Non-significant Outcomes Research Articles

Smartphone-based application to improve medication adherence in patients after surgical coronary revascularization

Secondary preventive therapies play a key role in the prevention of adverse events after coronary artery bypass grafting (CABG). However, adherence to secondary preventive drugs after CABG is often poor. With the increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve medication adherence. We aimed to evaluate the effectiveness and feasibility of using a smartphone-based application to improve medication adherence in patients after CABG. The Measurement and Improvement Studies of Surgical coronary revascularizatION: medication adherence (MISSION-2) study is a multicenter randomized controlled trial that planned to enroll over 1000 patients who underwent isolated CABG at one of four large teaching hospitals in China; all enrolled participants had access to a smartphone and were able to operate at least three smartphone applications. The investigators randomly assigned the participants to one of two groups: (1) the intervention group with an advanced smartphone application for 6 months which was designed specifically for this trial and did not exist before. Participants could receive medication reminders and cardiac health education by the smartphone application or (2) the control group with usual care. The primary outcome was CABG secondary preventive medication adherence as measured by the translated Chinese version of the 8-item Morisky Medication Adherence Scale (MMAS-8) at 6 months after randomization. The secondary outcomes were mortality, major adverse cardiovascular and cerebrovascular events (MACCE), cardiovascular rehospitalization, self-reported secondary preventive medication use after 6 months of follow-up, blood pressure (BP), body mass index (BMI), and self-reported smoking status. All analyses were conducted using the intention-to-treat principle. A total of 1000 patients (mean age, 57.28 [SD, 9.09] years; 85.5% male) with coronary heart disease after CABG were enrolled between September 2015 and September 2016 and were randomly assigned to the intervention (n = 501) or control group (n = 499). At 6 months, the proportion of low-adherence participants, categorized by MMAS-8 scores, was 11.8% in the intervention group and 11.7% in the control group (RR = 1.005, 95% CI 0.682 to 1.480, P = 1.000). Similar results were found in sensitivity analyses that considered participants who withdrew from the study, or were lost to follow-up as nonadherent. There were no significant differences in the secondary clinical outcome measures, and there were no significant differences in the primary outcome across the subgroups tested. In the intervention group, the proportion of participants who used and operated the application during the first month after CABG was 88.1%; however, the use rate decreased sharply from 42.5% in the second month to 9.2% by the end of the study (6 months). A smartphone-based application supporting secondary prevention among patients after CABG did not lead to a greater adherence to secondary preventive medications. The limited room for improvement in medication adherence and the low participants' engagement with the smartphone applications might account for these non-significant outcomes.

Discrepancies between Registered and Published Primary and Secondary Outcomes in Randomized Controlled Trials within the Plastic Surgery Literature: A Systematic Review.

Recent studies have identified a high incidence of discrepancy between registered and published outcomes in registered medical and surgical randomized controlled trials. This has not yet been studied in the plastic surgery literature. The authors systematically assessed plastic surgery randomized controlled trials published between 2012 and 2016 in seven high-impact plastic surgery journals. Data were collected from the registration website and published articles using a standardized data extraction form. A total of 145 randomized controlled trials were identified, with a 39 percent trial registration rate (n = 57). Forty-nine trials were included in the final analysis. Forty-three (88 percent) had a discrepancy between registered and published outcomes: 26 (53 percent) for primary outcome(s), and 39 (80 percent) for secondary outcome(s). The number of discrepancies in an individual trial ranged from one to seven for primary outcomes and one to 12 for secondary outcomes. Aesthetic surgery had the largest number of trials with outcome discrepancies (n = 15). The prevalence of unreported registered outcomes was 13 percent for primary outcomes and 38 percent for secondary outcomes. Registered nonsignificant primary outcomes were published as nonsignificant secondary outcomes in 30 percent of trials. Publishing new nonregistered secondary outcomes (65 percent) and changing the assessment timing of published primary outcomes (61 percent) were the most common types of discrepancies. Discrepancies favored a statistically significant positive outcome in 19 (44 percent) of the 43 trials with an outcome discrepancy. Discrepancies that resulted in published outcomes with improved patient relevance were found in eight trials (16 percent) for primary outcome discrepancies and 14 trials (29 percent) for secondary outcome discrepancies. The plastic surgery literature has high rates of discrepancies between registered and published trial outcomes. Outcome reporting discrepancy is even more problematic for secondary outcomes, an area of analysis that has previously been poorly studied. The high rate of discrepancy change favoring a statistically significant outcome and more patient-relevant outcomes may indicate the pressure to demonstrate significant results to be accepted for publication in high-impact journals.

Spin in abstracts of randomized controlled trials in dentistry: A cross-sectional analysis

BackgroundSpin in randomized controlled trial (RCT) abstracts can misguide clinicians. In this cross-sectional analysis, the authors assessed the prevalence of spin in RCT abstracts and explored the factors potentially influencing it. MethodsIn this cross-sectional analysis, the authors conducted a systematic search in top 10 dental journals based on Eigenfactor score and selected RCTs published in 2015 with statistically nonsignificant primary outcomes. The dentistry disciplines covered in these journals include general dentistry, dental research, oral implantology, endodontics, oral surgery, periodontology, and oral oncology. In these RCT abstracts, the authors assessed the prevalence of 3 different categories of spin and factors that could influence its presence using the t test and χ2 test. ResultsSpin assessment performed in the included 75 RCTs revealed the existence of spin in 23 abstracts (30.7%). Associations between the presence of spin in abstracts and the variables international collaborations, commercial support type, number of treatment arms, and journal impact factor were found to be statistically nonsignificant (P ≥ .05). ConclusionsApproximately one-third of the 75 RCT abstracts published in high-impact dental journals in 2015 with nonsignificant outcomes presented with some form of spin, irrespective of funding type and journal impact factor. Practical ImplicationsClinicians should be aware of the potential existence of spin in abstracts and be diligent in reading and appraising the full trial before incorporating its recommendations in clinical practice.

Remarkable effect of topical betamethasone valerate 0.1% on progress of psoriasis disease.

Introduction: Psoriasis is immuno-inflammatory condition devouring huge negative impact on patient’s life as compare to other diseases. Topical regimen is the standard treatment for mild to moderate psoriasis disease. The data of effectiveness of Betamethasone Valerate 0.1% on large number of psoriatic patients were being deficient in. Objectives: This study evaluates the Topical Betamethasone Valerate 0.1%impact on patient’s life in relation to efficacy and safety. Design: Interventional experimental study. Setting: Study was carried out Basic medical sciences institute (BMSI) alliance with Dermatology Department JPMC, Karachi. Period: June 2013 to June 2016. Methods: 75 chronic plaque type psoriatic patients prescribed Betamethasone Valerate (0.1%) topically along with placebo for 6 months once daily (one week interval after every three week application). The therapeutic effectiveness and safety of studied drug were assessed by means of PASI, DLQI and hsCRP. The results analyzed by using repeated ANOVA. Results: Results revealed that as compare to baseline all parameters were significantly reduced with mean percentage change were 75.001±0.0563, 72.215±3.17and 33.692±7.980 for PASI, DLQI and hsCRP respectively at the end of study. Safety profile of therapy showed non-significant outcomes. Conclusion: Betamethasone valerate 0.1% is better treatment option in mild to moderate psoriatic patients to improve quality of life and decrease disease severity.

Comparing the Outcome of Boost Dose of Intraoperative Radiotherapy with Electron (IOERT) and Low-kV X-Ray (IOXRT) and External Beam Radiotherapy (EBRT) in Breast Cancer After Neoadjuvant Chemotherapy

Background: In the large breast tumors or locally-advanced breast cancers, breast conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) had an acceptable local control, but greater risk of recurrence. Adding boost dose radiation to whole breast radiotherapy is involved with a reduced risk of recurrence. Boost radiotherapy can be delivered in 3 methods, including (1) external beam radiotherapy (EBRT), (2) intraoperative radiotherapy with electron (IOERT), and (3) intraoperative radiotherapy with low-kV X-ray (IOXRT). Objectives: This study compared the outcomes of these 3 methods with each other. Methods: Within 60 months, 217 unselected breast cancer patients in Cancer Research Center of Shahid Beheshti were under treatment with BCS after NACT. They received boost dose radiation in 3 groups; 115 patients in the EBRT group, 39 patients IOXRT group, and 63 patients in the IOERT group. All of them received WBRT after surgery. Results: The patients had large tumors or stage 3 breast cancer. Local recurrences were 1 (2.5%) in IOXRT, 2 (3.2%) in IOERT, and 1 (0.9%) in EBRT groups. Systemic recurrences were 4 (10.3%) in IOXRT, 10 (15.9%) in IOERT, and 16 (13.9%) in EBRT groups. Deaths were 3 (7.7%) in IOXRT, 2 (3.2%) in IOERT, and 10 (6.9%) in EBRT groups. Patients with any events were 4 (10.3%) in IOXRT, 11 (17.5%) in IOERT, and 33 (15.2%) in the EBRT group. Death due to distant metastases was lower in IOERT group, but it was not significant. No significant difference was observed in disease-free survival (DFS) among 3 groups. IOXRT group had non-significant, lower events, and better DFS. Especially, in non-PCR (non-pathologic complete response) patients, multivariate COX analysis showed better outcome (DFS) in IOXRT group (HR = 0.50), although it was not significant (P = 0.53). Conclusions: Intraoperative radiotherapy (IORT or IOXRT) as tumor bed boost during BCS after NACT had at least non-inferiority compared with EBRT. In non-PCR patient, IOXRT group had non-significant better outcomes (DFS).

Intellectual Disability After Gestational Exposure to Antidepressant Drugs: The Confidence Interval as a Compatibility Interval.

There is growing concern among statisticians that the use of P value dichotomization into significant and nonsignificant outcomes does not appropriately describe research findings; in fact, misconceptions about the very meaning of the P value abound. Many alternate approaches to interpreting data have been suggested. The use of the 95% confidence interval (CI) as a compatibility interval is one such approach. By this approach, the study estimate for an outcome is considered to be the most compatible with the population value for that outcome, and all the values in the 95% CI around that estimate are also considered to be compatible with the population value with decreasing likelihood of compatibility the greater the distance of the value from the study estimate. This concept is explained with the help of a study that examined the risk of intellectual disability (ID) in children who had been gestationally exposed to antidepressant drugs (ADs). A conventional interpretation of the study findings is that, after adjustment for confounders, AD exposure was not associated with an increased risk of ID; this, in fact, is also how the authors expressed their conclusions. However, when the 95% CI in the main analyses, subgroup analyses, and sensitivity analyses in this study are examined as compatibility intervals, it becomes apparent that, even after adjustment for confounders, a very sizeable range of values indicating increased risk is compatible with the population value. In contrast, the range of values indicating decreased or no risk is very small. The implication, therefore, is that adjustment for confounding attenuates the risk, but the risk probably remains elevated. There is uncertainty in this subjective conclusion, but this conclusion is more truthful than a conclusion that a significant risk was rendered nonsignificant by adjustment for confounding.

IDENTIFY BARRIERS AND THEIR ASSOCIATION WITH ADHERENCE TO PHYSIOTHERAPY TREATMENT AMONG RURAL AND URBAN GERIATRIC POPULATION IN PATIALA DISTRICT

Background: Adherence with the treatment has been identified as an essential factor that influences the success and outcomes of treatment. Undetected nonadherence is recognized as a reason for altered treatment programs and has been suggested as a reason for nonsignificant research outcomes. Methods: A total of 150 subjects (urban-30 females and 47 males, rural- 36 females and 37 males) were surveyed for information using structured self-questionnaire from outpatient physiotherapy centers, Punjabi University Patiala. Results: More than 95% (77 urban and 73 rural) of the elderly population. About 93.3% urban and 97.6% rural females were nonadherent whereas 91.4% urban and 100% rural males were nonadherent. Observations suggested a statistically significant relationship of barriers with adherence to physiotherapy treatment with location (p=0.0001*), physical therapy centre accessibility (p=0.0235*), difficulty travelling to physical therapy centre (p=0.0020*), paying expenses (p=0.0001*), longer treatment duration (p=0.0004*), less encouragement from family/spouse for exercise (p=0.0106*). A non-significant relationship was found with confidence to return to exercises once stopped (p=0.0998NS), difficulty in remembering exercises (p=0.7928NS), other medical condition (OA, incontinence) (p=0.0796NS), anxiety and depression (p=0.2860NS), ability to perform ADL/IDL (p=0.0888NS). Conclusion: The findings indicate that a very low level of adherence was observed among the elderly population to physical therapy treatment (6.6% urban, 2.7% rural females) and (8.5% urban, 0% of rural males). Elderly residing in rural areas are comparatively less adherent than urban elderly to physiotherapy treatment.

PDB71 - ASSESSING THE RELATIVE COST-EFFECTIVENESS OF EMPAGLIFLOZIN AND CANAGLIFLOZIN FOR THE TREATMENT OF TYPE 2 DIABETES PATIENTS WITH EXISTING CARDIOVASCULAR DISEASE IN THE UK

This study aimed to determine the relative cost-effectiveness of the sodium-glucose co-transporter-2 (SGLT-2) inhibitors empagliflozin and canagliflozin for the treatment of UK patients with type 2 diabetes (T2D) and established cardiovascular (CV) disease. A published model was used to simulate the treatment of T2D based on the UKPDS risk equations. This was used to extrapolate the clinical outcomes of the EMPA-REG OUTCOME and CANVAS trials for empagliflozin and canagliflozin, respectively, and compare the long-term economic impact from the UK NHS perspective. Hazard ratios (HRs) derived by Bucher indirect treatment comparison were used to simulate rates of the following clinical events: non-fatal myocardial infarction (MI), non-fatal stroke, hospitalisation for heart failure, CV-related mortality, progression of albuminuria, and a composite renal outcome. Adverse events included amputation, bone fracture, genital infection and renal injury. In the base case, HRs for non-significant outcomes were set to 1; absolute HRs were tested in a sensitivity analysis. Quality of life was captured via a baseline utility value, with permanent decrements associated with each event experienced. Treatment and disease management costs were derived from published sources. A lifetime horizon was used, with costs and QALYs discounted at 3.5%pa. In the base case analysis, each patient receiving empagliflozin was predicted to gain 0.99 life years (undiscounted) and 0.43 QALYs (discounted) versus canagliflozin. The predicted gain in life years resulted in a net incremental cost of £585 per patient over the horizon modelled; nevertheless, due to quality of life gains, an incremental cost-effectiveness ratio (ICER) of £1,376/QALY versus canagliflozin was estimated. Sensitivity analyses demonstrated that the ICER was relatively insensitive to varying key model parameters (remained <£8,000/QALY). Empagliflozin is expected to be cost-effective versus canagliflozin for the treatment of UK patients with T2D and established CV disease. This conclusion appears robust in various sensitivity analyses.

Role of Positive Airway Pressure Therapy for Obstructive Sleep Apnea in Patients With Stroke: A Randomized Controlled Trial.

Obstructive sleep apnea (OSA) is an independent risk factor for stroke. The objective of this study was to assess the effect of continuous positive airway pressure (CPAP) treatment on prevention of new vascular events among patients with stroke and OSA. Consecutive conscious patients presenting with first imaging-confirmed arterial stroke were included, 6 weeks or more after ictus. All patients underwent clinical and polysomnography (PSG) testing. Patients with an apnea-hypopnea index (AHI) of > 15 events/h were randomized to posttitration nightly CPAP treatment and non-CPAP (received best medical treatment) groups. On follow-up at 3, 6, and 12 months from randomization, evaluation was carried out for any new vascular events as the primary outcome measure, and for clinical stroke outcomes (using the Barthel Index and modified Rankin scale) and neuropsychological parameters as the secondary outcome measures. Among the 679 patients with stroke who were screened, 116 reported for PSG, 83 had AHI > 15 events/h, and 70 (34 in CPAP and 36 in non-CPAP) were randomized. Thirteen patients could not be randomized because of a lack of CPAP devices. Four patients crossed over from the CPAP to the non-CPAP group. Age (mean age 53.41 ± 9.85 in CPAP versus 52.69 ± 13.23 years in non-CPAP, P = .81) and sex distribution (24 males in CPAP versus 33 males in non-CPAP, P = .79) were similar in both groups. At 12-month follow-up, there was 1 vascular event (3.33%) in the CPAP group and 6 events (15%) in the non-CPAP group (P = .23). Modified Rankin scale score improvement by ≥ 1 at 12-month follow-up was found in significantly more patients in the CPAP group than in the non-CPAP group (53% versus 27%). These findings suggest significantly better stroke outcomes and statistically nonsignificant favorable outcomes in terms of recurrence of vascular events for patients with stroke and OSA who use CPAP treatment. Registry: Clinical Trials Registry - India, CTRI Registration No: CTRI/2016/07.007104, Title: Sleep Disordered Breathing in stroke patients: Effect of treatment trial, URL: http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=8682&EncHid=&userName=sleep%20disordered%20breathing.

Abstract WP316: Efficacy and Safety of Usage of Tirofiban for Patients With Acute Ischemic Stroke- A Meta-Analysis

Background: Tirofiban, a Glycoprotein IIb/IIIa inhibitor, has been used as an adjunctive therapy (adjunct to alteplase or antiplatelet) for patients with acute ischemic stroke. We aimed to conduct a systematic review and meta-analysis assessing both the efficacy and safety of tirofiban usage in ischemic stroke patients. Methods: We searched PubMED with the terms “tirofiban", and" ischemic stroke". Inclusion criteria were 1) randomized or non-randomized studies with two study arms; 2) inclusion data on mortality and/or symptomatic intracerebral hematoma (sICH); 3) modified Rankin Scale (mRS) used as an outcome measurement at 90 days; and 4) publication in the English language. We extracted data and calculated a summary odds ratio for sICH, mortality, and favorable outcomes (defined as mRS of 0 ≤1). Results: Five studies with 617 subjects suffering acute ischemic stroke were included in the analysis. Three studies included mRS data at 3 months which demonstrated that the trend of non-significant favorable outcomes in the Tirofiban group were non-significant (ORs=1.29; 95% CI=0.55-3.31; P=0.56). Two studies included data on sICH and there was no difference in risk of sICH. (ORs=0.52; 95% CI=0.09-3.-3; p=0.46). Four studies contained data on patients who died after treatment and there was no difference in the risk of mortality (ORs=1.06; 95% CI: 0.28-3.97; p=0.94). Conclusion: Our meta-analysis suggests that Tirofiban as an adjunct therapy to acute ischemic stroke does not increase the risk of sICH or death in stroke patients, but also does not increase the rate of favorable outcomes.

Exporters’ Innovativeness and New Product Performance: Organizational Structure as a Moderator

Although the predominant view is that firm-level innovativeness contributes positively to performance, existing studies also point to non-significant and negative performance outcomes. The inconclu...

CREST-2: Identifying the Best Method of Stroke Prevention for Carotid Artery Stenosis: National Institute of Neurological Disorders and Stroke Organizational Update.

One of the great achievements of modern medicine is the successful prevention of stroke and other cardiovascular diseases. Although the incidence of stroke has substantially declined over the last 30 years, ≈200 000 preventable stroke deaths still occur annually in the United States. According to a recent study based on the Greater Cincinnati/Northern Kentucky Stroke Study, annually ≈41 000 strokes in the United States are attributed to extracranial internal carotid artery stenosis. Early revascularization for symptomatic carotid stenosis—that is, in patients with recent ipsilateral stroke or TIA—is well established as effective at preventing ipsilateral stroke. Carotid stenosis in the absence of symptoms is extremely common, but the best treatment is unclear. While 2 randomized trials showed a benefit of carotid endarterectomy (CEA) over antiplatelet therapy with aspirin, the number needed to treat approaches 200. Does aggressive risk factor control change that balance? Population screening for carotid stenosis followed by revascularization is considered to cause net harm. Are complication rates from endarterectomy and stenting now low enough to justify expanding their indications in asymptomatic patients? The National Institute of Neurological Disorders and Stroke (NINDS)–funded CREST-2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) is an ambitious attempt to further refine the treatment of asymptomatic carotid stenosis. As one of the largest randomized stroke prevention trials, the first CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) was designed to compare the safety and efficacy of 2 stroke prevention procedures for carotid artery narrowing—CEA and carotid artery stenting (CAS)—in symptomatic and asymptomatic individuals. Starting in December 2000, this NINDS-funded trial enrolled >2500 patients at 117 sites in the United States and Canada. Because of slow enrollment, the trial took 9 years to complete. In 2010, the results of CREST indicated that the 2 revascularization procedures were equivalent for …

The significance of the trial outcome was associated with publication rate and time to publication

ObjectivesThis study aims to comprehensively assess the publication of clinical trial results and factors associated with their publication. Study Design and SettingPhase II and III trials of advanced breast cancer registered on ClinicalTrials.gov between October 1, 2000, and September 30, 2012, were identified. Publications were searched by using PubMed and reviewing those listed on the registry site. The main outcomes were publication rate, public availability of results, and time to publication. ResultsOf 352 phase II and 74 phase III trials, 12.5% and 31.1% were published, whereas 46.9% and 58.1% had publicly available results, respectively. Compared to those with significant results, studies with nonsignificant results had delays in time to publication (P < 0.001). Even after adjusting for funding source and phase type, the significance of study outcomes was a significant factor that affected time to publication (hazard ratio = 6.02; 95% confidence interval: 3.59, 10.07; P < 0.001), with trials with significant outcomes taking less time to publish than those with nonsignificant outcomes. ConclusionUnderreporting of results and nonpublication or delays in the publication of negative results were identified in registered trials of advanced breast cancer. Thus, further initiatives appear necessary to urgently address such publication bias.

Clinical relevance of the International Society for Heart and Lung Transplantation consensus classification of primary graft dysfunction after heart transplantation: Epidemiology, risk factors, and outcomes

Primary graft dysfunction (P-GD) is the leading cause of early mortality after heart transplantation (HT). In this 2-center study we analyze outcomes and risk factors of P-GD according to the recent consensus conference classification endorsed by International Society for Heart and Lung Transplantation. We included all adult HTs performed between 1999 and 2013. P-GD was graded as mild, moderate, and severe, according to International Society for Heart and Lung Transplantation recommendations, and analyzed separately from secondary GD. The primary end point was the combined occurrence of in-hospital death or emergency retransplantation. Early GD was found in 118 of 518 patients (23%), and 72 (13.9%) met the criteria for P-GD. Of these, 4 (5%) were mild, 33 (46%) moderate, and 35 (49%) severe and mostly characterized by biventricular involvement (78%). The end point occurred in 53 patients (10.2%). Overall, GD was a strong predictor of death-graft loss (odds ratio, 15.9; 95% confidence interval, 7.9-33.5; p < 0.01), with non-significant worse outcomes in P-GD (37%) vs secondary GD (27%) patients (p = 0.2). The study end point was more frequent in severe P-GD patients (65%) than in moderate (12%) or mild (0%; p < 0.01). Several known risk factors influenced the risk for P-GD, and the combination of specific donor and recipient risk factors accounted for approximately 22-times increased odds for P-GD. Donor age, recipient diabetes, ischemic time, and post-operative dialysis predicted non-recovery from P-GD. Consensus-defined P-GD identifies patients at major risk for early death and graft loss after HT, although the "mild" grade appeared under-represented and clinically irrelevant. The amplified negative effect of donor and recipient factors on P-GD risk underscores the need for appropriate donor-recipient match.

SEMIAUTOMATED QUANTITATIVE APPROACH TO CHARACTERIZE TREATMENT RESPONSE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Real-World Study.

To perform a quantitative study of the vascular microstructure in actively treated choroidal neovascularization by optical coherence tomographic angiography. Patients undergoing individualized anti-vascular endothelial growth factor therapy of minimum 12 months duration were included in this cross-sectional observational study and imaged using optical coherence tomographic angiography. En face optical coherence tomographic angiography images were analyzed for quantitative features, such as junction density, vessel length, and lacunarity using validated software (Angiotool). Patients were divided into 2 groups depending on their individualized treatment interval: "good responders, treated less frequently than 6 weeks" versus "poor responders, treated every 6 weeks or more frequently." Nonparametric testing was used to assess differences between these groups. Twenty-five eyes of 23 consecutive patients with a median 58-month history of choroidal neovascularization, treated by median of 34 anti-vascular endothelial growth factor injections, were included in the analysis. There was no significant difference between any of the microvascular choroidal neovascularization features between the 2 groups (P > 0.05). The semiautomated vessel segmentation software provides an objective and quantitative approach for choroidal neovascularization characterization. The consistently nonsignificant outcomes between the groups may provide evidence to support the "normalization hypothesis." This would suggest that regardless of treatment interval, individualized therapy in these eyes established vessel stability.

Atopy and Specific Cancer Sites: a Review of Epidemiological Studies.

Mounting evidence appears to link asthma and atopy to cancer susceptibility. This review presents and discusses published epidemiological studies on the association between site-specific cancers and atopy. PubMed was searched electronically for publications between 1995 and 2015, and cited references were researched manually. Quantitative studies relating to atopy, allergy, or asthma and cancer were identified and tabulated. Despite many exposure-related limitations, patterns in the studies were observed. Asthma, specifically, has been observed to be a risk factor for lung cancer. A protective effect of atopic diseases against pancreatic cancer has been shown consistently in case-control studies but not in cohort studies. Allergy of any type appears to be protective against glioma and adult acute lymphoblastic leukemia. Most studies on atopic diseases and non-Hodgkin lymphoma or colorectal cancer reported an inverse association. The other sites identified had varying and non-significant outcomes. Further research should be dedicated to carefully defined exposure assessments of "atopy" as well as the biological plausibility in the association between atopic diseases and cancer.

Composite Scores and Other Outcome Measures in Stroke Trials.

Randomized controlled trials represent the most useful tool to evaluate the effectiveness of a treatment in medical research. When designing a clinical trial, the choice of end points, assessment tools, and scores is crucial as they represent the prerequisites for the evaluation of outcomes and for the critical appraisal of findings. In stroke research, outcomes are mainly represented by composite end points focusing on the occurrence of cardiovascular and cerebrovascular events in trials on primary and secondary prevention and by measures of recovery and residual disability in acute stroke trials. Assessment tools which are more frequently used to evaluate recovery after acute stroke care include the National Institutes of Health Stroke Scale, the Modified Rankin Scale, the Barthel Index, the Glasgow Outcome Scale, and the Stroke Impact Scale. However, there is a wide heterogeneity of outcome measures across different trials, which makes it difficult to compare results and to draw definitive conclusions on the usefulness of the investigated strategies and treatments. Moreover, in some cases, details about outcomes are poorly reported with a tendency to focus on outcomes that are statistically significant while information about nonsignificant outcomes is frequently missed. There is an urgent need to improve the quality of designing, conducting, analyzing, and reporting data from randomized clinical trials in order to obtain complete, clear, and rigorous information on the effectiveness of management strategies in stroke care. Key properties of tools measuring outcome should include validity, reliability, and convenient statistical characteristics.

PO75A STANDARDISED ANATOMICAL AND FUNCTIONAL CLASSIFICATION OF CORTICAL AND SUBCORTICAL BRAIN FUNCTION FOR INTRAOPERATIVE MAPPING DURING AWAKE CRANIOTOMY

INTRODUCTION: Extent of resection for intrinsic brain tumors has been established as an important determinant of survival Intraoperative stimulation brain mapping enables significantly higher rates of GTR. Additionally, there has been a 4-fold increase publications related to awake craniotomy in the past decade (45% increase in past 5 years). However there are limited publications worldwide (n <300), which report a range of practices for assessing cortical function. A standardised approach is lacking, which may be a contributor. We propose a unified approach for intraoperative cognitive assessment based on validated neurocognitive practice. This will provide the field with a state-of-the-art approach to awake craniotomy. METHOD: We propose a battery of tests, using 7 lobes of the brain (frontal, parietal, temporal, occipital, insular, central, cingulate). Further fractionation of cognitive function is considered, using major cortical surface markings, and subcortical tracts (i.e. uncinate fasiciulus, arcuate fasiculus, superior longitudinal fasciculus etc.). Criteria for use include ease of delivery, replicability, lack of routine neuropsychology involvement and a tablet-base. RESULTS: Based on institutional experience over 24 months, anatomical dissection, and peer-reviewed cognitive neuroscientific findings of functional specialisation and network connectivity, a whole brain map has been designed with functional subdivision, and corresponding tasks with measurable behavioural outputs. CONCLUSION: The proposed classification will need consensus among surgeons and the neuroscience community establish a validated system with non-significant inter-observer variability and optimal functional outcomes.

The common characteristics and outcomes of multidisciplinary collaboration in primary health care: a systematic literature review.

Research on collaboration in primary care focuses on specific diseases or types of collaboration. We investigate the effects of such collaboration by bringing together the results of scientific studies. We conducted a systematic literature review of PubMed, CINAHL, Cochrane and EMBASE. The review was restricted to publications that test outcomes of multidisciplinary collaboration in primary care in high-income countries. A conceptual model is used to structure the analysis. Fifty-one studies comply with the selection criteria about collaboration in primary care. Approximately half of the 139 outcomes in these studies is non-significant. Studies among older patients, in particular, report non-significant outcomes (p < .05). By contrast, a higher proportion of significant results were found in studies that report on clinical outcomes. This review shows a large diversity in the types of collaboration in primary care; and also thus a large proportion of outcomes do not seem to be positively affected by collaboration. Both the characteristics of the structure of the collaboration and the collaboration processes themselves affect the outcomes. More research is necessary to understand the mechanism behind the success of collaboration, especially on the exact nature of collaboration and the context in which collaboration takes place.

Extracorporeal membrane oxygenation for very high-risk transcatheter aortic valve implantation

Introduction: Transcatheter aortic valve implantation (TAVI) can cause profound haemodynamic perturbation in the peri-operative period. Veno-arterial extracorporeal membrane oxygenation (ECMO) can be used to provide cardiorespiratory support during this time, either prophylactically or emergently. Methods: 100 TAVI procedures were performed between 2009 and 2013 in our institution. ECMO was used in 11 patients, including 8 prophylactic and 3 rescue cases. Rescue ECMO was required for ventricular fibrillation after valvuloplasty, and aortic annulus rupture. The criteria for prophylactic ECMO included heart failure requiring stabilisation pre-TAVI, haemodynamic instability with balloon aortic valvuloplasty performed to improve heart function pre-TAVI, moderate or severe left and/or right ventricular failure, or borderline haemodynamics at procedure. Differences in preoperative characteristics and postoperative outcomes between ECMO and non-ECMO TAVI patients were compared, and significant results were further assessed controlling for EuroSCORE. Results: Compared to TAVI patients who did not require ECMO, ECMO patients had significantly higher mean EuroSCORE (51 vs. 30%, p<.05). All-cause mortality occurred in nil prophylactic ECMO patients, one rescue ECMO patient, and two non-ECMO patients. The difference in mortality between ECMO and non-ECMO patients was not significantly different (9 vs. 2%; p>.05). Other non-significant outcomes (p<.05) included peri-procedural and spontaneous myocardial infarction (0 vs. 2% and 0 vs. 0%, respectively); disabling and non-disabling stroke (0 vs. 0% and 0 vs. 2%, respectively); transient ischaemic attack (0 vs. 0%); life-threatening, major and minor bleeding (12 vs. 3%, 0 vs. 12% and 38 vs. 13%, respectively); and major and minor vascular complications (12 vs. 5% and 0 vs. 13%, respectively). ECMO patients were more likely to develop acute renal failure than non-ECMO patients (36 vs. 8%, p<.05), which was most likely due to haemodynamic collapse and end-organ dysfunction in patients that required emergent ECMO rescue. Discussion: ECMO, in both prophylactic and rescue settings, is effective at providing cardiorespiratory support in very-high risk TAVI patients, and may have contributed to the low mortality in this series. Instituting prophylactic ECMO in an elective, controlled setting may help avoid consequences of intraoperative complications such as systemic hypoperfusion and acute renal failure, compared to emergent ECMO with rapid setup and cannulation. Limitations of this study include small patient sample size and observational nature. Future studies performed in a prospective, randomised fashion are required to evaluate the use of prophylactic ECMO, and to determine the ideal selection criteria.