses from community members versus families of children with congenital anomalies were compared.A total of 198 Ugandans were interviewed (91 family members, 80 community members). All participants (N = 198) believed that seeking surgical care would lead to poverty, 43% (n = 84) assumed fathers would abandon the child, and 26% (n = 45) thought a child with a congenital anomaly in their community had been left to die. Causes of anomalies were believed to be contraceptive methods (48%, n = 95), witchcraft (17%, n = 34), or drugs (10%, n = 19). Of family members, 25 (28%) were advised to allow the child to die. Families with affected children were more likely to have a lower income (P.001), believe anomalies could be treated (P = .007), but thought that allowing the child to die was best for the family (32% vs 9%; P.0001). Monthly household income50,000 Uganda shillings ($13 United States dollars) was a significant predictor of the father leaving the family (P = .024), being advised to not pursue medical care (P = .046), and believing that God should decide the child's fate (P = .047).Families face significant financial and social pressures when deciding to seek surgical care for a child with a congenital anomaly. Many children with anomalies may die and never reach a health facility to be counted, thus contributing to a hidden mortality.

Infectious disease poses a threat to reproductive fitness. However, the costs associated with infectious disease are often greater for females than males. Sexist attitudes toward females may have in part emerged from disease-avoidance concerns, in order to decrease infectious disease threat and promote reproductive success for females (and males indirectly). Across three studies, disease-avoidance tendencies were positively correlated with benevolent sexism (perceiving females as pure and in need of protection). Hostile sexism, or more traditional negative attitudes toward females, was inconsistently related to disease avoidance. Furthermore, right-wing authoritarianism partially accounted for the relation between disease avoidance and benevolent sexism, whereas right-wing authoritarianism fully accounted for the relation between disease avoidance and hostile sexism. By encouraging traditional sex roles and restricting female sexual behavior, benevolent sexism may reduce infectious disease threat in females, while maintaining positive relations between the sexes (unlike hostile sexism), which is important for reproduction.

Modern global surgery, which aims to provide improved and equitable surgical care worldwide, is a product of centuries of international care initiatives, some borne out of religious traditions, dating back to the first millennium. The first hospitals ( xenodochia) were established in the 4th and 5th centuries CE by the early Christian church. Early “missions,” a term introduced by Jesuit Christians in the 16th century to refer to the institutionalized expansion of faith, included medical care. Formalized Muslim humanitarian medical care was marked by organizations like the Aga Khan Foundation and the Islamic Association of North America in the 20th century. Secular medical humanitarian programs developed in the 19th century, notably with the creation of the International Committee of the Red Cross (1863) and the League of Nations Health Organization (1920) (which later became the World Health Organization [1946]). World War II catalyzed another proliferation of nongovernmental organizations, epitomized by the quintessential humanitarian health provider, Médecins Sans Frontières (1971). “Global health” as an academic endeavor encompassing education, service, and research began as an outgrowth of departments of tropical medicine and international health. The American College of Surgeons brought a surgical focus to global health beginning in the 1980s. Providing medical care in distant countries has a long tradition that parallels broad themes in history: faith, imperialism, humanitarianism, education, and service. Surgery as a focus of academic global health is a recent development that continues to gain traction.

Background and objectives Cancer poses a substantial health and economic burden on patients and caregivers in Canada. Previous reviews have estimated the indirect cost burden as work-related productivity losses associated with cancer. However, these estimates require updating and complementing with more comprehensive data that include relevant dimensions beyond labor market costs, such as patient time, lost leisure time and home productivity losses. Methods A systematic review of the literature was conducted to identify studies published from 2006 to 2020 that measured and reported the indirect costs borne by cancer patients and their caregivers in Canada, from the patient, caregiver, employer, and societal perspectives. Study characteristics and cost estimation methods were extracted from relevant studies. Costs estimates were reported and converted to 2020 CAD for the following categories: lost earnings, caregiving time costs, home production losses, patient time (leisure), morbidity-, disability-, premature mortality-related costs, friction costs, and overall productivity losses. A quality assessment of individual studies was conducted for included studies using the Newcastle–Ottawa Assessment Tool. Results In total, 3980 studies were identified, of which 18 Canadian studies met the inclusion criteria for review. One-third of the studies used or developed prediction models, 38% enrolled patient cohorts, and 27% used administrative databases. Over one-third of the studies were conducted at a national level (38%). All studies employed the human capital approach to estimate costs, and 16% also used the friction cost approach. Lost earnings were higher among self-employed patients (43% vs 24% among employees) and females ($8200 vs $3200 for males). Caregiver costs ranged from $15,786 to $20,414 per patient per year. Household productivity losses were estimated to be up to $238,904 per household per year. Patient time (leisure) costs were estimated to be between $13,000 and $18,704 per patient per year. Premature annual mortality costs were estimated to be $2.98 billion overall in Quebec. Friction costs incurred by employers were estimated between $6400 and $23,987 per patient per year. Societal productivity losses associated with cancer were estimated between $75 million to $317 million, annually. Conclusions This review suggests that the indirect cost burden of cancer is considerable from the patient, caregiver, employer, and societal perspectives. This up-to-date review of the literature provides a comprehensive understanding of the indirect cost burden by including non-labor market activity costs and by examining all relevant perspectives. These results provide a strong case for the government and employers to ensure there are supports in place to help patients and caregivers buffer the impact of cancer so they can continue to engage in productive activities and enjoy leisure time. Electronic supplementary material The online version of this article (10.1007/s40258-020-00619-z) contains supplementary material, which is available to authorized users.

Laparoscopic surgery has become standard of care in high-income countries but is rarely accessible in low- and middle-income countries (LMICs). This study assessed experience with laparoscopy and attitudes toward a low-cost laparoscopic system among surgeons in sub-Saharan Africa. A survey assessing current laparoscopic practice and feedback on a low-cost laparoscopic system was administered to attendees of the College of Surgeons of East, Central, and Southern Africa (COSECSA) Scientific Conference between December 4 and December 6, 2019 in Kampala, Uganda. Fifty-six surgeons from 14 countries participated. A majority were male (n = 46, 82%) general surgeons (n = 37, 66%) from tertiary/teaching hospitals (n = 36, 64%). For those with training in laparoscopy (n = 33, 59%), 22 (67%) reported less than 1 year of training and over half (n = 17, 52%) reported 1 month or less. Overall, a minority (n = 21, 38%) used laparoscopy in current practice, with 57% (n = 12) of those performing laparoscopy less than once per week. The most common laparoscopic surgeries performed were cholecystectomy (n = 15), diagnostic laparoscopy (n = 14), and appendectomy (n = 12). Few surgeons were performing more complex cases (n = 5). Barriers to laparoscopy included poor access to training equipment (n = 34, 61%), mentors (n = 33, 59%), laparoscopic equipment (n = 31, 55%), equipment maintenance (n = 25, 45%), access to consumable supplies (n = 21, 38%), and cost (n = 31, 55%). Fifty-two participants (93%) were interested in increasing their use of laparoscopy; the majority felt that a low-cost laparoscope (n = 52, 93%) and lift retractor for gasless laparoscopy (n = 46, 82%) would serve an unmet need in their practice. While the use of laparoscopy is currently limited in COSECSA countries, there is a significant interest among surgeons to increase implementation. A low-cost, durable laparoscopic system was viewed as a potential solution to the current barriers and could improve implementation in LMICs.

Gastroschisis silos are often unavailable in sub-Saharan Africa (SSA), contributing to high mortality. We describe a collaboration between engineers and surgeons in the United States and Uganda to develop a silo from locally available materials.Design criteria included the following:$5 cost, 5 ± 0.25 cm opening diameter, deformability of the opening construct, ≥ 500 mL volume, ≥ 30 N tensile strength, no statistical difference in the leakage rate between the low-cost silo and preformed silo, ease of manufacturing, and reusability. Pugh scoring matrices were used to assess designs. Materials considered included the following: urine collection bags, intravenous bags, or zipper storage bags for the silo and female condom rings or O-rings for the silo opening construct. Silos were assembled with clothing irons and sewn with thread. Colleagues in Uganda, Malawi, Tanzania, and Kenya investigated material cost and availability.Urine collection bags and female condom rings were chosen as the most accessible materials. Silos were estimated to cost $1 in SSA. Silos yielded a diameter of 5.01 ± 0.11 cm and a volume of 675 ± 7 mL. The iron + sewn seal, sewn seal, and ironed seal on the silos yielded tensile strengths of 31.1 ± 5.3 N, 30.1 ± 2.9 N, and 14.7 ± 2.4 N, respectively, compared with the seal of the current standard-of-care silo of 41.8 ± 6.1 N. The low-cost silos had comparable leakage rates along the opening and along the seal with the spring-loaded preformed silo. The silos were easily constructed by biomedical engineering students within 15 min. All silos were able to be sterilized by submersion.A low-cost gastroschisis silo was constructed from materials locally available in SSA. Further in vivo and clinical studies are needed to determine if mortality can be improved with this design.

The surgical workforce in sub-Saharan Africa is insufficient to meet population needs. Therefore, medical students should be encouraged to pursue surgical careers and “brain drain” must be minimized. It is unknown to what extent foreign aid priorities influence medical student career choices in Uganda. Medical students in Uganda completed an online survey examining their career choices and attitudes regarding career opportunities and funding priorities. Data were analyzed using descriptive statistics, and responses among men and women were compared using Fisher’s exact tests. Ninety-eight students participated. Students were most influenced by inspiring role models, employment opportunities and specialty fit with personal skills. Filling an underserved specialty was near the bottom of the influence scale. Women placed higher importance on advice from mentors (p = 0.049) and specialties with lower stress burden (p = 0.027). Men placed importance on opportunities in non-governmental organizations (p = 0.033) and academia (p = 0.050). Students expressed that the most supported specialties were infectious disease (n = 65, 66%), obstetrics (n = 15, 15%) and pediatrics (n = 7, 7%). Most students (n = 91, 93%) were planning a career in infectious disease. Fifty-three students (70%) indicated plans to leave Africa for residency. Female students were more likely to have a plan to leave (p = 0.027). Medical students in Uganda acknowledge the career opportunities for physicians in specialties prioritized by the Sustainable Development Goals. In order to avoid “brain drain” and encourage students to pursue careers in surgery, career opportunities including surgical residencies must be prioritized and supported in sub-Saharan Africa.

Background and Objective Psychosocial costs, or quality of life costs, account for psychological distress, pain, suffering and other negative experiences associated with cancer. They contribute to the overall economic burden of cancer that patients experience. But this category of costs remains poorly understood. This hinders opportunities to make the best cancer control policy decisions. This study explored the psychosocial cost burden associated with cancer, how studies measure psychosocial costs and the impact of this burden. Methods A systematic literature review of academic and grey literature published from 2008 to 2018 was conducted by searching electronic databases, guided by the Institute of Medicine’s conceptualization of psychosocial burden. Results were analyzed using a narrative synthesis and a weighted proportion of populations affected was calculated. Study quality was assessed using the Ottawa‐Newcastle instrument. Results A total of 25 studies were included. There was variation in how psychosocial costs were conceptualized and an inconsistent approach to measurement. Most studies measured social dimensions and focused on the financial consequences of paying for care. Fewer studies assessed costs associated with the other domains of this burden, including psychological, physical, and spiritual dimensions. Fourty‐four percent of cancer populations studied were impacted by psychosocial costs and this varied by disease site (38%‐71%). Two studies monetized the psychosocial cost burden, estimating a lifetime cost per case ranging from CAD$427753 to CAD$528769. Studies were of varying quality; 60% of cross‐sectional studies had a high risk of bias. Conclusions Consistency in approach to measurement would help to elevate this issue for researchers and decision makers. At two‐thirds of the total economic burden of cancer, economic evaluations should account for psychosocial costs to better inform decision‐making. More support is needed to address the psychosocial cost burden faced by patients and their families.

Global surgery, especially academic global surgery, is of tremendous interest to many surgeons. Classically, it entails personnel from high-income countries going to low- and middle-income countries and engaging in educational activities as well as procedures. Academic medical personnel have included students, residents, and attendings. The pervasive notion is that this is a win-win situation for the volunteers and the hosts, that is, a pathway to bilateral academic success. However, a critical examination demonstrates that it can easily become the bold new face of colonialism of a low- and middle-income country by a high-income country.

Background Low-dose computed tomography (CT) screening can reduce lung cancer mortality in people at high risk; adding a smoking cessation intervention to screening could further improve screening program outcomes. This study aimed to assess the impact of adding a smoking cessation intervention to lung cancer screening on clinical outcomes, costs and cost-effectiveness. Methods Using the OncoSim-Lung mathematical microsimulation model, we compared the projected lifetime impact of a smoking cessation intervention (nicotine replacement therapy, varenicline and 12 wk of counselling) in the context of annual low-dose CT screening for lung cancer in people at high risk to lung cancer screening without a cessation intervention in Canada. The simulated population consisted of Canadians born in 1940-1974; lung cancer screening was offered to eligible people in 2020. In the base-case scenario, we assumed that the intervention would be offered to smokers up to 10 times; each intervention would achieve a 2.5% permanent quit rate. Sensitivity analyses varied key model inputs. We calculated incremental cost-effectiveness ratios with a lifetime horizon from the health system's perspective, discounted at 1.5% per year. Costs are in 2019 Canadian dollars. Results Offering a smoking cessation intervention in the context of lung cancer screening could lead to an additional 13% of smokers quitting smoking. It could potentially prevent 12 more lung cancers and save 200 more life-years for every 1000 smokers screened, at a cost of $22 000 per quality-adjusted life-year (QALY) gained. The results were most sensitive to quit rate. The intervention would cost over $50 000 per QALY gained with a permanent quit rate of less than 1.25% per attempt. Interpretation Adding a smoking cessation intervention to lung cancer screening is likely cost-effective. To optimize the benefits of lung cancer screening, health care providers should encourage participants who still smoke to quit smoking.

Objective North American pediatric surgery training programs vary in exposure to index cases, while controversy exists regarding fellow participation in global surgery rotations. We aimed to compare the case logs of graduating North American pediatric surgery fellows with graduating Ugandan pediatric surgery fellows. Design The pediatric surgery training program at a regional Ugandan hospital hosts a collaboration between Ugandan and North American attending pediatric surgeons. Fellow case logs were compared to the Accreditation Council for Graduate Medical Education Pediatric Surgery Case Log 2018 to 19 National Data Report. Setting Mulago National Referral Hospital in Kampala, Uganda; and pediatric surgery training programs in the United States and Canada. Results Three Ugandan fellows completed training and submitted case logs between 2011 and 2019 with a mean of 782.3 index cases, compared to the mean 753 cases in North America. Ugandan fellows performed more procedures for biliary atresia (6.7 versus 4), Wilm's tumor (23.7 versus 5.7), anorectal malformation (45 versus 15.7), and inguinal hernia (158.7 versus 76.8). North American fellows performed more central line procedures (73.7 versus 30.7), cholecystectomies (27.3 versus 3), extracorporeal membrane oxygenation cannulations (16 versus 1), and congenital diaphragmatic hernia repairs (16.5 versus 5.3). All cases in Uganda were performed without laparoscopy. Conclusions Ugandan fellows have access to many index cases. In contrast, North American trainees have more training in laparoscopy and cases requiring critical care. Properly orchestrated exchange rotations may improve education for all trainees, and subsequently improve patient care.

Introduction and aims: Objective structured clinical examinations (OSCEs) play a pivotal role in medical education assessment. The Advanced Clinical Skills (ACS) OSCE examines clinical skills in psychiatry, general practice, obstetrics and gynaecology and paediatrics. This study examined if the 2020 ACS OSCE for fourth year medical students attending the National University of Ireland, Galway, was associated with any significant result differences compared to the equivalent 2019 OSCE. Additionally, we assessed students’ satisfaction and explored any organisational difficulties in conducting a face-to-face OSCE during the COVID-19 pandemic. Materials and methods: This study compared anonymised data between the 2019 and 2020 ACS OSCEs and analysed anonymised student feedback pertaining to the modified 2020 OSCE. Results: The mean total ACS OSCE result achieved in 2020 was statistically higher compared to the 2019 OSCE [62.95% (SD = 6.21) v. 59.35% (SD = 5.54), t = 6.092, p < 0.01], with higher marks noted in psychiatry (p = 0.001), paediatrics (p = 0.001) and general practice (p < 0.001) with more students attaining honours grades (χ2 = 27.257, df = 3, p < 0.001). No difference in failure rates were found. Students reported feeling safe performing the 2020 OSCE (89.2%), but some expressed face-mask wearing impeded their communication skills (47.8%). Conclusion: This study demonstrates that conducting a face-to-face OSCE during the pandemic is feasible and associated with positive student feedback. Exam validity has been demonstrated as there was no difference in the overall pass rate.

This study ascertains the views of UK stakeholders on the actual, and possible, impact of a public health licensing objective in their day-to-day work.Twenty-eight interviews were conducted with members of public health teams who were actively engaged in alcohol licensing in their local area between 2017 and 2019. Six teams were based in Scotland (where there is a public health licensing objective) and 14 in England (where there is no similar objective).Scottish participants reported that while challenges remained in applying the public health licensing objective, progress had been made and the objective was beneficial to their work. Participants in England felt that an objective would increase the legitimacy, value and impact of their contributions. In both Scotland and England, constructive relationships between PHTs, licensing authorities and other key stakeholders were developing suggesting that PHTs could have a sustainable and positive role in licensing.In many Scottish areas, the alcohol licensing system is evolving to take constructive account of its public health objective. In England, PHTs that have invested resources in engaging in this area have demonstrated an ability to work effectively within licensing systems. Strong support for the adoption of a public health licensing objective among these PHTs adds weights to calls for the UK Government to reconsider its previous decision not to introduce such an objective.

687 Background: The presence of sarcomatoid features in clear cell renal cell carcinoma (cRCC) has historically been associated with poor response to tyrosine kinase inhibitor (TKI) monotherapy and poor overall survival; however, immunotherapy (IO) combination therapies have shown more promise in treating this variant. Front-line anti-PD-1 based IO combinations used in ccRCC include ipilimumab/nivolumab (IO/IO) and several combinations of a VEGFR-targeted TKI with a PD-1 inhibitor (TKI/IO). Here, we compare progression-free survival after therapeutic 1st-line (PFS) and 2nd-line (PFS-2) in patients who received IO/IO vs TKI/IO combinations as 1st line treatment for metastatic ccRCC, and test whether the treatment effects differ based on the presence or absence of sarcomatoid dedifferentiation. Methods: A retrospective analysis was performed on patients with ccRCC initiating 1st line combination IO at Memorial Sloan Kettering Cancer Center between 1/1/2014 and 12/30/2020. Patient cohorts were defined by 1st line treatment type: IO/IO or TKI/IO. PFS and PFS-2 were estimated using the Kaplan-Meier method. Restricted mean survival time (RMST) was calculated for PFS and PFS-2 in each 1st line treatment group and modelled using a generalized linear model adjusted for IMDC risk. To test for heterogeneity of treatment effect among subgroups, sarcomatoid features (presence/absence) is included in the models and an interaction test is performed. Results: Ninety patients (28 sarcomatoid) received 1st line IO/IO and 83 (17 sarcomatoid) received 1st line TKI/IO. Median PFS time is 6.8 months (95% CI: 4.5, 12.2) for IO/IO and 21 months (95% CI: 15, 25) for TKI/IO, p=0.009. After adjusting for IMDC risk, and after 48 months of follow-up, RMST for PFS was 10 months for IO/IO and 24 months for TKI/IO (p=0.02) and RMST for PFS-2 was 20 months for IO/IO and 23 months for TKI/IO (p=0.24). In the RMST model, the interaction between treatment group and presence or absence of sarcomatoid features is not significant for PFS (0.95) or PFS-2 (0.29). Conclusions: For ccRCC patients treated with 1st line IO/IO or TKI/IO, adjusted RMST for PFS was significantly longer for the TKI/IO group, but there was no statistically significant difference in adjusted RMST for PFS-2. Anti-PD-1-based therapy is an effective approach to treating ccRCC with sarcomatoid features. [Table: see text]

BackgroundThe increasing demand for health care resources requires measures to evaluate the impact of cancer control approaches. A cancer simulation model can help integrate new knowledge to inform clinical and policy decisions. OncoSim-Breast is a breast cancer simulation model. This paper aims to describe the key assumptions in the OncoSim-Breast model and how well it reproduces more recent breast cancer trends and the observed effects in a randomized screening trial.MethodsThe OncoSim-Breast model simulates the onset, growth and spread of invasive and ductal carcinoma in situ tumours. The model combines Canadian cancer incidence, mortality, screening program and cost data to project population-level outcomes. Users can change the model input to answer specific policy questions. Here we report three validation exercises. First, we compared the model’s projected breast cancer incidence and stage distributions with the observed data in the Canadian Cancer Registry. Second, we compared OncoSim’s projected breast cancer mortality with the Vital Statistics. Third, we replicated the UK Age trial to compare the model’s projections with the trial’s observed screening effects.ResultsOncoSim-Breast’s projected incidence, mortality and stage distribution of breast cancer were close to the observed data in the Canadian Cancer Registry and the Vital Statistics. OncoSim-Breast also reproduced the breast cancer screening effects observed in the UK Age trial.InterpretationOncoSim-Breast’s ability to reproduce the observed population-level breast cancer trends and the screening effects in a randomized trial increases the confidence of using its results to inform policy decisions related to early detection of breast cancer.

Politics entails personal costs and benefits which may differ for youth from different sociocultural backgrounds. The at-stake hypothesis proposes that politically marginalized youth experience greater costs (e.g., stress, conflict) and benefits (e.g., empowerment) related to politics, whereas the at-risk hypothesis proposes that politically marginalized youth experience greater costs but lower benefits. In Study 1, we examined the factor structure of a new political costs and benefits measure among youth (N=1,056, Mage=15.91 years), and tested mental health and demographic correlates. Consistent with the at-stake hypothesis, marginalized youth experienced greater political costs and benefits than non-marginalized youth, although findings were nuanced. In Study 2, a sub-sample of participants (N=191, Mage=16.05 years) were recontacted from Study 1 to provide written explanations for why specific findings emerged. Adolescents’ reasons indicated that laws and policies disproportionately affect youth from marginalized populations, thus producing both negative and positive political experiences.

Background: Delayed presentation of surgical disease often leads to infection in low- and middle-income countries (LMICs). In addition, many primary infections require surgical intervention. The bu...

Background Acute traumatic coagulopathy has been described in adult trauma patients. Acute traumatic coagulopathy may be associated with higher mortality and morbidity in pediatric trauma patients. We aimed to (1) compare acute traumatic coagulopathy incidence among various age groups, using age-adjusted normal reference values for three tests of coagulation, and (2) compare acute traumatic coagulopathy–associated mortality by age. Methods We queried our institutional trauma database for all level 1 and 2 activations with an injury severity score ≥ 9 during 2012 to 2017. Demographics, injury information, and coagulation test results were collected. Coagulopathy was defined using published age-specific and assay-specific parameters. Variables were compared among age groups (children, adults, and older adults), and logistic regression was used to determine independent associations with mortality. Results A total of 1,983 patients were included with a median injury severity score of 17 and mortality of 12%. Prolonged partial thromboplastin time, prolonged international normalized ratio, and hypofibrinogenemia were all strongly associated with mortality among adults and children, but not among older adults (P .01, respectively). Logistic regression revealed an independent association between prolonged partial thromboplastin time and mortality (P Conclusion Prolonged partial thromboplastin time/international normalized ratio and hypofibrinogenemia were common among trauma patients of all ages and were associated with mortality among children and adults, but not older adults, perhaps implicating age-related hemostatic biologic differences.

The treatment of metastatic renal cell carcinoma (RCC) has been revolutionized by advances in immunotherapeutic and targeted agents. Therapeutic approaches to RCC in these categories have recently evolved to include immune checkpoint inhibitors, novel vascular endothelial growth factor receptor–targeting tyrosine kinase inhibitors, and combinations of those agents. Multiple regimens within each category have been approved for use in the first-line treatment of clear cell and non–clear cell RCC. However, few of these regimens have been directly compared, leading to a new clinical challenge for physicians: how to select a first-line treatment regimen for an individual patient from among multiple approved options. In the modern era of RCC management, the initial treatment selection therefore becomes highly personalized and depends on numerous patient-specific factors, including histopathologic and clinical features of the disease, comorbid conditions, and psychosocial and economic factors. This review details current first-line treatment options for the management of metastatic RCC and proposes a framework whereby treatment selection can be optimized for individual patients.

Although various demographic and psychosocial factors have been identified as correlates of influenza vaccine hesitancy, factors that promote infectious disease avoidance, such as disgust proneness, have been rarely examined. In two large national U.S. samples (Ns = 475 and 1007), we investigated whether disgust proneness was associated with retrospective accounts of influenza vaccine uptake, influenza vaccine hesitancy, and eventual influenza vaccine uptake, while accounting for demographics and personality. Across both studies, greater age, higher education, working in healthcare, and greater disgust proneness were significantly related to greater likelihood of previously receiving an influenza vaccine. In Study 2, which was a year-long longitudinal project, disgust proneness prospectively predicted influenza vaccine hesitancy and eventual vaccine uptake during the 2020-2021 influenza season. Findings from this project expand our understanding of individual-level factors associated with influenza vaccine hesitancy and uptake, highlighting a psychological factor to be targeted in vaccine hesitancy interventions.

Introduction: Global surgical care is increasingly recognized in the global health agenda and requires multidisciplinary engagement. Despite high interest among medical students, residents and other learners, many surgical faculty and health experts remain uniformed about global surgical care. Methods: We have operated an interdisciplinary graduate-level course in Global Surgical Care based on didactics and interactive group learning. Students completed a pre- and post-course survey regarding their learning experiences and results were analyzed using the Wilcoxon signed-rank test. Results: Fourteen students completed the pre-course survey, and 11 completed the post-course survey. Eleven students (79%) were enrolled in a Master’s degree program in global health, with eight students (57%) planning to attend medical school. The median ranking of surgery on the global health agenda was fifth at the beginning of the course and third at the conclusion (p = 0.11). Non-infectious disease priorities tended to stay the same or increase in rank from pre- to post-course. Infectious disease priorities tended to decrease in rank (HIV/AIDS, p = 0.07; malaria, p = 0.02; neglected infectious disease, p = 0.3). Students reported that their understanding of global health (p = 0.03), global surgery (p = 0.001) and challenges faced by the underserved (p = 0.03) improved during the course. When asked if surgery was an indispensable part of healthcare, before the course 64% of students strongly agreed, while after the course 91% of students strongly agreed (p = 0.3). Students reported that the interactive nature of the course strengthened their skills in collaborative problem-solving. Conclusions: We describe an interdisciplinary global surgery course that integrates didactics with team-based projects. Students appeared to learn core topics and held a different view of global surgery after the course. Similar courses in global surgery can educate clinicians and other stakeholders about strategies for building healthy surgical systems worldwide.

Background Significant limitations in pediatric surgical capacity exist in low- and middle-income countries, especially in rural regions. Recent global children’s surgical guidelines suggest training and support of general surgeons in rural regional hospitals as an effective approach to increasing pediatric surgical capacity. Methods Two years of a prospective clinical database of children’s surgery admissions at 2 regional referral hospitals in Uganda were reviewed. Primary outcomes included case volume and clinical outcomes of children at each hospital. Additionally, the disability-adjusted life-years averted by delivery of pediatric surgical services at these hospitals were calculated. Using a value of statistical life calculation, we also estimated the economic benefit of the pediatric surgical care currently being delivered. Results From 2016 to 2019, more than 300 surgical procedures were performed at each hospital per year. The majority of cases were standard general surgery cases including hernia repairs and intussusception as well as procedures for surgical infections and trauma. In-hospital mortality was 2.4% in Soroti and 1% in Lacor. Pediatric surgical capacity at these hospitals resulted in over 12,400 disability-adjusted life-years averted/year. This represents an estimated economic benefit of 10.2 million US dollars/year to the Ugandan society. Conclusion This investigation demonstrates that lifesaving pediatric procedures are safely performed by general surgeons in Uganda. General surgeons who perform pediatric surgery significantly increase surgical access to rural regions of the country and add a large economic benefit to Ugandan society. Overall, the results of the study support increasing pediatric surgical capacity in rural areas of low- and middle-income countries through support and training of general surgeons and anesthesia providers.