Enhanced Recovery after Elective Open Surgical Repair of Abdominal Aortic Aneurysm: A Complementary Overview through a Pooled Analysis of Proportions from Case Series Studies

Objectives: To evaluate the efficacy and safety of enhanced recovery after surgery (ERAS) programs in elective open surgical repair (OSR) of abdominal aortic aneurysm (AAA).Background: Open surgical repair of AAA is associated with high morbidity and mortality, prolonged hospital stay and high costs. ERAS programs contribute to the optimization of treatment by reducing hospital stay and improving clinical outcomes.Methods: A review of PubMed, EMBASE and LILACS databases was conducted. As only one randomized controlled trial was found, a pooled analysis of proportions from case series was conducted, considering it a complementary overview of the topic. Inclusion criteria were case series with more than five cases reported, adult patients who underwent an elective OSR of AAA and use of an ERAS program. ERAS was compared to conventional perioperative care. The pooled proportion and the confidence interval (CI) are shown for each outcome. The overlap of the CI suggests similar effect of the interventions studied.Results: Thirteen case series studies with ERAS involving 1,250 patients were compared to six case series with conventional care with a total of 1,429 patients. The pooled, respective proportions for ERAS and conventional care were: mortality, 1.51% [95% CI: 0.0091, 0.0226] and 3.0% [95% CI 0.0183, 0.0445]; and incidence of complications, 3.82% [95% CI 0.0259, 0.0528] and 4.0% [95% CI 0.03, 0.05].Conclusion: This review shows that ERAS and conventional care therapies have similar mortality and complication rates in OSR of AAA.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

Pooled analysis of trials comparing titanium-nitride-oxide-coated stents with paclitaxel-eluting stents in patients undergoing coronary stenting

We performed a pooled analysis of three trials comparing titanium-nitride-oxide-coated bioactive stents (BAS) with paclitaxel-eluting stents (PES) in 1,774 patients. All patients were followed for 12 months. The primary outcomes of interest were recurrent myocardial infarction (MI), death and target lesion revascularization (TLR). Secondary endpoints were stent thrombosis (ST) and major adverse cardiac events (MACE) including MI, death and TLR. There were 922 patients in the BAS group and 852 in the PES group. BAS significantly reduced the risk of recurrent MI (2.7% vs. 5.6%; risk ratio 0.50, 95% CI 0.31-0.81; p = 0.004) and MACE (8.9% vs. 12.6%; risk ratio 0.71, 95% CI 0.54-0.94; p = 0.02) during the 12 months of follow up. In contrast, the differences between BAS and PES were not statistically significant with respect to TLR (risk ratio 0.98, 95% CI 0.68-1.41), death (risk ratio 0.96, 95% CI 0.61-1.51) and definite ST (risk ratio 0.28, 95% CI 0.05-1.47). In conclusion, the results of this analysis suggest that BAS is effective in reducing TLR and improves clinical outcomes by reducing MI and MACE compared with PES.

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

A patient-level pooled analysis assessing the impact of the SYNTAX (synergy between percutaneous coronary intervention with taxus and cardiac surgery) score on 1-year clinical outcomes in 6,508 patients enrolled in contemporary coronary stent trials

This study sought to assess the impact of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SXscore) on clinical outcomes in patients undergoing percutaneous coronary intervention.

Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials

The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES).

Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Association between symptoms and quality of life in patients with schizophrenia: a pooled analysis of changes over time

Quality of life is an important outcome in the treatment of patients with schizophrenia. It has been suggested that patients' quality of life ratings (referred to as subjective quality of life, SQOL) might be too heavily influenced by symptomatology to be a valid independent outcome criterion. There has been only limited evidence on the association of symptom change and changes in SQOL over time. This study aimed to examine the association between changes in symptoms and in SQOL among patients with schizophrenia. A pooled data set was obtained from eight longitudinal studies that had used the Brief Psychiatric Rating Scale (BPRS) for measuring psychiatric symptoms and either the Lancashire Quality of Life Profile or the Manchester Short Assessment of Quality of Life for assessing SQOL. The sample comprised 886 patients with schizophrenia. After controlling for heterogeneity of findings across studies using linear mixed models, a reduction in psychiatric symptoms was associated with improvements in SQOL scores. In univariate analyses, changes in all BPRS subscales were associated with changes in SQOL scores. In a multivariate model, only associations between changes in the BPRS depression/anxiety and hostility subscales and changes in SQOL remained significant, with 5% and 0.5% of the variance in SQOL changes being attributable to changes in depression/anxiety and hostility respectively. All BPRS subscales together explained 8.5% of variance. The findings indicate that SQOL changes are influenced by symptom change, in particular in depression/anxiety. The level of influence is limited and may not compromise using SQOL as an independent outcome measure.

Factors influencing subjective quality of life in patients with schizophrenia and other mental disorders: a pooled analysis

Subjective quality of life (SQOL) is an important outcome in the treatment of patients with schizophrenia. However, there is only limited evidence on factors influencing SQOL, and little is known about whether the same factors influence SQOL in patients with schizophrenia and other mental disorders. This study aimed to identify the factors associated with SQOL and test whether these factors are equally important in schizophrenia and other disorders. For this we used a pooled data set obtained from 16 studies that had used either the Lancashire Quality of Life Profile or the Manchester Short Assessment of Quality of Life for assessing SQOL. The sample comprised 3936 patients with schizophrenia, mood disorders, and neurotic disorders. After controlling for confounding factors, within-subject clustering, and heterogeneity of findings across studies in linear mixed models, patients with schizophrenia had more favourable SQOL scores than those with mood and neurotic disorders. In all diagnostic groups, older patients, those in employment, and those with lower symptom scores had higher SQOL scores. Whilst the strength of the association between age and SQOL did not differ across diagnostic groups, symptom levels were more strongly associated with SQOL in neurotic than in mood disorders and schizophrenia. The association of employment and SQOL was stronger in mood and neurotic disorders than in schizophrenia. The findings may inform the use and interpretation of SQOL data for patients with schizophrenia.

Periprocedural and late consequences of overlapping Cypher sirolimus-eluting stents: pooled analysis of five clinical trials

OBJECTIVES: The purpose of this research was to determine the relative safety and efficacy of multiple (> or =2) overlapping Cypher sirolimus-eluting stents (SES) (Johnson ; Johnson, New Brunswick, New Jersey). BACKGROUND: Overlapping coronary stents are common. The periprocedural and late clinical and angiographic consequences of overlapped coronary stents are not clearly defined, particularly for drug-eluting stents. METHODS: All patients enrolled into five clinical trials of the SES were analyzed. Three of these trials were prospective randomized comparisons of the SES to the bare-metal stent (BMS), and two were prospective non-randomized trials of SES-treated patients with historical controls. All clinical and angiographic outcomes in overlap-stent-treated patients were compared by stent type and with single-stent-treated patients for the same stent device. RESULTS: In all, 575 patients with stent overlap (337 SES, 238 BMS) and 1,162 patients with single stents (697 SES, 465 BMS) were analyzed. Stent overlap was associated with a greater late lumen loss in stent and more frequent angiographic restenosis regardless of stent type. Among overlap-stent-treated patients, the SES provided similar magnitude of restenosis benefit as observed for single-stent-treated patients. Overlapped SES was not associated with an increase in myocardial infarction. CONCLUSIONS: The strategy of SES overlap, when required, is both safe and efficacious in reducing restenosis with no increase in the incidence of myocardial infarction or major adverse cardiovascular events, when compared with a bare metal coronary stent prosthesis.

Long-term outcomes of biodegradable polymer versus durable polymer drug-eluting stents in patients with diabetes a pooled analysis of individual patient data from 3 randomized trials

BACKGROUND There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). METHODS We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis. RESULTS Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio=0.95, 95% CI=0.74-1.21, P=0.67). Target lesion revascularization was also comparable between the groups (hazard ratio=0.89, 95% CI=0.65-1.22, P=0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio=0.52, 95% CI=0.28-0.96, P=0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4years (hazard ratio=0.15, 95% CI=0.03-0.70, P=0.02). CONCLUSIONS In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4years. Rates of stent thrombosis were significantly lower with BP-DES.

Comparison of Newer-Generation Drug-Eluting With Bare-Metal Stents in Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pooled Analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) Trials

OBJECTIVES This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. METHODS Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. RESULTS Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. CONCLUSIONS Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials

BACKGROUND The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. METHODS We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. FINDINGS Of 43,904 patients recruited in 26 trials of DES, 11,557 (26·3%) were women (mean age 67·1 years [SD 10·6]). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 [18·6%] women in the bare-metal stent group, 294 [7·8%] in the early-generation DES group, and 330 [6·3%] in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. INTERPRETATION The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. FUNDING Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.

Clinical outcomes of the resolute zotarolimus-eluting stent in patients with in-stent restenosis: 2-year results from a pooled analysis

OBJECTIVES This study sought to assess the clinical safety and effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in patients with in-stent restenosis (ISR) from 2 large trials. BACKGROUND ISR treatment is associated with higher rates of subsequent cardiac events compared with treatment of de novo lesions. Although drug-eluting stents (DES) are an option, second-generation DES are largely untested in the treatment of ISR. METHODS A total of 3,489 patients were pooled from the RAC (RESOLUTE All Comers) trial and the RESOLUTE International (RINT) registry. Two-year clinical endpoints included clinically driven target lesion revascularization (TLR), target lesion failure (TLF), cardiac death (CD), target vessel myocardial infarction (TVMI), combined CD or TVMI (CD/TVMI), and Academic Research Consortium definite and probable stent thrombosis (ST). RESULTS Overall, 281 patients (8.1%) received an R-ZES for ISR. Two-year TLR and TLF rates were significantly higher in ISR patients than in non-ISR patients (TLR: 12.7% vs. 4.3%, p = 0.003; TLF: 17.4% vs. 9.4%, p = 0.007); however, the CD/TVMI rate was not (6.9% vs. 6.1%, p = 0.711). Seven ISR patients had ST. Two-year outcomes by ISR stent type were similar: bare-metal stent (BMS)-ISR TLR was 12.5% and TLF was 17.2%; DES-ISR TLR was 13.0% and TLF was 18.8%. CD/TVMI was 7.3% and 7.2% for BMS-ISR and DES-ISR, respectively. CONCLUSIONS Using R-ZES to treat ISR appears equally safe in BMS-ISR and DES-ISR, with CD/TVMI rates comparable to 2-year outcomes in other clinical trials. Although revascularization rates are still higher in ISR lesions, the R-ZES offers an effective alternative for treatment of BMS-ISR and DES-ISR. (Randomized, Two-Arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; and RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [RINT]; NCT00752128).