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.     

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.     

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.     

Safety,effectiveness, and health care cost comparisons among elderly patients with venous thromboembolism prescribed warfarin or apixaban in the United States Medicare population

Abstract

Objective: To compare safety, effectiveness, and healthcare costs of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, recurrent venous thromboembolism (VTE), and all-cause hospitalization among elderly Medicare VTE patients prescribed warfarin vs apixaban.

Methods: Using 100% Medicare data, elderly patients prescribed apixaban or warfarin within 30 days after a VTE encounter were identified. Patients had continuous health plan enrollment and no parenteral or oral anticoagulant use ≤6 months preceding the VTE encounter. Cohorts were balanced using 1:1 propensity score matching (PSM). Cox proportional hazard models were used to assess the risk of MB, CRNM bleeding, recurrent VTE, and all-cause hospitalization. Generalized linear and two-part models were used to estimate MB-, recurrent VTE-, and all-cause related costs (per patient per month [PPPM]).

Results: In the pre-matched cohort, 25,284 (66.9%) patients were prescribed warfarin and 12,515 (33.1%) apixaban. After 1:1 PSM, 11,363 matched pairs of apixaban-warfarin patients were included for a mean follow-up of 4.0 and 4.4 months, respectively. Matched cohorts had a mean age of 78 years and mean Charlson Comorbidity Index score of 2.9. Warfarin was associated with a higher risk of MB (hazard ratio [HR]?=?1.31; 95% confidence interval [CI]?=?1.10–1.57) and CRNM bleeding (HR?=?1.31; 95% CI?=?1.19–1.43) vs apixaban. The risks of recurrent VTE (HR?=?0.96; 95% CI?=?0.70–1.33) and all-cause hospitalization (HR?=?1.05; 95% CI?=?0.99–1.12) were similar among warfarin and apixaban patients. Warfarin patients had higher MB-related ($147 vs $75; p?=?.003) and all-cause costs PPPM ($3,267 vs $3,033; p?<?.001), but similar recurrent VTE-related medical costs PPPM ($30 vs $36; p?=?.516) vs apixaban patients.

Conclusions: Warfarin was associated with significantly higher risk of MB and CRNM bleeding as well as higher MB-related and all-cause costs vs apixaban patients. Recurrent VTE risk and costs were similar among warfarin and apixaban patients.     

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.     

Association between Cardiovascular Drugs and Chronic Kidney Disease in Non‐Institutionalized Elderly Patients

Concern about the renal safety of commonly used cardiovascular drugs with demonstrated clinical benefit appears to be an obstacle to their use in the elderly. The objective was to describe the relationship between cardiovascular drugs and chronic kidney disease (CKD) in elderly individuals in the real‐life setting. This is an ancillary study of the prospective non‐interventional S.AGE (aged individuals) cohort. General physicians were free to prescribe any drug their patients needed. The participants were non‐institutionalized patients aged 65 years and older treated by their primary physician for either chronic pain or atrial fibrillation or type 2 diabetes mellitus. The estimated glomerular filtration rate (eGFR) derived from the CKD‐EPI formula was determined at inclusion and every year during 2 years of follow‐up. This study comprised 2505 patients aged 77.8 ± 6.2 years. At inclusion, the factors associated with CKD (eGFR < 60 ml/min/1.73 m²) in multivariate analysis were age, female gender, hypertension, heart failure, history of atherothrombotic disease and renin angiotensin system blockers, loop diuretics and calcium channel inhibitors. Introduction of each of these three drug classes during the follow‐up period led to only a small decrease in the eGFR: ?3.8 ± 12.7 (p < 0.0006), ?2.2 ± 12.0 (p < 0.003) and ?1.0 ± 13.4 ml/min./1.73 m² (NS), respectively. Only the introduction of loop diuretics was associated with CKD (OR 1.91, 95% CI: 1.25–2.90; p = 0.002). Renal safety of cardiovascular drugs in the elderly appears acceptable and should not be a barrier to their use.     

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.     

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.     

Restrictive versus liberal blood transfusion in patients with coronary artery disease: a meta-analysis

Objectives: To compare clinical outcomes between restrictive versus liberal blood transfusion strategies in patients with coronary artery disease (CAD).

Research design and methods: A literature search from January 1966 to May 2016 was performed in PubMed, EMBASE and Cochrane Library to find trials evaluating a restrictive hemoglobin transfusion trigger of ≤8?g/dL, compared with a more liberal trigger. Two study authors independently extracted data from the trials. The primary outcome was mortality and the secondary outcome was subsequent myocardial infarction. Relative risks (RRs) with their 95% confidence intervals (CIs) were assessed.

Results: Six trials involving 133,058 participants were included in this study. Pooled results revealed no difference in mortality between the liberal transfusion and restrictive transfusions (RR?=?1.17, 95% CI?=?0.91–1.52, P?=?.22). Subgroup analysis revealed that a restrictive transfusion strategy was associated with a higher risk of in-hospital mortality (RR?=?1.38, 95% CI?=?1.15–1.67, P?P?=?.03), compared with the liberal strategy. No significant difference was found between the liberal transfusion strategy and restrictive transfusion strategy in risk for subsequent myocardial infarction (RR?=?1.09, 95% CI?=?0.57–2.06, P?=?.80).

Limitations: Limitations include (1) limited number of trials, especially those evaluating myocardial infarction, (2) observed heterogeneity, (3) confounding by indication and other inherent bias may exist.

Conclusion: The findings suggest that restrictive blood transfusion was associated with higher in-hospital and 30?day mortality than liberal blood transfusion in CAD patients. The conclusions are mainly based on retrospective studies and should not be considered as recommendation before they are supported by randomized controlled trials.     

Adenocarcinoma histology is a poor prognostic factor in locally advanced cervical cancer

Objective: This retrospective study aimed to compare prognostic factors and survival between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in locally advanced cervical cancer treated at a single center.

Methods: All medical records of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB or IIIA,B, treated between 2004 and 2012, were reviewed. We treated patients with chemoradiotherapy (CRT) followed by brachytherapy (BT). Multivariate logistic regression and Cox proportional hazard models were used to analyze clinicopathological characteristics, patterns of care and outcomes.

Results: We included in the analysis 161 patients (52 AC; 109 SCC). Patients with AC were younger (age 50 vs. 55?years), more likely to die from the disease (HR: 1.60; 95% CI: 1.26–2.58; p?=?.001) and to have disease recurrence (HR: 1.69; 95% C.I: 1.21–2.12; p?=?.004) than those with SCC. The other significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in AC were FIGO stage (p?=?.001; p?=?.002), WHO status (0 vs. 1–3; p?=?.003; p?=?.04), and hemoglobin level (<12?g/dl>; p?=?.04; p?=?.02). The 5?year overall survival for stage II of AC and SCC was 63% and 82% (p?=?.03), and for IIIA,B it was 33.6% and 73% (p?=?.0005). The 5?year RFS for AC and SCC stage FIGO IIIA,B was 24% and 57% (p?=?.001).

Conclusions: Adenocarcinoma histology negatively impacts OS and RFS for advanced cervical cancer. Histology-specific therapy may be an opportunity for survival improvement in these women.     

Frequency and risk factors for mental disorders following pancreatitis: a nationwide cohort study

Objective: To investigate the frequency and risk factors for mental disorders following pancreatitis.

Methods: Patients with acute pancreatitis (AP) and chronic pancreatitis (CP) were identified (n?=?18,074) from a nationwide database in New Zealand (1998–2015). They were followed from their first hospital admissions for AP or CP to incident mental disorders. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression analyses.

Results: CP (vs AP) was associated with a significantly higher risk of mental disorders (adjusted HR?=?2.00 [95% CI?=?1.53–2.62]). Pre-existing diabetes (adjusted HR?=?8.99 [95% CI?=?6.23–12.96] for AP and adjusted HR?=?3.42 [95% CI?=?2.37–4.96] for CP) and post-pancreatitis diabetes mellitus (adjusted HR?=?7.10 [95% CI?=?4.14–12.19] for AP and adjusted HR?=?2.97 [95% CI?=?1.83–4.82] for CP) were risk factors for mental disorders in individuals following pancreatitis. Severe (adjusted HR?=?2.07 [95% CI?=?1.39–3.06] vs mild) and recurrent (adjusted HR?=?1.62 [95% CI?=?1.07–2.45] vs single episode) attacks were associated with significantly higher risks of mental disorders following AP.

Conclusions: Patients following CP, recurrent AP, severe AP, and those with diabetes are at high risk for developing mental disorders.     

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.     

Hospitalization risk in bipolar disorder patients treated with lurasidone versus other atypical antipsychotics

Objective: This observational study compared the risk of hospitalization for patients with bipolar disorder when treated with lurasidone versus other oral atypical antipsychotics.

Methods: This US commercial claims analysis (4 April 2010 through 24 September 2014) used the Optum Research Database to identify adult patients with bipolar disorder treated with oral atypical antipsychotics (N?=?11,132). The first claim for an atypical antipsychotic defined the index date, with pre-index and post-index periods of 180 and 360 days, respectively. Every month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, no/minimal treatment or other. Starting with the initial month of treatment, the risk of psychiatric or all-cause hospitalization in the subsequent month was examined based on treatment in the current month and pre-index covariates (age, gender, hospitalizations, emergency room visits, diagnoses for anxiety, alcohol abuse, substance abuse, hypertension, type 2 diabetes and obesity) and time-varying versions of the pre-index covariates using a marginal structural model.

Results: After controlling for covariates, relative to lurasidone, the odds of psychiatric and all-cause hospitalization, respectively, were 2–3 times higher for olanzapine (odds ratio [OR]?=?2.78, CI 1.09, 7.08, p?=?.032; OR?=?3.20, CI 1.24, 8.26, p?=?.016), quetiapine (OR?=?2.80, CI 1.13, 6.95, p?=?.026; OR?=?3.23, CI 1.29, 8.11, p?=?.013), risperidone (OR?=?2.50, CI 1.01, 6.21, p?=?.048; OR?=?2.79, CI 1.11, 7.02, p?=?.029), aripiprazole (OR?=?2.13, CI 0.87, 5.20, p?=?.097; OR?=?2.57, CI 1.04, 6.37, p?=?.041) and ziprasidone (OR =2.31, CI 0.91, 5.85, p?=?.079; OR?=?2.49, CI 0.97, 6.40, p?=?.058).

Conclusions: In this claims database analysis, lurasidone-treated patients with bipolar disorder had a significantly lower risk of psychiatric hospitalization compared to quetiapine, olanzapine and risperidone, but not aripiprazole or ziprasidone. Lurasidone-treated patients had a significantly lower risk of all-cause hospitalization compared to quetiapine, olanzapine, risperidone and aripiprazole, but not ziprasidone.     

Impact of increased venous pressure on kidney function and mortality in cardiovascular patients with preserved ejection fraction

Abstract

Background: Right but not left ventricular hemodynamic parameters have been found to be independently associated with adverse renal outcomes in patients with acute decompensated heart failure (HF).

Aim: To investigate the hemodynamic profile of patients without acute decompensated heart failure and left ventricular ejection fraction >50% referred for elective left and right heart catheterization and to correlate left and right filling pressures, stroke volume and arterial blood pressure to renal function parameters. Subsequently, we tested the hypothesis that right ventricle and left ventricle hemodynamic parameters can predict all-cause mortality in our non-HF subjects.

Methods: Between October 2009 and November 2010, 151 consecutive patients referred for elective left and right heart catheterization were studied and consequently followed up for a mean period of 8?years in order to identify all-cause mortality. Patient’s initial cohort was subdivided in two groups according to right atrial pressure. The RAPR_LOW group (Right Atrium Pressure ≤ 9?mmHg) and the RAPR_HIGH group (Right Atrium Pressure > 9mmHg)

Results: No correlation between blood pressure, pulmonary capillary wedges pressure, cardiac index, stroke volume and stroke volume index (SVI), and parameters of kidney function was observed. However, a weak, although, significant correlation between right atrial pressure (RAP) and modification of diet in renal disease (MDRD) (r = –0.202; p?=?.014) could be detected. RAPR_LOW patients had a statistically significant lower MDRD value of 16.6?mL/min/1.73 m² than RAPR_HIGH patients. Increased RAP (HR = 2.03; 95% [CI]: 1.05 to 3.9; p?=?.025) and age (HR = 1.08, 95% [CI] 1.04–1.12, p?<?.001) independently predicted all-cause mortality during follow up.

Conclusions: Our study demonstrates that right ventricular preload affects renal function in patients with preserved systolic function and that neither aortic systolic pressure nor left ventricle pressure indices were related to estimated glomerular filtration rate. Furthermore, we demonstrate for the first time that an increased RAP is able to predict a worse prognosis in patients with preserved ejection fraction independently of well-established risk factors, such as blood pressure and SVI.     

Association of high sensitivity C-reactive protein and abdominal aortic aneurysm: a meta-analysis and systematic review

Objective: To evaluate the association of high sensitivity C-reactive protein (hsCRP) with the presence of abdominal aortic aneurysm (AAA).

Methods: Medline, Cochrane, Embase, and Google Scholar databases were searched until 22 June 2016 using the keywords predictive factors, biomarkers, abdominal aortic aneurysm, prediction, high sensitivity C-reactive protein, and hsCRP. Prospective studies, retrospective studies, and cohort studies were included.

Results: Twelve case–control studies were included in the meta-analysis with a total of 8345 patients (1977 in the AAA group and 6368 in the control group). The pooled results showed that AAA patients had higher hsCRP value than the control group (difference in means?=?1.827, 95% CI?=?0.010 to 3.645, p?=?.049). Subgroup analysis found AAA patients with medium or small aortic diameter (<50?mm) had higher hsCRP plasma levels than the control group (difference in means?=?1.301, 95% CI?=?0.821 to 1.781, p?p?=?.272). Multi-regression analysis found the difference in means of hsCRP plasma levels between AAA and control groups decreased as aortic diameter increased (slope?=??0.04, p?Conclusions: Our findings suggest that hsCRP levels may possibly be used as a diagnostic biomarker for AAA patients with medium or small aortic diameter but not for AAA patients with large aortic diameter. The correlation between serum hsCRP level and AAA aneurysm is not conclusive due to the small number of included articles and between-study heterogeneity.     

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.     

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.     

Prognostic importance of the albumin to globulin ratio in metastatic gastric cancer patients

Aim: The aim of this study was to evaluate the prognostic importance of the albumin to globulin ratio (AGR) in terms of overall survival (OS) and progression free survival (PFS) in metastatic gastric cancer patients.

Methods: The patients diagnosed with metastatic gastric cancer between 2009 and April 2016 at the hospital have been studied retrospectively. The clinicopathological characteristics, laboratory, and treatment parameters have been assessed. AGR value has been calculated using the following formula (AGR?=?serum albumin/total protein???serum albumin).

Results: In total, 251 patients were included in the study population. The median value of AGR was 1.206 (range?=?0.460–3.130), and the cut-off value was set as 1.20. Based on the cut-off value, 126 patients were categorized in the low AGR group, while the remaining 125 patients were categorized in the high AGR group. ECOG (Eastern Cooperative Oncology Group) performance scores, CEA levels, CA19-9 levels, hemoglobin levels, lactate dehydrogenase levels, and liver metastasis ratios varied significantly between the low and high AGR groups (p?<?.05). The Kaplan-Meier curve has shown that, compared to the low AGR group, the high AGR group has better OS (12.2 vs 9.3 months, p?=?.002) and better PFS (8.0 vs 5.7 months, p?<?.001) rates. The univariate and multivariate analyses also proved that low AGR is an independent bad risk factor in metastatic gastric cancer patients, both in terms of OS (p?=?.019, Hazard Ratio (HR)?=?1.380, 95% Confidence Interval (CI)?=?1.055–1.805) and PFS (p?=?.002, HR?=?1.514, 95% CI?=?1.164–1.968).

Conclusion: In metastatic gastric cancer patients, AGR is an independent prognostic factor for OS and PFS. Thus, in this patient group, the low cost albumin and globulin which can be measured with routine clinical practice may be used as an appropriate prognostic tool.     

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.