Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Holtzman D[original query] |
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Estimating post-treatment recurrence after multidrug-resistant tuberculosis treatment among patients with and without HIV: the impact of assumptions about death and missing follow-up (preprint)
Sauer SM , Mitnick CD , Khan U , Hewison C , Bastard M , Holtzman D , Law S , Khan M , Padayachee S , Ahmed S , Isani AK , Krisnanda A , Vilbrun SC , Bektasov S , Kumsa A , Docteur W , Tintaya K , McNicol M , Atshemyan H , Voynilo T , Thwe TT , Seung K , Rich M , Huerga H , Khan P , Franke M . medRxiv 2023 29 Background: Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up. Method(s): We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-month post-treatment TB recurrence risk overall, and by HIV status. We used inverse-probability-weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights. Result(s): The estimated TB recurrence risk was 6.6 per 1000 (95% confidence interval (CI):3.2,11.2) when deaths were handled as non-recurrences, and 6.7 per 1000 (95% CI:2.8,12.2) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 24.2 (95% CI:14.1,37.0), 10.5 (95% CI:5.6,16.6), and 7.8 (95% CI:3.9,13.2) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability-weighting had a small but apparent impact on estimates. Conclusion(s): The estimated six-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Impact of 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among adults with HIV-United States, 2008-2018
Kobayashi M , Matanock A , Xing W , Adih WK , Li J , Gierke R , Almendares O , Reingold A , Alden N , Petit S , Farley MM , Harrison LH , Holtzman C , Baumbach J , Thomas A , Schaffner W , McGee L , Pilishvili T . J Acquir Immune Defic Syndr 2022 90 (1) 6-14 BACKGROUND: People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older. METHODS: We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs. RESULTS: In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively. CONCLUSIONS: Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH. |
COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021.
Johnson AG , Amin AB , Ali AR , Hoots B , Cadwell BL , Arora S , Avoundjian T , Awofeso AO , Barnes J , Bayoumi NS , Busen K , Chang C , Cima M , Crockett M , Cronquist A , Davidson S , Davis E , Delgadillo J , Dorabawila V , Drenzek C , Eisenstein L , Fast HE , Gent A , Hand J , Hoefer D , Holtzman C , Jara A , Jones A , Kamal-Ahmed I , Kangas S , Kanishka F , Kaur R , Khan S , King J , Kirkendall S , Klioueva A , Kocharian A , Kwon FY , Logan J , Lyons BC , Lyons S , May A , McCormick D , Mendoza E , Milroy L , O'Donnell A , Pike M , Pogosjans S , Saupe A , Sell J , Smith E , Sosin DM , Stanislawski E , Steele MK , Stephenson M , Stout A , Strand K , Tilakaratne BP , Turner K , Vest H , Warner S , Wiedeman C , Zaldivar A , Silk BJ , Scobie HM . MMWR Morb Mortal Wkly Rep 2022 71 (4) 132-138 Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status() indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended() additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged 18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),() case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and 65 years. Eligible persons should stay up to date with COVID-19 vaccinations. |
PEPFAR's Role in Protecting and Leveraging HIV Services in the COVID-19 Response in Africa.
Holtzman CW , Godfrey C , Ismail L , Raizes E , Ake JA , Tefera F , Okutoyi S , Siberry GK . Curr HIV/AIDS Rep 2022 19 (1) 1-11 PURPOSE OF REVIEW: We describe the impact of COVID-19 on PEPFAR programs in Africa and how PEPFAR adapted and leveraged its interventions to the changing landscape of the COVID-19 pandemic. RECENT FINDINGS: To mitigate the potential impact of COVID-19 on the HIV response and protect the gains, continuity of treatment was the guiding principle regarding the provision of services in PEPFAR-supported countries. As the COVID-19 pandemic matured, PEPFAR's approach evolved from a strictly "protect and salvage" approach to a "restore and accelerate" approach that embraced innovative adaptations in service and "person-centered" care. The impact of service delivery interruptions caused by COVID-19 on progress towards HIV epidemic control in PEPFAR-supported African countries remains undetermined. With COVID vaccine coverage many months away and more transmissible variants being reported, Africa may experience more pandemic surges. HIV programs will depend on nimble and innovative adaptations in prevention and treatment services in order to advance epidemic control objectives. |
Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status - 13 U.S. Jurisdictions, April 4-July 17, 2021.
Scobie HM , Johnson AG , Suthar AB , Severson R , Alden NB , Balter S , Bertolino D , Blythe D , Brady S , Cadwell B , Cheng I , Davidson S , Delgadillo J , Devinney K , Duchin J , Duwell M , Fisher R , Fleischauer A , Grant A , Griffin J , Haddix M , Hand J , Hanson M , Hawkins E , Herlihy RK , Hicks L , Holtzman C , Hoskins M , Hyun J , Kaur R , Kay M , Kidrowski H , Kim C , Komatsu K , Kugeler K , Lewis M , Lyons BC , Lyons S , Lynfield R , McCaffrey K , McMullen C , Milroy L , Meyer S , Nolen L , Patel MR , Pogosjans S , Reese HE , Saupe A , Sell J , Sokol T , Sosin D , Stanislawski E , Stevens K , Vest H , White K , Wilson E , MacNeil A , Ritchey MD , Silk BJ . MMWR Morb Mortal Wkly Rep 2021 70 (37) 1284-1290 COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies. |
The Changing Epidemiology of Hepatitis C Virus Infection in the United States During the Years 2010 to 2018
Holtzman D , Asher AK , Schillie S . Am J Public Health 2021 111 (5) e1-e7 Hepatitis C virus (HCV) infection remains an important cause of morbidity and mortality throughout the world, leading to serious health problems among those who are chronically infected. Since 1992, the Centers for Disease Control and Prevention has been collecting data on the incidence of HCV infection in the United States. In 2018, more than 50 000 individuals were estimated to have acute HCV infection.The most recently reported data on the prevalence of infection indicate that approximately 2.4 million people are living with hepatitis C in the United States. Transmission of HCV occurs predominantly through sharing contaminated equipment for injecting drugs.Two major events have had a significant impact on the incidence and prevalence of hepatitis C in the past few decades: the US opioid crisis and the discovery of curative treatments for HCV infection. To better understand the impact of these events, we examine reported trends in the incidence and prevalence of infection. (Am J Public Health. Published online ahead of print March 18, 2021: e1-e7. https://doi.org/10.2105/AJPH.2020.306149). |
Pneumococcal conjugate vaccine breakthrough infections: 2001-2016
Adebanjo TA , Pondo T , Yankey D , Hill HA , Gierke R , Apostol M , Barnes M , Petit S , Farley M , Harrison LH , Holtzman C , Baumbach J , Bennett N , McGuire S , Thomas A , Schaffner W , Beall B , Whitney CG , Pilishvili T . Pediatrics 2020 145 (3) BACKGROUND: Most countries use 3-dose pneumococcal conjugate vaccine (PCV) schedules; a 4-dose (3 primary and 1 booster) schedule is licensed for US infants. We evaluated the invasive pneumococcal disease (IPD) breakthrough infection incidence in children receiving 2 vs 3 primary PCV doses with and without booster doses (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0). METHODS: We used 2001-2016 Active Bacterial Core surveillance data to identify breakthrough infections (vaccine-type IPD in children receiving >/=1 7-valent pneumococcal conjugate vaccine [PCV7] or 13-valent pneumococcal conjugate vaccine [PCV13] dose) among children aged <5 years. We estimated schedule-specific IPD incidence rates (IRs) per 100 000 person-years and compared incidence by schedule (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0) using rate differences (RDs) and incidence rate ratios. RESULTS: We identified 71 PCV7 and 49 PCV13 breakthrough infections among children receiving a schedule of interest. PCV13 breakthrough infection rates were higher in children aged <1 year receiving the 2 + 0 (IR: 7.8) vs 3 + 0 (IR: 0.6) schedule (incidence rate ratio: 12.9; 95% confidence interval: 4.1-40.4); PCV7 results were similar. Differences in PCV13 breakthrough infection rates by schedule in children aged <1 year were larger in 2010-2011 (2 + 0 IR: 18.6; 3 + 0 IR: 1.4; RD: 16.6) vs 2012-2016 (2 + 0 IR: 3.6; 3 + 0 IR: 0.2; RD: 3.4). No differences between schedules were detected in children aged >/=1 year for PCV13 breakthrough infections. CONCLUSIONS: Fewer PCV breakthrough infections occurred in the first year of life with 3 primary doses. Differences in breakthrough infection rates by schedule decreased as vaccine serotypes decreased in circulation. |
Trends in prevalence of protective levels of hepatitis B surface antibody among adults aged 18-49 years with risk factors for hepatitis B virus infection-United States, 2003-2014
King H , Xing J , Dean HD , Holtzman D . Clin Infect Dis 2019 70 (9) 1907-1915 BACKGROUND: Hepatitis B virus (HBV) infection can be prevented through vaccination; however previous data show that only about 24%-45% of U.S. adults at high risk of HBV infection are protected. Our aims were to assess prevalence and trends in protective levels of hepatitis B surface antibody from 2003-2014 and explore factors associated with protection among U.S. adults at high risk. METHODS: Data were from the 2003-2014 National Health and Nutrition Examination Surveys. Our sample included adults, aged 18-49 years, who were tested for HBV and reported at least one of the following infection risks: history of STD, sex with men (for male respondents), infection with HIV, and injection drug use. We calculated the prevalence of hepatitis B surface antibody (anti-HBs, >/=10mIU/mL), indicative of immunity from vaccination among respondents for three 4-year time intervals (2003-2006, 2007-2010, and 2011-2014) and applied the Cochran-Mantel-Haenszel test to assess trends. Using multivariable logistic regression, we examined factors associated with positive anti-HBs serology. RESULTS: From 2003-2014, the prevalence of positive anti-HBs serology was 23.4%. Prevalence increased from 2003-2006 (16.3%) to 2007-2010 (27.3%), but no change occurred from 2007-2010 (27.3%) to 2011-2014 (28.1%). Among factors predicting positive anti-HBs serology were young age, female sex, and higher education. CONCLUSIONS: By 2014, less than one-third of adults, aged 18-49 years, at risk of infection exhibited anti-HBs >/=10 mIU/mL indicative of protection. Because these adults account for a substantial proportion of unprotected adults, targeted intervention strategies are essential to achieve the goal of hepatitis B elimination. |
The HCV care continuum: linkage to HCV care and treatment among patients at an urban health network, Philadelphia, PA
Coyle C , Moorman AC , Bartholomew T , Klein G , Kwakwa H , Mehta SH , Holtzman D . Hepatology 2019 70 (2) 476-486 BACKGROUND/AIMS: Improving care and treatment for persons infected with hepatitis C virus (HCV) can reduce HCV-related morbidity and mortality. Our primary objective was to examine the HCV care continuum among patients receiving care at five Federally Qualified Health Centers (FQHCs) in Philadelphia, PA where a testing and linkage to care program had been established. METHODS: Among the five FQHCs, one served a homeless population, two served public housing residents, one served a majority Hispanic population, and the last, a "test and treat" site, also provided HCV treatment to patients. We analyzed data from electronic health records of patients tested for HCV antibody from 2012-2016 and calculated the percentage of patients across nine steps of the HCV care continuum ranging from diagnosis to cure. We further explored factors associated with successful patient navigation through two steps of the continuum using multivariable logistic regression. RESULTS: Of 885 chronically infected patients, 92.2% received their RNA positive result, 82.7% were referred to an HCV provider, 69.4% were medically evaluated by the provider, 55.3% underwent liver disease staging, 15.0% initiated treatment, 12.0% completed treatment, 8.7% were assessed for sustained virologic response (SVR), and 8.0% achieved SVR. Regression results revealed that test and treat site patients were significantly more likely to be medically evaluated (aOR=2.76; 95% CI=1.82, 4.17) and undergo liver disease staging (aOR=1.92, 95% CI=1.02, 2.86) than patients at the other FQHCs combined. CONCLUSIONS: In this U.S. urban setting, over two-thirds of HCV-infected patients were linked to care. Although treatment uptake was low overall, it was highest at the test and treat site. Scaling up treatment services in HCV testing settings will be vital to improve the HCV care continuum. This article is protected by copyright. All rights reserved. |
Obesity, diabetes, and the risk of invasive group B Streptococcal disease in nonpregnant adults in the United States
Pitts SI , Maruthur NM , Langley GE , Pondo T , Shutt KA , Hollick R , Schrag SJ , Thomas A , Nichols M , Farley M , Watt JP , Miller L , Schaffner W , Holtzman C , Harrison LH . Open Forum Infect Dis 2018 5 (6) 1-7 Background. Rates of invasive group B Streptococcus (GBS) disease, obesity, and diabetes have increased in US adults. We hypothesized that obesity would be independently associated with an increased risk of invasive GBS disease. Methods. We identified adults with invasive GBS disease within Active Bacterial Core surveillance during 2010-2012 and used population estimates from the Behavioral Risk Factor Surveillance System to calculate invasive GBS incidence rates. We estimated relative risks (RRs) of invasive GBS using Poisson analysis with offset denominators, with obesity categorized as class I/II (body mass index [BMI] = 30-39.9 kg/m2) and class III (BMI >= 40.0 kg/m2). Results. In multivariable analysis of 4281 cases, the adjusted RRs of invasive GBS disease were increased for obesity (class I/ II: RR, 1.52; 95% confidence interval [CI], 1.14-2.02; and class III: RR, 4.87; 95% CI, 3.50-6.77; reference overweight) and diabetes (RR, 6.04; 95% CI, 4.77-7.65). The adjusted RR associated with class III obesity was 3-fold among persons with diabetes (95% CI, 1.38-6.61) and nearly 9-fold among persons without diabetes (95% CI, 6.41-12.46), compared with overweight. The adjusted RRs associated with diabetes varied by age and BMI, with the highest RR in young populations without obesity. Population attributable risks of invasive GBS disease were 27.2% for obesity and 40.1% for diabetes. Conclusions. Obesity and diabetes were associated with substantially increased risk of infection from invasive GBS. Given the population attributable risks of obesity and diabetes, interventions that reduce the prevalence of these conditions would likely reduce the burden of invasive GBS infection. |
Increases in acute hepatitis C virus infection related to a growing opioid epidemic and associated injection drug use, United States, 2004 to 2014
Zibbell JE , Asher AK , Patel RC , Kupronis B , Iqbal K , Ward JW , Holtzman D . Am J Public Health 2017 108 (2) e1-e7 OBJECTIVES: To compare US trends in rates of injection drug use (IDU), specifically opioid injection, with national trends in the incidence of acute HCV infection to assess whether these events correlated over time. METHODS: We calculated the annual incidence rate and demographic and risk characteristics of reported cases of acute HCV infection using surveillance data from 2004 to 2014 and the annual percentage of admissions to substance use disorder treatment facilities reporting IDU for the same time period by type of drug injected and demographic characteristics. We then tested for trends. RESULTS: The annual incidence rate of acute HCV infection increased more than 2-fold (from 0.3 to 0.7 cases/100 000) from 2004 to 2014, with significant increases among select demographic subgroups. Admissions for substance use disorder attributed to injection of heroin and prescription opioid analgesics increased significantly, with an almost 4-fold increase in prescription opioid analgesic injection. Significant increases in opioid injection mirrored those for reported cases of acute HCV infection among demographic subgroups. CONCLUSIONS: These findings strongly suggest that the national increase in acute HCV infection is related to the country's opioid epidemic and associated increases in IDU. (Am J Public Health. Published online ahead of print December 21, 2017: e1-e7. doi:10.2105/AJPH.2017.304132). |
Comparison of ICD-9 codes for depression and alcohol misuse to survey instruments suggests these codes should be used with caution
Boscarino JA , Moorman AC , Rupp LB , Zhou Y , Lu M , Teshale EH , Gordon SC , Spradling PR , Schmidt MA , Trinacty CM , Zhong Y , Holmberg SD , Holtzman D . Dig Dis Sci 2017 62 (10) 2704-2712 BACKGROUND: Research suggests depression and alcohol misuse are highly prevalent among chronic hepatitis C (CHC) patients, which is of clinical concern. AIMS: To compare ICD-9 codes for depression and alcohol misuse to validated survey instruments. METHODS: Among CHC patients, we assessed how well electronic ICD-9 codes for depression and alcohol misuse predicted these disorders using validated instruments. RESULTS: Of 4874 patients surveyed, 56% were male and 52% had a history of injection drug use. Based on the PHQ-8, the prevalence of depression was 30% compared to 14% based on ICD-9 codes within 12 months of survey, 37% from ICD-9 codes any time before or within 12 months after survey, and 48% from ICD-9 codes any time before or within 24 months after survey. ICD-9 codes predicting PHQ-8 depression had a sensitivity ranging from 59 to 88% and a specificity ranging from 33 to 65%. Based on the AUDIT-C, the prevalence of alcohol misuse was 21% compared to 3-23% using ICD-9 codes. The sensitivity of ICD-9 codes to predict AUDIT-C score ranged from 9 to 35% and specificity from 80 to 98%. Overall 39% of patients reported ever binge drinking, with a sensitivity of ICD-9 to predict binge drinking ranging from 7 to 33% and a specificity from 84 to 98%. More than half of patients had either an ICD-9 code for depression, a survey score indicating depression, or both (59%); more than one-third had the same patterns for alcohol misuse (36%). CONCLUSIONS: ICD-9 codes were limited in predicting current depression and alcohol misuse, suggesting that caution should be exercised when using ICD-9 codes to assess depression or alcohol misuse among CHC patients. |
Generalisability of vaccine effectiveness estimates: an analysis of cases included in a postlicensure evaluation of 13-valent pneumococcal conjugate vaccine in the USA
Link-Gelles R , Westreich D , Aiello AE , Shang N , Weber DJ , Rosen JB , Motala T , Mascola L , Eason J , Scherzinger K , Holtzman C , Reingold AL , Barnes M , Petit S , Farley MM , Harrison LH , Zansky S , Thomas A , Schaffner W , McGee L , Whitney CG , Moore MR . BMJ Open 2017 7 (8) e017715 OBJECTIVES: External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. DESIGN: Matched case-control study. SETTING: Thirteen active surveillance sites for invasive pneumococcal disease in the USA. PARTICIPANTS: Cases were identified from active surveillance and controls were age and zip code matched. OUTCOME MEASURES: Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. RESULTS: We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. CONCLUSIONS: We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted. |
Estimation of state-level prevalence of hepatitis C virus infection, US states and District of Columbia, 2010
Rosenberg ES , Hall EW , Sullivan PS , Sanchez TH , Workowski KA , Ward JW , Holtzman D . Clin Infect Dis 2017 64 (11) 1573-1581 Background.: Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the United States and a leading cause of morbidity and mortality. Previous analyses of the US National Health and Nutrition Examination Survey (NHANES) indicated approximately 3.6 million noninstitutionalized persons with antibody to HCV (anti-HCV). However, state-level prevalence remains less understood and cannot be estimated reliably from NHANES alone. Methods.: We used 3 publicly available government data sources to estimate anti-HCV prevalence in each US state among noninstitutionalized persons aged ≥18 years. A small-area estimation model combined indirect standardization of NHANES-based prevalence with logistic regression modeling of mortality data, listing acute or chronic HCV infection as a cause of death, from the National Vital Statistics System during 1999-2012. Model results were combined with US Census population sizes to estimate total number and prevalence of persons with antibody to HCV in 2010. Results.: National anti-HCV prevalence was 1.67% (95% confidence interval [CI], 1.53-1.90), or 3 911 800 (95% CI, 3 589 400- 4 447 500) adults in 2010. State-specific prevalence ranged from 0.71% (Illinois) to 3.34% (Oklahoma). The West census region had the highest region-specific prevalence (2.14% [95% CI, 1.96-2.48]); 10 of 13 states had rates above the national average. The South had the highest number of persons with anti-HCV (n = 1561600 [95% CI, 1 427 700-1 768 900]). The Midwest had the lowest region-specific prevalence (1.14% [95% CI, 1.04%-1.30%]). Conclusions.: States in the US West and South have been most impacted by hepatitis C. Estimates of HCV infection burden are essential to guide policy and programs to optimally prevent, detect, and cure infection. |
Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study
Link-Gelles R , Westreich D , Aiello AE , Shang N , Weber DJ , Holtzman C , Scherzinger K , Reingold A , Schaffner W , Harrison LH , Rosen JB , Petit S , Farley M , Thomas A , Eason J , Wigen C , Barnes M , Thomas O , Zansky S , Beall B , Whitney CG , Moore MR . SSM Popul Health 2016 2 587-594 In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geocoding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8–91.9%; adjusted estimate: 82.5%, 95% CI 65.6–91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES. |
Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study
Moore MR , Link-Gelles R , Schaffner W , Lynfield R , Holtzman C , Harrison LH , Zansky SM , Rosen JB , Reingold A , Scherzinger K , Thomas A , Guevara RE , Motala T , Eason J , Barnes M , Petit S , Farley MM , McGee L , Jorgensen JH , Whitney CG . Lancet Respir Med 2016 4 (5) 399-406 BACKGROUND: In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness. METHODS: Cases in children aged 2-59 months were identified through active surveillance in 13 sites. Controls were identified via birth registries and matched to cases by age and postal (zip) code. The primary objective was the vaccine effectiveness of at least one dose against the 13 serotypes included in PCV13. Secondary objectives included vaccine effectiveness against all-cause invasive pneumococcal disease, against antibiotic non-susceptible invasive pneumococcal disease, and among children with and without underlying conditions. Vaccine effectiveness was calculated as (1 - matched odds ratio) x 100%. FINDINGS: We enrolled 722 children with invasive pneumococcal disease and 2991 controls; PCV13 serotype cases (217 [30%]) included most commonly serotypes 19A (128 [18%]), 7F (32 [4%]), and 3 (43 [6%]). Vaccine effectiveness against PCV13 serotypes was 86.0% (95% CI 75.5 to 92.3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85.6% (95% CI 70.6 to 93.5) and 96.5% (82.7 to 100), respectively. We also identified statistically significant effectiveness against serotype 3 (79.5%, 95% CI 30.3 to 94.8) and against antibiotic non-susceptible invasive pneumococcal disease (65.6%, 44.9 to 78.7). Vaccine effectiveness against all-cause invasive pneumococcal disease was 60.2% (95% CI 46.8 to 70.3). Vaccine effectiveness was similar among children with (81.4%, 95% CI 45.4 to 93.6) and without (85.8%, 74.9 to 91.9) underlying conditions. INTERPRETATION: PCV13 appears highly effective against invasive pneumococcal disease among children in the USA in the context of routine and catch-up schedules, although some new vaccine antigens could not be assessed. PCV13 immunisation provides a robust strategy for combating pneumococcal antimicrobial resistance. FUNDING: Centers for Disease Control and Prevention. |
Annual report to the nation on the status of cancer, 1975-2012, featuring the increasing incidence of liver cancer
Ryerson AB , Eheman CR , Altekruse SF , Ward JW , Jemal A , Sherman RL , Henley SJ , Holtzman D , Lake A , Noone AM , Anderson RN , Ma J , Ly KN , Cronin KA , Penberthy L , Kohler BA . Cancer 2016 122 (9) 1312-37 BACKGROUND: Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. METHODS: Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. RESULTS: Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born after the 1938 to 1947 birth cohort. In contrast, there was a minimal birth cohort effect for NH Asian and Pacific Islanders (APIs). NH black men and Hispanic men had the lowest median age at death (60 and 62 years, respectively) and the highest average person-years of life lost per death (21 and 20 years, respectively) from liver cancer. HCV and liver cancer-associated death rates were highest among decedents who were born during 1945 through 1965. CONCLUSIONS: Overall, cancer incidence and mortality declined among men; and, although cancer incidence was stable among women, mortality declined. The burden of liver cancer is growing and is not equally distributed throughout the population. Efforts to vaccinate populations that are vulnerable to hepatitis B virus (HBV) infection and to identify and treat those living with HCV or HBV infection, metabolic conditions, alcoholic liver disease, or other causes of cirrhosis can be effective in reducing the incidence and mortality of liver cancer. (c) |
Prevention of antibiotic-nonsusceptible invasive pneumococcal disease with the 13-valent pneumococcal conjugate vaccine
Tomczyk SM , Lynfield R , Schaffner W , Reingold A , Miller L , Petit S , Holtzman C , Zansky SM , Thomas A , Baumbach J , Harrison LH , Farley MM , Beall B , McGee L , Gierke R , Pondo T , Kim L . Clin Infect Dis 2016 62 (9) 1119-25 BACKGROUND: Antibiotic-nonsusceptible invasive pneumococcal disease (IPD) decreased substantially after the US introduction of the pediatric 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. However, rates of antibiotic-nonsusceptible non-PCV7-type IPD increased during 2004-2009. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7. We assessed the impact of PCV13 on antibiotic-nonsusceptible IPD rates. METHODS: We defined IPD as pneumococcal isolation from a normally sterile site in a resident from 10 US surveillance sites. Antibiotic-nonsusceptible isolates were those intermediate or resistant to ≥1 antibiotic classes according to 2012 Clinical and Laboratory Standards Institute breakpoints. We examined rates of antibiotic-nonsusceptibility and estimated cases prevented between observed cases of antibiotic-nonsusceptible IPD and cases that would have occurred if PCV13 had not been introduced. RESULTS: From 2009-2013, rates of antibiotic-nonsusceptible IPD caused by serotypes included in PCV13 but not in PCV7 decreased from 6.5 to 0.5 per 100,000 in children aged <5 years and from 4.4 to 1.4 per 100,000 in adults aged ≥65 years. During 2010-2013, we estimated that 1,636 and 1,327 cases of antibiotic-nonsusceptible IPD caused by serotypes included in PCV13 but not in PCV7, were prevented among children aged <5 years (-97% difference) and among adults aged ≥65 years (-64% difference), respectively. Although we observed small increases in antibiotic-nonsusceptible IPD caused by non-PCV13 serotypes, no non-PCV13 serotype dominated among antibiotic-nonsusceptible strains. CONCLUSIONS: Following PCV13 introduction, antibiotic-nonsusceptible IPD decreased in multiple age groups. Continued surveillance is needed to monitor trends of non-vaccine serotypes. Pneumococcal conjugate vaccines are important tools in the approach to combat antibiotic resistance. |
Syringe service programs for persons who inject drugs in urban, suburban, and rural areas - United States, 2013
Des Jarlais DC , Nugent A , Solberg A , Feelemyer J , Mermin J , Holtzman D . MMWR Morb Mortal Wkly Rep 2015 64 (48) 1337-41 Reducing human immunodeficiency virus (HIV) infection rates in persons who inject drugs (PWID) has been one of the major successes in HIV prevention in the United States. Estimated HIV incidence among PWID declined by approximately 80% during 1990-2006. More recent data indicate that further reductions in HIV incidence are occurring in multiple areas. Research results for the effectiveness of risk reduction programs in preventing hepatitis C virus (HCV) infection among PWID have not been as consistent as they have been for HIV; however, a marked decline in the incidence of HCV infection occurred during 1992-2005 in selected U.S. locations when targeted risk reduction efforts for the prevention of HIV were implemented. Because syringe service programs (SSPs) have been one effective component of these risk reduction efforts for PWID, and because at least half of PWID are estimated to live outside major urban areas, a study was undertaken to characterize the current status of SSPs in the United States and determine whether urban, suburban, and rural SSPs differed. Data from a recent survey of SSPs were analyzed to describe program characteristics (e.g., size, clients, and services), which were then compared by urban, suburban, and rural location. Substantially fewer SSPs were located in rural and suburban than in urban areas, and harm reduction services( section sign) were less available to PWID outside urban settings. Because increases in substance abuse treatment admissions for drug injection have been observed concurrently with increases in reported cases of acute HCV infection in rural and suburban areas, state and local jurisdictions could consider extending effective prevention programs, including SSPs, to populations of PWID in rural and suburban areas. |
Trends in injection drug use among high school students, U.S., 1995-2013
Klevens RM , Jones SE , Ward JW , Holtzman D , Kann L . Am J Prev Med 2015 50 (1) 40-46 INTRODUCTION: Injection drug use is the most frequently reported risk behavior among new cases of hepatitis C virus infection, and recent reports of increases in infection are of great concern in many communities. This study assessed the prevalence and trends in injection drug use among U.S. high school students. METHODS: Data were from CDC's Youth Risk Behavior Surveillance System, which collects information on health risk behaviors at the national, state, and large urban school district levels. Analyses were conducted in 2014. RESULTS: In 2013, 1.7% of high school students nationwide had ever injected any illegal drug. Nationwide, ever injecting any illegal drug did not change significantly from 1995 to 2013, except among black non-Hispanic students. For this subgroup, both a significant linear increase from 1995 to 2013 and a significant quadratic trend were observed, with injection drug use increasing from 1995 to 2009 and decreasing from 2009 to 2013. Significant linear increases in injection drug use occurred in five states (Arkansas, Hawaii, Maine, Maryland, and New York) and six large urban school districts (Baltimore, Memphis, Miami-Dade County, New York City, Philadelphia, and Seattle). Significant linear decreases occurred in three states (Massachusetts, South Dakota, and West Virginia). Both a significant linear increase and quadratic trend were observed in Maine; quadratic trends were observed in Tennessee, Utah, and Palm Beach County, Florida. CONCLUSIONS: In some geographic areas and population groups, an increasing or high frequency of injection drug use was found among high school students, who should be targeted for prevention. |
Identification and linkage to care of HCV-infected persons in five health centers - Philadelphia, Pennsylvania, 2012-2014
Coyle C , Viner K , Hughes E , Kwakwa H , Zibbell JE , Vellozzi C , Holtzman D . MMWR Morb Mortal Wkly Rep 2015 64 (17) 459-63 Approximately three million persons in the United States are infected with hepatitis C virus (HCV), a blood-borne pathogen that is an increasing cause of liver disease and mortality in the United States. Treatments for HCV are curative, of short duration, and have few associated side effects, increasing the importance of identifying HCV-infected persons. Many persons with HCV infection were infected decades ago, before implementation of prevention measures and most are unaware of their infection, regardless of when it occurred. Most newly diagnosed cases are associated with injection drug use. Persons born during 1945-1965 have a fivefold higher risk of HCV infection than other adults and the highest risk for HCV-related morbidity and mortality. CDC recommends testing for this group, for persons who inject drugs, and others at risk for HCV infection. From October 2012 through July 2014, the National Nursing Centers Consortium (NNCC) carried out a project to integrate routine HCV testing and linkage-to-care in five federally qualified health centers in Philadelphia, PA, that primarily serve homeless persons and public housing residents. During the project period, 4,514 patients across the five centers were tested for HCV. Of these, 595 (13.2%) were HCV-antibody positive and 550 (92.4%) had a confirmatory HCV-RNA test performed. Of those who had a confirmatory HCV-RNA test performed, 390 (70.9%) were identified as having current (i.e., chronic) HCV infection (overall prevalence = 8.6%). Of those currently infected with HCV, 90% were informed of their status, 78% were referred to an HCV care specialist, and 62% went to the referred specialist for care. Replicable system modifications that improved HCV testing and care included enhancements to electronic medical records (EMRs), simplification of HCV testing protocols, and addition of a linkage-to-care coordinator. Findings from this project highlight the need for innovative strategies for HCV testing, care, and treatment, as well as the important role of community health centers in expanding access for patient populations disproportionately affected by HCV infection. |
Increases in hepatitis C virus infection related to injection drug use among persons aged ≤30 years - Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012
Zibbell JE , Iqbal K , Patel RC , Suryaprasad A , Sanders KJ , Moore-Moravian L , Serrecchia J , Blankenship S , Ward JW , Holtzman D . MMWR Morb Mortal Wkly Rep 2015 64 (17) 453-8 Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with approximately three million persons living with current infection. Percutaneous exposure to contaminated blood is the most efficient mode of transmission, and in the United States, injection drug use (IDU) is the primary risk factor for infection. State surveillance reports from the period 2006-2012 reveal a nationwide increase in reported cases of acute HCV infection, with the largest increases occurring east of the Mississippi River, particularly among states in central Appalachia. Demographic and behavioral data accompanying these reports show young persons (aged ≤30 years) from nonurban areas contributed to the majority of cases, with about 73% citing IDU as a principal risk factor. To better understand the increase in acute cases of HCV infection and its correlation to IDU, CDC examined surveillance data for acute case reports in conjunction with analyzing drug treatment admissions data from the Treatment Episode Data Set-Admissions (TEDS-A) among persons aged ≤30 years in four states (Kentucky, Tennessee, Virginia, and West Virginia) for the period 2006-2012. During this period, significant increases in cases of acute HCV infection were found among persons in both urban and nonurban areas, with a substantially higher incidence observed each year among persons residing in nonurban areas. During the same period, the proportion of treatment admissions for opioid dependency increased 21.1% in the four states, with a significant increase in the proportion of persons admitted who identified injecting as their main route of drug administration (an increase of 12.6%). Taken together, these increases indicate a geographic intersection among opioid abuse, drug injecting, and HCV infection in central Appalachia and underscore the need for integrated health services in substance abuse treatment settings to prevent HCV infection and ensure that those who are infected receive medical care. |
Estimating the number of persons who inject drugs in the United States by meta-analysis to calculate national rates of HIV and hepatitis C virus infections
Lansky A , Finlayson T , Johnson C , Holtzman D , Wejnert C , Mitsch A , Gust D , Chen R , Mizuno Y , Crepaz N . PLoS One 2014 9 (5) e97596 BACKGROUND: Injection drug use provides an efficient mechanism for transmitting bloodborne viruses, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Effective targeting of resources for prevention of HIV and HCV infection among persons who inject drugs (PWID) is based on knowledge of the population size and disparity in disease burden among PWID. This study estimated the number of PWID in the United States to calculate rates of HIV and HCV infection. METHODS: We conducted meta-analysis using data from 4 national probability surveys that measured lifetime (3 surveys) or past-year (3 surveys) injection drug use to estimate the proportion of the United States population that has injected drugs. We then applied these proportions to census data to produce population size estimates. To estimate the disease burden among PWID by calculating rates of disease we used lifetime population size estimates of PWID as denominators and estimates of HIV and HCV infection from national HIV surveillance and survey data, respectively, as numerators. We calculated rates of HIV among PWID by gender-, age-, and race/ethnicity. RESULTS: Lifetime PWID comprised 2.6% (95% confidence interval: 1.8%-3.3%) of the U.S. population aged 13 years or older, representing approximately 6,612,488 PWID (range: 4,583,188-8,641,788) in 2011. The population estimate of past-year PWID was 0.30% (95% confidence interval: 0.19 %-0.41%) or 774,434 PWID (range: 494,605-1,054,263). Among lifetime PWID, the 2011 HIV diagnosis rate was 55 per 100,000 PWID; the rate of persons living with a diagnosis of HIV infection in 2010 was 2,147 per 100,000 PWID; and the 2011 HCV infection rate was 43,126 per 100,000 PWID. CONCLUSION: Estimates of the number of PWID and disease rates among PWID are important for program planning and addressing health inequities. |
Expanding primary care capacity to treat hepatitis C virus infection through an evidence-based care model - Arizona and Utah, 2012-2014
Mitruka K , Thornton K , Cusick S , Orme C , Moore A , Manch RA , Box T , Carroll C , Holtzman D , Ward JW . MMWR Morb Mortal Wkly Rep 2014 63 (18) 393-8 Hepatitis C virus (HCV) infection is the leading reason for liver transplantation and a common cause of hepatocellular carcinoma, the most rapidly increasing cause of cancer-related deaths in the United States. Of the approximately 3 million persons living with HCV infection in the United States, an estimated 38% are linked to care, 11% are treated, and 6% achieve cure. Recent development of highly effective and well-tolerated medications, such as sofosbuvir and simeprevir, to treat chronic HCV infection shows promise in curbing rising HCV-related morbidity and mortality, with the potential to cure >90% of patients. To fully benefit from these new treatments, improvement in linkage to care and treatment is urgently needed.* Lack of provider expertise in HCV treatment and limited access to specialists are well-documented barriers to HCV treatment. In September 2012, CDC funded programs in Utah and Arizona to improve access to primary care providers with the capacity to manage and treat HCV infection. Both programs were modeled on the Extension for Community Healthcare Outcomes (Project ECHO), developed by the University of New Mexico's Health Sciences Center in 2003 to build primary care capacity to treat diseases among rural, underserved populations through videoconferencing and case-based learning in "teleECHO" clinics. To assess the effectiveness of these programs in improving primary care provider capacity and increasing the number of patients initiating treatment, process and patient outcome data for each state program were analyzed. In both states, Project ECHO was successfully implemented, training 66 primary care clinicians, predominantly from rural settings. Nearly all (93%) of the clinicians had no prior experience in care and treatment of HCV infection. In both states combined, 129 (46%) of HCV-infected patients seen in teleECHO clinics received antiviral treatment, more than doubling the proportion of patients expected to receive treatment. These findings demonstrate Project ECHO's ability to expand primary care capacity to treat HCV infection, notably among underserved populations. |
Confronting the emerging epidemic of HCV infection among young injection drug users
Valdiserri R , Khalsa J , Dan C , Holmberg S , Zibbell J , Holtzman D , Lubran R , Compton W . Am J Public Health 2014 104 (5) 816-21 Hepatitis C virus infection is a significant public health problem in the United States and an important cause of morbidity and mortality. Recent reports document HCV infection increases among young injection drug users in several US regions, associated with America's prescription opioid abuse epidemic. Incident HCV infection increases among young injectors who have recently transitioned from oral opioid abuse present an important public health challenge requiring a comprehensive, community-based response. We summarize recommendations from a 2013 Office of HIV/AIDS and Infectious Disease Policy convening of experts in epidemiology, behavioral science, drug prevention and treatment, and other research; community service providers; and federal, state, and local government representatives. Their observations highlight gaps in our surveillance, program, and research portfolios and advocate a syndemic approach to this emerging public health problem. |
Previous exposure to HCV among persons born during 1945-1965: prevalence and predictors, United States, 1999-2008
Smith BD , Beckett GA , Yartel A , Holtzman D , Patel N , Ward JW . Am J Public Health 2014 104 (3) 474-81 OBJECTIVES: We examined HCV exposure prevalence and predictors among persons in the United States born during 1945-1965. METHODS: With data from the 1999-2008 National Health and Nutrition Examination Survey, we calculated the proportion of persons born during 1945-1965 who tested positive for HCV antibody (anti-HCV) and analyzed the prevalence by sociodemographic and behavioral risk factors. RESULTS: Anti-HCV prevalence in the 1945-1965 birth cohort was 3.2% (95% confidence interval [CI] = 2.8%, 3.8%), substantially higher than among other adults (0.9%). Within the cohort, anti-HCV prevalence was higher among non-Hispanic Blacks (6.4%; 95% CI = 5.3%, 7.7%), persons with injection drug use histories (56.8%; 95% CI = 48.4%, 64.8%), and persons with elevated alanine aminotransferase levels (12.7%; 95% CI = 10.7%, 15.1%). Injection drug use (adjusted odds ratio = 98.4; 95% CI = 58.8, 164.5) was the strongest anti-HCV prevalence predictor. Among anti-HCV-positive persons, 57.8% reported having 2 or more alcoholic drinks daily. CONCLUSIONS: With the high prevalence of HCV among persons born during 1945-1965, the increasing morbidity and mortality associated with HCV, and reductions in liver cancer and HCV-related mortality when HCV is eradicated, it is critically important to identify persons with HCV and link them to appropriate care. |
Polypharmacy and risk of antiretroviral drug interactions among the aging HIV-infected population
Holtzman C , Armon C , Tedaldi E , Chmiel JS , Buchacz K , Wood K , Brooks JT . J Gen Intern Med 2013 28 (10) 1302-10 BACKGROUND: Among aging HIV-infected adults, polypharmacy and its consequences have not been well-described. OBJECTIVE: To characterize the extent of polypharmacy and the risk of antiretroviral (ARV) drug interactions among persons of different ages. DESIGN AND PARTICIPANTS: Cross-sectional analysis among patients within the HIV Outpatient Study (HOPS) cohort who were prescribed ARVs during 2006-2010. MAIN MEASURES: We used the University of Liverpool HIV drug interactions database to identify ARV/non-ARV interactions with potential for clinical significance. KEY RESULTS: Of 3,810 patients analyzed (median age 46 years, 34 % ≥ 50 years old) at midpoint of observation, 1,494 (39 %) patients were prescribed ≥ 5 non-ARV medications: 706 (54 %) of 1,312 patients ≥ 50 years old compared with 788 (32 %) of 2,498 patients < 50 years. During the five-year period, the number of patients who were prescribed at least one ARV/non-ARV combination that was contraindicated or had moderate or high evidence of interaction was 267 (7 %) and 1,267 (33 %), respectively. Variables independently associated with having been prescribed a contraindicated ARV/non-ARV combination included older age (adjusted odds ratio [aOR] per 10 years of age 1.17, 95 % CI 1.01-1.35), anxiety (aOR 1.78, 95 % CI 1.32-2.40), dyslipidemia (aOR 1.96, 95 % CI 1.28-2.99), higher daily non-ARV medication burden (aOR 1.13, 95 % CI 1.10-1.17), and having been prescribed a protease inhibitor (aOR 2.10, 95 % CI 1.59-2.76). Compared with patients < 50 years, older patients were more likely to have been prescribed an ARV/non-ARV combination that was contraindicated (unadjusted OR 1.44, 95 % CI 1.14-1.82), or had moderate or high evidence of interaction (unadjusted OR 1.29, 95 % CI 1.15-1.44). CONCLUSIONS: A substantial percentage of patients were prescribed at least one ARV/non-ARV combination that was contraindicated or had potential for a clinically significant interaction. As HIV-infected patients age and experience multiple comorbidities, systematic reviews of current medications by providers may reduce risk of such exposures. |
Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965
Smith BD , Morgan RL , Beckett GA , Falck-Ytter Y , Holtzman D , Teo CG , Jewett A , Baack B , Rein DB , Patel N , Alter M , Yartel A , Ward JW . MMWR Recomm Rep 2012 61 1-32 Hepatitis C virus (HCV) is an increasing cause of morbidity and mortality in the United States. Many of the 2.7-3.9 million persons living with HCV infection are unaware they are infected and do not receive care (e.g., education, counseling, and medical monitoring) and treatment. CDC estimates that although persons born during 1945-1965 comprise an estimated 27% of the population, they account for approximately three fourths of all HCV infections in the United States, 73% of HCV-associated mortality, and are at greatest risk for hepatocellular carcinoma and other HCV-related liver disease. With the advent of new therapies that can halt disease progression and provide a virologic cure (i.e., sustained viral clearance following completion of treatment) in most persons, targeted testing and linkage to care for infected persons in this birth cohort is expected to reduce HCV-related morbidity and mortality. CDC is augmenting previous recommendations for HCV testing (CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19]) to recommend one-time testing without prior ascertainment of HCV risk for persons born during 1945-1965, a population with a disproportionately high prevalence of HCV infection and related disease. Persons identified as having HCV infection should receive a brief screening for alcohol use and intervention as clinically indicated, followed by referral to appropriate care for HCV infection and related conditions. These recommendations do not replace previous guidelines for HCV testing that are based on known risk factors and clinical indications. Rather, they define an additional target population for testing: persons born during 1945-1965. CDC developed these recommendations with the assistance of a work group representing diverse expertise and perspectives. The recommendations are informed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, an approach that provides guidance and tools to define the research questions, conduct the systematic review, assess the overall quality of the evidence, and determine strength of the recommendations. This report is intended to serve as a resource for health-care professionals, public health officials, and organizations involved in the development, implementation, and evaluation of prevention and clinical services. These recommendations will be reviewed every 5 years and updated to include advances in the published evidence. |
Global burden of hepatitis C: considerations for healthcare providers in the United States
Averhoff FM , Glass N , Holtzman D . Clin Infect Dis 2012 55 Suppl 1 S10-5 An estimated 2%-3% of the world's population is living with hepatitis C virus (HCV) infection, and each year, >350.000 die of HCV-related conditions, including cirrhosis and liver cancer. The epidemiology and burden of HCV infection varies throughout the world, with country-specific prevalence ranging from <1% to >10%. In contrast to the United States and other developed countries, HCV transmission in developing countries frequently results from exposure to infected blood in healthcare and community settings. Hepatitis C prevention, care, and treatment programs must recognize country-specific epidemiology, which varies by setting and level of economic development. Awareness of the global epidemiology of HCV infection is important for US healthcare providers treating foreign-born patients from countries where HCV infection is endemic and for counseling patients who travel to these countries. Countries with a high burden of HCV infection also would benefit from establishing comprehensive prevention, care, and treatment programs. |
Aging in the United States: opportunities and challenges for public health
Anderson LA , Goodman RA , Holtzman D , Posner SF , Northridge ME . Am J Public Health 2012 102 (3) 393-395 Never before has the global population included as many older adults as it does today. Over the past century in the United States alone, the proportion of persons aged 65 years or older increased more than threefold, from 4.1% to 12.9%.1 This issue of the Journal devoted to “Healthy Aging” opens a dialogue for examining innovative roles for public health and the health care system in relation to a broad spectrum of priorities involving the aging population. Despite the acknowledged challenges of limited resources and economic uncertainty, as this issue's articles suggest, opportunities abound to improve the health and functioning of older adults and enhance intergenerational programs and policies that enrich all of society. Additional articles for this series will be published in subsequent Journal issues over the coming years. |
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