Pharmacy Assistance Programs for Oral Anticancer Drugs: A Narrative Review.

Oral anticancer medications (OAMs) are high priced with a significant cost-sharing burden to patients, which can lead to catastrophic financial, psychosocial, and clinical repercussions. Cost-conscious prescribing and inclusion of low-cost alternatives can help mitigate this burden, but cost transparency at the point of prescribing remains a major barrier to doing so. Pharmacy assistance programs, including co-payment cards and patient assistance programs administered by manufacturers and foundation-based grants, remain an essential resource for patients facing prohibitive co-payments for OAMs. However, access to these programs is fraught with complexities, including lack of trained financial navigators, limited transparency on eligibility criteria, onerous documentation burdens, and limits in available funding. Despite these drawbacks and the potential for such programs to incentivize manufacturers to keep list prices high, assistance programs have been demonstrated to improve financial well-being for patients with cancer. The increasing development of integrated specialty pharmacies with dedicated, trained pharmacy staff can help improve and standardize access to such programs, but these services are disproportionately available to patients seen at tertiary care centers. Multistakeholder interventions are needed to mitigate the burden of cost sharing for OAMs, including increased clinician knowledge of financial resources and novel assistance mechanisms, investment of institutions in trained financial navigation services and centralized platforms to identify assistance programs, and policies to cap out-of-pocket spending and improve transparency of rates charged by pharmacy benefit managers to a health plan.

Access to Financial Assistance Programs and Their Impact on Overall Spending on Oral Anticancer Medications at an Integrated Specialty Pharmacy.

PURPOSE: Financial assistance (FA) programs are increasingly used to help patients afford oral anticancer medications (OAMs), but access to such programs and their impact on out-of-pocket (OOP) spending has not been well explored. This study aimed to (1) characterize the impact of receipt of FA on both OOP spending and likelihood of catastrophic spending on OAMs and (2) evaluate racial/ethnic disparities in access to FA programs. METHODS: Patients with a cancer diagnosis prescribed an OAM anytime between January 1, 2021, and December 31, 2021 were included in this retrospective, single-center study at an integrated specialty pharmacy affiliated with a tertiary academic cancer center. Fixed-effect regression models were used to characterize the impact of receipt of FA on overall spending and likelihood of catastrophic spending on OAMs, as well as explore the association of race/ethnicity with receipt of FA. RESULTS: Across 1,186 patients prescribed an OAM, 37% received FA. Receipt of FA was associated with lower annual spending on OAMs (ß = -$1,236 US dollars [USD; 95% CI, -$1,841 to -$658], P < .001) but not reduced risk of catastrophic spending (odds ratio [OR], 0.442 [95% CI, 0.755 to 3.199], P = .23). Non-White patients (OR, 0.60 [95% CI, 0.43 to 0.85], P = .004) and patients who spoke English as a second language (OR, 0.46 [95% CI, 0.23 to 0.90], P = .02) were less likely to receive FA compared with White and English-speaking patients, respectively. CONCLUSION: FA programs can mitigate high OOP spending but not for patients who spend at catastrophic levels. There are racial/ethnic and language disparities in access to such programs. Future studies should evaluate access to FA programs across diverse delivery settings.

Proximity to endocrine-disrupting pesticides and risk of testicular germ cell tumors (TGCT) among adolescents: A population-based case-control study in California.

BACKGROUND: The incidence of testicular germ cell tumors (TGCT) is increasing steadily in the United States, particularly among Latinos. TGCT is thought to be initiated in utero and exposure to endocrine-disrupting chemicals, suspected contributors to TGCT pathogenesis, during this critical developmental period may contribute to the rise. OBJECTIVES: To assess the relationship between fetal exposure to agricultural endocrine-disrupting pesticides (EDPs) and TGCT risk among adolescents in a diverse population in California. METHODS: We conducted a registry-based case-control study of TGCT. Cases, diagnosed between 1997 and 2011, were 15-19 years of age (n = 381). Controls were matched on birth year and race/ethnicity (n = 762). Quantities (kilograms) of 33 pesticides applied within 3 km and 1 km radii of each individual's address before birth were estimated using the Pesticide Use Reporting database. Odds ratios (OR), 95% confidence intervals (CI), and population attributable risk (PAR) were calculated for each EDP (using log-2 transformed values). Risk models considered race/ethnicity, birth year, and neighborhood socioeconomic status. RESULTS: A doubling of nearby acephate applications (3 km and 1 km radii) and malathion applications (1 km radius) was associated with increased risks of TGCT among Latinos only (OR = 1.09; 95% CI:1.01-1.17; 1.30; 95% CI:1.08-1.57, and 1.19; 95% CI:1.01-1.39, respectively), whereas application of carbaryl within a 3 km radius increased TGCT risk in non-Latinos only (OR = 1.14, 95% CI:1.01-1.28). We estimate that acephate was associated with approximately 10% of the TGCT PAR, malathion with 3% and carbaryl with 1%. CONCLUSIONS: TGCT among adolescents in California was associated with prenatal residential proximity to acephate and malathion among Latinos, and with carbaryl among non-Latinos. These results suggest that the rise in TGCT risk among Latinos may be associated with exposure to these pesticides.

Identifying residual hotspots and mapping lower respiratory infection morbidity and mortality in African children from 2000 to 2017.

Lower respiratory infections (LRIs) are the leading cause of death in children under the age of 5, despite the existence of vaccines against many of their aetiologies. Furthermore, more than half of these deaths occur in Africa. Geospatial models can provide highly detailed estimates of trends subnationally, at the level where implementation of health policies has the greatest impact. We used Bayesian geostatistical modelling to estimate LRI incidence, prevalence and mortality in children under 5 subnationally in Africa for 2000-2017, using surveys covering 1.46 million children and 9,215,000 cases of LRI. Our model reveals large within-country variation in both health burden and its change over time. While reductions in childhood morbidity and mortality due to LRI were estimated for almost every country, we expose a cluster of residual high risk across seven countries, which averages 5.5 LRI deaths per 1,000 children per year. The preventable nature of the vast majority of LRI deaths mandates focused health system efforts in specific locations with the highest burden.

Publisher Correction: Mapping exclusive breastfeeding in Africa between 2000 and 2017.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mapping exclusive breastfeeding in Africa between 2000 and 2017.

Exclusive breastfeeding (EBF)-giving infants only breast-milk (and medications, oral rehydration salts and vitamins as needed) with no additional food or drink for their first six months of life-is one of the most effective strategies for preventing child mortality1-4. Despite these advantages, only 37% of infants under 6 months of age in Africa were exclusively breastfed in 20175, and the practice of EBF varies by population. Here, we present a fine-scale geospatial analysis of EBF prevalence and trends in 49 African countries from 2000-2017, providing policy-relevant administrative- and national-level estimates. Previous national-level analyses found that most countries will not meet the World Health Organization's Global Nutrition Target of 50% EBF prevalence by 20256. Our analyses show that even fewer will achieve this ambition in all subnational areas. Our estimates provide the ability to visualize subnational EBF variability and identify populations in need of additional breastfeeding support.

Variation in Childhood Diarrheal Morbidity and Mortality in Africa, 2000-2015.

BACKGROUND: Diarrheal diseases are the third leading cause of disease and death in children younger than 5 years of age in Africa and were responsible for an estimated 30 million cases of severe diarrhea (95% credible interval, 27 million to 33 million) and 330,000 deaths (95% credible interval, 270,000 to 380,000) in 2015. The development of targeted approaches to address this burden has been hampered by a paucity of comprehensive, fine-scale estimates of diarrhea-related disease and death among and within countries. METHODS: We produced annual estimates of the prevalence and incidence of diarrhea and diarrhea-related mortality with high geographic detail (5 km2) across Africa from 2000 through 2015. Estimates were created with the use of Bayesian geostatistical techniques and were calibrated to the results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. RESULTS: The results revealed geographic inequality with regard to diarrhea risk in Africa. Of the estimated 330,000 childhood deaths that were attributable to diarrhea in 2015, more than 50% occurred in 55 of the 782 first-level administrative subdivisions (e.g., states). In 2015, mortality rates among first-level administrative subdivisions in Nigeria differed by up to a factor of 6. The case fatality rates were highly varied at the national level across Africa, with the highest values observed in Benin, Lesotho, Mali, Nigeria, and Sierra Leone. CONCLUSIONS: Our findings showed concentrated areas of diarrheal disease and diarrhea-related death in countries that had a consistently high burden as well as in countries that had considerable national-level reductions in diarrhea burden. (Funded by the Bill and Melinda Gates Foundation.).

Global disability-adjusted life-year estimates of long-term health burden and undernutrition attributable to diarrhoeal diseases in children younger than 5 years.

BACKGROUND: Diarrhoea is a leading cause of death and illness globally among children younger than 5 years. Mortality and short-term morbidity cause substantial burden of disease but probably underestimate the true effect of diarrhoea on population health. This underestimation is because diarrhoeal diseases can negatively affect early childhood growth, probably through enteric dysfunction and impaired uptake of macronutrients and micronutrients. We attempt to quantify the long-term sequelae associated with childhood growth impairment due to diarrhoea. METHODS: We used the Global Burden of Diseases, Injuries, and Risk Factors Study framework and leveraged existing estimates of diarrhoea incidence, childhood undernutrition, and infectious disease burden to estimate the effect of diarrhoeal diseases on physical growth, including weight and height, and subsequent disease among children younger than 5 years. The burden of diarrhoea was measured in disability-adjusted life-years (DALYs), a composite metric of mortality and morbidity. We hypothesised that diarrhoea is negatively associated with three common markers of growth: weight-for-age, weight-for-height, and height-for-age Z-scores. On the basis of these undernutrition exposures, we applied a counterfactual approach to quantify the relative risk of infectious disease (subsequent diarrhoea, lower respiratory infection, and measles) and protein energy malnutrition morbidity and mortality per day of diarrhoea and quantified the burden of diarrhoeal disease due to these outcomes caused by undernutrition. FINDINGS: Diarrhoea episodes are significantly associated with childhood growth faltering. We found that each day of diarrhoea was associated with height-for-age Z-score (-0·0033 [95% CI -0·0024 to -0·0041]; p=4·43 × 10-14), weight-for-age Z-score (-0·0077 [-0·0058 to -0·0097]; p=3·19â€ˆ× 10-15), and weight-for-height Z-score (-0·0096 [-0·0067 to -0·0125]; p=7·78 × 10-11). After addition of the DALYs due to the long-term sequelae as a consequence of undernutrition, the burden of diarrhoeal diseases increased by 39·0% (95% uncertainty interval [UI] 33·0-46·6) and was responsible for 55 778 000 DALYs (95% UI 49 125 400-62 396 200) among children younger than 5 years in 2016. Among the 15 652 300 DALYs (95% UI 12 951 300-18 806 100) associated with undernutrition due to diarrhoeal episodes, more than 84·7% are due to increased risk of infectious disease, whereas the remaining 15·3% of long-term DALYs are due to increased prevalence of protein energy malnutrition. The burden of diarrhoea has decreased substantially since 1990, but progress has been greater in long-term (78·7% reduction [95% UI 69·3-85·5]) than in acute (70·4% reduction [95% UI 61·7-76·5]) DALYs. INTERPRETATION: Diarrhoea represents an even larger burden of disease than was estimated in the Global Burden of Disease Study. In order to adequately address the burden of its long-term sequelae, a renewed emphasis on controlling the risk of diarrhoea incidence may be required. This renewed effort can help further prevent the potential lifelong cost on child health, growth, and overall potential. FUNDING: Bill & Melinda Gates Foundation.

Global Assessment of Schistosomiasis Control Over the Past Century Shows Targeting the Snail Intermediate Host Works Best.

BACKGROUND: Despite control efforts, human schistosomiasis remains prevalent throughout Africa, Asia, and South America. The global schistosomiasis burden has changed little since the new anthelmintic drug, praziquantel, promised widespread control. METHODOLOGY: We evaluated large-scale schistosomiasis control attempts over the past century and across the globe by identifying factors that predict control program success: snail control (e.g., molluscicides or biological control), mass drug administrations (MDA) with praziquantel, or a combined strategy using both. For data, we compiled historical information on control tactics and their quantitative outcomes for all 83 countries and territories in which: (i) schistosomiasis was allegedly endemic during the 20th century, and (ii) schistosomiasis remains endemic, or (iii) schistosomiasis has been "eliminated," or is "no longer endemic," or transmission has been interrupted. PRINCIPAL FINDINGS: Widespread snail control reduced prevalence by 92 ± 5% (N = 19) vs. 37 ± 7% (N = 29) for programs using little or no snail control. In addition, ecological, economic, and political factors contributed to schistosomiasis elimination. For instance, snail control was most common and widespread in wealthier countries and when control began earlier in the 20th century. CONCLUSIONS/SIGNIFICANCE: Snail control has been the most effective way to reduce schistosomiasis prevalence. Despite evidence that snail control leads to long-term disease reduction and elimination, most current schistosomiasis control efforts emphasize MDA using praziquantel over snail control. Combining drug-based control programs with affordable snail control seems the best strategy for eliminating schistosomiasis.

Infection with schistosome parasites in snails leads to increased predation by prawns: implications for human schistosomiasis control.

Schistosomiasis - a parasitic disease that affects over 200 million people across the globe - is primarily transmitted between human definitive hosts and snail intermediate hosts. To reduce schistosomiasis transmission, some have advocated disrupting the schistosome life cycle through biological control of snails, achieved by boosting the abundance of snails' natural predators. But little is known about the effect of parasitic infection on predator-prey interactions, especially in the case of schistosomiasis. Here, we present the results of laboratory experiments performed on Bulinus truncatus and Biomphalaria glabrata snails to investigate: (i) rates of predation on schistosome-infected versus uninfected snails by a sympatric native river prawn, Macrobrachium vollenhovenii, and (ii) differences in snail behavior (including movement, refuge-seeking and anti-predator behavior) between infected and uninfected snails. In predation trials, prawns showed a preference for consuming snails infected with schistosome larvae. In behavioral trials, infected snails moved less quickly and less often than uninfected snails, and were less likely to avoid predation by exiting the water or hiding under substrate. Although the mechanism by which the parasite alters snail behavior remains unknown, these results provide insight into the effects of parasitic infection on predator-prey dynamics and suggest that boosting natural rates of predation on snails may be a useful strategy for reducing transmission in schistosomiasis hotspots.