Temporal Trends in Treatment Outcomes for HIV-1 and HIV-2-Infected Adults Enrolled in C?te d'Ivoire's National Antiretroviral Therapy Program

Background

In Côte d''Ivoire during 2004–2007, numbers of ART enrollees increased from <5,000 to 36,943. Trends in nationally representative ART program outcomes have not yet been reported.

Methodology/Principal Findings

We conducted a retrospective chart review to assess trends in patient characteristics and attrition [death or loss to follow-up (LTFU)] over time, among a nationally representative sample of 3,682 adults (≥15 years) initiating ART during 2004–2007 at 34 health facilities. Among ART enrollees during 2004–2007, median age was 36, the proportion female was 67%, the proportion HIV-2-infected or dually HIV-1&2 reactive was 5%, and median baseline CD4⁺ T-cell (CD4) count was 135 cells/µL. Comparing cohorts initiating ART in 2004 with cohorts initiating ART in 2007, median baseline weight declined from 55 kg to 52 kg (p = 0.008) and the proportion weighing <45 kg increased from 17% to 22% (p = 0.014). During 2004–2007, pharmacy-based estimates of the percentage of new ART enrollees ≥95% adherent to ART declined from 74% to 60% (p = 0.026), and twelve-month retention declined from 86% to 69%, due to increases in 12-month mortality from 2%–4% and LTFU from 12%–28%. In univariate analysis, year of ART initiation was associated with increasing rates of both LTFU and mortality. Controlling for baseline CD4, weight, adherence, and other risk factors, year of ART initiation was still strongly associated with LTFU but not mortality. In multivariate analysis, weight <45 kg and adherence <95% remained strong predictors of LTFU and mortality.

Conclusions

During 2004–2007, increasing prevalence among ART enrollees of measured mortality risk factors, including weight <45 kg and ART adherence <95%, might explain increases in mortality over time. However, the association between later calendar year and increasing LTFU is not explained by risk factors evaluated in this analysis. Undocumented transfers, political instability, and patient dissatisfaction with crowded facilities might explain increasing LTFU.     

Antiretroviral Therapy Uptake,Attrition, Adherence and Outcomes among HIV-Infected Female Sex Workers: A Systematic Review and Meta-Analysis

Purpose

We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.

Methods

We systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran''s Q test and I² statistic).

Results

39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%–48%, I² = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%–94%, I² = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%–81%, I² = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%–11%, I² = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%–11%, I² = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%–83%, I² = 36%, 4 studies), and 57% (95% CI: 46%–68%, I² = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm³ (4 studies).

Conclusions

Despite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.     

A Meta-Analysis of Anti-Vascular Endothelial Growth Factor Remedy for Macular Edema Secondary to Central Retinal Vein Occlusion

Background

Central retinal vein occlusion (CRVO) associates with severe vision outcome and no proven beneficial treatment. Our meta-analysis intended to appraise the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents in macular edema (ME) following CRVO.

Methods

Data were collected and analyzed by Review Manager 5.2.1. We employed a random-effects model to eliminate between-study heterogeneity. N_fs (called fail-safe number) was calculated to evaluate the publication bias.

Results

We included 5 trials consisting 323 cases and 281 controls. Primary outcomes showed that overall comparison of anti-VEGF agents with placebo control yielded a 374% and 136% increased tendency for a gain of 15 letters or more on Early Treatment Diabetic Retinopathy Study (ETDRS) chart (95% confidence interval [95% CI]: 2.43–9.23; P<0.00001; I² = 59%, 95% CI: 1.60–3.49; P<0.0001; I² = 0%, respectively) at 6 and 12 months. Secondary outcomes showed that a 90% and 77% decreased risk at 6 and 12 months for a loss of 15 letters or more. The overall mean difference showed a statistically significance in best-corrected visual acuity (BCVA) on each time point. However, changes of central retinal thickness (CRT) lost significance at 12 months after 6-month as-needed treatment. The incidence of adverse events (AEs) had no statistical difference between anti-VEGF and placebo groups. Subgroup analyses indicated that patients receiving Aflibercept got the highest tendency to gain 15 letters or more (OR = 9.78; 95% CI: 4.43–21.56; P<0.00001). Age controlled analysis suggested a weaken tendency of BCVA improvement in age over 50 (MD = 12.26; 95% CI: 7.55–16.98; P<0.00001). Subgroup analysis by clinical classification showed a strengthen difference of BCVA changes at 6 months in ischemic type (MD = 19.65 letters, 95% CI: 13.15 to 26.14 letters, P<0.00001).

Conclusions

Our results showed that anti-VEGF agents were superior to placebo in CRVO-ME treatment with no statistically significant AEs, especially in younger people and for ischemic type.     

Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database

Background

Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.

Methods

Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed.

Results

Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based).

Conclusions

The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.     

Docetaxel,Cisplatin and Fluorouracil (DCF) Regimen Compared with Non-Taxane-Containing Palliative Chemotherapy for Gastric Carcinoma: A Systematic Review and Meta-Analysis

Background

Gastric carcinoma (GC) is one of the highest cancer-mortality diseases with a high incidence rate in Asia. For surgically unfit but medically fit patients, palliative chemotherapy is the main treatment. The chemotherapy regimen of docetaxel, cisplatin and 5-fluorouracil (DCF) has been used to treat the advanced stage or metastatic GC. It is necessary to compare effectiveness and toxicities of DCF regimen with non-taxane-containing palliative chemotherapy for GC.

Methods

PubMed, EmBase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched to select relative randomized controlled trials (RCTs) comparing DCF to non-taxane-containing chemotherapy for patients with palliatively resected, unresectable, recurrent or metastatic GC. Primary outcome measures were 1-year and 2-year overall survival (OS) rates. Secondary outcome measures were median survival time (MST), median time to progression (TTP), response rate and toxicities.

Results

Twelve RCTs were eligible and 1089 patients were analyzed totally (549 in DCF and 540 in control). DCF regimen increased partial response rate (38.8% vs 27.9%, p = 0.0003) and reduced progressive disease rate (18.9% vs 33.3%, p = 0.0005) compared to control regimen. Significant improvement of 2-year OS rate was found in DCF regimen (RR = 2.03, p = 0.006), but not of 1-year OS rate (RR = 1.22, p = 0.08). MST was significantly prolonged by DCF regimen (p = 0.039), but not median TTP (p = 0.054). Both 1-year OS rate and median TTP had a trend of prolongation by DCF regimen. Chemotherapy-related mortality was comparable (RR = 1.23, p = 0.49) in both regimens. In grade I-IV toxicities, DCF regimen showed a major raise of febrile neutropenia (RR = 2.33, p<0.0001) and minor raises of leucopenia (RR = 1.25, p<0.00001), neutropenia (RR = 1.19, p<0.00001), and diarrhea (RR = 1.59, p<0.00001), while in other toxicities there were no significant differences.

Conclusion

DCF regimen has better response than non-taxane containing regimen and could potentially improve the survival outcomes. The chemotherapy-related toxicity of DCF regimen is acceptable to some extent.     

Association between Apolipoprotein E Gene Polymorphism and the Risk of Coronary Artery Disease in Chinese Population: Evidence from a Meta-Analysis of 40 Studies

Background

Epidemiological studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphism and coronary artery disease (CAD) risk which developed inconsistent conclusions. To derive a more precise estimation of the relationship in Chinese population, we performed this meta-analysis.

Methods

Databases, including PubMed, EMbase, Web of Science, CBMdisc and CNKI, were searched to get the genetic association studies. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Review Manager 5.1.2 and Stata 11.0.

Results

We identified a total of 40 studies, including 4,564 CAD cases and 3,985 controls. The results showed evidence for significant association between ApoE ε4 allele and CAD risk (for ε2/ε4 vs. ε3/ε3: OR = 1.86, 95% CI = 1.42–2.43, p<0.00001; for ε3/ε4 vs. ε3/ε3: OR = 2.34, 95% CI = 2.07–2.65, p<0.00001; for ε4/ε4 vs. ε3/ε3: OR = 2.89, 95% CI = 1.87–4.47, p<0.00001; for ε4 allele vs. ε3 allele: OR = 2.11, 95% CI = 1.91–2.35, p<0.00001).

Conclusions

The present meta-analysis suggests an association between ApoE ε4 allele and increased risk of CAD in Chinese population. However, due to the small sample size in most of the included studies and the selection bias existed in some studies, the results should be interpreted with caution.     

Prognostic Role of Pre-Treatment Serum AFP-L3% in Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

Background

Serum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.

Methods

Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.

Results

Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively).

Conclusion

The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration.     

Efficacy of Short-Term High-Dose Statin Pretreatment in Prevention of Contrast-Induced Acute Kidney Injury: Updated Study-Level Meta-Analysis of 13 Randomized Controlled Trials

Background

There have been conflicting results across the trials that evaluated prophylactic efficacy of short-term high-dose statin pre-treatment for prevention of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary angiography (CAG). The aim of the study was to perform an up-to-date meta-analysis regarding the efficacy of high-dose statin pre-treatment in preventing CIAKI.

Methods and Results

Randomized-controlled trials comparing high-dose statin versus low-dose statin or placebo pre-treatment for prevention of CIAKI in patients undergoing CAG were included. The primary endpoint was the incidence of CIAKI within 2–5days after CAG. The relative risk (RR) with 95% CI was the effect measure. This analysis included 13 RCTs with 5,825 total patients; about half of them (n = 2,889) were pre-treated with high-dose statin (at least 40 mg of atorvastatin) before CAG, and the remainders (n = 2,936) pretreated with low-dose statin or placebo. In random-effects model, high-dose statin pre-treatment significantly reduced the incidence of CIAKI (RR 0.45, 95% CI 0.35–0.57, p<0.001, I² = 8.2%, NNT 16), compared with low-dose statin or placebo. The benefit of high-dose statin was consistent in both comparisons with low-dose statin (RR 0.47, 95% CI 0.34–0.65, p<0.001, I² = 28.4%, NNT 19) or placebo (RR 0.34, 95% CI 0.21–0.58, p<0.001, I² = 0.0%, NNT 16). In addition, high-dose statin showed significant reduction of CIAKI across various subgroups of chronic kidney disease, acute coronary syndrome, and old age (≥60years), regardless of osmolality of contrast or administration of N-acetylcystein.

Conclusions

High-dose statin pre-treatment significantly reduced overall incidence of CIAKI in patients undergoing CAG, and emerges as an effective prophylactic measure to prevent CIAKI.     

Predictors of Raised Viral Load during Antiretroviral Therapy in Patients with and without Prior Antiretroviral Use: A Cross-Sectional Study

Objectives

In Lagos, Nigeria, Médecins Sans Frontières (MSF) and the Ministry of Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based clinic. We performed a cross-sectional study to compare factors associated with raised viral load between patients with (“experienced”) and without (“naïve”) prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also examined factors influencing ARV adherence in experienced patients prior to clinic entry.

Methods

We included adult patients receiving ART from MSF who answered a questionnaire about previous antiretroviral use. Multivariate logistic regression was used to estimate odds ratios (OR) for raised viral load (≥1000 copies/mL).

Results

1246 (96%) patients answered: 1075 (86%) reported no, and 171 (14%) some, prior ARV exposure. ARV-naïve patients were more immunosuppressed at baseline: 65% vs 37% (p<0.001) had CD4<200; 17% vs 9% (p = 0.013) were WHO stage 4. Proportionately more experienced than naïve patients had raised viral loads (20% vs 9%, p<0.001) on ART in the MSF/MoH clinic. Raised viral load was associated with prior ARV experience (adjusted OR = 3.74, 95%CI 2.09–6.70, p<0.001) and complete interruption of current ART (adjusted OR = 3.71, 95%CI 2.06–6.68, p<0.001). Higher CD4 at time of VL and a higher self-rated score of recent adherence were associated with lower OR of a raised viral load. Among experienced patients who missed pills before joining MSF/MoH, most common reasons were because ARVS were not affordable (58%) or available (33%), with raised viral load associated with being unsure how to take them (OR = 3.16, 95%CI 1.10–9.12, p = 0.033).

Conclusions

Patients previously exposed to ARVs had increased OR of raised viral load. The cost and availability of ARVs were common reasons for missing ARVs before joining the MSF/MoH clinic, and inadequate patient knowledge was associated with raised viral load.     

Traditional but Not HIV-Related Factors Are Associated with Nonalcoholic Fatty Liver Disease in Asian Patients with HIV-1 Infection

Background

The prevalence and factors associated with nonalcoholic fatty liver disease (NAFLD) are largely unknown in HIV-1 monoinfected patients.

Methods

The present study elucidated the prevalence and factors associated with NAFLD among Asian patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Diagnosis of NAFLD was based on the liver to kidney contrast and diffusion in hepatic echogenicity. Uni- and multi-variate logistic regression analyses were applied to estimate factors associated with NAFLD.

Results

435 Asian patients free of chronic hepatitis B or C virus infection and without excessive alcohol intake were analyzed. NAFLD was diagnosed in 135 (31%) patients. Obesity (BMI >30 kg/m²) was evident in 18 (4.1%) patients, and BMI was >25 kg/m² in 103 (24%). Multivariate analysis identified higher BMI (per 1 kg/m² increment, adjusted OR = 1.198; 95% CI, 1.112–1.290; p<0.001), dyslipidemia (adjusted OR = 2.045; 95% CI, 1.183–3.538; p = 0.010), and higher ALT to AST ratio (per 1 increment, adjusted OR = 3.557; 95% CI, 2.129–5.941; p<0.001) as significant factors associated with NAFLD. No HIV-specific variables, including treatment with dideoxynucleoside analogues (didanosine, stavudine, and zalcitabine) and cumulative duration of antiretroviral therapy (ART), were associated with NAFLD.

Conclusions

The incidence of NALFD among Asian patients with HIV-1 infection is similar to that in Western countries. NAFLD was associated with high BMI, dyslipidemia, and high ALT/AST ratio, but not with HIV-related factors. The results highlight the importance of early recognition and management of NAFLD and traditional factors associated with NAFLD for Asian patients with HIV-1 infection.     

Clinical,Immunological and Treatment-Related Factors Associated with Normalised CD4+/CD8+ T-Cell Ratio: Effect of Na?ve and Memory T-Cell Subsets

Background

Although effective antiretroviral therapy(ART) increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+/CD8+ ratio have not been well described.

Methods

A cross-sectional study in a cohort of ambulatory HIV+ patients. We used flow cytometry on fresh blood to determine expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+(central memory), CD45RO+CD62L-(effector memory) and CD45RO-CD62L+(naïve) alongside routine T-cell subsets(absolute, percentage CD4+ and CD8+ counts), HIVRNA and collected demographic and treatment data. Relationship between CD4+/CD8+ T-cell ratio and expanded T-cell subsets was determined using linear regression analysis. Results are median[IQR] and regression coefficients unless stated.

Results

We recruited 190 subjects, age 42(36–48) years, 65% male, 65.3% Caucasian, 91% on ART(52.6% on protease inhibitors), 78.4% with HIVRNA<40cps/ml and median ART duration 6.8(2.6–10.2) years. Nadir and current CD4+ counts were 200(112–309) and 465(335–607) cells/mm³ respectively. Median CD4+/CD8+ ratio was 0.6(0.4–1.0), with 26.3% of subjects achieving CD4+/CD8+ ratio>1. Of the expanded CD4+ T-cell subsets, 27.3(18.0–38.3)% were naïve, 36.8(29.0–40.0)% central memory and 27.4(20.0–38.5)% effector memory. Of the CD8+ T-cells subsets, 16.5(10.2–25.5)% were naïve, 19.9(12.7–26.6)% central memory and 41.0(31.8–52.5)% effector memory. In the multivariable adjusted analysis, total cumulative-ART exposure(+0.15,p = 0.007), higher nadir CD4+ count(+0.011,p<0.001) and higher %CD8+ naive T-cells(+0.0085,p<0.001) were associated with higher CD4+/CD8+ ratio, higher absolute CD8+ T-cell(-0.0044,p<0.001) and higher %CD4+ effector memory T-cells(-0.004,p = 0.0036) were associated with lower CD4+/CD8+ ratio. Those with CD4+/CD8+ ratio>1 had significantly higher median %CD8+ naive T-cells; 25.4(14.0–36.0)% versus 14.4(9.4–21.6)%, p<0.0001, but significantly lower absolute CD8+ count; 464(384.5–567) versus 765(603–1084) cells/mm³, p<0.001.

Conclusions

Study suggests important role for naïve CD8+ T-cell populations in normalisation of the immune response to HIV-infection. How these findings relate to persistent immune activation on ART requires further study.     

Disinhibition in Risky Sexual Behavior in Men,but Not Women,during Four Years of Antiretroviral Therapy in Rural,Southwestern Uganda

Background

In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy.

Methods

We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count.

Results

506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29–39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p<0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95%CI 0.74–0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95%CI 1.14–1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95%CI 0.92–1.67, p = 0.16).

Conclusions

Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pre-treatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.     

A Meta-Analysis of Apolipoprotein E Gene ε2/ε3/ε4 Polymorphism for Gallbladder Stone Disease

Background

Numerous studies have investigated the relationship between apolipoprotein (Apo) E gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of a common ε2/ε3/ε4 polymorphism in Apo E gene on the risk of gallbladder stone disease.

Method

Data were analyzed using the RevMan software (V5.1) and a random-effects model was applied irrespective of between-study heterogeneity. Publication bias was weighed using the fail-safe number.

Results

There were 17 study populations totaling 1773 cases and 2751 controls for ε2/ε3/ε4 polymorphism of Apo E gene. Overall comparison of alleles ε2 with ε3 in all study populations yielded a 16% decreased risk for GSD (95% confidence interval [95% CI]: 0.68–1.05; P = 0.31; I² = 13%), and comparison of alleles ε4 with ε3 yielded a 25% increased risk (95% confidence interval [95% CI]: 0.97–1.61; P = 0.0003; I² = 63%). Subgroup analysis by study design indicated that the magnitude of association in hospital-based studies was largely significantly strengthened for ε4 allelic model (odds ratio [OR]  = 1.46; 95% CI: 1.05–2.02; p = 0.0007; I² = 65%). Subgroup analysis by age of controls indicated a remarkably significant elevation in the magnitude of association in age >50 subgroups in ε4 allelic model (OR = 1.50; 95% CI: 1.03–2.19; p = 0.0009; I² = 72%). Moreover, subgroup analysis by cases gender indicated a reduction in the magnitude of association in male<30% studies for E2/2 genotypic model (OR = 0.32; 95% CI: 0.07–1.49; p = 0.16; I² = 45%).

Conclusions

Our results reveal that Apo E gene ε4 allele is a risk factor of gallbladder stone disease, especially in elder people and Chinese population.     

Mortality among Methadone Maintenance Clients in China: A Six-Year Cohort Study

Objective

To assess the overall mortality of methadone maintenance treatment (MMT) clients in China and its associated factors.

Methods

A total of 1,511 MMT clients, all of whom enrolled in China''s first eight MMT clinics between March and December 2004, were included in this cohort study and followed for approximately six years, until June 2010. Mortality and its predictors were examined using Cox proportional hazards regression models.

Results

A total of 154 deaths were observed within 5,391 person-years (PY) of follow-up for an all-cause mortality rate of 28.6 per 1,000 PY. The leading causes of death were drug overdose (33.8%), HIV/AIDS-unrelated disease (21.4%), and HIV/AIDS (16.9%). The all-cause mortality rate of clients engaged in MMT for one year or less was roughly three times that of clients who stayed in MMT for four years or more (14.0 vs. 4.6, p<0.0001), HIV-positive subjects was nearly four times mortality rate than that of HIV-negative individuals (28.1 vs.6.8, p<0.0001). ART-naive HIV-positive subjects had approximately two times higher mortality rate than those receiving ART (31.2 vs. 17.3, <0.0001). After adjusting for confounding variables, we found that being male (HR = 1.63, CI: 1.03–2.57, p = 0.0355) and being HIV-positive (HR = 5.16, CI: 3.70–7.10, p<0.0001) were both associated with higher risk of death whereas increased durations of methadone treatment were associated with a lower risk of death (HR = 0.26, CI: 0.18–0.38, p<0.0001 for two to three years, HR = 0.08, CI: 0.05–0.14, p<0.0001 for four or more years).

Conclusion

Overall mortality was high among MMT clients in China. Specific interventions aimed at decreasing mortality among MMT clients are needed. Our study supports the need for keeping client at MMT longer and for expanding ART coverage and suggests the potential benefits of integrated MMT and ART services for drug users in China.     

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

Background

Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models.

Results

A total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08–1.54), with significant evidence of heterogeneity among these studies (p<0.001, I² = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05–1.77) for diabetic men and 1.28 (0.75–2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14–1.55), with evident heterogeneity between studies (p = 0.002, I² = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30–1.82) and women (RR 1.50, 95% CI: 1.05–2.14).

Conclusion

These findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer.     

Helminthic Infections Rates and Malaria in HIV-Infected Pregnant Women on Anti-Retroviral Therapy in Rwanda

Background

Within sub-Saharan Africa, helminth and malaria infections cause considerable morbidity in HIV-positive pregnant women and their offspring. Helminth infections are also associated with a higher risk of mother-to-child HIV transmission. The aim of this study was to determine the prevalence of, and the protective and risk factors for helminth and malaria infections in pregnant HIV-positive Rwandan women receiving anti-retroviral therapy (ART).

Methodology and principle findings

Pregnant females (n = 980) were recruited from health centres in rural and peri-urban locations in the central and eastern provinces of Rwanda. Helminth infection was diagnosed using the Kato Katz method whilst the presence of Plasmodium falciparum was identified from blood smears. The prevalence of helminth infections was 34.3%; of malaria 13.3%, and of co-infections 6.6%. Helminth infections were more common in rural (43.1%) than peri-urban (18.0%; p<0.0005) sites. A CD4 count ≤350 cells/mm³ was associated with a higher risk of helminth infections (odds ratio, 3.39; 95% CIs, 2.16–5.33; p<0.0005) and malaria (3.37 [2.11–5.38]; p<0.0005) whilst helminth infection was a risk factor for malaria infection and vice versa. Education and employment reduced the risk of all types of infection whilst hand washing protected against helminth infection (0.29 [0.19–0.46]; p<0.0005);). The TDF-3TC-NVP (3.47 [2.21–5.45]; p<0.0005), D4T-3TC-NVP (2.47 [1.27–4.80]; p<0.05) and AZT-NVP (2.60 [1.33–5.08]; p<0.05) regimens each yielded higher helminth infection rates than the AZT-3TC-NVP regimen. Anti-retroviral therapy had no effect on the risk of malaria.

Conclusion/significance

HIV-positive pregnant women would benefit from the scaling up of de-worming programs alongside health education and hygiene interventions. The differential effect of certain ART combinations (as observed here most strongly with AZT-3TC-NVP) possibly protecting against helminth infection warrants further investigation.     

Role of Traditional Risk Factors and Antiretroviral Drugs in the Incidence of Chronic Kidney Disease,ANRS CO3 Aquitaine Cohort,France, 2004–2012

Objective

To examine the role of antiretroviral drugs (ART), HIV-related and traditional risk factors on the incidence of chronic kidney disease (CKD) in HIV-infected patients.

Design

Prospective hospital-based cohort of HIV-infected patients from 2004 to 2012.

Methods

CKD was defined using MDRD equation as an estimated glomerular filtration rate (eGFR) less than 60 ml/mn/1.73 m² at 2 consecutive measurements ≥3 months apart. Poisson regression models were used to study determinants of CKD either measured at baseline or updated. ART exposure was classified as ever or never. We additionally tested the role of tenofovir (TDF), whether or not prescribed concomitantly with a Protease Inhibitor (PI), taking into account the cumulative exposure to the drug.

Results

4,350 patients (74% men) with baseline eGFR>60 ml/mn/1.73 m² were followed for a median of 5.8 years. At the end of follow-up, 96% had received ART, one third of them (35%) jointly received TDF and a PI. Average incidence rate of CKD was 0.95% person-years of follow-up. Incidence of CKD was higher among women (IRR = 2.2), older patients (>60 y vs <45 y: IRR = 2.5 and 45–60 y: IRR = 1.7), those with diabetes (IRR = 1.9), high blood pressure (IRR = 1.5), hyperlipidemia (IRR = 1.5), AIDS stage (IRR = 1.4), low baseline eGFR (IRR = 15.8 for 60<eGFR<70 ml/mn/1.73 m² vs >90 and IRR = 7.1 for 70<eGFR<80 ml/mn/1.73 m²), current CD4+<200 cells/mm³ vs >500/mm³ (IRR = 2.5), and exposure to TDF (IRR = 2.0). Exposure to TDF was even strongly associated with CKD when co-administered with PIs (IRR = 3.1 vs 1.3 when not, p<0,001). A higher risk of CKD was found when tenofovir exposure was >12 months [IRR = 3.0 with joint PIs vs 1.3 without (p<0.001)]. A vast majority of those developing CKD (76.6%) had a baseline eGFR between 60 and 80 ml/mn/1.73 m².

Conclusion

In patients with eGFR between 60 and 80 mL/min/1.73 m², a thorough control of CKD risk factors is warranted. The use of TDF, especially when co-administered with PIs, should be mentioned as a relative contraindication in presence of at least one of these risk factors.     

Does Minimally-Invasive Pancreaticoduodenectomy Have Advantages over Its Open Method? A Meta-Analysis of Retrospective Studies

Background

While more and more open procedures now routinely performed using laparoscopy, minimally invasive pancreaticoduodenectomy (MIPD) remains one of the most challenging abdominal procedures. Therefore, we carried out this meta-analysis to evaluate whether MIPD is safe, feasible and worthwhile.

Methods

PubMed, EMBASE, and Cochrane Library were searched to identify studies published between January 1994 and November 2013 comparing MIPD with open pancreaticoduodenectomy (OPD). Intraoperative outcomes, oncologic safety, postoperative complications, and postoperative recovery were evaluated.

Results

11 retrospective studies representing 869 patients (327 MIPDs, 542 OPDs) were included. MIPD was associated with a reduction in estimated blood loss (MD −361.93 ml, 95% CI −519.22 to −204.63 ml, p<0.001, I² = 94%), wound infection (OR 0.41, 95% CI 0.22 to 0.78, p = 0.007, I² = 0%), and hospital stay (MD −2.64 d, 95% CI −4.23 to −1.05 d, p = 0.001, I² = 78%). However, it brings longer operative time (MD 105 min, 95% CI 49.73 to 160.26 min, p<0.001, I² = 93%). There were no significant differences between the two procedures in likelihood of overall complications (p = 0.05), pancreatic fistula (PF) (p = 0.86), delayed gastric empting (DGE) (p = 0.96), positive surgical margins (p = 0.07), retrieval of lymph nodes (p = 0.48), reoperation (p = 0.16) and mortality (p = 0.64).

Conclusions

Our results suggest that MIPD is currently safe, feasible and worthwhile. But considering the selection bias, complexity of MIPD and lack of long-term oncologic outcomes, we suggest it be performed in a high-volume pancreatic surgery center in selected patients.     

Influence of Body Mass Index (BMI) on Functional Improvements at 3 Years Following Total Knee Replacement: A Retrospective Cohort Study

Background

The number of patients presenting for total knee replacement who are classified as obese is increasing. The functional benefits of performing TKR in these patients are unclear.

Aim

To assess the influence pre-operative body mass index has upon knee specific function, general health status and patient satisfaction at 3 years following total knee replacement.

Design

Retrospective comparative cohort study using prospectively collected data from an institutional arthroplasty register.

Methods

1367 patients were assessed using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Medical Outcomes Trust Short Form-36 (SF-36) scores supplemented by a validated measure of satisfaction pre-operatively and subsequently at 1,2 and 3 year post-operatively. Comparisons were made by dividing the cohort into 4 groups based on body mass index (BMI) 18.5–25.0 kg/m² (n = 253);>25.0–30.0 kg/m² (n = 559);>30.0−35.0 kg/m² (n = 373);>35.0 kg/m² (n = 182).

Results

Despite lower pre-operative, 1 and 3 year WOMAC and SF-36 scores patients with the highest BMIs >35.0 kg/m² experienced similar improvements to patients with a ‘normal‘ BMI (18.5–25.0 kg/m²) at 1 year (Difference in WOMAC improvement = 0.0 (95%CI −5.2 to 5.2), p = 1.00) and this improvement was sustained at up to 3 years (Difference in 1 year to 3 year improvement = 2.2 (95%CI: −2.1 to 6.5), p = 1.00). This effect was also observed for the SF-36 mental and physical component scores. Despite equivalent functional improvements levels of satisfaction in the >35.0 kg/m² group were lower than for any other BMI group (>35.0 kg/m² = 84.6% satisfied versus 18.5–5.0 kg/m² = 93.3% satisfied,p = 0.01) as was the proportion of patients who stated they would have the operation again (>35.0 kg/m² = 69.6% versus 18.5–25.0 kg/m² = 82.2%,p = 0.01).

Conclusion

Obese and morbidly obese patients gain as much functional benefit from total knee replacement as patients with lesser body mass indexes. This benefit is maintained for up to 3 years following surgery. However, these patients are less satisfied with their knee replacement and almost a third would not have the operation again.