Incidence, prevalence and risk factors for hepatitis C in Danish prisons

Hepatitis C virus (HCV) infection is prevalent among people in prison and prisons could therefore represent a unique opportunity to test risk groups for HCV. The aim of this sero-epidemiological study was to determine the incidence and prevalence of HCV infection and the corresponding risk factors in Danish prisons. Participants, recruited from eight Danish prisons, were tested for HCV using dried blood spots and filled out a questionaire with demographic data and risk factors for HCV infection. In total, 76.9% (801/1041) of all eligible prisoners consented to participate. The prevalence of HCV RNA positive prisoners was 4.2% (34/801) and the in-prison incidence rate was 0.7-1.0 per 100PY overall and 18-24/100PY among PWIDs. Infected prisoners were older than the overall population with a mean age of 42 years and only 17.6% (6/34) were younger than 35 years. The prevalence of PWID was 8.5% (68/801) and only 3% (2/68) of PWID were younger than 25 years. Among the PWID, 85.3% (58/68) had ever received opioid substitution therapy (OST) and 47.1% (32/68) were currently receiving OST. Risk factors associated with HCV infection were intravenous drug use, age ≥ 40 years, and being incarcerated ≥ 10 years. In conclusion, the prevalence of PWID in Danish prisons is low, possibly reflecting a decrease in injecting among the younger generation. This together with OST coverage could explain the low prevalence of HCV infection. However among PWIDs in prison the incidence remains high, suggesting a need for improved HCV prevention in prison

Systematic review of influenza resistance to the neuraminidase inhibitors

<p>Abstract</p> <p>Background</p> <p>Antivirals play a critical role in the prevention and the management of influenza. One class of antivirals, neuraminidase inhibitors (NAIs), is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu^®) and zanamivir (Relenza^®); and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of antiviral resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread resistance to zanamivir. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review.</p> <p>The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance.</p> <p>Methods</p> <p>We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms.</p> <p>Results</p> <p>We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%). The incidence rate for all zanamivir resistance studies was 0%. Only one study measured incidence of antiviral resistance among subjects given peramivir and was reported to be 0%. Subgroup analyses detected higher incidence rates among influenza A patients, especially for H1N1 subtype influenza. Considerable heterogeneity between studies precluded definite inferences about subgroup results for immunocompromised patients, in-patients, and children. A meta-analysis of 4 studies reporting association between oseltamivir-resistance and pneumonia yielded a statistically significant risk ratio of 4.2 (95% CI 1.3 to 13.1, p = 0.02). Oseltamivir-resistance was not statistically significantly associated with other clinical complications and symptoms.</p> <p>Conclusion</p> <p>Our results demonstrate that that a substantial number of patients may become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance may be significantly associated with pneumonia. In contrast, zanamivir resistance has been rarely reported to date.</p

Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C

Background A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin still represents standard treatment of chronic hepatitis C infection in the majority of patients. However, it is not established which of the two licensed peginterferon products, peginterferon alpha‐2a or peginterferon alpha‐2b, is the most effective and has a better safety profile. Objectives To systematically evaluate the benefits and harms of peginterferon alpha‐2a versus peginterferon alpha‐2b in head‐to‐head randomised clinical trials in patients with chronic hepatitis C. Search methods We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS until October 2013. We also searched conference abstracts, journals, and grey literature. Selection criteria We included randomised clinical trials comparing peginterferon alpha‐2a versus peginterferon alpha‐2b given with or without co‐intervention(s) (for example, ribavirin) for chronic hepatitis C. Quasi‐randomised studies and observational studies as identified by the searches were also considered for assessment of harms. Our primary outcomes were all‐cause mortality, liver‐related morbidity, serious adverse events, adverse events leading to treatment discontinuation, other adverse events, and quality of life. The secondary outcome was sustained virological response in the blood serum. Data collection and analysis Two authors independently used a standardised data collection form. We meta‐analysed data with both the fixed‐effect and the random‐effects models. For each outcome we calculated the relative risk (RR) with 95% confidence interval (CI) based on intention‐to‐treat analysis. We used domains of the trials to assess the risk of systematic errors (bias) and trial sequential analyses to assess the risks of random errors (play of chance). Intervention effects on the outcomes were assessed according to GRADE. Main results We included 17 randomised clinical trials which compared peginterferon alpha‐2a plus ribavirin versus peginterferon alpha‐2b plus ribavirin in 5847 patients. All trials had a high risk of bias. Very few trials reported data on very few patients for the patient‐relevant outcomes all‐cause mortality, liver‐related morbidity, serious adverse events, and quality of life. Accordingly, we were unable to conduct meta‐analyses on all‐cause mortality, liver‐related morbidity, and quality of life. Twelve trials reported on adverse events leading to discontinuation of treatment without clear evidence of a difference between the two peginterferons (197/2171 (9.1%) versus 311/3169 (9.9%); RR 0.84, 95% CI 0.57 to 1.22; I2 = 44%; low quality evidence). A trial sequential analysis showed that we could exclude a relative risk reduction of 20% or more on this outcome. Peginterferon alpha‐2a significantly increased the number of patients who achieved a sustained virological response in the blood serum compared with peginterferon alpha‐2b (1069/2099 (51%) versus 1327/3075 (43%); RR 1.12, 95% CI 1.06 to 1.18; I2= 0%, 12 trials; moderate quality evidence). Trial sequential analyses supported this result. Subgroup analyses based on risk of bias, viral genotype, and treatment history yielded similar results. Trial sequential analyses supported the results in patients with genotypes 1 and 4, but not in patients with genotypes 2 and 3

Impact of gut microbiota composition on black cutworm, Agrotis ipsilon (hufnagel) metabolic indices and pesticide degradation

Abstract Endosymbionts are known to have significant effects on their insect hosts, including nutrition, reproduction, and immunity. Insects gut microbiota is a critical component that affects their physiological and behavioral characteristics. The black cutworm (BCW), Agrotis ipsilon, is an economically important lepidopteran pest that has a diverse gut microbiome composed of nine species belonging to three phyla: Proteobacteria, Actinobacteria, and Firmicutes. This study was conducted to investigate the diversity of gut bacteria isolated from BCW larvae and moths and their effects on metabolism and pesticide degradation. The bacterial isolates were identified using the 16 S rRNA gene. The study showed that the gut microbiome composition significantly affected the metabolism of BCW larvae. Based on the screening results of synthesis of digestive enzymes and pesticide degradation, Brachybacterium conglomeratum and Glutamicibacter sp were selected to perform the remaining experiments as single isolates and consortium. The consortium-fed larvae showed high metabolic indices compared to antibiotic-fed larvae and the control. The gut bacteria were also shown to degrade three pesticide groups. Concerns regarding the health risk of chlorpyrifos have been raised due to its extensive use in agriculture. The isolated B. conglomeratum was more effective in chlorpyrifos degradation than the consortium. Furthermore, the study also examined the presence of sex related endosymbionts (Wolbachia, Spiroplasma, and Rickettsia) in the reproductive tissues of adults. The outcomes demonstrated that none of the examined endosymbionts existed. In conclusion, the study highlights the importance of the gut microbiome in insect physiology and behavior and its potential applications in biotechnology. It provides insights into developing eco-friendly pest control and bioremediation strategies using gut bacteria

Evolution of Heterogeneity (I²) Estimates and Their 95% Confidence Intervals in Large Meta-Analyses

<div><h3>Background</h3><p>Assessment of heterogeneity is essential in systematic reviews and meta-analyses of clinical trials. The most commonly used heterogeneity measure, <em>I²</em>, provides an estimate of the proportion of variability in a meta-analysis that is explained by differences between the included trials rather than by sampling error. Recent studies have raised concerns about the reliability of <em>I²</em> estimates, due to their dependence on the precision of included trials and time-dependent biases. Authors have also advocated use of 95% confidence intervals (CIs) to express the uncertainty associated with <em>I²</em> estimates. However, no previous studies have explored how many trials and events are required to ensure stable and reliable <em>I²</em> estimates, or how 95% CIs perform as evidence accumulates.</p> <h3>Methodology/Principal Findings</h3><p>To assess the stability and reliability of <em>I²</em> estimates and their 95% CIs, in relation to the cumulative number of trials and events in meta-analysis, we looked at 16 large Cochrane meta-analyses - each including a sufficient number of trials and events to reliably estimate <em>I²</em> - and monitored the <em>I²</em> estimates and their 95% CIs for each year of publication. In 10 of the 16 meta-analyses, the <em>I²</em> estimates fluctuated more than 40% over time. The median number of events and trials required before the cumulative <em>I²</em> estimates stayed within +/−20% of the final <em>I²</em> estimate was 467 and 11. No major fluctuations were observed after 500 events and 14 trials. The 95% confidence intervals provided good coverage over time.</p> <h3>Conclusions/Significance</h3><p><em>I²</em> estimates need to be interpreted with caution when the meta-analysis only includes a limited number of events or trials. Confidence intervals for <em>I²</em> estimates provide good coverage as evidence accumulates, and are thus valuable for reflecting the uncertainty associated with estimating <em>I²</em>.</p> </div

Presents the evolution of the cumulative <i>I²</i> estimates and their associated 95% confidence intervals (CIs) over the accumulation of trials in meta-analyses (1) to (8).

<p>The cumulative <i>I²</i> are represented by the dot-dashed line ( ), and their associated cumulative 95% CIs are represented by the dotted lines ( ).</p