Real-World Progression-Free Survival as an Endpoint in Lung Cancer: Replicating Atezolizumab and Docetaxel Arms of the OAK Trial Using Real-World Data.

Evaluating cancer treatments in real-world data (RWD) requires informative endpoints. This study replicated the atezolizumab and docetaxel arms of the OAK trial using RWD and compared progression-free survival (PFS) outcomes derived from abstracted physician's notes in RWD (rwPFS) against PFS outcomes derived from the clinical trial PFS (ctPFS). Atezolizumab and docetaxel arms of the phase III OAK randomized controlled trial (RCT; NCT02008227) were replicated in a US nationwide real-world database using selected OAK inclusion/exclusion criteria and propensity score-based adjustment for baseline prognostic variables. Concordance of outcomes was assessed using Kaplan-Meier medians and hazard ratios (HRs). The RWD cohorts comprised 133 patients on atezolizumab and 479 patients on docetaxel. After adjustment, prognostic variables were balanced between RCT arms and corresponding RWD cohorts. The rwPFS and ctPFS outcomes showed better concordance for docetaxel (2.99 vs. 3.52 months; HR: 0.99, 95% confidence interval (CI): 0.85-1.15) than for atezolizumab (3.71 vs. 2.76 months; HR: 0.8, 95% CI: 0.61-1.02). Excluding events labeled "pseudo-progression" from both RWD and RCT improved concordance for atezolizumab (4.24 vs. 4.14 months; HR: 0.95, 95% CI: 0.70-1.25). These findings were robust across sensitivity analyses. Replicating RCTs using RWD and comparing outcomes can help characterize RWD endpoints. Similarity of results between rwPFS and ctPFS at the cohort level may depend on drug category, highlighting the need for further studies to verify and understand when the corresponding outcomes can be compared, including within the same patient.

Long-Lasting Epigenetic Changes in the Dopamine Transporter in Adult Animals Exposed to Amphetamine during Embryogenesis: Investigating Behavioral Effects.

The dopamine transporter (DAT) is an integral member of the dopaminergic system and is responsible for the release and reuptake of dopamine from the synaptic space into the dopaminergic neurons. DAT is also the major target of amphetamine (Amph). The effects of Amph on DAT have been intensively studied; however, the mechanisms underlying the long-term effects caused by embryonal exposure to addictive doses of Amph remain largely unexplored. As in mammals, in the nematode C. elegans Amph causes changes in locomotion which are largely mediated by the C. elegans DAT homologue, DAT-1. Here, we show that chronic embryonic exposures to Amph alter the expression of DAT-1 in adult C. elegans via long-lasting epigenetic modifications. These changes are correlated with an enhanced behavioral response to Amph in adult animals. Importantly, pharmacological and genetic intervention directed at preventing the Amph-induced epigenetic modifications occurring during embryogenesis inhibited the long-lasting behavioral effects observed in adult animals. Because many components of the dopaminergic system, as well as epigenetic mechanisms, are highly conserved between C. elegans and mammals, these results could be critical for our understanding of how drugs of abuse initiate predisposition to addiction.

Left truncation in linked data: A practical guide to understanding left truncation and applying it using SAS and R.

Time-to-event data such as time to death are broadly used in medical research and drug development to understand the efficacy of a therapeutic. For time-to-event data, right censoring (data only observed up to a certain point of time) is common and easy to recognize. Methods that use right censored data, such as the Kaplan-Meier estimator and the Cox proportional hazard model, are well established. Time-to-event data can also be left truncated, which arises when patients are excluded from the sample because their events occur before a specific milestone, potentially resulting in an immortal time bias. For example, in a study evaluating the association between biomarker status and overall survival, patients who did not live long enough to receive a genomic test were not observed in the study. Left truncation causes selection bias and often leads to an overestimate of survival time. In this tutorial, we used a nationwide electronic health record-derived de-identified database to demonstrate how to analyze left truncated and right censored data without bias using example code from SAS and R.

Physical oral care prevents ventilator-associated pneumonia in Vietnam: A prospective interventional study.

BACKGROUND: Ventilator-associated pneumonia (VAP) has emerged as a critical issue in the intensive care unit (ICU) because of its high burden on patients and medical staff. Here, we examined the potential for reducing VAP incidence through physical oral care interventions without any medication. METHODS: This prospective interventional study compared VAP incidence during an 8-month baseline period (usual oral care) and a 9-month intervention period (physical oral care with sponge brush) among patients who received mechanical ventilation for >48 h in a tertiary care hospital in Vietnam from 2017 to 2019. Physical oral care was provided by general ICU nurses who had been trained by dentists and infection control nurses. VAP was diagnosed using the Clinical Pulmonary Infection Score. RESULTS: In total, 423 patients were enrolled in the baseline group and 454 patients were enrolled in the intervention group; 303 and 300 patients, respectively, were included in the analysis. Two hundred thirty-eight VAP episodes were identified: 135 (44.6%) during the baseline period and 103 (34.3%) during the intervention period. Univariate analysis revealed significant reduction of VAP occurrence in the intervention period (odds ratio = 0.65; 95% confidence interval = 0.47-0.90; P = 0.010). The incidences of VAP per 1000 ventilator-days were 63.4 (135/2128) during the baseline period and 48.4 (103/2128) during the intervention period (P = 0.038). CONCLUSIONS: Physical oral care without any medication (e.g., chlorhexidine) reduced VAP incidence in the ICU. This method could be used to reduce VAP incidence, particularly in countries with limited medical resources.

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non-Small Cell Lung Cancer Trials Using Real-World Data.

PURPOSE: The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was to replicate control arms from four non-small cell lung cancer (NSCLC) randomized controlled trials (RCT) to analyze overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) using RWD. PATIENTS AND METHODS: This study used RWD from a nationwide de-identified database and a clinico-genomic database to replicate OS, PFS, and ORR endpoints in the chemotherapy control arms of four first-line NSCLC RCTs evaluating atezolizumab [IMpower150-wild-type (WT), IMpower130-WT, IMpower131, and IMpower132]. Additional objectives were to develop a definition of real-world PFS (rwPFS) and to evaluate the real-world response rate (rwRR) endpoint. RESULTS: Baseline demographic and clinical characteristics were balanced after application of propensity score weighting methods. For rwPFS and OS, RWD external controls were generally similar to their RCT control counterparts. Across all four trials, the hazard ratio (HR) point estimates comparing trial controls with external controls were closer to 1.0 for the PFS endpoint than for the OS endpoint. An exploratory assessment of rwRR in RWD revealed a slight but nonsignificant overestimation of RCT ORR, which was unconfounded by baseline characteristics. CONCLUSIONS: RWD can be used to reasonably replicate the OS and PFS of chemotherapy control arms of first-line NSCLC RCTs. Additional studies can provide greater insight into the utility of RWD in drug development.

Effectiveness of Additional Risk Minimization Measures for Atezolizumab in the European Union.

BACKGROUND: A Guide for Healthcare Professionals (HCP Guide) and patient alert card (PAC) for atezolizumab as additional risk minimization measures for physicians were distributed to raise awareness and help in the detection and management of immune-related adverse drug reactions. OBJECTIVES: The main objective of this study was to assess the receipt, knowledge, and behaviors of physicians regarding the atezolizumab HCP Guide and PAC. METHODS: A multi-country, one-wave, observational, cross-sectional, web-based, self-reported physician survey was conducted to assess the level of knowledge of key messages related to immune-related adverse drug reactions summarized in the atezolizumab HCP Guide and PAC among physicians (oncologists, pulmonologists, and urologists) prescribing atezolizumab in six European countries (Denmark, Germany, Italy, Spain, Sweden, and the UK). Responses regarding the receipt, understanding and use of the materials, and knowledge and behavior related to the HCP Guide and PAC are presented as percentages and continuous scores scaled out of 100 points, with corresponding 95% confidence intervals (CIs). RESULTS: Among 313 physicians (255 oncologists, 30 pulmonologists, and 28 urologists), 77.4% received the HCP Guide and 74.2% the PAC. The HCP Guide was read by 71.3% of the 267 physicians who received the materials, and the mean usage score was 69.5 (95% CI 66.0-72.9), and 57.1% of physicians had scores ≥ 70. The HCP Guide was completely understood by 85.4% of physicians who had read it. Mean knowledge scores were 63.9 (95% CI 62.1-65.7) and 39.4% of physicians had correct knowledge scores ≥ 70. Mean knowledge scores were 66.8 (95% CI 64.9-68.7) for receipt of both the HCP Guide and PAC, 59.4 (95% CI 55.5-63.4) for one of the materials, and 60.8 (95% CI 55.4-66.2) for having received none of the materials. Mean behavior scores were 78.9 (95% CI 76.8-81.0), and 74.8% of physicians had behavior scores ≥ 70. The mean behavior score was 79.0 (95% CI 76.5-81.5) for those who received both the HCP Guide and PAC, 76.9 (95% CI 72.2-81.5) for receipt of one of the materials, and 81.5 (95% CI 75.0-88.0) for those who received none of the materials. CONCLUSIONS: The study assessed the effectiveness of the atezolizumab additional risk minimization educational materials among physicians in six European countries, using process indicators. The educational materials reached over 70% of target physicians, 57.1% of whom reported using them. Knowledge and behavior related to immune-related adverse drug reactions for atezolizumab were no better in those who received the additional risk minimization educational materials. The results support the safe use of atezolizumab by these physician groups and contributed to the European Medicines Agency permitting removal of the HCP Guide.

Maternal and Infant Adverse Outcomes Associated with Mild and Severe Preeclampsia during the First Year after Delivery in the United States.

OBJECTIVE: The burden of preeclampsia severity on the health of mothers and infants during the first year after delivery is unclear, given the lack of population-based longitudinal studies in the United States. STUDY DESIGN: We assessed maternal and infant adverse outcomes during the first year after delivery using population-based hospital discharge information merged with vital statistics and birth certificates of 2,021,013 linked maternal-infant births in California. We calculated sampling weights using the National Center for Health Statistics data to adjust for observed differences in maternal characteristics between California and the rest of the United States. Separately, we estimated the association between preeclampsia and gestational age and examined collider bias in models of preeclampsia and maternal and infant adverse outcomes. RESULTS: Compared with women without preeclampsia, women with mild and severe preeclampsia delivered 0.66 weeks (95% confidence interval [CI]: 0.64, 0.68) and 2.74 weeks (95% CI: 2.72, 2.77) earlier, respectively. Mild preeclampsia was associated with an increased risk of having any maternal adverse outcome (relative risk [RR] = 1.95; 95% CI: 1.93, 1.97), as was severe preeclampsia (RR = 2.80; 95% CI: 2.78, 2.82). The risk of an infant adverse outcome was increased for severe preeclampsia (RR = 2.15; 95% CI: 2.14, 2.17) but only marginally for mild preeclampsia (RR = 0.99; 95% CI: 0.98, 1). Collider bias produced an inverse association for mild preeclampsia and attenuated the association for severe preeclampsia in models for any infant adverse outcome. CONCLUSION: Using multiple datasets, we estimated that severe preeclampsia is associated with a higher risk of maternal and infant adverse outcomes compared with mild preeclampsia, including an earlier preterm delivery.

Association of diabetes-related kidney disease with cardiovascular and non-cardiovascular outcomes: a retrospective cohort study.

BACKGROUND: Diabetes-related kidney disease is associated with end-stage renal disease and mortality, but opportunities remain to quantify its association with cardiovascular and non-cardiovascular morbidity outcomes. METHODS: We used the Truven Health MarketScan Commercial Claims and Encounters Database, 2010-2014, which includes specific health services records for employees and their dependents from a selection of large employers, health plans, and government and public organizations. We used administrative claims data to quantify the association between diabetes-related kidney disease and end-stage renal disease, myocardial infarction, congestive heart failure, stroke, and infections. Cox proportional hazard regression models were used to estimate adjusted hazard ratios of developing complications. RESULTS: Among 2.2 million patients with diabetes, 7.1% had diabetes-related kidney disease: 13.5%, stage 1-2; 33.8%, stage 3; 13.2% stages 4-5; 39.5%, unknown stage. In multivariable Cox proportional hazard models adjusted for demographic characteristics, baseline comorbid conditions, and total hospital days during the baseline period, hazard ratios for each outcome increased with greater diabetes-related kidney disease severity (stage 1-2 vs. stage 4-5) compared with no diabetes-related kidney disease: myocardial infarction, 1.2 (95% confidence interval 1.1-1.4) and 3.1 (2.9-3.4); congestive heart failure, 1.7 (1.6-1.9) and 5.6 (5.3-5.8); stroke, 1.3 (1.2-1.5) and 2.3 (2.1-2.5); infection, 1.4 (1.3-1.5) and 2.9 (2.8-3.0). Among patients with stage 4-5 disease, 36-month cumulative incidence was nearly 22.8% for congestive heart failure, and 25.8% for infections. CONCLUSIONS: Diabetes-related kidney disease appears to be formally diagnosed at a more advanced stage than might be expected, given clinical practice guidelines. Risks of cardiovascular and non-cardiovascular outcomes are high.

Comparative effectiveness of first-line nab-paclitaxel versus paclitaxel monotherapy in triple-negative breast cancer.

Aim: This observational study evaluated the effectiveness of nab-paclitaxel versus paclitaxel monotherapy as first-line (1L) treatment for metastatic triple-negative breast cancer (mTNBC). Materials & methods: 200 patients from the US Flatiron Health electronic health record-derived database (mTNBC diagnosis, January 2011-October 2016) who received 1L nab-paclitaxel (n = 105) or paclitaxel (n = 95) monotherapy were included. Overall survival and time to next treatment were evaluated. Results: The adjusted overall survival hazard ratio was 0.98 (95% CI: 0.67-1.44), indicating a similar risk of death between groups. Adjusted time to next treatment hazard ratio was 0.89 (95% confidence interval: 0.62-1.29). Conclusion: Nab-paclitaxel and paclitaxel monotherapy showed similar efficacy, suggesting their interchangeability as 1L treatments for mTNBC.

Building a network for multicenter, prospective research of central nervous system infections in South America: Process and lessons learned.

Multicenter collaborative networks are essential for advancing research and improving clinical care for a variety of conditions. Research networks are particularly important for central nervous system infections, which remain difficult to study due to their sporadic occurrence and requirement for collection and testing of cerebrospinal fluid. Establishment of long-term research networks in resource-limited areas also facilitates diagnostic capacity building, surveillance for emerging pathogens, and provision of appropriate treatment where needed. We review our experience developing a research network for encephalitis among twelve hospitals in five Peruvian cities since 2009. We provide practical suggestions to aid other groups interested in advancing research on central nervous system infections in resource-limited areas.

Reduction in the IL-6 level at 24 h after admission to the intensive care unit is a survival predictor for Vietnamese patients with sepsis and septic shock: a prospective study.

BACKGROUND: Sepsis and septic shock are common problems in intensive care units (ICUs). The mortality of patients with sepsis or septic shock is high. We investigated if reduction in the serum concentration of the cytokines tumor necrosis factor α, interleukin (IL)-6 and IL-10, and the rate of change in the IL-6 level at 24 h after ICU admission were survival predictors for patients with sepsis and septic shock in a Vietnamese population. METHODS: This was a prospective study conducted at an ICU in Cho Ray Hospital, Vietnam, from October 2014 to October 2016. Patients diagnosed with sepsis or septic shock using validated international guidelines were enrolled. Plasma samples were collected upon (T0) and 24 h after (T24) ICU admission for measurement of cytokine concentrations. Blood tests were done to detect organ dysfunction. The duration of ICU stays, hospital stay, APACHE II and SOFA scores, and the in-hospital mortality were compared between survival and non-survival groups. Univariate logistic regression and multivariate analysis were done to determine the association between survival and IL-6 reduction at 24 h after ICU admission. RESULTS: A total of 123 patients were enrolled. The concentration (in pg/mL) of IL-6 at To was 413.3 in survivors and 530.0 in non- survivors. At T24, the IL-6 level was 65.4 for survivors and 286.9 for non-survivors. The survival rate was 39.0%. At T24, the concentrations of IL-6 and the reduction in IL-6 level were predictors of survival in patients with sepsis and septic shock. We found a significant association between IL-6 reduction and survival at ≥86% with Odds Ratio (OR) 5.67, 95% Confidence Interval (CI); 1.27-25.3, compared with an increase in the IL-6 rate of change. CONCLUSIONS: Our findings suggested that a reduction in the IL-6 level of ≥86% at 24 h from ICU admission is a survival predictor for patients with sepsis and septic shock in our population.

The Lifetime Health Burden of Delayed Graft Function in Kidney Transplant Recipients in the United States.

Background. Although delayed graft function (DGF) is associated with an increased risk of acute rejection and decreased graft survival, there are no estimates of the long-term or lifetime health burden of DGF. Objectives. To estimate the long-term and lifetime health burden of DGF, defined as the need for at least one dialysis session within the first week after transplantation, for a cohort representative of patients who had their first kidney transplant in 2014. Methods. Data from the United States Renal Data System (USRDS; 2001-2014) were used to estimate a semi-Markov parametric multi-state model with three disease states. Maximum length of follow-up was 13.7 years, and a microsimulation model was used to extrapolate results over a lifetime. The impact of DGF was assessed by simulating the model for each patient in the cohort with and without DGF. Results. At the end of 13.7 years of follow-up, DGF reduces the probability of having a functioning graft from 52% to 32%, increases the probability of being on dialysis from 10% to 19%, and increases the probability of death from 38% to 50% relative to transplant recipients who do not experience DGF. A typical transplant recipient with DGF (median age = 53) is observed to lose 0.87 quality-adjusted life-years (QALYs). Extrapolated over a lifetime, the same 53-year-old DGF patient is projected to lose 3.01 (95% confidence interval: 2.33, 3.70) QALYs relative to a transplant recipient with the same characteristics who does not experience DGF. Conclusions. The lifetime health burden of DGF is substantial. Understanding these consequences will help health care providers weigh kidney transplant decisions and inform policies for patients in the context of varying risks of DGF.

A review of Vietnam's healthcare reform through the Direction of Healthcare Activities (DOHA).

OBJECTIVE: This article provides a comprehensive review of the healthcare reform process driven by the Vietnamese Ministry of Health's Direction of Healthcare Activities (DOHA) scheme. METHODS: We reviewed policy documents relating to DOHA, along with historical literature and background information describing its formation. RESULTS: DOHA (Chi dao tuyen in Vietnamese) literally means guidance line or level in English. It requires healthcare facilities at higher government administration levels to support those at lower levels (the four levels being central, provincial, district, and commune), to help lower level hospitals to provide medical services for local communities in primary care settings and reduce the number of patients in higher level (central and provincial) hospitals. Since the 1990s, there have been too many patients attending higher level hospitals, and DOHA has therefore focused on technical skills transfer training to help alleviate this situation. Designated core central hospitals now provide technical skills transfer to provincial hospitals. Professional technical lists for each level of health facility have enabled strong commitment and proactive ownership of the process of training management in both higher and lower level hospitals. CONCLUSION: The DOHA scheme has accelerated the necessary up-skilling of healthcare at lower level public hospitals across Vietnam. These reforms are highly relevant for other countries with limited healthcare resources.

Short-term costs of preeclampsia to the United States health care system.

BACKGROUND: Preeclampsia is a leading cause of maternal morbidity and mortality and adverse neonatal outcomes. Little is known about the extent of the health and cost burden of preeclampsia in the United States. OBJECTIVE: This study sought to quantify the annual epidemiological and health care cost burden of preeclampsia to both mothers and infants in the United States in 2012. STUDY DESIGN: We used epidemiological and econometric methods to assess the annual cost of preeclampsia in the United States using a combination of population-based and administrative data sets: the National Center for Health Statistics Vital Statistics on Births, the California Perinatal Quality Care Collaborative Databases, the US Health Care Cost and Utilization Project database, and a commercial claims data set. RESULTS: Preeclampsia increased the probability of an adverse event from 4.6% to 10.1% for mothers and from 7.8% to 15.4% for infants while lowering gestational age by 1.7 weeks (P < .001). Overall, the total cost burden of preeclampsia during the first 12 months after birth was $1.03 billion for mothers and $1.15 billion for infants. The cost burden per infant is dependent on gestational age, ranging from $150,000 at 26 weeks gestational age to $1311 at 36 weeks gestational age. CONCLUSION: In 2012, the cost of preeclampsia within the first 12 months of delivery was $2.18 billion in the United States ($1.03 billion for mothers and $1.15 billion for infants), and was disproportionately borne by births of low gestational age.

Predictors of incident epilepsy in older adults: The Cardiovascular Health Study.

OBJECTIVE: To determine the prevalence, incidence, and predictors of epilepsy among older adults in the Cardiovascular Health Study (CHS). METHODS: We analyzed data prospectively collected in CHS and merged with data from outpatient Medicare administrative claims. We identified cases with epilepsy using self-report, antiepileptic medication, hospitalization discharge ICD-9 codes, and outpatient Medicare ICD-9 codes. We used Cox proportional hazards regression to identify factors independently associated with incident epilepsy. RESULTS: At baseline, 42% of the 5,888 participants were men and 84% were white. At enrollment, 3.7% (215 of 5,888) met the criteria for prevalent epilepsy. During 14 years of follow-up totaling 48,651 person-years, 120 participants met the criteria for incident epilepsy, yielding an incidence rate of 2.47 per 1,000 person-years. The period prevalence of epilepsy by the end of follow-up was 5.7% (335 of 5,888). Epilepsy incidence rates were significantly higher among blacks than nonblacks: 4.44 vs 2.17 per 1,000 person-years (p < 0.001). In multivariable analyses, risk of incident epilepsy was significantly higher among blacks compared to nonblacks (hazard ratio [HR] 4.04, 95% confidence interval [CI] 1.99-8.17), those 75 to 79 compared to those 65 to 69 years of age (HR 2.07, 95% CI 1.21-3.55), and those with history of stroke (HR 3.49, 95% CI 1.37-8.88). CONCLUSIONS: Epilepsy in older adults in the United States was common. Blacks, the very old, and those with history of stroke have a higher risk of incident epilepsy. The association with race remains unexplained.

The financial burden and health care utilization patterns associated with amnestic mild cognitive impairment.

INTRODUCTION: Individuals with amnestic mild cognitive impairment (aMCI) are at elevated risk of developing Alzheimer's disease (AD) dementia. METHODS: With data from the Aging, Demographics, and Memory Study, we used the Clinical Dementia Rating Sum of Boxes classifications to conduct a cross-sectional analysis assessing the relationship between cognitive state and various direct and indirect costs and health care utilization patterns. RESULTS: Patients with aMCI had less medical expenditures than patients with moderate and severe AD dementia (P < .001) and were also significantly less likely to have been hospitalized (P = .04) and admitted to nursing home (P < .001). Compared to individuals with normal cognition, patients with aMCI had significantly less household income (P = .018). DISCUSSION: Patients with aMCI had lower medical expenditures than patients with AD dementia. Poor cognitive status was linearly associated with lower household income, higher medical expenditures, higher likelihood of nursing and home care services, and lower likelihood of outpatient visits.

The Changing Epidemiology of Human T-Cell Lymphotropic Virus Type 1 Infection in Peruvian Female Sex Workers, 1993-2010.

Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus to be reported and is associated with neoplastic, neurological, autoimmune, and infectious complications. HTLV-1 is endemic in Peru, with the highest prevalence reported among commercial sex workers. Seroprevalence data collected from Peruvian female sex workers (FSWs) working in Callao over three study periods between 1993 and 2010 were used to examine the secular trend in HTLV-1 prevalence. Between 1993 and 2010, the prevalence of HTLV-1 decreased significantly from 14.5% to 3.1% (P < 0.01). The prevalence of HTLV-1 seropositivity differed significantly by birth cohort (1922-1959, 1960-1969, 1970-1979, and 1980-1992), and for each of the four birth cohorts, the prevalence did not significantly decrease by screening year (P > 0.07). There were no cases of HTLV-1 detected among FSW born after 1979 (N = 224). Participant characteristics associated with HTLV-1 seropositivity were birth in the Andes Mountains region, age, increased time in sex work, younger age of starting sex work, and human immunodeficiency virus (HIV) seropositivity. The secular trend in declining prevalence persisted after adjustment for age, time in sex work, place of birth, and HIV serostatus, with the odds of HTLV-1 infection decreasing approximately 16% per year (adjusted odds ratio = 0.84, 95% confidence interval = 0.78, 0.90). The increasing use of condoms by later birth cohorts noted in our analysis, as well as the increasing availability of free condoms provided by the Peruvian government-which started in the late 1980s before this study-may have been responsible for declining HTLV seroprevalence.

Value of improved lipid control in patients at high risk for adverse cardiac events.

OBJECTIVES: Lipid-lowering therapy (LLT) is suboptimally used in patients with hyperlipidemia in the 2 highest statin benefit groups (SBGs), as categorized by the American College of Cardiology and the American Heart Association. This study estimated the social value of reducing low-density lipoprotein cholesterol (LDL-C) levels by 50% for patients in SBGs 1 and 2 who have been treated with standard LLT but have not reached LDL-C goal, as well as the potential value of PCSK9 inhibitors for patients in these groups. STUDY DESIGN: Simulation model. METHODS: We used National Health and Nutrition Examination Surveys (NHANES) and US Census data to project the population of SBGs 1 and 2 in the time period 2015 to 2035. We used insurance claims data to estimate incidence rates of major adverse cardiac events (MACEs), and NHANES with National Vital Statistics data to estimate cardiovascular disease mortality rates. Using established associations between LDL-C and MACE risk, we estimated the value of reducing LDL-C levels by 50%. We incorporated results from a meta-analysis to estimate the value of PSCK9 inhibitors. RESULTS: Among those treated with LLT with LDL-C > 70 mg/dL in SBGs 1 and 2, the cumulative value of reducing LDL-C levels by 50% would be $2.9 trillion from 2015 to 2035, resulting primarily from 1.6 million deaths averted. The cumulative value of PCSK9 inhibitors would range from $3.4 trillion to $5.1 trillion (1.9-2.8 million deaths averted), or $12,000 to $17,000 per patient-year of treatment. CONCLUSIONS: Lowering LDL-C in high-risk patients with hyperlipidemia has enormous potential social value. For patients in these high-risk groups, PCSK9 inhibitors may have considerable net value depending on the final prices payers ultimately select.

Assessing Needs for Cancer Education and Support in American Indian and Alaska Native Communities in the Northwestern United States.

American Indians and Alaska Natives (AI/ANs) experience significant cancer disparities. To inform future public health efforts, a web-based needs assessment survey collected quantitative and qualitative data from AI/AN community health workers and cancer survivors in the northwestern United States. Content analysis of qualitative responses identified themes to contextualize quantitative results. Seventy-six AI/AN respondents (93% female) described substantial unmet needs for education and resources to assist cancer survivors, including a shortage of patient navigators, support groups, and home health care workers. Fear of negative outcomes, a culturally rooted avoidance of discussing illness, and transportation difficulties were cited as major barriers to participation in cancer education and receipt of health services. Face-to-face contact was overwhelmingly preferred for community education and support, but many respondents were receptive to other communication channels, including e-mail, social media, and webinars. Survey results highlight the importance of culturally sensitive approaches to overcome barriers to cancer screening and education in AI/AN communities. Qualitative analysis revealed a widespread perception among respondents that available financial and human resources were insufficient to support AI/AN cancer patients' needs.

The burden of mental health in lymphatic filariasis.

BACKGROUND: Neglected Tropical Diseases (NTDs) afflict around one billion individuals in the poorest parts of the world with many more at risk. Lymphatic filariasis is one of the most prevalent of the infections and causes significant morbidity in those who suffer the clinical conditions, particularly lymphedema and hydrocele. Depressive illness has been recognised as a prevalent disability in those with the disease because of the stigmatising nature of the condition. No estimates of the burden of depressive illness of any neglected tropical disease have been undertaken to date despite the recognition that such diseases have major consequences for mental health not only for patients but also their caregivers. METHODS: We developed a mathematical model to calculate the burden of Disability- Adjusted Life Years (DALY) attributable to depressive illness in lymphatic filariasis and that of their caregivers using standard methods for calculating DALYs. Estimates of numbers with clinical disease was based on published estimates in 2012 and the numbers with depressive illness from the available literature. RESULTS: We calculated that the burden of depressive illness in filariasis patients was 5.09 million disability-adjusted life years (DALYs) and 229,537 DALYs attributable to their caregivers. These figures are around twice that of 2.78 million DALYs attributed to filariasis by the Global Burden of Disease study of 2010. CONCLUSIONS: Lymphatic filariasis and other neglected tropical diseases, notably Buruli Ulcer, cutaneous leishmaniasis, leprosy, yaws, onchocerciasis and trachoma cause significant co morbidity associated with mental illness in patients. Studies to assess the prevalence of the burden of this co-morbidity should be incorporated into any future assessment of the Global Burden of neglected tropical diseases. The prevalence of depressive illness in caregivers who support those who suffer from these conditions is required. Such assessments are critical for neglected tropical diseases which have such a huge global prevalence and thus will contribute a significant burden of co-morbidity attributable to mental illness.