Influence of Preseason Antibodies Against Influenza Virus on Risk of Influenza Infection Among Healthcare Personnel.

BACKGROUND: The association of hemagglutination inhibition (HAI) antibodies with protection from influenza among healthcare personnel (HCP) with occupational exposure to influenza viruses has not been well-described. METHODS: The Respiratory Protection Effectiveness Clinical Trial was a cluster-randomized, multisite study that compared medical masks to N95 respirators in preventing viral respiratory infections among HCP in outpatient healthcare settings for 5180 participant-seasons. Serum HAI antibody titers before each influenza season and influenza virus infection confirmed by polymerase chain reaction were studied over 4 study years. RESULTS: In univariate models, the risk of influenza A(H3N2) and B virus infections was associated with HAI titers to each virus, study year, and site. HAI titers were strongly associated with vaccination. Within multivariate models, each log base 2 increase in titer was associated with 15%, 26% and 33%-35% reductions in the hazard of influenza A(H3N2), A(H1N1), and B infections, respectively. Best models included preseason antibody titers and study year, but not other variables. CONCLUSIONS: HAI titers were associated with protection from influenza among HCP with routine exposure to patients with respiratory illness and influenza season contributed to risk. HCP can be reassured about receiving influenza vaccination to stimulate immunity.

Risk Factors for Healthcare Personnel Infection With Endemic Coronaviruses (HKU1, OC43, NL63, 229E): Results from the Respiratory Protection Effectiveness Clinical Trial (ResPECT).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a large risk to healthcare personnel (HCP). Quantifying the risk of coronavirus infection associated with workplace activities is an urgent need. METHODS: We assessed the association of worker characteristics, occupational roles and behaviors, and participation in procedures with the risk of endemic coronavirus infection among HCP who participated in the Respiratory Protection Effectiveness Clinical Trial (ResPECT), a cluster randomized trial to assess personal protective equipment to prevent respiratory infections and illness conducted from 2011 to 2016. RESULTS: Among 4689 HCP seasons, we detected coronavirus infection in 387 (8%). HCP who participated in an aerosol-generating procedure (AGP) at least once during the viral respiratory season were 105% (95% confidence interval, 21%-240%) more likely to be diagnosed with a laboratory-confirmed coronavirus infection. Younger individuals, those who saw pediatric patients, and those with household members <5 years of age were at increased risk of coronavirus infection. CONCLUSIONS: Our analysis suggests that the risk of HCP becoming infected with an endemic coronavirus increases approximately 2-fold with exposures to AGPs. Our findings may be relevant to the coronavirus disease 2019 (COVID-19) pandemic; however, SARS-CoV-2, the virus that causes COVID-19, may differ from endemic coronaviruses in important ways. CLINICAL TRIALS REGISTRATION: NCT01249625.

N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel: A Randomized Clinical Trial.

Importance: Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections. Objective: To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP. Design, Setting, and Participants: A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups. Interventions: Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness. Main Outcomes and Measures: The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed. Results: Among 2862 randomized participants (mean [SD] age, 43 [11.5] years; 2369 [82.8%]) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, [95% CI, -0.5% to 2.5%]; P = .18) (adjusted odds ratio [OR], 1.18 [95% CI, 0.95-1.45]). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons [95% CI, -48.2 to 4.4]; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, [95% CI, -33.3 to 15.4]; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons [95% CI, -28.2 to 10.9]; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons [95% CI, -23.8 to 1.3]; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group. Conclusions and Relevance: Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza. Trial Registration: ClinicalTrials.gov Identifier: NCT01249625.

The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel.

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).

Triggering interventions for influenza: the ALERT algorithm.

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.

Safety of zoster vaccine in elderly adults following documented herpes zoster.

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.

Perspectives on contingency management for alcohol use and alcohol-associated conditions among people in care with HIV.

BACKGROUND: Contingency management (CM) is an evidence-based approach for reducing alcohol use; however, its implementation into routine HIV primary care-based settings has been limited. We evaluated perspectives on implementing CM to address unhealthy alcohol use and associated conditions for people with HIV in primary care settings. METHODS: From May 2021 to August 2021, we conducted two focus groups with staff involved in delivering the intervention (n = 5 Social Workers and n = 4 Research Coordinators) and individual interviews (n = 13) with a subset of participants involved in the multi-site Financial Incentives, Randomization, and Stepped Treatment (FIRST) trial. Qualitative data collection and analyses were informed by the Promoting Action on Research Implementation in Health Service (PARIHS) implementation science framework, including evidence (perception of CM), context (HIV primary care clinic and CM procedures), and facilitation (feasibility outside the research setting). RESULTS: Several major themes were identified. Regarding the evidence, participants lacked prior experience with CM, but the intervention was well received and, by some, perceived to lead to lasting behavior change. Regarding the clinical context for the reward schedule, the use of biochemical testing, specifically fingerstick phosphatidylethanol testing, and the reward process were perceived to be engaging and gratifying for both staff and patients. Participants indicated that the intervention was enhanced by its co-location within the HIV clinic. Regarding facilitation, participants suggested addressing the intervention's feasibility for non-research use, simplifying the reward structure, and rewarding non-abstinence in alcohol use. CONCLUSIONS: Among patients and staff involved in a clinical trial, CM was viewed as a helpful, positive, and feasible approach to addressing unhealthy alcohol use and related conditions. To enhance implementation, future efforts may consider simplified approaches to the reward structure and expanding rewards to non-abstinent reductions in alcohol consumption.

Preschool-Aged Household Contacts as a Risk Factor for Viral Respiratory Infections in Healthcare Personnel.

Background: Viral respiratory infections (VRIs) are common and are occupational risks for healthcare personnel (HCP). VRIs can also be acquired at home and other settings among HCPs. We sought to determine if preschool-aged household contacts are a risk factor for VRIs among HCPs working in outpatient settings. Methods: We conducted a secondary analysis of data from a cluster randomized trial at 7 medical centers in the United States over 4 influenza seasons from 2011-2012 to 2014-2015. Adult HCPs who routinely came within 6 feet of patients with respiratory infections were included. Participants were tested for respiratory viruses whenever symptomatic and at 2 random times each season when asymptomatic. The exposure of interest was the number of household contacts 0-5 years old (preschool-aged) at the beginning of each HCP-season. The primary outcome was the rate of polymerase chain reaction-detected VRIs, regardless of symptoms. The VRI incidence rate ratio (IRR) was calculated using a mixed-effects Poisson regression model that accounted for clustering at the clinic level. Results: Among the 4476 HCP-seasons, most HCPs were female (85.4%) and between 30 and 49 years of age (54.6%). The overall VRI rate was 2.04 per 100 person-weeks. In the adjusted analysis, HCPs having 1 (IRR, 1.22 [95% confidence interval {CI}, 1.05-1.43]) and ≥2 (IRR, 1.35 [95% CI, 1.09-1.67]) preschool-aged household contacts had higher VRI rates than those with zero preschool-aged household contacts. Conclusions: Preschool-aged household contacts are a risk factor for developing VRIs among HCPs working in outpatient settings.

Contingency management with stepped care for unhealthy alcohol use among individuals with HIV: Protocol for a randomized controlled trial.

BACKGROUND: Although unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial. METHODS: PWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described. CONCLUSIONS: The FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH. CLINICALTRIALS: gov identifier: NCT03089320.

Impact of mandatory vaccination of healthcare personnel on rates of influenza and other viral respiratory pathogens.

OBJECTIVE: The implementation of mandatory influenza vaccination policies among healthcare personnel (HCP) is controversial. Thus, we examined the affect of mandatory influenza vaccination policies among HCP working in outpatient settings. SETTING: Four Veterans' Affairs (VA) health systems and three non-VA medical centers. METHODS: We analyzed rates of influenza and other viral causes of respiratory infections among HCP working in outpatient sites at 4 VA health systems without mandatory influenza vaccination policies and 3 non-VA health systems with mandatory influenza vaccination policies. RESULTS: Influenza vaccination was associated with a decreased risk of influenza (odds ratio, 0.17; 95% confidence interval [CI], 0.13-0.22) but an increased risk of other respiratory viral infections (incidence rate ratio, 1.26; 95% CI, 1.02-1.57). CONCLUSIONS: Our fitted regression models suggest that if influenza vaccination rates in clinics where vaccination was not mandated had equalled those where vaccine was mandated, HCP influenza infections would have been reduced by 52.1% (95% CI, 51.3%-53.0%). These observations, their possible causes, and additional strategies to reduce influenza and other viral respiratory illnesses among HCP working in ambulatory clinics warrant further investigation.

Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial.

BACKGROUND: The herpes zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However, its safety has not been described in depth. OBJECTIVE: To describe local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults. DESIGN: Randomized, placebo-controlled trial with enrollment from November 1998 to September 2001 and follow-up through April 2004 (mean, 3.4 years). A Veterans Affairs Coordinating Center generated the permutated block randomization scheme, which was stratified by site and age. Participants and follow-up study personnel were blinded to treatment assignments. (ClinicalTrials.gov registration number: NCT00007501) SETTING: 22 U.S. academic centers. PARTICIPANTS: 38 546 immunocompetent adults 60 years or older, including 6616 who participated in an adverse events substudy. INTERVENTION: Single dose of herpes zoster vaccine or placebo. MEASUREMENTS: Serious adverse events and rashes in all participants and inoculation-site events in substudy participants during the first 42 days after inoculation. Thereafter, vaccination-related serious adverse events and deaths were monitored in all participants, and hospitalizations were monitored in substudy participants. RESULTS: After inoculation, 255 (1.4%) vaccine recipients and 254 (1.4%) placebo recipients reported serious adverse events. Local inoculation-site side effects were reported by 1604 (48%) vaccine recipients and 539 (16%) placebo recipients in the substudy. A total of 977 (56.6%) of the vaccine recipients reporting local side effects were aged 60 to 69 years, and 627 (39.2%) were older than 70 years. After inoculation, herpes zoster occurred in 7 vaccine recipients versus 24 placebo recipients. Long-term follow-up (mean, 3.39 years) showed that rates of hospitalization or death did not differ between vaccine and placebo recipients. LIMITATIONS: Participants in the substudy were not randomly selected. Confirmation of reported serious adverse events with medical record data was not always obtained. CONCLUSION: Herpes zoster vaccine is well tolerated in older, immunocompetent adults. PRIMARY FUNDING SOURCE: Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development; grants from Merck to the Veterans Affairs Cooperative Studies Program; and the James R. and Jesse V. Scott Fund for Shingles Research.

Outpatient healthcare personnel knowledge and attitudes towards infection prevention measures for protection from respiratory infections.

BACKGROUND: Healthcare personnel (HCP) knowledge and attitudes toward infection control measures are important determinants of practices that can protect them from transmission of infectious diseases. METHODS: Healthcare personnel were recruited from Emergency Departments and outpatient clinics at seven sites. They completed knowledge surveys at the beginning and attitude surveys at the beginning and end of each season of participation. Attitudes toward infection prevention and control measures, especially medical masks and N95 respirators, were compared. The proportion of participants who correctly identified all components of an infection control bundle for seven clinical scenarios was calculated. RESULTS: The proportion of participants in the medical mask group who reported at least one reason to avoid using medical masks fell from 88.5% on the pre-season survey to 39.6% on the post-season survey (odds ratio [OR] for preseason vs. postseason 0.11, 95% CI 0.10-0.14). Among those wearing N95 respirators, the proportion fell from 87.9% to 53.6% (OR 0.24, 95% CI 0.21-0.28). Participants correctly identified all components of the infection control bundle for 4.9% to 38.5% of scenarios. CONCLUSIONS: Attitudes toward medical masks and N95 respirators improved significantly between the beginning and end of each season. The proportion of HCP who correctly identified the infection control precautions needed for clinical scenarios was low, but it improved over successive years of participation in the study.

Take-home kits to detect respiratory viruses among healthcare personnel: Lessons learned from a cluster randomized clinical trial.

BACKGROUND: Health care personnel (HCP) working in outpatient settings routinely interact with patients with acute respiratory illnesses. Absenteeism following symptom development and lack of staff trained to obtain samples limit efforts to identify pathogens among infected HCP. METHODS: The Respiratory Protection Effectiveness Clinical Trial assessed respiratory infection incidence among HCP between 2011 and 2015. Research assistants obtained anterior nasal and oropharyngeal swabs from HCP in the workplace following development of respiratory illness symptoms and randomly while asymptomatic. Participants received take-home kits to self-collect swabs when absent from work. Samples mailed to a central laboratory were tested for respiratory viruses by reverse transcription polymerase chain reaction. RESULTS: Among 2,862 participants, 3,467 swabs were obtained from symptomatic participants. Among symptomatic HCP, respiratory virus was detected in 904 of 3,467 (26.1%) samples. Self-collected samples by symptomatic HCP at home had higher rates of viral detection (40.3%) compared to 24% obtained by trained research assistants in the workplace (P < .001). CONCLUSIONS: In this randomized clinical trial, take-home kits were an easily implemented, effective method to self-collect samples by HCP. Other studies have previously shown relative equivalence of self-collected samples to those obtained by trained healthcare workers. Take-home kit self-collection could diminish workforce exposures and decrease the demand for personnel protective equipment worn to protect workers who collect respiratory samples.

Integrated stepped alcohol treatment for patients with HIV and at-risk alcohol use: a randomized trial.

BACKGROUND: At-risk levels of alcohol use threaten the health of patients with HIV (PWH), yet evidence-based strategies to decrease alcohol use and improve HIV-related outcomes in this population are lacking. We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among PWH and at-risk alcohol use. METHODS: In this multi-site, randomized trial conducted between January 28, 2013 through July 14, 2017, we enrolled PWH and at-risk alcohol use [defined as alcohol consumption of ≥ 14 drinks per week or ≥ 4 drinks per occasion in men ≤ 65 years old or ≥ 7 drinks per week or ≥ 3 drinks per occasion in women or men > 65 years old]. ISAT (n = 46) involved: Step 1- Brief Negotiated Interview with telephone booster, Step 2- Motivational Enhancement Therapy, and Step 3- Addiction Physician Management. Treatment as usual (TAU) (n = 47) involved receipt of a health handout plus routine care. Analyses were conducted based on intention to treat principles. RESULTS: Despite a multi-pronged approach, we only recruited 37% of the target population (n = 93/254). Among ISAT participants, 50% advanced to Step 2, among whom 57% advanced to Step 3. Participants randomized to ISAT and TAU had no observed difference in drinks per week over the past 30 days at week 24 (primary outcome) [least square means (Ls mean) (95% CI) = 8.8 vs. 10.6; adjusted mean difference (AMD) (95% CI) = - 0.4 (- 3.9, 3.0)]. CONCLUSION: An insufficient number of patients were interested in participating in the trial. Efforts to enhance motivation of PWH with at-risk alcohol use to engage in alcohol-related research and build upon ISAT are needed. Trial registration Clinicaltrials.gov: NCT01410123, First posted August 4, 2011.

A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses.

A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human beta-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results.

Integrated stepped alcohol treatment for patients with HIV and liver disease: A randomized trial.

BACKGROUND: There is no known safe level of alcohol use among patients with HIV and liver disease. We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use, HIV, and liver outcomes among patients with HIV and liver disease. METHODS: In this multi-site, randomized trial conducted between January 28, 2013 through July 15, 2016, we enrolled 95 patients with HIV and liver disease [defined as having active hepatitis C infection or FIB-4 score > 1.45]. ISAT (n = 49) involved: Step 1- Brief Negotiated Interview with telephone booster, Step 2- Motivational Enhancement Therapy, and Step 3- Addiction Physician Management. Treatment as usual (TAU) (n = 46) involved receipt of a health handout plus routine care. Analyses were conducted based on intention to treat. RESULTS: Among ISAT participants, 55% advanced to Step 2, among whom 70% advanced to Step 3. Participants randomized to ISAT and TAU increased abstinence (primary outcome) over time. Abstinence rates were non-significantly higher by self-report (38% vs. 23%, adjusted odds ratio [AOR] [95% CI] = 2.6 [0.8, 9.0]) and phosphatidylethanol (43% vs. 32%, AOR [95% CI] = 1.8 [0.5, 6.3] among those randomized to ISAT vs. TAU at week 24. VACS Index scores (AMD [95% CI] = 1.1 [-3.2, 5.5]) and the proportion with an undetectable HIV viral load (AOR [95% CI] = 0.3 [0.1, 1.3]) did not differ by group at week 24 (p values >0.05). ISAT had non-significantly lower FIB-4 scores (adjusted mean difference [AMD] [95% CI] = -0.2 [-0.9, 0.5]), ALT (AMD [95% CI] = -7 [-20, 7]) and AST (AMD [95% CI] = -4 [-15, 7]) at week 24 compared to TAU. CONCLUSION: ISAT is feasible and potentially effective at enhancing delivery of evidence-based alcohol treatment to promote alcohol abstinence and improve liver biomarkers among patients with HIV and liver disease.

Integrated stepped alcohol treatment for patients with HIV and alcohol use disorder: a randomised controlled trial.

BACKGROUND: We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among patients living with HIV and alcohol use disorder. METHODS: In this multisite, randomised controlled trial, conducted in five Veterans Affairs-based HIV clinics in the USA (Atlanta, GA; Brooklyn-Manhattan, NY; Dallas and Houston, TX; and Washington, DC), we recruited people living with HIV and an alcohol use disorder who were not otherwise receiving formal alcohol treatment. Patients were eligible if they were aged 18 years or older, HIV positive, English speaking, and met criteria for alcohol use disorder by the Diagnostic and Statistical Manual for Mental Disorders-IV criteria for alcohol abuse or dependence. Key exclusion criteria included if the patient was acutely suicidal or had a psychiatric condition that affected their ability to participate in counselling interventions, or if they had any medical conditions that would preclude completing the study or cause harm during the course of the study. Using a web-based clinical trial management system, we randomly assigned participants (1:1) to receive ISAT or treatment as usual; patients, investigators, and clinicians were unmasked to allocation. ISAT involved three steps: step 1, addiction physician management, comprising eight sessions; step 2, addiction physician management plus motivational enhancement therapy, comprising four sessions; and step 3, specialty referral. Participants were stepped up at weeks 4 and 12 if they exceeded a priori drinking criteria. Treatment as usual involved referral to substance use treatment services. The primary outcome was number of drinks per week over the past 30 days at week 24 by use of the timeline followback method, assessed in the intention-to-treat population. Adverse events were tracked throughout the study period in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, number NCT01410123. FINDINGS: Between Jan 28, 2013, and July 14, 2017, 128 of 351 patients assessed for eligibility were eligible and randomly assigned to receive ISAT (n=63) or treatment as usual (n=65). Mean age was 54 years (range 23-70), 125 (98%) of 128 participants were men, and 101 (79%) were black. 25 (20%) were lost to follow-up. In the ISAT group, of 57 participants who did not die or withdraw, 30 (52%) advanced to step 2, and 17 (57%) of 30 advanced to step 3. 32 (51%) of 63 participants assigned to ISAT versus 17 (26%) of 65 assigned to treatment as usual received at least one alcohol treatment medication (p=0·004). Participants in both groups decreased their alcohol consumption, but at week 24 we did not detect a difference in number of drinks per week between the groups (least squares mean 10·4 drinks per week [SD 16·5] in the ISAT group vs 15·6 drinks per week [SD 17·6] in the treatment as usual group; adjusted mean difference -4·2, 95% CI -9·4 to 0·9; p=0·11). One adverse event occurred that was possibly related to treatment occurred in the ISAT group (headache). INTERPRETATION: ISAT increases the receipt of alcohol treatment medications and counselling without changes in drinking at week 24. Strategies to implement and enhance ISAT are needed. Future efforts should focus on promoting ISAT with attention to enhancing patient engagement and retention in alcohol-related care. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

Impact of pneumococcal vaccination on the incidence of pneumonia by HIV infection status among patients enrolled in the Veterans Aging Cohort 5-Site Study.

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons have a high incidence of pneumonia and pneumococcal disease. Benefits of vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) among these patients continue to be debated. METHODS: The impact of PPV vaccination on the incidence of pneumonia events (i.e., the composite of pneumococcal pneumonia and pneumonia due to nonspecified organisms) was examined among participants in the Veterans Aging Cohort 5-Site Study, an ongoing prospective study of HIV-infected patients matched to an HIV-uninfected control group. Dates of PPV vaccination and pneumonia were determined by retrospective review of electronic medical records. Time to events was measured for up to 2 years from PPV vaccination or from enrollment for vaccinated and unvaccinated patients, respectively. Kaplan-Meier and Cox proportional hazards regression methods were used to examine the incidence of pneumonia by HIV infection and PPV vaccination status. RESULTS: Among 692 HIV-uninfected and 934 HIV-infected study participants, 59% were vaccinated with PPV. The 2-year incidence of pneumonia was 6% (97 participants developed pneumonia). HIV-infected patients had a higher rate of pneumonia (hazard ratio, 5.81; 95% confidence interval, 3.15-10.71); overall, vaccinated patients showed a trend toward lower risk of pneumonia (hazard ratio, 0.75; 95% confidence interval, 0.50-1.13). Among HIV-infected patients, after controlling for HIV-specific and other variables, vaccination significantly reduced the risk of pneumonia (hazard ratio, 0.65; 95% confidence interval, 0.42-1.00); current smoking, low hemoglobin level, and low CD4 cell count significantly increased such risk. The effect of PPV vaccination among HIV-uninfected patients was not significant. CONCLUSIONS: Among HIV-infected patients, PPV vaccination offered protection against pneumonia. Smoking cessation needs to be pursued as an additional strategy for preventing pneumonia.