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PURPOSE The CDC's National Program of Cancer Registries has expanded the use of electronic reporting to collect more timely information on newly diagnosed cancers. The adoption, implementation, and use of electronic reporting vary significantly among central cancer registries. We identify factors affecting the adoption of electronic reporting among these registries. METHODS Directors and data managers of nine National Program of Cancer Registries took part in separate 1-hour telephone interviews in early 2019. Directors were asked about their registry's key data quality goals; staffing, resources, and tools used to aid processes; their definition and self-perception of electronic reporting adoption; key helpers and challenges; and cost and sustainability implications for adoption of electronic reporting. Data managers were asked about specific data collection processes, software applications, electronic reporting adoption and self-perception, information technology infrastructure, and helpers and challenges to data collection and processing, data quality, and sustainability of approach. RESULTS Larger registries identified organizational capacity and technical expertise as key aides. Other help for implementing electronic reporting processes came from partnerships, funding availability, management support, legislation, and access to an interstate data exchange. Common challenges among lower adopters included lack of capacity at both registry and data source levels, insufficient staffing, and a lack of information technology or technical support. Other challenges consisted of automation and interoperability of software, volume of cases received, state political environment, and quality of data received. CONCLUSION Feedback from the formative evaluation yielded several useful solutions that can guide implementation of electronic reporting and help refine the technical assistance provided to registries. Our findings may help guide future process and economic evaluations of electronic reporting and identify best practices to strengthen registry operations.

Background The high prevalence of HIV among adolescent girls and young women aged 15–24 in Eastern and Southern Africa indicates a substantial need for accessible HIV prevention and treatment services in this population. Amidst this need, Zambia has yet to meet global testing and treatment targets among adolescent girls and young women living with HIV. Increasing access to timely, high-quality HIV services in this population requires addressing the intensified anticipated and experienced stigma that adolescent girls and young women often face when seeking HIV care, particularly stigma in the health facility setting. To better understand the multi-level drivers and manifestations of health facility stigma, we explored health workers’ perceptions of clinic- and community-level stigma against adolescent girls and young women seeking sexual and reproductive health, including HIV, services in Lusaka, Zambia. Methods We conducted 18 in-depth interviews in August 2020 with clinical and non-clinical health workers across six health facilities in urban and peri-urban Lusaka. Data were coded in Dedoose and thematically analyzed. Results Health workers reported observing manifestations of stigma driven by attitudes, awareness, and institutional environment. Clinic-level stigma often mirrored community-level stigma. Health workers clearly described the negative impacts of stigma for adolescent girls and young women and seemed to generally express a desire to avoid stigmatization. Despite this lack of intent to stigmatize, results suggest that community influence perpetuates a lingering presence of stigma, although often unrecognized and unintended, in health workers and clinics. Conclusions These findings demonstrate the overlap in health workers’ clinic and community roles and suggest the need for multi-level stigma-reduction approaches that address the influence of community norms on health facility stigma. Stigma-reduction interventions should aim to move beyond fostering basic knowledge about stigma to encouraging critical thinking about internal beliefs and community influence and how these may manifest, often unconsciously, in service delivery to adolescent girls and young women.

Research Objective: The objective of this study was to evaluate the insurance, employment, and financial experiences of young (age ≤ 39 years) female breast cancer patients and assess factors associated with any changes in their financial situation. Previous literature has shown that younger women are more likely to be diagnosed with late-stage disease that requires more-intensive treatments, while significant medical expenditures, productivity losses, financial hardship, and changes in employment and work productivity have been found in patients of all ages. Methods: A sample of women who were diagnosed with breast cancer between the ages of 18 and 39 years and residing in the states of California, Florida, Georgia, and North Carolina were identified. The sample included women who were (1) diagnosed with ductal carcinoma in situ (D05.90; 8500/2) or invasive breast cancer (C50; 8500/3) between January 2013 and December 2014; (2) between the ages of 18 and 39 years at the time of diagnosis; and (3) alive at the time of data extraction. We contacted 3,659 women by mail; 2,927 were alive with deliverable addresses. Of those, 830 women returned completed surveys, yielding a response rate of 28.4%. The survey instrument included 66 questions on demographics, insurance status, employment history, out-of-pocket cost, and overall financial well-being. Multivariate analysis was used to identify factors associated with financial decline. Principal Findings: About half of the women (47.4%) reported that treatment expenditures were higher than anticipated, and almost two-thirds (65.3%) had not discussed treatment costs with their care team. Almost a third of the patients (31.8%) reported treatment nonadherence due to cost. Factors associated with not receiving recommended care included very young age ( Citation Format: Florence Tangka, Sujha Subramanian, Madeleine Jones, Patrick Edwards, Tim Flanigan, Jenya Kaganova, Kevin Smith, Cheryll Thomas, Nikki Hawkins, Temeika Fairley, Gery Guy, Juan Rodriguez. Insurance coverage, employment status, and financial wellbeing of young women diagnosed with breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-45.

Integrated service delivery, providing coordinated services in a convenient manner, is important in HIV prevention and treatment for adolescents as they have interconnected health care needs related to HIV care, sexual and reproductive health and disease prevention. This review aimed to (1) identify key components of adolescent-responsive integrated service delivery in low and middle-income countries, (2) describe projects that have implemented integrated models of HIV care for adolescents, and (3) develop action steps to support the implementation of sustainable integrated models. We developed an implementation science-informed conceptual framework for integrated delivery of HIV care to adolescents and applied the framework to summarize key data elements in ten studies or programs across seven countries. Key pillars of the framework included (1) the socioecological perspective, (2) community and health care system linkages, and (3) components of adolescent-focused care. The conceptual framework and action steps outlined can catalyze design, implementation, and optimization of HIV care for adolescents.

Lack of family involvement is barrier to antiretroviral therapy adherence among adolescent girls and young women (AGYW). This study assessed family support for AGYW's engagement along the HIV care continuum to inform the design of a family-focused intervention in Lusaka, Zambia. We conducted 16 in-depth interviews and four focus group discussions with 40 AGYW living with HIV. Three strategies were identified to strengthen family support. First, emotional and instrumental support are highly valued by AGYW and should be further developed or reinforced. Second, AGYW wanted more informational support and open discussion of HIV from family, and an intervention should aim to enhance these types of support. Third, existing appraisal support reinforced anticipated stigma among AGYW and discouraged disclosure, yet participants wished for more interactions with peers living with HIV. Appraisal support should therefore be reframed to help AGYW decide to whom they should disclose and how to do so safely.

PURPOSE: Breast cancer is the leading cause of cancer-related deaths in women younger than 40 years. We aim to evaluate cost as a barrier to care among female breast cancer patients diagnosed between 18 to 39 years. METHODS: In early 2017, we distributed a survey to women diagnosed with breast cancer between the ages of 18 and 39 years, as identified by the central cancer registries of California, Georgia, North Carolina, and Florida. We used multivariable statistics to explore cost-related barriers to receiving breast cancer care for the 830 women that completed the survey. RESULTS: About half of the women (47.4%) reported spending more on breast cancer care than expected, and almost two-thirds (65.3%) had not discussed costs with their care team. A third of the patients (31.8%) indicated forgoing care due to cost. Factors associated with not receiving anticipated care due to cost included age less than35 years at diagnosis, self-insurance, comorbid conditions, and late-stage diagnosis. CONCLUSION: Previous studies using breast cancer registry data have not included detailed insurance information and care received by young women. Young women with breast cancer frequently forgo breast cancer care due to cost. Our results highlight the potential for policies that facilitate optimal care for young breast cancer patients which could include the provision of comprehensive insurance coverage.

Large differences exist in the coverage and quality of cancer surveillance systems across the world, with limited data currently available from low-resource settings. Information on the resources required to register cancer cases are needed in order for global, national, regional, and local stakeholders to adequately support cancer registry operations. The objective of this study is to estimate the cost of cancer registration and report the cost per cancer incident case, the cost per inhabitant in the area covered by the registry, and cost allocated to specific registry activities. The International Registry Costing Tool (IntRegCosting Tool) of the Centers for Disease Control and Prevention was used to assess the costs and resources used by 4 registries in sub-Saharan Africa (Zimbabwe, Uganda, Kenya, and Seychelles). The cost of registering a cancer case ranged from $9 to $96, with lower costs in low- and middle-income countries than in the high-income country. The cost of cancer registration at the population level is very low, ranging from 1 to 17 cents per person. The detailed cost information provided in this manuscript can help registries in in sub-Saharan Africa understand the cost of their registry operations and identify approaches to improve efficiency to meet program priorities. Furthermore, it provides additional evidence to inform funding and resource allocation decisions to advance cancer registration in the region.

The economic burden of breast cancer for women under 50 in the United States remains largely unexplored, in part because young women make up a small proportion of breast cancer cases overall. To address this knowledge gap, we conducted a web-based survey to compare data from breast cancer survivors 18–39 years of age at first diagnosis and 40–49 years of age at first diagnosis. We administered a survey to a national convenience sample of 416 women who were 18–49 years of age at the time of their breast cancer diagnosis. We analyzed factors associated with financial decline using multivariate regression. Survivors 18–39 years of age at first diagnosis were more likely to report Stage II–IV breast cancer (P<0.01). They also quit their jobs more often (14.6%) than older survivors (4.4%; P<0.01) and faced more job performance issues (55.7% and 42.8%, respectively; P=0.02). For respondents in both groups, financial decline was more likely if the survivor had at least one comorbid condition (odds ratios: 2.36–3.21) or was diagnosed at Stage II–IV breast cancer (odds ratios: 2.04–3.51).

Background: The costs of cancer registration have previously been estimated for registries in the continental United States and many international registries; however, to date, there has been no economic assessment of population-based registries in the US-Affiliated Pacific Islands. This study estimates the costs and factors affecting the operations of US-Affiliated Pacific Island population-based cancer registries. Methods: The web-based International Registry Costing Tool1 was used to collect costs, resources used, cancer cases processed, and other registry characteristics from the Pacific Regional Central Cancer Registry (PRCCR), Federated States of Micronesia National Cancer Registry, and nine satellite jurisdictional registries within the US Pacific Islands. The registries provided data on costs for June 30, 2016–June 29, 2017, and cases processed during 2014. Results: Local host institutions provided a vital source of support for US-Affiliated Pacific Islands registries, covering substantial fixed costs, such as management and overhead. The cost per cancer case processed had an almost tenfold variation across registries, with the average total cost per case of about $1,413. The average cost per inhabitant in the US-Affiliated Pacific Islands was about $1.77 per person. Discussion: The challenges of collecting data from dispersed populations spread across multiple islands of the US-Affiliated Pacific Islands are likely leading factors driving the magnitude of the registries’ cost per case. The economic information from this study provides a valuable source of activity-based cost data that can both help guide cancer control initiatives and help registries improve operations and efficiency.

Purpose There is limited research linking data sources to evaluate the multifactorial impacts on the quality of treatment received and financial burden among young women with breast cancer. To address this gap and support future evaluation efforts, we examined the utility of combining patient survey and cancer registry data. Patient and Methods We administered a survey to women, aged 18–39 years, with breast cancer from four U.S. states. We conducted a systematic response-rate analysis and evaluated differences between racial groups. Survey responses were linked with cancer registry data to assess whether surveys could reliably supplement registry data. Results A total of 830 women completed the survey for a response rate of 28.4 %. Blacks and Asian/Pacific Islanders were half as likely to respond as white women. Concordance between survey and registry data was high for demographic variables (Cohen’s kappa [k]: 0.879 to 0.949), moderate to high for treatments received (k: 0.467 to 0.854), and low for hormone receptor status (k: 0.167 to 0.553). Survey items related to insurance status, employment, and symptoms revealed racial differences. Conclusion Cancer registry data, supplemented by patient surveys, can provide a broader understanding of the quality of care and financial impacts of breast cancer among young women.

BACKGROUND Among countries in sub-Saharan Africa, Zambia has one of the highest incidences of HIV. Adolescent girls and young women (AGYW) are a particularly affected group because of their social and economic vulnerability. OBJECTIVE The goal of this study is to test a multilevel package of interventions at the community and health system levels in Zambia in order to connect AGYW with a source of regular care, which will in turn allow for sustainable, successful implementation of regular HIV testing and adherence to antiretroviral treatment. METHODS We will adapt prior tools to create the SHIELD (Support for HIV Integrated Education, Linkages to Care, and Destigmatization) intervention to educate and empower Zambian AGYW of 10-24 years of age and their families and to create community-based youth clubs to foster peer support. We will also develop integrated wellness care clinics to offer a youth-friendly environment that provides tailored clinical services. We will perform formative research, including focus groups and in-depth interviews, among AGYW, caregivers, and stakeholders to help inform the development and tailoring of the interventions. A cluster-randomized controlled trial will be implemented in Lusaka, with six clinic catchment areas randomized into three groups: zones with integrated wellness care clinics and SHIELD intervention, zones with only SHIELD intervention, and control zones with no intervention. We will assess HIV testing among the HIV-negative or unknown (HIV-/u) cohort, and retention in care along with viral load suppression will be evaluated in the HIV-positive (HIV+) cohort. We will use in-depth interviews and surveys to collect staff and stakeholder feedback after the trial. Cost-effectiveness of the interventions and return-on-investment impacts will be quantified using a microsimulation model. RESULTS Interim results are expected in 2021, and the final results are expected in 2022. If this multilevel intervention is successful in establishing a comprehensive care continuum for HIV-affected AGYW, the Zambian Ministry of Health may advocate for expansion to additional settings to support national scale-up. CONCLUSIONS This integrated service delivery model can also be a platform to implement additional preventive services, so HIV-/u and HIV+ AGYW can receive comprehensive, integrated services. CLINICALTRIAL ClinicalTrials.gov NCT03995953; https://clinicaltrials.gov/ct2/show/NCT03995953

Background: The economic cost of breast cancer is a major personal and public health problem in the United States. This study aims to evaluate the insurance, employment, and financial experiences of young female breast cancer survivors and to assess factors associated with financial decline. Methods: We recruited 830 women under 40 years of age diagnosed with breast cancer between January 2013 and December 2014. The study population was identified through California, Florida, Georgia, and North Carolina population-based cancer registries. The cross-sectional survey was fielded in 2017 and included questions on demographics, insurance, employment, out-of-pocket costs, and financial well-being. We present descriptive statistics and multivariate analysis to assess factors associated with financial decline. Results: Although 92.5% of the respondents were continuously insured over the past 12 months, 9.5% paid a “higher price than expected” for coverage. Common concerns among the 73.4% of respondents who were employed at diagnosis included increased paid (55.1%) or unpaid (47.3%) time off, suffering job performance (23.2%), and staying at (30.2%) or avoiding changing (23.5%) jobs for health insurance purposes. Overall, 47.0% experienced financial decline due to treatment-related costs. Patients with some college education, multiple comorbidities, late stage diagnoses, and self-funded insurance were most vulnerable. Conclusions: The breast cancer diagnosis created financial hardship for half the respondents and led to myriad challenges in maintaining employment. Employment decisions were heavily influenced by the need to maintain health insurance coverage. Impact: This study finds that a breast cancer diagnosis in young women can result in employment disruption and financial decline.

Introduction Cancer registration is an important activity for informing cancer control activities. Cancer registries in Sub-Saharan Africa have limited resources to effectively operate because of competing priorities. To date, there has not been an assessment of the resources and funding needed to perform all the activities essential for cancer registration in Kenya. Evidence will help registries to quantify and advocate for the funds needed to sustain, enhance, and expand high quality cancer registration in Kenya. Methods In this study, we used the Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool ( IntRegCosting Tool ) to evaluate the funding, cost, and labor resources used to perform the cancer registry operations in Nairobi County for two annual periods between July 2012 and June 2014. Results Funding from grants, research studies, and international organizations provided 70% of the registry operations' cost. For both time periods, the most-costly registry activities were related to administration, management, and training, along with data acquisition activities such as data abstraction, entry, and validation. Even among these core registry activities, however, substantial variations existed. Conclusions Stable funding for cancer registry operations is necessary to sustain core registry activities in other to deliver high-quality data, which in turn is necessary to foster evidence-based policies to improve cancer outcomes. As stakeholders look into expanding the Nairobi Cancer Registry into a national program, the cost data provided in this study will help justify the funding required for sustaining and expanding registry activities.

The key aims of this study were to identify sources of support for cancer registry activities, to quantify resource use and estimate costs to operate registries in low- and middle-income countries (LMIC) at different stages of development across three continents.Using the Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool (IntRegCosting Tool), cost and resource use data were collected from eight population-based cancer registries, including one in a low-income country (Uganda [Kampala)]), two in lower to middle-income countries (Kenya [Nairobi] and India [Mumbai]), and five in an upper to middle-income country (Colombia [Pasto, Barranquilla, Bucaramanga, Manizales and Cali cancer registries]).Host institution contributions accounted for 30%-70% of total investment in cancer registry activities. Cancer registration involves substantial fixed cost and labor. Labor accounts for more than 50% of all expenditures across all registries. The cost per cancer case registered in low-income and lower-middle-income countries ranged from US $3.77 to US $15.62 (United States dollars). In Colombia, an upper to middle-income country, the cost per case registered ranged from US $41.28 to US $113.39. Registries serving large populations (over 15 million inhabitants) had a lower cost per inhabitant (less than US $0.01 in Mumbai, India) than registries serving small populations (under 500,000 inhabitants) [US $0.22] in Pasto, Colombia.This study estimates the total cost and resources used for cancer registration across several countries in the limited-resource setting, and provides cancer registration stakeholders and registries with opportunities to identify cost savings and efficiency improvements. Our results suggest that cancer registration involve substantial fixed costs and labor, and that partnership with other institutions is critical for the operation and sustainability of cancer registries in limited resource settings. Although we included registries from a variety of limited-resource areas, information from eight registries in four countries may not be large enough to capture all the potential differences among the registries in limited-resource settings.

Background Maintaining population-based registries requires adequate and sustained resources; however, to date there has been no systematic evaluation to identify the resource needs for cancer registration in most countries, including Colombia. A systematic assessment of the costs can quantify the funding required and identify processes to improve efficiency of cancer registries. Methods The Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool ( IntRegCosting Tool) was tailored specifically for the Colombian registries and was used to collect resource use data from five regional population-based cancer registries: Barranquilla, Bucaramanga, Cali, Manizales, and Pasto. The registries provided cost data for the year 2013 and cancer cases corresponding to the year 2010. Results We identified an almost threefold variation in the average cost per case (77,932 to 214,082 Colombian pesos or US $41 to US $113 in 2013) across the registries, but there were also substantial differences in data collection approaches, types of data collected, and activities performed. Cost per inhabitant varied between 95 and 415 Colombian pesos (US $0.05 to US $0.22). Between 20% and 45% of the total cost was due to fixed cost activities. Conclusions The detailed economic information presented in this study constitutes a valuable source of activity-based cost data that registries can use to compare operations, assess key factors that lead to differences in cost per case, and identify potential approaches to improve efficiencies. Furthermore, the knowledge gained from studying the Colombian registries can help inform the planning and operations of other registries in the region.

The objective of this study was to determine the major financial barriers that affect people's access to oral cancer treatment in India. Barriers researched included not only the direct medical costs, but also the direct non-medical costs, such as transportation and lodging, and the indirect cost of missing work or family duties. Four hundred patients from two regions in southern India responded to a 2014 survey that asked about access and barriers to care. Traditionally, policies to increase screening, diagnosis and treatment of oral cancer have focused on affordable or free medical services for low-income groups; however, the hidden costs associated with receiving care are a significant burden. Transportation, lodging, loss of wages, and time away from family duties are key barriers to oral cancer care that policy makers should address.

Noncommunicable diseases (NCDs) are the main cause of death worldwide. In addition, the incidence, prevalence, and death rates from NCDs are expected to increase in the future. No single discipline can address the issues of prevention, early detection, access to care, and appropriate treatment that are needed to improve outcomes for NCDs; this growing need will require transdisciplinary collaborations. Improving outcomes in NCDs is clearly a difficult endeavor that will require significant efforts. However, previous research and program implementation indicate that improving outcomes for NCDs is an achievable goal. Given the tremendous impact of NCDs on morbidity, mortality, and costs worldwide, there is little doubt that efforts to improve NDC outcomes are much needed. Recognizing the importance of new strategies and interventions addressing NCDS globally, RTI funded the projects described here to assess how the institute’s range of expertise could be focused on the reduction of NCDs. The projects described in this book focus on the risk factors or treatment (or both) of one or more of the four NCDs that are responsible for the greatest impact on morbidity and mortality: cardiovascular disease, cancer, diabetes, and chronic respiratory diseases. The pilot projects were carried out in low- and middle-income countries, which are disproportionately affected by NCDs. The lessons learned from these initial pilot projects have great potential to be increased in their scale and reduce the devastating impact of noncommunicable diseases.

The functionality of modern cities relies heavily on interdependent infrastructure systems such as those for water, power, and transportation. Disruptions often propagate within and across physical infrastructure networks and result in catastrophic consequences. The reaction of communities to disasters (e.g., seeking alternatives) may further transfer and aggravate the burden on surviving infrastructures, which may facilitate cascading secondary disruptions. Hence, a holistic analysis framework that integrates infrastructure interdependencies and community behaviors is needed to evaluate a citys vulnerability to disruptions and to assess the impact of a disaster. U.S. Army doctrine requires that commanders understand, visualize, and describe the infrastructure component of the Joint Operating Environment to accomplish the Armys missions of protecting, restoring, and developing infrastructure. To this end, a game-theoretical equilibrium model has been developed in a multilayer infrastructure network, to systematically investigate the mutual influence between the infrastructures and the communities. In this model, two types of infrastructure failure patterns are formulated to capture general network interdependencies; network equilibrium is ex-tended into infrastructure and community systems to address redistribution of demand for life-supporting resources; the societal impact of disasters is estimated based on resource demand loss, cost increase, and total infrastructure failure. A real-world case study was implemented to demonstrate the proposed model and algorithm, and to reveal insights.

Background This report describes the resources required to support the integrated approach of the Barbados National Registry for Chronic Non-communicable Diseases (BNR) to non-communicable disease (NCD) case registration, and to identify differences in cost for collecting and maintaining information on cancer and cardiovascular disease (CVD) case registration. Methods We used the modified Centers for Disease Control and Prevention’s International Registry Costing Tool to collect data from the CVD and cancer registries. We used cancer and CVD cost data for the annual period April 2014 through March 2015 to estimate the total cost and cost per case. We used prospectively collected average annual CVD cases, and for cancer cases we assumed 2 or 3 years are needed for retrospective data collection. Results The Ministry of Health provided 56% of the resources for the registries. Labor accounted for over 70% of both registries’ budgets, while management and administration, along with data collection and analysis, incurred the highest costs per case. Total variable cost activities related to data collection and analysis were higher for the CVD component (US$131,297) than the cancer component (US$58,917). The CVD cost per case (US$489) was in between the cancer 2-year (US$382) and the cancer 3-year (US$573) cost-per-case estimates. Conclusion These findings indicate that there are substantial fixed costs related to management and administration of NCD registries. All registries need management and administration support. When registries are combined, management and administration costs can be shared. We project that registries that can share fixed-cost infrastructure are likely to incur a lower total cost per case.

Background The objectives of this study are (1) to estimate the cost of operating the Kampala Cancer Registry (KCR) and (2) to use cost data from the KCR to project the resource needs and cost of expanding and sustaining cancer registration in Uganda, focusing on the recently established Gulu Cancer Registry (GCR) in rural Northern Uganda. Methods We used Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool ( IntRegCosting Tool ) to estimate the KCR's activity-based cost for 2014. We grouped the registry activities into fixed cost, variable core cost, and variable other cost activities. After a comparison KCR and GCR characteristics, we used the cost of the KCR to project the likely ongoing costs for the new GCR. Results The KCR incurred 42% of its expenditures in fixed cost activities, 40% for variable core cost activities, and the remaining 18% for variable other cost activities. The total cost per case registered was 28,201 Ugandan shillings (approximately US $10 in 2014) to collect and report cases using a combination of passive and active cancer data collection approaches. The GCR performs only active data collection, and covers a much larger area, but serves a smaller population compared to the KCR. Conclusion After identifying many differences between KCR and GCR that could potentially affect the cost of registration, our best estimate is that the GCR, though newer and in a rural area, should require fewer resources than the KCR to sustain operations as a stand-alone entity. The optimal structure of the GCR needs to be determined in the future.

Optically pure L-(+)-C alpha-methyl-arginine and D-(-)-C alpha-methyl-arginine were synthesized. Experimental results indicated that DL-C alpha-methyl-arginine methyl ester could be resolved by trypsin, but workup posed a technical difficulty. Chemical resolution at the stage of DL-C alpha-methyl-ornithine, followed by selective guanidination using N,N'-di-Cbz-S-methylisothiourea and hydrogenolysis provided a effective and practical method for the synthesis of optically pure C alpha-methyl-arginine.

Introduction The prevalence of non-communicable diseases (NCDs) is rising in low- and middle-income countries, including Kenya, disproportionately to the rest of the world. Our objective was to quantify patient payments to obtain NCD screening, diagnosis, and treatment services in the public and private sector in Kenya and evaluate patients’ ability to pay for the services. Methods and findings We collected payment data on cardiovascular diseases, diabetes, breast and cervical cancer, and respiratory diseases from Kenyatta National Hospital, the main tertiary public hospital, and the Kibera South Health Center—a public outpatient facility, and private sector practitioners and hospitals. We developed detailed treatment frameworks for each NCD and used an itemization cost approach to estimate payments. Patient affordability metrics were derived from Kenyan government surveys and national datasets. Results compare public and private costs in U.S. dollars. NCD screening costs ranged from $4 to $36, while diagnostic procedures, particularly for breast and cervical cancer, were substantially more expensive. Annual hypertension medication costs ranged from $26 to $234 and $418 to $987 in public and private facilities, respectively. Stroke admissions ($1,874 versus $16,711) and dialysis for chronic kidney disease ($5,338 versus $11,024) were among the most expensive treatments. Cervical and breast cancer treatment cost for stage III (curative approach) was about $1,500 in public facilities and more than $7,500 in the private facilities. A large proportion of Kenyans aged 15 to 49 years do not have health insurance, which makes NCD services unaffordable for most people given the overall high cost of services relative to income (average household expenditure per adult is $413 per annum). Conclusions There is substantial variation in patient costs between the public and private sectors. Most NCD diagnosis and treatment costs, even in the public sector, represent a substantial economic burden that can result in catastrophic expenditures.

Geometric modeling is the cornerstone of computer-aided design (CAD). Currently, geometric modeling is done either interactively, using the geometric constructs (i.e., line, circle, etc.) supported by the CAD system, or by writing a program that generates the geometry of interest automatically. While both interactive and automatic geometric modeling are more efficient than manual drafting, they have their limitations. This paper describes an approach to geometric modeling that is superior to the interactive and automated modeling approaches with respect to ease of use, flexibility, and cost-effectiveness. This approach involves defining a geometry linguistically and then generating the geometry from its linguistic definition automatically. The approach manifests itself in three activities: (1) linguistically representing the geometry using a suitable vocabulary; (2) translating the linguistic definition of the geometry into a logic program; and (3) generating the geometry via logical deduction in a logic-based CAD system. These activities are discussed and illustrated in the context of the geometry of a simple bridge structure.

A general method was developed for the synthesis of serine or threonine containing cyclic peptides utilizing the β-hydroxyl side-chain of these residues as an anchor point to Wang resin. The peptide chain was assembled by conventional Fmoc/tBu solid-phase chemistry followed by palladium catalyzed exposure of the allyl protected C-terminus group and on-resin cyclization. The cyclic heptapeptide stylostatin 1 was prepared to demonstrate the utility of this technique.

A mild N-alkylation method has been developed for the synthesis of N-alkylated pyridiniumcarboxylic acids, using Ag2O-H2O catalysis to enhance the low-reactivity of pyridinecarboxylic acids. Two approaches were undertaken for the synthesis of a series of GnRH antagonists containing pyridinium moieties at the side chain: (1) incorporation of Npy-alkylated D-pyridylalanine during solid phase peptide chain assembly, and (2) coupling of the N-alkylated pyridinium-carboxylic acid to the resin-bound e-amino group of a D-lysine on a solid support.

Calcitonin gene-related peptide (CGRP), a potent dilator of cerebral and dural vasculature, is known to be elevated in plasma and cerebral spinal fluid during migraine attacks. Selective blockade of the CGRP receptor offers the promise of controlling migraine headache more effectively and without the side-effects associated with the use of triptans. Our efforts to develop a novel, peptide-based CGRP antagonist focused on the C-terminal portion of the peptide which is known to bind the receptor but lack agonist properties. Extensive SAR studies of the C-terminal CGRP (27-37) region identified a novel cyclic structure: Bz-Val-Tyr-cyclo[Cys-Thr-Asp-Val-Gly-Pro-Phe-Cys]-Phe-NH(2) (23) with a kb value of 0.126 nM against the cloned human CGRP receptor. Additional SAR studies directed at enhancement of potency and improvement of physicochemical properties yielded a series of analogs with kb values in the 0.05-0.10 nM range.

A mild N-alkylation method has been developed for the synthesis of N-alkylated pyridiniumcarboxylic acids, using Ag2O-H2O catalysis to enhance the low-reactivity of pyridinecarboxylic acids. Two approaches were undertaken for the synthesis of a series of GnRH antagonists containing pyridinium moieties at the side chain: (1) incorporation of Npy-alkylated D-pyridylalanine during solid phase peptide chain assembly, and (2) coupling of the N-alkylated pyridinium-carboxylic acid to the resin-bound e-amino group of a D-lysine on a solid support.

Extensive structure–activity relationship studies utilizing a β-MSH-derived cyclic nonapeptide, Ac-Tyr-Arg-[Cys-Glu-His- d -Phe-Arg-Trp-Cys]-NH 2 ( 3 ), led to identification of a series of novel MC-4R selective disulfide-constrained hexapeptide analogs including Ac-[hCys-His- d -Phe-Arg-Trp-Cys]-NH 2 ( 12 ). The structural modifications associated with profound influence on MC-4R potency and selectivity were ring size, ring conformation, and the aromatic substitution of the d -Phe7. These cyclic peptide analogs provide novel and enhanced reagents for use in the elucidation of melanocortin-4 receptor-related physiology, and may additionally find application in the treatment of obesity and related metabolic disorders.

A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food intake and body weight models.

About 25 conformationally constrained antagonists of LHRH have been synthesized in order to gain some information about the bioactive conformation of antagonists. The constraints include various C-methyl residues, N-methyl groups, prolines and the 6-7 lactam. The antagonists were evaluated in the rat antiovulatory assay, in a pituitary cell membrane binding assay and by NMR. The results will be discussed and a model of the bioactive conformation proposed.