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In 2022, provisional data indicated that more than two thirds (68%) of the reported 107,081 drug overdose deaths in the United States involved synthetic opioids other than methadone, principally illicitly manufactured fentanyls (IMFs) (1). Xylazine, a nonopioid sedative not approved for human use and with no known antidote, has been increasingly detected in IMF products in the U.S. drug supply* and in IMF-involved overdose deaths (2). Limited studies suggest xylazine can cause central nervous system depression, respiratory depression, bradycardia, and hypotension in humans (3,4); chronic use might lead to severe withdrawal symptoms † as well as skin ulcerations (4). This report uses data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS) to describe IMF-involved § overdose deaths with and without xylazine detected that occurred during January 2019-June 2022. Among 21 jurisdictions, which included 20 states and the District of Columbia, the monthly percentage of IMF-involved deaths with xylazine detected increased 276%, from 2.9% to 10.9%. Among IMF-involved deaths during January 2021-June 2022 in 32 jurisdictions, xylazine was detected in a higher percentage of jurisdictions in the Northeast U.S. Census Bureau region; listing detected xylazine as a cause of death varied across jurisdictions. Expanded postmortem and illicit drug product testing for xylazine is needed to clarify prevalence in drug supplies; further investigation of xylazine's effects on humans is necessary to characterize morbidity and overdose risk. It is important for overdose prevention and response messages to highlight the potential presence of xylazine in IMF products and emphasize the need for respiratory and cardiovascular support to address the sedative effects of xylazine., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Introduction: Drug overdose deaths increased approximately 30% from 2019 to 2020 in the United States. Examining rates by demographic and social determinants of health characteristics can identify disproportionately affected populations and inform strategies to reduce drug overdose deaths., Methods: Data from the State Unintentional Drug Overdose Reporting System (SUDORS) were used to analyze overdose death rates from 2019 to 2020 in 25 states and the District of Columbia. Rates were examined by race and ethnicity and county-level social determinants of health (e.g., income inequality and treatment provider availability)., Results: From 2019 to 2020, drug overdose death rates increased by 44% and 39% among non-Hispanic Black (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, respectively. Significant disparities were found across sex, age, and racial and ethnic subgroups. In particular, the rate in 2020 among Black males aged ≥65 years (52.6 per 100,000) was nearly seven times that of non-Hispanic White males aged ≥65 years (7.7). A history of substance use was frequently reported. Evidence of previous substance use treatment was lowest for Black persons (8.3%). Disparities in overdose deaths, particularly among Black persons, were larger in counties with greater income inequality. Opioid overdose rates in 2020 were higher in areas with more opioid treatment program availability compared with areas with lower opioid treatment availability, particularly among Black (34.3 versus 16.6) and AI/AN (33.4 versus 16.2) persons., Conclusions and Implications for Public Health Practice: Health disparities in overdose rates continue to worsen, particularly among Black and AI/AN persons; social determinants of health, such as income inequality, exacerbate these inequities. Implementation of available, evidence-based, culturally responsive overdose prevention and response efforts that address health disparities impacting disproportionately affected populations are urgently needed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background and Aims: Tracking specific drugs contributing to drug overdose deaths is limited when relying on death certificate (DC) data alone. This study aimed to determine whether integrating DC data with medical examiner/coroner reports, including postmortem toxicology and death investigation findings, would enhance identification of (1) heroin and pharmaceutical morphine involvement in overdose deaths and (2) fentanyl source (illicitly manufactured versus pharmaceutical)., Design: Retrospective analysis of heroin, pharmaceutical morphine, illicitly manufactured fentanyl (IMF) and pharmaceutical fentanyl involvement in fatal overdoses. DC and toxicology data were compared with enhanced definitions integrating overdose scene, witness and toxicology evidence., Setting: United States: 38 states and the District of Columbia, participating in Centers for Disease Control and Prevention (CDC)-funded opioid overdose death surveillance., Cases: Opioid overdose decedents from funded jurisdictions; deaths during 1 January 2018-31 December 2019., Measurements: Using medical examiner/coroner report data, deaths with 6-acetylmorphine and/or morphine detected by postmortem toxicology were defined as confirmed, probable or suspected heroin deaths, or probable pharmaceutical morphine deaths. Fentanyl was defined as probable or suspected IMF or probable pharmaceutical fentanyl., Findings: The enhanced definition defined 18 393 deaths as confirmed, probable, or suspected heroin deaths (including 2678 with morphine listed as cause of death on the DC) and 404 as probable pharmaceutical morphine deaths. Among deaths with fentanyl detected, 89.3% were defined as probable or suspected IMF and 1.0% as probable pharmaceutical fentanyl. Fentanyl source could not be determined for 9.7% of deaths., Conclusions: Integrating drug overdose scene, witness and toxicology findings can improve identification of specific drugs contributing to overdose deaths and enhance overdose intervention targeting., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Drug overdose deaths involving stimulants, including cocaine and psychostimulants with abuse potential (e.g., methamphetamine), have been increasing, partly because of co-involvement with opioids. Stimulant-involved overdose deaths have disproportionately increased among non-Hispanic Black (Black) and non-Hispanic American Indian/Alaskan Native (AI/AN) persons; however, the role of opioids in exacerbating disproportionate stimulant-involved death rates is unclear., Methods: Analysis of National Vital Statistics System multiple cause-of-death mortality files examined age-adjusted cocaine- and psychostimulant-involved death rates. Analyses of death rates stratified by racial and ethnic group and opioid co-involvement included: 1) Joinpoint regression of 2004-2019 trends, 2) changes in rates from 2018 to 2019, and 3) demographic and geographic characteristics of 2019 deaths., Results: From 2004 to 2019, cocaine and psychostimulant-involved death rates were higher for Black and AI/AN persons, respectively. Among all groups, increases in cocaine-involved overdose rates were largely driven by opioid co-involvement, particularly after 2013. From 2004 to 2019, rates for psychostimulant-involved deaths increased with and without opioid co-involvement. Rates for overdoses co-involving cocaine and synthetic opioids increased from 2018 to 2019 for Hispanic, non-Hispanic White (White), and Black persons. Psychostimulant-involved overdose rates with and without synthetic opioid co-involvement increased among Hispanic, White, and Black persons. In 2019, Black and AI/AN persons continued to experience higher cocaine- and psychostimulant-involved death rates, respectively., Conclusions: Stimulant-involved deaths continue to increase, and the role of opioids in driving these deaths varies by race and ethnicity. Ensuring equitable access to proven prevention and treatment interventions and incorporating social determinants of health into future research around effective pharmacotherapies may help reduce stimulant-involved overdose deaths., (Published by Elsevier B.V.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Deaths involving synthetic opioids other than methadone (synthetic opioids), which largely consist of illicitly manufactured fentanyl; psychostimulants with abuse potential (e.g., methamphetamine); and cocaine have increased in recent years, particularly since 2013 (1,2). In 2019, a total of 70,630 drug overdose deaths occurred, corresponding to an age-adjusted rate of 21.6 per 100,000 population and a 4.3% increase from the 2018 rate (20.7) (3). CDC analyzed trends in age-adjusted overdose death rates involving synthetic opioids, psychostimulants, cocaine, heroin, and prescription opioids during 2013-2019, as well as geographic patterns in synthetic opioid- and psychostimulant-involved deaths during 2018-2019. From 2013 to 2019, the synthetic opioid-involved death rate increased 1,040%, from 1.0 to 11.4 per 100,000 age-adjusted (3,105 to 36,359). The psychostimulant-involved death rate increased 317%, from 1.2 (3,627) in 2013 to 5.0 (16,167) in 2019. In the presence of synthetic opioid coinvolvement, death rates for prescription opioids, heroin, psychostimulants, and cocaine increased. In the absence of synthetic opioid coinvolvement, death rates increased only for psychostimulants and cocaine. From 2018 to 2019, the largest relative increase in the synthetic opioid-involved death rate occurred in the West (67.9%), and the largest relative increase in the psychostimulant-involved death rate occurred in the Northeast (43.8%); these increases represent important changes in the geographic distribution of drug overdose deaths. Evidence-based prevention and response strategies including substance use disorder treatment and overdose prevention and response efforts focused on polysubstance use must be adapted to address the evolving drug overdose epidemic., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3). Efforts related to all opioids, particularly deaths involving synthetic opioids, should be strengthened to sustain and accelerate declines in opioid-involved deaths. Comprehensive surveillance and prevention measures are critical to reducing opioid-involved deaths, including continued surveillance of evolving drug use and overdose, polysubstance use, and the changing illicit drug market; naloxone distribution and outreach to groups at risk for IMF exposure; linkage to evidence-based treatment for persons with substance use disorders; and continued partnerships with public safety., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

In 2016, a total of 63,632 persons died from drug overdoses in the United States (1). Drug overdose deaths involving cocaine, psychostimulants with abuse potential (psychostimulants), or both substances combined increased 42.4% from 12,122 in 2015 to 17,258 in 2016.* Psychostimulants with abuse potential include drugs such as methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, methylphenidate (Ritalin), and caffeine. From 2015 to 2016, cocaine-involved and psychostimulant-involved death rates increased 52.4% and 33.3%, respectively (1). A total of 70,237 persons died from drug overdoses in the United States in 2017; approximately two thirds of these deaths involved an opioid (2). CDC analyzed 2016-2017 changes in age-adjusted death rates involving cocaine and psychostimulants by demographic characteristics, urbanization levels, U.S. Census region, 34 states, and the District of Columbia (DC). CDC also examined trends in age-adjusted cocaine-involved and psychostimulant-involved death rates from 2003 to 2017 overall, as well as with and without co-involvement of opioids. Among all 2017 drug overdose deaths, 13,942 (19.8%) involved cocaine, and 10,333 (14.7%) involved psychostimulants. Death rates increased from 2016 to 2017 for both drug categories across demographic characteristics, urbanization levels, Census regions, and states. In 2017, opioids were involved in 72.7% and 50.4% of cocaine-involved and psychostimulant-involved overdoses, respectively, and the data suggest that increases in cocaine-involved overdose deaths from 2012 to 2017 were driven primarily by synthetic opioids. Conversely, increases in psychostimulant-involved deaths from 2010 to 2017 occurred largely independent of opioids, with increased co-involvement of synthetic opioids in recent years. Provisional data from 2018 indicate that deaths involving cocaine and psychostimulants are continuing to increase. † Increases in stimulant-involved deaths are part of a growing polysubstance landscape. Increased surveillance and evidence-based multisectoral prevention and response strategies are needed to address deaths involving cocaine and psychostimulants and opioids. Enhancing linkage to care, building state and local capacity, and public health/public safety collaborations are critical components of prevention efforts., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Invasive cervical cancer is the most prevalent cancer among women in Sub-Saharan Africa. In 2013, the World Health Organization (WHO) emitted recommendations to start Highly Active Antiretroviral Therapy (HAART) regardless of CD4 count. Although HAART has been shown to reduce the prevalence of high-risk human papillomavirus (HR-HPV) genotypes, it is unclear whether it confers a protective effect specifically for HPV 16. This review summarizes the existing evidence regarding the effect of HAART on HPV 16 infection, as this genotype may not be influenced by immunity level and explores its implications for Sub Saharan Africa. A comprehensive literature review was undertaken and quality assessment was carried out on the selected papers. Four cohort studies and three cross-sectional studies were identified for which the overall quality score assessment ranged from weak/moderate (Score of 1.8) to strong (Score of 3). The evidence yielded by our review was conflicting. Thus, the high heterogeneity between study populations and results did not allow us to draw any firm conclusions as to whether HAART has an impact on HPV 16 acquisition/prevalence. As only three studies were conducted in Africa, there are insufficient grounds for solid comparison between geographic regions. In light of inadequate data, HPV unvaccinated women on HAART should still receive more frequent follow-up., Competing Interests: The authors have declared that no competing interests exist.

In 2016, 63,632 drug overdose deaths occurred in the United States, 42,249 (66.4%) of which involved opioids (1). The development of prevention programs are hampered by a lack of timely data on specific substances contributing to and circumstances associated with fatal overdoses. This report describes opioid overdose deaths (referred to as opioid deaths) for decedents testing positive for prescription opioids (e.g., oxycodone and hydrocodone), illicit opioids (e.g., heroin, illicitly manufactured fentanyl, and fentanyl analogs), or both prescription and illicit opioids, and describes circumstances surrounding the overdoses, in 11 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* During July 2016-June 2017, among 11,884 opioid overdose deaths, 17.4% of decedents tested positive for prescription opioids only, 58.7% for illicit opioids only, and 18.5% for both prescription and illicit opioids (type of opioid could not be classified in 649 [5.5%] deaths). Approximately one in 10 decedents had been released from an institutional setting in the month preceding the fatal overdose. Bystanders were reportedly present in approximately 40% of deaths; however, naloxone was rarely administered by a layperson. Enhanced surveillance data from 11 states provided more complete information on the substances involved in and circumstances surrounding opioid overdose deaths. Consistent with other emerging evidence and recommendations, † these data suggest prevention efforts should prioritize naloxone distribution to persons misusing opioids or using high dosage prescription opioids and to their family members and friends. In addition, these data suggest a need to expand treatment and support for persons who have experienced a nonfatal overdose and to expand treatment in detention facilities and upon release., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed

Competing Interests: No conflicts of interest were reported.

The 63,632 drug overdose deaths in the United States in 2016 represented a 21.4% increase from 2015; two thirds of these deaths involved an opioid (1). From 2015 to 2016, drug overdose deaths increased in all drug categories examined; the largest increase occurred among deaths involving synthetic opioids other than methadone (synthetic opioids), which includes illicitly manufactured fentanyl (IMF) (1). Since 2013, driven largely by IMF, including fentanyl analogs (2-4), the current wave of the opioid overdose epidemic has been marked by increases in deaths involving synthetic opioids. IMF has contributed to increases in overdose deaths, with geographic differences reported (1). CDC examined state-level changes in death rates involving all drug overdoses in 50 states and the District of Columbia (DC) and those involving synthetic opioids in 20 states, during 2013-2017. In addition, changes in death rates from 2016 to 2017 involving all opioids and opioid subcategories,* were examined by demographics, county urbanization levels, and by 34 states and DC. Among 70,237 drug overdose deaths in 2017, 47,600 (67.8%) involved an opioid. † From 2013 to 2017, drug overdose death rates increased in 35 of 50 states and DC, and significant increases in death rates involving synthetic opioids occurred in 15 of 20 states, likely driven by IMF (2,3). From 2016 to 2017, overdose deaths involving all opioids and synthetic opioids increased, but deaths involving prescription opioids and heroin remained stable. The opioid overdose epidemic continues to worsen and evolve because of the continuing increase in deaths involving synthetic opioids. Provisional data from 2018 indicate potential improvements in some drug overdose indicators; § however, analysis of final data from 2018 is necessary for confirmation. More timely and comprehensive surveillance data are essential to inform efforts to prevent and respond to opioid overdoses; intensified prevention and response measures are urgently needed to curb deaths involving prescription and illicit opioids, specifically IMF., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objectives: In sub-Saharan Africa, substantial international funding along with evidence-based clinical practice have resulted in an unparalleled scale-up of access to antiretroviral treatment at a higher CD4 count. The role and timing of highly active antiretroviral therapy (HAART) in mediating cervical disease remains unclear. The aim of this article is to systematically review all evidence pertaining to Africa and identify research gaps regarding the epidemiological association between HAART use and the presence of premalignant/malignant cervical lesions., Method: Five databases were searched until January 2017 to retrieve relevant literature from sub-Saharan Africa. Publications were included if they addressed prevalence, incidence or clearance of human papillomavirus (HPV) infection in women undergoing HAART as well as cytological or histological neoplastic abnormalities., Results: 22 studies were included, of which seven were prospective studies. Women receiving HAART are less likely to develop squamous intraepithelial lesions (SILs). There is evidence that duration of HAART along with the CD4 count may reduce the prevalence of high-risk HPV (HR-HPV), suggesting that without HAART, severe immunosuppression increases the risk of becoming or remaining infected with HR-HPV. Furthermore, according to existent literature, the CD4 count, rather than HAART coverage or its duration, plays a central role in the prevalence of cervical intraepithelial neoplasia (CIN) 2 and CIN 3., Conclusion: Our findings suggest a positive impact of HAART duration, in conjunction and interaction with CD4 count, on reducing the prevalence of HR-HPV. The greatest treatment effect might be seen among women starting at the lowest CD4 count, which may have a more instrumental role in cervical oncogenesis than either HAART use or the treatment duration on the prevalence of CIN 2 and CIN 3. There is still insufficient evidence to show a clear association between HAART coverage and the incidence of invasive cervical cancer. Enhanced surveillance on the impact of HAART treatment is crucial., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC., Methods: PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya., Results: The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%)., Conclusion: HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted., Competing Interests: The authors have declared that no competing interests exist.

To date, no study has evaluated the short- and long-term effects air pollution exposure on emphysematous subjects who have undergone lung volume reduction surgery (LVRS). Data from the National Emphysema Treatment Trial study (1998-2003) included 1,218 subjects, aged 39 to 84. Daily values of ambient fine particulate matter (aerodynamic diameter < 2.5 μm; PM2.5) and ozone were obtained. Mixed-effects models tested the association between short- and long-term pollutant concentrations and changes in pulmonary function. Cumulative air pollution exposure was strongly associated with worsened respiratory function and symptoms. Mean PM2.5 was associated with poorer lung function. Lagged exposures were poorly associated with respiratory health outcomes. There were detrimental respiratory and pulmonary effects observed in response to even low levels of ambient air pollutants among study participants. These results are indicative that exposures even below those of air quality standards may still pose significant risks to severe chronic obstructive pulmonary disease (COPD) subjects.

Objectives: Epidemiologic studies have documented a disproportionate burden of chronic diseases in Appalachia, showing the area to be underserved by the health-care system. Nothing is known about how the health status of the Appalachian population compares with other rural or non-rural populations in the same state. We examined the associations among county type, health insurance category, and health outcomes in poorer adult Ohioans., Methods: We obtained data from the 2008 Ohio Family Health Survey, a complex landline- and cell phone-based survey of 50,944 noninstitutionalized households. We constructed bivariate analyses examining health status measures across various insurance categories and metropolitan, suburban, rural, and Appalachian counties in Ohio., Results: Medicaid enrollees living in Appalachian and rural counties tended to be in poorer health and have a greater prevalence of smoking than non-Medicaid enrollees. Within rural and Appalachian regions, Medicaid enrollees were more likely than non-Medicaid enrollees to have lower self-rated health (54.8%, 95% confidence interval [CI] 44.1, 65.5 in rural regions and 52.1%, 95% CI 44.7, 59.5 in Appalachian regions). Appalachian and rural Medicaid enrollees were at an increased likelihood of having several chronic diseases compared with non-Medicaid enrollees., Conclusion: Our findings suggest that rural and Ohio Appalachian Medicaid enrollees were more likely to have hypertension, cardiovascular disease, and overall poorer health than non-Medicaid enrollees. These findings have important policy implications for health-care reform, highlighting regional disparities in provider coverage. These underserved regions would need an increase in the provider base to positively impact proposed Medicaid expansion programs.

Nationally, death rates from prescription opioid pain reliever (OPR) overdoses quadrupled during 1999-2010, whereas rates from heroin overdoses increased by <50%. Individual states and cities have reported substantial increases in deaths from heroin overdose since 2010. CDC analyzed recent mortality data from 28 states to determine the scope of the heroin overdose death increase and to determine whether increases were associated with changes in OPR overdose death rates since 2010. This report summarizes the results of that analysis, which found that, from 2010 to 2012, the death rate from heroin overdose for the 28 states increased from 1.0 to 2.1 per 100,000, whereas the death rate from OPR overdose declined from 6.0 per 100,000 in 2010 to 5.6 per 100,000 in 2012. Heroin overdose death rates increased significantly for both sexes, all age groups, all census regions, and all racial/ethnic groups other than American Indians/Alaska Natives. OPR overdose mortality declined significantly among males, persons aged <45 years, persons in the South, and non-Hispanic whites. Five states had increases in the OPR death rate, seven states had decreases, and 16 states had no change. Of the 18 states with statistically reliable heroin overdose death rates (i.e., rates based on at least 20 deaths), 15 states reported increases. Decreases in OPR death rates were not associated with increases in heroin death rates. The findings indicate a need for intensified prevention efforts aimed at reducing overdose deaths from all types of opioids while recognizing the demographic differences between the heroin and OPR-using populations. Efforts to prevent expansion of the number of OPR users who might use heroin when it is available should continue.

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Purpose: To evaluate the feasibility of a multi-station three dimensional (3D) T1-weighted turbo spin echo (TSE) dark-blood Sampling Perfection with Application optimized Contrasts using different flip angle Evolution sequence (T1w-SPACE), to assess aorta, iliac, and superficial femoral (SFA) arteries (inflow vessels) by comparing it with a multi-station contrast enhanced MR angiography (CE-MRA) with identical resolution., Materials and Methods: A total of 6 volunteers and 14 peripheral arterial disease (PAD) patients were included in the study. Abdominal and thigh T1w-SPACE and lower leg time-resolved MRA (TR-MRA) with low dose contrast were followed by 3-station CE-MRA. Quantitative measurements of lumen area at 17 locations from T1w-SPACE and CE-MRA were obtained. Additionally, vessel wall areas at the same locations were obtained from the T1w-SPACE images., Results: Quantitative comparison of lumen areas with T1w-SPACE and CE-MRA revealed strong correlation between the two techniques and strong inter-observer agreement for each of the two imaging methods (r > 0.9; P < 0.001). Localized vessel wall area measurements obtained in PAD patients were significantly greater compared with those obtained in normal volunteers (mean difference 43.75 +/- 12.46 mm(2); P < 0.001). Stenosis severity obtained from T1w-SPACE localized measurements showed significant arterial area stenosis in PAD patients., Conclusion: T1w-SPACE imaging of inflow vessels is feasible, and in addition to CE-MRA has the ability to assess atherosclerotic plaque and vascular remodeling., ((c) 2009 Wiley-Liss, Inc.)

Objectives: This study sought to evaluate indexes of pulmonary artery (PA) stiffness in patients with pulmonary hypertension (PH) using same-day cardiac magnetic resonance (CMR) and right heart catheterization (RHC)., Background: Pulmonary artery stiffness is increased in the presence of PH, although the relationship to PH severity has not been fully characterized., Methods: Both CMR and RHC were performed on the same day in 94 patients with known or suspected PH. According to the RHC, patients were classified as having no PH (n = 13), exercise-induced PH (EIPH) only (n = 6), or PH at rest (n = 75). On CMR, phase-contrast images were obtained perpendicular to the pulmonary trunk. From CMR and RHC data, PA areas and indexes of stiffness (pulsatility, compliance, capacitance, distensibility, elastic modulus, and the pressure-independent stiffness index beta) were measured at rest., Results: All quantified indexes showed increased PA stiffness in patients with PH at rest in comparison with those with EIPH or no PH. Despite the absence of significant differences in baseline pressures, patients with EIPH had lower median compliance and capacitance than patients with no PH: 15 (interquartile range: 9 to 19.8) mm2/mm Hg versus 8.4 (interquartile range: 6 to 10.3) mm2/mm Hg, and 5.2 (interquartile range: 4.4 to 6.3) mm3/mm Hg versus 3.7 (interquartile range: 3.1 to 4.1) mm3/mm Hg, respectively (p < 0.05). The different measurements of PA stiffness, including stiffness index beta, showed significant correlations with PA pressures (r2 = 0.27 to 0.73). Reduced PA pulsatility (<40%) detected the presence of PH at rest with a sensitivity of 93% and a specificity of 63%., Conclusions: Pulmonary artery stiffness increases early in the course of PH (even when PH is detectable only with exercise and before overt pressure elevations occur at rest). These observations suggest a potential contributory role of PA stiffness in the development and progression of PH.

The renin-angiotensin system (RAS) may play a role in vascular aging. The authors hypothesized that blockade of the angiotensin II type 1 receptor with an angiotensin receptor blocker in healthy elderly subjects improves vascular compliance and endothelial function. Thirty-five healthy elderly subjects were randomized to valsartan or placebo in a double-blind crossover study after baseline testing for pulse wave velocity, aortic augmentation index, and brachial artery flow-mediated dilation. Angiotensin II type 1 receptor blockade with valsartan improved vascular compliance but not flow-mediated dilation. Changes in pulse wave velocity with valsartan were correlated with change in central systolic blood pressure and pulse pressure and remained associated on multivariate analysis. Change in pulse wave velocity after adjusting for degree of blood pressure change, age, and sex remained correlated with assignment to the angiotensin receptor blocker but not placebo. These data suggest that angiotensin II type 1 receptor blockade improves aging-related vascular compliance without alterations in flow-mediated dilation. Mechanisms regulating compliance and endothelial function are complex and may not necessarily converge in aging.