Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Anabolic Androgenic Steroids Misuse In The City Of São Paulo: A Qualitative Study [o Uso Indevido De Anabolizantes Na Cidade De São Paulo: Um Estudo Qualitativo]

Objective: To investigate the reasons, implications and patterns of anabolic androgenic steroid (AAS) use in 40 non-athletic youths, in the city of São Paulo. Methods: A qualitative study was conducted with intentional sampling and based on criteria obtained by the snowball technique and from in-depth interviews with 40 users/ex-users of AAS, utilizing a semi-structured questionnaire based on key-word information. The size of the sample was determined by the theoretical saturation of information. Results: Men and youths are the principal users of AAS, who utilize them at doses much higher than therapeutic doses and also combine various AAS (stacking). AAS are utilized during determined periods of time (cycles), starting with low doses which are gradually increased (pyramid). An "inadequate body" is usually the reason cited for the use of MS. The most frequently reported side effects are aggressivity, hepatic problems, gynecomastia, cardiovascular complaints, dermatologic effects, sexual problems, lowered immunity, masculinizing effects in women and dependence. Discussion: The difficulty of social/affective relationships due to an inadequate body is the alleged motive for the use of AAS. A poor understanding of the effects of AAS, along with the distorted view these youths have of their body, propels them to utilize AAS indefinitely. Conclusions: The use of high doses of AAS and of mixtures of various AAS in an attempt to improve appearance results in exposure to the side effects of these drugs. Disinformation, an unattainable body image, low self-esteem, the search for admiration of their body, makes these youths chronic users of AAS. The illegality of their sale and the adverse effects of AAS do not impede youths from using them, indicating that more precise information on these drugs needs to be accessible, as long as the stereotype of the muscular man should not be promoted by the media.5212534Alen, M., Reinila, M., Vihko, R., Response of serum hormones to androgen administration in power athletes (1985) Med Sci Sports Exerc, 17, pp. 354-359Council report. Medical and nonmedical use of anabolic-androgenic steroids (1990) JAMA, 264 (22), pp. 2923-2927Biernack, P., Waldorf, D., Snowball sampling-problems and techniques of chain referral sampling (1981) Sociological Methods and Research, 10, pp. 141-163Brower, K.J., Blow, F.C., Beresford, T.P., Fuelling, C., Anabolic steroid dependence (1989) J Clin Psychiat, 50 (1), pp. 31-33Brower, K.J., Blow, F.C., Young, J.P., Hill, E.M., Symptons and correlates of anabolic-androgenic dependence (1991) Br J Addict, 86, pp. 759-768Buckley, W.E., Yesalis, C.E., Friedl, K.E., Anderson, W.A., Streit, A.L., Wright, J.E., Estimated prevalence of anabolic steroid use among male high school seniors (1988) JAMA, 260 (23), pp. 3441-3445Cohen, J.C., Noakes, T.D., Benade, A.J., Hypercholesterolemia in male power lifters using anabolic-androgenic steroids (1988) Psy Sports Med, 16, pp. 49-56Corcoran, J.P., Longo, E.D., Psychologycal treatment of anabolic steroid-dependent individuals (1992) J Subst Abuse Treat, 29 (3), pp. 229-235Creswell, J.W., (1998) Qualitative Inquiry and Research Design: Choosing among Five Traditions, , USA: SAGE PublicationsDaigle, R.D., Anabolic steroids (1990) J Psychoative Drugs, 22, pp. 77-80Diaz, A., Barruti, M., Doncel, C., (1992) The Lines of Success? A Study on the Nature and Extent of Cocaine Use in Barcelona, , Barcelona: Laboratorio de Sociología ICESBDygment, P.G., The adolescent athlete and ergogenic aids (1987) J Adolesc Health Care, 8, pp. 68-73Friedl, K.E., Yesalis, C.E., Self-treatment of gynecomastia in body-builders who use anabolic steroids (1989) Psy Sports Med, 17, pp. 67-79Goldberg, L., Bents, R., Bosworth, E., Trevisan, L., Elliot, D.L., Anabolic steroid education and adolescents: Do scare tatics work? (1991) Pediatrics, 87 (3), pp. 283-286Grossman, C.J., Interations between the gonadal steroids and the immune system (1985) Science, 227, pp. 257-261Hurley, B.F., High-density-lipoprotein cholesterol in body-builders vs. powerlifters-negative effects of androgen use (1984) JAMA, 252, pp. 507-513Johansson, P., Halberg, M., Kindlundh, A., Nyberg, The effect on opioid peptides in the rat brain, after chronic treatment with anabolic androgenic steroid, nandrolone decanoate (2000) Brain Res Bull, 51, pp. 413-418Johnson, M.D., Anabolic steroid use in adolescent athletes (1990) Pediatr Clin North Am, 37 (5), pp. 1111-1123Karch, S.B., (1993) The Patology of Drug Abuse, , USA: CRC PressKomoroski, E.M., Rickert, V.I., Adolescent body image and attitudes to anabolic steroid use (1992) Am J Dis Child, 146, pp. 823-828Kopera, H., The history of anabolic steroid and review of clinical experience with anabolic steroids (1985) Acta Endocrinol, 271, pp. 11-18Korkia, P., Stimson, G.V., (1993) Anabolic Steroid Use in Great Britain (an Exploratory Investigation), p. 4. , The Centre (For Research on Drugs and Health Behaviour)Lamb, D.R., Anabolic steroids in athletics: How well do they work and how dangerous are they? (1994) Amer J Sports Med, 12, pp. 31-37Landry, G.L., Primos, W.A., Anabolic steroid abuse (1990) Adv Pediatr, 37, pp. 185-205Levandowski, R., McIerney, V.K., Scott, D.I., Anabolic steroids: Performance enhancers? (1991) N J Med, 88, pp. 663-664Lukas, S.E., CNS effects and abuse liability of anabolic-androgenic steroids (1996) Ann Rev Pharmacol Toxicol, 36, pp. 333-357Minayo, M.C.S., (1993) O Desafio do Conhecimento: Pesquisa Qualitativa em Saúde, , São Paulo: Hucitec-AbrascoMurad, F., Haynes, R.C., (1996) The Pharmacological Basis of Therapeutics, 7th Ed., , Goodman LS, Guilman A, Rall TW et al., editors. New York: MacMillan Publishing Co(1997) NIDA Notes. Research Advances, p. 12Patton, M.Q., (1990) Qualitative Evaluation and Research Methods, , London: Sage PublicationsPorcerelli, J.H., Sandler, B.A., Narcissism and Empathy in Steroid Users (1995) Am J Psychiatry, 152, pp. 1672-1674Pope, H., Kouri, E.M., Hudson, J.I., Effects of supraphysiological doses of testosterone on mood and agression in normal men (2000) Arch Gen Psychiatry, 57, pp. 133-140Pope, H.G., Phillips, K.A., Olivardia, R., (2000) The Adonis Complex (The Secret Crisis of Male Body Obsession), , New York: The Free PressSiegel, R.K., New patterns of cocaine use: Changing doses and routes (1985) Cocaine Use in America: Epidemiologic and Clinical Perspective, , Kozel N, Adams EH, editors. Rockville: NIDA - USASpano, F., Ryan, W.G., Tamoxifen for gynecomastia induced by anabolic steroids? (1984) N Engl J Med, 311, pp. 861-862Strauss, R.H., Liggett, M.T., Lanese, R.R., Anabolic steroid use and abuse and perceived effects in to weight-trained women athletes (1985) JAMA, 253, pp. 2871-2873(1994) Qualitative Research for Health Programmes, , Geneva: WHO - Division of Mental HealthWhyte, W.F., (1943) Street Corner Society, , Chicago: University of Chicago PressWilson, J.D., Androgen abuse by athletes (1988) Endocrinol Rev, 9, pp. 181-199Wilson, J.D., Aiman, J., Mac Donald, P.C., The patogenesis of gynecomastia (1980) Adv in Intern Med, 25, pp. 1-32Wilson, J.D., Griffin, J.E., The use and misuse of androgens (1980) Metabolism, 29, pp. 1278-129

Current Perspectives on the Clinical Research and Medicalization of Psychedelic Drugs for Addiction Treatments: Safety, Efficacy, Limitations and Challenges

Mental health disorders and substance use disorders (SUDs) in particular, contribute greatly to the global burden of disease. Psychedelics, including entactogens and dissociative substances, are currently being explored for the treatment of SUDs, yet with less empirical clinical evidence than for other mental health disorders, such as depression or post-traumatic stress disorder (PTSD). In this narrative review, we discuss the current clinical research evidence, therapeutic potential and safety of psilocybin, lysergic acid diethylamide (LSD), ketamine, 3,4-methylenedioxymethamphetamine (MDMA) and ibogaine, particularly in the context of the SUD treatment. Our aim was to provide a balanced overview of the current research and findings on potential benefits and harms of psychedelics in clinical settings for SUD treatment. We highlight the need for more clinical research in this particular treatment area and point out some limitations and challenges to be addressed in future research

Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence

The brain adapts to chronic ethanol intoxication by altering synaptic and ion-channel function to increase excitability, a homeostatic counterbalance to inhibition by alcohol. Delirium tremens occurs when those adaptations are unmasked during withdrawal, but little is known about whether the primate brain returns to normal with repeated bouts of ethanol abuse and abstinence. Here, we show a form of bidirectional plasticity of pacemaking currents induced by chronic heavy drinking within the inferior olive of cynomolgus monkeys. Intracellular recordings of inferior olive neurons demonstrated that ethanol inhibited the tail current triggered by release from hyperpolarization (Itail). Both the slow deactivation of hyperpolarization-activated cyclic nucleotide-gated channels conducting the hyperpolarization-activated inward current and the activation of Cav3.1 channels conducting the T-type calcium current (IT) contributed to Itail, but ethanol inhibited only the IT component of Itail. Recordings of inferior olive neurons obtained from chronically intoxicated monkeys revealed a significant up-regulation in Itail that was induced by 1 y of daily ethanol self-administration. The up-regulation was caused by a specific increase in IT which (i) greatly increased neurons’ susceptibility for rebound excitation following hyperpolarization and (ii) may have accounted for intention tremors observed during ethanol withdrawal. In another set of monkeys, sustained abstinence produced the opposite effects: (i) a reduction in rebound excitability and (ii) a down-regulation of Itail caused by the down-regulation of both the hyperpolarization-activated inward current and IT. Bidirectional plasticity of two hyperpolarization-sensitive currents following chronic ethanol abuse and abstinence may underlie persistent brain dysfunction in primates and be a target for therapy

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Depression, anxiety, hopelessness and quality of life in users of cocaine/crack in outpatient treatment

Abstract Objective: To identify symptoms of anxiety, depression, and feelings of hopelessness in patients in outpatient treatment for substance dependency and to test for correlations with various aspects of their quality of life. Methods: A cross-sectional study of a sample of 25 men in recuperation from substance dependency, selected by convenience. We assessed symptoms of depression (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), hopelessness (Beck Hopelessness Scale), and quality of life (World Health Organization Quality of Life instrument-Abbreviated version [WHOQOL-Bref]), and also analyzed sociodemographic profile, substance abuse, and family history. Categorical variables were expressed as frequencies and percentages and quantitative variables as means and standard deviations or as medians and interquartile ranges. We also analyzed Spearman correlations to a 5% significance level. Results: The study revealed prevalence rates of 32% for depression, 24% for anxiety, and 12% for hopelessness, at a moderate/severe level. Correlations between Beck scales and WHOQOL-Bref were significant; but impacts differed in the four areas evaluated. Conclusions: Overall, we observe global negative impacts on subjects' lives, affecting their psychiatric symptoms and quality of life and their relationships and occupational factors to a similar degree. The results show that the lower the scores on these scales, the better the quality of life in some areas, indicating that there is a negative correlation between psychiatric symptoms and quality of life