Lesion Length Impacts Long Term Outcomes of Drug-Eluting Stents and Bare Metal Stents Differently

Background

Long lesions have been associated with adverse outcomes in percutaneous coronary interventions with bare metal stents (BMS). However, the exact impact of lesion length on the short- and long-term outcomes of drug-eluting stent (DES) implantations is not as clear.

Methods and Results

This study compared the impact of lesion length on angiographic and clinical outcomes of BMS and DES in a single-center prospective registry. Lesion length was divided into tertiles. The primary endpoints were angiographically defined binary in-stent restenosis (ISR) rate and major adverse cardiac event (MACE). Of the 4,312 de novo lesions in 3,447 consecutive patients in the CAPTAIN registry, 2,791 lesions (of 2,246 patients) received BMS, and the remaining 1,521 lesions (of 1,201 patients) received DES. The mean follow-up duration was 4.5 years. The longer the lesion, the higher the ISR rate (14%, 18%, and 29%, p<0.001) and the lower the MACE-free survivals (p = 0.007) in the BMS group. However, lesion length showed no such correlation with ISR rates (4.7%, 3.3%, and 7.8%, p = 0.67) or MACE-free survivals (p = 0.19) in the DES group.

Conclusions

In our single-center prospective registry, lesion length defined in tertiles has no impact on the short-term (ISR) or long-term (MACE) outcomes of patients implanted with DES. In contrast, longer lesion correlates with higher ISR and MACE rates in BMS group.     

An Updated Meta-Analysis of Randomized Controlled Trials Assessing the Effect of Sorafenib in Advanced Hepatocellular Carcinoma

Background

The efficacy of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of sorafenib for treating patients with advanced HCC.

Methods

The PubMed, Embase, and Web of Science databases were searched. Eligible studies were randomized controlled trials (RCTs) that assessed sorafenib therapy in patients with advanced HCC. The outcomes included overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicities. Hazard ratio (HR) and risk ratio (RR) were used for the meta-analysis and were expressed with 95% confidence intervals (CIs).

Results

Seven RCTs, with a total of 3807 patients, were included in this meta-analysis. All patients received sorafenib alone, or with other chemotherapeutic regimens. Pooled estimates showed that sorafenib improved the OS (HR = 0.74, 95% CI: 0.61, 0.90; P = 0.002), or TTP outcomes (HR = 0.69, 95% CI: 0.55, 0.86; P = 0.001). Subgroup analysis revealed that sorafenib was more effective in the patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1–2 (HR = 0.77, 95% CI: 0.60, 1.0; P = 0.05), or macroscopic vascular invasion (MVI), and/or extrahepatic spread (EHS) (HR = 0.65, 95% CI: 0.46, 0.93; P = 0.02), in terms of OS. Patients who received sorafenib did not have a higher ORR (RR = 0.85, 95% CI: 0.65, 1.11; P = 0.10). In addition, there was a slight increase in toxicity in the sorafenib group.

Conclusion

Treatment with sorafenib significantly improved OS and TTP in patients with advanced HCC. Additional large-scale, well-designed RCTs are needed to evaluate the efficacy of sorafenib-based therapy in the treatment of advanced HCC.     

Drug-Eluting versus Bare-Metal Stent for Treatment of Saphenous Vein Grafts: A Meta-Analysis

Background

Saphenous vein grafts develop an aggressive atherosclerotic process and the efficacy of drug eluting stents (DES) in treating saphenous vein graft (SVG) lesions has not been convincingly demonstrated. The aim of this study was to review and analyze the current literature for controlled studies comparing DES versus bare metal stents (BMS) for treatment of SVG stenoses.

Methodology/Principal Findings

We searched several scientific databases and conference proceedings up to March 15, 2010 for controlled studies comparing target vessel revascularization (TVR) between DES and BMS. Summary odds ratios (OR) for the primary endpoint TVR and secondary endpoints infarction, stent thrombosis and death were calculated using random-effect models. A total of 29 studies (3 randomized controlled trials RCT) involving 7549 (202 in RCT) patients were included. The need for target vessel revascularization in the DES group tended to be lower compared to BMS for the 3 RCT (OR 0.50 [0.24–1.00]; p = 0.051) and for observational studies (0.62 [0.49–0.79]; p<0.001). There was no significant difference in the risk for myocardial infarction in the RCT (OR 1.25 [0.22–6.99]; p = 0.250) but a lower risk for DES based on the observational studies 0.68 [0.49–0.95]; p = 0.023. The risk for stent thrombosis was found to be non-different in the RCT (OR 0.78 [0.03–21.73], p = 0.885) while it was in favor of DES in the observational studies (0.58 [0.38 – 0.84]; p<0.001). The mortality was not significantly different between DES and BMS in the RCT''s (OR 2.22 [0.17 – 29.50]; p = 0.546) while the observation studies showed a decreased mortality in the DES group (0.69 [0.55–0.85]; p<0.001).

Conclusion

DES may decrease TVR rate in treatment of SVG stenoses. No differences in reinfarction rate, stent thrombosis or mortality was found between the DES and BMS groups in the RCT''s while the observational data showed lower risk for myocardial infarction, stent thrombosis and death in the DES group. This may be a result of patient selection bias in the observational studies or represent a true finding that was not the detected in the RCT analysis due to limited statistical power.     

A Meta-Analysis of Unilateral versus Bilateral Pedicle Screw Fixation in Minimally Invasive Lumbar Interbody Fusion

Study Design

Meta-analysis.

Background

Bilateral pedicle screw fixation (PS) after lumbar interbody fusion is a widely accepted method of managing various spinal diseases. Recently, unilateral PS fixation has been reported as effective as bilateral PS fixation. This meta-analysis aimed to comparatively assess the efficacy and safety of unilateral PS fixation and bilateral PS fixation in the minimally invasive (MIS) lumbar interbody fusion for one-level degenerative lumbar spine disease.

Methods

MEDLINE/PubMed, EMBASE, BIOSIS Previews, and Cochrane Library were searched through March 30, 2014. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on unilateral versus bilateral PS fixation in MIS lumbar interbody fusion that met the inclusion criteria and the methodological quality standard were retrieved and reviewed. Data on participant characteristics, interventions, follow-up period, and outcomes were extracted from the included studies and analyzed by Review Manager 5.2.

Results

Six studies (5 RCTs and 1 CCT) involving 298 patients were selected. There were no significant differences between unilateral and bilateral PS fixation procedures in fusion rate, complications, visual analogue score (VAS) for leg pain, VAS for back pain, Oswestry disability index (ODI). Both fixation procedures had similar length of hospital stay (MD = 0.38, 95% CI = −0.83 to 1.58; P = 0.54). In contrast, bilateral PS fixation was associated with significantly more intra-operative blood loss (P = 0.002) and significantly longer operation time (P = 0.02) as compared with unilateral PS fixation.

Conclusions

Unilateral PS fixation appears as effective and safe as bilateral PS fixation in MIS lumbar interbody fusion but requires less operative time and causes less blood loss, thus offering a simple alternative approach for one-level lumbar degenerative disease.     

An Updated Meta-Analysis of the Efficacy and Safety of Acupuncture Treatment for Cerebral Infarction

Background

Ischemic stroke is the second most common cause of death and the primary cause of disability throughout the world. Acupuncture is frequently advocated as an adjunct treatment during stroke rehabilitation. The aim of this study was to update the clinical efficacy and safety of acupuncture for cerebral infarction.

Methods

Randomized controlled trials (RCT) on acupuncture treating cerebral infarction were searched from the following databases: PubMed, EMBASE, Cochrane Library, CNKI, CMB and VIP from inception to October 2013. The data of RCTs meeting the inclusive criteria were extracted according to Cochrane methods. The meta-analyses were conducted using Rev Man 5.0 software.

Results

A total of 25 trials involving 2224 patients were included. The results of this meta-analysis showed that the groups receiving acupuncture (observation group) were superior to the comparison groups (control group), with significant differences in the Clinical Efficacy Rates [OR = 4.04, 95%CI (2.93, 5.57), P<0.001], Fugl-Meyer Assessment [MD = 11.22, 95%CI (7.62, 14.82), P<0.001], Barthel Index Score [MD = 12.84, 95%CI (9.85, 15.82), P<0.001], and Neurological Deficit Score [MD = −2.71, 95% CI (−3.84, −1.94), P<0.001]. Three trials reported minor adverse events.

Conclusion

Current evidence provisionally demonstrates that acupuncture treatment is superior to either non-acupuncture or conventional therapy for cerebral infarction. Despite this conclusion, given the often low quality of the available trials, further large scale RCTs of better quality are still needed.     

Prevention Effect of Allopurinol on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Meta-Analysis of Prospective Randomized Controlled Trials

Background

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs) have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP). However, these results remained controversial.

Objective

To conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP.

Methods

Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ² test with the significance set P<0.10 or I²>50%.

Results

Six RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986) and 9.9%(98/988) respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39–1.42) with significant heterogeneity (I² = 70.4%, P = 0.005). When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (I_moderate ² = 82.3%, P_moderate = 0.018). Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (I_mild ² = 62.8%, P_mild = 0.068).

Conclusion

The prophylactic use of allopurinol in different dosages and administration time had no effect in preventing incidence and severity of PEP.     

Association between B Vitamins Supplementation and Risk of Cardiovascular Outcomes: A Cumulative Meta-Analysis of Randomized Controlled Trials

Background

Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base.

Methodology and Principal Findings

In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93–1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97–1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90–1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93–1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85–1.03; P = 0.18).

Conclusion/Significance

B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.     

Cemented versus Uncemented Hemiarthroplasty for Femoral Neck Fractures in Elderly Patients: A Meta-Analysis

Objective

Controversy still exists regarding using cemented or uncemented hemiarthroplasty for femoral neck fractures in elderly patients. The aim of this study is to compare the effectiveness and safety of the two surgical techniques in femoral neck fracture patients over 70 years old.

Methods

We searched PUBMED, EMBASE, Cochrane Library, CNKI and VIP Database from inception to December 2012 for relevant randomized controlled trials (RCTs). Outcomes of interest include postoperative hip function, residue pain, complication rates, mortality, reoperation rate, operation time and intraoperative blood loss. Odds ratios (OR) and weighted mean differences (WMD) from each trial were pooled using random-effects model or fixed-effects model given on the heterogeneity of the included studies.

Results

7 RCTs involving 1,125 patients (1,125 hips) were eligible for meta-analysis. Our results demonstrate that cemented hemiarthroplasty is associated with better postoperative hip function (OR = 0.48, 95% CI, 0.31–0.76; P = 0.002), lower residual pain (OR = 0.43, 95%CI, 0.29–0.64; P<0.0001), less implant-related complications (OR = 0.15, 95%CI, 0.09–0.26; P<0.00001) and longer operation time (WMD = 7.43 min, 95% CI, 5.37–9.49 min; P<0.00001). No significant difference was observed between the two groups in mortality, cardiovascular and cerebrovascular complications, local complications, general complications, reoperation rate and intraoperative blood loss.

Conclusions

Compared with uncemented hemiarthroplasty, the existing evidence indicates that cemented hemiarthroplasty can achieve better hip function, lower residual pain and less implant-related complications with no increased risk of mortality, cardiovascular and cerebrovascular complications, general complications, local complications and reoperation rate in treating elderly patients with femoral neck fractures.     

No Survival Benefit from Adding Cetuximab or Panitumumab to Oxaliplatin-Based Chemotherapy in the First-Line Treatment of Metastatic Colorectal Cancer in KRAS Wild Type Patients: A Meta-Analysis

Background

The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (MAbs) remains controversial in colorectal cancer (CRC). The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC) through meta-analysis.

Methods

Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) were searched. Eligible studies were randomized controlled trials (RCTs) which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab) in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. Hazard ratios (HR) and risk ratio (RR) were used for the meta-analysis and were expressed with 95% confidence intervals.

Results

This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn’t result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95) or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13). The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75) or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36). Patients who received combined therapy didn’t have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]). Toxicities slightly increased in anti-EGFR drugs group.

Conclusions

The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in survival benefit and response rate. More RCTs are warranted to evaluate the combination of chemotherapy and targeted therapy.     

Predictors of Two Months Culture Conversion in Multidrug-Resistant Tuberculosis: Findings from a Retrospective Cohort Study

Background

Various studies have reported culture conversion at two months as a predictor of successful treatment outcome in multidrug-resistant tuberculosis (MDR-TB).

Objectives

The present study was conducted with the aim to evaluate the rate and predictors of culture conversion at two months in MDR-TB patients.

Methods

All confirmed pulmonary MDR-TB patients enrolled for treatment at Lady Reading Hospital Peshawar, Pakistan from 1 January to 31 December 2012 and met the inclusion criteria were reviewed retrospectively. Rate and predictors of culture conversion at two months were evaluated.

Results

Eighty seven (53.4%) out of 163 patients achieved culture conversion at two months. In a multivariate analysis lung cavitation at baseline chest X-ray (P = 0.006, OR = 0.349), resistance to ofloxacin (P = 0.041, OR = 0.193) and streptomycin (P = 0.017, OR = 0.295) had statistically significant (P<0.05) negative association with culture conversion at two months.

Conclusion

A reasonable proportion of patients achieved culture conversion at two months. Factors negatively associated with culture conversion at two months can be easily identified either before diagnosis or early in the course of MDR-TB treatment. This may help in better care of individual patients by identifying them early and treating them vigorously.     

Pioglitazone Improves In Vitro Viability and Function of Endothelial Progenitor Cells from Individuals with Impaired Glucose Tolerance

Background

Evidence suggests that the PPARγ-agonist insulin sensitizer pioglitazone, may provide potential beneficial cardiovascular (CV) effects beyond its anti-hyperglycaemic function. A reduced endothelial progenitor cell (EPC) number is associated with impaired glucose tolerance (IGT) or diabetes, conditions characterised by increased CV risk.

Aim

To evaluate whether pioglitazone can provide benefit in vitro in EPCs obtained from IGT subjects.

Materials and Methods

Early and late-outgrowth EPCs were obtained from peripheral blood mononuclear cells of 14 IGT subjects. The in vitro effect of pioglitazone (10 µM) with/without PPARγ-antagonist GW9662 (1 µM) was assessed on EPC viability, apoptosis, ability to form tubular-like structures and pro-inflammatory molecule expression.

Results

Pioglitazone increased early and late-outgrowth EPC viability, with negligible effects on apoptosis. The capacity of EPCs to form tubular-like structures was improved by pioglitazone in early (mean increase 28%; p = 0.005) and late-outgrowth (mean increase 30%; p = 0.037) EPCs. Pioglitazone reduced ICAM-1 and VCAM-1 adhesion molecule expression in both early (p = 0.001 and p = 0.012 respectively) and late-outgrowth (p = 0.047 and p = 0.048, respectively) EPCs. Similarly, pioglitazone reduced TNFα gene and protein expression in both early (p = 0.034;p = 0.022) and late-outgrowth (p = 0.026;p = 0.017) EPCs compared to control. These effects were prevented by incubation with the PPARγ-antagonist GW9662.

Conclusion

Pioglitazone exerts beneficial effects in vitro on EPCs isolated from IGT subjects, supporting the potential implication of pioglitazone as a CV protective agents.     

High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

Background

Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention.

Methods

We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment.

Results

Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; P<0.00001) and 39% relative reduction in MACE (OR: 0.61; 95% CI: 0.45–0.83; P = 0.002). The benefit of high-dose statin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious.

Conclusions

High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for patients with acute coronary syndrome.     

Postoperative Vision-Related Quality of Life in Macula-Off Rhegmatogenous Retinal Detachment Patients and Its Relation to Visual Function

Objective

To determine the vision-related quality of life (VR-QOL) after surgery for macula-off rhegmatogenous retinal detachment (RRD) in relation to visual acuity, contrast acuity, and color vision.

Methods

In a prospective observational study, we included 55 patients with a macula-off RRD. Best corrected visual acuity (BCVA), color vision (saturated and desaturated color confusion indices (CCI)) and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the fellow control eye, and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was filled out.

Results

Operated and fellow control eyes differed significantly in mean LogMAR BCVA (P<0.0001), median Log contrast acuity (P<0.0001), saturated CCI (P = 0.009), and desaturated CCI (P = 0.016). Significant correlations were observed between the NEI VFQ-25 overall composite score and postoperative LogMAR BCVA (R = −0.551, P<0.0001), contrast acuity (R = 0.472, P<0.0001), saturated CCI (R = −0.315, P = 0.023), and desaturated CCI (R = −0.283, P = 0.044).

Conclusions

A lower VR-QOL was highly correlated to a worse postoperative BCVA and contrast acuity and to a lesser extent to color vision disturbances.     

Red Blood Cell Distribution Width and Long-Term Outcome in Patients Undergoing Percutaneous Coronary Intervention in the Drug-Eluting Stenting Era: A Two-Year Cohort Study

Background

Previous studies suggest the higher the red blood cell distribution width (RDW) the greater the risk of mortality in patients with coronary artery disease (CAD). However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD.

Methods

In total of 2169 non-anemic patients (1468 men, mean age 60.2±10.9 years) with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%), Quartile 2 (12.27%≤RDW<13%), Quartile 3 (13%≤RDW<13.5%), and Quartile 4 (RDW≥13.5).

Results

The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.15–1.62, P<0.001) and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04–1.39, P = 0.013). The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05).

Conclusion

High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES.     

Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema: A Meta-Analysis of Randomized Controlled Trials

Objective

To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with laser (RBZ + Laser) versus laser monotherapy for the treatment of diabetic macular edema (DME).

Methods

A comprehensive literature search using PUBMED, ClinicalTrials.gov, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing RBZ or RBZ + Laser to laser monotherapy in patients with DME. Efficacy estimates were determined by comparing weighted mean differences (WMD) in the change of best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline, and the risk ratios (RR) for the proportions of patients with at least 15 letters change from baseline. Safety analysis estimated the RR of cardiac disorders at 6 to 12 months in RBZ therapy vs. laser monotherapy. Statistical analysis was performed using the RevMan 5.1 software.

Results

Seven RCTs were selected for this meta-analysis, including 1749 patients (394 patients in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser group). RBZ and RBZ + Laser were superior to laser monotherapy in the mean change of BCVA and CMT from baseline (WMD = 5.65, 95% confidence interval (CI), 4.44–6.87, P<0.00001; WMD  = 5.02, 95% CI, 3.83–6.20, P<0.00001, and WMD  = −57.91, 95% CI, −77.62 to −38.20, P<0.00001; WMD  = −56.63, 95% CI, −104.81 to −8.44, P = 0.02, respectively). The pooled RR comparing the proportions of patients with at least 15 letters improvement or deterioration were also in favor of RBZ and RBZ + Laser (RR = 2.94, 95% CI, 1.82–4.77, P<0.00001; RR = 2.04, 95% CI, 1.50–2.78, P<0.00001, and RR = 0.21, 95% CI, 0.06–0.71, P = 0.01; RR = 0.52, 95% CI, 0.29–0.95, P = 0.03, respectively). There were no significant differences between RBZ and RBZ + Laser for any of the parameters. There were no difference in the safety profile between RBZ and laser.

Conclusion

RBZ and RBZ + Laser had better visual and anatomic outcomes than laser monotherapy in the treatment of DME. RBZ + Laser seemed to be equivalent to RBZ.     

Drug-eluting stents in patients with chronic kidney disease: a prospective registry study

Background

Chronic kidney disease (CKD) is strongly associated with adverse outcomes after percutaneous coronary intervention (PCI). There are limited data on the effectiveness of drug-eluting stents (DES) in patients with CKD.

Methodology/Principal Findings

Of 3,752 consecutive patients enrolled in the Guthrie PCI Registry between 2001 and 2006, 436 patients with CKD - defined as a creatinine clearance <60 mL/min - were included in this study. Patients who received DES were compared to those who received bare metal stents (BMS). Patients were followed for a mean duration of 3 years after the index PCI to determine the prognostic impact of stent type. Study end-points were all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and the composite of major adverse cardiovascular events (MACE), defined as death, MI or TVR. Patients receiving DES in our study, by virtue of physician selection, had more stable coronary artery disease and had lower baseline risk of thrombotic or restenotic events. Kaplan-Meier estimates of proportions of patients reaching the end-points were significantly lower for DES vs. BMS for all-cause death (p = 0.0008), TVR (p = 0.029) and MACE (p = 0.0015), but not MI (p = 0.945) or ST (p = 0.88). Multivariable analysis with propensity adjustment demonstrated that DES implantation was an independent predictor of lower rates of all-cause death (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.25–0.92), TVR (HR 0.50, 95% CI 0.27–0.94) and MACE (HR 0.62, 95% CI 0.41–0.94).

Conclusions

In a contemporary PCI registry, selective use of DES in patients with CKD was safe and effective in the long term, with lower risk of all-cause death, TVR and MACE and similar risk of MI and ST as compared with BMS. The mortality benefit may be a result of selection bias and residual confounding, or represent a true finding; a hypothesis that warrants clarification by randomized clinical trials.     

Interspinous Spacer versus Traditional Decompressive Surgery for Lumbar Spinal Stenosis: A Systematic Review and Meta-Analysis

Background

Dynamic interspinous spacers, such as X-stop, Coflex, DIAM, and Aperius, are widely used for the treatment of lumbar spinal stenosis. However, controversy remains as to whether dynamic interspinous spacer use is superior to traditional decompressive surgery.

Methods

Medline, Embase, Cochrane Library, and the Cochrane Controlled Trials Register were searched during August 2013. A track search was performed on February 27, 2014. Study was included in this review if it was: (1) a randomized controlled trial (RCT) or non-randomized prospective comparison study, (2) comparing the clinical outcomes for interspinous spacer use versus traditional decompressive surgery, (3) in a minimum of 30 patients, (4) with a follow-up duration of at least 12 months.

Results

Two RCTs and three non-randomized prospective studies were included, with 204 patients in the interspinous spacer (IS) group and 217 patients in the traditional decompressive surgery (TDS) group. Pooled analysis showed no significant difference between the IS and TDS groups for low back pain (WMD: 1.2; 95% CI: −10.12, 12.53; P = 0.03; I² = 66%), leg pain (WMD: 7.12; 95% CI: −3.88, 18.12; P = 0.02; I² = 70%), ODI (WMD: 6.88; 95% CI: −14.92, 28.68; P = 0.03; I² = 79%), RDQ (WMD: −1.30, 95% CI: −3.07, 0.47; P = 0.00; I² = 0%), or complications (RR: 1.39; 95% CI: 0.61, 3.14; P = 0.23; I² = 28%). The TDS group had a significantly lower incidence of reoperation (RR: 3.34; 95% CI: 1.77, 6.31; P = 0.60; I² = 0%).

Conclusion

Although patients may obtain some benefits from interspinous spacers implanted through a minimally invasive technique, interspinous spacer use is associated with a higher incidence of reoperation and higher cost. The indications, risks, and benefits of using an interspinous process device should be carefully considered before surgery.     

A Meta-Analysis of Core Stability Exercise versus General Exercise for Chronic Low Back Pain

Objective

To review the effects of core stability exercise or general exercise for patients with chronic low back pain (LBP).

Summary of Background Data

Exercise therapy appears to be effective at decreasing pain and improving function for patients with chronic LBP in practice guidelines. Core stability exercise is becoming increasingly popular for LBP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with chronic LBP.

Methods

Published articles from 1970 to October 2011 were identified using electronic searches. For this meta-analysis, two reviewers independently selected relevant randomized controlled trials (RCTs) investigating core stability exercise versus general exercise for the treatment of patients with chronic LBP. Data were extracted independently by the same two individuals who selected the studies.

Results

From the 28 potentially relevant trials, a total of 5 trials involving 414 participants were included in the current analysis. The pooling revealed that core stability exercise was better than general exercise for reducing pain [mean difference (−1.29); 95% confidence interval (−2.47, −0.11); P = 0.003] and disability [mean difference (−7.14); 95% confidence interval (−11.64, −2.65); P = 0.002] at the time of the short-term follow-up. However, no significant differences were observed between core stability exercise and general exercise in reducing pain at 6 months [mean difference (−0.50); 95% confidence interval (−1.36, 0.36); P = 0.26] and 12 months [mean difference (−0.32); 95% confidence interval (−0.87, 0.23); P = 0.25].

Conclusions

Compared to general exercise, core stability exercise is more effective in decreasing pain and may improve physical function in patients with chronic LBP in the short term. However, no significant long-term differences in pain severity were observed between patients who engaged in core stability exercise versus those who engaged in general exercise.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42011001717.     

The Influence of the Patient-Clinician Relationship on Healthcare Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes.

Design

Systematic review and meta-analysis.

Data Sources

Electronic databases EMBASE and MEDLINE and the reference sections of previous reviews.

Eligibility Criteria for Selecting Studies

Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions.

Results

Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = −.23 to .66. Using a random-effects model, the estimate of the overall effect size was small (d = .11), but statistically significant (p = .02).

Conclusions

This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.     

Monocarboxylate Transporters 1–4 in NSCLC: MCT1 Is an Independent Prognostic Marker for Survival

Introduction

Monocarboxylate transporters (MCTs) 1–4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC.

Methods

Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I–IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4.

Results

In univariate analyses; ↓MCT1 (P = 0.021) and ↑MCT4 (P = 0.027) expression in cancer cells, and ↑MCT1 (P = 0.003), ↓MCT2 (P = 0.006), ↓MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3–2.8, P = 0.001), ↓MCT2 (HR: 2.4, CI 95%: 1.5–3.9, P<0.001), ↓MCT3 (HR: 1.9, CI 95%: 1.1–3.5, P = 0.031) and ↑MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1–2.7, P = 0.016) were significant independent poor prognostic markers for DSS.

Conclusions

We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.