Faculty Bibliography

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 StartingTreatment forEthanol inPrimary 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 24weeks, 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.

Background. Acute respiratory infections (ARI) are common among healthcare personnel (HCP); however, the risk factors associated with ARI in this population are not well studied. While typically thought to be contracted through the mucous membranes of the nose and mouth, there has been speculation of transmission of respiratory viruses via the conjunctiva. Methods. During 12 weeks of the 2013-4 and 2014-5 respiratory virus seasons, participating HCP in 7 locations across the US reported use of corrective eyewear (glasses or contacts) in a baseline survey and were surveyed daily for ARI symptoms. When symptomatic, a combined nasal and throat swab was obtained. In addition, two swabs were obtained at separate, randomly assigned times regardless of symptoms. Samples were tested for 13 viruses by RT-PCR/ESI-MS (Abbott Molecular). Paired pre- and post-season blood samples were tested for influenza antibodies with a >=4- fold antibody increase defined as influenza infection. Participants were stratified into those who wore only glasses, only contacts, alternated between both, or wore neither. Results were analyzed using chi-square tests. Results. Of the 3341 eligible participants, 1386 wore glasses, 145 contacts, 576 both and 1234 neither. The proportion of positive swabs did not differ substantially across groups. The incidence of individual pathogens was similar between groups (p = 0.6) except for rhinovirus/enterovirus which showed varying levels of incidence (Figure 1). Serology identified 214 cases of influenza A and 62 cases of influenza B (Figure 2). Incidence of serological influenza infection was different between groups (10.3% contacts, 9.6% glasses, 7.3% neither, 6.6% both), which was marginally significant (p = 0.052) but driven by a marked higher rate of influenza B infection in the contacts group. This difference was not seen in the PCR confirmed 92 cases of influenza A or 8 of influenza B (p = 0.9). Conclusion. Use of corrective eyewear affected the rate of respiratory infection in HCP, especially those due to rhinovirus/enterovirus and influenza B. Contacts were associated with the highest infection risk in both virological and serological results. The conjunctiva as a potential route of entry for respiratory pathogens requires further study. (Figure Presented)

BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. DISCUSSION: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010).

Importance: Antiretroviral therapy (ART) has converted human immunodeficiency virus (HIV) infection into a chronic condition, and patients now undergo a variety of surgical procedures, but current surgical outcomes are inadequately characterized. Objective: To compare 30-day postoperative mortality in patients with HIV infection receiving ART with the rates in uninfected individuals. Design, Setting, and Participants: Retrospective analysis of nationwide electronic medical record data from the US Veterans Health Administration Healthcare System, October 1, 1996, to September 30, 2010. Common inpatient surgical procedures were grouped using the Healthcare Cost and Utilization Project Clinical Classification System to match HIV-infected and uninfected patients in a 1:2 ratio. Data on 1641 patients with HIV infection receiving combination ART who were undergoing inpatient surgery were compared with data on 3282 procedure-matched, uninfected comparators. Poisson regression models of 30-day postoperative mortality were adjusted for procedure year, age, Charlson Comorbidity Index score, hemoglobin level, albumin level, HIV infection, CD4 cell count, and HIV-1 RNA level. Main Outcomes and Measures: All-cause 30-day postoperative mortality. Results: The most common procedures in both groups were cholecystectomy (10.5%), hip arthroplasty (10.5%), spine surgery (9.8%), herniorrhaphy (7.4%), and coronary artery bypass grafting (7.0%). In patients with HIV infection, CD4 cell distributions were 80.0% with 200/muL or more, 16.3% with 50/muL to 199/muL, and 3.7% with less than 50/muL; 74.1% of patients with HIV infection had undetectable HIV-1 RNA. Human immunodeficiency virus infection was associated with higher 30-day postoperative mortality compared with the mortality in uninfected patients (3.4% [56 patients]) vs 1.6% [53]); incidence rate ratio [IRR], 2.11; 95% CI, 1.41-3.17; P < .001). CD4 cell count was inversely associated with mortality, but HIV-1 RNA provided no additional information. After adjustment, patients with HIV infection had increased mortality compared with uninfected patients at all CD4 cell count strata (>/=500/muL: IRR, 1.92; 95% CI, 1.02-3.60; P = .04; 200-499/muL: IRR, 1.89; 95% CI, 1.20-2.98; P = .01; 50-199/muL: IRR, 2.66; 95% CI, 1.29-5.47; P = .01; and <50/muL: IRR, 6.21; 95% CI, 3.55-10.85; P < .001). Hypoalbuminemia (IRR, 4.35; 95% CI, 2.78-6.81; P < .001) and age in decades (IRR, 1.47; 95% CI, 1.23-1.76; P < .001) were also strongly associated with mortality. Conclusions and Relevance: Current postoperative mortality rates among individuals with HIV infection who are receiving ART are low and are influenced as much by hypoalbuminemia and age as by CD4 cell status. Human immunodeficiency virus infection and CD4 cell count are only 2 of many factors associated with surgical outcomes that should be incorporated into surgical decision making.

Background. The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. Methods. Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. Results. The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. Conclusions. Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8

BACKGROUND: Early, accurate predictions of the onset of influenza season enable targeted implementation of control efforts. Our objective was to develop a tool to assist public health practitioners, researchers, and clinicians in defining the community-level onset of seasonal influenza epidemics. METHODS: Using recent surveillance data on virologically confirmed infections of influenza, we developed the Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm, a method to identify the period of highest seasonal influenza activity. We used data from 2 large hospitals that serve Baltimore, Maryland and Denver, Colorado, and the surrounding geographic areas. The data used by ALERT are routinely collected surveillance data: weekly case counts of laboratory-confirmed influenza A virus. The main outcome is the percentage of prospective seasonal influenza cases identified by the ALERT algorithm. RESULTS: When ALERT thresholds designed to capture 90% of all cases were applied prospectively to the 2011-2012 and 2012-2013 influenza seasons in both hospitals, 71%-91% of all reported cases fell within the ALERT period. CONCLUSIONS: The ALERT algorithm provides a simple, robust, and accurate metric for determining the onset of elevated influenza activity at the community level. This new algorithm provides valuable information that can impact infection prevention recommendations, public health practice, and healthcare delivery.

Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3-85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed >/=1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. Conclusions. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons >/=60 years of age with no contraindications, regardless of a prior history of HZ.

STUDY DESIGN.: Retrospective analysis of nationwide Veterans Health Administration clinical and administrative data. OBJECTIVE.: Examine the association between HIV infection and the rate of spine surgery for degenerative spine disease. SUMMARY OF BACKGROUND DATA.: Combination antiretroviral therapy has prolonged survival in HIV-infected patients, increasing the prevalence of chronic conditions such as degenerative spine disease that may require spine surgery. METHODS.: We studied all HIV-infected patients under care in the Veterans Health Administration from 1996 to 2008 (n = 40,038) and uninfected comparator patients (n = 79,039) matched on age, sex, race, year, and geographic region. The primary outcome was spine surgery for degenerative spine disease, defined by International Classification of Diseases, Ninth Revision procedure and diagnosis codes. We used a multivariate Poisson regression to model spine surgery rates by HIV infection status, adjusting for factors that might affect suitability for surgery (demographics, year, comorbidities, body mass index, combination antiretroviral therapy, and laboratory values). RESULTS.: Two hundred twenty-eight HIV-infected and 784 uninfected patients underwent spine surgery for degenerative spine disease during 700,731 patient-years of follow-up (1.44 surgeries per 1000 patient-years). The most common procedures were spinal decompression (50%) and decompression and fusion (33%); the most common surgical sites were the lumbosacral (50%) and cervical (40%) spine. Adjusted rates of surgery were lower for HIV-infected patients (0.86 per 1000 patient-years of follow-up) than for uninfected patients (1.41 per 1000 patient-years; incidence rate ratio 0.61, 95% confidence interval: 0.51-0.74, P < 0.001). Among HIV-infected patients, there was a trend toward lower rates of spine surgery in patients with detectable viral load levels (incidence rate ratio 0.76, 95% confidence interval: 0.55-1.05, P = 0.099). CONCLUSION.: In the Veterans Health Administration, HIV-infected patients experience significantly reduced rates of surgery for degenerative spine disease. Possible explanations include disease prevalence, emphasis on treatment of nonspine HIV-related symptoms, surgical referral patterns, impact of HIV on surgery risk-benefit ratio, patient preferences, and surgeon bias.