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1.  The Starting Treatment for Ethanol in Primary care Trials (STEP Trials): Protocol for Three Parallel Multi-Site Stepped Care Effectiveness Studies for Unhealthy Alcohol Use in HIV-Positive Patients 
Unhealthy alcohol use is common among HIV-positive patients, yet effective evidence-based treatments are rarely provided in clinical settings providing HIV care. Further, given patient variability in response to initial treatments, stepped care approaches may be beneficial. We describe the rationale, aims and study design for the current Starting Treatment for Ethanol in Primary care Trials (STEP Trials); three parallel randomized controlled effectiveness trials being conducted in five Infectious Disease Clinics. Participants meeting criteria for: 1) at-risk drinking, 2) moderate alcohol use with liver disease (MALD), or 3) alcohol use disorder (AUD) are randomized to integrated stepped care versus treatment as usual. For those with at-risk drinking or MALD, integrated stepped care starts with a one session brief intervention and follow-up 2-week telephone booster. Based on pre-specified nonresponse criteria, participants may be “stepped up” at week 4 to receive four sessions of motivational enhancement therapy (MET) and “stepped up” again at week 12 for addiction physician management (APM) and consideration of alcohol pharmacotherapy. For those with AUD, integrated stepped care begins with APM. Non-responders may be “stepped up” at week 4 to receive MET and again at week 12 for a higher level of care (e.g. intensive outpatient program). The primary outcome is alcohol consumption assessed at 24 weeks, and secondary outcome is the VACS Index, a validated measure of HIV morbidity and mortality risk. Results from the STEP Trials should inform future research and the implementation of interventions to address unhealthy alcohol use among HIV-positive individuals.
doi:10.1016/j.cct.2016.11.008
PMCID: PMC5253227  PMID: 27876616
Multicenter study; Randomized controlled trial; Algorithms; HIV; Alcohol
2.  Association Between Depressive Disorders and Incident Acute Myocardial Infarction in Human Immunodeficiency Virus–Infected Adults 
JAMA cardiology  2016;1(8):929-937.
IMPORTANCE
With the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)–infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population.
OBJECTIVE
To examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV.
DESIGN, SETTING, AND PARTICIPANTS
Included in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998–2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015.
MAIN OUTCOMES AND MEASURES
Incident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009.
RESULTS
The mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05–1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04–1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05–1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00–1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87–1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI.
CONCLUSIONS AND RELEVANCE
We report novel evidence that HIV-infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population.
doi:10.1001/jamacardio.2016.2716
PMCID: PMC5621480  PMID: 27557332
3.  Proceedings of the 14th annual conference of INEBRIA 
Holloway, Aisha S. | Ferguson, Jennifer | Landale, Sarah | Cariola, Laura | Newbury-Birch, Dorothy | Flynn, Amy | Knight, John R. | Sherritt, Lon | Harris, Sion K. | O’Donnell, Amy J. | Kaner, Eileen | Hanratty, Barbara | Loree, Amy M. | Yonkers, Kimberly A. | Ondersma, Steven J. | Gilstead-Hayden, Kate | Martino, Steve | Adam, Angeline | Schwartz, Robert P. | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | McNeely, Jennifer | Berman, Anne H. | Kolaas, Karoline | Petersén, Elisabeth | Bendtsen, Preben | Hedman, Erik | Linderoth, Catharina | Müssener, Ulrika | Sinadinovic, Kristina | Spak, Fredrik | Gremyr, Ida | Thurang, Anna | Mitchell, Ann M. | Finnell, Deborah | Savage, Christine L. | Mahmoud, Khadejah F. | Riordan, Benjamin C. | Conner, Tamlin S. | Flett, Jayde A. M. | Scarf, Damian | McRee, Bonnie | Vendetti, Janice | Gallucci, Karen Steinberg | Robaina, Kate | Clark, Brendan J. | Jones, Jacqueline | Reed, Kathryne D. | Hodapp, Rachel M. | Douglas, Ivor | Burnham, Ellen L. | Aagaard, Laura | Cook, Paul F. | Harris, Brett R. | Yu, Jiang | Wolff, Margaret | Rogers, Meighan | Barbosa, Carolina | Wedehase, Brendan J. | Dunlap, Laura J. | Mitchell, Shannon G. | Dusek, Kristi A. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla T. | Hosler, Colleen | O’Grady, Kevin E. | Brown, Barry S. | Angus, Colin | Sherborne, Sidney | Gillespie, Duncan | Meier, Petra | Brennan, Alan | de Vargas, Divane | Soares, Janaina | Castelblanco, Donna | Doran, Kelly M. | Wittman, Ian | Shelley, Donna | Rotrosen, John | Gelberg, Lillian | Edelman, E. Jennifer | Maisto, Stephen A. | Hansen, Nathan B. | Cutter, Christopher J. | Deng, Yanhong | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Bedimo, Roger | Gibert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria C. | Simberkoff, Michael S. | Justice, Amy C. | Bryant, Kendall J. | Fiellin, David A. | Giles, Emma L. | Coulton, Simon | Deluca, Paolo | Drummond, Colin | Howel, Denise | McColl, Elaine | McGovern, Ruth | Scott, Stephanie | Stamp, Elaine | Sumnall, Harry | Vale, Luke | Alabani, Viviana | Atkinson, Amanda | Boniface, Sadie | Frankham, Jo | Gilvarry, Eilish | Hendrie, Nadine | Howe, Nicola | McGeechan, Grant J. | Ramsey, Amy | Stanley, Grant | Clephane, Justine | Gardiner, David | Holmes, John | Martin, Neil | Shevills, Colin | Soutar, Melanie | Chi, Felicia W. | Weisner, Constance | Ross, Thekla B. | Mertens, Jennifer | Sterling, Stacy A. | Shorter, Gillian W. | Heather, Nick | Bray, Jeremy | Cohen, Hildie A. | McPherson, Tracy L. | Adam, Cyrille | López-Pelayo, Hugo | Gual, Antoni | Segura-Garcia, Lidia | Colom, Joan | Ornelas, India J. | Doyle, Suzanne | Donovan, Dennis | Duran, Bonnie | Torres, Vanessa | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Paroz, Sophie | Bertholet, Nicolas | Daeppen, Jean-Bernard | Satterfield, Jason M. | Gregorich, Steven | Alvarado, Nicholas J. | Muñoz, Ricardo | Kulieva, Gozel | Vijayaraghavan, Maya | Adam, Angéline | Cunningham, John A. | Díaz, Estela | Palacio-Vieira, Jorge | Godinho, Alexandra | Kushir, Vladyslav | O’Brien, Kimberly H. M. | Aguinaldo, Laika D. | Sellers, Christina M. | Spirito, Anthony | Chang, Grace | Blake-Lamb, Tiffany | LaFave, Lea R. Ayers | Thies, Kathleen M. | Pepin, Amy L. | Sprangers, Kara E. | Bradley, Martha | Jorgensen, Shasta | Catano, Nico A. | Murray, Adelaide R. | Schachter, Deborah | Andersen, Ronald M. | Rey, Guillermina Natera | Vahidi, Mani | Rico, Melvin W. | Baumeister, Sebastian E. | Johansson, Magnus | Sinadinovic, Christina | Hermansson, Ulric | Andreasson, Sven | O’Grady, Megan A. | Kapoor, Sandeep | Akkari, Cherine | Bernal, Camila | Pappacena, Kristen | Morley, Jeanne | Auerbach, Mark | Neighbors, Charles J. | Kwon, Nancy | Conigliaro, Joseph | Morgenstern, Jon | Magill, Molly | Apodaca, Timothy R. | Borsari, Brian | Hoadley, Ariel | Scott Tonigan, J. | Moyers, Theresa | Fitzgerald, Niamh M. | Schölin, Lisa | Barticevic, Nicolas | Zuzulich, Soledad | Poblete, Fernando | Norambuena, Pablo | Sacco, Paul | Ting, Laura | Beaulieu, Michele | Wallace, Paul George | Andrews, Matthew | Daley, Kate | Shenker, Don | Gallagher, Louise | Watson, Rod | Weaver, Tim | Bruguera, Pol | Oliveras, Clara | Gavotti, Carolina | Barrio, Pablo | Braddick, Fleur | Miquel, Laia | Suárez, Montse | Bruguera, Carla | Brown, Richard L. | Capell, Julie Whelan | Paul Moberg, D. | Maslowsky, Julie | Saunders, Laura A. | McCormack, Ryan P. | Scheidell, Joy | Gonzalez, Mirelis | Bauroth, Sabrina | Liu, Weiwei | Lindsay, Dawn L. | Lincoln, Piper | Hagle, Holly | Wallhed Finn, Sara | Hammarberg, Anders | Andréasson, Sven | King, Sarah E. | Vargo, Rachael | Kameg, Brayden N. | Acquavita, Shauna P. | Van Loon, Ruth Anne | Smith, Rachel | Brehm, Bonnie J. | Diers, Tiffiny | Kim, Karissa | Barker, Andrea | Jones, Ashley L. | Skinner, Asheley C. | Hinman, Agatha | Svikis, Dace S. | Thacker, Casey L. | Resnicow, Ken | Beatty, Jessica R. | Janisse, James | Puder, Karoline | Bakshi, Ann-Sofie | Milward, Joanna M. | Kimergard, Andreas | Garnett, Claire V. | Crane, David | Brown, Jamie | West, Robert | Michie, Susan | Rosendahl, Ingvar | Andersson, Claes | Gajecki, Mikael | Blankers, Matthijs | Donoghue, Kim | Lynch, Ellen | Maconochie, Ian | Phillips, Ceri | Pockett, Rhys | Phillips, Tom | Patton, R. | Russell, Ian | Strang, John | Stewart, Maureen T. | Quinn, Amity E. | Brolin, Mary | Evans, Brooke | Horgan, Constance M. | Liu, Junqing | McCree, Fern | Kanovsky, Doug | Oberlander, Tyler | Zhang, Huan | Hamlin, Ben | Saunders, Robert | Barton, Mary B. | Scholle, Sarah H. | Santora, Patricia | Bhatt, Chirag | Ahmed, Kazi | Hodgkin, Dominic | Gao, Wenwu | Merrick, Elizabeth L. | Drebing, Charles E. | Larson, Mary Jo | Sharma, Monica | Petry, Nancy M. | Saitz, Richard | Weisner, Constance M. | Young-Wolff, Kelly C. | Lu, Wendy Y. | Blosnich, John R. | Lehavot, Keren | Glass, Joseph E. | Williams, Emily C. | Bensley, Kara M. | Chan, Gary | Dombrowski, Julie | Fortney, John | Rubinsky, Anna D. | Lapham, Gwen T. | Forray, Ariadna | Olmstead, Todd A. | Gilstad-Hayden, Kathryn | Kershaw, Trace | Dillon, Pamela | Weaver, Michael F. | Grekin, Emily R. | Ellis, Jennifer D. | McGoron, Lucy | McGoron, Lucy
doi:10.1186/s13722-017-0087-8
PMCID: PMC5606215
4.  Fracture prediction with modified-FRAX in older HIV-infected and uninfected men 
Background
FRAX® is a validated, computer-based clinical fracture risk calculator that estimates 10-year risk of major osteoporotic (clinical spine, forearm, hip or shoulder) fracture, and hip fracture alone. It is widely used for decision-making in fracture prevention, but may underestimate risk in HIV-infected individuals. Some experts recommend considering HIV a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals.
Methods
From the Veterans Aging Study Virtual Cohort (VACS-VC), we included 24451 HIV-infected and uninfected 50-70 year old men with complete data in year 2000 to approximate all but two factors (i.e. history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. Accuracy of the modified-FRAX calculation was compared by observed/estimated (O/E) ratios of fracture by HIV status.
Results
Accuracy of modified-FRAX was less for HIV-infected (O/E=1.62, 95%CI: 1.45, 1.81) than uninfected men (O/E=1.29, 95%CI: 1.19, 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E=1.20, 95%CI: 1.08, 1.34). However, only 3-6% of men with incident fractures were correctly identified by the modified-FRAX using accepted FRAX thresholds for pharmacologic therapy.
Conclusions
Modified-FRAX underestimated fracture rates more in older HIV-infected than otherwise similar uninfected men. Accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case-finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV-infected individuals.
doi:10.1097/QAI.0000000000000998
PMCID: PMC4942335  PMID: 27003493
fracture incidence; HIV; men; FRAX
5.  Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era 
JAMA cardiology  2017;2(5):536-546.
IMPORTANCE
With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis.
OBJECTIVES
To investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors.
DESIGN, SETTING, AND PARTICIPANTS
This study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of the analysis were October 2015 to November 2016.
EXPOSURE
Human immunodeficiency virus infection.
MAIN OUTCOMES AND MEASURES
Outcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%–49%), HFrEF (EF<40%), and HF of unknown type (EF missing).
RESULTS
Among 98 015 participants, the mean (SD) age at enrollment in the study was 48.3 (9.8) years, 97.0% were male, and 32.2% had HIV infection. During a median follow-up of 7.1 years, there were 2636 total HF events (34.6% were HFpEF, 15.5% were borderline HFpEF, 37.1% were HFrEF, and 12.8% were HF of unknown type). Compared with uninfected veterans, HIV-infected veterans had an increased risk of HFpEF (hazard ratio [HR], 1.21; 95% CI, 1.03–1.41), borderline HFpEF (HR, 1.37; 95% CI, 1.09–1.72), and HFrEF (HR, 1.61; 95% CI, 1.40–1.86). The risk of HFrEF was pronounced in veterans younger than 40 years at baseline (HR, 3.59; 95% CI, 1.95–6.58). Among HIV-infected veterans, time-updated HIV-1 RNA viral load of at least 500 copies/mL compared with less than 500 copies/mL was associated with an increased risk of HFrEF, and time-updated CD4 cell count less than 200 cells/mm3 compared with at least 500 cells/mm3 was associated with an increased risk of HFrEF and HFpEF.
CONCLUSIONS AND RELEVANCE
Individuals who are infected with HIV have an increased risk of HFpEF, borderline HFpEF, and HFrEF compared with uninfected individuals. The increased risk of HFrEF can manifest decades earlier than would be expected in a typical uninfected population. Future research should focus on prevention, risk stratification, and identification of the mechanisms for HFrEF and HFpEF in the HIV-infected population.
doi:10.1001/jamacardio.2017.0264
PMCID: PMC5541383  PMID: 28384660
6.  Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era: 1997–2012 
AIDS (London, England)  2016;30(11):1795-1806.
Objective
Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.
Design
Prospective cohort study.
Methods
We followed 44,787 HIV+ and 96,852 demographically-matched uninfected persons during 1997–2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates (IR) and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with IR and IRR period trend p-values for cancer groupings and specific cancer types.
Results
We observed 3,714 incident cancer diagnoses in HIV+ and 5,760 in uninfected persons. The HIV+ all cancer crude IR increased between 1997–2000 and 2009–2012 (p-trend=0.0019). However, after standardization, we observed highly significant HIV+ IR declines for all cancer (25% decline; p-trend<0.0001), AIDS-defining cancers (ADC; 55% decline; p-trend<0.0001), non-AIDS-defining cancers (NADC; 15% decline; p-trend=0.0003), and non-virus-related NADC (20% decline; p-trend<0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; p-trend<0.0001), ADC (from 19 to 5.5; p-trend<0.0001), and non-virus-related NADC (from 1.4 to 1.2; p-trend=0.049); and borderline significant IRR declines for NADC (from 1.6 to 1.4; p-trend=0.078) and virus-related NADC (from 4.9 to 3.5; p-trend=0.071).
Conclusion
Improved HIV care resulting in improved immune function most likely contributed to the HIV+ IR and the IRR declines. Further promotion of early and sustained ART, improved ART regimens, reduction of traditional cancer risk factor (e.g., smoking) prevalence, and evidence-based screening could contribute to future cancer incidence declines among HIV+ persons.
doi:10.1097/QAD.0000000000001112
PMCID: PMC4925286  PMID: 27064994
acquired immunodeficiency syndrome; HIV infections; neoplasms; cancer; Veterans
7.  Current use of statins reduces risk of HIV rebound on suppressive HAART 
PLoS ONE  2017;12(3):e0172175.
Background
Despite compelling evidence for activity against HIV-1 in vitro, a virologic effect of statins has not been shown in clinical studies. Given their short plasma half-lives, such an effect may be transient and only apparent during ongoing exposure.
Methods
We studied all HIV infected US-Veterans who started HAART 1995–2011, had a documented HIV viral load (VL) >1000 copies/mL, reached an undetectable VL on HAART, and had ≥1 follow-up VL within 13 months. We defined virologic failure (VF) as the first VL >1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. We built a time-updated drug exposure model for antiretrovirals (ARVs), statins, and other cardiovascular drugs (CVMs), investigating current use (yes/no), recent use (proportion of days used), and categorical use (ever/never). We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin and CVM use and VF.
Results
19,324 veterans met inclusion criteria. Median follow-up was 13 months (IQR: 5–32 months); 63% experienced VF after a median time of 9 months (IQR 4–21 months). Almost 1/3 patients ever used statins but exposure comprised only 41% of follow-up time covered after initial prescription. Unadjusted, current statin use was associated with a hazard ratio (HR) for VF of 0.60 (CI: 0.56–0.65). This remained statistically significant after multivariate adjustment (MVA) for demographics, HIV and HAART parameters [HR 0.81 (CI: 0.75–0.88), p<0.001] and IPW (truncation <1%/>99%) HR: 0.83 (CI: 0.75–0.92), p<0.001]. No independent association was observed for other CVMs. The association between categorical-statin use and VF after MVA was much weaker: HR 0.94 (CI: 0.88–1.00, p = 0.04).
Conclusion
Current statin exposure was associated with reduced risk of VF in univariate, multivariate, and inverse-probability-weighted models. Our results highlight the importance of time-updated medication exposure models for observational studies.
doi:10.1371/journal.pone.0172175
PMCID: PMC5331966  PMID: 28249009
8.  Depression and HIV Infection are Risk Factors for Incident Heart Failure Among Veterans: Veterans Aging Cohort Study 
Circulation  2015;132(17):1630-1638.
Background
Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among HIV+ adults. We assessed the association between HIV, depression and incident HF.
Methods and Results
Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (N = 81,427; 26,908 HIV+, 54,519 HIV-) were categorized into four groups: HIV- without major depressive disorder (MDD) [reference]; HIV- with MDD; HIV+ without MDD; and HIV+ with MDD. ICD-9 codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 follow-up years, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% CI, 8.20–10.6). In Cox proportional hazards models, HIV+ participants with MDD had significantly higher risk of HF [adjusted hazard ratio (aHR) = 1.68; 95% CI, 1.45–1.95] compared to HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (aHR = 1.21; 1.06–1.37 and 1.29; 1.11–1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (aHR = 0.76; 0.58–0.99).
Conclusions
Our study is the first to suggest MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF; and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.
doi:10.1161/CIRCULATIONAHA.114.014443
PMCID: PMC4624488  PMID: 26358261
HIV infection; depression; psychiatric comorbidity; heart failure; epidemiology
9.  Proceedings of the 13th annual conference of INEBRIA 
Watson, Rod | Morris, James | Isitt, John | Barrio, Pablo | Ortega, Lluisa | Gual, Antoni | Conner, Kenneth | Stecker, Tracy | Maisto, Stephen | Paroz, Sophie | Graap, Caroline | Grazioli, Véronique S | Daeppen, Jean-Bernard | Collins, Susan E | Bertholet, Nicolas | McNeely, Jennifer | Kushnir, Vlad | Cunningham, John A. | Crombie, Iain K | Cunningham, Kathryn B | Irvine, Linda | Williams, Brian | Sniehotta, Falko F | Norrie, John | Melson, Ambrose | Jones, Claire | Briggs, Andrew | Rice, Peter | Achison, Marcus | McKenzie, Andrew | Dimova, Elena | Slane, Peter W | Grazioli, Véronique S. | Collins, Susan E. | Paroz, Sophie | Graap, Caroline | Daeppen, Jean-Bernard | Baggio, Stéphanie | Dupuis, Marc | Studer, Joseph | Gmel, Gerhard | Magill, Molly | Grazioli, Véronique S. | Tait, Robert J. | Teoh, Lucinda | Kelty, Erin | Geelhoed, Elizabeth | Mountain, David | Hulse, Gary K. | Renko, Elina | Mitchell, Shannon G. | Lounsbury, David | Li, Zhi | Schwartz, Robert P. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla | Hosler, Colleen | Dusek, Kristi | Brown, Barry S. | Finnell, Deborah S. | Holloway, Aisha | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | Wallhed Finn, Sara | Andreasson, Sven | Dvorak, Robert D. | Kramer, Matthew P. | Stevenson, Brittany L. | Sargent, Emily M. | Kilwein, Tess M. | Harris, Sion K. | Sherritt, Lon | Copelas, Sarah | Knight, John R. | Mdege, Noreen D | McCambridge, Jim | Bischof, Gallus | Bischof, Anja | Freyer-Adam, Jennis | Rumpf, Hans-Juergen | Fitzgerald, Niamh | Schölin, Lisa | Toner, Paul | Böhnke, Jan R. | Veach, Laura J. | Currin, Olivia | Dongre, Leigh Z. | Miller, Preston R. | White, Elizabeth | Williams, Emily C. | Lapham, Gwen T. | Bobb, Jennifer J. | Rubinsky, Anna D. | Catz, Sheryl L. | Shortreed, Susan | Bensley, Kara M. | Bradley, Katharine A. | Milward, Joanna | Deluca, Paolo | Khadjesari, Zarnie | Watson, Rod | Fincham-Campbell, Stephanie | Drummond, Colin | Angus, Kathryn | Bauld, Linda | Baumann, Sophie | Haberecht, Katja | Schnuerer, Inga | Meyer, Christian | Rumpf, Hans-Jürgen | John, Ulrich | Gaertner, Beate | Barrault-Couchouron, Marion | Béracochéa, Marion | Allafort, Vincent | Barthélémy, Valérie | Bonnefoi, Hervé | Bussières, Emmanuel | Garguil, Véronique | Auriacombe, Marc | Saint-Jacques, Marianne | Dorval, Michel | M’Bailara, Katia | Segura-Garcia, Lidia | Ibañez-Martinez, Nuria | Mendive-Arbeloa, Juan Manuel | Anoro-Perminger, Manel | Diaz-Gallego, Pako | Piñar-Mateos, Mª Angeles | Colom-Farran, Joan | Deligianni, Marianthi | Yersin, Bertrand | Adam, Angeline | Weisner, Constance | Chi, Felicia | Lu, Wendy | Sterling, Stacy | Kraemer, Kevin L. | McGinnis, Kathleen A. | Fiellin, David A. | Skanderson, Melissa | Gordon, Adam J. | Robbins, Jonathan | Zickmund, Susan | Korthuis, P. Todd | Edelman, E. Jennifer | Hansen, Nathan B. | Cutter, Christopher J. | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Maisto, Stephen A. | Bedimo, Roger | Gilbert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria | Simberkoff, Michael | Justice, Amy C. | Bryant, Kendall J. | Berman, Anne H | Shorter, Gillian W | Bray, Jeremy W | Barbosa, Carolina | Johansson, Magnus | Hester, Reid | Campbell, William | Souza Formigoni, Maria Lucia O. | Andrade, André Luzi Monezi | Sartes, Laisa Marcorela Andreoli | Sundström, Christopher | Eék, Niels | Kraepelien, Martin | Kaldo, Viktor | Fahlke, Claudia | Hernandez, Lynn | Becker, Sara J. | Jones, Richard N. | Graves, Hannah R. | Spirito, Anthony | Diestelkamp, Silke | Wartberg, Lutz | Arnaud, Nicolas | Thomasius, Rainer | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Malan, Zelra | Mash, Bob | Everett-Murphy, Katherine | Grazioli, Véronique S. | Studer, Joseph | Mohler-Kuo, M. | Bertholet, Nicolas | Gmel, Gerhard | Doi, Lawrence | Cheyne, Helen | Jepson, Ruth | Luna, Vanesa | Echeverria, Leticia | Morales, Silvia | Barroso, Teresa | Abreu, Ângela | Aguiar, Cosma | Stewart, Duncan | Abreu, Angela | Brites, Riany M. | Jomar, Rafael | Marinho, Gerson | Parreira, Pedro | Seale, J. Paul | Johnson, J. Aaron | Henry, Dena | Chalmers, Sharon | Payne, Freida | Tuck, Linda | Morris, Akula | Gonçalves, Cátia | Besser, Bettina | Casajuana, Cristina | López-Pelayo, Hugo | Balcells, María Mercedes | Teixidó, Lídia | Miquel, Laia | Colom, Joan | Hepner, Kimberly A. | Hoggatt, Katherine. J. | Bogart, Andy | Paddock, Susan. M. | Hardoon, Sarah L | Petersen, Irene | Hamilton, Fiona L | Nazareth, Irwin | White, Ian R. | Marston, Louise | Wallace, Paul | Godfrey, Christine | Murray, Elizabeth | Sovinová, Hana | Csémy, Ladislav
doi:10.1186/s13722-016-0062-9
PMCID: PMC5032602  PMID: 27654147
10.  Effects of Pegylated Interferon/Ribavirin on Bone Turnover Markers in HIV/Hepatitis C Virus-Coinfected Patients 
Abstract
HIV/hepatitis C virus (HCV) patients have a 3-fold increased fracture incidence compared to uninfected patients. The impact of HCV therapy on bone health is unclear. We evaluated bone turnover markers (BTM) in well-controlled (HIV RNA <50 copies/ml) HIV/HCV-coinfected patients who received pegylated interferon-α and ribavirin (PEG-IFN/RBV) in ACTG trial A5178. Early virologic responders (EVR: ≥2 log HCV RNA drop at week 12) continued PEG-IFN/RBV and non-EVRs were randomized to continuation of PEG-IFN alone or observation. We assessed changes in C-terminal telopeptide of type 1 collagen (CTX; bone resorption marker) and procollagen type I intact N-terminal propeptide (P1NP; bone formation marker), and whether BTM changes were associated with EVR, complete early virologic response (cEVR: HCV RNA <600 IU/ml at week 12), or PEG-IFN treatment. A total of 192 subjects were included. After 12 weeks of PEG-IFN/RBV, CTX and P1NP decreased: −120 pg/ml and −8.48 μg/liter, respectively (both p < 0.0001). CTX declines were greater in cEVR (N = 91; vs. non-cEVR (N = 101; p = 0.003). From week 12 to 24, CTX declines were sustained among EVR patients who continued PEG-IFN/RBV (p = 0.027 vs. non-EVR) and among non-EVR patients who continued PEG-IFN alone (p = 0.022 vs. Observation). Median decreases of P1NP in EVR vs. non-EVR were similar at weeks 12 and 24. PEG-IFN-based therapy for chronic HCV markedly reduces bone turnover. It is unclear whether this is a direct IFN effect or a result of HCV viral clearance, or whether they will result in improved bone mineral density. Further studies with IFN-free regimens should explore these questions.
doi:10.1089/aid.2015.0204
PMCID: PMC4817562  PMID: 26499270
11.  Validated Risk Score for Predicting 6‐Month Mortality in Infective Endocarditis 
Park, Lawrence P. | Chu, Vivian H. | Peterson, Gail | Skoutelis, Athanasios | Lejko‐Zupa, Tatjana | Bouza, Emilio | Tattevin, Pierre | Habib, Gilbert | Tan, Ren | Gonzalez, Javier | Altclas, Javier | Edathodu, Jameela | Fortes, Claudio Querido | Siciliano, Rinaldo Focaccia | Pachirat, Orathai | Kanj, Souha | Wang, Andrew | Clara, Liliana | Sanchez, Marisa | Casabé, José | Cortes, Claudia | Nacinovich, Francisco | Fernandez Oses, Pablo | Ronderos, Ricardo | Sucari, Adriana | Thierer, Jorge | Kogan, Silvia | Spelman, Denis | Athan, Eugene | Harris, Owen | Kennedy, Karina | Gordon, David | Papanicolas, Lito | Korman, Tony | Kotsanas, Despina | Dever, Robyn | Jones, Phillip | Konecny, Pam | Lawrence, Richard | Rees, David | Ryan, Suzanne | Feneley, Michael P. | Harkness, John | Jones, Phillip | Ryan, Suzanne | Jones, Phillip | Ryan, Suzanne | Jones, Phillip | Post, Jeffrey | Reinbott, Porl | Ryan, Suzanne | Gattringer, Rainer | Wiesbauer, Franz | Andrade, Adriana Ribas | de Brito, Ana Cláudia Passos | Guimarães, Armenio Costa | Grinberg, Max | Mansur, Alfredo José | Strabelli, Tania Mara Varejao | Vieira, Marcelo Luiz Campos | de Medeiros Tranchesi, Regina Aparecida | Paiva, Marcelo Goulart | de Oliveira Ramos, Auristela | Weksler, Clara | Ferraiuoli, Giovanna | Golebiovski, Wilma | Lamas, Cristiane | Karlowsky, James A. | Keynan, Yoav | Morris, Andrew M. | Rubinstein, Ethan | Jones, Sandra Braun | Garcia, Patricia | Fica, Alberto | Mella, Rodrigo Montagna | Fernandez, Ricardo | Franco, Liliana | Jaramillo, Astrid Natalia | Barsic, Bruno | Bukovski, Suzana | Krajinovic, Vladimir | Pangercic, Ana | Rudez, Igor | Vincelj, Josip | Freiberger, Tomas | Pol, Jiri | Zaloudikova, Barbora | Ashour, Zainab | El Kholy, Amani | Mishaal, Marwa | Osama, Dina | Rizk, Hussien | Aissa, Neijla | Alauzet, Corentine | Alla, Francois | Campagnac, Catherine | Doco‐Lecompte, Thanh | Selton‐Suty, Christine | Casalta, Jean‐Paul | Fournier, Pierre‐Edouard | Raoult, Didier | Thuny, Franck | Delahaye, Francois | Delahaye, Armelle | Vandenesch, Francois | Donal, Erwan | Donnio, Pierre Yves | Flecher, Erwan | Michelet, Christian | Revest, Matthieu | Chevalier, Florent | Jeu, Antoine | Rémadi, Jean Paul | Rusinaru, Dan | Tribouilloy, Christophe | Bernard, Yvette | Chirouze, Catherine | Hoen, Bruno | Leroy, Joel | Plesiat, Patrick | Naber, Christoph | Neuerburg, Carl | Mazaheri, Bahram | Naber, Christoph | Neuerburg, Carl | Athanasia, Sophia | Deliolanis, Ioannis | Giamarellou, Helen | Thomas, Tsaganos | Giannitsioti, Efthymia | Mylona, Elena | Paniara, Olga | Papanicolaou, Konstantinos | Pyros, John | Mylona, Elena | Paniara, Olga | Papanikolaou, Konstantinos | Pyros, John | Sharma, Gautam | Francis, Johnson | Nair, Lathi | Thomas, Vinod | Venugopal, Krishnan | Hannan, Margaret M. | Hurley, John P. | Cahan, Amos | Gilon, Dan | Israel, Sarah | Korem, Maya | Strahilevitz, Jacob | Rubinstein, Ethan | Strahilevitz, Jacob | Durante‐Mangoni, Emanuele | Mattucci, Irene | Pinto, Daniela | Agrusta, Federica | Senese, Alessandra | Ragone, Enrico | Utili, Riccardo | Cecchi, Enrico | De Rosa, Francesco | Forno, Davide | Imazio, Massimo | Trinchero, Rita | Grossi, Paolo | Lattanzio, Mariangela | Toniolo, Antonio | Goglio, Antonio | Raglio, Annibale | Ravasio, Veronica | Rizzi, Marco | Suter, Fredy | Carosi, Giampiero | Magri, Silvia | Signorini, Liana | Kanafani, Zeina | Kanj, Souha S. | Sharif‐Yakan, Ahmad | Abidin, Imran | Tamin, Syahidah Syed | Martínez, Eduardo Rivera | Soto Nieto, Gabriel Israel | van der Meer, Jan T.M. | Chambers, Stephen | Holland, David | Morris, Arthur | Raymond, Nigel | Read, Kerry | Murdoch, David R. | Dragulescu, Stefan | Ionac, Adina | Mornos, Cristian | Butkevich, O.M. | Chipigina, Natalia | Kirill, Ozerecky | Vadim, Kulichenko | Vinogradova, Tatiana | Halim, Magid | Liew, Yee‐Yun | Tan, Ru‐San | Logar, Mateja | Mueller‐Premru, Manica | Commerford, Patrick | Commerford, Anita | Deetlefs, Eduan | Hansa, Cass | Ntsekhe, Mpiko | Almela, Manuel | Armero, Yolanda | Azqueta, Manuel | Castañeda, Ximena | Cervera, Carlos | Falces, Carlos | Garcia‐de‐la‐Maria, Cristina | Fita, Guillermina | Gatell, Jose M. | Heras, Magda | Llopis, Jaime | Marco, Francesc | Mestres, Carlos A. | Miró, José M. | Moreno, Asuncion | Ninot, Salvador | Paré, Carlos | Pericas, Juan M. | Ramirez, Jose | Rovira, Irene | Sitges, Marta | Anguera, Ignasi | Font, Bernat | Guma, Joan Raimon | Bermejo, Javier | Garcia Fernández, Miguel Angel | Gonzalez‐Ramallo, Victor | Marín, Mercedes | Muñoz, Patricia | Pedromingo, Miguel | Roda, Jorge | Rodríguez‐Créixems, Marta | Solis, Jorge | Almirante, Benito | Fernandez‐Hidalgo, Nuria | Tornos, Pilar | de Alarcón, Arístides | Parra, Ricardo | Alestig, Eric | Johansson, Magnus | Olaison, Lars | Snygg‐Martin, Ulrika | Pachirat, Pimchitra | Pussadhamma, Burabha | Senthong, Vichai | Casey, Anna | Elliott, Tom | Lambert, Peter | Watkin, Richard | Eyton, Christina | Klein, John L. | Bradley, Suzanne | Kauffman, Carol | Bedimo, Roger | Corey, G. Ralph | Crowley, Anna Lisa | Douglas, Pamela | Drew, Laura | Fowler, Vance G. | Holland, Thomas | Lalani, Tahaniyat | Mudrick, Daniel | Samad, Zaniab | Sexton, Daniel | Stryjewski, Martin | Woods, Christopher W. | Lerakis, Stamatios | Cantey, Robert | Steed, Lisa | Wray, Dannah | Dickerman, Stuart A. | Bonilla, Hector | DiPersio, Joseph | Salstrom, Sara‐Jane | Baddley, John | Patel, Mukesh | Stancoven, Amy | Levine, Donald | Riddle, Jonathan | Rybak, Michael | Cabell, Christopher H. | Baloch, Khaula | Corey, G. Ralph | Dixon, Christy C. | Fowler, Vance G. | Harding, Tina | Jones‐Richmond, Marian | Sanderford, Bob | Sanderford, Bob | Stafford, Judy | Stafford, Judy | Anstrom, Kevin | Athan, Eugene | Bayer, Arnold S. | Cabell, Christopher H. | Corey, G. Ralph | Fowler, Vance G. | Hoen, Bruno | Karchmer, A. W. | Miró, José M. | Murdoch, David R. | Sexton, Daniel J. | Bayer, Arnold S. | Cabell, Christopher H. | Chu, Vivian | Corey, G. Ralph | Durack, David T. | Eykyn, Susannah | Fowler, Vance G. | Hoen, Bruno | Miró, José M. | Moreillon, Phillipe | Olaison, Lars | Raoult, Didier | Rubinstein, Ethan | Sexton, Daniel J.
Background
Host factors and complications have been associated with higher mortality in infective endocarditis (IE). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE.
Methods and Results
Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ICE]–Prospective Cohort Study [PCS], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry (ICE‐PLUS, 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE‐PCS cohort and 342 of 1197 (28.6%) in the ICE‐PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE, causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables.
Conclusions
Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE.
doi:10.1161/JAHA.115.003016
PMCID: PMC4859286  PMID: 27091179
infection; mortality; prognosis; surgery; valves; Infectious Endocarditis; Valvular Heart Disease; Mortality/Survival; Clinical Studies
12.  Impact of Early Valve Surgery on Outcome of Staphylococcus aureus Prosthetic Valve Infective Endocarditis: Analysis in the International Collaboration of Endocarditis–Prospective Cohort Study 
Chirouze, Catherine | Alla, François | Fowler, Vance G. | Sexton, Daniel J. | Corey, G. Ralph | Chu, Vivian H. | Wang, Andrew | Erpelding, Marie-Line | Durante-Mangoni, Emanuele | Fernández-Hidalgo, Nuria | Giannitsioti, Efthymia | Hannan, Margaret M. | Lejko-Zupanc, Tatjana | Miró, José M. | Muñoz, Patricia | Murdoch, David R. | Tattevin, Pierre | Tribouilloy, Christophe | Hoen, Bruno | Clara, Liliana | Sanchez, Marisa | Nacinovich, Francisco | Oses, Pablo Fernandez | Ronderos, Ricardo | Sucari, Adriana | Thierer, Jorge | Casabé, José | Cortes, Claudia | Altclas, Javier | Kogan, Silvia | Spelman, Denis | Athan, Eugene | Harris, Owen | Kennedy, Karina | Tan, Ren | Gordon, David | Papanicolas, Lito | Eisen, Damon | Grigg, Leeanne | Street, Alan | Korman, Tony | Kotsanas, Despina | Dever, Robyn | Jones, Phillip | Konecny, Pam | Lawrence, Richard | Rees, David | Ryan, Suzanne | Feneley, Michael P. | Harkness, John | Jones, Phillip | Ryan, Suzanne | Jones, Phillip | Ryan, Suzanne | Jones, Phillip | Post, Jeffrey | Reinbott, Porl | Ryan, Suzanne | Gattringer, Rainer | Wiesbauer, Franz | Andrade, Adriana Ribas | de Brito, Ana Cláudia Passos | Guimarães, Armenio Costa | Grinberg, Max | Mansur, Alfredo José | Siciliano, Rinaldo Focaccia | Strabelli, Tania Mara Varejao | Vieira, Marcelo Luiz Campos | de Medeiros Tranchesi, Regina Aparecida | Paiva, Marcelo Goulart | Fortes, Claudio Querido | de Oliveira Ramos, Auristela | Ferraiuoli, Giovanna | Golebiovski, Wilma | Lamas, Cristiane | Santos, Marisa | Weksler, Clara | Karlowsky, James A. | Keynan, Yoav | Morris, Andrew M. | Rubinstein, Ethan | Jones, Sandra Braun | Garcia, Patricia | Cereceda, M | Fica, Alberto | Mella, Rodrigo Montagna | Barsic, Bruno | Bukovski, Suzana | Krajinovic, Vladimir | Pangercic, Ana | Rudez, Igor | Vincelj, Josip | Freiberger, Tomas | Pol, Jiri | Zaloudikova, Barbora | Ashour, Zainab | El Kholy, Amani | Mishaal, Marwa | Rizk, Hussien | Aissa, Neijla | Alauzet, Corentine | Alla, Francois | Campagnac, Catherine | Doco-Lecompte, Thanh | Selton-Suty, Christine | Casalta, Jean-Paul | Fournier, Pierre-Edouard | Habib, Gilbert | Raoult, Didier | Thuny, Franck | Delahaye, François | Delahaye, Armelle | Vandenesch, Francois | Donal, Erwan | Donnio, Pierre Yves | Michelet, Christian | Revest, Matthieu | Tattevin, Pierre | Violette, Jérémie | Chevalier, Florent | Jeu, Antoine | Sorel, Claire | Tribouilloy, Christophe | Bernard, Yvette | Chirouze, Catherine | Hoen, Bruno | Leroy, Joel | Plesiat, Patrick | Naber, Christoph | Neuerburg, Carl | Mazaheri, Bahram | Naber, Christoph | Neuerburg, Carl | Athanasia, Sofia | Giannitsioti, Efthymia | Mylona, Elena | Paniara, Olga | Papanicolaou, Konstantinos | Pyros, John | Skoutelis, Athanasios | Sharma, Gautam | Francis, Johnson | Nair, Lathi | Thomas, Vinod | Venugopal, Krishnan | Hannan, Margaret | Hurley, John | Gilon, Dan | Israel, Sarah | Korem, Maya | Strahilevitz, Jacob | Rubinstein, Ethan | Strahilevitz, Jacob | Casillo, Roberta | Cuccurullo, Susanna | Dialetto, Giovanni | Durante-Mangoni, Emanuele | Irene, Mattucci | Ragone, Enrico | Tripodi, Marie Françoise | Utili, Riccardo | Cecchi, Enrico | De Rosa, Francesco | Forno, Davide | Imazio, Massimo | Trinchero, Rita | Tebini, Alessandro | Grossi, Paolo | Lattanzio, Mariangela | Toniolo, Antonio | Goglio, Antonio | Raglio, Annibale | Ravasio, Veronica | Rizzi, Marco | Suter, Fredy | Carosi, Giampiero | Magri, Silvia | Signorini, Liana | Baban, Tania | Kanafani, Zeina | Kanj, Souha S. | Yasmine, Mohamad | Abidin, Imran | Tamin, Syahidah Syed | Martínez, Eduardo Rivera | Soto Nieto, Gabriel Israel | van der Meer, Jan T.M. | Chambers, Stephen | Holland, David | Morris, Arthur | Raymond, Nigel | Read, Kerry | Murdoch, David R. | Dragulescu, Stefan | Ionac, Adina | Mornos, Cristian | Butkevich, O.M. | Chipigina, Natalia | Kirill, Ozerecky | Vadim, Kulichenko | Vinogradova, Tatiana | Edathodu, Jameela | Halim, Magid | Lum, Luh-Nah | Tan, Ru-San | Lejko-Zupanc, Tatjana | Logar, Mateja | Mueller-Premru, Manica | Commerford, Patrick | Commerford, Anita | Deetlefs, Eduan | Hansa, Cass | Ntsekhe, Mpiko | Almela, Manuel | Armero, Yolanda | Azqueta, Manuel | Castañeda, Ximena | Cervera, Carlos | del Rio, Ana | Falces, Carlos | Garcia-de-la-Maria, Cristina | Fita, Guillermina | Gatell, Jose M. | Marco, Francesc | Mestres, Carlos A. | Miró, José M. | Moreno, Asuncion | Ninot, Salvador | Paré, Carlos | Pericas, Joan | Ramirez, Jose | Rovira, Irene | Sitges, Marta | Anguera, Ignasi | Font, Bernat | Guma, Joan Raimon | Bermejo, Javier | Bouza, Emilio | Fernández, Miguel Angel Garcia | Gonzalez-Ramallo, Victor | Marín, Mercedes | Muñoz, Patricia | Pedromingo, Miguel | Roda, Jorge | Rodríguez-Créixems, Marta | Solis, Jorge | Almirante, Benito | Fernandez-Hidalgo, Nuria | Tornos, Pilar | de Alarcón, Arístides | Parra, Ricardo | Alestig, Eric | Johansson, Magnus | Olaison, Lars | Snygg-Martin, Ulrika | Pachirat, Orathai | Pachirat, Pimchitra | Pussadhamma, Burabha | Senthong, Vichai | Casey, Anna | Elliott, Tom | Lambert, Peter | Watkin, Richard | Eyton, Christina | Klein, John L. | Bradley, Suzanne | Kauffman, Carol | Bedimo, Roger | Chu, Vivian H. | Corey, G. Ralph | Crowley, Anna Lisa | Douglas, Pamela | Drew, Laura | Fowler, Vance G. | Holland, Thomas | Lalani, Tahaniyat | Mudrick, Daniel | Samad, Zaniab | Sexton, Daniel | Stryjewski, Martin | Wang, Andrew | Woods, Christopher W. | Lerakis, Stamatios | Cantey, Robert | Steed, Lisa | Wray, Dannah | Dickerman, Stuart A. | Bonilla, Hector | DiPersio, Joseph | Salstrom, Sara-Jane | Baddley, John | Patel, Mukesh | Peterson, Gail | Stancoven, Amy | Afonso, Luis | Kulman, Theresa | Levine, Donald | Rybak, Michael | Cabell, Christopher H. | Baloch, Khaula | Chu, Vivian H. | Corey, G. Ralph | Dixon, Christy C. | Fowler, Vance G. | Harding, Tina | Jones-Richmond, Marian | Pappas, Paul | Park, Lawrence P. | Redick, Thomas | Stafford, Judy | Anstrom, Kevin | Athan, Eugene | Bayer, Arnold S. | Cabell, Christopher H. | Chu, Vivian H. | Corey, G. Ralph | Fowler, Vance G. | Hoen, Bruno | Karchmer, A. W. | Miró, José M. | Murdoch, David R. | Sexton, Daniel J. | Wang, Andrew | Bayer, Arnold S. | Cabell, Christopher H. | Chu, Vivian | Corey, G. Ralph | Durack, David T. | Eykyn, Susannah | Fowler, Vance G. | Hoen, Bruno | Miró, José M. | Moreillon, Phillipe | Olaison, Lars | Raoult, Didier | Rubinstein, Ethan | Sexton, Daniel J.
Using appropriate analytical methods to examine data from the International Collaboration on Endocarditis–Prospective Cohort Study, we found that early valve surgery was not associated with reduced 1-year mortality in Staphylococcus aureus prosthetic valve infective endocarditis.
Background. The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis–Prospective Cohort Study.
Methods. Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use.
Results. EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non–S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39–1.15]; P = .15).
Conclusions. In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.
doi:10.1093/cid/ciu871
PMCID: PMC4366581  PMID: 25389255
endocarditis; prosthetic valve; surgery; 1-year mortality
13.  Human immunodeficiency virus infection, cardiovascular risk factor profile and risk for acute myocardial infarction 
Background
Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV infected (HIV+) patients. We assessed the association between HIV and incident AMI within CVDRF strata.
Methods
Cohort
81322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study-Virtual Cohort (prospective study of HIV+ and matched HIV− veterans). Veterans were followed from first clinical encounter on/after 4/1/2003 until AMI/death/last follow-up date (12/31/2009).
Predictors
HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood-pressure (BP), BP medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ non-optimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs.
Outcome
Incident AMI (defined using enzyme, EKG clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates). Statistics: Cox models adjusted for demographics, comorbidity, and substance use.
Results
858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates. Compared to HIV− veterans, AMI rates among HIV+ veterans with similar CVDRF profiles were higher. Compared to HIV− veterans without major CVDRFs, HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0 95%CI: 1.0–3.9, p=0.044).
Conclusion
The prevalence of optimal cardiac health is low in this cohort. Among those without major CVDRFs, HIV+ veterans have twice the AMI risk. Compared to HIV− veterans with high CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people.
doi:10.1097/QAI.0000000000000419
PMCID: PMC4441201  PMID: 25588033
HIV; optimal cardiovascular health; myocardial infarction
14.  Acute and Chronic Immune Biomarker Changes During Interferon/Ribavirin Treatment in HIV-HCV Co-infected Patients 
Journal of viral hepatitis  2014;22(1):25-36.
Chronic viral infections lead to persistent immune activation, which is alleviated by eradicating or suppressing the infection. To understand the effects of interferon treatment on immune system activation by chronic infections, we evaluated kinetic patterns of a broad spectrum of serum biomarkers during HCV treatment in HIV/HCV co-infected patients. HCV viral load and 50 biomarkers were analyzed at baseline and 27 time points during pegylated interferon and ribavirin (IFN/RBV) treatment of 12 HIV/HCV co-infected patients. We evaluated biomarker changes from baseline for each time point, and biomarker correlations with clinical parameters, treatment response and liver histopathology. IL-1α, IL-12p40, IL-1RA, IP-10, MIG, MIP-1α/1β, HGF, sCD40L, TRAIL and leptin increased in the first day. IL-12p70, IL-17A, IL-10, GROα, IL-8, MCP-3, IL-4, and M-CSF peaked later during week 1. IL-1α, HGF, IP-10, MIP-1α, TRAIL, sCD40L, IL-10, IL-12p70, MCP-3, FGFb, ENA-78, TGFβ, IL-2, IFNγ, IL-6, IL-15, IL-7, and PDGF-BB decreased below baseline over the course of treatment. Higher BMI, baseline HCV viral load and leptin levels were associated with lack of sustained virological response. ENA-78 was associated with sustained viral response. Positive correlations were found between liver inflammation and baseline CD4 count, sVCAM, and HGF; fibrosis stage and HGF; liver steatosis, BMI and leptin. Our findings suggest IFN/RBV treatment initially increases levels of several biomarkers, but eventually leads to a decline in many immune markers. These findings shed light on the relationship between IFN treatment and immune activation by chronic viral infections, such as HCV.
doi:10.1111/jvh.12226
PMCID: PMC4127161  PMID: 24506344
HIV; HCV; immune response; antiviral treatment; interferon
15.  Impact of empiric weight-based vancomycin dosing on nephrotoxicity and mortality in geriatric patients with methicillin-resistant Staphylococcus aureus bacteremia 
What is known and objective
Few studies have evaluated the effect of vancomycin dosing on the health outcomes in geriatric patients. Data are needed to determine if higher vancomycin dosing strategies are more effective in geriatric patients and/or lead to excessive rates of adverse events.
Methods
This study used a subset of patients ages ≥ 65 years from a multicenter, retrospective, cohort study of methicillin resistant Staphylococcus aureus (MRSA) bacteremia. Patients received ≥ 48 hours of empiric vancomycin between 07/01/2002 and 06/30/2008. We compared the incidence of nephrotoxicity and in-hospital mortality in patients who received guideline-recommended dosing (at least 15 mg/kg/dose) to patients who received lower dosing. Multivariable generalized mixed effects models were constructed to determine independent risk factors for nephrotoxicity and in-hospital mortality.
Results and discussion
Half of the cohort (46% of 92 patients) received guideline-recommended dosing. Empiric use of weight-based dosing did increase the percentage of patients achieving a vancomycin trough ≥ 15 mg/L (57% vs. 42%). Nephrotoxicity occurred in 32% of patients and 26% died during their hospitalization. Guideline-recommended dosing was not associated with significant changes in nephrotoxicity (OR 1.03; 95% CI 0.38–2.82) or in-hospital mortality (OR 1.01; 95% CI 0.40–2.54) in the multivariable analysis.
What is new and conclusion
In this study of geriatric patients, guideline-recommended dosing was not associated with significant changes in nephrotoxicity or mortality. Since 40% of the patients who received guideline-recommended dosing failed to achieve a target vancomycin trough of ≥ 15 mg/L, future studies should focus on dosing strategies to increase target attainment rate.
doi:10.1111/jcpt.12203
PMCID: PMC4211949  PMID: 25200273
16.  Empiric Weight-Based Vancomycin in Intensive Care Unit Patients with Methicillin-Resistant Staphylococcus Aureus Bacteremia 
Background
We have conducted previous studies in all hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia to determine safety and effectiveness of guideline-recommended, weight-based dosing of vancomycin. In these studies, we observed that severely ill patients (Pitt bacteremia score ≥ 4 or ICU patients) were at an increased risk of mortality and/or nephrotoxicity. Therefore, we conducted a subanalysis of the effect of guideline-recommended vancomycin dosing on in-hospital mortality and nephrotoxicity in intensive care unit (ICU) patients with MRSA bacteremia.
Methods
This multicenter, retrospective, cohort study was conducted in a subset of ICU patients from a previous MRSA bacteremia study. Patients were ≥18 years old and received ≥48 hours of empiric vancomycin from 07/01/2002 to 06/30/2008. We compared the incidence of nephrotoxicity and in-hospital mortality in patients that received guideline-recommended dosing (at least 15 mg/kg/dose) to patients that received non-guideline-recommended dosing of vancomycin. Multivariable generalized linear mixed-effects models were constructed to determine independent risk factors for in-hospital mortality and nephrotoxicity.
Results
Guideline-recommended dosing was received by 34% of patients (n=137). Nephrotoxicity occurred in 35% of patients receiving guideline-recommended dosing and 39% receiving non-guideline-recommended dosing (p=0.67). In-hospital mortality rate was 24% among patients who received guideline-recommended dosing compared with 31% for non-guideline-recommended dosing (p=0.40). Guideline-recommended dosing was not associated with nephrotoxicity (OR 1.10; 95% CI 0.43–2.79) or in-hospital mortality (OR 0.54; 95% CI 0.22–1.36) in the multivariable analysis.
Conclusions
Guideline-recommended dosing of vancomycin in ICU patients with MRSA bacteremia is not significantly associated with nephrotoxicity or in-hospital mortality. However, the 7% absolute difference for in-hospital mortality suggests larger studies are needed.
doi:10.1097/MAJ.0000000000000262
PMCID: PMC4207850  PMID: 24762747
Vancomycin; weight; ICU; MRSA; nephrotoxicity
17.  CD8+ T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort 
BioMed Research International  2015;2015:246870.
Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3) had increased AMI risk (adjusted HR = 1.82, P < 0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts ≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts <200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.
doi:10.1155/2015/246870
PMCID: PMC4320893  PMID: 25688354
18.  Escherichia coli Sequence Type 131 (ST131) Subclone H30 as an Emergent Multidrug-Resistant Pathogen Among US Veterans 
Among US veterans in 2011, Escherichia coli ST131, primarily its H30 subclone, accounted for most antimicrobial-resistant E. coli clinical isolates and was the dominant E. coli strain overall. Possible contributors included multidrug resistance, extensive virulence gene content, and ongoing transmission.
Background. Escherichia coli sequence type 131 (ST131), typically fluoroquinolone-resistant (FQ-R) and/or extended-spectrum β-lactamase (ESBL)–producing, has emerged globally. We assessed its prevalence and characteristics among US veterans.
Methods. In 2011, 595 de-identified E. coli clinical isolates were collected systematically within 3 resistance groups (FQ-susceptible [FQ-S], FQ-R, and ESBL-producing) from 24 nationally distributed Veterans Affairs Medical Centers (VAMCs). ST131 and its H30 subclone were detected by polymerase chain reaction and compared with other E. coli for molecular traits, source, and resistance profiles.
Results. ST131 accounted for 78% (184/236) of FQ-R and 64.2% (79/123) of ESBL-producing isolates, but only 7.2% (17/236) of FQ-S isolates (P < .001). The H30 subclone accounted for ≥95% of FQ-R and ESBL-producing, but only 12.5% of FQ-S, ST131 isolates (P < .001). By back-calculation, 28% of VAMC E. coli isolates nationally represented ST131. Overall, ST131 varied minimally in prevalence by specimen type, inpatient/outpatient source, or locale; was the most prevalent ST, followed distantly by ST95 and ST12 (13% each); and accounted for ≥40% (β-lactams), >50% (trimethoprim-sulfamethoxazole , multidrug), or >70% (ciprofloxacin, gentamicin) of total antimicrobial resistance. FQ-R and ESBL-producing ST131 isolates had higher virulence scores than corresponding non-ST131 isolates. ST131 pulsotypes overlapped extensively among VAMCs.
Conclusions. Among US veterans, ST131, primarily its H30 subclone, accounts for most antimicrobial-resistant E. coli and is the dominant E. coli strain overall. Possible contributors include multidrug resistance, extensive virulence gene content, and ongoing transmission. Focused attention to ST131, especially its H30 subclone, could reduce infection-related morbidity, mortality, and costs among veterans.
doi:10.1093/cid/cit503
PMCID: PMC3792724  PMID: 23926176
Escherichia coli infections; ST131; antimicrobial resistance; veterans; extended-spectrum beta-lactamases
19.  The RADAR Study: Week 48 Safety and Efficacy of RAltegravir Combined with Boosted DARunavir Compared to Tenofovir/Emtricitabine Combined with Boosted Darunavir in Antiretroviral-Naive Patients. Impact on Bone Health 
PLoS ONE  2014;9(8):e106221.
Background
NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.
Methods
In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48.
Results
Using an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (−0.25 vs. −0.71 mg/dL (p = 0.270), and eGFR (−4.4 vs. −7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. −7 g/cm2 with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = −0.394, p = 0.003 for CTX; and R = −0.477, p<0.001 for P1NP).
Conclusion
The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.
Trial Registration
ClinicalTrials.gov NCT 00677300
doi:10.1371/journal.pone.0106221
PMCID: PMC4149560  PMID: 25170938
20.  Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study 
Background
Previous studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB).
Methods
Adults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model.
Results
Overall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08).
Conclusions
Over one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.
doi:10.1186/2050-6511-14-12
PMCID: PMC3575285  PMID: 23402420
Adverse events; Nephrotoxicity; Vancomycin; Dosing; Weight; Obesity; MRSA
21.  Empiric guideline-recommended weight-based vancomycin dosing and mortality in methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study 
BMC Infectious Diseases  2012;12:104.
Background
No studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia.
Methods
This was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature.
Results
A total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39]) or multivariable (OR 0.71, 95%CI 0.33-1.55) analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity.
Conclusions
Empiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.
doi:10.1186/1471-2334-12-104
PMCID: PMC3532187  PMID: 22540223
Weight; Obesity; Efficacy; MRSA; Vancomycin; Bacteremia
22.  Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy 
HIV-infected patients on highly active antiretroviral therapy (HAART) develop a complex of body composition changes known, including peripheral fat loss (lipoatrophy) and central fat accumulation (lipohypertrophy). These changes may cause significant patient distress, which could in turn interfere with adherence to antiretroviral therapy. Treatment options – including antiretroviral switch, insulin sensitizers, and surgical approaches – have been associated with limited success and potential complications. The observation that low growth hormone levels are associated with central fat accumulation among HIV patients has led to the development of tesamorelin (a growth hormone releasing hormone analog) for the management of central fat accumulation. Randomized controlled trials have shown that administration of tesamorelin is safe and effective in reducing central fat accumulation among HIV-infected patients. This effect is transient, however, and its association with improved cardiovascular risk remains unclear.
doi:10.2147/HIV.S14561
PMCID: PMC3218714  PMID: 22096409
HAART; HIV; tesamorelin; lipodystrophy
23.  Incidence of Non-AIDS-Defining Malignancies in HIV-Infected Vs. Non-Infected Patients in the HAART Era: Impact of Immunosuppression 
Background
The incidence of non-AIDS-defining malignancies (non-ADM) is reported as unchanged or increasing in the HAART era. Whether incidence of non-ADM is significantly higher in HIV-infected than in HIV-uninfected patients remains unclear.
Methods
Incidence rates of malignancies were calculated in a cohort of veterans in care for HIV-infected and age, race, and gender-matched uninfected patients from 1997 to 2004. For HIV-infected patients CD4 counts closest to first observation date were compared between those with and without cancer.
Results
33,420 HIV-infected and 66,840 HIV-uninfected patients were followed for a median of 5.1 and 6.4 years. The Incidence rate ratio [IRR] of HIV-infected to HIV-uninfected was 1.6 (1260 vs. 841/100,000 person-years; 95% CI: 1.5–1.7). IRR for individual cancers was highest for anal cancer (14.9; CI: 10.1–22.1). Among HIV-infected patients, median CD4 counts were lower for those with non-ADM (249 vs. 270, p=0.02), anal cancer (154 vs. 270; p<0.001), and Hodgkin’s (217 vs. 270; p=0.03). Prostate cancer was associated with a higher CD4 count (310 vs. 270; p<0.001).
Conclusions
In the HAART era, the incidence of non-ADMs is higher among HIV-infected than HIV-uninfected patients, adjusting for age, race, and gender. Some non-ADMs do not appear to be associated with significantly lower CD4 counts.
doi:10.1097/QAI.0b013e3181b033ab
PMCID: PMC2814969  PMID: 19617846
AIDS-defining malignancies; Non-AIDS-defining malignancies; Incidence; HAART
24.  Multicenter Evaluation of Vancomycin Dosing – Emphasis on Obesity 
The American journal of medicine  2008;121(6):515-518.
Background
There is a paucity of data available regarding the dosing of antimicrobials in obesity. However, data are available demonstrating that vancomycin should be dosed based on actual body weight.
Methods
This study was conducted at two tertiary care medical centers that did not have pharmacy-guided vancomycin dosing programs or other institutional vancomycin dosing policies or protocols. Patients who received vancomycin between 7/1/2003 and 6/30/2006 were stratified by body mass index and randomly selected from the computer-generated queries. Patients ≥ 18 years of age and a creatinine clearance ≥ 60 ml/min who received vancomycin for ≥ 36 hours were included.
Results
Data were collected on a random sampling of 421 patients, stratified by body mass index, who met the inclusion criteria. Most patients in each body mass index category received a fixed dose of vancomycin 2 grams daily divided into two doses (underweight 82%, normal weight 90%, overweight 86%, obese 91%). Adequate initial dosing (≥ 10 mg/kg/dose) was achieved for 100% of underweight, 99% of normal weight, 93.9% of overweight, and 27.7% of obese patients (p < 0.0001). Ninety-seven percent of underweight, 46% of normal weight, 1% of overweight, and 0.6% of obese patients received ≥ 15 mg/kg/dose recommended by several Infectious Diseases Society of America guidelines. Pharmacists also failed to correct inadequate dosing as only 3.3% of patients receiving < 10 mg/kg/dose had their regimen changed in the first 24 hours of therapy.
Conclusion
In this multi-center pilot study, obese patients routinely received inadequate empiric vancomycin utilizing a lenient assessment of dosing. Greater efforts should be undertaken to ensure patients received weight-based dosing as inadequate dosing can lead to subtherapeutic concentrations and potentially worse clinical outcomes.
doi:10.1016/j.amjmed.2008.01.046
PMCID: PMC2577897  PMID: 18501233
Obesity; vancomycin; dosing
25.  Prospective Randomized Trial of Empiric Therapy with Trimethoprim-Sulfamethoxazole or Doxycycline for Outpatient Skin and Soft Tissue Infections in an Area of High Prevalence of Methicillin-Resistant Staphylococcus aureus▿  
To evaluate empirical therapy with trimethoprim-sulfamethoxazole or doxycycline for outpatient skin and soft tissue infections in an area of high prevalence of methicillin-resistant Staphylococcus aureus, a randomized, prospective, open-label investigation was performed. The overall clinical failure rate was 9%, with all failures occurring in the trimethoprim-sulfamethoxazole group. However, there was no significant difference between the clinical failure rate of empirical trimethoprim-sulfamethoxazole therapy and that of doxycycline therapy.
doi:10.1128/AAC.00206-07
PMCID: PMC1913240  PMID: 17502411

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