Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC). METHODS: We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR). RESULTS: Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR. CONCLUSIONS: This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization's recommendation to avoid using NNRTIs in countries where levels of PDR are high.

Hemosiderin in sputum macrophages may predict infective exacerbations of chronic obstructive pulmonary disease: a retrospective observational study.

BACKGROUND: Infective exacerbations of COPD are common and are accompanied by neutrophilic bronchitis in sputum. Increased respiratory iron content has been associated with respiratory tract infection, though it is unclear if this represents a predisposing factor for infection or the sequelae of inflammation. Iron overload, as assessed in the airways, may be an important biomarker for recurrent infective exacerbations of COPD. The purpose of our study was to determine if hemosiderin in sputum macrophages is related to infective exacerbations of COPD. METHODS: We undertook a retrospective observational study of 54 consecutive patients who presented with an exacerbation of COPD and had sputum examined including assessment for hemosiderin in alveolar macrophages. The relation between infective exacerbations in the previous two years and the percent of hemosiderin-positive macrophages was analyzed with linear regression. To account for the non-parametric distribution of infective exacerbations, negative binomial regression modelling was used to account for other covariates. RESULTS: The percent of hemosiderin positive alveolar macrophages (hemosiderin index), analyzed parametrically and non-parametrically, demonstrated a significant correlation with increasing numbers of infective exacerbations in the previous two years. In a multivariate regression analysis, hemosiderin index was an independent predictor of infective exacerbations. COPD patients with raised hemosiderin index (≥20%) had higher levels of sputum IL-6 compared to patients with lower levels (<20%). CONCLUSIONS: High hemosiderin index in sputum alveolar macrophages measured at the time of AECOPD may be related to the frequency of infective exacerbations of COPD.

The methodological quality of dose-response meta-analyses needed substantial improvement: a cross-sectional survey and proposed recommendations.

OBJECTIVES: To investigate methodological quality of published dose-response meta-analysis (DRMA) and explore study characteristics associated with the quality. STUDY DESIGN AND SETTING: We searched three databases for published DRMAs and used a modified AMSTAR (15 items) checklist to assess the methodological quality. We summarized the compliance of those DRMAs to the AMSTAR items and used multivariable regression analysis to explore the association between prespecified study characteristics with the overall methodological quality. RESULTS: We identified 529 DRMAs. Of the methodological quality items, six were well complied (80% or more) and six poorly complied (30% or fewer) by these DRMAs. The median score was nine points [first and third quartile: 7, 10] and only 64/529 had score over 10 points. Regression analysis suggested that studies with more authors (ß = 0.19; 95% confidence interval [CI]: 0.05, 0.33), published more recently (ß = 0.29; 95% CI: 0.21, 0.36), with financial support (ß = 0.41; 95% CI: 0.13, 0.70), conducted by authors from European (other regions vs. European, ß = -0.68; 95% CI: -1.05, -0.31) were associated with better methodological quality. CONCLUSION: The methodological quality of published DRMAs was suboptimal. Substantial efforts are warranted to improve the quality, including developing methodology guideline, involving more methodological trained authors, and so forth.

A cluster randomised trial of a classroom communication resource program to change peer attitudes towards children who stutter among grade 7 students.

BACKGROUND: Classroom-based stuttering intervention addressing negative peer attitudes, perceptions, teasing and bullying of children who stutter (CWS) is required as part of holistic stuttering management because of its occurrence in primary school. This study was conducted in 2017, in 10 primary schools in the Western Cape, South Africa within lower (second and third) and higher (fourth and fifth) quintiles. OBJECTIVES: The primary objective of this study was to determine treatment effect at six months after intervention of grade 7 participants (Classroom Communication Resource [CCR] intervention versus no CCR) using global Stuttering Resource Outcomes Measure (SROM) scores in school clusters. The secondary objective was to determine grade 7 participant treatment effect on the SROM subscales including Positive Social Distance (PSD), Social Pressure (SP) and Verbal Interaction (VI). The subgroup objective was to determine any difference in the primary outcome between schools between and across quintile clusters (lower and higher). METHODS: Once schools were stratified into lower and higher quintile (which are defined according to geographical location, fee per school and resources) subgroup clusters, schools were assigned randomly to control and intervention groups consisting of grade 7 participants who were typically aged ≥ 11 years. Teachers received 1 h of training before administering the single-dose CCR intervention over a 60-90-min session. The CCR intervention included a social story, role-play and discussion. All participants viewed a video of a CWS and stuttering was defined at baseline. The SROM measured peer attitudes at six months after intervention. Randomisation was stratified by quintile group using a 1:1 allocation ratio. Full blinding was not possible; however, the outcome assessor was partially blinded and the analyst was also blinded. Generalised estimating equations (GEE) was used assuming an exchangeable correlation structure to analyse the data adopting an intention-to-treat principle. Multiple imputation was used to handle missing data. Criterion for statistical significance was set at alpha = 0.05. RESULTS: Ten schools were randomly allocated to control (k = 5) and intervention groups (k = 5), with n = 223 participants allocated to intervention and n = 231 to control groups. A total of 454 participants completed the SROMs in control (n = 231) and intervention (n = 223) groups and were analysed at baseline and six months after intervention. There was no statistically significant difference on the global SROM score (mean difference - 0.11; 95% confidence interval [CI] - 1.56-1.34; p = 0.88). There were also no significant differences on SROM subscales: PSD (mean difference 1.04; 95% CI - 1.02-311; p = 0.32), SP (mean difference - 0.45; 95% CI - 1.22-0.26; p = 0.21) and VI (mean difference 0.05; 95% CI - 1.01-1.11; p = 0.93). Additionally, there was no significant subgroup effect on the global SROM score (lower versus higher quintile subgroups) (interaction p value = 0.52). No harms were noted or reported. CONCLUSION: No statistically significant differences were noted. It is possible that the time frame was too short to note changes in peer attitudes and that further study is required to confirm the findings of this study. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03111524 . Registered on 9 March 2017.

A pilot study to determine the feasibility of a cluster randomised controlled trial of an intervention to change peer attitudes towards children who stutter.

BACKGROUND:  While randomised controlled trials (RCTs) are considered the gold standard of research, prior study is needed to determine the feasibility of a future large-scale RCT study. Objectives: This pilot study, therefore, aimed to determine feasibility of an RCT by exploring: (1) procedural issues and (2) treatment effect of the Classroom Communication Resource (CCR), an intervention for changing peer attitudes towards children who stutter. Method: A pilot cluster stratified RCT design was employed whereby the recruitment took place first at school-level and then at individual level. The dropout rate was reported at baseline, 1 and 6 months post-intervention. For treatment effect, schools were the unit of randomisation and were randomised to receive either the CCR intervention administered by teachers or usual practice, using a 1:1 allocation ratio. The stuttering resource outcomes measure (SROM) measured treatment effect at baseline, 1 and 6 months post-intervention overall and within the constructs (positive social distance, social pressure and verbal interaction). Results: For school recruitment, 11 schools were invited to participate and 82% (n = 9) were recruited. Based on the school recruitment, N = 610 participants were eligible for this study while only n = 449 were recruited, where there was n = 183 in the intervention group and n = 266 in the control group. The dropout rate from recruitment to baseline was as follows: intervention, 23% (n = 34), and control, 6% (n = 15). At 1 month a dropout rate of 7% (n = 10) was noted in the intervention and 6% (n = 15) in the control group, whereas at 6 months, dropout rates of 7% (n = 10) and 17% (n = 44) were found in the intervention and control groups, respectively. For treatment effect on the SROM, the estimated mean differences between intervention and control groups were (95% Confidence Interval (CI): -1.07, 5.11) at 1 month and 3.01 (95% CI: -0.69, 6.69) at 6 months. A statistically significant difference was observed at 6 months on the VI subscale of the SROM, with 1.35 (95% CI: 0.58, 2.13). Conclusion: A high recruitment rate of schools and participants was observed with a high dropout rate of participants. Significant differences were only noted at 6 months post-intervention within one of the constructs of the SROM. These findings suggest that a future RCT study is warranted and feasible.