Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials

Objectives: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).

Patients and methods: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.

Results: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR?=?0.95; 95% CI, 0.89–1.02; P?=?.132) though significantly prolonged PFS (HR?=?0.82; 95% CI, 0.75–0.90; P?<?.001). Combination therapy significantly increased ORR (RR?=?1.32; 95% CI, 1.09–1.60; P?=?.005) and DCR (RR?=?1.26; 95% CI, 1.17–1.36, P?<?.001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR?=?1.54; 95% CI, 1.22–1.95; P?<?.001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR?=?1.49; 95% CI, 1.16–1.91; P?=?.002), but did not develop more diarrhea (RR?=?2.02; 95% CI, 0.86–4.77; P?=?.107) or rash (RR?=?1.29, 95% CI, 0.90–1.85; P?=?.172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.

Conclusions: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.     

Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials

Objectives:

To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed.

Patients and methods:

The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.

Results:

The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR?=?0.61, 95% CI 0.48 to 0.79, P?<?0.001 for bevacizumab; HR?=?0.71, 95% CI 0.59 to 0.87, P?=?0.001 for VEGFRIs; and HR?=?0.67, 95% CI 0.62 to 0.72, P?<?0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR?=?0.90, 95% CI 0.80 to 1.01, P?=?0.079), VEGFRIs showed no improvement (HR?=?0.92, 95% CI 0.75 to 1.11, P?=?0.368), and trebananib demonstrated a significant prolongation (HR?=?0.81, 95% CI 0.67 to 0.99, P?=?0.036). Bevacizumab was associated with more class-specific adverse events (RR?=?4.05, 95% CI 1.99 to 8.27, P?<?0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR?=?2.60, 95% CI 0.84 to 8.00, P?=?0.097).

Conclusions:

Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.     

Increased risk of severe infections in non-small-cell lung cancer patients treated with pemetrexed: a meta-analysis of randomized controlled trials

Background and aims: Infections related to pemetrexed have been reported in clinical trials. It is not yet clear whether this drug increases infection risk or not. This meta-analysis assessed the overall incidence and risk of severe infections (≥ grade 3) associated with the use of pemetrexed in non-small-cell lung cancer patients.

Methods: The databases of PubMed, Embase, and the Cochrane Library were searched for relevant studies published up to December 2015. Eligible studies included randomized controlled trials (RCTs) of pemetrexed for non-small-cell lung cancer patients that reported grade 3–5 infection and febrile neutropenia. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models, according to the heterogeneity of the included studies.

Results: Seven randomized controlled trials were included, comprising 1848 patients. The incidence of severe infection and febrile neutropenia due to pemetrexed was 5.7% (95% CI: 3.2–8.3%) and 1.3% (95% CI: 0.7–2.0%), respectively. The use of pemetrexed was associated with an increased risk of severe infection (RR 1.61, 95% CI: 1.07–2.44, P?=?.02) and febrile neutropenia (RR 4.28, 95% CI: 1.08–17.01, P?=?.04).

Conclusion: The use of pemetrexed was associated with an increased risk of developing severe infections and febrile neutropenia in non-small-cell lung cancer patients. Frequent clinical monitoring and management of infections should be emphasized during pemetrexed treatment. More studies are needed to reveal the mechanism of the increased risk of severe infections.     

Uric acid and incident chronic kidney disease in dyslipidemic individuals

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60?mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: ?6?mg/dL.

Results: After excluding patients with baseline eGFR <60?mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR?=?4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69?mL/min/1.73 m² (IQR?=?0.45–2.33). Multivariate analysis showed that baseline UA levels (HR?=?1.26; 95% CI?=?1.09–1.45, p?=?.001), female gender (HR?=?1.74; 95% CI?=?1.14–2.65, p?=?.01), age (HR?=?1.10; 95% CI?=?1.07–1.12, p?p?=?.03), cardiovascular disease (HR?=?1.62; 95% CI?=?1.02–2.58, p?=?.04), decreased baseline renal function (eGFR <90?mL/min/1.73 m²) (HR?=?2.38; 95% CI?=?1.14–4.81, p?=?.02), and low-density lipoprotein cholesterol reduction (HR?=?0.995; 95% CI?=?0.991–0.998, p?=?.01) were associated with incident CKD. Additionally, patients with UA ≥6?mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR?=?2.01; 95% CI?=?1.11–3.65, p?=?.02).

Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.     

Association of waterpipe smoking with myocardial infarction and determinants of metabolic syndrome among catheterized patients

Background: Waterpipe smoking is a rising global public health epidemic perceived by many users to be less harmful, though its toxicity overlaps or even exceeds that of cigarette smoking. Short-term cardiovascular changes due to waterpipe smoking are well established, but longer-term health impacts are still not fully elucidated.

Objective: We aim to investigate the association of waterpipe smoking with myocardial infarction among patients undergoing cardiac catheterization.

Methods: The study was performed on Lebanese patients referred for cardiac catheterization. Patient’s blood was collected for metabolic measures and questionnaires were filled out to include socio-demographic, behavioral and pertinent medical characteristics of the study subjects.

Results: Myocardial infarction is significantly and independently associated with waterpipe smoking, with odds ratio (OR) of 1.329 (95% CI: [1.04–1.68]; p?=?.021), which is lower than that for cigarette smoking (OR?=?1.87, 95% CI: [1.63–2.15]; p?p?=?.032).

Conclusion: The study provides yet another evidence for the adverse cardiovascular effects of waterpipe smoking on a clinical level. The harmful effects of waterpipe smoking should be underscored by health care professionals.     

Role of aspirin in the primary prevention of cardiovascular disease in diabetes mellitus: a meta-analysis

Objective: To evaluate the benefits of aspirin in people with diabetes mellitus for the primary prevention of cardiovascular disease.

Research design/methods: We searched MEDLINE and Cochrane database for randomized, controlled trials of aspirin in people with diabetes and no cardiovascular disease. Relative risks were determined using random-effects meta-analysis.

Main outcome measures: Risk reduction of aspirin compared with control groups for major cardiovascular events.

Results: Six trials consisting of 7374 patients with diabetes showed no benefits of aspirin compared with non-aspirin users with regard to overall mortality, risk reduction (relative risk (RR) = 0.96, 95% CI 0.78 – 1.18, p = 0.71), major cardiovascular events (RR = 0.90, 95% CI 0.78 – 1.05, p = 0.17) and myocardial infarction (RR = 0.95, 95% CI 0.76 – 1.18, p = 0.63). Risk of major bleeding in the aspirin compared with the non-aspirin group was not significant (RR = 2.49, 95% CI 0.70 – 8.84, p = 0.16).

Conclusions: Aspirin therapy did not reduce the risk of cardiovascular events. Existing trials were limited by small patient numbers and low cardiovascular event rates. The use of aspirin cannot be routinely recommended for primary prevention of cardiovascular events in diabetes.     

Is rheumatoid arthritis associated with reduced immunogenicity of the influenza vaccination? A systematic review and meta-analysis

Objective: To determine whether immunogenicity and safety of the influenza vaccination in rheumatoid arthritis (RA) patients are significantly different from those in a healthy population.

Methods: PubMed, MEDLINE, Embase, Cochrane Library and Web of Science were searched on 31 August 2016. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality and outcomes. The primary outcome was seroprotection (SP) rate after immunization.

Results: Thirteen studies were included. The SP rates did not significantly differ between the RA patients and healthy controls for the H3N2 (RR?=?0.96, 95% CI, 0.82 to 1.13, p?=?.64) and B strain (RR?=?0.95, 95% CI 0.84 to 1. 08, p?=?.44). Nevertheless, RA was associated with a significant decrease in SP rate for the H1N1 strain (RR?=?0.72, 95% CI 0.60 to 0.86, p?p?=?.04).

Conclusions: Immunogenicity was significantly different between RA patients and healthy controls for the H1N1 strain, but not for the H3N2 or B strains. Adverse event rates were higher in RA patients. Adjuvant and special kinds of immunosuppressive biologics may play an important role in immunogenicity of inactivated influenza vaccines for RA patients.     

Evaluation of the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite as clinical endpoints in multiple sclerosis clinical trials: quantitative meta-analyses

Objectives: This study compared the sensitivity of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) as clinical endpoints in multiple sclerosis (MS) clinical trials.

Methods: Medline (1946 through 12 September 2014) and Embase (1974 through 12 September 2014) databases searches were conducted using keywords and Medical Subject Heading (MeSH) terms related to MS, EDSS, and MSFC. Only studies that used the EDSS and MSFC as endpoints were assessed. All statistical analyses were conducted using comprehensive meta-analysis (CMA). The percentages of the overall changes in EDSS and MSFC were compared. The relative risks were calculated in randomized clinical trials (RCTs).

Results: A total of 123 studies were identified. There were nine studies (6 case series and 3 RCTs) included in the analysis. In the case series, the EDSS change rate in MS patients was 33.5% (95% CI: 12.9–63.2%) and the MSFC change rate was 30.3% (95% CI: 9.2–65.2%). In RCTs, patients who take the drug would be 22.9 times as likely as patients who did not take the drug to experience a change in the EDSS scale (RR?=?22.9, 95% CI?=?0.996–1.517, p?=?0.055). Patients who take the drug would be 48.9 times as likely as patients who did not take the drug to experience a change in the MSFC scale (RR?=?48.9, 95% CI?= CI?=?0.916–2.419, p?=?0.108).

Limitations: This study focused only on MS patient improvement (positive changes) on the EDSS and MSFC. More studies are needed to include patient deterioration (negative changes) on EDSS and MSFC.

Conclusions: There is controversy about the sensitivity of the EDSS and MSFC in detecting the progression of MS disease. The EDSS and MSFC are effective tools to assess the clinical severity and progression of MS disease. MSFC is more sensitive than EDSS in detecting the progression of MS disease.     

Warfarin therapy in Chinese patients with atrial fibrillation treated with percutaneous coronary intervention: a 5 year follow-up retrospective cohort study

Objective: To evaluate warfarin use in Chinese patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) by investigating the stroke and major adverse cardiac and cerebral events (MACCEs) and bleeding events.

Methods: Retrospective cohort study of the 5?year follow-up of 1134 patients with AF who underwent PCI. The patients were grouped according to whether they received warfarin or not. Baseline characteristics and the occurrence of MACCEs and bleeding events were compared between the two groups using the CHA2DS2-VASc and HAS-BLED scoring. Cox regression analysis was used to identify factors related to the occurrence of MACCEs and bleeding.

Results: Overall MACCE (p?=?.008) and mortality (p?=?.004) rates were significantly lower in the warfarin group compared with the non-warfarin group. Major bleeding, minor bleeding and overall bleeding were comparable in the two groups. Recurrent myocardial infarction (HR?=?10.129, 95% CI?=?4.737–21.655; p?<?.001) and a baseline CHA2DS2-VASc score >4 (HR?=?2.035, 95% CI?=?1.121–3.692; p?=?.019) were independent predictors of MACCEs in the warfarin group. A baseline HAS-BLED score ≥3 (HR?=?5.498, 95% CI?=?3.773–8.013; p?<?.001) and previous bleeding (HR?=?3.058, 95% CI?=?1.319–7.088; p?=?.009) were independent predictors of bleeding.

Conclusions: Warfarin reduces the incidence of MACCEs but does not increase bleeding events in Chinese patients with AF who underwent PCI. For patients taking warfarin, recurrent myocardial infarction and a baseline CHA2DS2-VASc score >4 were related to MACCE occurrence.     

Impact of gender on statin efficacy

ABSTRACT

Objective: To determine the impact of statin therapy on the combined endpoint of cardiovascular events in women and men separately.

Research design and methods: A systematic literature search through May 2006 was conducted to identify randomized, controlled statin trials evaluating the gender specific incidence of cardiovascular events. Weighted averages were reported as relative risks (RRs) with 95% confidence intervals (CI) calculated via random-effects model.

Main outcome measures: The primary outcome measured was a composite endpoint of all cardiovascular events. Secondary outcomes measured included death, myocardial infarction (MI), and stroke.

Results: Fifteen trials were included in this meta-analysis. Cardiovascular events were reduced in men (RR 0.76 [95% CI 0.70, 0.81]) and women (RR 0.79 [95% CI 0.69, 0.90]). Reductions in mortality, MI, and stroke predominantly contributed to the reduction in cardiovascular events in men taking statins. Women did not have a reduction in mortality or stroke, suggesting that the reductions in cardiac events may have been predominantly due to reductions in need for revascularization and/or unstable angina.

Conclusions: Statins reduced the risk of cardiovascular events in men and women, but women on statins may not have reductions in mortality and stroke like their male counterparts.     

Relationship of obesity to adverse events in myocardial infarction patients without primary percutaneous coronary intervention: results from the Occluded Artery Trial (OAT)

Objective: Our goal was to investigate the “obesity paradox” in myocardial infarction populations without primary percutaneous coronary intervention (PPCI).

Methods: The Occluded Artery Trial (OAT, Clinicaltrials.gov: NCT00004562) is a randomized, multicenter study to investigate the influence of routine percutaneous coronary intervention (PCI) on the clinical outcomes of myocardial infarction patients without PPCI. We stratified these patients into three groups according to body mass index (BMI): normal, 18.5?kg/m²?≤?BMI?<?25?kg/m²; overweight, 25?kg/m²?≤?BMI?<?30?kg/m²; obese, BMI?≥?30?kg/m². The purpose of our study was to investigate the effects of BMI on the primary endpoint (all-cause mortality) and the secondary endpoint (cardiac death, non-cardiac death or New York Heart Association [NYHA] class IV heart failure) in the population enrolled in the OAT.

Results: A total of 2153 patients (99.4%) constituted the final study population. We found that obese patients were younger and were more likely to have cardiovascular risk factors compared with other BMI groups. A U-shaped relationship was observed between BMI and all-cause mortality. The adjusted hazard ratios (HRs) were 0.892 (95% CI: 0.658–1.210, p?=?.460) for normal weight patients and 0.671 (95% CI: 0.508–0.888, p?=?.013) for overweight patients compared with obese patients. The same pattern was also observed for non-cardiac death. The adjusted HRs were 0.919 (95% CI: 0.601–1.40, p?=?.663) for normal weight patients and 0.524 (95% CI: 0.346–0.792, p?=?.004) for overweight patients compared with obese patients. We did not find any statistical differences among BMI categories in terms of cardiac death or NYHA class IV heart failure.

Conclusions: A U-shaped relationship was observed between BMI and all-cause mortality or non-cardiac death. Overweight patients have the lowest risk of all-cause mortality, which may be attributed to their having the lowest risk of non-cardiac death of the groups studied.     

Postoperative leg position following total knee arthroplasty influences blood loss and range of motion: a meta-analysis of randomized controlled trials

Aim Postoperative leg position has been reported as an efficient and convenient technique to minimize blood loss and improve early recovery following total knee arthroplasty (TKA); however, no single study was large enough to definitively determine optimal leg position. Therefore, we performed a meta-analysis pooling the results from randomized controlled trials (RCTs) to evaluate the effect of postoperative leg position on blood loss and range of motion (ROM) in TKA.

Methods Potential academic articles were identified from the Cochrane Library, Medline (1966–October 2015), PubMed (1966–October 2015), Embase (1980–October 2015), ScienceDirect (1985–October 2015) and other databases. Gray studies were identified from the references of included literature reports. The pooling of data was analyzed by RevMan 5.1.

Results Ten RCTs were included in the meta-analysis. There were significant differences in the total blood loss (mean difference [MD]?=??130.66, 95% CI: ?198.74 to ?62.57, P?=?0.0002), hidden blood loss (MD?=??73.27, 95% CI: ?117.57 to ?28.96, P?=?0.001), blood transfusion requirement (risk difference [RD]?=??0.10, 95% CI: ?0.19 to ?0.22, P?=?0.02), postoperative hemoglobin level (MD?=?0.73, 95% CI: 0.42 to 1.04, P?<?0.00001) and range of motion (MD?=?3.79, 95% CI: 1.43 to 6.14, P?=?0.002) between the flexion group and extension group. No significant differences were found regarding length of hospital stay, deep vein thrombosis (DVT) and wound infection between the two groups.

Conclusions This meta-analysis indicated that the postoperative flexion position of the leg in TKA was effective and safe, significantly decreasing total blood loss, hidden blood loss and blood transfusion requirement. In addition, the postoperative range of motion is significantly improved by the flexion position of the leg.     

Efficacy of zofenopril in combination with amlodipine in patients with acute myocardial infarction: a pooled individual patient data analysis of four randomized,double-blind,controlled, prospective studies

Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as compared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients.

Methods: This was a post-hoc analysis of pooled individual patient data from the four large randomized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitalization for cardiovascular causes.

Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR?=?0.66; and 95% confidence interval, CI?=?0.44–0.98; p?=?.039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR?=?0.78; 95% CI?=?0.63–0.97; p?=?.026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR?=?0.76; 95% CI?=?0.61–0.94); p?=?.013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering.

Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1?year.     

Comparative effectiveness of coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) in elderly patients with diabetes

Objective: To compare the relative effectiveness of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) among elderly patients with diabetes regarding acute myocardial infarction (AMI), stroke, repeat revascularization, and all-cause mortality.

Methods: A retrospective cohort study was conducted using the 2006–2008 5% national sample of Medicare claims data. Elderly (≥65 years) beneficiaries with at least two claims of diabetes separated by ≥30 days and who had at least one inpatient claim for multi-vessel CABG or PCI between 1 July 2006 and 30 June 2008 were identified. The date of beneficiary’s first CABG or PCI was defined as the index date. All patients were followed from the index date to 31 December 2008 for outcomes. CABG and PCI patients were 1:1 matched on propensity scores and index dates. Cox proportional hazards models were used to compare postoperative outcomes between patients undergoing CABG versus PCI.

Results: The matched sample consisted of 4430 patients (2215 in each group). The Cox proportional hazards models showed that, compared to patients undergoing PCI, CABG was associated with a lower risk of postoperative AMI (hazard ratio [HR]: 0.494; 95% CI: 0.396–0.616; p?<?.0001), repeat revascularization (HR: 0.194; 95% CI: 0.149–0.252; p?<?.0001), the composite outcome (HR: 0.523; 95% CI: 0.460–0.595; p?<?.0001), and all-cause mortality (HR: 0.775; 95% CI: 0.658–0.914; p?=?.0024); postoperative risk of stroke was not significantly different between the two groups (HR: 0.965; 95% CI: 0.812–1.148; p?=?.691).

Conclusions: CABG appears to be the preferred revascularization strategy for elderly patients with diabetes and coronary heart disease. However, this result should be interpreted considering study limitations, for example, several patient clinical variables and physician-related factors which may affect procedure outcomes are not available in the data. Clinical decisions should be individualized considering all patient- and physician-related factors.     

Titanium cages versus autogenous iliac crest bone grafts in anterior cervical discectomy and fusion treatment of patients with cervical degenerative diseases: a systematic review and meta-analysis

Objective: A systematic review and partial meta-analysis is conducted to compare the efficacy and safety of anterior cervical decompression and fusion procedures employing either rectangular titanium cages or iliac crest autografts in patients suffering from cervical degenerative disc diseases.

Methods: Medline, PubMed, CENTRAL, and Google Scholar databases were searched up to June 2015, using the key words cervical discectomy; bone transplantation; titanium cages; and iliac crest autografts. Outcomes of interbody fusion rates were compared using odds ratios (ORs) with 95% confidence intervals (CIs). Values of the Japanese Orthopaedic Association score, and visual analog scale before and after operation were also compared.

Results: The rate of interbody fusion was similar between patients in the iliac crest autograft and titanium cage groups (pooled OR?=?0.33, 95% CI?=?0.07 to 1.66, P?=?.178). The overall analysis showed that patients in the two groups did not have significantly different post-surgery Japanese Orthopaedic Association score (pooled difference in means?=??0.05, 95% CI?=?0.73 to 0.63, P?=?.876). Improvement in arm and neck pain scores were assessed with a visual analog scale and differed significantly between patients in the iliac crest autograft and titanium cage groups (pooled difference in means?=?0.16, 95% CI?=??0.44 to 0.76, P?=?.610; and pooled difference in means?=??0.44, 95% CI?=??2.23 to 1.36, P?=?.634, respectively).

Conclusions: Our results suggest that the use of titanium cages constitutes a safe and efficient alternative to iliac crest bone autografts for anterior cervical discectomy with fusion.     

The effect of antibiotic prophylaxis for acute pelvic inflammatory disease after hysterosalpingography: a retrospective cohort study

Aims: Concerns about acute pelvic inflammatory disease (PID) after hysterosalpingography (HSG) have been raised since 1980. However, the effectiveness of prophylactic antibiotics remains unclear. This study investigated the effect of antibiotic prophylaxis in women undergoing HSG.

Methods: Women undergoing HSG between 2000 and 2012 were screened from the Taiwan National Health Insurance Research Database for eligibility. The prophylactic cohort included patients using any antibiotics of 1st-generation cephalosporins, doxycycline, clindamycin, and metronidazole, within 7 days before HSG (n?=?3257). Patients not using any antibiotics were registered as the non-prophylactic cohort (n?=?4662). An unconditional logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute PID after HSG associated with prophylactic antibiotics.

Results: The cumulative incidences of acute PID after HSG were 0.46% and 1.42% in the prophylactic and non-prophylactic cohorts, respectively. Prophylactic patients had a significantly reduced estimated relative risk of acute PID compared with non-prophylactic patients (adjusted OR?=?0.33, 95% CI?=?0.19–0.58; p?=?.001). Doxycycline users had the lowest adjusted OR of 0.20 (95% CI?=?0.04–0.81; p?=?.02), followed by users of 1st-generation cephalosporins (adjusted OR?=?0.35, 95% CI?=?0.18–0.68; p?=?.002). Multivariate sub-group analysis verified this protective effect for almost all sub-groups of prophylactic patients.

Conclusions: Antibiotic prophylaxis is associated with a decreased estimated relative risk of acute PID in HSG patients. Doxycycline and 1st-generation cephalosporins may be effective prophylactic regimens for HSG.     

Impact of intraoperative MRI-guided resection on resection and survival in patient with gliomas: a meta-analysis

Objective: This study addressed the benefit of intraoperative magnetic resonance imaging (iMRI) compared with conventional neuronavigation-guided resection in patients with gliomas.

Research design and methods: The Medline, PubMed, Cochrane, and Google Scholar databases were searched up to 26 September 2015. Randomized controlled trials (RCTs), two-arm prospective studies, and retrospective studies in patients with glioblastoma/glioma who had received surgical treatment were included.

Main outcome measures: The primary outcome measures were the extent of tumor resection and tumor size reduction for using iMRI-guided or conventional neuronavigation-guided neurosurgery. Secondary outcomes included impact of surgery on 6 month progression-free survival (PFS), 12 month overall survival (OS) rates and surgical duration.

Results: We found that iMRI was associated with greater rate of gross total resection (rGTR) compared with conventional neuronavigation procedures (3.16, 95% confidence interval [CI] 2.07–4.83, P?P values ≥.065). Intraoperative MRI was associated with a higher rate of progression-free survival (PFS) compared with conventional neuronavigation (odds ratio, 1.84; 95% CI 1.15–2.95; P?=?.012), but the rate of overall survival (OS) between groups was similar (P?=?.799). Limitations of the study included the fact that data from non-RCTs was used, the small study population, and heterogeneity of outcomes across studies.

Conclusions: Our findings indicate that iMRI more frequently resulted in more complete resections leading to improved PFS in patients with malignant gliomas.     

Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p?p?p?p?=?0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p?=?0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p?=?0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p?=?0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.     

Risk of peripheral edema in cancer patients treated with MEK inhibitors: a systematic review and meta-analysis of clinical trials

Background: MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors.

Materials and methods: The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau², Chi², and I² analyses.

Results: A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR?=?3.05, 95% CI?=?1.98–4.70; p?p?=?.24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p?=?.03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved.

Conclusion: This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.     

Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen

Objective: To evaluate intravenous (IV) acetaminophen (APAP) vs oral APAP use as adjunctive analgesics in cholecystectomy patients by comparing associated hospital length of stay (LOS), hospital costs, opioid use, and rates of nausea/vomiting, respiratory depression, and bowel obstruction.

Methods: We conducted a retrospective analysis of the Premier Database (January 2012 to September 2015) including cholecystectomy patients who received either IV APAP or oral APAP. Differences in LOS, hospitalization costs, mean daily morphine equivalent dose (MED), and potential opioid-related adverse events were estimated. Multivariable logistic regression was performed for the binary outcomes and instrumental variable regressions, using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for continuous outcomes. Models were adjusted for patient demographics, clinical risk factors, and hospital characteristics.

Results: Among 61,017 cholecystectomy patients, 31,133 (51%) received IV APAP. Subjects averaged 51 and 57 years of age, respectively, in the IV and oral APAP cohorts. In the adjusted models, IV APAP was associated with 0.42 days shorter LOS (95% CI?=?–0.58 to –0.27; p?p?p?=?.0005), and lower rates of respiratory depression (odds ratio [OR]?=?0.89, 95% CI?=?0.82–0.97; p?=?.006), and nausea and vomiting (OR?=?0.86, 95% CI?=?0.86–0.86; p?Conclusions: In patients having cholecystectomy, the addition of IV APAP to perioperative pain management is associated with shorter LOS, lower costs, reduced opioid use, and less frequent nausea/vomiting and respiratory depression compared to oral APAP. These findings should be confirmed in a prospective study comparing IV and oral APAP.