Identifying opportunities for high resolution pesticide usage data to improve the efficiency of endangered species pesticide risk assessment.

The US pesticide registration and review process requires regular re-assessment of the risk of pesticide use to species listed under the Endangered Species Act (ESA), yet current assessment methods are inefficient when applied to hundreds of pesticides potentially impacting multiple species across a continent. Thus, many pesticides remain on the market without complete review. We assessed the value of using high resolution pesticide usage data in the risk assessment process to rapidly improve process efficiency. By using data available only in California, we found that high resolution data increased the number of species deemed not likely to be adversely affected by pesticides from <5 % to nearly 50 %. Across the contiguous US, we predicted that 48 % of species would be deemed not likely to be adversely affected using high resolution data, compared to 20 % without. However, if such data were available in just 11 states, 68 % of the available gains in efficiency could be obtained. Overall, using existing high-resolution data in California and a focused collection of such information from 11 other states could reduce risk assessment burden across the contiguous U.S. by one-quarter.

A multi-taxonomic, trait-based framework for assessing macroplastic vulnerability.

Individual interactions with plastic pollution have been documented in hundreds of marine species. However, the population and community level effects of these interactions remain poorly understood. Trait-based approaches provide a method for assessing the relative vulnerability of populations or communities to plastic pollution when empirical studies and data are limited. We conducted a literature review and identified 22 traits that influence likelihood of exposure, species sensitivity, and population resilience to the physical impacts of macroplastic. The resulting trait-based framework provides a process for assessing the relative vulnerability of marine biota to macroplastic ingestion and entanglement. Our framework can be applied to develop vulnerability indices for marine taxonomic groups that can inform targeted management efforts, identify priorities for long-term monitoring, and identify species for future quantitative risk assessments.

A decision framework for estimating the cost of marine plastic pollution interventions.

Marine plastic pollution has emerged as one of the most pressing environmental challenges of our time. Although there has been a surge in global investment for implementing interventions to mitigate plastic pollution, there has been little attention given to the cost of these interventions. We developed a decision support framework to identify the economic, social, and ecological costs and benefits of plastic pollution interventions for different sectors and stakeholders. We calculated net cost as a function of six cost and benefit categories with the following equation: cost of implementing an intervention (direct, indirect, and nonmonetary costs) minus recovered costs and benefits (monetary and nonmonetary) produced by the interventions. We applied our framework to two quantitative case studies (a solid waste management plan and a trash interceptor) and four comparative case studies, evaluating the costs of beach cleanups and waste-to-energy plants in various contexts, to identify factors that influence the costs of plastic pollution interventions. The socioeconomic context of implementation, the spatial scale of implementation, and the time scale of evaluation all influence costs and the distribution of costs across stakeholders. Our framework provides an approach to estimate and compare the costs of a range of interventions across sociopolitical and economic contexts.

Un Marco de Decisión para Estimar el Costo de Intervenciones en la Contaminación Marina por Plástico Resumen La contaminación marina por plásticos ha emergido como uno de los retos ambientales más prioritarios de nuestro tiempo. Mientras ha habido un aumento en la inversión global para implementar intervenciones para mitigar la contaminación por plásticos, se ha dado poca atención al costo de estas intervenciones. Desarrollamos un marco de soporte a las decisiones para identificar los costos y beneficios económicos, sociales y ecológicos de las intervenciones en la contaminación por plástico para diferentes sectores y partes interesadas. Calculamos el costo neto como una función de 6 categorías de costo y beneficio con la siguiente ecuación: costo de la implementación de una intervención (costos directos, indirectos y no monetarios) menos los costos y beneficios recuperados (monetarios y no monetarios) producidos por las intervenciones. Aplicamos nuestro marco a 2 estudios de caso cuantitativos (un plan de manejo de residuos sólidos y un interceptor de basura) y 4 casos de estudio comparativos evaluando los costos de limpieza de playas y plantas de transformación de desechos a energía en varios contextos para identificar los factores que influyen en los costos de las intervenciones de la contaminación por plástico. El contexto socioeconómico de la implementación, la escala espacial de la implementación y la escala de tiempo de evaluación influyen en los costos y distribución de costos entre las partes interesadas. Nuestro marco proporciona una aproximación para estimar y comparar los costos de una gama de intervenciones en contextos sociopolíticos y económicos.

Revisiting racial differences in ESRD due to ADPKD in the United States.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) affects all races. Whether the progression of ADPKD varies by race remains unclear. METHODS: In this retrospective cohort study from 2004 to 2013 non-Hispanic blacks and non-Hispanic whites of all ages classified in the US Renal Data System (USRDS) with incident ESRD from ADPKD (n = 23,647), hypertension/large vessel disease (n = 296,352), or diabetes mellitus (n = 451,760) were stratified into five-year age categories ranging from < 40 to > 75 (e.g., < 40, 40-44, 45-49, …, 75+). The Cochran-Mantel-Haenszel test was used to determine the association of race and incidence of ESRD from ADPKD, diabetes, or hypertension. The difference in the proportions of ESRD in non-Hispanic black and non-Hispanic white patients at each age categorical bin was compared by two-sample proportion test. The age of ESRD onset between non-Hispanic black and non-Hispanic white patients at each year was compared using two-sample t-test with unequal variance. RESULTS: 1.068% of non-Hispanic blacks and 2.778% of non-Hispanic whites had ESRD attributed to ADPKD. Non-Hispanic blacks were less likely than non-Hispanic whites to have ESRD attributed to ADPKD (odds ratio (OR) (95% CI) = 0.38 (0.36-0.39), p <  0.0001). Using US Census data as the denominator to adjust for population differences non-Hispanic blacks were still slightly under-represented (OR (95% CI) 0.94 (0.91-0.96), p = 0.004). However, non-Hispanic blacks with ADPKD had a younger age of ESRD (54.4 years ±13) than non-Hispanic whites (55.9 years ±12.8) (p <  0.0001). For those < 40 years old, more non-Hispanic blacks had incident ESRD from ADPKD than non-Hispanic whites (9.49% vs. 7.68%, difference (95% CI) = 1.81% (0.87-2.84%), p <  0.001) for the combined years examined. CONCLUSIONS: As previously shown, we find the incidence of ESRD from ADPKD in non-Hispanic blacks is lower than in non-Hispanic whites. Among the younger ADPKD population (age < 40), however, more non-Hispanic blacks initiated dialysis than non-Hispanic whites. Non-Hispanic blacks with ADPKD initiated dialysis younger than non-Hispanic whites. A potential implication of these findings may be that black race should be considered an additional risk factor for progression in ADPKD.

Preimplantation Genetic Diagnosis Counseling in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary forms of chronic kidney disease. Mutations within PKD1 or PKD2 lead to innumerable fluid-filled cysts in the kidneys and in some instances, end-stage renal disease (ESRD). Affected individuals have a 50% chance of passing the mutation to each of their offspring. Assisted reproductive technology using preimplantation genetic diagnosis (PGD) allows these individuals to reduce this risk to 1% to 2%. We assess the disease burden of 8 individuals with ADPKD who have undergone genetic testing in preparation for PGD. Clinical features that predict high risk for progression to ESRD in patients with ADPKD include genotype, early onset of hypertension, a urologic event before age 35 years, and a large height-adjusted total kidney volume. Patients may have a family history of intracranial aneurysms or complications involving hepatic cysts, which may further influence the decision to pursue PGD. We also explore the cost, risks, and benefits of using PGD. All patients with ADPKD of childbearing potential, regardless of risk for progression to ESRD or risk for a significant disease burden, will likely benefit from genetic counseling.

PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models.

Phosphoinositide-3 kinase (PI3K)-δ and PI3K-γ are preferentially expressed in immune cells, and inhibitors targeting these isoforms are hypothesized to have anti-inflammatory activity by affecting the adaptive and innate immune response. We report on a potent oral PI3K-δ and PI3K-γ inhibitor (IPI-145) and characterize this compound in biochemical, cellular, and in vivo assays. These studies demonstrate that IPI-145 exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation. We explored the therapeutic value of combined PI3K-δ and PI3K-γ blockade, and IPI-145 showed potent activity in collagen-induced arthritis, ovalbumin-induced asthma, and systemic lupus erythematosus rodent models. These findings support the hypothesis that inhibition of immune function can be achieved through PI3K-δ and PI3K-γ blockade, potentially leading to significant therapeutic effects in multiple inflammatory, autoimmune, and hematologic diseases.

Effects of electronic prescribing on formulary compliance and generic drug utilization in the ambulatory care setting: a retrospective analysis of administrative claims data.

OBJECTIVE: Electronic prescribing (e-prescribing) provides formulary information at the point of care. The objective of this study was to assess the effects of e-prescribing on formulary compliance and generic utilization. METHODS: This was a retrospective analysis of pharmacy claims data from a large national managed care organization. A sample of 95 providers using predominantly e-prescribing was randomly selected (e-prescriber group). A matched sample of 95 traditional prescribers was selected (traditional prescriber group), matched to the e-prescriber group by zip code and medical specialty. A total of 110,975 paid pharmacy claims, for the 12 months from August 1, 2001, through July 31, 2002, were analyzed to assess the effect of e-prescribing on formulary compliance and generic utilization. All paid pharmacy claims were examined for each group; for the e-prescriber group, this included all claims, not just those prescribed using an e-prescribing device. A written qualitative survey was distributed to physicians and office managers to assess e-prescribing usage, sources of formulary information, and effects of e-prescribing on office resources. RESULTS: Both predominantly e-prescribers and traditional prescribers demonstrated high levels of formulary compliance, 83.2% versus 82.8%, respectively (P=0.32). Formulary compliance for these groups did not differ from the overall prescriber population (82.0%). There was not a difference in generic drug utilization rates between e-prescribers and traditional prescribers (absolute rates 37.3% versus 36.9%, P=0.18). Qualitative survey responses supported previously reported research indicating reductions in calls both to and from pharmacies for prescription orders. CONCLUSIONS: An examination of paid pharmacy claims from a large, national managed care organization demonstrated no differences between predominantly e-prescribers and traditional prescribers in measures of formulary compliance or generic drug utilization. Future studies should examine keystroke data at the point of care to observe more detail about drug selection methods.