Joseph S. Doyle

Treatment of Hepatitis C Virus Infection Among People Who Are Actively Injecting Drugs: A Systematic Review and Meta-analysis

BACKGROUND Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID. METHODS A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection. RESULTS Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was 56% (95% confidence interval [CI], 50%-61%) for all genotypes, 37% (95% CI, 26%-48%) for genotypes 1/4, and 67% (95% CI, 56%-78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%-89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%-27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9-6.1) per 100 person-years. CONCLUSIONS HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID.

Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis

Insomnia is a prevalent condition, with 5% to 15% of adults meeting formal diagnostic criteria for chronic insomnia (15) (now termed insomnia disorder [6]) and one third reporting dissatisfaction with sleep. Insomnia is associated with both medical and psychiatric comorbidity, being linked to anxiety; depression (7); chronic health problems, such as hypertension (8, 9) and type 2 diabetes (10); health care use; nonmotor vehicle accidents; pain (11); and use of medication and alcohol (1215). Symptoms of insomnia have functional consequences even in the absence of a formal diagnosis (16), with the high economic burden of the condition largely mediated through the productivity cost of work absenteeism (17). Hypnotics, such as benzodiazepines and related drugs, are the most commonly used treatment for insomnia, with around 6% to 10% of U.S. adults using hypnotics in 2010 (18) and 27 daily doses of such drugs being taken per 1000 U.S. persons (19). In Australia, around 90% of primary care encounters for insomnia result in hypnotic prescription (20). Furthermore, despite a lack of evidence, use of second-generation antipsychotics (such as quetiapine) is also increasing, possibly due to patient and physician dissatisfaction with available treatments and a perceived lack of alternatives (21, 22). In this context, considering nonpharmacologic treatment options for insomnia disorder is important. Cognitive behavioral therapy for insomnia (CBT-i) is an effective nonpharmacologic treatment that improves sleep outcomes with minimal adverse effects (23) and is preferred by patients to drug therapy (24). The approach to CBT-i has been refined in recent years, and it is now most commonly studied as a combined cognitive and behavioral treatment incorporating some or all of 5 components. The components are described in Table 1, and although the precise efficacy of each has not been determined, the package of care is more effective than separate delivery of the cognitive or behavioral components (25). Although previous meta-analyses have been performed (2629), no recent meta-analysis has assessed the efficacy of this now-established package of care. We present a meta-analysis of the efficacy of CBT-i on sleep diary outcomes, compared with control, for the treatment of adults with chronic insomnia. Table 1. Components of CBT-i Methods We performed a systematic review and meta-analysis in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines, using methods from the Cochrane Handbook for Systematic Reviews of Interventions. The predetermined methods were registered online with PROSPERO (CRD42012002863) (30), with full methods presented in section 1 of the Supplement. Supplement. Supplementary Material Data Sources and Searches We searched MEDLINE, EMBASE, PsycINFO, CINAHL, the Cochrane Library, and PubMed Clinical Queries from inception to 31 March 2015 with the terms sleeplessness, chronic insomnia, insomniac, insomnia, insomni*, sleep initiation and maintenance disorders, cognitive behavioural therapy, cognitive behavioral therapy, cognitive behavioural therapies, cognitive behavioral therapies, sleep hygiene, stimulus control, relaxation, relaxation techniques, behavior modification, behavior therapy, cognitive therapy, imagery, and psychotherapy in any language. We also reviewed the reference lists of 4 review articles on the topic (2628, 31) and briefly screened references by using the same search strategy without limitation to randomized, controlled trials. Study Selection Eligible studies were randomized, controlled trials involving CBT-i in adults (aged 18 years) with chronic insomnia. We defined CBT-i as multimodal therapy delivered in person on at least 2 occasions and incorporating at least 2 of the 5 most widely accepted components of CBT-i: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation therapy. For the primary analysis, acceptable control groups included sham therapy, waiting list, no treatment, sleep hygiene, or information provision. Studies were excluded if medical, sleep, or psychiatric comorbid conditions were listed as inclusion criteria, but they were not excluded on the basis of the frequency of comorbid conditions in included patients. We adopted this approach because excluding all studies that allowed patients with comorbid conditions would have markedly depleted the number of included studies, and because patients with chronic insomnia seen in clinical practice are likely to have a range of noninteracting comorbid conditions. Moreover, because only a subgroup of included studies reported the proportion of patients with comorbid conditions, we wished to avoid penalizing studies that reported in greater detail. Data Extraction and Quality Assessment Two authors independently confirmed the eligibility of studies, with all discrepancies resolved by consensus. One of these 2 authors extracted data, which were verified by a third author. We contacted the corresponding author of all included studies published after 1 January 2000 to request clarification of data and methods. Study quality assessments were performed independently by the 2 authors who extracted and verified data using the Cochrane Collaboration tool for assessing risk of bias (32). Data Synthesis and Analysis Our main outcome measures of interest were sleep diary measures of sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%) (Table 2). These end points were assessed at 3 time points that we defined for the purpose of this analysis: immediately after treatment, early follow-up (4 weeks to <6 months after completion of the intervention), and late follow-up (6 to 12 months after completion of the intervention). Because studies most frequently reported results as the mean and SD at a point in time rather than the SD of the mean change over time, the SD of the change over time was imputed in most cases. All analyses used random-effects models, with heterogeneity assessed using the I 2 statistic and publication bias assessed with funnel plots and the Egger test (33, 34). Table 2. Glossary Six sensitivity analyses were performed that were limited to studies with particular intervention characteristics. First, we limited the analysis to studies incorporating sleep restriction because this may be among the most effective components of CBT-i (35). Second, because the optimal dosage of CBT-i is unknown but may be 4 sessions (36), we limited the analysis to studies involving at least 4 in-person contacts. Third, to consider the incremental effect of CBT-i incorporating a greater number of components, we limited the analysis to studies involving at least 4 components. Fourth, we limited the analysis to studies using a comparator group other than sleep hygiene because this may or may not be an effective stand-alone treatment (31). Fifth, we restricted the analysis to studies delivering treatment on an individual basis only, rather than in a group setting. Finally, to determine whether a tendency existed for studies with significant results to follow patients longer, we restricted the posttreatment analysis to studies with follow-up time points. In addition, we performed 3 sensitivity analyses in which we varied the correlation coefficients used to impute SDs. All statistical tests were 2-tailed, with P values less than 0.05 considered statistically significant. Statistical analyses were performed using Stata, version 13.0 (StataCorp), and R, version 3.1.3 (R Foundation for Statistical Computing). Role of the Funding Source This study received no funding. Results Our formal search strategy identified 292 references for review of the title and abstract. Of these, the full text was obtained and reviewed for 91 articles that were considered potentially appropriate for inclusion, and 20 studies met all inclusion criteria (although only 19 contributed data to the pooled estimates presented). The study flow diagram with reasons for exclusion is presented in Figure 1. Figure 1. Summary of evidence search and selection. CBT-i = cognitive behavioral therapy for insomnia; RCT = randomized, controlled trial. * Restricted to references not returned on MEDLINE search. Study Characteristics Table 3 shows descriptive data for the 20 included studies, which involved a total of 1162 patients (range, 20 to 201 patients), with values presented for only the groups that contributed data to this meta-analysis when possible. Most study populations were of late or middle age (mean age, 55.6 years), and 9 studies incorporated age restrictions as exclusion criteria. Sex was predominantly female (64.3%), and most studies were performed in developed countries (n= 19). Of the studies excluded on the basis of the population studied, 5 enrolled hypnotic-dependent patients, 1 enrolled obese persons, 3 enrolled patients with any comorbid condition, 1 enrolled patients with moderate to severe hot flashes, and 3 did not require a formal diagnosis of insomnia. Most studies referenced accepted definitions for insomnia (n= 17), most often an edition of the Diagnostic and Statistical Manual of Mental Disorders (n= 13), the International Classification of Sleep Disorders (n= 7), or both (Table 3). Nineteen studies excluded patients on the basis of presence of comorbid conditions, with all of these excluding patients with psychiatric or sleep-related comorbid conditions, 17 excluding those with medical comorbid conditions, 17 excluding those with medication or drug use, 4 excluding pregnant women, and 3 excluding shift workers. However, approaches differed in whether any comorbid condition was sufficient for exclusion or whether only patients with severe, unstable, or treatment-requiring conditions were excluded. Fourteen studies screened all patients with polysomnography at baseline to detect unrecognized sleep disorders. Table 3. Characteristics of Rando

Are needle and syringe programmes associated with a reduction in HIV transmission among people who inject drugs: a systematic review and meta-analysis

BACKGROUND Needle and syringe programmes (NSP) aim to reduce the risk of HIV by providing people who inject drugs (PWID) with sterile injecting equipment. A recent review of reviews (ROR) concluded that there was only tentative evidence to support the effectiveness of NSP in reducing HIV. We carried out a systematic review and meta-analysis to assess the association between NSP and HIV transmission. METHODS Relevant primary articles presenting data on the risk of HIV transmission associated with NSP were identified in two stages: (i) from reviews identified in two published RORs (covering the period 1980-2008); and (ii) a literature search of CINAHL, Cochrane Library, EMBASE, MEDLINE and PsychINFO for primary articles published since the most recent high quality review (covering the period 2008-12). Study results were synthesized using random-effects meta-analysis. RESULTS There were 12 studies comprising at least 12 000 person-years of follow-up. Exposure to NSP was associated with a reduction in HIV transmission: pooled effect size 0·66 [95% confidence interval (CI) 0·43, 1·01] across all studies, and 0·42 (95% CI 0·22, 0·81) across six higher quality studies (according to the Newcastle-Ottawa tool). CONCLUSIONS There is evidence to support the effectiveness of NSP in reducing the transmission of HIV among PWID, although it is likely that other harm reduction interventions have also contributed to the observed reduction in HIV risk. NSP should be considered as just one component of a programme of interventions to reduce both injecting risk and other types of HIV risk behaviour.

Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia.

Resistance in virus-infected stem cell transplant recipients illustrates the need for surveillance.

Epidemiology of Infections Acquired in Intensive Care Units

Infections acquired in the intensive care unit (ICU) are associated with significant morbidity and mortality. Using surveillance data collected in the United States and internationally, we describe contemporary rates, sites, and pathogens responsible for common ICU-acquired infections. Emerging pathogens are outlined, including a systematic review of published ICU infection outbreaks from 2005 to 2010. Compared with a similar review of outbreaks conducted in 2003, multiresistant gram-negative bacteria (eg, ACINETOBACTER and PSEUDOMONAS species) were more commonly reported, whereas resistant STAPHYLOCOCCUS AUREUS was reported less frequently. Advances in ICU infection prevention, including central line bundles, chlorhexidine body wash, and hand hygiene interventions occurred during this period. We also describe how changes in the pattern of antimicrobial use can affect the prevalence of multiresistant pathogens.

Murray Valley encephalitis: a review of clinical features, diagnosis and treatment

Murray Valley encephalitis virus (MVEV) is a mosquito‐borne virus that is found across Australia, Papua New Guinea and Irian Jaya.

Eradication of hepatitis C infection: The importance of targeting people who inject drugs

Hepatitis C virus (HCV) affects ~170 million people worldwide and causes significant morbidity and mortality.1 In high-income countries, people who inject drugs (PWID) are at greatest risk of HCV infection.2 Until recently HCV eradication seemed unlikely, but recent advances in HCV treatment and improved understanding of the effectiveness of harm-reduction intervention effectiveness give reason for optimism. Current HCV treatments can cure ~75% of patients and new drugs will further improve effectiveness (over 90% cure) and improve tolerability.3 If HCV treatment can be delivered effectively to those at highest risk of onward transmission, significant reductions in future HCV cases are possible. The feasibility of disease eradication must be assessed on both scientific criteria (e.g., epidemiological susceptibility, effective and practical intervention available, and demonstrated feasibility of elimination) and political criteria (e.g., burden of disease, cost of intervention).4 With effective, curative treatment now available, HCV meets these criteria.

Treatment scale-up to achieve global HCV incidence and mortality elimination targets: a cost-effectiveness model

Aims The WHOs draft HCV elimination targets propose an 80% reduction in incidence and a 65% reduction in HCV-related deaths by 2030. We estimate the treatment scale-up required and cost-effectiveness of reaching these targets among injecting drug use (IDU)-acquired infections using Australian disease estimates. Methods A mathematical model of HCV transmission, liver disease progression and treatment among current and former people who inject drugs (PWID). Treatment scale-up and the most efficient allocation to priority groups (PWID or patients with advanced liver disease) were determined; total healthcare and treatment costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) compared with inaction were calculated. Results 5662 (95% CI 5202 to 6901) courses per year (30/1000 IDU-acquired infections) were required, prioritised to patients with advanced liver disease, to reach the mortality target. 4725 (3278–8420) courses per year (59/1000 PWID) were required, prioritised to PWID, to reach the incidence target; this also achieved the mortality target, but to avoid clinically unacceptable HCV-related deaths an additional 5564 (1959–6917) treatments per year (30/1000 IDU-acquired infections) were required for 5 years for patients with advanced liver disease. Achieving both targets in this way cost

Prescribing trends before and after implementation of an antimicrobial stewardship program

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Current and emerging antiviral treatments for hepatitis C infection

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