Incidence of Herpes Zoster and Postherpetic Neuralgia and Herpes Zoster Vaccination Uptake in a US Administrative Claims Database.

Background: The objective of this study was to estimate the annual incidence rates of herpes zoster (HZ) and postherpetic neuralgia (PHN) among individuals aged ≥19 years and the proportion who received HZ vaccination among those aged ≥50 years. Methods: This observational cohort study was conducted with administrative claims data from HealthVerity and included insured individuals across the US. Crude and US age- and sex-standardized incidence rates of HZ and PHN were calculated from 1 January 2019 to 31 May 2022 by calendar year in persons aged ≥19 years. Outcomes were defined as ≥1 ICD-10 diagnosis code for HZ or PHN. Analyses were stratified by age, sex, and immunocompromised status. Among those aged ≥50 years, the proportion who received 1 or 2 doses of recombinant zoster vaccine (Shingrix) or 1 dose of Zostavax was calculated. Results: Standardized annual incidence rates from 2019 to 2021 were 542 to 685 per 100 000 person-years for HZ and 35 to 38 per 100 000 person-years for PHN. Rates were highest among females, older adults, and individuals who were immunocompromised. From 1 January 2019 to 31 May 2022, 4.3% and 9.0% of persons aged ≥50 years received 1 and 2 doses of Shingrix, respectively, and 0.2% received 1 dose of Zostavax. Conclusions: In this US claims database analysis, HZ and PHN were more frequent among older adults, females, and individuals who were immunocompromised. Between 1 January 2019 and 31 May 2022, 9% of persons aged ≥50 years received 2 doses of the Shingrix vaccine. Greater efforts are needed to increase vaccine uptake against HZ, especially for those at highest risk.

Prevalence of Diagnosed Genital Herpes and Antiviral Treatment in the United States.

BACKGROUND: Genital herpes is a common sexually transmitted infection caused by the herpes simplex virus. Contemporary United States (US) population-based epidemiologic data on genital herpes are limited. This study aimed to provide nationally representative estimates of genital herpes prevalence and treatment using a large US health insurance claims database. METHODS: This observational cohort study used administrative claims data from HealthVerity. Crude and age- and sex-standardized prevalence rates of genital herpes and recurrent genital herpes were calculated for the years 2019 to 2021. The distribution of patients with prevalent genital herpes who received episodic or suppressive antiviral therapy was also estimated. RESULTS: From 2019 to 2021, the standardized prevalence of genital herpes and recurrent genital herpes ranged from 236 to 280 cases per 100,000 person-years and 81 to 98 cases per 100,000 person-years, respectively. The prevalence of genital herpes was highest among those aged 25-29 years (prevalence range: 497 to 582), female patients (prevalence range: 348 to 404), and those with a history of HIV infection (prevalence range: 1608 to 2080). The prevalence of recurrent genital herpes was also highest in these groups. From 2019 to 2021, two-thirds of patients (65% to 68%) with prevalent genital herpes received antiviral medications; the majority received episodic therapy (80%) rather than suppressive therapy (20%). CONCLUSIONS: The burden of genital herpes and recurrent genital herpes in the US is substantial, with the highest rates observed in young adults, women, and immunocompromised individuals. About two-thirds receive antiviral treatment each year.

Testing for Cytomegalovirus Among Individuals Who Were Immunocompromised, 2018-2022.

This cohort study investigates rates of cytomegalovirus testing before and during the COVID-19 pandemic among individuals who were immunocompromised.

Association of Social Support with Mild Cognitive Impairment and Dementia Among Older Women: The Women's Health Initiative Memory Study.

BACKGROUND: Social support may be a modifiable risk factor for cognitive impairment. However, few long-term, large prospective studies have examined associations of various forms of social support with incident mild cognitive impairment (MCI) and dementia. OBJECTIVE: To examine associations of perceived social support with incident MCI and dementia among community-dwelling older women. METHODS: This prospective cohort study included 6,670 women from the Women's Health Initiative Memory Study who were cognitively unimpaired at enrollment. We used Cox proportional hazards models to assess associations between perceived social support with incident MCI, dementia, or either MCI/dementia during an average 10.7 (SD = 6.1)-year follow-up. Modelling was repeated for emotional/information support, affection support, tangible support, and positive social interaction subscales of social support. RESULTS: Among 6,670 women (average age = 70 years [SD = 3.8]; 97.0% non-Hispanic/Latina; 89.8% White), greater perceived social support was associated with lower risk of MCI/dementia after adjustment for age, ethnicity, race, hormone therapy, education, income, diabetes, hypertension, and body mass index (Tertile [T]3 versus T1: HR = 0.85, 95% CI 0.74-0.99; ptrend = 0.08). Associations were significant for emotional/information support (T3 versus T1: HR = 0.84, 95% CI 0.72-0.97; ptrend = 0.04) and positive social interaction (T3 versus T1: HR = 0.85, 95% CI 0.73-0.99; ptrend = 0.06) subscales. Associations were attenuated and not significant after adjustment for depressive symptom severity. OBJECTIVE: Perceived social support, emotional/information support, and positive social interaction were associated with incident MCI/dementia among older women. Results were not significant after adjustment for depressive symptom severity. Improving social support may reduce risk of MCI and dementia in older women.

The Association of Epigenetic Age Acceleration and Multimorbidity at Age 90 in the Women's Health Initiative.

BACKGROUND: Epigenetic age acceleration (EAA), a measure of accelerated biological aging, has been associated with an increased risk of several age-related chronic conditions. This is the first study to prospectively examine the relationship between EAA and both multimorbidity count and a weighted multimorbidity score among long-lived postmenopausal women. METHODS: We included 1 951 women from the Women's Health Initiative who could have survived to age 90. EAA was estimated using the Horvath pan-tissue, Hannum, PhenoAge, and GrimAge "clocks." Twelve chronic conditions were included in the multimorbidity count. The multimorbidity score was weighted for each morbidity's relationship with mortality in the study population. Using mixed-effects Poisson and linear regression models that included baseline covariates associated with both EAA and multimorbidity, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for the relationships between each EAA measure at the study baseline with both multimorbidity count and weighted multimorbidity score at age 90, respectively. RESULTS: For every one standard deviation increase in AgeAccelPheno, the rate of multimorbidity accumulation increased 6% (RR = 1.06; 95% CI = 1.01-1.12; p = .025) and the multimorbidity score by 7% (RR = 1.07; 95% CI = 1.01-1.13; p = .014) for women who survived to age 90. The results for a one standard deviation increase in AgeAccelHorvath, AgeAccelHannum, and AgeAccelGrim with multimorbidity accumulation and score were weaker compared to AgeAccelPheno, and the latter 2 did not reach statistical significance. CONCLUSION: AgeAccelPheno and AgeAccelHannum may predict multimorbidity count and score at age 90 in older women and, thus, may be useful as a biomarker predictor of multimorbidity burden in the last decades of life.

Analysis of Epigenetic Age Acceleration and Healthy Longevity Among Older US Women.

Importance: Accelerated biological aging is associated with decreased physical capability and cognitive functioning, which are associated with increased risk of morbidity and mortality. Objective: We investigated associations between epigenetic age acceleration (EAA), a biomarker associated with aging, and healthy longevity among older women. Design, Setting, and Participants: This cohort study was a secondary analysis of participants in the Women's Health Initiative (WHI) who were eligible to survive to age 90 years by September 30, 2020. Participants were located in multiple centers. This study was restricted to women with genome-wide DNA methylation data, generated from baseline blood samples within 3 WHI ancillary studies. Median (IQR) follow-up times from baseline were 21.6 (19.6-22.9) years and 21.4 (19.8-22.7) years for women who survived to age 90 years with and without intact mobility, respectively, and 13.2 (8.8-16.7) for women who did not survive to age 90 years. Data were analyzed from December 2020 to July 2021. Exposures: EAA was estimated using 4 established "clocks": Horvath pantissue, Hannum, Pheno, and Grim. Main Outcomes and Measures: Using multinomial logistic regression, odds ratios (ORs) and 95% CIs were estimated for 3 healthy longevity outcomes for each clock: survival to age 90 years with intact mobility, survival to age 90 years without intact mobility, and no survival to age 90 years. Results: Among 1813 women, there were 464 women (mean [SD] age at baseline, 71.6 [3.5] years) who survived to age 90 years with intact mobility and cognitive functioning, 420 women (mean [SD] age at baseline, 71.3 [3.2] years) who survived to age 90 years without intact mobility and cognitive functioning, and 929 women (mean [SD] age at baseline, 70.2 [3.4] years) who did not survive to age 90 years. Women who survived to age 90 years with intact mobility and cognitive function were healthier at baseline compared with women who survived without those outcomes or who did not survive to age 90 years (eg, 143 women [30.8%] vs 101 women [24.0%] and 202 women [21.7%] with 0 chronic conditions). The odds of surviving to age 90 years with intact mobility were lower for every 1 SD increase in EAA compared with those who did not survive to age 90 years as measured by AgeAccelHorvath (OR, 0.82; 95% CI, 0.69-0.96; P = .01), AgeAccelHannum (OR, 0.67; 95% CI, 0.56-0.80; P < .001), AgeAccelPheno (OR, 0.60; 95% CI, 0.51-0.72; P < .001), and AgeAccelGrim (OR, 0.68; 95% CI, 0.55-0.84; P < .001). ORs were similar for women who survived to age 90 years with intact mobility and cognitive function (eg, AgeAccelHorvath: OR per 1 SD increase in EAA, 0.83; 95% CI, 0.71-0.98; P = .03) compared with women who did not survive to age 90 years. Conclusions and Relevance: These findings suggest that EAA may be a valid biomarker associated with healthy longevity among older women and may be used for risk stratification and risk estimation of future functional and cognitive aging. Outcomes suggest that future studies may focus on the potential for public health interventions to counteract EAA and its association with poor health outcomes to lower disease burden while increasing longevity.

A survey of distracted driving and electronic device use among app-based and taxi drivers.

OBJECTIVES: The purpose of this study was to identify, characterize and compare attitudes, beliefs, behaviors and other factors related to electronic device (ED) use and distracted driving (DD) among taxi and app-based drivers. METHODS: A survey among drivers in San Diego and across the United States was used to collect self-reported attitudes and behaviors among taxi and app-based passenger-carrying drivers from October 1, 2016 to January 31, 2017. Chi-square or Fisher's exact test was used to assess the difference between sociodemographics, ED use, ED use attitudes, and citation and crash history by driver type. Prevalence ratios were assessed for differences in ED use and ED use attitudes by driver type using Poisson regression models with robust error variance and a log link function. The final models adjusted for age, sex, level of experience, education and English fluency. All analyses were performed using SAS version 9.4. RESULTS: Of the 175 drivers that met eligibility criteria, 131 reported driving for app-based services and 44 identified as taxi drivers. Compared to taxi drivers, app-based drivers were more likely to be female, native English speaking, and have fewer than 3 years of experience in the transportation business. All drivers reported at least one type of DD while the car was in motion. App-based drivers were significantly more likely to use a smartphone while driving (adjusted prevalence ratio (APR): 1.42), report that while driving it is safe or very safe to accept a call (APR: 1.73), receive/respond to a passenger request (APR: 3.40), or process a payment (APR: 5.39). Taxi drivers were more likely to either receive a citation for ED use (31.8% v 7.6%, p < 0.001) or be in a collision while using ED (29.6% v 4.6%, p < 0.001). Almost all drivers who received a citation or who were involved in a crash reported becoming somewhat or significantly more cautious about using ED while driving. CONCLUSIONS: Drivers in the small passenger-carrying transportation industry engage in DD frequently due to occupational demands. Given the known increased crash risk with DD, effective policies and interventions for app-based and taxi drivers are needed.

Evaluation of Light Physical Activity Measured by Accelerometry and Mobility Disability During a 6-Year Follow-up in Older Women.

Importance: Almost 1 in 4 women older than 65 years is unable to walk 2 to 3 blocks, and mobility disability is a key factor associated with loss of independence. Lack of moderate to vigorous-intensity physical activity is associated with mobility disability, but whether lighter physical activity is associated with mobility disability is unknown. Objective: To determine the association of light-intensity physical activity and incident mobility disability among older women. Design, Setting, and Participants: This prospective cohort study included women enrolled in the Objectively Measured Physical Activity and Cardiovascular Health study, an ancillary study of the Women's Health Initiative, between March 2012 and April 2014, with follow-up through March 31, 2018. The Women's Health Initiative was a population-based, multisite study that recruited from 40 clinical sites across the US. Participants in the present analysis included 5735 of 7058 ambulatory, community-dwelling women aged 63 years and older who returned an accelerometer with usable data, were free of mobility disability, and had follow-up data on mobility status. Data were analyzed from August 2018 to May 2019. Exposures: Light-intensity physical activity, defined as movement requiring energy expenditure between 1.6 and 2.9 metabolic equivalents, captured using an accelerometer over 7 days. Main Outcomes and Measures: Incident mobility disability, defined as the first self-reported inability to walk 1 block or up a flight of stairs at annual follow-up, and persistent incident mobility disability, defined as incident mobility loss that persisted through the end of follow-up. Results: A total of 5735 participants were included for primary analysis of all incident mobility disability (mean [SD] age, 78.5 [6.6] years [range, 63-97 years]; 2811 [49.0%] White participants). Compared with women in the lowest quartile of light-intensity physical activity, lower risk of incident mobility disability was observed in quartile 2 (multivariable hazard ratio [HR], 0.78; 95% CI, 0.67-0.90), quartile 3 (HR, 0.60; 95% CI, 0.51-0.71), and quartile 4 (HR, 0.60; 95% CI, 0.51-0.71) (P < .001). This beneficial association was stronger for persistent mobility disability in quartile 2 (multivariable HR, 0.72; 95% CI, 0.60-0.85), quartile 3 (HR, 0.55; 95% CI, 0.46-0.67), and quartile 4 (HR, 0.52; 95% CI, 0.42-0.63) (P < .001). Stratified analyses showed the association was stronger among women with a body mass index of less than 30.0 (HR, 0.73; 95% CI, 0.66-0.82) compared with women with a body mass index of 30.0 or higher (HR, 0.91; 95% CI; 0.79-1.04; P = .04 for interaction). Conclusions and Relevance: In this cohort study, increased time spent in light-intensity physical activity was associated with reduced incident mobility disability. These findings support placing greater emphasis on promoting light-intensity physical activity for preserving mobility in later life.

The Relationship of Accelerometer-Assessed Standing Time With and Without Ambulation and Mortality: The WHI OPACH Study.

BACKGROUND: Self-reported time spent standing has been associated with lower risk of mortality. No previous studies have examined this association using device-measured standing. METHOD: This was a prospective cohort study of 5878 older (median age = 80 years), racial/ethnically diverse, community-dwelling women in the WHI Objective Physical Activity and Cardiovascular Health Study (OPACH). Women wore accelerometers for 1 week and were followed for mortality. The study applied previously validated machine learning algorithms to ActiGraph GT3X+ accelerometer data to separately measure time spent standing with and without ambulation. Cox proportional hazards models were used to estimate mortality risk adjusting for potential confounders. Effect modification by age, body mass index, moderate-to-vigorous physical activity, sedentary time, physical functioning, and race/ethnicity was evaluated. RESULTS: There were 691 deaths during 26 649 person-years of follow-up through March 31, 2018 (mean follow-up = 4.8 years). In fully adjusted models, all-cause mortality risk was lower among those with more standing without ambulation (quartile [Q] 4 vs Q1 HR = 0.63; 95% CI = 0.49-0.81, p-trend = .003) and more standing with ambulation (Q4 vs Q1 HR = 0.50; 95% CI = 0.35-0.71, p-trend < .001). Associations of standing with ambulation and mortality were stronger among women with above-median sedentary time (HR = 0.51; 95% CI = 0.38-0.68) compared to women with below-median sedentary time (HR = 0.80; 95% CI = 0.59-1.07; p-interaction = .02). CONCLUSIONS: In this prospective study among older women, higher levels of accelerometer-measured standing were associated with lower risks of all-cause mortality. Standing is an achievable approach to interrupting prolonged sedentary time, and if not contraindicated, is a safe and feasible behavior that appears to benefit health in older ages.

Twitter Communication During an Outbreak of Hepatitis A in San Diego, 2016-2018.

Objectives. To examine how and what information is communicated via social media during an infectious disease outbreak.Methods. In the context of the 2016 through 2018 hepatitis A outbreak in San Diego County, California, we used a grounded theory-based thematic analysis that employed qualitative and quantitative approaches to uncover themes in a sample of public tweets (n = 744) from Twitter, a primary platform used by key stakeholders to communicate to the public during the outbreak.Results. Tweets contained both general and hepatitis A-specific information related to the outbreak, restatements of policy and comments critical of government responses to the outbreak, information with the potential to shape risk perceptions, and expressions of concern regarding individuals experiencing homelessness and their role in spreading hepatitis A. We also identified misinformation and common channels of content driving themes that emerged in our sample.Conclusions. Public health professionals may identify real-time public risk perceptions and concerns via social media during an outbreak and target responses that fulfill the informational needs of those who seek direction and reassurance during times of uncertainty.

Indicators of potential health-related social needs and the association with perceived health and well-being outcomes among community-dwelling medicare beneficiaries.

PURPOSE: Health-related social needs (HRSNs) can make older adults' more vulnerable and impact their health, well-being, and ability to age-in-place. The current study assessed the prevalence of potential HRSNs (pHRSNs) across several domains (e.g., transportation, social isolation) and explored the associations with health and well-being outcomes in a sample of Medicare beneficiaries. METHODS: Cross-sectional analyses were conducted with a representative sample of community-dwelling Medicare beneficiaries (N = 5758) from the 2012 National Health and Aging Trends Study. Binary indicators of pHRSNs were created for five domains: medical and utility financial needs (MUFN), housing, nutrition, social isolation, and transportation. Outcomes were depression/anxiety, self-rated health, meaning/satisfaction, perceived control/adaptability. Variables were weighted, and multivariate regression models assessed associations between pHRSN variables and outcomes, controlling for sociodemographics and health conditions. RESULTS: Of the estimated 32 million community-dwelling beneficiaries, approximately 13.3 million were positive for ≥ 1 pHRSN and 11.4 million for ≥ 2 pHRSNs. The prevalence by domain was 7% for housing, 8% for transportation, 12% for UMFN and nutrition, and 33% for social isolation. Each domain, except for housing, was significantly (p < .05) associated with at least two of the four outcomes, where being positive for a pHRSN was associated with greater depression/anxiety and poorer self-rated general health. CONCLUSIONS: Over 40% of Medicare beneficiaries had ≥ 1 pHRSN indicators, which means they are more vulnerable and that may limit their ability to age-in-place. Given the growing aging population, better measures and methods are needed to identify, monitor, and address HRSNs. For example, leveraging existing community-based services through coordinated care may be an effective strategy to address older adults' HRSNs.

Conservative management of suspicious melanocytic lesions of the iris.

PURPOSE: The diagnosis of iris melanoma can be difficult, with no established diagnostic criteria currently available. Careful monitoring of patients with suspicious iris lesions is one approach to managing these tumors. We determined the risk of malignant transformation and melanoma-related mortality in patients under observation to evaluate the validity of this management approach. METHODS: This was a retrospective chart review of patients with suspicious iris lesions diagnosed at Massachusetts Eye and Ear Infirmary (MEE) between 1975 and 2014. All patients with an initial diagnosis of suspicious iris lesion followed and/or treated after malignant transformation at the MEE in this 39-year period were included in the cohort. Rates of malignant transformation and melanoma-related mortality were calculated. Treatment outcomes after proton beam irradiation were evaluated in patients who developed iris melanomas during observation. RESULTS: Two hundred thirty-four patients had a diagnosis of suspicious iris lesion (median follow-up, 5.8 years). Malignant transformation occurred in 16 (6.8%) patients with suspicious lesions during the observation period (median follow-up, 9.9 years). All patients diagnosed with iris melanomas were treated with proton beam irradiation (PBI). Complications after treatment included cataract (18.8%), secondary glaucoma (6.3%), and neovascular glaucoma (12.5%). Two of 16 patients (12.5%) who developed iris melanomas died of metastatic melanoma 32.6 months and 10 years after treatment with PBI. Both cases had been followed regularly to monitor for malignant transformation of their suspicious lesions (8.2 years and 3.2 years before melanoma diagnosis, respectively). CONCLUSIONS: These data suggest that suspicious iris lesions have low malignant potential, and a conservative approach to the management of these lesions is appropriate. Survival does not appear to be compromised with an observational approach, and there is potential for preservation of good visual function because vision-threatening treatments can be avoided.

Safety and efficacy of rivaroxaban for the secondary prevention following acute coronary syndromes among biomarker-positive patients: Insights from the ATLAS ACS 2-TIMI 51 trial.

BACKGROUND:: Despite dual antiplatelet therapy, persistent thrombin generation and thrombin-mediated platelet activation account in part for the residual risk of atherothrombotic disease among patients with prior acute coronary syndrome (ACS). Inhibition of thrombin generation among high-risk ACS patients (biomarker-positive ACS) with the factor Xa inhibitor rivaroxaban may limit ongoing thrombus formation and myocardial necrosis and thereby improve clinical outcomes. OBJECTIVES AND METHODS:: ATLAS ACS 2-TIMI 51 was a double-blind, placebo-controlled clinical trial that randomized ACS patients to either rivaroxaban 2.5 mg b.i.d., rivaroxaban 5 mg b.i.d., or placebo plus standard-of-care antiplatelet therapy for a mean of 13.1 months and up to 31 months ( N=15,526). This post-hoc analysis evaluates the safety and efficacy of rivaroxaban among biomarker-positive ACS patients with and without a history of prior stroke of transient ischemic attack in the ATLAS ACS 2-TIMI 51 trial. RESULTS:: A total of 12,626 biomarker-positive ACS patients were included in this analysis. Among biomarker-positive patients without a prior history of stroke or transient ischemic attack, rivaroxaban 2.5 b.i.d. was associated with a reduction in the primary efficacy endpoint (composite of cardiovascular death, myocardial infarction, or stroke) as compared with placebo (hazard ratio=0.80, 95% confidence interval (0.68-0.94), p=0.007) at the expense of an increase in non-coronary-artery-bypass-graft-related Thrombolysis in Myocardial Infarction major bleeding (1.9% vs. 0.7%, p<0.0001), but not a significant increase in either intracranial hemorrhage (0.4% vs. 0.2%, p=0.11) or fatal bleeding (0.1% vs. 0.3%, p=0.16). CONCLUSION:: Rivaroxaban 2.5 mg b.i.d. was associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, or stroke with no increase in fatal bleeding. Biomarker-positive patients with no prior history of stroke or transient ischemic attack may be a optimal target population to receive "dual pathway" therapy with rivaroxaban plus dual antiplatelet therapy for secondary prevention following ACS.

Emerging Evidence for Infectious Causes of Cancer in the United States.

Worldwide, infectious agents currently contribute to an estimated 15% of new cancer cases. Most of these (92%, or 2 million new cancer cases) are attributable to 4 infectious agents: Helicobacter pylori, human papillomavirus, and hepatitis B and C viruses. A better understanding of how infectious agents relate to the US cancer burden may assist new diagnostic and treatment efforts. We review US-specific crude mortality rates from infection-associated cancers and describe temporal and spatial trends since 1999. We review the US-specific evidence for infection-cancer associations by reporting available estimates for attributable fractions for the infection-cancer associations. Death due to cancers with established infectious associations varies geographically, but estimates for the US attributable fraction are limited to a few observational studies. To describe the burden of infection-associated cancer in the United States, additional observational studies are necessary to estimate the prevalence of infection nationally and within subpopulations. As infectious associations emerge to explain cancer etiologies, new opportunities and challenges to reducing the burden arise. Improved estimates for the United States would help target interventions to higher-risk subpopulations.

Identifying waterborne disease prone areas using geospatial approach along the right bank of Yamuna River in Delhi.

This paper presents a spatial risk analysis of waterborne diseases using analytical hierarchy process that rely on geographical information system (GIS)-automated techniques. We selected nine parameters for assessing waterborne diseases prone areas (WBDP). All the weighted parameter layers were integrated to obtain WBDP map. Of the total WBDP area, 42% area was found under medium category, 34% and 24% area under high and low category, respectively. We have also empirically analysed the factors influencing WBDP areas using regression model. Results revealed that explanatory variables like purification of water, washing hand before drinking and eating, and Surface Water Quality Index (SWQI) are the most influential and positively associated while dipping hand in the vessel is negatively associated with the WBD. Further, WBDP areas were validated by analysing their relationship with the actual incidences of WBD(s). Our study may prove to be beneficial for managing and formulating guidelines for the WBDP areas in similar geographical regions. Abbreviations: GIS: Geographical information system; WBDP: Water borne diseases prone areas; SWQI: Surface water quality index; WBD: Water borne Disease; MDG: Millennium Development Goal; AHP: Analytical hierarchical process; GPS: Global Positioning System; NCR: National Capital Region; IDW: Inverse distance weighted; pH: Potential of Hydrogen; TDS: Total dissolved solid; COD: Chemical Oxygen Demand; BOD: Biochemical Oxygen Demand; TA: Total alkalinity; TH: Total Hardness; Cl: Chlorination; SO4: Sulphate, NO3: Nitrate; FL: Floride; ICMR: Indian Council of Medical Research; ISB: Indian Standards Bureau; RW: Relative weights; WQI: Water Quality Index; DJB: Delhi Jal Board; MDG: Millennium Development Goals; GWQI: Ground Water Quality Index; MCD: Municipality Corporation of Delhi; CPCB: Central Pollution Control Board.

Competing risk analysis in a large cardiovascular clinical trial: An APEX substudy.

Competing risk methods are time-to-event analyses that account for fatal and/or nonfatal events that may potentially alter or prevent a subject from experiencing the primary endpoint. Competing risk methods may provide a more accurate and less biased estimate of the incidence of an outcome but are rarely applied in cardiology trials. APEX investigated the efficacy of extended-duration betrixaban versus standard-duration enoxaparin to prevent a composite of symptomatic deep-vein thrombosis (proximal or distal), nonfatal pulmonary embolism, or venous thromboembolism (VTE)-related death in acute medically ill patients (n = 7513). The aim of the current analysis was to determine the efficacy of betrixaban vs standard-duration enoxaparin accounting for non-VTE-related deaths using the Fine and Gray method for competing risks. The proportion of non-VTE-related death was similar in both the betrixaban (133, 3.6%) and enoxaparin (136, 3.7%) arms, P = .85. Both the traditional Kaplan-Meier method and the Fine and Gray method accounting for non-VTE-related death as a competing risk showed equal reduction of VTE events when comparing betrixaban to enoxaparin (HR/SHR = 0.65, 95% 0.42-0.99, P = 0.046). Due to the similar proportion of non-VTE-related deaths in both treatment arms and the use of a univariate model, the Fine and Gray method provided identical results to the traditional Cox model. Using the Fine and Gray method in addition to the traditional Cox proportional hazards method can indicate whether the presence of a competing risk, which is dependent of the outcome, altered the risk estimate.

Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial Substudy.

BACKGROUND: Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. METHODS AND RESULTS: This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). CONCLUSIONS: Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.

Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy.

BACKGROUND: Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization. METHODS: Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y12 inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group 2); or the reference arm of dose-adjusted VKA daily with a similar DAPT stratification (group 3). The present post hoc analysis assessed the end point of all-cause mortality or recurrent hospitalization for an adverse event, which was further classified as the result of bleeding, a cardiovascular cause, or another cause blinded to treatment assignment. RESULTS: The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66-0.94; P=0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62-0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not. CONCLUSIONS: Among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus DAPT was associated with a reduced risk of all-cause mortality or recurrent hospitalization for adverse events compared with standard-of-care VKA plus DAPT. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).

BACKGROUND: Stroke is a morbid and potentially mortal complication among patients hospitalized with acute medical illness. The potential of extended-duration thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of stroke compared with standard-dose enoxaparin in this population was assessed in this retrospective APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban). METHODS: Hospitalized acutely medically ill subjects (n=7513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35-42 days) or standard-dose subcutaneous enoxaparin (40 mg once daily for 10±4 days) for venous thromboprophylaxis. Stroke events were adjudicated by an independent, blinded event adjudication committee. RESULTS: The mean age of study participants was 76 years; 45% were male; 13% had had a stroke; and 45% had congestive heart failure. There were fewer all-cause strokes (0.54% versus 0.97%; relative risk [RR]=0.56; 95% confidence interval, 0.32-0.96; P=0.032; adjusted RR=0.43%; number needed to treat=233) and ischemic strokes (0.48% versus 0.91%; RR=0.53; 95% confidence interval, 0.30-0.94; P=0.026; adjusted RR=0.43%; number needed to treat=233) among patients treated with betrixaban versus enoxaparin through 77 days of follow-up. Among high-risk subjects, those with congestive heart failure or ischemic stroke as their index event, betrixaban reduced the risk of all-cause stroke (0.72% versus 1.48%; RR=0.49; 95% confidence interval, 0.26-0.90; P=0.019; adjusted RR=0.76%; number needed to treat=132) and ischemic stroke (0.63% versus 1.38%; RR=0.45; 95% confidence interval, 0.24-0.87; P=0.014; adjusted RR=0.75%; number needed to treat=134) compared with enoxaparin. CONCLUSIONS: Among hospitalized medically ill patients, extended-duration betrixaban significantly reduced all-cause stroke and ischemic stroke through 77 days of follow-up CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01583218.

Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I).

BACKGROUND: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein-mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction. METHODS: The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy). RESULTS: A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar. CONCLUSIONS: Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02108262.