Systematic Review of Peer Support for Breastfeeding Continuation: Metaregression Analysis of the Effect of Setting, Intensity, and Timing

Objective To examine the effect of setting, intensity, and timing of peer support on breast feeding. Design Systematic review and metaregression analysis of randomised controlled trials. Data sources Cochrane Library, Medline, CINAHL, the National Research Register, and British Nursing Index were searched from inception or from 1980 to 2011. Review methods Study selection, data abstraction, and quality assessment were carried out independently and in duplicate. Risk ratios and 95% confidence intervals were calculated for individual studies and pooled. Effects were estimated for studies grouped according to setting (high income countries, low or middle income countries, and the United Kingdom), intensity (<5 and ≥5 planned contacts), and timing of peer support (postnatal period with or without antenatal care), and analysed using metaregression for any and exclusive breast feeding at last study follow-up. Results Peer support interventions had a significantly greater effect on any breast feeding in low or middle income countries (P<0.001), reducing the risk of not breast feeding at all by 30% (relative risk 0.70, 95% confidence interval 0.60 to 0.82) compared with a reduction of 7% (0.93, 0.87 to 1.00) in high income countries. Similarly, the risk of non-exclusive breast feeding decreased significantly more in low or middle income countries than in high income countries: 37% (0.63, 0.52 to 0.78) compared with 10% (0.90, 0.85 to 0.97); P=0.01. No significant effect on breast feeding was observed in UK based studies. Peer support had a greater effect on any breastfeeding rates when given at higher intensity (P=0.02) and only delivered in the postnatal period (P<0.001), although no differences were observed of its effect on exclusive breastfeeding rates by intensity or timing. Conclusion Although peer support interventions increase breastfeeding continuation in low or middle income countries, especially exclusive breast feeding, this does not seem to apply in high income countries, particularly the United Kingdom, where breastfeeding support is part of routine postnatal healthcare. Peer support of low intensity does not seem to be effective. Policy relating to provision of peer support should be based on more specific evidence on setting and any new peer services in high income countries need to undergo concurrent evaluation

Predicting the chance of live birth for women undergoing IVF: a novel pretreatment counselling tool

STUDY QUESTION Which pretreatment patient variables have an effect on live birth rates following assisted conception? SUMMARY ANSWER The predictors in the final multivariate logistic regression model found to be significantly associated with reduced chances of IVF/ICSI success were increasing age (particularly above 36 years), tubal factor infertility, unexplained infertility and Asian or Black ethnicity. WHAT IS KNOWN ALREADY The two most widely recognized prediction models for live birth following IVF were developed on data from 1991 to 2007; pre-dating significant changes in clinical practice. These existing IVF outcome prediction models do not incorporate key pretreatment predictors, such as BMI, ethnicity and ovarian reserve, which are readily available now. STUDY DESIGN, SIZE, DURATION In this cohort study a model to predict live birth was derived using data collected from 9915 women who underwent IVF/ICSI treatment at any CARE (Centres for Assisted Reproduction) clinic from 2008 to 2012. Model validation was performed on data collected from 2723 women who underwent treatment in 2013. The primary outcome for the model was live birth, which was defined as any birth event in which at least one baby was born alive and survived for more than 1 month. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were collected from 12 fertility clinics within the CARE consortium in the UK. Multivariable logistic regression was used to develop the model. Discriminatory ability was assessed using the area under receiver operating characteristic (AUROC) curve, and calibration was assessed using calibration-in-the-large and the calibration slope test. MAIN RESULTS AND THE ROLE OF CHANCE The predictors in the final model were female age, BMI, ethnicity, antral follicle count (AFC), previous live birth, previous miscarriage, cause and duration of infertility. Upon assessing predictive ability, the AUROC curve for the final model and validation cohort was (0.62; 95% confidence interval (CI) 0.61–0.63) and (0.62; 95% CI 0.60–0.64) respectively. Calibration-in-the-large showed a systematic over-estimation of the predicted probability of live birth (Intercept (95% CI) = −0.168 (−0.252 to −0.084), P < 0.001). However, the calibration slope test was not significant (slope (95% CI) = 1.129 (0.893–1.365), P = 0.28). Due to the calibration-in-the-large test being significant we recalibrated the final model. The recalibrated model showed a much-improved calibration. LIMITATIONS, REASONS FOR CAUTION Our model is unable to account for factors such as smoking and alcohol that can affect IVF/ICSI outcome and is somewhat restricted to representing the ethnic distribution and outcomes for the UK population only. We were unable to account for socioeconomic status and it may be that by having 75% of the population paying privately for their treatment, the results cannot be generalized to people of all socioeconomic backgrounds. In addition, patients and clinicians should understand this model is designed for use before treatment begins and does not include variables that become available (oocyte, embryo and endometrial) as treatment progresses. Finally, this model is also limited to use prior to first cycle only. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is the first study to present a novel, up-to-date model encompassing three readily available prognostic factors; female BMI, ovarian reserve and ethnicity, which have not previously been used in prediction models for IVF outcome. Following geographical validation, the model can be used to build a user-friendly interface to aid decision-making for couples and their clinicians. Thereafter, a feasibility study of its implementation could focus on patient acceptability and quality of decision-making. STUDY FUNDING/COMPETING INTEREST None

HLA tapasin independence: broader peptide repertoire and HIV control.

Human leukocyte antigen (HLA) class I allotypes vary in their ability to present peptides in the absence of tapasin, an essential component of the peptide loading complex. We quantified tapasin dependence of all allotypes that are common in European and African Americans (n = 97), which revealed a broad continuum of values. Ex vivo examination of cytotoxic T cell responses to the entire HIV-1 proteome from infected subjects indicates that tapasin-dependent allotypes present a more limited set of distinct peptides than do tapasin-independent allotypes, data supported by computational predictions. This suggests that variation in tapasin dependence may impact the strength of the immune responses by altering peptide repertoire size. In support of this model, we observed that individuals carrying HLA class I genotypes characterized by greater tapasin independence progress more slowly to AIDS and maintain lower viral loads, presumably due to increased breadth of peptide presentation. Thus, tapasin dependence level, like HLA zygosity, may serve as a means to restrict or expand breadth of the HLA-I peptide repertoire across humans, ultimately influencing immune responses to pathogens and vaccines

Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen?. We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the “no direct effect†assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The “no direct effect†assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada

Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/μL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/μL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk

Male circumcision for prevention of heterosexual acquisition of HIV in men

Background: Male circumcision is defined as the surgical removal of all or part of the foreskin of the penis and may be practiced as part of a religious ritual, as a medical procedure, or as part of a traditional ritual performed as an initiation into manhood. Since the 1980s, over 30 observational studies have suggested a protective effect of male circumcision on HIV acquisition in heterosexual men. In 2002, three randomised controlled trials to assess the efficacy of male circumcision for preventing HIV acquisition in men commenced in Africa. This review evaluates the results of these trials, which analysed the effectiveness and safety of male circumcision for preventing acquisition of HIV in heterosexual men. Objectives: To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse Search strategy: We formulated a comprehensive and exhaustive search strategy in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress). In June 2007 we searched the following electronic journal and trial databases: MEDLINE, EMBASE, and CENTRAL. We also searched the electronic conference databases NLM Gateway and AID Search and the trials registers ClinicalTrials.gov and Current Controlled Trials. We contacted researchers and relevant organizations and checked reference lists of all included studies. Selection criteria: Randomised controlled trials of male circumcision versus no circumcision in HIV-negative heterosexual men with HIV incidence as the primary outcome. Data collection and analysis: Two review authors independently assessed study eligibility, extracted data, and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. Data were considered clinically homogeneous and meta-analyses and sensitivity analyses were performed. Main results: Three large RCTs of men from the general population were conducted in South Africa (N = 3 274), Uganda (N = 4 996) and Kenya (N = 2 784) between 2002 and 2006. All three trials were stopped early due to significant findings at interim analyses. We combined the survival estimates for all three trials at 12 months and also at 21 or 24 months in a meta-analysis using available case analyses using the random effects model. The resultant incidence risk ratio (IRR) was 0.50 at 12 months with a 95% confidence interval (CI) of 0.34 to 0.72; and 0.46 at 21 or 24 months (95% CI: 0.34 to 0.62). These IRRs can be interpreted as a relative risk reduction of acquiring HIV of 50% at 12 months and 54% at 21 or 24 months following circumcision. There was little statistical heterogeneity between the trial results (χ2 = 0.60; df = 2; p = 0.74 and χ2 = 0.31; df = 2; p = 0.86) with the degree of heterogeneity quantified by the I2 at 0% in both analyses. We investigated the sensitivity of the calculated IRRs and conducted meta-analyses of the reported IRRs, the reported per protocol IRRs, and reported full intention-to-treat analysis. The results obtained did not differ markedly from the available case meta-analysis, with circumcision displaying significant protective effects across all analyses. We conducted a meta-analysis of the secondary outcomes measuring sexual behaviour for the Kenyan and Ugandan trials and found no significant differences between circumcised and uncircumcised men. For the South African trial the mean number of sexual contacts at the 12-month visit was 5.9 in the circumcision group versus 5 in the control group, which was a statistically significant difference (p &lt; 0.001). This difference remained statistically significant at the 21-month visit (7.5 versus 6.4; p = 0.0015). No other significant differences were observed. Incidence of adverse events following the surgical circumcision procedure was low in all three trials. Reporting of methodological quality was variable across the three trials, but overall, the potential for significant biases affecting the trial results was judged to be low to moderate given the large sample sizes of the trials, the balance of possible confounding variables across randomised groups at baseline in all three trials, and the employment of acceptable statistical early stopping rules. Authors' conclusions: There is strong evidence that medical male circumcision reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months. Incidence of adverse events is very low, indicating that male circumcision, when conducted under these conditions, is a safe procedure. Inclusion of male circumcision into current HIV prevention measures guidelines is warranted, with further research required to assess the feasibility, desirability, and cost-effectiveness of implementing the procedure within local contexts. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley &amp; Sons, Ltd.Revie