| 1. |
- Falk Delgado, Alberto, et al.
(author)
-
Clinical outcome after surgical clipping or endovascular coiling for cerebral aneurysms : a pragmatic meta- analysis of randomized and non- randomized trials with short- and long- term follow- up
- 2017
-
In: JOURNAL OF NEUROINTERVENTIONAL SURGERY. - : BMJ PUBLISHING GROUP. - 1759-8478 .- 1759-8486. ; 9:3, s. 264-
-
Journal article (peer-reviewed)abstract
- Background Two randomized trials have evaluated clipping and coiling in patients with ruptured aneurysms. Aggregated evidence for management of ruptured and unruptured aneurysms is missing. Objective To conduct a meta- analysis evaluating clinical outcome after aneurysm treatment. Methods PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials. gov were searched for studies evaluating aneurysm treatment. The primary outcome measure was an independent clinical outcome ( modified Rankin scale 0- 2, Glasgow Outcome Scale 4- 5, or equivalent). Secondary outcomes were poor outcome and mortality. ORs were calculated on an intention- to- treat basis with 95% Cls. Outcome heterogeneity was evaluated with Cochrane's Q test ( significance level cut- off value at < 0.10) and l(2) ( significance cut- off value > 50%) with the Mantel-Haenszel method for dichotomous outcomes. A p value < 0.05 was regarded as statistically significant. Results Searches yielded 18 802 articles. All titles were assessed, 403 abstracts were evaluated, and 183 full-text articles were read. One- hundred and fifty articles were qualitatively assessed and 85 articles were included in the meta- analysis. Patients treated with coiling ( randomized controlled trials ( RCTs)) had higher independent outcome at short- term follow- up ( OR= 0.67, 95% Cl 0.57 to 0.79). Independent outcome was favored for coiling at intermediate and long- term follow-up ( RCTs and observational studies combined-OR= 0.80, 0.68 to 0.94 and OR= 0.81, 0.71 to 0.93, respectively). Independent outcome and lower mortality was favored after coiling in unruptured aneurysms ( database registry studies) at short- term follow- up ( OR= 0.34, 0.29 to 0.41 and OR= 1.74, 1.52 to 1.98, respectively). Conclusions This meta- analysis evaluating clinical outcome after coiling or clipping for intracranial aneurysms, indicates a higher independent outcome and lower mortality after coiling.
|
|
| 2. |
- Falk Delgado, Alberto, et al.
(author)
-
Complete Lymph Node Dissection in Melanoma : A Systematic Review and Meta-Analysis
- 2017
-
In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:12, s. 6825-6829
-
Research review (peer-reviewed)abstract
- Background: The aim of this meta-analysis was to estimate the survival after immediate complete lymph node dissection (CLND) compared to observation only (OO) or delayed CLND in patients with melanoma and lymph node metastasis.Materials and Methods: A systematic search was performed in: PubMed, Web of Science, Cochrane Library, CINAHL, Clinical trials and Embase. Eligible studies were randomized controlled trials (RCTs) comparing: CLND with OO, or immediate CLND with delayed CLND.Results: Four RCTs were included. There was no difference in melanoma-specific survival (MSS) (HR=0.91, 95% CI=0.77-1.08, p=0.29). In a sensitivity analysis, MSS was higher after immediate CLND compared to delayed CLND in patients with nodal metastasis (HR=0.63, 95% CI=0.35-0.74, p=0.0004) without evidence of heterogeneity.Conclusion: CLND appears to have no additional survival benefit after SNB compared to OO. However, subgroup analysis suggests a time-dependent benefit for early surgical lymph node removal compared to delayed or none.
|
|
| 3. |
- Falk Delgado, Alberto, et al.
(author)
-
Inconsistent Reporting Between Meta-analysis Protocol and Publication – A Cross-Sectional Study
- 2017
-
In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:9, s. 5101-5107
-
Journal article (peer-reviewed)abstract
- Background: Inconsistent reporting in published meta-analyses compared to registered protocol are poorly understood. The aim of the study was to assess inconsistencies between registered protocols and published reports among oncology drug meta-analyses.Materials and Methods: A cross-sectional study was performed including oncology drug meta-analyses published between January 1st and November 14th 2016 with a published protocol. Two investigators extracted data on: selection criteria, outcome(s) and statistical plan in protocol and manuscript, plus self-acknowledgement of inconsistent reporting between protocol and publication.Results: Protocol registration was present in 19% (23/119) of all oncology drug meta-analyses. In meta-analyses with protocol (n= 23), 70% (16/23) had issues with inconsistent reporting between protocol and published report concerning; inclusion criteria, comparator group, intervention, outcome (PICO) or statistical analysis. Self-acknowledgement of changes between protocol and publication was found in 50% (8/16).Conclusion: In meta-analyses with protocol, discrepancies between registered protocols and publications are frequent.
|
|
| 4. |
- Falk Delgado, Alberto, et al.
(author)
-
Melanoma Sentinel-Node Metastasis.
- 2017
-
In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 377:9, s. 891-892
-
Journal article (peer-reviewed)
|
|
| 5. |
- Falk Delgado, Alberto, et al.
(author)
-
Ruptured carotid-ophthalmic aneurysm treatment : a non-inferiority meta-analysis comparing endovascular coiling and surgical clipping
- 2017
-
In: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 31:3, s. 345-349
-
Journal article (peer-reviewed)abstract
- Introduction: Aneurysms of the carotid-ophthalmic segment are relatively rare, comprising only five percent of all intracranial aneurysms. There is no consensus regarding the optimal management for ruptured carotid-ophthalmic aneurysms, whether endovascular coiling or surgical clipping provide the most favourable patient outcome. The aim of this meta-analysis is to analyse these two treatment modalities for ruptured carotid-ophthalmic aneurysms with respect to independent clinical outcome.Methods: We performed a systematic literature search in PubMed, Cochrane Central Registry of Controlled Trials and Clinicaltrials.gov for treatment of ruptured carotid-ophthalmic aneurysms, comparing endovascular coiling and surgical clipping. Primary outcome in the study was independent clinical patient outcome at follow up (defined as Glasgow Outcome Scale four–five). Secondary outcomes were poor clinical patient outcome, mortality and total angiographic occlusion. The meta-analysis was performed using the Mantel–Haenszel method for dichotomous outcome.Results: Four studies met the inclusion criteria and were included in the meta-analysis. In total, 152 patients were included. Sixty-seven of these patients were treated with endovascular coiling and 85 patients were treated with microsurgical clipping. The proportion of patients with an independent clinical outcome after coiling and clipping was comparable, OR 1.04 (95% CI: 0.40, 2.71). The proportion of patients with an independent outcome in the endovascular group was 76% and in the surgical group 71%. Mortality between the two treatment arms was equal.Conclusion: Clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms was comparable between surgical clipping and endovascular coiling. There was no proven difference in clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms but the evidence was based on few studies of moderate to low quality and we cannot rule out the possibility of a difference in clinical outcome between the two treatment modalities.
|
|
| 6. |
- Falk Delgado, Alberto, et al.
(author)
-
Self-declared stock ownership and association with positive trial outcome in randomized controlled trials with binary outcomes published in general medical journals : a cross-sectional study
- 2017
-
In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18
-
Journal article (peer-reviewed)abstract
- Background: Describe the prevalence and types of conflicts of interest (COI) in published randomized controlled trials (RCTs) in general medical journals with a binary primary outcome and assess the association between conflicts of interest and favorable outcome. Methods: Parallel-group RCTs with a binary primary outcome published in three general medical journals during 2013-2015 were identified. COI type, funding source, and outcome were extracted. Binomial logistic regression model was performed to assess association between COI and funding source with outcome. Results: A total of 509 consecutive parallel-group RCTs were included in the study. COI was reported in 74% in mixed funded RCTs and in 99% in for-profit funded RCTs. Stock ownership was reported in none of the non-profit RCTs, in 7% of mixed funded RCTs, and in 50% of for-profit funded RCTs. Mixed-funded RCTs had employees from the funding company in 11% and for-profit RCTs in 76%. Multivariable logistic regression revealed that stock ownership in the funding company among any of the authors was associated with a favorable outcome (odds ratio = 3.53; 95% confidence interval = 1.59-7.86; p < 0.01). Conclusion: COI in for-profit funded RCTs is extensive, because the factors related to COI are not fully independent, a multivariable analysis should be cautiously interpreted. However, after multivariable adjustment only stock ownership from the funding company among authors is associated with a favorable outcome.
|
|
| 7. |
- Falk Delgado, Alberto, et al.
(author)
-
The association of funding source on effect size in randomized controlled trials : 2013-2015-a cross-sectional survey and metaanalysis
- 2017
-
In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18
-
Journal article (peer-reviewed)abstract
- Background: Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. Methods: Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients' having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. Results: Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72-2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25-1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26-1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. Conclusions: For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit-and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.
|
|
| 8. |
- Delgado, Anna F., et al.
(author)
-
Discrimination between Glioma Grades II and III Using Dynamic Susceptibility Perfusion MRI : A Meta-Analysis
- 2017
-
In: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 38:7, s. 1348-1355
-
Journal article (peer-reviewed)abstract
- BACKGROUND: DSC perfusion has been evaluated in the discrimination between low-grade and high-grade glioma but the diagnostic potential to discriminate beween glioma grades II and III remains unclear.PURPOSE: Our aim was to evaluate the diagnostic accuracy of relative maximal CBV from DSC perfusion MR imaging to discriminate glioma grades II and III.DATA SOURCES: A systematic literature search was performed in PubMed/MEDLINE, Embase, Web of Science, and ClinicalTrials.gov.STUDY SELECTION: Eligible studies reported on patients evaluated with relative maximal CBV derived from DSC with a confirmed neuropathologic diagnosis of glioma World Health Organization grades II and III. Studies reporting on mean or individual patient data were considered for inclusion.DATA ANALYSIS: Data were analyzed by using inverse variance with the random-effects model and receiver operating characteristic curves describing optimal cutoffs and areas under the curve. Bivariate diagnostic random-effects meta-analysis was used to calculate diagnostic accuracy.DATA SYNTHESIS: Twenty-eight studies evaluating 727 individuals were included in the meta-analysis. Individual data were available from 10 studies comprising 190 individuals. The mean difference of relative maximal CBV between glioma grades II and III (n = 727) was 1.76 (95% CI, 1.27-2.24; P < .001). Individual patient data (n = 190) had an area under the curve of 0.77 for discriminating glioma grades II and III at an optimal cutoff of 2.02. When we analyzed astrocytomas separately, the area under the curve increased to 0.86 but decreased to 0.61 when we analyzed oligodendrogliomas.LIMITATIONS: A substantial heterogeneity was found among included studies.CONCLUSIONS: Glioma grade III had higher relative maximal CBV compared with glioma grade II. A high diagnostic accuracy was found for all patients and astrocytomas; however, the diagnostic accuracy was substantially reduced when discriminating oligodendroglioma grades II and III.
|
|
| 9. |
- Falk Delgado, Alberto, et al.
(author)
-
Outcome switching in randomized controlled oncology trials reporting on surrogate endpoints: a cross-sectional analysis
- 2017
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 9206-
-
Journal article (peer-reviewed)abstract
- Inconsistent reporting of clinical trials is well-known in the literature. Despite this, factors associated with poor practice such as outcome switching in clinical trials are poorly understood. We performed a cross-sectional analysis to evaluate the prevalence of, and the factors associated with outcome switching. PubMed and Embase were searched for pharmaceutical randomized controlled trials (RCTs) in oncology reporting on a surrogate primary outcome published in 2015. Outcome switching was present in 18% (39/216). First-author male sex was significantly more likely associated with outcome switching compared to female sex with an OR of 3.05 (95% CI 1.07–8.64, p = 0.04) after multivariable adjustment. For-profit funded RCTs were less likely associated with outcome switching compared to non-profit funded research with an OR of 0.22 (95% CI 0.07–0.74, p = 0.01). First author male sex was more likely associated with outcome switching compared to female sex in drug oncology RCTs reporting on a primary surrogate endpoint. For-profit funded research was less likely associated with outcome switching compared to research funded by non-profit organizations. Furthermore, 18 percent of drug oncology trials reporting on a surrogate endpoint could have a higher risk of false positive results due to primary outcome switching.
|
|
| 10. |
- Backman, Samuel, et al.
(author)
-
Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations
- 2017
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated. Recent studies of DNA-methylation have revealed distinct clusters of PPGL that share DNA methylation patterns and driver mutations, as well as identified potential biomarkers for malignancy. However, these findings have not been adequately validated in independent cohorts. In this study we use an array-based genome-wide approach to study the methylome of 39 PPGL and 4 normal adrenal medullae. We identified two distinct clusters of tumours characterized by different methylation patterns and different driver mutations. Moreover, we identify genes that are differentially methylated between tumour subcategories, and between tumours and normal tissue.
|
|
