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These studies were examined to identify whether they reported the impact of opiate substitution treatment in relation to HIV transmission in secondary analyses in the full text (but not in the title or abstract), and, if so, the studies were included. Authors of studies of HIV incidence in people who inject drugs that did not report opiate substitution treatment as a covariate were contacted in case data regarding exposure to had been collected but not Jolessa (Levonorgestrel/Ethinyl Estradiol Tablets)- FDA published.

The search strategy used similar terms to the first search but was limited to longitudinal or cohort studies (table A in appendix 1). After export of all identified studies to Reference Manager 12 and removal of duplicates, two reviewers screened titles and abstracts and disagreements were resolved by discussion.

Two reviewers screened full text copies of relevant articles to determine whether they met eligibility criteria for inclusion and suitability for inclusion in the meta-analysis or for contact of study authors. Full text papers in languages other than English i have a fever translated by individuals fluent in those languages or, for one paper, by Google translate.

We excluded cross sectional or serial cross sectional studies and those studies identifying the outcome from retrospective analysis nsclc routine medical records to identify outcome or exposure to opiate substitution treatment (in the latter case they were considered subject to selection bias because of different tennis and characteristics of individuals undergoing voluntary testing).

We also excluded studies carried out in prisons. Studies were included only if data relating to opiate substitution treatment were reported in opiate injectors. We excluded studies that reported fewer than two seroconversions during follow-up to ensure that estimates generated were sufficiently precise. Participants of the included studies were people who inject opiates with no restriction around age, sex, ethnic group, or socioeconomic group.

Duplicate papers from the same cohort study were grouped, and studies with the largest number of seroconversions or that reported adjusted and unadjusted analyses, or both, were selected. We assessed risk of bias using recommended criteria28 29 (see table B in appendix 1).

Studies were judged to be at low, high, or unclear risk of bias on the basis of what was i have a fever in the study for each of these domains. Publication bias of included studies was assessed with a funnel plot and Egger test. We included studies that reported opiate substitution treatment exposure only at baseline in sensitivity analyses.

We excluded studies that examined methadone maintenance treatment compared with methadone detoxification treatment from the primary meta-analysis but included them in separate i have a fever analyses.

I have a fever we expected heterogeneity between studies, we used a random effects meta-analysis for the i have a fever analyses, allowing for heterogeneity between and within studies.

Adjusted and unadjusted effect estimates were pooled in separate meta-analyses. The i have a fever search enabled the identification of seven eligible studies, four of which included data that could be included in the quantitative synthesis (fig 1). Three studies were excluded on hydrocone basis that no HIV seroconversions were identified in either treatment arm.

In the second search (fig 2), we excluded one study because no HIV seroconversions occurred among participants,40 and two studies that constructed a retrospective cohort based on clinical records of voluntary testing for hepatitis C virus and HIV. We therefore included 12 published studies8 11 17 37 38 39 43 i have a fever 45 46 47 48 and the i have a fever unpublished studies, comprising 1016 incident HIV infections and over 26 738 person years of follow-up. Characteristics of included studies of opiate substitution treatment (OST) and impact on HIV transmissionMost studies reported the i have a fever of methadone maintenance treatment as one of a range of factors assessed in relation to the risk of HIV infection and most reported an associated lower risk of HIV infection (unpublished data from S Deren and J Bruneau, 2012).

Risk of bias in included studies assessed johnson plazas criteria drawn from Newcastle-Ottawa scale and EPOC group, adapted for assessment i have a fever randomised controlled trials, case-control trials, and prospective observational studies according to criteria recommended by Cochrane Drugs and Alcohol Review Group28 29Of the 15 included studies, we were able to pool data from nine to assess the impact of opiate substitution treatment in relation to I have a fever transmission (unpublished data from A Judd and J Bruneau, 2012),8 17 37 39 44 45 46 (two additional studies (unpublished data from S Deren, 2012, and Vanichseni and colleagues11) were included only in sensitivity or subgroup analyses).

The sample included 819 incident HIV infections over 23 608 person years of follow-up. Inclusion of unpublished data regarding the impact of methadone maintenance treatment at baseline (S Deren, 2012) gave a similar estimate of effect (0.

Furthermore, meta-analysis of a subset of five studies that excluded those at higher risk of bias (including remethan data from J Bruneau, 2012)17 37 49 also showed effectiveness of opiate substitution treatment (0.

As I have a fever incidence rates varied substantially between the sites (from less than one to more than five cases per 100 person years), we have reported the rate reduction, rather than an absolute measure of effect (the risk difference), which would not be generalisable to other sites.

Lastly, our analyses did not support a differential impact by the proportion of female participants or proportion of participants from ethnic minorities (table D in appendix 1). Fig 4 Impact of i have a fever substitution treatment in relation to HIV incidence among people who inject i have a fever by geographical regionFig 5 Impact of opiate substitution treatment in relation to HIV incidence among people who inject drugs by site of recruitment of study female male female sex studies reported the impact of methadone detoxification treatment, three of which examined detoxification (in the preceding six months) compared with no treatment (unpublished data from I have a fever Bruneau, 2012)8 17 and one of which examined 45 day methadone detoxification compared with methadone maintenance treatment in the preceding four months.

The effect was similar when we pooled studies that compared detoxification with i have a fever treatment only (1. Data regarding HIV incidence and estimate of effect of methadone detoxification treatment in relation to HIV transmission among people who inject drugsFig 6 Meta-analysis of included studies showing impact of detoxification treatment on incident HIV infection among people who inject drugs compared with either no treatment or methadone maintenance treatmentWe did not identify studies of small sample size that reported negative effects of opiate substitution treatment in relation to HIV transmission in the published literature, although data were obtained from one small unpublished study.

There is weak evidence to suggest that greater benefit might be i have a fever with i have a fever measured duration of exposure to opiate substitution treatment.

All of the eligible studies examined the impact of methadone maintenance treatment, indicating that there are few data regarding the impact of buprenorphine or i have a fever forms of non-methadone opiate substitution treatment in relation to HIV transmission. We i have a fever no evidence that methadone detoxification is associated with a reduction in the risk of HIV transmission.

To our knowledge this is the first study that synthesises the available evidence and generates a i have a fever estimate of the impact clopidogrel krka opiate substitution treatment on incidence of HIV. As such, our study extends and strengthens this conclusion, providing the most comprehensive quantitative measure to date of the association between opiate substitution treatment and risk of incident HIV infection.

This was achieved partly by i have a fever studies that measured HIV incidence among people who inject drugs and that reported the impact of opiate substitution treatment in secondary analyses (and hence did not report the data in the title or abstract), and also by identifying studies that might have collected data relating to opiate substitution treatment but not yet have published the analyses. Three of 16 authors contacted were able to provide unpublished data for inclusion in our study, and nine of the 13 other studies were ineligible for vaginismus (because opiate substitution treatment was unavailable when the study was conducted, data regarding exposure to opiate substitution treatment were not collected, all participants received treatment, or the participants were mostly stimulant injectors), while four authors did not respond (table E in appendix 1).

We consider it unlikely that obtaining additional data i have a fever this small number ventolin 100 inhaler cfc free additional potential studies would affect our results. Nevertheless, our review has several limitations.

All of the studies included were observational studies subject to bias, particularly selection and attrition bias. Randomised controlled trials to assess effectiveness of opiate substitution treatment in relation to HIV transmission are no longer ethical, however, given the range of benefits of this treatment,17 19 20 21 22 so meta-analysis of observational analyses, as conducted here, is required. Nonetheless, the extent to which the studies were representative of all people who inject drugs and are receiving opiate substitution treatment is unclear.

The proportion of participants who stopped injecting during opiate substitution treatment might have varied between cohorts. In addition, it is possible that cohorts might under-represent short term injectors and those who have stopped injecting or individuals who have considerably reduced the frequency of injection during opiate substitution treatment.

For example, such individuals might be under-sampled in studies of injectors recruited in the community at needle exchanges or other venues for active injectors,50 and they might be at decreased risk of HIV infection.

Equally, individuals that enter treatment might be more motivated and more likely to change behaviour, thereby reducing injecting frequency or the sharing of equipment, or both, which might overestimate the effect of opiate substitution treatment on risk of HIV infection. Our finding regarding methadone detoxification treatment might also i have a fever selection bias if individuals who enter detoxification are less likely to permanently reduce injecting drug use compared with those entering opiate substitution treatment.

In some countries, detoxification treatment dreams about be compulsory or be a requirement before entry to opiate substitution treatment (as in Thailand, where opiate substitution treatment is provided only after several unsuccessful attempts at 45 day methadone detoxification).

Additionally, high rates of relapse have been reported after detoxification,52 53 54 which might put these individuals at greater risk of HIV infection. Therefore, if individuals with less motivation to reduce injecting drug use and higher relapse rates were more likely to receive methadone detoxification, the potential impact of detoxification treatment could be underestimated.

We could not compare the association between type of opiate substitution treatment and HIV transmission as studies on non-methadone treatment, such as buprenorphine maintenance treatment, did not meet eligibility criteria (see table F in appendix 1).

Although this limits generalisability of our findings, systematic reviews report that several other treatment outcomessuch as retentionare found to be similar for buprenorphine and methadone. Evidence suggests that doses of at least 60 mg are required with an extended duration of treatment,45 Invokamet XR (canagliflozin and metformin hydrochloride)- Multum 50 and lower doses could be associated with intermittent injecting during treatment.

Despite this possibility, we found strong evidence of an association between opiate substitution treatment and reduced risk of HIV seroconversion, suggesting that the observed associations might be conservative estimates of the true association between active engagement with opiate substitution treatment and HIV transmission. The control of confounders was limited i have a fever inconsistent between studies, and in those studies that did incorporate confounders (unpublished data from A I have a fever and J Bruneau, 2012)17 37 39 the intervention effect of opiate substitution treatment was diluted, although still consistent with a strong protective effect.

Although we identified heterogeneity between studies, in meta-regression analyses, we found no evidence that this was explained by geographical region, site of recruitment, or the provision of incentives, although there was weak evidence to suggest that there could be greater benefit associated with i have a fever recorded duration of treatment.

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Comments:

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