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Background Patients with cardiometabolic disease, specifically, stroke, heart disease and diabetes have a high prevalence of polypharmacy. Interventions to better manage or reduce polypharmacy in these populations may help improve patient outcomes. However, there is a paucity of data in this area, which needs to be investigated. Aim of the review The purpose of this scoping review was to identify and synthesize the available evidence pertaining to polypharmacy interventions in patients with cardiometabolic disease(s) and to determine what outcomes measures are assessed in these studies. Methods We followed an evidence-based scoping review guiding framework to address our study objectives. Three electronic databases (MEDLINE, EMBASE, CINAHL) were searched for all relevant studies up to May 2019. The Cochrane Library was also searched; studies included in relevant reviews were screened for inclusion. Reference lists of all included papers were also manually reviewed to identify additional articles. Polypharmacy interventions and measures used to assess efficacy were qualitatively described. Results Overall, six studies met the inclusion criteria. The majority of interventions were clinical pharmacist interventions reporting on a variety of outcomes including surrogate markers, quality of life and patient satisfaction, drug-related problems, and healthcare utilization and costs. The findings from the included studies generally indicated positive effects but had high risk of bias. Conclusions Existing polypharmacy interventions have some efficacy at improving a variety of patient and healthcare system outcomes. Increased frequency and duration of follow-up with patients led to significant improvements in quality of life, disease control and cost-savings in outpatient and in-patient settings. However, our analysis of the identified studies suggests low-quality evidence and significant knowledge gaps regarding patients with stroke and cardiometabolic multimorbidity. This signals a need for further high-quality research to both confirm these findings and include these other high-risk patient populations to validate these findings.

Syringe vending machines (SVMs) are intended to supplement the standard syringe exchange programs to access hard-to-reach groups and to cover unserved geographical areas. This report describes how we adapted SVMs to deliver interventions and collect research data as part of a study of smart SVMs (SSVMs) in Tbilisi, Georgia.To create SSVMs, we upgraded commercial vending machines and developed a computer program to track and record interactions and to display messages related to study procedures. Preferred locations for SSVMs, product specifications, and the mode of operation were determined through formative input from people who inject drugs (PWID). SSVMs were installed near pharmacies and serve both the general population and PWID. The "hidden" interactive menu for the PWID prevention kits was displayed on the screen only when a special plastic card was used. The plastic cards were distributed to the clients of fixed syringe exchange programs and to their peers who were not in contact with harm-reduction services.Ten SSVMs were operational in Tbilisi as of March 2021, with more than 800 PWID using them on a regular basis. More than half of sterile equipment kits were distributed during weekends and night hours.Our innovative SSVM integrates features for intervention delivery and research data collection. It can be used for testing a variety of interventions beyond syringes (e.g., distribution of HIV/hepatitis C virus self-tests) and provides opportunities for serving various at-risk groups that might not otherwise access these products and services (e.g., men who have sex with men, commercial sex workers).

Background To address the overdose crisis in the United States, expert groups have been nearly unanimous in calls for increasing access to evidence-based treatment and overdose reversal drugs. In some places there have also been calls for implementing supervised consumption sites (SCSs). Some cities—primarily in coastal urban areas—have explored the feasibility and acceptability of introducing them. However, the perspectives of community stakeholders from more inland and rural areas that have also been hard hit by opioids are largely missing from the literature. Methods To examine community attitudes about implementing SCSs for people who use opioids (PWUO) in areas with acute opioid problems, the research team conducted in-depth interviews and focus groups in four counties: Ashtabula and Cuyahoga Counties in Ohio, and Carroll and Hillsborough Counties in New Hampshire, two states with high rates of opioid overdose. Participants were policy, treatment, and criminal justice professionals, frontline harm reduction and service providers, and PWUO. Results Key informants noted benefits to SCSs, but also perceived potential drawbacks such as that they may enable opioid use, and potential practical barriers, including lack of desire among PWUO to travel to an SCS after purchasing opioids and fear of arrest. Key informants generally believed their communities likely would not currently accept SCSs due to cultural, resource, and practical barriers. They viewed publication of evidence on SCSs and community education as essential for fostering acceptance. Conclusions Despite cultural and other barriers, implementation of SCSs may be more feasible in urban communities with existing (and perhaps more long-standing) harm reduction programs, greater treatment resources, and adequate transportation, particularly if there is strong evidence to support them.

Asians and Pacific Islanders (API) have large disparities in utilization of substance use treatment compared to other racial groups. In this study, we analyzed factors that shape API experiences accessing and engaging in community-based treatment from the perspective of treatment providers. We conducted semi-structured interviews with 40 treatment providers who work with API clients in treatment programs in San Francisco and Los Angeles. We analyzed the transcribed interview data in ATLAS.ti using a content analysis approach. There were three main findings. First, treatment providers found the API category itself is too broad and heterogeneous to meaningfully explain substance use patterns. Second, beyond race/ethnicity, structural factors such as poverty, neighborhood, housing, and age had an impact on API substance use. Third, factors such as family, immigration status, religion, language, stigma played complex roles in API treatment experiences, contingent on how client, programs, and providers attended to differences in these categories.

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis, and its early rise in patients with chronic kidney disease is independently associated with all-cause mortality. Since inflammation is characteristic of chronic kidney disease and associates with increased plasma FGF23 we examined whether inflammation directly stimulates FGF23. In a population-based cohort, plasma tumor necrosis factor (TNF) was the only inflammatory cytokine that independently and positively correlated with plasma FGF23. Mouse models of chronic kidney disease showed signs of renal inflammation, renal FGF23 expression and elevated systemic FGF23 levels. Renal FGF23 expression coincided with expression of the orphan nuclear receptor Nurr1 regulating FGF23 in other organs. Antibody-mediated neutralization of TNF normalized plasma FGF23 and suppressed ectopic renal Fgf23 expression. Conversely, TNF administration to control mice increased plasma FGF23 without altering plasma phosphate. Moreover, in Il10-deficient mice with inflammatory bowel disease and normal kidney function, plasma FGF23 was elevated and normalized upon TNF neutralization. Thus, the inflammatory cytokine TNF contributes to elevated systemic FGF23 levels and also triggers ectopic renal Fgf23 expression in animal models of chronic kidney disease.

Purpose To develop an electrocorticography (ECoG) grid by using deposition of conductive nanoparticles in a polymer thick film on an organic substrate (PTFOS) that induces minimal, if any, artifacts on computed tomographic (CT) and magnetic resonance (MR) images and is safe in terms of tissue reactivity and MR heating. Materials and Methods All procedures were approved by the Animal Care and Use Committee and complied with the Public Health Services Guide for the Care and Use of Animals. Electrical functioning of PTFOS for cortical recording and stimulation was tested in two mice. PTFOS disks were implanted in two mice; after 30 days, the tissues surrounding the implants were harvested, and tissue injury was studied by using immunostaining. Five neurosurgeons rated mechanical properties of PTFOS compared with conventional grids by using a three-level Likert scale. Temperature increases during 30 minutes of 3-T MR imaging were measured in a head phantom with no grid, a conventional grid, and a PTFOS grid. Two neuroradiologists rated artifacts on CT and MR images of a cadaveric head specimen with no grid, a conventional grid, and a PTFOS grid by using a four-level Likert scale, and the mean ratings were compared between grids. Results Oscillatory local field potentials were captured with cortical recordings. Cortical stimulations in motor cortex elicited muscle contractions. PTFOS implants caused no adverse tissue reaction. Mechanical properties were rated superior to conventional grids (χ(2) test, P < .05). The temperature increase during MR imaging for the three cases of no grid, PTFOS grid, and conventional grid was 3.84°C, 4.05°C, and 10.13°C, respectively. PTFOS induced no appreciable artifacts on CT and MR images, and PTFOS image quality was rated significantly higher than that with conventional grids (two-tailed t test, P < .05). Conclusion PTFOS grids may be an attractive alternative to conventional ECoG grids with regard to mechanical properties, 3-T MR heating profile, and CT and MR imaging artifacts. (©) RSNA, 2016 Online supplemental material is available for this article.

Open access is fast becoming the norm across science. Sharing research data broadly has the potential to accelerate scientific progress, optimize the value of data, and promote scientific integrity. However, data sharing also poses new practical and ethical challenges to the conduct of research with human participants. This article provides an overview of how open access to research data has impacted the core principles of research ethics-respect for persons, beneficence, and justice-and, in turn, how a reinterpretation of these principles translates to procedures for the protection of the rights and wellbeing of human research participants. (PsycINFO Database Record

BACKGROUND: Few previous retrospective studies suggest that Plasmodium ovale wallikeri seems to have a longer latency period and produces deeper thrombocytopaenia than Plasmodium ovale curtisi. Prospective studies were warranted to better assess interspecies differences. METHODS: Patients with imported P. ovale spp. infection diagnosed by thick or thin film, rapid diagnostic test (RDT) or polymerase chain reaction (PCR) were recruited between March 2014 and May 2017. All were confirmed by DNA isolation and classified as P. o. curtisi or P. o. wallikeri using partial sequencing of the ssrRNA gene. Epidemiological, analytical and clinical differences were analysed by statistical methods. RESULTS: A total of 79 samples (35 P. o. curtisi and 44 P. o. wallikeri) were correctly genotyped. Males predominate in wallikeri group (72.7%), whereas were 48.6% in curtisi group. Conversely, 74.3% of curtisi group were from patients of African ethnicity, whilst 52.3% of Caucasians were infected by P. o. wallikeri. After performing a multivariate analysis, more thrombocytopaenic patients (p = 0.022), a lower number of platelets (p = 0.015), a higher INR value (p = 0.041), and shorter latency in Caucasians (p = 0.034) were significantly seen in P. o. wallikeri. RDT sensitivity was 26.1% in P. o. curtisi and 42.4% in P. o. wallikeri. Nearly 20% of both species were diagnosed only by PCR. Total bilirubin over 3 mg/dL was found in three wallikeri cases. Two patients with curtisi infection had haemoglobin under 7 g/dL, one of them also with icterus. A wallikeri patient suffered from haemophagocytosis. Chemoprophylaxis failed in 14.8% and 35% of curtisi and wallikeri patients, respectively. All treated patients with various anti-malarials which included artesunate recovered. Diabetes mellitus was described in 5 patients (6.32%), 4 patients of wallikeri group and 1 curtisi. CONCLUSIONS: Imported P. o. wallikeri infection may be more frequent in males and Caucasians. Malaria caused by P. o. wallikeri produces more thrombocytopaenia, a higher INR and shorter latency in Caucasians and suggests a more pathogenic species. Severe cases can be seen in both species. Chemoprophylaxis seems less effective in P. ovale spp. infection than in P. falciparum, but any anti-malarial drug is effective as initial treatment. Diabetes mellitus could be a risk factor for P. ovale spp. infection. This study has been funded with a grant FIB-PI14-04 from the Foundation for Biomedical Research of the Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain. Sí

CD4+ Foxp3+ regulatory T cells (Tregs) are an essential component of immune homeostasis. Modulation of Treg function has been proposed as a means of treating autoimmune conditions and preventing rejection of organ transplants, although achieving this goal will require a detailed understanding of Treg signaling pathways. Signaling within Tregs is known to differ considerably from that observed in other T cell subsets. Of note, Tregs are the only cell type known to constitutively express CD25, the main ligand-binding subunit of the IL-2 receptor. The PI(3)K/Akt/mTOR cascade constitutes a major signaling pathway downstream of IL-2 and is closely tied to cellular metabolism. Due to increasing recognition of the links between cellular fuel usage and immune cell function, the interplay between IL-2 signaling and Treg metabolism represents an important space for exploration and a potential approach for immunomodulation. Here, we discuss how IL-2 may affect Treg metabolism via PI(3)K signaling, as well as the effects of altered metabolism on Treg lineage stability and suppressor function.

The limited epidemiological data in Lebanon suggest that HIV incident cases are predominantly among men who have sex with men (MSM). We assessed the prevalence of HIV and demographic correlates of condom use and HIV testing among MSM in Beirut. Respondent-driven sampling was used to recruit 213 participants for completion of a behavioral survey and an optional free rapid HIV test. Multivariate regression analysis was used to examine demographic correlates of unprotected anal sex and any history of HIV testing. Nearly half (47 %) were under age 25 years and 67 % self-identified as gay. Nearly two-thirds (64 %) reported any unprotected anal intercourse (UAI) with men in the prior 3 months, including 23 % who had unprotected anal intercourse with men whose HIV status was positive or unknown (UAIPU) to the participant. Three men (1.5 % of 198 participants tested) were HIV-positive; 62 % had any history of HIV testing prior to the study and testing was less common among those engaging in UAIPU compared to others (33 % vs. 71 %). In regression analysis, men in a relationship had higher odds of having UAI but lower odds of UAIPU and any university education was associated with having UAI; those with any prior history of HIV testing were more likely to be in a relationship and have any university education. HIV prevention efforts for MSM need to account for the influence of relationship dynamics and promotion of testing needs to target high-risk MSM.

In X-linked hypophosphatemia (XLH) and in its murine homologue, the Hyp mouse, increased circulating concentrations of fibroblast growth factor 23 (FGF-23) are critical to the pathogenesis of disordered metabolism of phosphate (P(i)) and 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. In this study, we hypothesized that in Hyp mice, FGF-23-mediated suppression of renal 1,25(OH)(2)D production and P(i) reabsorption depends on activation of mitogen-activated protein kinase (MAPK) signaling. Wild-type and Hyp mice were administered either vehicle or the MEK inhibitor PD0325901 (12.5 mg/kg) orally daily for 4 days. At baseline, the renal abundance of early growth response 1 (egr1) mRNA was approximately 2-fold greater in Hyp mice than in wild-type mice. Treatment with PD0325901 greatly suppressed egr1 mRNA abundance in both wild-type and Hyp mice. In Hyp mice, PD0325901 induced an 8-fold increase in renal 1α-hydroxylase mRNA expression and a 4-fold increase in serum 1,25(OH)(2)D concentrations compared with vehicle-treated Hyp mice. Serum P(i) levels in Hyp mice increased significantly after treatment with PD0325901, and the increase was associated with increased renal Npt2a mRNA abundance and brush-border membrane Npt2a protein expression. These findings provide evidence that in Hyp mice, MAPK signaling is constitutively activated in the kidney and support the hypothesis that the FGF-23-mediated suppression of renal 1,25(OH)(2)D production and P(i) reabsorption depends on activation of MAPK signaling via MEK/ERK1/2. These findings demonstrate the physiologic importance of MAPK signaling in the actions of FGF-23 in regulating renal 1,25(OH)(2)D and P(i) metabolism.

This study applies a chronic illness framework to evaluate treatment outcomes among individuals dependent on methamphetamine (MA). Using growth curve modeling, health-related quality of life (HRQOL) trajectories of MA-dependent individuals (N = 723) were examined over a 1-year period. Results show greater improvements in mental HRQOL trajectories as a function of treatment completion and continued care, although fairly static trajectories in physical health status. Other factors affecting HRQOL trajectories included gender, psychosocial functioning, drug use severity, and health impairment. Results extend research on treatment evaluations for MA dependence, highlighting the importance of continued service utilization for improved quality of life outcomes.

The Sexual Acquisition and Transmission of HIV Cooperative Agreement Program (SATHCAP) examined the role of drug use in the sexual transmission of the human immunodeficiency virus (HIV) from traditional high-risk groups, such as men who have sex with men (MSM) and drug users (DU), to lower risk groups in three US cities and in St. Petersburg, Russia. SATHCAP employed respondent-driven sampling (RDS) and a dual high-risk group sampling approach that relied on peer recruitment for a combined, overlapping sample of MSM and DU. The goal of the sampling approach was to recruit an RDS sample of MSM, DU, and individuals who were both MSM and DU (MSM/DU), as well as a sample of sex partners of MSM, DU, and MSM/DU and sex partners of sex partners. The approach efficiently yielded a sample of 8,355 participants, including sex partners, across all four sites. At the US sites—Los Angeles, Chicago, and Raleigh–Durham—the sample consisted of older (mean age = 41 years), primarily black MSM and DU (both injecting and non-injecting); in St. Petersburg, the sample consisted of primarily younger (mean age = 28 years) MSM and DU (injecting). The US sites recruited a large proportion of men who have sex with men and with women, an important group with high potential for establishing a generalized HIV epidemic involving women. The advantage of using the dual high-risk group approach and RDS was, for the most part, the large, efficiently recruited samples of MSM, DU, and MSM/DU. The disadvantages were a recruitment bias by race/ethnicity and income status (at the US sites) and under-enrollment of MSM samples because of short recruitment chains (at the Russian site).

The results of a focused search of the literature on empirical studies of substance abuse treatment outcomes with Hispanic adults are reviewed. Also provided are key research opportunities and recommendations on substance abuse treatment for Hispanics. The paper is divided into two major sections: the first focuses on behavioral drug treatment studies on Hispanic adults, and the second identifies published original articles in pharmacotherapy for substance abuse disorders in Hispanic populations. The authors found a common theme that appears to cut across research on behavioral treatment and pharmacotherapy, namely that more empirical research is needed to determine which treatments are efficacious with Hispanic populations. For treatment modalities not associated with promising effect sizes with Hispanic samples, cultural modifications may be needed to improve the compatibility of the treatment with Hispanic culture. For those treatments found to have promising effect sizes with Hispanic populations, follow-up analyses and/or studies should be conducted to ascertain whether the treatment is differentially efficacious with various Hispanic subgroups, with Hispanics at different levels of acculturation, and with Hispanics from various socioeconomic backgrounds. The authors stress the need for theory-driven interventions to be developed specifically for well-characterized Hispanic subgroups (e.g., suburban, middle-income Puerto Ricans living in the Northeast).

Limited access to positive reinforcers is a central feature in behavioral formulations of substance use and depression, and evidence suggests both disorders share similar environmental contexts. The Behavioral Therapy for Depression in Drug Dependence (BTDD) was developed to target the density of potential reinforcers in a patient's environment to reduce both depression and illicit substance use using therapeutic techniques from three operant based treatment programs, Community Reinforcement Approach, Changing Reinforcement Events, and Treatment-plan Contingency Management. Results of an uncontrolled Stage Ia trial (n = 29), indicated 48% of the participants demonstrated at least a 50% reduction in baseline depression scores during the 16-session treatment program. Those designated as treatment responders completed more out-of-session behavioral activities, attended more treatment sessions, and demonstrated less benzodiazepine use during the program than non-responders. There were no changes in opiate and cocaine use. BTDD may be a useful adjunct to methadone maintenance for treating comorbid depressive disorders.

Background— After myocardial ischemia, prolonged suppression of fatty acid metabolism may persist despite restoration of blood flow, which is called metabolic stunning. We hypothesized that a branched-chain fatty acid, β-methyl- p -[ 123 I]-iodophenyl-pentadecanoic acid (BMIPP), might identify the presence of myocardial ischemia late after demand ischemia at rest up to 30 hours later. Methods and Results— In 32 patients with exercise-induced ischemia on thallium SPECT, BMIPP was injected at rest within 30 hours of ischemia. SPECT images were acquired beginning 10 minutes after injection (early) and again 30 minutes after injection (delayed). Thallium and BMIPP SPECT data were read separately by 3 observers blinded to other imaging and clinical data. Agreement between BMIPP and thallium data for the presence of an abnormality on the patient level was 91% (95% CI, 75 to 98) for the early BMIPP data and 94% (95% CI, 79 to 99) for the delayed BMIPP data. Agreement between delayed BMIPP and thallium was 95% among 21 patients studied on the same day, a mean of 6.2±1.4 hours after exercise-induced ischemia, and 91% among the 11 patients studied on the next calendar day, a mean of 24.9±2.6 hours after ischemia ( P =NS). The magnitude of resting BMIPP metabolic defect by semiquantitative visual analysis was correlated to the magnitude of exercise-induced thallium perfusion defect ( r =0.6, P r =0.5, P =0.005 for delayed BMIPP). Conclusions— Metabolic imaging with BMIPP identifies patients with recent exercise-induced myocardial ischemia. These findings support the concept that BMIPP imaging can successfully demonstrate the metabolic imprint of a stress-induced ischemic episode, also known as ischemic memory.

We conducted a literature search to review studies that presented quantitative data on sexually transmitted disease (STD) screening in non-traditional settings in the United States. We examined the studies for evidence of the feasibility of screening, population size reached, acceptability, yield, and potential for contributing to STD control. We found 17 studies in jails, eight in emergency room, five in schools and 15 in other community settings. Jail-based and emergency room-based STD screenings have the highest yields and the largest numbers screened and thus hold significant promise as settings for routine STD screening. More research needs to be done in school and community settings to better identify their potential.

Disadvantaged racial and ethnic minorities in the U.S. are strikingly over-represented in the juvenile justice and adult criminal justice systems. This paper briefly reviews the extent of over-representation attributable primarily to drug offenses and an earlier conceptual framework introduced by Iguchi and colleagues showing how the use of incarceration as a key drug control tool has disproportionately affected the health and well being of racial and ethnic minority communities. We then provide observations from the field that demonstrate how the implementation of a quality assessment approach might be used to mitigate procedural/structural biases that contribute to disparities in minority confinement, and ultimately, to reduce disparities in access to resources and health care.

Most smokers do not plan to quit in the next 6 months. The authors previously demonstrated that percentile schedules shape lower breath carbon monoxide (BCO) levels in smokers trying to quit (R. J. Lamb, A. R. Morral, K. C. Kirby, M. Y. Iguchi, & G. Galbicka, 2004). In that study, the authors set reinforcement criteria based on the 9 most recent samples. In this study, the authors examined whether a more responsive procedure using the 4 most recent samples is more effective in smokers not trying to quit. Following institution of the contingencies in both groups, BCO levels were substantially reduced, and readiness to quit and cessation self-efficacy increased. However, more individuals in the 4-sample window group achieved a BCO level below 4 ppm, indicating recent abstinence. These individuals did so more rapidly and for a greater number of visits.

Contingency management interventions effectively reduce or eliminate some individuals' problem substance use. Typically, those who do not benefit never experience the reward or planned contingency available through the intervention because they never produce the behavior (often abstinence) on which the reward is contingent. With two analog studies, we examine whether the effectiveness contingency management interventions improves when contingencies are arranged in ways that improve the likelihood of all participants experiencing the available reward. Participants were smokers not planning to quit. In Study 1, smokers were paid $0, 1, 3, 10, or 30 each day for 5 days for delivery of breath carbon monoxide (CO) levels either ≤4 ppm or below half the median of their baseline levels. Higher payment amounts and the easier target criterion resulted in a higher likelihood of participants meeting criterion. Once participants met the 4 ppm criterion, however, they often maintained this behavior even in the absence of payments for reduced breath CO levels. An ineffective contingency management system was made effective based on these results. Study 2 examined the effectiveness of percentile schedules at reducing breath CO levels. Percentile schedules shaped lower breath CO levels. The effectiveness of percentile schedules in shaping abstinence was tested in treatment seekers, and percentile schedules were found to be effective at shaping abstinence.

The Methamphetamine Treatment Project (MTP) offers the opportunity to examine co-occurring psychiatric conditions in a sample of 1016 methamphetamine users participating in a multisite outpatient treatment study between 1999-2001. Participants reported high levels of psychiatric symptoms, particularly depression and attempted suicide, but also anxiety and psychotic symptoms. They also reported high levels of problems controlling anger and violent behavior, with a correspondingly high frequency of assault and weapons charges. Findings continue to support the value of integrated treatment for co-occurring conditions, especially the importance of training counseling staff to handle psychotic symptoms when needed.

Substance-using intimate partners negatively influence individuals' substance abuse treatment engagement and drug use, but little else is known about effects of intimate relationships on treatment. We examine how relationship dynamics (power, control, dependence, insecurity and decision-making power) influence treatment engagement, and whether this differs by gender and partner drug use. Sixty-four heroin users (42 men, 22 women) receiving methadone detoxification treatment in Los Angeles were interviewed at treatment entry and submitted daily diaries of drug use throughout the 21-day treatment. Total number of reported heroin-free days in the first eight treatment days was the dependent variable. Bivariate analyses revealed, that compared to men, women were more likely to have substance-using partners, reported greater power over a partner and greater household decision-making power in their relationships. Multivariate analysis indicated that individuals whose partners had more control over them reported fewer days abstinent. Among individuals with heroin-using partners, greater household decision-making power was associated with more days abstinent, but there was no association for individuals with non-using partners. Relationship power dynamics may be important influences on the treatment process, and some dimensions of power may interact with partner drug use status.

Antiretroviral therapy is being increasingly delayed until later stages of illness. Therefore, prior to prescribing HAART, providers are emphasizing the need for patients to be ready to adhere well to the treatment regimen. Unfortunately, providers are no better than chance at predicting a patient's adherence, and there are no established methods for accurately assessing a patient's adherence readiness. This pilot study assessed the utility of a series of up to five 1-week placebo practice trials accompanied by adherence counseling as a clinical tool to both assess and improve adherence readiness.Participants were not prescribed treatment until they demonstrated readiness, which was defined as 90+% adherence during a single practice trial. Once HAART was initiated, adherence to one selected antiretroviral was monitored for 4 weeks. Electronic monitoring caps were used to measure adherence.Twenty men enrolled in the study at two HIV outpatient clinics in Southern California. Mean age was 33, 50% were non-White, 35% were employed, 30% had not completed high school, 15% were Spanish monolingual, and 30% had unstable housing. Nine participants achieved 90+% adherence in the first practice trial, with an additional 8 participants demonstrating readiness after two to four practice trials; two participants withdrew from the study because of intolerance of the restrictions related to the use of the caps; and one participant was removed from the study after no effort was given during two practice trials. Of the 17 participants who completed the program and demonstrated adherence readiness, 15 started on an antiretroviral regimen and 2 decided to defer treatment indefinitely. Of the 15 who started therapy, 13 (87%) achieved 90+% adherence during the first month of antiretroviral therapy. The sample's mean adherence during the first 4 weeks of treatment was 93% (SD = 13).These results suggest that once a patient is able to adhere well to a 1-week practice trial they are likely to adhere equally well to HAART. A larger controlled study is needed to further assess the effectiveness of practice trials as a clinical tool for both assessing and improving adherence readiness.

The rate-limiting, hormonally regulated step in the biological activation of vitamin D is its 1alpha-hydroxylation to 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] in the kidney, catalyzed by the mitochondrial cytochrome P450 enzyme, P450c1alpha. We previously cloned the human P450c1alpha cDNA and gene, and identified 14 different mutations, including 7 missense, in 19 patients with 1alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type 1. None of the missense mutations encoded a protein with detectable enzymatic activity in vitro. Although there is phenotypic variation among such patients, the molecular basis of this variation is unknown. We analyzed 6 additional patients with clinical and radiographic features of rickets; in 4 patients the laboratory abnormalities were typical of 1alpha-hydroxylase deficiency, but in 2 they were unusually mild [mild hypocalcemia and normal serum 1,25-(OH)(2)D concentration]. Direct sequencing revealed that all patients had P450c1alpha mutations on both alleles. Five new and 2 known mutations were identified. The new mutations included a 5-bp deletion with a 6-bp novel insertion causing a frameshift in exon 2, and a G to A change at +1 of intron 2; a minigene experiment proved that this intronic mutation prevented proper splicing. Three new missense mutations were found and tested by expressing the mutant cDNA in mouse Leydig MA-10 cells. The R389G mutant was totally inactive, but mutant L343F retained 2.3% of wild-type activity, and mutant E189G retained 22% of wild-type activity. The two mutations that confer partial enzyme activity in vitro were found in the 2 patents with mild laboratory abnormalities, suggesting that such mutations contribute to the phenotypic variation observed in patients with 1alpha-hydroxylase deficiency.

This study investigates the relationship between discrimination and substance abuse among Latina/os, and further examines whether this relationship differs by gender and type of discrimination. Analyses focus on the Latina/o respondents (n=1,039 men; n=1,273 women) from the National Latino and Asian American Study carried out from 2002–2003. Outcomes were alcohol abuse and drug abuse measured using DSM-IV definitions and criteria. Additional covariates included immigrant characteristics and demographics. Analyses were completed using gender-stratified multinomial logistic regression. Men reported more discrimination (39.6% versus 30.3%) and had higher prevalence of alcohol abuse (16.5% versus 4.5%) and drug abuse (9.5% versus 2.3%) than women. Discrimination was significantly associated with increased risk of alcohol abuse for women and increased risk of drug abuse for men. Men and women also varied in the types of discrimination (e.g. racial versus gender) reported, and in the associations between these types of discrimination and substance use. These data indicate that discrimination is associated with different substance abuse outcomes between genders. Future research should consider the mechanisms that explain these differences.

After drug treatment counselors at a community-based methadone treatment clinic were trained in implementing a contingency management (CM) intervention, baseline measures of performance revealed that, on average, counselors were meeting the performance criteria specified by the treatment protocol about 42% of the time. Counselors were exposed to graphical feedback and a drawing for cash prizes in an additive within-subjects design to assess the effectiveness of these interventions in improving protocol adherence. Counselor performance measures increased to 71% during the graphical feedback condition, and to 81% during the drawing. Each counselor's performance improved during the intervention conditions. Additional analyses suggested that counselors did not have skill deficits that hindered implementation. Rather, protocol implementation occurred more frequently when consequences were added, thereby increasing the overall proportion of criteria met. Generalizations, however, may be limited due to a small sample size and possible confounding of time and intervention effects. Nonetheless, present results show promise that feedback and positive reinforcement could be used to improve technology transfer of behavioral interventions into community clinic settings.

Research increasingly suggests the importance of studying drug abuse from the perspective of the behavior of individuals within the context of environments. Drug markets are a critical component of this context, one that has not received due research attention. To better understand drug markets, researchers must consider the entire range of factors that affect the decisions of sellers and drug users.

Although many studies document the use of the MMPI to classify opiate users, the predictive validity of the resulting subgroups is rarely reported. In this study, we used cluster analysis to identify MMPI profile types that predicted differential response to methadone maintenance treatment. Participants (N = 151) completed MMPIs shortly after entry into treatment. Cluster analysis of MMPI scores produced four distinct subgroups that differed significantly in severity of psychosocial problems measured at admission and on the mean number of drug-free urine specimens submitted during the 24-week study period. Cluster 1 participants evidenced low levels of psychological disturbance, improved their urinalysis results over time, and submitted the most posttest drug-free urine specimens. Cluster 2 was the only other group that improved significantly over time, even though these patients were the most psychologically disturbed. The results suggest the relation between psychological problems and outcome may be more complex than is commonly assumed.

The secosteroid hormone, 1,25-dihydroxyvitamin D [1,25(OH)2D], plays a crucial role in normal bone growth, calcium metabolism, and tissue differentiation. The key step in the biosynthesis of 1,25(OH)2D is its 1 alpha-hydroxylation from 25-hydroxyvitamin D (25-OHD) in the kidney. Because its expression in the kidney is very low, we cloned and sequenced cDNA for 25-OHD-1 alpha-hydroxylase (P450c1 alpha) from human keratinocytes, in which 1 alpha-hydroxylase activity and mRNA expression can be induced to be much greater. P450c1 alpha mRNA was expressed at much lower levels in human kidney, brain, and testis. Mammalian cells transfected with the cloned P450c1 alpha cDNA exhibit robust 1 alpha-hydroxylase activity. The identity of the 1,25(OH)2D3 product synthesized in transfected cells was confirmed by HPLC and gas chromatography-mass spectrometry. The gene encoding P450c1 alpha was localized to chromosome 12, where the 1 alpha-hydroxylase deficiency syndrome, vitamin D-dependent rickets type 1 (VDDR-1), has been localized. Primary cultures of human adult and neonatal keratinocytes exhibit abundant 1 alpha-hydroxylase activity, whereas those from a patient with VDDR-1 lacked detectable activity. Keratinocyte P450c1 alpha cDNA from the patient with VDDR-1 contained deletion/frameshift mutations either at codon 211 or at codon 231, indicating that the patient was a compound heterozygote for two null mutations. These findings establish the molecular genetic basis of VDDR-1, establish a novel means for its study in keratinocytes, and provide the sequence of the key enzyme in the biological activation of vitamin D.

This pilot study used snowball recruitment methods and intensive interviews to assess personal drug-using networks and HIV risk behavior of injection drug users (IDUs). Index subjects were 22 methadone maintenance patients reporting current drug injection who were interviewed about personal drug-using networks both current and prior to treatment entry. The index subjects were then asked to recruit other network members to the study. Ninety-seven network members were identified and 40 interviewed, including 18 not in treatment. Index IDUs reported fewer co-IDUs for the treatment period than the pre-treatment period, suggesting a reduction in risk of exposure to HIV. The combination of snowball recruitment and intensive interview procedures constitutes a useful method for studying IDU networks.

OBJECTIVE: As part of a synthesis of evidence regarding the efficacy and safety of ephedra, the authors describe data on psychiatric adverse events from reports submitted to the Food and Drug Administration (FDA). METHOD: The authors reviewed all 1,820 adverse event reports related to dietary supplements containing herbal ephedra from FDA MedWatch files as of Sept. 30, 2001. Fifty-seven serious psychiatric events were reported. RESULTS: The most commonly reported events were psychosis, severe depression, mania or agitation, hallucinations, sleep disturbance, and suicidal ideation. Ten events involved physical harm to self or others; five events resulted in legal action due to criminal behavior. Twenty-six events resulted in hospitalization, at least six of which were involuntary. Of importance, two-thirds of all cases involved patients with preexisting psychiatric conditions and /or use of other medications or illicit substances. CONCLUSIONS: Clinicians should be aware that serious psychiatric symptoms co...

This mixed methods study examined motivations and barriers to substance abuse treatment entry and treatment continuation among Asian American and Pacific Islander (AAPI) substance users. AAPI substance users (N= 61) were recruited from substance abuse treatment programs in California and Hawaii. Semi-structured interviews and interviewer-administered surveys assessed barriers and facilitators to entering substance abuse treatment. Barriers included peer pressure, family influences, and face loss concerns. Facilitators included peer support, involvement in the criminal justice system, a perceived need for treatment, and culturally competent substance abuse treatment services. Family and peer influences may act as both facilitators and impediments. AAPI substance using populations face many of the same individual-level and structural and systems barriers to entry to treatment as other substance using populations. However, similar to other racial/ethnic minority groups, it is important to address cultural differences and develop culturally competent substance abuse treatments for the AAPI population. © 2013 Elsevier Inc.

Background Based on a stress-coping framework, the present study investigates the relationship between discrimination and substance use, and the moderating effects of gender. Methods This cross-sectional study analyzes data from Latina/o young adults aged 18–25 ( N =401) from Brooklyn, New York. Multinomial logistic regression was used to test the association between discrimination and substance use. Results Discrimination was significantly associated with increased odds of substance use adjusting for covariates (e.g. age, education). Gender was a moderator. Discrimination was associated with increased risk of alcohol/cannabis and hard drug use among young Latina women. However, discrimination was associated with decreased risk of alcohol/cannabis use and increased risk of hard drug use among young Latino men. Conclusion These findings suggest that discrimination is generally associated with risk for substance use, but further that the outcomes vary by gender. Future research should explore gender-specific dimensions of discrimination and their associations with other outcomes.

The mitochondrial enzyme 25-hydroxyvitamin D 1α-hydroxylase, which is encoded by the CYP27B1 gene, converts 25OHD to the biological active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D). Renal 1α-hydroxylase activity is the principal determinant of the circulating 1,25(OH)2D concentration and enzyme activity is tightly regulated by several factors. Fibroblast growth factor-23 (FGF-23) decreases serum 1,25(OH)2D concentrations by suppressing CYP27B1 mRNA abundance in mice. In extra-renal tissues, 1α-hydroxylase is responsible for local 1,25(OH)2D synthesis, which has important paracrine actions, but whether FGF-23 regulates CYP27B1 gene expression in extra-renal tissues is unknown. We sought to determine whether FGF-23 regulates CYP27B1 transcription in the kidney and whether extra-renal tissues are target sites for FGF-23-induced suppression of CYP27B1. In HEK293 cells transfected with the human CYP27B1 promoter, FGF-23 suppressed promoter activity by 70%, and the suppressive effect was blocked by CI-1040, a specific inhibitor of extracellular signal regulated kinase 1/2. To examine CYP27B1 transcriptional activity in vivo, we crossed fgf-23 null mice with mice bearing the CYP27B1 promoter-driven luciferase transgene (1α-Luc). In the kidney of FGF-23 null/1α-Luc mice, CYP27B1 promoter activity was increased by 3-fold compared to that in wild-type/1α-Luc mice. Intraperitoneal injection of FGF-23 suppressed renal CYP27B1 promoter activity and protein expression by 26% and 60% respectively, and the suppressive effect was blocked by PD0325901, an ERK1/2 inhibitor. These findings provide evidence that FGF-23 suppresses CYP27B1 transcription in the kidney. Furthermore, we demonstrate that in FGF-23 null/1α-Luc mice, CYP27B1 promoter activity and mRNA abundance are increased in several extra-renal sites. In the heart of FGF-23 null/1α-Luc mice, CYP27B1 promoter activity and mRNA were 2- and 5-fold higher, respectively, than in control mice. We also observed a 3- to 10-fold increase in CYP27B1 mRNA abundance in the lung, spleen, aorta and testis of FGF-23 null/1α-Luc mice. Thus, we have identified novel extra-renal target sites for FGF-23-mediated regulation of CYP27B1.

In this paper, we explore the understudied phenomenon of “low-frequency” heroin injection in a sample of street-recruited heroin injectors not in drug treatment. We conducted a cross-sectional study of 2,410 active injection drug users (IDUs) recruited in San Francisco, California from 2000 to 2005. We compare the sociodemographic characteristics and injection risk behaviors of low-frequency heroin injectors (low-FHI; one to 10 self-reported heroin injections in the past 30 days) to high-frequency heroin injectors (high-FHI; 30 or more self-reported heroin injections in the past 30 days). Fifteen percent of the sample met criteria for low-FHI. African American race, men who have sex with men (MSM) behavior, and injection and noninjection methamphetamine use were independently associated with low-FHI. Compared to high-FHI, low-FHI were less likely to report syringe sharing and nonfatal heroin overdose. A small but significant proportion of heroin injectors inject heroin 10 or less times per month. Additional research is needed to qualitatively examine low-frequency heroin injection and its relationship to drug use trajectories.

We interviewed 265 cocaine-experienced methadone patients about situations that occasioned their cocaine use and strategies they used to avoid cocaine use. Subjects identified an average of 15 situations that occasioned cocaine use. The three most frequently identified were having the drug present (86% of subjects), being offered the drug (85%) and having money available (83%). Subjects reporting fewer situations also reported longer periods of lifetime abstinence (p < 0.01). A principal components analysis extracted 10 groups of situations that were most frequently identified in combination. Subjects identified a median of seven strategies for avoiding cocaine use ; however, there was large inter-subject variability. This variance was not accounted for by demographic variables, employment status or treatment experience. The three strategies identified most frequently were avoiding people and places (81%), thinking about what they could lose (76%) and leaving the situation (66%). The total number and type (reactive vs. proactive) of strategies identified by subjects had no relationship to cocaine abstinence, although four specific strategies (thinking about what could be lost, leaving the situation, moving to a new area and using a different drug) were positively correlated with cocaine abstinence. We discuss implications of these results for clinical practice.

We applied the stages-of-change model of Prochaska and DiClemente to the problem of drug use among methadone maintenance patients to examine correlates of different stages of treatment readiness. The 276 subjects were divided into stage categories based on self-reported drug use and questionnaire responses regarding plans to discontinue unauthorized drug use in the future. Confirmatory factor analytic procedures validated four process scales derived from a 60-item questionnaire. Each stage was characterized by a profile of change-process scores largely consistent with predictions, though these scores did not distinguish stages as clearly as has been reported in previous research. Analysis of subject characteristics revealed that those in the Precontemplation stage reported significantly longer treatment tenures than subjects in any other stage besides Maintenance.

Methadone client volunteers completed the Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1967) and MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) on consecutive days. MMPI2 T-scores were lower by a mean of 4.7 on the clinical scales; when 5 points were added to MMPI-2 T-scores the mean difference was 2.3. Rank order of subjects on scale T-scores was not significantly different between the two instruments. High-point similarity for clinically elevated profile pairs ranged from 61% to 92%, depending upon definition of similarity.

Substance use is high among gay and bisexual men attending weekend dance events, yet little research has investigated motivations for drug use and contextual factors influencing use in these settings. We hypothesized that beliefs about peer drug use interact with individuals’ own drug use intentions to predict use. 489 men attending weekend dance events completed an anonymous assessment asking about their own and their beliefs about other attendants’ drug use intentions – 47% completed a follow-up assessment after the event. Forty-four percent reported intending to use ecstasy at the event; intentions to use GHB, marijuana, cocaine, unprescribed Erectile Dysfunction Drugs (EDDs), and poppers were also high. Perceptions about other attendant’s drug use predicted use among those intending and those not intending to use drugs. Normative beliefs are important predictors of drug use at weekend dance events; event-specific prevention strategies should encompass messages that correct misperceptions of drug use among party attendants.

The argument for universal alcohol screening in primary care is based on the assumption that most heavy drinkers routinely visit a doctor. This study examines whether drinking status is associated with higher or lower odds of visiting a doctor in the past year among California adults. As a point of comparison, the study also examines whether drinking status is associated with the odds of visiting an emergency room. Data came from the 2007 California Health Interview Survey. Multivariate logistic regression was used to examine the odds of visiting a doctor and an emergency room for abstainers, moderate drinkers, monthly binge drinkers, and weekly binge drinkers. After controlling for demographics, health coverage, and health status, binge drinkers had the same odds of visiting a doctor and the emergency room as moderate drinkers. Among binge drinkers, female gender, health coverage, and high blood pressure were associated with visiting a primary care doctor.

This study examined substance use (intended and actual), unprotected sex, and HIV disclosure practices (disclosure and questioning) among HIV-positive men who have sex with men (MSM) at two party-oriented vacations, where substance use and sexual risk may be heightened.A random sample of 489 MSM attending one of two party-oriented vacations participated in PartyIntents, a short-term longitudinal survey. Nearly half (47%) completed a follow-up assessment at the event or online for up to 2 weeks after the event. We examined rates of baseline intentions to use substances, actual substance use, and unprotected intercourse among HIV-positive men in attendance.Rates among HIV-negative men were estimated for comparison. Multiple logistic regression was used to assess the impact of illegal drug use and HIV status on unprotected anal intercourse (UAI).HIV-positive attendees (17%) were significantly more likely than HIV-negative attendees to use nitrite inhalants (or "poppers") (24.3% vs. 10.7%). HIV-positive attendees were also significantly more likely to have insertive UAI (64.3% vs. 34.1%) and receptive UAI (68.8% vs. 22.2%). Multivariate models showed associations between HIV status and illegal drug use with UAI (for HIV status, odds ratio [OR] = 4.5, p = .001; for any illegal drug use, OR = 16.4, p.001). There was no evidence that the influence of drug use moderated risk by HIV status. Rates of HIV disclosure and questioning did not differ by HIV status.HIV-positive men attending these events engaged in higher rates of illegal drug use and sexual risk than HIV-negative men. Prevention campaigns targeting MSM at high-risk events should include messages geared toward HIV-positive men.

Objective To examine the impact of sexuality education practices on adolescent birthrates while controlling for demographic characteristics and religious/political factors at a state level. Design Prospective cohort study. Setting Twenty-four states, from 1997 through 2005. Participants Girls aged 15 to 17 years. Main Exposure The state sexuality education practices (ie, sexually transmitted disease prevention, pregnancy prevention, condom efficacy) for 1996 through 2004 from the Centers for Disease Control and Prevention School Health Profiles Survey. Main Outcome Measures State birthrates for girls aged 15 to 17 years for 1997 through 2005 from the Centers for Disease Control and Prevention. Results In a longitudinal, unadjusted model, our findings provide evidence that increased sexuality education within school curricula is associated with lower adolescent birthrates (average sexuality education topics β = −0.61; P = .001). However, the effect of sexuality education disappeared when taking into consideration the demographic characteristics, religiosity, and abortion policies of the state (average sexuality education topics β = −0.12; P = .26). States with higher religiosity rankings and greater political conservatism had higher adolescent birthrates. Conclusions The effects of sexuality education were constrained by state characteristics and do not independently explain the considerable variations in adolescent birthrates found across states. Our findings underscore the strong influence of state characteristics on adolescent birthrates above and beyond sexuality education, which must be considered when evaluating the efficacy of sexuality education programs.

The Beck Hopelessness Scale (BHS) was administered to 2379 intravenous drug users who were not in treatment, unaware of their human-immunodeficiency-virus (HIV) status and seeking HIV testing and counselling. Three BHS principal components were identified reflecting resignation to the futility of changing the future, rejection of the possibility of a hopeful future, and acceptance of the inevitability of a hopeless future. The principal component scores representing these three dimensions were positively related to self-reported depression and suicidal ideation; the rejection scores were positively correlated with confirmed HIV seropositivity.

We examined the effect of women's perceptions of sexual partner risks on condom use. Women from three US cities (n = 1,967) were recruited to provide data on HIV risks. In univariate models, increased odds of condom use were associated with perceiving that partners had concurrent partners and being unaware of partners': (a) HIV status, (b) bisexuality, (c) concurrency; and/or (d) injection drug use. In multivariate models, neither being unaware of the four partner risk factors nor perceiving a partner as being high risk was associated with condom use. Contextual factors associated with decreased odds of condom use were having sex with a main partner, homelessness in the past year, alcohol use during sex, and crack use in the past 30 days. Awareness of a partner's risks may not be sufficient for increasing condom use. Contextual factors, sex with a main partner in particular, decrease condom use despite awareness of partner risk factors.

In this article, we present the first report on the antibacterial activity and cytotoxicity of poly(amidoamine) (PAMAM) dendrimers immobilized on three types of titanium-based substrates with and without calcium phosphate coating. We show that the amino-terminated PAMAM dendrimers modified with various percentages (0–60%) of poly(ethylene glycol) (PEG) strongly adsorbed on the titanium-based substrates. The resultant dendrimer films effectively inhibited the colonization of the Gram-negative bacteria Pseudomonas aeruginosa (strain PAO1) and, to a lesser extent, the Gram-positive bacteria Staphylococcus aureus (SA). The antibacterial activity of the films was maintained even after storage of the samples in PBS for up to 30 days. In addition, the dendrimer films had a low cytotoxicity to human bone mesenchymal stem cells (hMSCs) and did not alter the osteoblast gene expression promoted by the calcium phosphate coating.

As the number of men and women entering treatment for substance use disorders continues to increase across the country, it becomes vitally important to understand their quality of life (QOL) or perceived health status, in order to inform treatment efforts for improving such outcomes. To date, QOL assessments among methamphetamine (MA) dependent users are limited. This paper examines QOL health status among a sample of 838 treatment seeking MA users at admission. Using regression analysis, predictors of QOL are examined among MA users. Predictors of poor QOL among MA users at treatment admission included being female, white, high school educated or more, married, experiencing psychosocial dysfunction (lifetime trauma, suicide, social conflict), reporting a high frequency of both MA and polydrugs for 15 days or more in the past month, chronicity of MA and polydrug use, injection use, and having co-morbid medical and psychiatric impairment. Employment status was the only factor related to better health status perceptions. This study expands the scope of scholarly examination of MA-dependent users entering treatment, as there has not been a development of coherent profiles of QOL among representative samples of clinical MA-abusing populations to date.

This report describes successful angioplasty of a total coronary occlusion in a single-ostium coronary anomaly in a patient presenting with an acute myocar dial infarction.