Human saliva modifies growth, biofilm architecture, and competitive behaviors of oral streptococci.

The bacteria within supragingival biofilms participate in complex exchanges with other microbes inhabiting the same niche. One example is the mutans group streptococci (Streptococcus mutans), implicated in the development of tooth decay, and other health-associated commensal streptococci species. Previously, our group transcriptomically characterized intermicrobial interactions between S. mutans and several species of oral bacteria. However, these experiments were carried out in a medium without human saliva. To better mimic their natural environment, we first evaluated how inclusion of saliva affected growth and biofilm formation of eight Streptococcus species individually and found saliva to positively benefit growth rates while negatively influencing biofilm biomass accumulation and altering spatial arrangement. These results carried over during evaluation of 29 saliva-derived isolates of various species. Surprisingly, we also found that addition of saliva increased the competitive behaviors of S. mutans in coculture competitions against commensal streptococci that led to increases in biofilm microcolony volumes. Through transcriptomically characterizing mono- and cocultures of S. mutans and Streptococcus oralis with and without saliva, we determined that each species developed a nutritional niche under mixed-species growth, with S. mutans upregulating carbohydrate uptake and utilization pathways while S. oralis upregulated genome features related to peptide uptake and glycan foraging. S. mutans also upregulated genes involved in oxidative stress tolerance, particularly manganese uptake, which we could artificially manipulate by supplementing in manganese leading to an advantage over its opponent. Our report highlights observable changes in microbial behaviors through leveraging environmental- and host-supplied resources over their competitors. IMPORTANCE: Dental caries (tooth decay) is the most prevalent disease for both children and adults nationwide. Caries are initiated from demineralization of the enamel due to organic acid production through the metabolic activity of oral bacteria growing in biofilm communities attached to the tooth's surface. Mutans group streptococci are closely associated with caries development and initiation of the cariogenic cycle, which decreases the amount of acid-sensitive, health-associated commensal bacteria while selecting for aciduric and acidogenic species that then further drives the disease process. Defining the exchanges that occur between mutans group streptococci and oral commensals in a condition that closely mimics their natural environment is of critical need toward identifying factors that can influence odontopathogen establishment, persistence, and outgrowth. The goal of our research is to develop strategies, potentially through manipulation of microbial interactions characterized here, that prevent the emergence of mutans group streptococci while keeping the protective flora intact.

Human Saliva Modifies Growth, Biofilm Architecture and Competitive Behaviors of Oral Streptococci.

The bacteria within supragingival biofilms participate in complex exchanges with other microbes inhabiting the same niche. One example are the mutans group streptococci (Streptococcus mutans), implicated in the development of tooth decay, and other health-associated commensal streptococci species. Previously, our group transcriptomically characterized intermicrobial interactions between S. mutans and several species of oral bacteria. However, these experiments were carried out in a medium that was absent of human saliva. To better mimic their natural environment, we first evaluated how inclusion of saliva affected growth and biofilm formation of eight streptococci species individually, and found saliva to positively benefit growth rates while negatively influencing biomass accumulation and altering spatial arrangement. These results carried over during evaluation of 29 saliva-derived isolates of various species. Surprisingly, we also found that addition of saliva increased the competitive behaviors of S. mutans in coculture competitions against commensal streptococci that led to increases in biofilm microcolony volumes. Through transcriptomically characterizing mono- and cocultures of S. mutans and Streptococcus oralis with and without saliva, we determined that each species developed a nutritional niche under mixed-species growth, with S. mutans upregulating carbohydrate uptake and utilization pathways while S. oralis upregulated genome features related to peptide uptake and glycan foraging. S. mutans also upregulated genes involved in oxidative stress tolerance, particularly manganese uptake, which we could artificially manipulate by supplementing in manganese to give it an advantage over its opponent. Our report highlights observable changes in microbial behaviors via leveraging environmental- and host-supplied resources over their competitors.

Association between cannabis use disorder symptom severity and probability of clinically-documented diagnosis and treatment in a primary care sample.

BACKGROUND: Brief cannabis screening followed by standardized assessment of symptoms may support diagnosis and treatment of cannabis use disorder (CUD). This study tested whether the probability of a medical provider diagnosing and treating CUD increased with the number of substance use disorder (SUD) symptoms documented in patients' EHRs. METHODS: This observational study used EHR and claims data from an integrated healthcare system. Adult patients were included who reported daily cannabis use and completed the Substance Use Symptom Checklist, a scaled measure of DSM-5 SUD symptoms (0-11), during routine care 3/1/2015-3/1/2021. Logistic regression estimated associations between SUD symptom counts and: 1) CUD diagnosis; 2) CUD treatment initiation; and 3) CUD treatment engagement, defined based on Healthcare Effectiveness Data and Information Set (HEDIS) ICD-codes and timelines. We tested moderation across age, gender, race, and ethnicity. RESULTS: Patients (N=13,947) were predominantly middle-age, male, White, and non-Hispanic. Among patients reporting daily cannabis use without other drug use (N=12,568), the probability of CUD diagnosis, treatment initiation, and engagement increased with each 1-unit increase in Symptom Checklist score (p's<0.001). However, probabilities of diagnosis, treatment, and engagement were low, even among those reporting ≥2 symptoms consistent with SUD: 14.0% diagnosed (95% CI: 11.7-21.6), 16.6% initiated treatment among diagnosed (11.7-21.6), and 24.3% engaged in treatment among initiated (15.8-32.7). Only gender moderated associations between Symptom Checklist and diagnosis (p=0.047) and treatment initiation (p=0.012). Findings were similar for patients reporting daily cannabis use with other drug use (N=1379). CONCLUSION: Despite documented symptoms, CUD was underdiagnosed and undertreated in medical settings.

Psychometric Performance of a Substance Use Symptom Checklist to Help Clinicians Assess Substance Use Disorder in Primary Care.

Importance: Substance use disorders (SUDs) are underrecognized in primary care, where structured clinical interviews are often infeasible. A brief, standardized substance use symptom checklist could help clinicians assess SUD. Objective: To evaluate the psychometric properties of the Substance Use Symptom Checklist (hereafter symptom checklist) used in primary care among patients reporting daily cannabis use and/or other drug use as part of population-based screening and assessment. Design, Setting, and Participants: This cross-sectional study was conducted among adult primary care patients who completed the symptom checklist during routine care between March 1, 2015, and March 1, 2020, at an integrated health care system. Data analysis was conducted from June 1, 2021, to May 1, 2022. Main Outcomes and Measures: The symptom checklist included 11 items corresponding to SUD criteria in the Diagnostic and Statistical Manual for Mental Disorders (Fifth Edition) (DSM-5). Item response theory (IRT) analyses tested whether the symptom checklist was unidimensional and reflected a continuum of SUD severity and evaluated item characteristics (discrimination and severity). Differential item functioning analyses examined whether the symptom checklist performed similarly across age, sex, race, and ethnicity. Analyses were stratified by cannabis and/or other drug use. Results: A total of 23 304 screens were included (mean [SD] age, 38.2 [5.6] years; 12 554 [53.9%] male patients; 17 439 [78.8%] White patients; 20 393 [87.5%] non-Hispanic patients). Overall, 16 140 patients reported daily cannabis use only, 4791 patients reported other drug use only, and 2373 patients reported both daily cannabis and other drug use. Among patients with daily cannabis use only, other drug use only, or both daily cannabis and other drug use, 4242 (26.3%), 1446 (30.2%), and 1229 (51.8%), respectively, endorsed 2 or more items on the symptom checklist, consistent with DSM-5 SUD. For all cannabis and drug subsamples, IRT models supported the unidimensionality of the symptom checklist, and all items discriminated between higher and lower levels of SUD severity. Differential item functioning was observed for some items across sociodemographic subgroups but did not result in meaningful change (<1 point difference) in the overall score (0-11). Conclusions and Relevance: In this cross-sectional study, a symptom checklist, administered to primary care patients who reported daily cannabis and/or other drug use during routine screening, discriminated SUD severity as expected and performed well across subgroups. Findings support the clinical utility of the symptom checklist for standardized and more complete SUD symptom assessment to help clinicians make diagnostic and treatment decisions in primary care.

Integrating Alcohol-Related Prevention and Treatment Into Primary Care: A Cluster Randomized Implementation Trial.

Importance: Unhealthy alcohol use is common and affects morbidity and mortality but is often neglected in medical settings, despite guidelines for both prevention and treatment. Objective: To test an implementation intervention to increase (1) population-based alcohol-related prevention with brief interventions and (2) treatment of alcohol use disorder (AUD) in primary care implemented with a broader program of behavioral health integration. Design, Setting, and Participants: The Sustained Patient-Centered Alcohol-Related Care (SPARC) trial was a stepped-wedge cluster randomized implementation trial, including 22 primary care practices in an integrated health system in Washington state. Participants consisted of all adult patients (aged ≥18 years) with primary care visits from January 2015 to July 2018. Data were analyzed from August 2018 to March 2021. Interventions: The implementation intervention included 3 strategies: practice facilitation; electronic health record decision support; and performance feedback. Practices were randomly assigned launch dates, which placed them in 1 of 7 waves and defined the start of the practice's intervention period. Main Outcomes and Measures: Coprimary outcomes for prevention and AUD treatment were (1) the proportion of patients who had unhealthy alcohol use and brief intervention documented in the electronic health record (brief intervention) for prevention and (2) the proportion of patients who had newly diagnosed AUD and engaged in AUD treatment (AUD treatment engagement). Analyses compared monthly rates of primary and intermediate outcomes (eg, screening, diagnosis, treatment initiation) among all patients who visited primary care during usual care and intervention periods using mixed-effects regression. Results: A total of 333 596 patients visited primary care (mean [SD] age, 48 [18] years; 193 583 [58%] female; 234 764 [70%] White individuals). The proportion with brief intervention was higher during SPARC intervention than usual care periods (57 vs 11 per 10 000 patients per month; P < .001). The proportion with AUD treatment engagement did not differ during intervention and usual care (1.4 vs 1.8 per 10 000 patients; P = .30). The intervention increased intermediate outcomes: screening (83.2% vs 20.8%; P < .001), new AUD diagnosis (33.8 vs 28.8 per 10 000; P = .003), and treatment initiation (7.8 vs 6.2 per 10 000; P = .04). Conclusions and Relevance: In this stepped-wedge cluster randomized implementation trial, the SPARC intervention resulted in modest increases in prevention (brief intervention) but not AUD treatment engagement in primary care, despite important increases in screening, new diagnoses, and treatment initiation. Trial Registration: ClinicalTrials.gov Identifier: NCT02675777.

Validity of the Single-Item Screen-Cannabis (SIS-C) for Cannabis Use Disorder Screening in Routine Care.

Importance: Cannabis use is prevalent and increasing, and frequent use intensifies the risk of cannabis use disorder (CUD). CUD is underrecognized in medical settings, but a validated single-item cannabis screen could increase recognition. Objective: To evaluate the Single-Item Screen-Cannabis (SIS-C), administered and documented in routine primary care, compared with a confidential reference standard measure of CUD. Design, Setting, and Participants: This diagnostic study included a sample of adult patients who completed routine cannabis screening between January 28 and September 12, 2019, and were randomly selected for a confidential survey about cannabis use. Random sampling was stratified by frequency of past-year use and race and ethnicity. The study was conducted at an integrated health system in Washington state, where adult cannabis use is legal. Data were analyzed from May 2021 to March 2022. Exposures: The SIS-C asks about frequency of past-year cannabis use with responses (none, less than monthly, monthly, weekly, daily or almost daily) documented in patients' medical records. Main Outcomes and Measures: The Diagnostic and Statistical Manual, Fifth Edition (DSM-5) Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM) for past-year CUD was completed on a confidential survey and considered the reference standard. The SIS-C was compared with 2 or more criteria on the CIDI-SAM, consistent with CUD. All analyses were weighted, accounting for survey design and nonresponse, to obtain estimates representative of the health system primary care population. Results: Of 5000 sampled adult patients, 1688 responded to the cannabis survey (34% response rate). Patients were predominantly middle-aged (weighted mean [SD] age, 50.7 [18.1]), female or women (weighted proportion [SE], 55.9% [4.1]), non-Hispanic (weighted proportion [SE], 96.7% [1.0]), and White (weighted proportion [SE], 74.2% [3.7]). Approximately 6.6% of patients met criteria for past-year CUD. The SIS-C had an area under receiver operating characteristic curve of 0.89 (95% CI, 0.78-0.96) for identifying CUD. A threshold of less than monthly cannabis use balanced sensitivity (0.88) and specificity (0.83) for detecting CUD. In populations with a 6% prevalence of CUD, predictive values of a positive screen ranged from 17% to 34%, while predictive values of a negative screen ranged from 97% to 100%. Conclusions and Relevance: In this diagnostic study, the SIS-C had excellent performance characteristics in routine care as a screen for CUD. While high negative predictive values suggest that the SIS-C accurately identifies patients without CUD, low positive predictive values indicate a need for further diagnostic assessment following positive results when screening for CUD in primary care.

Opioid use disorder from poppy seed tea successfully treated with buprenorphine in primary care: a case report.

BACKGROUND: Poppy seeds contain morphine and other opioid alkaloids and are commercially available in the United States. Users of poppy seed tea (PST) can consume several hundred morphine milligram equivalents per day, and opioid dependence from PST use can develop. We report a case of a patient with chronic pain and PST use leading to opioid use disorder (OUD). This case represents the first published report of OUD from PST successfully treated with buprenorphine (BUP) in a primary care setting. The provider in this case used a unique model of care with an opioid prescribing support team to deliver safe and effective care. CASE PRESENTATION: A 47-year-old man with chronic pain and prescription opioid use presented to primary care to discuss a flare of shoulder pain, and revealed in subsequent conversation a long-standing use of PST to supplement pain control. Attempts at cessation resulted in severe withdrawal symptoms, leading to return to PST use. The primary care provider consulted the VA Puget Sound SUpporting Primary care Providers in Opioid Risk reduction and Treatment (SUPPORT) team to evaluate the patient for OUD. The patient discontinued all opioids, and initiated BUP under the supervision of the primary care provider. He remained on a stable dosage, without relapse, 24 months later. CONCLUSIONS: PST, which can be made through purchase of readily available poppy pods, carries risk for development of OUD and overdose. Herein we highlight the utility of a primary care opioid prescribing support team in empowering a primary care provider to prescribe BUP to treat a patient with complex OUD.

Prevalence of substance use and substance-related disorders among US Veterans Health Administration patients.

BACKGROUND: Substance use and related disorders are common among US Veterans, but the population burden of has never been directly assessed among Veterans Health Administration (VA) patients. We surveyed VA patients to measure substance use and related disorders in the largest US integrated healthcare system. METHODS: We surveyed N = 6000 outpatients from 30 geographically-representative VA healthcare systems. We assessed substance use (lifetime, past 12-month, daily in past 3 months) and past 12-month disorders following DSM-5 criteria and estimated the association with Veteran characteristics (age, gender, race/ethnicity, socioeconomic status, VA utilization). RESULTS: Alcohol was the most commonly-reported substance (24% used past 12 months, 11% daily in past 3 months, 10% met criteria for alcohol use disorder), followed by cannabis (42% lifetime use, 12% use in past 12 months, 5% daily use in past 3 months, 3% met criteria for cannabis use disorder). Overall, 5% met criteria for non-alcohol drug use disorder (13% for substance use disorder (SUD)). SUD prevalence was highest for young Veterans and those who were unemployed or otherwise not employed for wages. Past 12-month cannabis use was common, even among older adults (65-74 years: 10%; 75 and older: 2%). CONCLUSIONS: Prevalence data are important inputs into decisions around population health monitoring, treatment capacity, and quality measurement strategies. Substance use and SUD are more prevalent than previously reported, and VA may need to screen for non-alcohol drugs to identify patients who need care. More tailored assessment may be needed for cannabis use, high-prevalence subgroups, and older adults.

The relationship of smoking and unhealthy alcohol use to the HIV care continuum among people with HIV in an integrated health care system.

INTRODUCTION: Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination. METHODS: Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined. RESULTS: The overall sample (N = 8958) had a mean age of 48.0 years; was 91.3 % male; 54.0 % white, 17.6 % Latino, 15.1 % black, and 9.6 % other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR = 1.60 [95 % CI 1.03-2.48]), not retained (OR = 1.30 [95 % CI 1.13-1.50]), and HIV RNA not in control (OR = 1.91 [95 % CI 1.60-2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR = 2.83 [95 % CI 1.40-5.71]), although the interaction did not reach significance (p = 0.18). CONCLUSIONS: In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes.

Costs of using evidence-based implementation strategies for behavioral health integration in a large primary care system.

OBJECTIVE: To describe the cost of using evidence-based implementation strategies for sustained behavioral health integration (BHI) involving population-based screening, assessment, and identification at 25 primary care sites of Kaiser Permanente Washington (2015-2018). DATA SOURCES/STUDY SETTING: Project records, surveys, Bureau of Labor Statistics compensation data. STUDY DESIGN: Labor and nonlabor costs incurred by three implementation strategies: practice coaching, electronic health records clinical decision support, and performance feedback. DATA COLLECTION/EXTRACTION METHODS: Personnel time spent on these strategies was estimated for five broad roles: (a) project leaders and administrative support, (b) practice coaches, (c) clinical decision support programmers, (d) performance metric programmers, and (e) primary care local implementation team members. PRINCIPAL FINDING: Implementation involved 286 persons, 18 131 person-hours, costing $1 587 139 or $5 per primary care visit with screening or $38 per primary care visit identifying depression, suicidal thoughts and/or alcohol or substance use disorders, in a single year. The majority of person-hours was devoted to project leadership (35%) and practice coaches (34%), and 36% of costs were for the first three sites. CONCLUSIONS: When spread across patients screened in a single year, BHI implementation costs were well within the range for commonly used diagnostic assessments in primary care (eg, laboratory tests). This suggests that implementation costs alone should not be a substantial barrier to population-based BHI.

Health care utilization and HIV clinical outcomes among newly enrolled patients following Affordable Care Act implementation in a California integrated health system: a longitudinal study.

BACKGROUND: The Affordable Care Act (ACA) has increased insurance coverage for people with HIV (PWH) in the United States. To inform health policy, it is useful to investigate how enrollment through ACA Exchanges, deductible levels, and demographic factors are associated with health care utilization and HIV clinical outcomes among individuals newly enrolled in insurance coverage following implementation of the ACA. METHODS: Among PWH newly enrolled in an integrated health care system (Kaiser Permanente Northern California) in 2014 (N = 880), we examined use of health care and modeled associations between enrollment mechanisms (enrolled in a Qualified Health Plan through the California Exchange vs. other sources), deductibles (none, $1-$999 and > = $1000), receipt of benefits from the California AIDS Drug Assistance Program (ADAP), demographic factors, and three-year patterns of health service utilization (primary care, psychiatry, substance treatment, emergency, inpatient) and HIV outcomes (CD4 counts; viral suppression at HIV RNA < 75 copies/mL). RESULTS: Health care use was greatest immediately after enrollment and decreased over 3 years. Those with high deductibles were less likely to use primary care (OR = 0.64, 95% CI = 0.49-0.84, p < 0.01) or psychiatry OR = 0.59, 95% CI = 0.37, 0.94, p = 0.03) than those with no deductible. Enrollment via the Exchange was associated with fewer psychiatry visits (rate ratio [RR] = 0.40, 95% CI = 0.18-0.86; p = 0.02), but ADAP was associated with more psychiatry visits (RR = 2.22, 95% CI = 1.24-4.71; p = 0.01). Those with high deductibles were less likely to have viral suppression (OR = 0.65, 95% CI = 0.42-1.00; p = 0.05), but ADAP enrollment was associated with viral suppression (OR = 2.20, 95% CI = 1.32-3.66, p < 0.01). Black (OR = 0.35, 95% CI = 0.21-0.58, p < 0.01) and Hispanic (OR = 0.50, 95% CI = 0.29-0.85, p = 0.01) PWH were less likely to be virally suppressed. CONCLUSIONS: In this sample of PWH newly enrolled in an integrated health care system in California, findings suggest that enrollment via the Exchange and higher deductibles were negatively associated with some aspects of service utilization, high deductibles were associated with worse HIV outcomes, but support from ADAP appeared to help patients achieve viral suppression. Race/ethnic disparities remain important to address even among those with access to insurance coverage.

Racial/ethnic and gender differences in receipt of brief intervention among patients with unhealthy alcohol use in the U.S. Veterans Health Administration.

OBJECTIVE: Brief intervention (BI) for unhealthy alcohol use is a top prevention priority for adults in the U.S, but rates of BI receipt vary across patients. We examine BI receipt across race/ethnicity and gender in a national cohort of patients from the Department of Veterans Affairs (VA)-the largest U.S. integrated healthcare system and a leader in implementing preventive care for unhealthy alcohol use. METHODS: Among 779,041 VA patients with documented race/ethnicity and gender who screened positive for unhealthy alcohol use (AUDIT-C score ≥ 5) between 10/1/09 and 5/30/13, we fit Poisson regression models to estimate the predicted prevalence of BI (EHR-documented advice to reduce or abstain from drinking) across race/ethnicity and gender. RESULTS: Rates of BI were lowest among Black women (67%), Black men (68%), and Asian/Pacific Islander women (68%), and highest among white men (75%), Hispanic men (75%), and Asian/Pacific Islander men (75%). A significant race/ethnicity by gender interaction indicated that the associations between race/ethnicity and gender with BI depended on the other factor. Gender differences were largest among Asian/Pacific Islander patients and were nonsignificant among American Indian/Alaska Native patients. Adjustment for covariates not expected to be on the causal pathway (e.g., age, year of AUDIT-C screen) slightly attenuated but did not change the direction of results. CONCLUSIONS: Receipt of BI for unhealthy alcohol use varied by race/ethnicity and gender, and the impact of one factor depended on the other. Black women, Black men, and Asian/Pacific Islander women had the lowest rates of receiving recommended alcohol-related care. We found these disparities in a healthcare system that has implemented universal alcohol screening and incentivized BI for all patients with unhealthy alcohol use, suggesting that reducing disparities in alcohol-related care may require targeted interventions.

Integration of screening, assessment, and treatment for cannabis and other drug use disorders in primary care: An evaluation in three pilot sites.

BACKGROUND: This pilot study evaluated whether use of evidence-based implementation strategies to integrate care for cannabis and other drug use into primary care (PC) as part of Behavioral Health Integration (BHI) increased diagnosis and treatment of substance use disorders (SUDs). METHODS: Patients who visited the three pilot PC sites were eligible. Implementation strategies included practice coaching, electronic health record decision support, and performance feedback (3/2015-4/2016). BHI introduced annual screening for past-year cannabis and other drug use, a Symptom Checklist for DSM-5 SUDs, and shared decision-making about treatment options. Main analyses tested whether the proportions of PC patients diagnosed with, and treated for, new cannabis or other drug use disorders (CUDs and DUDs, respectively), differed significantly pre- and post-implementation. RESULTS: Of 39,599 eligible patients, 57% and 59% were screened for cannabis and other drug use, respectively. Among PC patients reporting daily cannabis use (2%) or any drug use (1%), 51% and 37%, respectively, completed an SUD Symptom Checklist. The proportion of PC patients with newly diagnosed CUD increased significantly post-implementation (5 v 17 per 10,000 patients, p < 0.0001), but not other DUDs (10 vs 13 per 10,000, p = 0.24). The proportion treated for newly diagnosed CUDs did not increase post-implementation (1 vs 1 per 10,000, p = 0.80), but did for those treated for newly diagnosed other DUDs (1 vs 3 per 10,000, p = 0.038). CONCLUSIONS: A pilot implementation of BHI to increase routine screening and assessment for SUDs was associated with increased new CUD diagnoses and a small increase in treatment of new other DUDs.

Prevalence and Correlates of Unhealthy Alcohol and Drug Use Among Men Who Have Sex with Men Prescribed HIV Pre-exposure Prophylaxis in Real-World Clinical Settings.

Pre-exposure prophylaxis (PrEP) is effective in preventing HIV acquisition among men who have sex with men (MSM). However, little is known about unhealthy substance use among MSM initiating PrEP in real-world settings. Unhealthy substance use is a risk factor for HIV acquisition and non-adherence to treatment, and may also impact PrEP use. MSM who were prescribed PrEP from 2015 to 2017 at clinics in Providence, Rhode Island and New Haven, Connecticut were recruited to participate in a prospective observational study. Structured clinical assessments were used to assess demographics, HIV risk behaviors, and unhealthy alcohol (alcohol use disorders identification test [AUDIT]-C scores ≥ 4) and drug use (use of any drugs in the past 3 months). Bivariate and multivariate analyses were performed to determine demographics and behaviors associated with unhealthy alcohol and drug use. Among 172 MSM initiating PrEP, 64% were white and 40% were 25-34 years old. Participants reported a median of 3 (IQR 2-7) sexual partners in the last 3 months; 20% reported an HIV positive partner. Unhealthy alcohol and any drug use were reported by 54 and 57%, respectively, and 76% reported at least one of the two. The majority of drug use reported was marijuana and poppers (41 and 26% of participants, respectively). Relative to those without unhealthy alcohol use, unhealthy alcohol use was independently associated with any drug use (adjusted odds ratio [AOR] = 2.57, 95% CI 1.32-5.01). Frequent drug use was associated with younger age (< 25 years, AOR 4.27, 95% CI 1.51-12.09). Unhealthy alcohol use is common among MSM taking PrEP. Drug use other than marijuana and poppers was uncommon among our cohort. Further efforts may be needed to understand the influence of unhealthy alcohol and other substance use on PrEP outcomes and to engage MSM who use drugs for PrEP.

Dietary nitrate supplementation enhances short but not longer duration running time-trial performance.

PURPOSE: This study evaluated the effects of dietary nitrate (NO3-) supplementation on physiological functioning and exercise performance in trained runners/triathletes conducting short and longer-distance treadmill running time-trials (TT). METHOD: Eight trained male runners or triathletes completed four exercise performance tests comprising a 10 min warm up followed by either a 1500 or 10,000 m treadmill TT. Exercise performance tests were preceded 3 h before the exercise by supplementation with either 140 ml concentrated nitrate-rich (~12.5 mmol nitrate) (BRJ) or nitrate-deplete (~0.01 mmol nitrate) (PLA) beetroot juice. RESULTS: BRJ supplementation significantly elevated plasma [NO2-] (P < 0.05). Resting blood pressure and exercise [Formula: see text] were not significantly different between BRJ and PLA (P > 0.05). However, post-exercise blood [lactate] was significantly greater in BRJ following the 1500 m TT (6.6 ± 1.2 vs. 6.1 ± 1.5 mM; P < 0.05), but not significantly different between conditions in the 10,000 m TT (P > 0.05). Performance in the 1500 m TT was significantly faster in BRJ vs. PLA (319.6 ± 36.2 vs. 325.7 ± 38.8 s; P < 0.05). Conversely, there was no significant difference in 10,000 m TT performance between conditions (2643.1 ± 324. 1 vs. 2649.9 ± 319.8 s, P > 0.05). CONCLUSION: Acute BRJ supplementation significantly enhanced 1500 m, but not 10,000 m TT performance. These findings suggest that BRJ might be ergogenic during shorter distance TTs which allow for a high work rate, but not during longer distance TTs, completed at a lower work rate.

Ingestion of a Nitric Oxide Enhancing Supplement Improves Resistance Exercise Performance.

Mosher, SL, Sparks, SA, Williams, EL, Bentley, DJ, and Mc Naughton, LR. Ingestion of a nitric oxide enhancing supplement improves resistance exercise performance. J Strength Cond Res 30 (12): 3520-3524, 2016-Studies have established that supplementation of nitrate increases nitric oxide which in turn improves exercise performance. The current study aimed to investigate the effects of nitrate ingestion on performance of bench press resistance exercise until failure. Twelve recreationally active (age, 21 ± 2 years, height, 177.2 ± 4.0 cm, weight, 82.49 ± 9.78 kg) resistance-trained men participated in the study. The study used a double-blind, randomized cross-over design, where participants ingested either 70 ml of "BEET It Sport" nitrate shot containing 6.4 millimoles (mmol·L) or 400 mg of nitrate or a blackcurrant placebo drink. Participants completed a resistance exercise session, consisting of bench press exercise at an intensity of 60% of their established 1 repetition maximum (1RM), for 3 sets until failure with 2 minutes rest interval between sets. The repetitions completed, total weight lifted, local and general rate of perceived exertion (RPE), and blood lactate were all measured. The results showed a significant difference in repetitions to failure (p ≤ 0.001) and total weight lifted (p ≤ 0.001). However, there were no significant difference between blood lactate over the 2 trials (p = 0.238), and no difference in Local (p = 0.807) or general (p = 0.420) indicators of fatigue as measured by RPE. This study demonstrates that nitrate supplementation has the potential to improve resistance training performance and work output compared with a placebo.

Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study.

Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed.

The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial.

RATIONALE: Tea has anecdotally been associated with stress relief, but this has seldom been tested scientifically. OBJECTIVES: To investigate the effects of 6 weeks of black tea consumption, compared with matched placebo, on subjective, cardiovascular, cortisol and platelet responses to acute stress, in a parallel group double-blind randomised design. MATERIALS AND METHODS: Seventy-five healthy nonsmoking men were withdrawn from tea, coffee and caffeinated beverages for a 4-week wash-out phase during which they drank four cups per day of a caffeinated placebo. A pretreatment laboratory test session was carried out, followed by either placebo (n = 38) or active tea treatment (n = 37) for 6 weeks, then, a final test session. Cardiovascular measures were obtained before, during and after two challenging behavioural tasks, while cortisol, platelet and subjective measures were assessed before and after tasks. RESULTS: The tasks induced substantial increases in blood pressure, heart rate and subjective stress ratings, but responses did not differ between tea and placebo treatments. Platelet activation (assessed using flow cytometry) was lower following tea than placebo treatment in both baseline and post-stress samples (P < 0.005). The active tea group also showed lower post-task cortisol levels compared with placebo (P = 0.032), and a relative increase in subjective relaxation during the post-task recovery period (P = 0.036). CONCLUSIONS: Compared with placebo, 6 weeks of tea consumption leads to lower post-stress cortisol and greater subjective relaxation, together with reduced platelet activation. Black tea may have health benefits in part by aiding stress recovery.

Association between coffee consumption and markers of inflammation and cardiovascular function during mental stress.

BACKGROUND: Coffee is widely consumed in the Western diet and therefore has important implications for public health. Research findings pertaining to the effects of coffee consumption on cardiovascular health are conflicting, and the role of caffeine is not clear. OBJECTIVE: To examine the relationship between coffee intake, inflammation and cardiovascular function at baseline and during mental stress, both cross-sectionally and after a 4-week period of withdrawal of coffee during which intake of caffeine was maintained. METHODS: Eighty-five healthy, non-smoking men with varying coffee-drinking habits were recruited. Blood pressure, heart rate, and markers of inflammation [C-reactive protein (CRP), von Willebrand factor antigen (vWF)], were measured at baseline and during mental stress. These measures were repeated after a 4-week period of withdrawal of coffee, during which intake of caffeine was maintained. Habitual levels of coffee and caffeine consumption were assessed from a self-reported questionnaire, and saliva samples for the analysis of caffeine concentrations were collected regularly throughout the period of withdrawal, to confirm compliance. RESULTS: Multiple linear regression analysis of pre-withdrawal data, adjusted for age, body mass index and intake of tea, red wine, fruit, vegetables, oily fish and dietary supplements revealed that coffee consumption was positively related to baseline systolic blood pressure, and increased heart rate and vWF responses to mental stress. Four weeks after withdrawal of coffee, the heightened vWF and heart rate responses to stress in habitual coffee drinkers persisted, whereas baseline systolic blood pressure had decreased. Total caffeine intake was unrelated to any measures of physiological function. CONCLUSIONS: Habitual coffee consumption is associated with heightened acute vascular inflammatory responses to mental stress, although these effects are not affected by short-term abstinence from coffee. These findings suggest that the relationship between coffee and markers of cardiovascular risk may be explained by residual or unmeasured confounding factors.