Impact of Xpert MTB/RIF Testing on Tuberculosis Management and Outcomes in Hospitalized Patients in Uganda

Rationale

The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.

Objective

To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.

Methods

We prospectively enrolled consecutive, hospitalized, Ugandan TB suspects in two phases: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.

Results

477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73–84%) and specificity (190/199, 96%, 95% CI: 92–98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31–54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0–26] vs. 0 [IQR 0–1], p<0.001), and for smear-negative TB (35 [IQR 22–55] vs. 22 [IQR 0–33], p = 0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0–5] vs. 0 [IQR 0–2], p = 0.06) and for smear-negative TB (7 [IQR 3–53] vs. 6 [IQR 1–61], p = 0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: −21% to +27%, p = 0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: −34 to +46%, p = 0.77).

Conclusions

Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.     

Risk Factors for Renal Scarring and Deterioration of Renal Function in Primary Vesico-Ureteral Reflux Children: A Long-Term Follow-Up Retrospective Cohort Study

Background and Purpose

The aim was to identify the risk factors for renal scarring and deteriorating renal function in children with primary vesico-ureteral reflux (VUR).

Materials and Methods

Patients with primary VUR admitted to the National Cheng Kung University Hospital were retrospectively analyzed. The outcomes were renal scarring, assessed by technetium-99 m dimercaptosuccinic acid scanning, and renal function, assessed by estimated glomerular filtration rate. Univariate and multivariate models were applied to identify the corresponding independent predictors.

Results

A total of 173 patients with primary VUR were recruited. The median age of VUR diagnosis was 10.0 months (IQR: 4.0–43.0 months). After adjusting for confounding factors, it was found that older age of VUR diagnosis (≥5 years vs. <1 year, adjusted OR = 2.78, 95% CI = 1.00–7.70, p = 0.049), higher grade of VUR (high grade [IV–V] vs. none, adjusted OR = 15.17, 95% CI = 5.33–43.19, p<0.0001; low grade [I–III] vs. none, adjusted OR = 5.72, 95% CI = 2.43–13.45, p<0.0001), and higher number of UTI (≥2 vs. 0, adjusted OR = 3.21, 95% CI = 1.06–9.76, p = 0.039) were risk factors for renal scarring, whereas a younger age of VUR diagnosis (≥5 years vs. <1 year, adjusted HR = 0.16, 95% CI: 0.05–0.51, p = 0.002), renal scarring (yes vs. no, adjusted HR = 3.66, 95% CI: 1.32–10.16, p = 0.013), and APN (yes vs. no, adjusted HR = 3.10, 95% CI: 1.05–9.14, p = 0.041) were risk factors for developing chronic kidney disease stage 2 or higher.

Conclusions

Our findings expand on the current knowledge of risk factors for renal scarring and deteriorating renal function, and this information can be used to modify the management and treatment of VUR.     

Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis

Background

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

Methods

We firstly performed a hospital-based case-control study involving 165 NPC cases and 191 cancer-free controls in central-south China, and then conducted a meta-analysis with six case-control studies to evaluate the association between NPC risk and CCND1 G870A polymorphism.

Results

The case-control study found a significant association between CCND1 G870A polymorphism and NPC risk in various comparison models (AA vs. GG: OR = 2.300, 95% CI 1.089–4.857, p = 0.029; AG vs. GG: OR = 2.832, 95% CI 1.367–5.867, p = 0.005; AA/AG vs. GG: OR = 2.597, 95% CI 1.288–5.237, p = 0.008; AA vs. AG/GG: OR = 0.984, 95% CI 0.638–1.518, p = 0.944). Further meta-analysis showed that there was no significant association between CCND1 G870A polymorphism and NPC risk in overall analysis. In the stratified analysis by race, however, significant associations were only found in Caucasians (for the allele model A vs. G: OR = 0.75, 95% CI 0.59–0.97, p = 0.03; for the co-dominant model AA vs. GG: OR = 0.52, 95% CI 0.32–0.86, p = 0.01; for the dominant model AA/AG vs. GG: OR = 0.49, 95% CI 0.32–0.74, p<0.01; for the recessive model AA vs. AG/GG: OR = 0.90, 95% CI 0.61–1.34, p = 0.60).

Conclusions

A significant association between CCND1 G870A polymorphism and NPC risk was found in the central-southern Chinese population. The meta-analysis indicated that CCND1 G870A polymorphism may contribute to the development of NPC in Caucasians.     

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.     

Genetic Variation in the Interleukin-28B Gene Is Associated with Spontaneous Clearance and Progression of Hepatitis C Virus in Moroccan Patients

Background

Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population.

Methods

We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5′ allelic discrimination assay.

Results

The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99–11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19–66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99–3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08–8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40–3.93; p = 0.0100).

Conclusions

In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection.     

Stent Thrombosis is the Primary Cause of ST-Segment Elevation Myocardial Infarction following Coronary Stent Implantation: A Five Year Follow-Up of the SORT OUT II Study

Background

The widespread use of coronary stents has exposed a growing population to the risk of stent thrombosis, but the importance in terms of risk of ST-segment elevation myocardial infarctions (STEMIs) remains unclear.

Methods

We studied five years follow-up data for 2,098 all-comer patients treated with coronary stents in the randomized SORT OUT II trial (mean age 63.6 yrs. 74.8% men). Patients who following stent implantation were readmitted with STEMI were included and each patient was categorized ranging from definite- to ruled-out stent thrombosis according to the Academic Research Consortium definitions. Multivariate logistic regression was performed on selected covariates to assess odds ratios (ORs) for definite stent thrombosis.

Results

85 patients (4.1%), mean age 62.7 years, 77.1% men, were admitted with a total of 96 STEMIs, of whom 60 (62.5%) had definite stent thrombosis. Notably, definite stent thrombosis was more frequent in female than male STEMI patients (81.8% vs. 56.8%, p = 0.09), and in very late STEMIs (p = 0.06). Female sex (OR 3.53 [1.01–12.59]) and clopidogrel (OR 4.43 [1.03–19.01]) was associated with increased for definite stent thrombosis, whereas age, time since stent implantation, use of statins, initial PCI urgency (STEMI [primary PCI], NSTEMI/unstable angina [subacute PCI] or stable angina [elective PCI]), and glucose-lowering agents did not seem to influence risk of stent thrombosis.

Conclusion

In a contemporary cohort of coronary stented patients, stent thrombosis was evident in more than 60% of subsequent STEMIs.     

Association between Methylenetetrahydrofolate Reductase C677T Polymorphism and Susceptibility to Cervical Cancer: A Meta-Analysis

Background

To assess the association between MTHFR polymorphism and cervical cancer risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, and Web of Science databases, we identified outcome data from all articles estimating the association between MTHFR polymorphism and cervical cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 12 studies with 2,924 cases (331 cervical intraepithelial neoplasia (CIN) I, 742 CIN II/III, 1851 invasive cervical cancer) and 2,581 controls were identified. There was no significant association between MTHFR C677T polymorphism and CIN I risk (T vs. C, OR = 1.10, 95% CI = 0.92–1.31; TT vs. CC, OR = 1.14, 95% CI = 0.78–1.68; TT+CT vs. CC, OR = 1.22, 95% CI = 0.94–1.58; TT vs. CT+CC, OR = 0.99, 95% CI = 0.70–1.40). For the CIN II/III, lack of an association was also found (T vs. C, OR = 1.08, 95% CI = 0.95–1.23; TT vs. CC, OR = 1.15, 95% CI = 0.87–1.52; TT+CT vs. CC, OR = 1.13, 95% CI = 0.94–1.35; TT vs. CT+CC, OR = 1.07, 95% CI = 0.83–1.38). The T allele had significant association to susceptibility of invasive cervical cancer in recessive model (TT vs. CT+CC, OR = 1.23, 95% CI = 1.02–1.49). On subgroup analysis by ethnicity, similarly significant differences in T vs. C, TT vs. CC, and recessive model were found in Asians.

Conclusion

The present meta-analysis suggested that MTHFR C677T polymorphism were to substantially contribute to invasive cervical cancer in recessive model.     

A Frequent PNPLA3 Variant Is a Sex Specific Disease Modifier in PSC Patients with Bile Duct Stenosis

Background & Aims

Primary sclerosing cholangitis predominantly affects males and is an important indication for liver transplantation. The rs738409 variant (I148M) of the PNPLA3 gene is associated with alcoholic and non-alcoholic liver disease and we evaluated its impact on the disease course of PSC.

Methods

The I148M polymorphism was genotyped in 121 German PSC patients of a long-term prospective cohort and 347 Norwegian PSC patients.

Results

In the prospective German cohort, actuarial survival free of liver transplantation was significantly reduced for I148M carriers (p = 0.011) compared to wildtype patients. This effect was restricted to patients with severe disease, as defined by development of dominant stenosis (DS) requiring endoscopic intervention. DS patients showed markedly decreased survival (p = 0.004) when carrying the I148M variant (I148M: mean 13.8 years; 95% confidence interval: 11.6–16.0 vs. wildtype: mean 18.6 years; 95% confidence interval: 16.3–20.9) while there was no impact on survival in patients without a DS (p = 0.87). In line with previous observations of sex specific effects of the I148M polymorphism, the effect on survival was further restricted to male patients (mean survival 11.9 years; 95% confidence interval: 10.0–14.0 in I148M carriers vs. 18.8 years; 95% confidence interval: 16.2–21.5 in wildtype; p<0.001) while female patients were unaffected by the polymorphism (p = 0.65). These sex specific findings were validated in the Norwegian cohort (p = 0.013).

Conclusions

In male PSC patients with severe disease with bile duct stenosis requiring intervention, the common I148M variant of the PNPLA3 gene is a risk factor for reduced survival.     

Consistent Condom Use Increases the Regression Rate of Cervical Intraepithelial Neoplasia 2–3

Objective

Cervical intraepithelial neoplasia grades 2-3 (CIN2-3) are usually treated by cone excision, although only 30% progress to cancer and 6–50% regress spontaneously. The aim of this study was to examine the influence of clinical factors like smoking habits, number of lifetime sexual partners, age at first sexual intercourse, sexual activity span and hormonal versus non-hormonal contraception type on the regression rate of CIN2-3.

Methods

In this prospective population-based cohort study 170 women aged 25–40 with abnormal cytology and colposcopy-directed biopsies showing first time onset CIN2-3 were consecutively included. The interval between biopsy and cone excision was standardized to minimum 12 weeks. Regression was defined as ≤CIN1 in the cone biopsy.

Results

The regression rate was 22%. Consistent condom use, defined as those women whose partners used condoms for all instances of sexual intercourse, was infrequent (n = 20, 12%). In univariate analysis consistent condom use, hormonal contraception and age at first sexual intercourse significantly predicted regression. In a multivariate analysis only consistent condom use remained as an independent predictor of regression (regression rate 55%, p = 0.001, hazard ratio = 4.4).

Conclusion

Consistent condom use between punch biopsy and cone excision in first-time onset CIN2-3 patients significantly increases the regression rate.     

Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status

Introduction

Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations.

Patients and Methods

We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number – defined as mean of 3 to 5 fusion signals in ≥10% of cells). All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease.

Results

No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37%) tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048). Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045). A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885).

Conclusion

Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy.     

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background

A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims

To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods

We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m², and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results

In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).

Conclusions

A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.     

Coronary Collateral Circulation in Patients of Coronary Ectasia with Significant Coronary Artery Disease

Objectives

Patients with coronary ectasia (CE) usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development.

Methods

We evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD), defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.

Results

73 patients (13.2%) had CE lesions which were most located in the right coronary artery (53.4%). Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03), higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027) and poorer coronary collateral (58.2% vs 71.2%, p = 0.040). Patients with poor collateral (n = 331) had a higher incidence of CE (15.7% vs 9.5%, p = 0.040) and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001). Multivariate analysis showed diabetes (odd ratio (OR) 0.630, p = 0.026), CE (OR = 0.544, p = 0.048), and number of diseased vessels (OR = 2.488, p<0.001) were significant predictors of coronary collaterals development.

Conclusion

The presence of CE was associated with poorer coronary collateral development in patients with SCAD.     

Prophylactic Cranial Irradiation May Impose a Detrimental Effect on Overall Survival of Patients with Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis

Purpose

To determine the role of brain metastases (BM) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) by performing a meta-analysis of the RCTs (randomized controlled clinical trials) and non-RCTs (non-randomized controlled clinical trials) published in the literature.

Methods

A meta-analysis was performed using trials identified through PubMed, EMBASE and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included BM, OS, median survival (MS), response rate (RR), Hazard ratios (HRs) and odds ratios (ORs), and their 95% confidence intervals (CIs) were pooled using ReMan software.

Results

Twelve trials (6 RCTs and 6 non-RCTs) involving 1,718 NSCLC patients met the inclusion criteria. They were grouped on the basis of study design for separate Meta-analyses. The results showed that prophylactic cranial irradiation (PCI) reduced the risk of BM as compared with non-PCI in NSCLC patients (OR = 0.30, 95% [CI]: 0.21–0.43, p<0.00001). However, HRs for OS favored non-PCI (HR = 1.19, 95% [CI]: 1.06–1.33, p = 0.004), without evidence of heterogeneity between the studies.

Conclusion

Our results suggest that although PCI decreased the risk of BM, it may impose a detrimental effect on OS of NSCLC patients.     

Comparative Effectiveness of Homoeopathic vs. Conventional Therapy in Usual Care of Atopic Eczema in Children: Long-Term Medical and Economic Outcomes

Background

One in five children visiting a homeopathic physician suffers from atopic eczema.

Objectives

We aimed to examine the long-term effectiveness, safety and costs of homoeopathic vs. conventional treatment in usual medical care of children with atopic eczema.

Methods

In this prospective multi-centre comparative observational non-randomized rater-blinded study, 135 children (48 homoeopathy, 87 conventional) with mild to moderate atopic eczema were included by their respective physicians. Depending on the specialisation of the physician, the primary treatment was either standard conventional treatment or individualized homeopathy as delivered in routine medical care. The main outcome was the SCORAD (SCORing Atopic Dermatitis) at 36 months by a blinded rater. Further outcomes included quality of life, conventional medicine consumption, safety and disease related costs at six, 12 and 36 months after baseline. A multilevel ANCOVA was used, with physician as random effect and the following fixed effects: age, gender, baseline value, severity score, social class and parents’ expectation.

Results

The adjusted mean SCORAD showed no significant differences between the groups at 36 months (13.7 95% CI [7.9–19.5] vs. 14.9 [10.4–19.4], p = 0.741). The SCORAD response rates at 36 months were similar in both groups (33% response: homoeopathic 63.9% vs. conventional 64.5%, p = 0.94; 50% response: 52.0% vs. 52.3%, p = 0.974). Total costs were higher in the homoeopathic versus the conventional group (months 31–36 200.54 Euro [132.33–268.76] vs. 68.86 Euro [9.13–128.58], p = 0.005).

Conclusions

Taking patient preferences into account, while being unable to rule out residual confounding, in this long-term observational study, the effects of homoeopathic treatment were not superior to conventional treatment for children with mild to moderate atopic eczema, but involved higher costs.     

Mitral Tissue Inhibitor of Metalloproteinase 2 Is Associated with Mitral Valve Surgery Outcome

Background

Matrix metalloproteinases play a role in regulating cardiac remodeling. We previously reported an association between tissue inhibitor of metalloproteinase 2 (TIMP-2) expression and mitral valve (MV) disease. However, the determinants and prognostic value of mitral TIMP2 after MV surgery are unknown.

Methods

This retrospective study of 164 patients after MV surgery in a tertiary medical center in Taiwan assessed mitral TIMP2 on a semiquantitative scale (0–2) by immunohistochemical staining. The primary endpoints were the composite of cardiovascular death and heart failure admission.

Results

Mean age was 50.4±13.7 years. After a mean follow-up period of 101±59 months, primary endpoints had occurred in 25 (15.2%) subjects. Patients with and without primary endpoint events significantly differed in terms of age (56.6±14.4 vs. 49.2±13.4 years, respectively; p = 0.013) and left ventricular end-systolic diameter (LVESD) (39.7±8.2 vs. 35.5±7.5 mm, p = 0.010) at surgery. The TIMP2 had a significant dose-dependent association with development of a primary endpoint (p = 0.002). Kaplan–Meier analysis showed that TIMP2 expression has a significant positive association with primary endpoint-free survival (log-rank test; p = 0.004). Cox regression analysis showed that independent predictors of primary endpoints were TIMP2 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.12–0.65; p = 0.003), age (HR 1.05; 95% CI 1.02–1.09; p = 0.003) and LVESD (HR 1.05; 95% CI 1.01–1.10; p = 0.020).

Conclusions

The lack of mitral TIMP2 expression is associated with increases in cardiovascular death and heart failure following MV surgery.     

Progesterone Receptor Status and Ki-67 Index May Predict Early Relapse in Luminal B/HER2 Negative Breast Cancer Patients: A Retrospective Study

Purpose

Few studies has documented early relapse in luminal B/HER2-negative breast cancer. We examined prognostic factors for early relapse among these patients to improve treatment decision-making.

Patients and Methods

A total 398 patients with luminal B/HER2-negative breast cancer were included. Kaplan-Meier curves were applied to estimate disease-free survival and Cox regression to identify prognostic factors.

Results

Progesterone receptor (PR) negative expression was associated with higher tumor grade (p<.001) and higher Ki-67 index (p = .010). PR-negative patients received more chemotherapy than the PR-positive group (p = .009). After a median follow-up of 28 months, 17 patients (4.3%) had early relapses and 8 patients (2.0%) died of breast cancer. The 2-year disease-free survival was 97.7% in the PR-positive and 90.4% in the PR-negative groups (Log-rank p = .002). Also, patients with a high Ki-67 index (defined as >30%) had a reduced disease-free survival (DFS) when compared with low Ki-67 index group (≤30%) (98.0% vs 92.4%, respectively, Log-rank p = .013). In multivariate analysis, PR negativity was significantly associated with a reduced DFS (HR = 3.91, 95% CI 1.29–11.88, p = .016).

Conclusion

In this study, PR negativity was a prognostic factor for early relapse in luminal B/HER2-negative breast cancer, while a high Ki-67 index suggested a higher risk of early relapse.     

Outcomes of Sustained-Release Formulation of Valproate and Topiramate Monotherapy in Patients with Epilepsy: A Multi-Centre,Cohort Study

Background

New-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown.

Methodology/Principal Findings

Two broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR).Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HR = 0.62, [95% CI 0.49–0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HR = 0.73, [95% CI 0.62–0.86]; p = 0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HR = 1.01, [95% CI 0.84–1.23]; p = 0.88) and time to 24-month remission (34.7% vs. 25.2%; HR = 1.11, [95% CI 0.88–1.42]; p = 0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (p = 0.70).

Conclusions

The SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.     

Maternal Methylenetetrahydrofolate Reductase C677T Polymorphism and Down Syndrome Risk: A Meta-Analysis from 34 Studies

Background

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis.

Aim

A meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome.

Methods

PubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR) with 95%confidence interval were calculated for risk assessment.

Results

Thirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR = 1.26, 95% CI = 1.09–1.46, p = 0.001; for TT vs. CC, OR = 1.49, 95% CI = 1.13–1.97, p = 0.008; for CT vs. CC, OR = 1.29, 95% CI = 1.10–1.51, p = 0.001; for TT+CT vs. CC, OR = 1.35, 95% CI = 1.13–1.60, p = 0.0008; for TT vs. CT+CC, OR = 0.76, 95% CI = 0.60–0.94, p = 0.01).

Conclusion

The results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.     

Indirect Effect of 7-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Carriage in Newborns in Rural Gambia: A Randomised Controlled Trial

Background

Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies.

Methods

Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2–30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study.

Results

57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26–0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87–1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50–0.92], p = 0.013 in control villages and HR 0.31 [0.19–0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06–2.06], p = 0.022) and (HR 1.52 [1.11–2.10], p = 0.010 respectively) were significantly higher.

Conclusion

PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring.

Trial Registration

ISRCTN Register 51695599