Prevalence and severity of abscesses and cellulitis, and their associations with other health outcomes, in a community-based study of people who inject drugs in London, UK.

BACKGROUND: Skin and soft tissue infections (SSTI) are a common but preventable cause of morbidity and mortality among people who inject drugs (PWID). They can be severe, and hospitalisations of PWID with SSTI are rising. The most common SSTI presentations are abscesses and cellulitis. METHODS: We used data from Care & Prevent, a cross-sectional community survey of PWID in London. We reported the lifetime prevalence of SSTI, severity of infections, key risk factors, and associated sequelae. Pictorial questions were used to assess SSTI severity. RESULTS: We recruited 455 PWID. SSTI lifetime prevalence was high: 64% reported an abscess and/or cellulitis. Over one-third (37%) reported a severe infection, 137 (47%) reported hospitalisation. SSTIrisk factors were: aged 35+ years, injecting once or more times a day, subcutaneous or intra-muscular injections, and making four or more attempts to achieve an injection. Those who reported having other health conditions were at higher odds of having an abscess or cellulitis, with risk tending to increase with number of reported conditions. Half (46%) employed self-care for their worst SSTI, and 43% waited for ten or more days before seeking medical care or not seeking medical care at all. CONCLUSIONS: Abscess and cellulitis are very common among PWID in London. We corroborate findings indicating SSTIs are associated with risks, e.g. venous access problems, as well as other co-morbid conditions: septicaemia, endocarditis, DVT, and kidney disease. These co-morbidities may impact SSTIs severity and outcomes. Delayed healthcare seeking potentially exacerbates infection severity, which in turn increases poorer health outcomes and complications.

Lung function in men with and without HIV.

OBJECTIVES: Initial studies suggest HIV-positive persons may be at increased risk for chronic lung diseases such as chronic obstructive pulmonary disease, but have commonly relied on single-center designs, lacked HIV-negative controls, or assessed lung function with only spirometry. We tested differences in spirometry and single-breath diffusing capacity for carbon monoxide (DLCO) in persons with and without HIV. DESIGN: Cross-sectional, observational study. METHODS: Participants were enrolled from the Multicenter AIDS Cohort Study, a longitudinal cohort study of men who have sex with men (both HIV-positive and HIV-negative) at four sites in the United States. Standardized spirometry and DLCO testing were performed in all eligible, consenting participants at routine study visits. We tested associations between HIV status and spirometry and DLCO results, using linear and logistic regression. RESULTS: Among 1067 men, median age was 57 years, prevalence of current marijuana (30%), and cigarette (24%) use was high, and another 45% were former cigarette smokers. Median forced expiratory volume in 1 s was 97% of predicted normal and DLCO was 85% of predicted normal. HIV-positive persons demonstrated no statistical difference in forced expiratory volume in 1 s compared with HIV-negative persons, but had worse DLCO (adjusted difference -2.6% of predicted; 95% confidence interval: -4.7 to -0.6%) and a higher risk of DLCO impairment (odds ratio for DLCO < 60% of predicted 2.97; 95% confidence interval: 1.36-6.47). Lower DLCO was associated with lower nadir CD4 cell counts. CONCLUSION: HIV-positive men are at increased risk of abnormal gas exchange, indicated by low DLCO, compared with men without HIV.

A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine ("ice") dependence.

BACKGROUND: There are currently no approved pharmacotherapies for managing methamphetamine dependence. N-acetylcysteine (NAC) has been found to reduce the craving for methamphetamine and other drugs, but its effect on methamphetamine use and other clinically related endpoints are uncertain. The N-ICE trial is evaluating the safety and efficacy of NAC as a take-home pharmacotherapy for methamphetamine dependence. METHODS/DESIGN: This is a two-arm parallel double-blind placebo-controlled three-site randomised trial (ratio 1:1) using permuted block randomisation, with variable block sizes. It is stratified by site, sex and whether the methamphetamine is injected or not. Participants (N = 180; 60 per site) need to be dependent on methamphetamine, interested in reducing their methamphetamine use and not currently receiving treatment for substance use disorders. The trial is being conducted in outpatient settings in Melbourne, Geelong and Wollongong, Australia. Participants will receive either 2400 mg oral NAC or a matched placebo, delivered as a take-home medication for 12 weeks. Two 600 mg capsules are self-administered in the morning and two more in the evening. Adherence is being monitored using eCAP™ medication bottle lids, which record the date and time of each occasion the bottle is opened. The primary outcome is methamphetamine use during the 12-week trial medication period, measured as (a) days of use, assessed using the timeline followback, and (b) methamphetamine-positive saliva tests, taken weekly. Secondary measures include weekly assessment of methamphetamine craving, severity of methamphetamine dependence, methamphetamine withdrawal symptoms and psychiatric symptoms (depression, suicidality, psychotic symptoms and hostility). Adverse events are monitored at each weekly assessment. Tolerability is assessed using the Treatment Satisfaction Questionnaire for Medication. DISCUSSION: The N-ICE trial is the first clinical trial to assess whether NAC can reduce methamphetamine use. This trial will improve our understanding of the potential utility of NAC in managing methamphetamine dependence and clinically related outcomes. If found to be effective, take-home NAC could be a potentially scalable and affordable pharmacotherapy option for treating methamphetamine dependence. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618000366257 . Registered on 29 May 2018.

Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist.

Receptor-type protein tyrosine phosphatase D (PTPRD) is a neuronal cell-adhesion molecule/synaptic specifier that has been implicated in addiction vulnerability and stimulant reward by human genomewide association and mouse cocaine-conditioned place-preference data. However, there have been no reports of effects of reduced expression on cocaine self-administration. There have been no reports of PTPRD targeting by any small molecule. There are no data about behavioral effects of any PTPRD ligand. We now report (i) robust effects of heterozygous PTPRD KO on cocaine self-administration (These data substantially extend prior conditioned place-preference data and add to the rationale for PTPRD as a target for addiction therapeutics.); (ii) identification of 7-butoxy illudalic acid analog (7-BIA) as a small molecule that targets PTPRD and inhibits its phosphatase with some specificity; (iii) lack of toxicity when 7-BIA is administered to mice acutely or with repeated dosing; (iv) reduced cocaine-conditioned place preference when 7-BIA is administered before conditioning sessions; and (v) reductions in well-established cocaine self-administration when 7-BIA is administered before a session (in WT, not PTPRD heterozygous KOs). These results add to support for PTPRD as a target for medications to combat cocaine use disorders. 7-BIA provides a lead compound for addiction therapeutics.

Wearable Biosensors to Detect Physiologic Change During Opioid Use.

INTRODUCTION: Opioid analgesic use is a major cause of morbidity and mortality in the US, yet effective treatment programs have a limited ability to detect relapse. The utility of current drug detection methods is often restricted due to their retrospective and subjective nature. Wearable biosensors have the potential to improve detection of relapse by providing objective, real time physiologic data on opioid use that can be used by treating clinicians to augment behavioral interventions. METHODS: Thirty emergency department (ED) patients who were prescribed intravenous opioid medication for acute pain were recruited to wear a wristband biosensor. The biosensor measured electrodermal activity, skin temperature and locomotion data, which was recorded before and after intravenous opioid administration. Hilbert transform analyses combined with paired t-tests were used to compare the biosensor data A) within subjects, before and after administration of opioids; B) between subjects, based on hand dominance, gender, and opioid use history. RESULTS: Within subjects, a significant decrease in locomotion and increase in skin temperature were consistently detected by the biosensors after opioid administration. A significant change in electrodermal activity was not consistently detected. Between subjects, biometric changes varied with level of opioid use history (heavy vs. nonheavy users), but did not vary with gender or type of opioid. Specifically, heavy users demonstrated a greater decrease in short amplitude movements (i.e. fidgeting movements) compared to non-heavy users. CONCLUSION: A wearable biosensor showed a consistent physiologic pattern after ED opioid administration and differences between patterns of heavy and non-heavy opioid users were noted. Potential applications of biosensors to drug addiction treatment and pain management should be studied further.

Infective endocarditis in intravenous drug users: a review article.

Approximately 10% of infective endocarditis (IE) involves the right side of the heart with the majority of these cases occurring in intravenous drug users. Patients are less likely to present with classical IE signs of a new murmur and peripheral stigmata, are more frequently immunocompromised and often have significant social difficulties. These factors result in both diagnostic and therapeutic challenges in this patient group that are not often seen in other patient populations with IE.

The role of depression chronicity and recurrence on neurocognitive dysfunctions in HIV-infected adults.

Research assessing whether major depressive disorders (MDD) impacts neurocognitive functions in HIV+ persons has yielded inconsistent results. However, none have considered the role of MDD remission, chronicity, and stability on treatment. Ninety-five HIV+ adults clinically stable on combined antiretroviral treatment completed a psychiatric interview, a depression scale, a neuropsychological, daily living, and cognitive complaints assessments at baseline and 18 months. Participants were screened for current (within 12 months of study entry) alcohol and/or substance use disorder. History of alcohol and/or substance abuse disorder prior to the 12 months entry screen and MDD treatments were recorded. Participants were grouped into two psychiatric nomenclatures: (1) lifetime: no MD episode (MDE), single MDE life-event treated and fully remitted, chronic MDD treated and stable, chronic MDD treated and unstable, and baseline untreated MDE; (2) recent: last 2 years MDE (yes or no). We found that lifetime and recent psychiatric history were more strongly associated with decreased in independence in daily living and cognitive complaints than with baseline neuropsychological performance. However, lack of full remission, instability on treatment in chronic MDD, and severity of symptoms in current MDE were factors in whether MDD impacted baseline neuropsychological performance. Depressive symptoms improved at follow-up in those with baseline moderate-severe symptoms, and MDD was not associated with neurocognitive change at 18 months. A history of alcohol and/or substance abuse disorder was significantly more frequent in those with treated and unstable chronic MDD but it was not associated with neuropsychological performance. MDD recurrence, chronicity profiles, and associated comorbidities are keys factors to understand any potential impact on neurocognitive abilities in HIV infection. More comprehensive consideration of these complex effects could serve at constructively updating the HAND diagnostic criteria.

Stroke in HIV-infected African Americans: a retrospective cohort study.

The risk of having a first stroke is nearly twice as high among African Americans compared to Caucasians. HIV/AIDS is an independent risk factor for stroke. Our study aimed to report the risk factors and short-term clinical outcomes of African Americans with HIV infection and new-onset stroke admitted at the Johns Hopkins Hospitals (2000-2012). Multivariate linear regression was used to examine the association between potential predictors and odds of an unfavorable outcome, defined as a higher modified Rankin Scale (mRS) score on hospital discharge. African Americans comprised 105/125 (84%) of HIV-infected new-onset stroke inpatients (median age 50 years; 69% men; median CD4 140/mL; ischemic 77%; 39% taking highly active antiretroviral therapy). Vascular risk factors were common: hypertension (67%), cigarette smoking (66%), dyslipidemia (42%), hepatitis C (48%), intravenous drug abuse (32%), and prior myocardial infarction (29%). Prior aspirin and statin use were uncommon (18%, 9%). Unfavorable outcome (mRS score 4-6, n = 22 of 90 available records) was noted in 24% of patients, including seven in-hospital deaths. On multivariate analyses, higher CD4 count on hospital admission was associated with a lower mRS (-0.2 mRS points per 1 unit increase in CD4, 95% CI (-0.3, 0), p = 0.03). Intracerebral hemorrhage was also associated with a lower mRS (1.0 points lower, 95% CI (0.2, 1.8) compared to ischemic stroke, p = 0.01) after adjustment for other potential predictors. This underscores the importance of HIV infection on functional stroke outcomes beyond its recognized influence on stroke risk.

LIVER FIBROSIS IN COMBINED COURSE OF CHRONIC HEPATITIS C AND HIV INFECTION.

The urgency of the problem connected with HIV infection and parenteral forms of viral hepatitis largely stems from common epidemiological, social and economic indices. HIV infection accelerates progression of liver disease associated with HCV infection, especially in patients with more severe immunodeficiency. The aim of the study was to compare results of liver elastometry in patients co-infected with HIV/CHC and those monoinfected with CHC. Verification of the diagnosis was carried out on the basis of clinical-anamnestic data, by taking into account the epidemiological history of patients and confirming the results of enzyme immunoassay with the definition of markers of hepatitis C in paired sera and polymerase chain reaction with the detection of RNA virus in blood plasma. The degree of liver fibrosis was measured on a scale of METAVIR by means of FibroScan apparatus. The article presents the results of the comparative assessment of liver fibrosis in patients co-infected with HIV/CHC and those monoinfected with CHC. It suggests that patients co-infected with HIV/CHC are at a higher risk of severe fibrosis and cirrhosis.

The selective dopamine D3 receptor antagonist, SR 21502, reduces cue-induced reinstatement of heroin seeking and heroin conditioned place preference in rats.

BACKGROUND: Because the role of dopamine (DA) D3 receptors has been investigated primarily in relation to cocaine-related behaviors little is known of the role of these receptors in heroin seeking. PURPOSES: To investigate the effect of the selective DA D3 receptor antagonist, SR 21502, on cue-induced reinstatement of heroin seeking and heroin conditioned place preference (CPP). METHODS: In experiment 1, rats were trained to self-administer intravenous heroin for 15 days followed by extinction. Following extinction animals were treated with one of several SR 21502 doses (0, 7.5, 10 or 15mg/kg) and a cue-induced reinstatement test was conducted. In experiment 2, animals were conditioned to experience heroin in one compartment of a CPP apparatus and saline in the other. On the test day animals were treated with 0, 3.75, 7.5, 10 or 15mg/kg of SR 21502 and tested for their CPP. RESULTS: The results from experiment 1 showed a significant dose-related reduction in cue-induced reinstatement of active lever pressing in the 7.5 and 10mg groups and an absence of the reinstatement effect in the 15mg group. In experiment 2, animals treated with vehicle or 3.75mg of SR 21502 showed significant heroin place preferences but those treated with the higher doses showed no CPP. CONCLUSIONS: Our findings suggest that DA D3 receptors play a significant role in heroin approach behaviors driven by conditioned stimuli. As such, we propose that SR 21502 holds potential as an effective pharmacotherapeutic agent for relapse prevention and should be studied further.

COMPARATIVE ANALYSIS OF COMBINED COURSE OF CHRONIC HEPATITIS C AND HIV DEPENDING ON THE ROUTE OF INFECTION.

At present, an infection caused by the hepatitis C virus is common among HIV-infected patients. The rapid growth of drug addiction, sexual route of infection transmission, HIV and HCV infection among young people, low efficiency of treatment and lack of specific means of prevention clearly means that this pathology is to be listed among the first in the modern infectology. The aim of the study was to investigate the characteristics of the course of chronic hepatitis C in HIV-infected patients, depending on the route of infection. Study design was open, non-randomized and prospective. A total of 58 HIV-infected patients with chronic hepatitis C registered in the dispensary at Karaganda Regional Center for Prevention and Control of AIDS were examined. The diagnosis of HIV infection was verified by immune blotting. Etiological hepatitis verification was performed by means of enzyme immunoassay and polymerase chain reaction. We present the clinical and laboratory results of HIV-infected patients with chronic hepatitis C, depending on the route of infection. Patients with the sexually transmitted infection experienced asymptomatic course of the disease. In comparison, injecting drug users showed greater clinical symptomatology and a moderate level of activity of the infectious process. These clinical and laboratory findings suggest that the characteristics of the course of chronic hepatitis C in HIV-infected patients depends on the route of infection.

Oral health-related quality of life among an Australian sample of people who inject drugs.

OBJECTIVES: People who inject drugs (PWID) have poor oral health. However, their oral health-related quality of life (OHRQoL) is unknown. Our study was designed to measure the OHRQoL of PWID. METHODS: The Oral Health Impact Profile-14 (OHIP-14) was administered to 794 PWID recruited in Australian capital cities as part of the 2013 Illicit Drug Reporting System (IDRS). Three OHIP-14 summary indicators were examined: "Prevalence" (proportion reporting ≥1 item at least "fairly often"), "severity" (mean total OHIP-14 score), and "extent" (number of impacts reported at least "fairly often"). Associations between "prevalence" and "extent" and variables drawn from the health, drug use, and social domains were investigated. RESULTS: All OHIP-14 summary indicators among IDRS participants were significantly higher than in the general Australian population. In multivariate analysis, the "prevalence" indicator was significantly and positively associated with female gender [adjusted odds ratio (AOR) = 1.75, 95% CI 1.27-2.38], those born in Australia (AOR = 2, 95% CI 1.25-3.23), not completing Year 10 compared with those who had completed Year 12 or a higher qualification (AOR = 1.59, 95% CI 1.03-2.44), and methadone treatment (AOR = 1.61, 95% CI 1.14-2.29). The "extent" indicator was significantly and positively associated with female gender [adjusted incidence rate ratio (AIRR) = 1.56, 95% CI 1.19-2.08], unemployment (AIRR = 1.59, 95% CI 1.01-2.44), and having an injecting career of 10-20 years (AIRR = 1.76, 95% CI 1.03-3.01). CONCLUSIONS: PWID have poorer OHRQoL than the Australian general population. Poor OHRQoL was particularly common in female PWID and those with longer injecting careers. Interventions to improve the oral health of PWID may improve their OHRQoL.

Factors related to HIV-associated neurocognitive impairment differ with age.

Over 50% of HIV-infected (HIV+) persons are expected to be over age 50 by 2015. The pathogenic effects of HIV, particularly in cases of long-term infection, may intersect with those of age-related illnesses and prolonged exposure to combined antiretroviral therapy (cART). One potential outcome is an increased prevalence of neurocognitive impairment in older HIV+ individuals, as well as an altered presentation of HIV-associated neurocognitive disorders (HANDs). In this study, we employed stepwise regression to examine 24 features sometimes associated with HAND in 40 older (55-73 years of age) and 30 younger (32-50 years of age) HIV+, cART-treated participants without significant central nervous system confounds. The features most effective in generating a true assessment of the likelihood of HAND diagnosis differed between older and younger cohorts, with the younger cohort containing features associated with drug abuse that were correlated to HAND and the older cohort containing features that were associated with lipid disorders mildly associated with HAND. As the HIV-infected population grows and the demographics of the epidemic change, it is increasingly important to re-evaluate features associated with neurocognitive impairment. Here, we have identified features, routinely collected in primary care settings, that provide more accurate diagnostic value than a neurocognitive screening measure among younger and older HIV individuals.

Surgical treatment of infective endocarditis in active intravenous drug users: a justified procedure?

BACKGROUND: Infective endocarditis is a life threatening complication of intravenous drug abuse, which continues to be a major burden with inadequately characterised long-term outcomes. We reviewed our institutional experience of surgical treatment of infective endocarditis in active intravenous drug abusers with the aim of identifying the determinants long-term outcome of this distinct subgroup of infective endocarditis patients. METHODS: A total of 451 patients underwent surgery for infective endocarditis between January 1993 and July 2013 at the University Hospital of Heidelberg. Of these patients, 20 (7 female, mean age 35 ± 7.7 years) underwent surgery for infective endocarditis with a history of active intravenous drug abuse. Mean follow-up was 2504 ± 1842 days. RESULTS: Staphylococcus aureus was the most common pathogen detected in preoperative blood cultures. Two patients (10%) died before postoperative day 30. Survival at 1, 5 and 10 years was 90%, 85% and 85%, respectively. Freedom from reoperation was 100%. Higher NYHA functional class, higher EuroSCORE II, HIV infection, longer operating time, postoperative fever and higher requirement for red blood cell transfusion were associated with 90-day mortality. CONCLUSIONS: In active intravenous drug abusers, surgical treatment for infective endocarditis should be performed as extensively as possible and be followed by an aggressive postoperative antibiotic therapy to avoid high mortality. Early surgical intervention is advisable in patients with precipitous cardiac deterioration and under conditions of staphylococcal endocarditis. However, larger studies are necessary to confirm our preliminary results.