Browsing by Subject "Global health"

Traumatic brain injury (TBI) is the most common cause of death and disability globally. TBI is a leading cause of resource consumption and disproportionately affects LMICs. Innovative solutions are required to address this high burden of TBI. Prognostic models could provide a solution since the models enhance diagnostic ability of physicians, thereby helping to tailor treatments more effectively. This study aims to evaluate the feasibility of a prognostic model developed in Tanzania for TBI patients amongst Kilimanjaro Christian Medical Center (KCMC) healthcare providers and Duke affiliated healthcare providers. Duke health system participants were included primarily to gain insight from a different context with more established practices to inform the TBI tool implementation strategy at KCMC. To evaluate the feasibility of integrating the TBI tool into potential workflows co-design interviews were conducted with emergency physicians and nursing staff. Qualitatively, the tool was assessed using human centered design (HCD) techniques. Our research design methods were created using the Consolidated Framework for Implementation Research which considers overarching characteristics of successful implementation to contribute to theory development and verification of implementation strategies across multiple contexts. Findings of this study will aid in determining under what conditions a TBI prognostic model intervention will work at KCMC and the potential use of HCD in implementation research.

Drug-resistant tuberculosis (DR-TB) is a threat to TB control globally. South Africa has the third highest epidemic of DR-TB – following only Russia and China, two much more populous countries. South Africa has stringent guidelines for treating DR-TB; however, little is known about adherence to these guidelines. Additionally, little is known about age appropriate treatment, particularly in youth (13-24 years) who may have differing needs than adults with DR-TB. South Africa also has the world’s largest HIV epidemic – nearly 18% of the population is infected with HIV. Individuals with HIV are 26 to 31 times more likely to become infected with TB than individuals without HIV. Among individuals in South Africa with TB, there is a 57-68% HIV coinfection rate.

This dissertation includes a systematic literature review (Chapter 2) exploring barriers to TB treatment initiation in sub-Saharan Africa with an emphasis on children and youth. Additionally, time to treatment was assessed per South African guidelines (i.e. initiating treatment within five days of diagnosis) and total days from DR-TB diagnosis to DR-TB treatment initiation. This analysis included multi-level modeling with fixed patient- (sex, history of TB, HIV coinfection) and system-characteristics (urban-rural location, province) and random effects of treatment site. Guidelines were further evaluated, by assessing through descriptive statistics and logistic regression, receipt of guideline recommended care in terms of correct medications prescribed, correct dosage prescribed, and correct frequency prescribed at treatment initiation (correct regimen).

Barriers exist for all individuals with TB to initiate treatment regardless of age. These barriers are at the patient- and system-level and include: costs, health seeking behaviors, and infrastructure. More research is needed to identify barriers specifically among children and youth, as only four articles reviewed focused on these vulnerable populations. The time to DR-TB treatment is delayed for 84% of South Africans, and age did not predict delays. Seventeen percent of individuals coinfected with HIV receive care per guidelines compared to 12% of those without coinfection. Additionally, receipt of correct medications was prescribed to 88% of patients, yet only 33% received correct medications and doses, and still, only 30% received the full correct regimen. Age was not a strong predictor for receipt of correct guideline based treatment. In conclusion, more research must be focused on younger individuals with TB, particularly DR-TB. More research investigating guideline recommended care is essential to improve patient outcomes, prevent the transmission of DR-TB in communities, and to prevent further drug resistance.

The prevalence of hyperlipidemia, along with other non-communicable diseases, is on the rise in low- and middle-income countries. Given the resource-limited setting, a myriad of diagnostic challenges exist with traditional laboratory-based lipid tests, including mobility, timeliness, and laboratory infrastructure. Novel technology in the form of "point of care" devices seeks to overcome such barriers by providing immediate results without dependency on significant laboratory infrastructure. CardioChek PA (Polymer Technology Systems, Inc., Indianapolis, United States) is a point of care lipid measuring device and is readily available in Kenya. However, it has not been validated in this setting. In this study, I assess the accuracy of CardioChek PA with respect to standard laboratory-based testing, which is currently the gold standard.

In Webuye, Kenya, two blood samples were collected from 246 subjects to simultaneously measure the lipid levels via both CardioChek PA and the gold standard. All subjects were adults, and geographic stratified sampling methods were applied. Statistical analysis of the novel device's accuracy was based on percent bias, which is the standardized approach established by the National Cholesterol Education Program (NCEP) of the National Institute of Health (NIH). The NCEP suggests that percent bias be ≤±3% for low-density lipoprotein (LDL) cholesterol, ≤±5% for high-density lipoprotein (HDL) cholesterol, ≤±5% for total cholesterol (TC), and ≤±4% for triglycerides (TG). Misclassification rates and absolute percent bias were also analyzed.

This study found the CardioChek PA analyzer to be substantially inaccurate for LDL cholesterol (-25.9% bias), HDL cholesterol (-8.2% bias), and TC (-15.9% bias). For TG, the CardioChek PA performed well with a percent bias of 0.03%. However, the TG absolute percent bias (27.7%) and proportion of patients outside of the NCEP range (85%) reflected substantial inaccuracy of measurements. Moreover, those patients at higher risk of complications from hyperlipidemia were most likely to be misclassified into a lower risk category. Thus, we conclude that CardioChek PA is inaccurate and not suitable for our clinical setting. Furthermore, the findings highlight the need to validate new diagnostic tools in the appropriate setting prior to scale up regardless of its potential for novel utility.

Cervical cancer is the fourth most common female cancer in the world, primarily caused by the human papillomavirus (HPV). It about 570, 000 women annually, killing more than half of those affected. Approximately 90% of cervical cancer mortality occurs in low- and middle- income countries and this number is expected to rise to 98% by 2030, furthering global disparities in health care. Even within high-income countries where cervical cancer incidence and mortality has decreased drastically - by over 70% over the last 50 years - regional and racial disparities in cervical cancer mortality continue to exist among people with limited access to health care. The drastic decrease in incidence and mortality among high-income countries can be primarily attributed to a multi-tiered screening and treatment approach.

The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends screening with the Papanicolau (Pap) smear/Cytology every 3 years from the age of 21-29 years. For women aged 30-65 years, HPV and Pap smear co-testing every 5 years, or HPV alone every 3 years is recommended. Positive results have a variety of follow up management recommendations. For a high-risk result, a Colposcopy-guided biopsy is performed to provide diagnostic conformation and classification of pre-cancer or cancer. Colposcopy involves application of contrast agents (3-5% acetic acid and/or Schillers iodine) onto the cervix. These sources of contrast produce changes in pre-cancerous lesions which are illuminated and magnified using a a colposcope. Biopsies (small pieces of tissue) are taken from the highlighted lesion regions and sent to a pathologist, which then informs treatment management.

This approach to screening, diagnosis and treatment, though highly effective, requires expensive equipment for cytology, colposcopy and histopathology analysis which may not be available in resource-limited settings. It also involves multiple visits for each tier with long wait times for results in between, leading to high rates of loss to follow-up among women.

Due to these limitations, the WHO recommends a screen-and-treat approach which involves a single visit with visual inspection of the cervix with the naked eye after application of acetic acid (VIA) followed by treatment with cryotherapy, which involves killing pre-cancerous cells with extremely low-temperatures or by LEEP for non-cryotherapy eligible women. Recently changes have been made to WHO guidelines recommending utilization of HPV screening in combination with or over the VIA test, where available followed by treatment. However due to limitations in cost and time to attain results associated with HPV tests, VIA is still recommended and used in most resource-limited settings.

VIA on its own is however not an appropriate measure due to lack of sensitivity, from visualizing cervix changes with the naked eye, lack of specificity associated with features which might also be seen in benign lesions and in other cervical trauma and inter-provider variability. Additionally, the lack of documentation with VIA limits quality control and opportunities for training. Finally, the speculum used not only in VIA but in all aspects of screening has been demonstrated as a barrier and associated with pain/discomfort, vulnerability and fear.

The goal of this work is to overcome these barriers using three main aims (1) develop a portable, low-cost cervix imaging device, the Callascope, that can be used without the speculum and potentially enable self-imaging for cervical cancer screening. (2) Validate the device through clinical studies and in-depth interviews, to determine feasibility of visualizing the cervix with a provider and by the patient, and (3) develop algorithms for automated classification of pre-cancer to reduce inaccuracies and inter-provider variability.

For aim 1, different designs were explored for an introducer which would replace the speculum, using 3D computer-aided design (CAD) software, and mechanical testing simulations were performed on each. Designs were rapidly prototyped and tested using a custom vaginal phantom across a range of vaginal pressures and uterine tilts to select an optimal design. Two final designs were tested on fifteen volunteers to assess cervix visualization, comfort and usability as compared to the speculum and the optimal design, a curved-tip inserter, was selected for subsequent use. Additionally, a smaller version of the Pocket Colposcope, a low-cost imaging device with image quality on par with higher end colposcope, was developed to accommodate the introducer and enable use without the speculum. Image quality assessment was performed to compare the smaller 2MP Pocket Colposcope, referred to as the Callascope to that of the original 5 MP Pocket Colposcope.

The final introducer device has a slim tubular body with a funnel-like curved tip measuring approximately 2.5-2.8 cm in diameter. The introducer has a channel through which the Callascope, a 2 megapixel (MP) mini camera with LED illumination fits to enable image capture. Mechanical finite element testing simulations with an applied pressure of 15 cm H2O indicated a high factor of safety (90.9) for the inserter. Testing of the device with a custom vaginal phantom, across a range of supine vaginal pressures and uterine tilts (retroverted, anteverted and sideverted), demonstrated image capture with a visual area comparable to that of the speculum for a normal/axial positioned uteri and significantly better than that of the speculum for anteverted and sideverted uteri (p<0.00001). A channel enabling application of liquid contrasts (Acetic acid or Lugol’s iodine) by spraying was developed and tested for ability to cover spray targets. Image quality testing with resolution and color targets demonstrated comparable image quality at low magnification.

For aim 2, 3 main clinical studies were conducted to assess the feasibility of the device as well as various in-depth interviews to understand attitudes towards the Callascope and acceptability for self-screening. For the clinical studies, a pilot was first conducted with fifteen volunteers through physician-assisted insertion to assess cervix visualization, comfort and usability as well as to optimize the design. Results showed adequate cervix visualization for 83% of patients. In addition, questionnaire responses from volunteers indicated a 92.3% overall preference for the inserter over the speculum and all indicated that the inserter was more comfortable than the speculum.

This was followed by a clinical study in which a physician imaged the cervix of patients using both the speculum and Callascope in a 2×2 crossover design for n=28 patients. The clinical study data indicated that the Callascope enabled similar visualization compared to the speculum while significantly improving patient experience. With physician insertion and manipulation, the Callascope enabled cervix visualization for 82% of the participants.

The third study involved a feasibility study with 12 volunteers for home-based self-cervix imaging with the Callascope. Eighty-three percent of participants were able to visualize their cervix with the Callascope on the first try and 100% after multiple attempts.

Finally, a clinical study on a small cohort of women was used to test the contrast application on the cervix. These studies indicated sufficient contrast application coverage over the entire cervix using 2ml of liquid in a 10ml syringe.

In-depth interviews were conducted in Durham to assess women’s knowledge about reproductive health, cervical cancer screening and attitudes towards the speculum and the Callascope. Themes from the interviews showed high lack of knowledge about cervical cancer screening, unfavorable attitudes towards the speculum examination procedure and overall preference for the Callascope over the speculum-based exam.

For the third aim, I developed a series of methods and algorithms for automated analysis of cervigrams (colposcopy images of the cervix) with various contrasts and a combination of the contrasts. First, I developed algorithms to pre-process pathology-labeled cervigrams and to extract simple but powerful color and textural-based features. The features were used to train a support vector machine model to classify cervigrams based on corresponding pathology for visual inspection with acetic acid (VIA), visual inspection with Lugol’s iodine (VILI), green illumination vascular imaging (GIVI) and various combination of these contrasts. The initial framework built on VIA and VILI achieved a sensitivity, specificity, and accuracy of 81.3%, 78.6%, and 80.0%, respectively when used to distinguish cervical intraepithelial neoplasia (CIN+) relative to normal and benign tissues. This is superior to the average values achieved by expert physicians on the same data set for discriminating normal/benign from CIN+ (sensitivity=77%, specificity=51%, accuracy=63%). For next steps, the methods used were extrapolated to a larger data set and results for VIA only, VIA+GIVI, VIA+VILI, and VIA+VILI+GIVI were explored. With additional contrast, diagnostic accuracy was increased. The results suggest that utilizing simple color- and textural-based features from VIA, VILI and GIVI images may provide unbiased automation of cervigrams, and that combining contrasts improved on only VIA use. This would enable automated expert-level diagnosis of cervical pre-cancer at the point-of-care.

Although two-thirds of the global cancer mortality burden is predicted to occur in low- and middle-income countries (LMICs), citizens of these countries have disproportionately less access to resources and facilities to provide effective care. Surgery, radiation therapy, and chemotherapy form the foundation of effective cancer care in high-income countries (HICs), but these modalities are largely unavailable in LMICs. Stemming from this disparity, long-term cancer survival rates are lower, and the mortality-to-incidence ratio is higher in LMICs. With limited healthcare spending and a large portion of expenditures out-of-pocket, non-communicable diseases such as cancer lead to financial catastrophe for millions of families annually and are a barrier to global development. To expand global access to cancer care and buttress the anti-cancer capabilities of overextended healthcare systems in LMICs, it is necessary to develop a therapy compatible with the constraints imposed by resource-limited settings.

To accomplish this goal, the work presented here describes a low-cost injectable ablative therapy suitable for widespread use in LMICs. This therapy is a modification of an existing technique entailing intratumoral injection of ethanol to induce necrosis of malignant cells (termed “ethanol ablation”) utilized to reduce tumor volume with either curative or palliative intent. Modifications are based on analysis of the mechanics of the injection process and entail the incorporation of the water-insoluble, ethanol-soluble polymer ethyl cellulose and reduction of the infusion rate and volume. Ethanol ablation is one of the original forms of tumor ablation, treatments in which the tumor microenvironment is altered via chemical or thermal means to destroy malignant tissue, and has achieved widespread clinical success in HICs. It is appealing for use in LMICs because it is low-cost, portable, electricity-independent, and minimally invasive. However, injected ethanol is highly pressurized and forms cracks within tissue leading to excessive leakage and an unpredictable distribution of injected ethanol, poor tumor coverage, and damage to adjacent organs. With the recognition of pressure-induced crack formation as a source of leakage, reducing the infusion rate and volume will improve localization. Further, the incorporation of ethyl cellulose is likely to reduce leakage because it forms a gel upon exposure to the aqueous tissue environment and reduces the permeability of fractured tissue. These innovations are poised to improve upon ethanol ablation while retaining its suitability for use in resource-limited settings.

Three specific aims were proposed to establish crack formation as a limiting factor for efficacy of ethanol ablation, characterize this novel tumor ablation technique and develop a framework for tailoring treatment protocols to specific lesion types and sizes. The first aim described the rheological properties of ethyl cellulose-ethanol and the gelling behavior upon exposure to water and found that reducing the infusion rate and incorporating ethyl cellulose decreased leakage in tissue-mimicking surrogates and improved ablative efficacy in chemically induced squamous cell carcinoma tumors in the hamster oral cavity. The viscosity of ethyl cellulose-ethanol solutions increases with the ethyl cellulose concentration, which has been found to improve localization of injected solutions. Further, as expected from a water-insoluble polymer, gel formation increases with higher ethyl cellulose concentrations and higher water-to-ethanol ratios as well. These findings motivate the use of higher ethyl cellulose concentrations and low infusion volumes, and indicate that gel forms upon injection as water diffuses into and ethanol diffuses away from the injection site.

Tissue-mimicking surrogates composed of agarose were utilized because they are transparent and poroelastic. This makes visualization of injected ethanol feasible in a material that replicates the dynamics of tissue’s mechanical response to infusion. In these surrogates, ethyl cellulose was demonstrated to reduce leakage and increase the distribution volume of injected ethanol, but only at moderate infusion rates. At infusion rates typically used in conventional ethanol ablation (approximately 100 mL/hr), excessive leakage was observed for pure ethanol and ethyl cellulose-ethanol alike. This result, taken in context with the established linear relationship between infusion pressure and rate, suggests that reducing the infusion rate is necessary to localize injected ethanol in addition to incorporating ethyl cellulose.

To demonstrate proof-of-concept of improved therapeutic efficacy, chemically induced oral squamous cell carcinoma tumors in the hamster oral cavity were utilized as they are similar to human primary tumors. Further, since they protrude from the surface of the oral cavity and injected fluid is not confined by adjacent tissue, they are susceptible to leakage and more difficult to treat. To evaluate conventional ethanol ablation in this model, high-rate (100 mL/hr) infusions were performed with an infusion volume 4x greater than the tumor volume. This protocol led to regression of only 4 of 13 treated tumors. However, with the reduction of the infusion rate to 10 mL/hr and infusion volume to a quarter of tumor volume, and the incorporation ethyl cellulose, 7 of 7 tumors regressed completely. In the absence of ethyl cellulose, reduction of infusion rate and volume led to regression of 0 of 5 tumors.

With the characterization of ethyl cellulose-ethanol and demonstration of proof-of-concept in Aim 1, the objective of Aim 2 was to investigate the role of infusion pressure in the mechanics of crack formation, as well as of ethyl cellulose in preventing leakage. Pressure-induced crack formation has been described to occur at a material-inherent critical pressure dictated by the fracture toughness and elasticity and can be quantified as the maximum pressure achieved during the infusion of air. In this aim, transparent tissue-mimicking surrogates were fabricated to match the critical pressure of ex vivo swine liver. To determine the relevance of the critical pressure, infusions were performed with two contrast agents dissolved in ethanol– one smaller than the surrogate pore size (fluorescein) and one larger (graphite). When the agarose pore structure was unfractured, only fluorescein was visible. After it was fractured, both contrast agents were visible. Using this system, fracture was observed to occur at the critical pressure and a modified technique to detect fractures via infusion pressure was established. While previous studies have demonstrated that fracture can be observed during the infusion, this is only possible with low-viscosity fluids unlike ethyl cellulose-ethanol. In these studies, it was demonstrated that unfractured agarose retains an elevated post-infusion pressure, but fractured agarose allows the pressure to dissipate rapidly. This result allows for non-invasive detection of crack formation in tissue during infusion of viscous fluids.

In ex vivo swine liver, as was the case in tissue-mimicking surrogates, crack formation was detected when the critical pressure was exceeded and increased leakage. In these studies, the injected ethanol distribution was determined by adding fluorescein to the injection solution, freezing tissue after the infusion, sectioning it, and imaging with a fluorescent microscope. Since the infusion pressure increases with rate and volume, this finding motivates the use of low rates and volumes when possible to improve localization. For low-volume infusions in which the pressure remained below the critical pressure, there was minimal leakage. While leakage, and the infusion pressure, increased with infusion rate (from 1 to 10 mL/hr) for pure ethanol, it did not increase for 6% ethyl cellulose-ethanol. The gel formation behavior of ethyl cellulose reduces leakage in the presence of infusion-induced cracks.

Having established proof-of-concept of ethyl cellulose-ethanol and its mechanism of action in localizing injected ethanol, the focus of Aim 3 was to characterize computed tomography (CT) imaging as rapid, non-destructive method to visualize injected ethanol, optimize the ethyl cellulose concentration, and investigate the relationship between the injected ethanol distribution and resultant extent of induced necrosis. Since ethanol is less attenuating of x-rays than water or tissue, it is readily visible with CT imaging. However, the accuracy of extraction of ethanol concentration from CT imaging has not yet been established. Utilizing ethanol-water mixtures as in vitro surrogates, the random and systematic components of measurement error were quantified, with the combined error defined as the root sum square of both components. The random error component arises from the variance of the radiodensity of a solution of fixed concentration. The systematic error component was quantified as the difference between the predicted and true radiodensity of ethanol-water mixtures, with the predicted value determined by a linear two-point calibration equation with pure water and ethanol at the extremes. The total measurement error was 13.4% with both components contributing approximately equal amounts. This error is low enough to confidently delineate between treated and untreated tissue.

Having established the utility of CT imaging to quantify the ethanol distribution volume, the ethyl cellulose concentration was optimized in ex vivo rat liver tissue submerged in buffer over a wider range of concentrations than has been feasible in previous models. The optimal ethyl cellulose concentration was defined as the formulation that maximized the volume of tissue infiltrated with a cytotoxic (> 20%) ethanol concentration. In these studies, 12% ethyl cellulose maximized the ethanol distribution volume by 8-fold in comparison to pure ethanol. It also led to the most spherical distributions as defined by the aspect ratio quantified as the ratio of the radius of gyration to the effective radius. These results were confirmed in in vivo rat liver in which 12% ethyl cellulose-ethanol yielded a distribution volume 3-times greater than pure ethanol.

In addition to improving localization of injected ethanol, 12% ethyl cellulose increased the extent of induced necrosis by 6-times in comparison to pure ethanol. Necrosis was quantified by excising treated tissue 24 hours post-ablation, cryopreserving, sectioning, and staining it with NADH-diaphorase. There was an approximate one-to-one equivalence of the ethanol distribution volume with the necrotic volume for 12% ethyl cellulose-ethanol. This validates the concentration-based thresholding strategy utilized to determine the ethanol distribution volume and confirms the utility of CT imaging. CT imaging is particularly appealing to assess the morphology of the ablative extent as three-dimensional reconstruction of the ablative extent from pathology is challenging. The equivalence between the distribution volume visualized with CT imaging and necrotic volume determined via pathology motivates further use of CT imaging in optimization of the ablation parameters. Pure ethanol had a necrotic volume of nearly half of the injected ethanol volume. While the comparison of this relationship between pure ethanol and 12% ethyl cellulose-ethanol was not statistically significant, it is indicative of prolonged exposure time achieved by ethyl cellulose that may be caused by delayed vascular clearance in vivo. This aim establishes CT imaging with concentration-based thresholding as a non-destructive, high-throughput method to optimize ablation parameters and tailor treatment to specific lesion types and sizes.

In conclusion, the objective of this work was to establish ethyl cellulose-ethanol ablation as an effective tumor ablation technique suitable for use in resource-limited settings with the goal of expanding global access to cancer treatment. In pursuit of this goal, aim 1 assessed the rheological and gelling behavior of ethyl cellulose-ethanol, established improved localization, and demonstrated proof-of-concept in treatment of chemically induced oral tumors. Aim 2 investigated the relationship between crack formation and infusion pressure, adapted an established model to detect crack formation by demonstrating that post-infusion pressure dissipation is characteristic of fractured tissue, and found that ethyl cellulose decreases leakage when cracks do form. Finally, aim 3 characterized the ethanol concentration measurement accuracy of CT imaging, optimized the ethyl cellulose concentration, and investigated the relationship between ethanol distribution volume and the resultant extent of induced necrosis. Ultimately, this work demonstrates that ethyl cellulose reduces leakage associated with ethanol ablation, improves therapeutic efficacy, and establishes a methodology for further optimization and to tailor treatment for specific applications.

Background: Universal healthcare has been promoted by organizations including the World Health Organization and United Nations as a means of ensuring healthcare access for vulnerable populations. Despite momentum towards universal healthcare, especially among Southeast Asian nations, little research has been conducted to understand healthcare equity in nations that have already implemented universal healthcare. This paper assesses equity in healthcare access in Brunei Darussalam using results from the Brunei Darussalam Health System Survey (HSS).

Methods: Data were gathered using a nationally-representative survey of 1,197 households across four districts in Brunei Darussalam. The Health System Survey aimed to measure individual's expectations and utilization of the Brunei national healthcare system. Data were analyzed using descriptive statistics and multinomial logistic regression to identify respondent- and household-level characteristics that affect healthcare utilization and expenditures.

Results: HSS data suggest that healthcare utilization in Brunei varies by ethnicity, district of residence, health status, and income. When compared to other ethnic groups, Chinese households were significantly less likely to utilize public healthcare and significantly more likely to utilize private healthcare services. Indigenous groups also demonstrated significantly lower rates of private healthcare utilization compared to other ethnicities. Temburong district had the lowest rates of both private and public healthcare utilization and was associated with a 2.67 decreased likelihood of using public healthcare in the past six months. When stratifying for health status, data indicate that healthcare utilization in Brunei is proportional to healthcare need, with 93 percent of respondents in poor health reporting using government hospitals 12 or more times in the past six months compared to 76 percent of respondents in excellent health reporting using healthcare only once in the past six months. Income was also found to be positively associated with increased healthcare expenditures and private healthcare use.

Conclusion: This study highlights an example of a universal healthcare system in Southeast Asia and indicates that a well-funded universal healthcare system can reduce significant utilization disparities. Substantial financial resources do not, however, guarantee equity among rural and minority populations and universal healthcare efforts should incorporate measures to understand and address barriers to healthcare among these groups.

Cervical cancer disproportionately burdens women in low-resource settings, with over 85% of cervical cancer deaths occurring in developing countries due to lack of access to effective, high-quality screening programs that facilitate early detection and treatment. The aim of this study is to evaluate whether the performance of a transvaginal digital colposcope (TVDC) developed at Duke University is equivalent to the more expensive standard-of-care colposcope at identifying precancerous lesions of the cervix. Thirty-five paired cervix images, with confirmed pathologies and blinded by device, were sent electronically to six physicians, at four separate institutions, Duke University Medical Center (Durham, North Carolina, USA), La Liga Peruana de Lucha Contra el Cancer (Lima, Peru), Cancer Institute WIA (Chennai, India), and Kenyatta University (Nairobi, Kenya). Physicians completed a 1-page survey assessing cervix characteristics and overall severity of precancerous lesions for each image. Analysis included percent agreement between devices as well as identifying patterns across misdiagnosed images. The agreement between physicians using each device is 80.1% with kappa of 0.6049. The TVDC performed equivalent to standard-of-care colposcopy at identifying precancerous lesions of the cervix. Implications of these findings have the potential to create increased access to a culturally appropriate screening technology, thus reducing the burden of cervical cancer throughout the developing world.

Background: Globally, there is often a gap between medical need and access to care, and this is particularly true for surgical care for children. In Guatemala, for instance, families frequently pursue care outside of the government health system. Using a structured anthropologic approach, we sought to explore the barriers to surgical care for children in Guatemala, suspecting both financial and cultural barriers were the primary obstacles families had to face.

Study design: Twenty-nine parents/guardians of children receiving surgical care at two non-governmental organizations (NGOs) in Guatemala and 7 health care providers participated in semi-structured interviews to explore what they believed to be the impediments to care. Transcripts were analyzed using a grounded theory approach. Current models for barriers to care were critiqued and a novel Framework for Barriers to Pediatric Surgery in Guatemala (FBPSG) was developed, which highlights both the existence, and centrality, of fear and mistrust in families' experience.

Results: Families and providers identified financial costs, geography, and systems limitations as the primary barriers to care. Mistrust and fear were also voiced. In addition, health literacy and cultural issues were also thought to be relevant by providers.

Conclusions: Due to biases inherent in this sample, parents/guardians did not necessarily report the same perceived barriers as healthcare providers - e.g., education/health literacy and language - and may have represented a "best case" scenario compared to more disadvantaged populations in this specific Central American context. Nonetheless, financial concerns were some of the most salient barriers for families seeking pediatric surgical care in Guatemala, with systems limitations (waiting time) and geographic factors (distance/transit) also being highlighted. Fear and mistrust were found to be deeper barriers to care and warrant reevaluation of organizational heuristics to date. NGOs can address these worries by working with individuals and organizations already known by and trusted in target communities and by providing good quality medical treatment and interpersonal care.

Background: Outbreaks of infectious diseases such as Ebola have dramatic economic impacts on affected nations due to significant direct costs and indirect costs, as well as increased expenditure by the government to meet the health and security crisis. Despite its dense population, Nigeria was able to contain the outbreak swiftly and was declared Ebola free on 13th October 2014. Although Nigeria’s Ebola containment success was multifaceted, the private sector played a key role in Nigeria’s fight against Ebola. An epidemic of a disease like Ebola, not only consumes health resources but also detrimentally disrupts trade and travel to impact both public and private sector resulting in the ‘fearonomic’ effect of the contagion. In this thesis, I have defined ‘fearonomics’ or the ‘fearonomic effects’ of a disease as the intangible and intangible economic effects of both informed and misinformed aversion behavior exhibited by individuals, organizations, or countries during an outbreak. During an infectious disease outbreak, there is a significant potential for public-private sector collaborations that can help offset some of the government’s cost of controlling the epidemic.

Objective: The main objective of this study is to understand the ‘fearonomics’ of Ebola in Nigeria and to evaluate the role of the key private sector stakeholders in Nigeria’s Ebola response.

Methods: This retrospective qualitative study was conducted in Nigeria and utilizes grounded theory to look across different economic sectors in Nigeria to understand the impact of Ebola on Nigeria’s private sector and how it dealt with the various challenges posed by the disease and its ‘fearonomic effects'.

Results: Due to swift containment of Ebola in Nigeria, the economic impact of the disease was limited especially in comparison to the other Ebola-infected countries such as Liberia, Sierra Leone, and Guinea. However, the 2014 Ebola outbreak had more than a just direct impact on the country’s economy and despite the swift containment, no economic sector was immune to the disease’s fearonomic impact. The potential scale of the fearonomic impact of a disease like Ebola was one of the key motivators for the private sector engagement in the Ebola response.

The private sector in Nigeria played an essential role in facilitating the country’s response to Ebola. The private sector not only provided in-cash donations but significant in-kind support to both the Federal and State governments during the outbreak. Swift establishment of an Ebola Emergency Operation Centre (EEOC) was essential to the country’s response and was greatly facilitated by the private sector, showcasing the crucial role of private sector in the initial phase of an outbreak. The private sector contributed to Nigeria’s fight against Ebola not only by donating material assets but by continuing operations and partaking in knowledge sharing and advocacy. Some sector such as the private health sector, telecom sector, financial sector, oil and gas sector played a unique role in orchestrating the Nigerian Ebola response and were among the first movers during the outbreak.

This paper utilizes the lessons from Nigeria’s containment of Ebola to highlight the potential of public-private partnerships in preparedness, response, and recovery during an outbreak.

Despite the clear benefits to women, families, and society, family planning is not universal. In 2015,12 percent of married or in-union women who want to prevent or delay pregnancy were are not currently using a method of family planning in 2015. In Africa, this rate is even higher, at 24 percent. In order to meet the unmet need for family planning, new approaches to service delivery are required. A critical question for anyone interested in ensuring universal access to sexual and reproductive health-care services like family planning is how to create new products, services and implementation models that work for users. The objective of this case study is to describe how Human Centered Design (HCD) was used to develop a digital marketplace for family planning in Kenya, called Nivi, and draw lessons for broader application to global health challenges. By using the HCD approach, we sought to better understand the challenges users face with the Nivi platform and the opportunities that exist to make improvements. By incorporating HCD, we were able to build a service with greater potential for use and usability for Nivi users. We believe that taking an HCD approach allowed us to build a product that has the potential to meet the unmet need for family planning services in Kenya. This case study highlights the strengths and challenges to inform the use of HCD for other health applications in emerging markets.