Search

BackgroundHeart failure (HF) necessitates frequent transport by emergency medical services (EMS), but few studies have been conducted to evaluate predictors of EMS use and of multiple EMS transports that are amenable to intervention.ObjectivesTo characterize prehospital clinical status of community-dwelling adults with reported HF who used EMS across 8 years and to evaluate predictors of EMS use and multiple EMS transports.MethodsData were from a database in a large Midwestern county. Descriptive statistics, logistic and negative binomial regression were used for analysis.ResultsEMS transports were evaluated for 6582 adults with 16,905 transports. The most common chief complaints were respiratory problems, feeling sick, and chest pain. Shortness of breath, chest pain, level of consciousness, age, gender, race, and hospital site predicted multiple transports.ConclusionsClinicians need to educate patients with HF about ways to manage shortness of breath and chest pain and when to activate EMS.

BackgroundHeart failure (HF) necessitates frequent transport by emergency medical services (EMS), but few studies have been conducted to evaluate predictors of EMS use and of multiple EMS transports that are amenable to intervention.ObjectivesTo characterize prehospital clinical status of community-dwelling adults with reported HF who used EMS across 8 years and to evaluate predictors of EMS use and multiple EMS transports.MethodsData were from a database in a large Midwestern county. Descriptive statistics, logistic and negative binomial regression were used for analysis.ResultsEMS transports were evaluated for 6582 adults with 16,905 transports. The most common chief complaints were respiratory problems, feeling sick, and chest pain. Shortness of breath, chest pain, level of consciousness, age, gender, race, and hospital site predicted multiple transports.ConclusionsClinicians need to educate patients with HF about ways to manage shortness of breath and chest pain and when to activate EMS.

BACKGROUND:Synthesis of psychometric properties of substance use measures to identify patterns of use and substance use disorders remains limited. To address this gap, we sought to systematically evaluate the psychometric properties of measures to detect substance use and misuse. METHODS:We conducted a systematic review and meta-analysis of literature on measures of substance classes associated with HIV risk (heroin, methamphetamine, cocaine, ecstasy, alcohol) that were published in English before June 2016 that reported at least one of the following psychometric outcomes of interest: internal consistency (alpha), test-retest/inter-rater reliability (kappa), sensitivity, specificity, positive predictive value, and negative predictive value. We used meta-analytic techniques to generate pooled summary estimates for these outcomes using random effects and hierarchical logistic regression models. RESULTS:Findings across 387 paper revealed that overall, 65% of pooled estimates for alpha were in the range of fair-to-excellent; 44% of estimates for kappa were in the range of fair-to-excellent. In addition, 69, 97, 37 and 96% of pooled estimates for sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were in the range of moderate-to-excellent. CONCLUSION:We conclude that many substance use measures had pooled summary estimates that were at the fair/moderate-to-excellent range across different psychometric outcomes. Most scales were conducted in English, within the United States, highlighting the need to test and validate these measures in more diverse settings. Additionally, the majority of studies had high risk of bias, indicating a need for more studies with higher methodological quality.

BackgroundThe role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.ObjectiveTo assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).Design, setting, and participantsWe identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT).Outcome measurements and statistical analysisBiochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.Results and limitationsA total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS).ConclusionsWPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.Patient summaryWhen men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.

BackgroundOral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is highly effective for HIVprevention, yet long-term effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM).MethodsThis cross-sectional analysis included HIV-negative MSM either on PrEP (n = 37) or not (n = 37) selected from an ongoing cohort using propensity score matching. Rectal swabs were used to examine microbiome composition using 16S ribosomal ribonucleic acid gene sequencing, and associations between PrEP use and microbiota abundance were examined. Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants (n = 15).ResultsPre-exposure prophylaxis use was associated with a significant increase in Streptococcus abundance (adjusted P = .015). Similar associations were identified using least absolute shrinkage and selection operator (LASSO) regression, confirming the increase in Streptococcus and also showing increased Mitsuokella, Fusobacterium, and decreased Escherichia/Shigella. Increased Fusobacterium was significantly associated with increasing TFV exposure.ConclusionsOral TDF/FTC for PrEP is associated with rectal microbiome changes compared to well matched controls, specifically increased Streptococcus and Fusobacterium abundance. This study highlights the need for future investigations of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP.

BackgroundOral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is highly effective for HIVprevention, yet long-term effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM).MethodsThis cross-sectional analysis included HIV-negative MSM either on PrEP (n = 37) or not (n = 37) selected from an ongoing cohort using propensity score matching. Rectal swabs were used to examine microbiome composition using 16S ribosomal ribonucleic acid gene sequencing, and associations between PrEP use and microbiota abundance were examined. Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants (n = 15).ResultsPre-exposure prophylaxis use was associated with a significant increase in Streptococcus abundance (adjusted P = .015). Similar associations were identified using least absolute shrinkage and selection operator (LASSO) regression, confirming the increase in Streptococcus and also showing increased Mitsuokella, Fusobacterium, and decreased Escherichia/Shigella. Increased Fusobacterium was significantly associated with increasing TFV exposure.ConclusionsOral TDF/FTC for PrEP is associated with rectal microbiome changes compared to well matched controls, specifically increased Streptococcus and Fusobacterium abundance. This study highlights the need for future investigations of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP.

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R2 = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes.

ObjectiveWe employed a high-dimensional covariate adjustment method in microbiome analysis to better control for behavioural and clinical confounders, and in doing so examine the effects of HIV on the rectal microbiome.DesignThree hundred and eighty-three MSM were grouped into four HIV viremia categories: HIV negative (n = 200), HIV-positive undetectable (HIV RNA  200 copies/ml; n = 45).MethodsWe performed 16S rRNA gene sequencing on rectal swab samples and used inverse probability of treatment-weighted marginal structural models to examine differences in microbial composition by HIV viremia category.ResultsHIV viremia explained a significant amount of variability in microbial composition in both unadjusted and covariate-adjusted analyses (R = 0.011, P = 0.02). Alterations in bacterial taxa were more apparent with increasing viremia. Relative to the HIV-negative group, HIV-positive undetectable participants showed depletions in Brachyspira, Campylobacter and Parasutterella, while suppressed participants demonstrated depletions in Barnesiella, Brachyspira and Helicobacter. The microbial signature of viremic men was most distinct, showing enrichment in inflammatory genera Peptoniphilus, Porphyromonas and Prevotella and depletion of Bacteroides, Brachyspira and Faecalibacterium, among others.ConclusionOur study shows that, after accounting for the influence of multiple confounding factors, HIV is associated with dysbiosis in the gastrointestinal microbiome in a dose-dependent manner. This analytic approach may allow for better identification of true microbial associations by limiting the effects of confounding, and thus improve comparability across future studies.

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R2 = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes.

BackgroundHuman immunodeficiency virus type 1 (HIV-1) infection alters the human intestinal microbiome; however, behavioral factors driving these changes remain poorly defined. Here we examine the effects of substance use and sex behavior on the microbiome during HIV-1 infection.MethodsArchival rectal swab specimens, urine drug test results, and responses to substance use and sex behavior questionnaires were obtained from 37 HIV-positive participants at 2 time points, separated by 6 months, in a cohort examining the effects of substance use in men who have sex with men (MSM). Microbiome profiling was performed using 16S ribosomal RNA gene sequencing, and associations with behavioral factors were examined using 0-inflated negative binomial regression. Further analysis of selected variables of interest was performed using propensity scores to account for multiple confounders.ResultsUsing permutational multivariate analysis of variance, we found that receptive anal intercourse, methamphetamine use, and marijuana use were among the most important drivers of microbiome variation. Propensity score-adjusted analyses revealed that methamphetamine use and marijuana use displayed unique associations; methamphetamine use was associated with an increased abundance of Porphyromonas and Granulicatella organisms and a decreased abundance of Ruminococcus, Collinsella, and Parabacteroides organisms, whereas marijuana use was associated with an increased abundance of Ruminococcus, Clostridium cluster IV, Solobacterium, and Fusobacterium organisms and a decreased abundance of Acidaminococcus, Prevotella, Dialister, Anaerostipes, and Dorea organisms.ConclusionsDrug use and sex behavior are important factors associated with intestinal dysbiosis during chronic HIV-1 infection among young MSM.

BackgroundPrevious studies have suggested that varenicline, an α4β2 nicotinic receptor partial agonist, and α7 nicotinic receptor full agonist, may be effective for the treatment of methamphetamine (MA) dependence due to dopaminergic effects, relief of glutamatergic and cognitive dysfunction, and activation of nicotinic cholinergic systems. This study aimed to determine if varenicline (1 mg BID) resulted in reduced methamphetamine use compared to placebo among treatment-seeking MA-dependent volunteers.MethodsTreatment-seeking MA-dependent volunteers were randomized to varenicline 1 mg twice daily (n = 27) or placebo (n = 25) and cognitive behavioral therapy for 9 weeks. The primary outcomes were the proportion of participants achieving end-of-treatment-abstinence (EOTA, MA-negative urine specimens during weeks 8 and 9) and the treatment effectiveness score (TES, number of MA-negative urine specimens) for varenicline versus placebo.ResultsThere was no significant difference in EOTA between varenicline (15%, 4/27) and placebo (20%, 5/25; p = 0.9). There was some suggestion that urinary confirmed medication compliance corresponded with EOTA in the varenicline condition, though it did not reach statistical significance, OR = 1.57 for a 100 ng/ml increase in urine varenicline, p = 0.10, 95% CI (0.99, 3.02). There was no significant difference in mean TES in the varenicline condition (8.6) compared to the placebo condition (8.1), and treatment condition was not a statistically significant predictor of TES, IRR = 1.01, p = 0.9, 95% CI (0.39, 2.70).ConclusionsThe results of this study indicate that 1 mg varenicline BID was not an effective treatment for MA dependence among treatment-seeking MA-dependent volunteers.

Background and settingBlack men who have sex with men (BMSM) in the United States have disproportionately high HIV infection rates. Social networks have been shown to influence HIV risk behavior; however, little is known about whether they affect the risk of HIV seroconversion. This study uses data from the BROTHERS (HPTN 061) study to test whether contextual factors related to social networks are associated with HIV seroconversion among BMSM.MethodsWe analyzed data from the BROTHERS study (2009-2011), which examined a multicomponent intervention for BMSM in 6 US cities. We ran a series of Cox regression analyses to examine associations between time-dependent measures of network support (personal/emotional, financial, medical, and social participation) and time to HIV seroconversion. We ran unadjusted models followed by models adjusted for participant age at enrollment and study location.ResultsA total of 1000 BMSM tested HIV negative at baseline and were followed at 6- and 12-month study visits. Twenty-eight men tested HIV positive. In adjusted hazard ratio models, study participants who remained HIV negative had higher proportions of social network members who provided personal/emotional {0.92 [95% confidence interval (CI): 0.85 to 0.99]}, medical [0.92 (95% CI: 0.85 to 0.99)], or social participation [0.91 (95% CI: 0.86 to 0.97)] support.ConclusionFindings suggest that the increased presence of social network support can be protective against HIV acquisition. Future research should explore the processes that link social network support with sexual and other transmission risk behaviors as a basis to inform HIV prevention efforts.

ObjectiveWe sought to evaluate the effectiveness and safety of utilizing radiotherapy (RT) with standard fractionation, with or without intraoperative RT (IORT), to treat locally recurrent rectal cancer (LRRC).MethodsRetrospective review of 25 patients with LRRC treated with standard fractionation RT from 2005 to 2011. 15 patients (60%) had prior pelvic RT and 10 (40%) had synchronous metastases. The median equivalent dose in 2-Gy fractions was 30 and 49.6 Gy in patients with and without prior RT, respectively. 23 patients (92%) received concurrent chemotherapy and 16 (64%) underwent surgical resection. Eight patients (33.3%, four with and four without prior RT) received IORT. A competing risks model was developed to estimate the cumulative incidence of local failure with death treated as a competing event.ResultsMedian follow-up was 36.9 months after the date of local recurrence. 3-year rates of overall survival (OS), local control (LC) and death with LC were 51.6%, 73.3% and 69.2%, respectively. On multivariable analysis, surgical resection was significantly predictive of improved OS (p

BackgroundSince 2011, in the United States, quadrivalent human papillomavirus (HPV) vaccine has been recommended for boys aged 11 to 12 years, men through age 21, and men who have sex with men (MSM) through age 26. We assessed HPV vaccination coverage and factors associated with vaccination among young MSM (YMSM) and transgender women (TGW) in 2 cities.MethodsDuring 2012-2014, 808 YMSM and TGW aged 18 to 26 years reported vaccination status in a self-administered computerized questionnaire at 3 sexually transmitted disease (STD) clinics in Los Angeles and Chicago. Associations with HPV vaccination were assessed using bivariate and multivariable models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).ResultsFew of the diverse participants (Hispanic/Latino, 38.0%; white, 27.0%; and black/African American, 17.9%) reported receiving 1 or more HPV vaccine doses (n = 111 [13.7%]) and even fewer reported 3 doses (n = 37 [4.6%]). A multivariable model found associations between vaccination and having a 4-year college degree or higher (aOR, 2.83; CI, 1.55-5.17) and self-reported STDs (aOR, 1.21; CI, 1.03-1.42). In a model including recommendation variables, the strongest predictor of vaccination was a health care provider recommendation (aOR, 11.85; CI, 6.70-20.98).ConclusionsHuman papillomavirus vaccination coverage was low among YMSM and TGW in this 2-US city study. Our findings suggest further efforts are needed to reach YMSM seeking care in STD clinics, increase strong recommendations from health care providers, and integrate HPV vaccination with other clinical services such as STD testing.

Background and aimsHigh rates of loss to follow-up represent a significant challenge to clinical trials of pharmacological treatments for methamphetamine (MA) use disorder. We aimed to estimate and test the relationship between achieving and maintaining abstinence in the initial weeks of study participation and subsequent retention in such trials, hypothesizing that participants able to achieve early abstinence would be less likely to drop out.DesignData from four randomized controlled trials (RCTs) of pharmacological treatments for MA use disorder were pooled and analyzed using a random-effects approach.SettingAll trials were conducted in the greater Los Angeles, CA, USA area.ParticipantsA total of 440 participants were included; trials were conducted between 2004 and 2014.MeasurementsParticipants' ability to achieve a brief period of initial abstinence was measured as the number of MA-negative urine screens completed in the first 2 weeks of the trials. Outcomes were the likelihood of dropout, i.e. missing two consecutive weeks of scheduled urine drug screens, and the number of days participants were retained in the trials.FindingsStudy participants achieved an average of three (of six possible) negative urine screens during the first 2 weeks of the trials, 51% dropped out and the average number of days retained was 60 (of 90 maximum). Each additional negative urine screen achieved during the first 2 weeks of the study reduced multiplicatively the odds of dropout by 41% [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.53, 0.66]. Abstinence was also a significant predictor of retention time; the hazard ratio for non-completion was 0.75 per additional negative urine screen (95% CI = 0.71, 0.80).ConclusionsParticipants in randomized controlled trials of pharmacological treatments for methamphetamine use disorder who are able to achieve a brief period of early abstinence are retained longer in the trials and are less likely to drop out overall.