Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Impact of early, weekly drinking on latent classes of alcohol involvement progression and recovery: Evidence from the NESARC Waves 1 and 2.

Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.Introduction: Early drinkers have been found to have higher risk of developing alcohol use disorder; however, the association of early drinking with progression to problematic alcohol involvement that does not meet disorder criteria (i.e., subclinical problems) or to severe stages of alcohol involvement, sex-specific associations, and relationship of early drinking with alcohol recovery have rarely been investigated. Methods: Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we applied latent transition analyses to investigate the impact of weekly drinking before age 18 on alcohol progression and recovery operationalized as three classes of alcohol involvement using abuse and dependence indicators. We analyzed data separately for male (n = 12,276) and female (n = 14,750) drinkers and applied propensity score methods to address confounding. Results: We observed significant associations between early, weekly drinking and alcohol involvement class membership at Wave 1 for both males and females. For males, early, weekly drinking was also associated with greater odds of transitioning from moderate to severe alcohol problems (aOR = 3.19, 95% CI = 1.72, 5.35). For females, early, weekly drinking predicted the transition from no to severe problems (aOR = 2.98, 95% CI = 1.11–8.00). Contrary to our hypothesis, early, weekly drinking was associated with greater likelihood of transition from severe to no problems for males (aOR = 3.23, 95% CI = 1.26, 8.26). Discussion: Frequent, early drinking seems to be an important indicator of drinking progression with differential associations by sex. This information is useful to identify those at greater risk of progressing to severe drinking problems to intervene appropriately.https://doi.org/10.1016/j.abrep.2022.10041

Promoting Evidence-Based Tobacco Cessation Treatment in Community Mental Health Clinics: Protocol for a Prepost Intervention Study

BackgroundTobacco smoking is highly prevalent among persons with serious mental illness (SMI) and is the largest contributor to premature mortality in this population. Evidence-based smoking cessation therapy with medications and behavioral counseling is effective for persons with SMI, but few receive this treatment. Mental health providers have extensive experience working with clients with SMI and frequent treatment contacts, making them well positioned to deliver smoking cessation treatment. However, few mental health providers feel adequately trained to deliver this treatment, and many providers believe that smokers with SMI are not interested in quitting or have concerns about the safety of smoking cessation pharmacotherapy, despite substantial evidence to the contrary. ObjectiveWe present the protocol for the pilot “IMPACT” (Implementing Action for Tobacco Smoking Cessation Treatment) study, which aims to pilot test a multicomponent implementation intervention to increase the delivery of evidence-based tobacco smoking cessation treatment in community mental health clinics. MethodsWe are using a prepost observational design to examine the effects of an implementation intervention designed to improve mental health providers’ delivery of the following four evidence-based practices related to smoking cessation treatment: (1) assessment of smoking status, (2) assessment of willingness to quit, (3) behavioral counseling, and (4) pharmacotherapy prescribing. To overcome key barriers related to providers’ knowledge and self-efficacy of smoking cessation treatment, the study will leverage implementation strategies including (1) real-time and web-based training for mental health providers about evidence-based smoking cessation treatment and motivational interviewing, including an avatar practice module; (2) a tobacco smoking treatment protocol; (3) expert consultation; (4) coaching; and (5) organizational strategy meetings. We will use surveys and in-depth interviews to assess the implementation intervention’s effects on providers’ knowledge and self-efficacy, the mechanisms of change targeted by the intervention, as well as providers’ perceptions of the acceptability, appropriateness, and feasibility of both the evidence-based practices and implementation strategies. We will use data on care delivery to assess providers’ implementation of evidence-based smoking cessation practices. ResultsThe IMPACT study is being conducted at 5 clinic sites. More than 50 providers have been enrolled, exceeding our recruitment target. The study is ongoing. ConclusionsIn order for persons with SMI to realize the benefits of smoking cessation treatment, it is important for clinicians to implement evidence-based practices successfully. This pilot study will result in a set of training modules, implementation tools, and resources for clinicians working in community mental health clinics to address tobacco smoking with their clients. Trial Registration: ClinicalTrials.gov NCT04796961; https://clinicaltrials.gov/ct2/show/NCT04796961 Trial RegistrationClinicalTrials.gov NCT04796961; https://clinicaltrials.gov/ct2/show/NCT04796961 International Registered Report Identifier (IRRID)DERR1-10.2196/4478