Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the CASCADE collaboration from 1987 to 2003

OBJECTIVES: To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. METHODS: The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individual's nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. RESULTS: Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. CONCLUSIONS: Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.     

Short-term CD4 cell response after highly active antiretroviral therapy initiated at different times from seroconversion in 1,500 seroconverters

The effect of HIV infection duration and CD4 cell count on short-term CD4 response was evaluated in treatment-naive seroconverters using logistic regression adjusted for CD4 count before highly active antiretroviral therapy (HAART) as well as for exposure category, age, sex, acute infection, and cohort. This association was also investigated in pretreated seroconverters, further adjusting for prior therapy. CD4 response (increase of >100 cells/microL at 6 months) was more likely if HAART was initiated in the first year following seroconversion (OR = 1.50 [95% CI: 1.07-2.10] compared with 2-5 years). There was no improvement in response from initiating HAART with CD4 count >350 cells/microL compared with 201 to 350 cells/microL. Below 200 cells/microL, however, the chance of a CD4 response appeared to be reduced (OR = 0.72 [95% CI: 0.40-1.28] for 0-200 cells/microL compared with 201-350 cells/microL, P = 0.26). Results were similar for pretreated individuals. Further, in pretreated individuals, a CD4 response was less likely if the CD4 nadir was lower than the pre-HAART CD4 count (OR = 0.18 [95% CI: 0.10-0.36] for >150 cells/microL difference between nadir and pre-HAART CD4 count vs. no difference, P < 0.001). Given the limitations of observational studies, particularly the inability to control for unmeasured confounders, these findings suggest that the initiation of HAART within the first year following seroconversion appears to improve short-term immunologic response. After that time, there is little to be gained in terms of short-term response from initiating HAART before reaching a CD4 count of 200 cells/microL.     

Using psychometric ability to improve education in ultrasound-guided regional anaesthesia: a multicentre randomised controlled trial

The learning curve for novices developing regional anaesthesia skills, such as real-time ultrasound-guided needle manipulation, may be affected by innate visuospatial ability, as this influences spatial cognition and motor co-ordination. We conducted a multinational randomised controlled trial to test if novices with low visuospatial ability would perform better at an ultrasound-guided needling task with deliberate practice training than with discovery learning. Visuospatial ability was evaluated using the mental rotations test-A. We recruited 140 medical students and randomly allocated them into low-ability control (discovery learning), low-ability intervention (received deliberate practice), high-ability control, and high-ability intervention groups. Primary outcome was the time taken to complete the needling task, and there was no significant difference between groups: median (IQR [range]) low-ability control 125 s (69–237 [43–600 s]); low-ability intervention 163 s (116–276 [44–600 s]); high-ability control 130 s (80–210 [41–384 s]); and high-ability intervention 177 s (113–285 [43–547 s]), p = 0.06. No difference was found using the global rating scale: mean (95%CI) low-ability control 53% (95%CI 46–60%); low-ability intervention 61% (95%CI 53–68%); high-ability control 63% (95%CI 56–70%); and high-ability intervention 66% (95%CI 60–72%), p = 0.05. For overall procedure pass/fail, the low-ability control group pass rate of 42% (14/33) was significantly less than the other three groups: low-ability intervention 69% (25/36); high-ability control 68% (25/37); and high-ability intervention 85% (29/34) p = 0.003. Further research is required to determine the role of visuospatial ability screening in training for ultrasound-guided needle skills.     

Ten‐year attrition and antiretroviral therapy response among HIV‐positive adults: a sex‐based cohort analysis from eight West African countries

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.     

Mesh compared with non-mesh methods of open groin hernia repair: systematic review of randomized controlled trials

BACKGROUND: Open tension-free methods of groin hernia repair have been widely adopted despite little rigorous evaluation. METHODS: Information was assimilated from all randomized or quasi-randomized trials comparing open mesh with open non-mesh methods to assess benefits and safety. Electronic databases were searched and members of the EU Hernia Trialists Collaboration consulted to identify trials. Prespecified data items were extracted from reports, and quantitative or, if not possible, qualitative meta-analysis was performed. RESULTS: Fifteen eligible trials, which included 4005 participants, were identified. There were similar numbers of complications in each group, with few data to address short-term pain and length of stay in hospital. Return to usual activities was quicker in the mesh group for seven of ten trials (P not significant). There were fewer reported recurrences in the mesh groups: overall 21 (1.4 per cent) of 1513 versus 72 (4.4 per cent) of 1634 (odds ratio 0.39 (95 per cent confidence interval 0.25-0. 59); P < 0.001). CONCLUSION: Although the rigorous search maximized trial identification, formal meta-analysis was limited by the variation in trial reporting. Within the data available, mesh repair was associated with fewer recurrences.     

Laparoscopic compared with open methods of groin hernia repair: systematic review of randomized controlled trials

BACKGROUND: The place of laparoscopic groin hernia repair remains controversial. Individual randomized controlled trials alone have not provided statistically reliable results when considering recurrence, potentially serious complications and chronic pain. METHODS: A rigorous systematic review was performed of published data from all relevant randomized or quasi-randomized trials. Electronic databases were searched and members of the EU Hernia Trialists Collaboration consulted to identify trials. Prespecified data items were extracted from reports and, where possible, quantitative meta-analysis was performed. RESULTS: Thirty-four published reports of eligible trials were included, involving 6804 participants. Sample sizes ranged from 20 to 1051, with follow-up from 6 weeks to 36 months. Duration of operation was longer in the laparoscopic groups (P < 0.001, Sign test). Operative complications were uncommon for both methods, but visceral and vascular injuries were more frequent in the laparoscopic group (4.7 per 1000 versus 1. 1 per 1000). Postoperative pain was less among laparoscopic groups (P = 0.08). Length of hospital stay did not differ significantly between groups (P = 0.50), but return to usual activity was earlier for laparoscopic groups (P < 0.001). Chronic pain and numbness were reported for only a small minority of trials. Overall, recurrences did not differ between groups, but comparison of laparoscopic with open non-mesh repair favoured laparoscopic methods, significantly so for transabdominal preperitoneal repair (Peto odds ratio 0.56 (95 per cent confidence interval 0.33-0.93); P = 0.026). CONCLUSION: Although the rigorous search maximized trial identification, variation in trial reporting made formal meta-analysis difficult. Laparoscopic repair was associated with less postoperative pain and more rapid return to normal activities, but it takes longer to perform and may increase the risk of rare, but serious, complications.     

One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6–20.7) and 32.3 (95% CI 27.3–38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58–5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.     

黑素细胞及相关细胞群参与白癜风发病的研究进展

【摘要】 白癜风发病机制复杂，黑素细胞缺失是核心。目前认为除黑素细胞自身缺陷外，表皮和真皮细胞群的功能异常及其与黑素细胞的交互作用对白癜风的发病同样重要，充分而准确地了解不同病期白癜风皮肤全层细胞、组织的病理生理状态，对认识和治疗白癜风有重要作用。本文旨在综述黑素细胞及相关细胞群在白癜风发病中作用的研究进展。