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Studies with negative results are less likely to be published than others, potentially leading to publication bias. Introduced in 2000, trial registration could have participated in decreasing the proportion of unpublished studies. We assessed the proportion of negative randomized controlled trials (RCT) over the last 20 years. We searched Medline for RCT published in 2000, 2005, 2010, 2015, and 2020 in the British Medical Journal, the Journal of the American Medical Association, the Lancet, and the New England Journal of Medicine. The primary endpoint was the proportion of negative (final comparison on the primary study-endpoint without statistical significance or favoring the control arm) studies published in 2000 and 2020. Factors independently associated with the publication of negative studies were identified using multivariable analysis. A total of 1,542 studies were included. The proportion of negative RCT significantly increased between 2000 and 2020 (from 27.6% to 37.4%; P = 0.01), however, the trend over time was not significant (P = 0.203). In multivariable analysis, the following factors were associated with a higher proportion of published negative studies: superiority (P < 0.001), two-group trials (P < 0.001), number of patients ≥510 (P < 0.001), cardiology trials (P = 0.003), emergency/critical care trials (P < 0.001), obstetrics trials (P = 0.032), surgery trials (P = 0.006), pneumology trials (P = 0.029). Exclusive industry funding was associated with a lower proportion of published negative studies (P < 0.001). The proportion of published negative studies in 2020 was higher only when compared to 2000. During the two decades, no trend was noticeable. There is no clear relationship between trial registration and the publication of negative results over time., (© 2025 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: It is frequent to find overlapping network meta-analyses (NMAs) on the same topic with differences in terms of both treatments included and effect estimates. We aimed to evaluate the impact on effect estimates of selecting different treatment combinations (ie, network geometries) for inclusion in NMAs., Design: Multiverse analysis, covering all possible NMAs on different combinations of treatments., Setting: Data from a previously published NMA exploring the comparative effectiveness of 22 treatments (21 antidepressants and a placebo) for the treatment of acute major depressive disorder., Participants: Cipriani et al explored a dataset of 116 477 patients included in 522 randomised controlled trials., Main Outcome Measures: For each possible treatment selection, we performed an NMA to estimate comparative effectiveness on treatment response and treatment discontinuation for the treatments included (231 between-treatment comparisons). The distribution of effect estimates of between-treatment comparisons across NMAs was computed, and the direction, magnitude and statistical significance of the 1st and 99th percentiles were compared., Results: 4 116 254 different NMAs concerned treatment response. Among possible network geometries, 172/231 (74%) pairwise comparisons exhibited opposite effects between the 1st and 99th percentiles, 57/231 (25%) comparisons exhibited statistically significant results in opposite directions, 118 of 231 (51%) comparisons derived results that were both significant and non-significant at 5% risk and 56/231 (24%) treatment pairs obtained consistent results with only significant differences (or only non-significant differences) at 5% risk. Comparisons based on indirect evidence only were associated with greater variability in effect estimates. Comparisons with small absolute values observed in the complete NMA more frequently obtained statistically significant results in opposite directions. Similar results were observed for treatment discontinuation., Conclusion: In this multiverse analysis, we observed that the selection of treatments to be included in an NMA could have considerable consequences on treatment effect estimations., Trial Registration: https://osf.io/mb5dy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Strategies for achieving high resolution varies between manufacturers. In CT, the helical mode with narrow collimation has long been considered as the gold standard for high-resolution imaging. More recently, incremental modes with small dexels and focal spot, have been developed but have not been compared with helical acquisitions under optimal conditions. The aim of this work is to compare the high-resolution acquisition strategies currently proposed by recent MSCT., Methods: Three CT systems were compared. A phantom was used to evaluate geometric accuracy, uniformity, scan slice geometry, and spatial resolution. Human dry bones were used to test different protocols on real bone architecture. A blind visual analysis was conducted by trained CT users for classifying the different acquisitions (p-values)., Results: All systems give satisfactory results in terms of geometric accuracy and uniformity. The in-plane MTF at 5% were respectively 13.4, 15.9 and 18.1 lp/cm. Dry-bones evaluation confirms that acquisition#3 is considered as the best., Conclusions: The incremental acquisition coupled with à small focal spot, and a high-sampling detector, overpasses the reference of low-pitch helical acquisitions for high-resolution imaging. Cortical bone, bony vessels, and tumoral matrix analysis are the very next challenges that will have to be managed to improve normal and pathologic bone imaging thanks to the availability UHR-CT systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Prone position is a key component to treat hypoxemia in patients with severe acute respiratory distress syndrome. However, most studies evaluating it exclude patients with brain injuries without any medical evidence., Methods: This study includes a systematic review to determine whether brain-injured patients were excluded in studies evaluating prone position on acute respiratory distress syndrome; a prospective study including consecutive brain-injured patients needing prone position. The primary endpoint was the evaluation of cerebral blood flow using transcranial Doppler after prone positioning. Secondary outcomes were intracranial pressure, cerebral perfusion pressure, and tissue oxygen pressure., Results: From 8,183 citations retrieved, 120 studies were included in the systematic review. Among them, 90 studies excluded brain-injured patients (75%) without any justification, 16 included brain-injured patients (4 randomized, 7 nonrandomized studies, 5 retrospective), and 14 did not retrieve brain-injured data. Eleven patients were included in the authors' pilot study. No reduction of cerebral blood flow surrogates was observed during prone positioning, with diastolic speed values (mean ± SD) ranging from 37.7 ± 16.2 cm/s to 45.2 ± 19.3 cm/s for the right side (P = 0.897) and 39.6 ± 18.2 cm/s to 46.5 ± 21.3 cm/s for the left side (P = 0.569), and pulsatility index ranging from 1.14 ± 0.31 to 1.0 ± 0.32 for the right side (P = 0.145) and 1.14 ± 0.31 to 1.02 ± 0.2 for the left side (P = 0.564) before and during prone position., Conclusions: Brain-injured patients are largely excluded from studies evaluating prone position in acute respiratory distress syndrome. However, cerebral blood flow seems not to be altered considering increasing of mean arterial pressure during the session. Systematic exclusion of brain-injured patients appears to be unfounded, and prone position, while at risk in brain-injured patients, should be evaluated on these patients to review recommendations, considering close monitoring of neurologic and hemodynamic parameters., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Objective: Percutaneous balloon compression (PBC) is a popular treatment option for trigeminal neuralgia. However, the efficacy of PBC is widely considered to be associated with the occurrence of sensitive complications, although neither this correlation nor the underlying mechanisms have been established. The objectives of the present study were to identify factors predicting time to pain recurrence after PBC and identify factors predicting a severe sensitive complication., Methods: The authors conducted a retrospective study on patients who underwent PBC for the first time between 1985 and 2019 in two French hospitals. Data were retrieved from patients' medical records. Potential clinical and radiological predictors for time to pain recurrence and severe sensitive complication were evaluated using a Cox model and a logistic regression, respectively., Results: A total of 131 patients were included in the study, with a median follow-up of 3.0 years. Pain recurrence occurred in 77 patients, and the median time to pain recurrence was 2.0 years. In the multivariate analysis, six independent factors predicting pain recurrence were identified: 1) longer duration of presurgical symptoms; 2) localization of the pain along the mandibular branch of the trigeminal nerve (V3); 3) atypical pain; 4) diagnosis of multiple sclerosis; 5) use of a medical device not specifically adapted for trigeminal neuralgia surgery; and 6) duration of balloon compression > 60 seconds. Regarding the secondary objective, 26 patients presented a severe sensitive complication after PBC, which the authors defined as the development of a new sensitivity disorder of the cornea, deafferentation pain known as anesthesia dolorosa, and/or long-lasting hypoesthesia augmentation characterized by the new appearance or increase in size or intensity of an area of hypoesthesia in the face for at least 3 months. The only predictor associated with a severe sensitive complication in the multivariate analysis was compression duration > 60 seconds., Conclusions: These results show that the risk of postoperative complications can be assessed at the patient level, the most important modifiable parameter being the time of compression by the balloon. Although this study shows the relevance of a personalized medicine approach, its clinical application remains to be validated.

Background: Different methodological choices such as inclusion/exclusion criteria and analytical models can yield different results and inferences when meta-analyses are performed. We explored the range of such differences, using several methodological choices for indirect comparison meta-analyses to compare nalmefene and naltrexone in the reduction of alcohol consumption as a case study., Methods: All double-blind randomized controlled trials (RCTs) comparing nalmefene to naltrexone or one of these compounds to a placebo in the treatment of alcohol dependence or alcohol use disorders were considered. Two reviewers searched for published and unpublished studies in MEDLINE (August 2017), the Cochrane Library, Embase, and ClinicalTrials.gov and contacted pharmaceutical companies, the European Medicines Agency, and the Food and Drug Administration. The indirect comparison meta-analyses were performed according to different inclusion/exclusion criteria (based on medical condition, abstinence of patients before inclusion, gender, somatic and psychiatric comorbidity, psychological support, treatment administered and dose, treatment duration, outcome reported, publication status, and risk of bias) and different analytical models (fixed and random effects). The primary outcome was the vibration of effects (VoE), i.e. the range of different results of the indirect comparison between nalmefene and naltrexone. The presence of a "Janus effect" was investigated, i.e. whether the 1st and 99th percentiles in the distribution of effect sizes were in opposite directions., Results: Nine nalmefene and 51 naltrexone RCTs were included. No study provided a direct comparison between the drugs. We performed 9216 meta-analyses for the indirect comparison with a median of 16 RCTs (interquartile range = 12-21) included in each meta-analysis. The standardized effect size was negative at the 1st percentile (- 0.29, favouring nalmefene) and positive at the 99th percentile (0.29, favouring naltrexone). A total of 7.1% (425/5961) of the meta-analyses with a negative effect size and 18.9% (616/3255) of those with a positive effect size were statistically significant (p < 0.05)., Conclusions: The choice of inclusion/exclusion criteria and analytical models for meta-analysis can result in entirely opposite results. VoE evaluations could be performed when overlapping meta-analyses on the same topic yield contradictory result., Trial Registration: This study was registered on October 19, 2016, in the Open Science Framework (OSF, protocol available at https://osf.io/7bq4y/ ).

Purpose: Limited pelvic nodal relapse of prostatic cancer is a paramount challenge for locoregional salvage treatments. Salvage whole pelvis radiation therapy as considered in the BLINDED trial is an attractive option, but there are concerns about its toxicity. This article describes early toxicity with the technique., Methods and Materials: BLINDED was a prospective multicenter phase 2 trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron emission tomography-positive pelvic lymph nodes, combined with 6-month androgen blockade. The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathologic pelvic lymph nodes. Early toxicity was defined as toxicity until 1 year after radiation therapy. Patients quality of life was assessed using the European Organisation for Research and Treatment of Cancer questionnaires (QLQ-C30 and QLQ-PR25)., Results: Seventy-four patients were recruited in 15 French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included 67 patients. Half had received prior prostatic irradiation. Median age was 67.7 ± 6.5 years. Grade 2 acute urinary toxicity was observed in 9 of 67 patients (13.4%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Three patients (4.4%) had grade 3 urinary toxicity. Grade 2 acute digestive toxicity was observed in 10 of 67 patients (14.9%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Patients with prior prostate bed irradiation did not exhibit increased urinary or digestive toxicity. The European Organisation for Research and Treatment of Cancer questionnaire scores at 1 year did not worsen significantly., Conclusions: The acute and 1-year toxicity of the BLINDED protocol was satisfactory, even in patients with a history of prostatic irradiation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: To establish the maximum tolerated dose of abiraterone acetate plus prednisone (AA) combined with salvage radiotherapy (SRT) and goserelin in a phase 1 study in men with rising PSA following radical prostatectomy., Methods: AA was given during one month before SRT at 1000 mg PO once daily, then 750 mg (Dose Level 1, DL1) or 1000 mg (DL2) during 5 months combined with 6-months goserelin by injection on the first day of irradiation (scheme NEO) or one month before starting SRT (scheme CONCO)., Results: In scheme NEO at DL1, 2/9 patients did not achieve castration levels of testosterone. 4/9 patients (44%) presented with grade 3 liver enzyme elevation. In scheme CONCO testosterone dropped to undetectable levels. At DL1, 6 patients were recruited, with no dose limiting toxicities. At DL2, 2/3 patients presented with grade 3 liver enzyme elevation occurring during SRT., Conclusions: When AA was administered without goserilin, only 78% achieved castration levels. AA combined with SRT and goserilin did not increase pelvic toxicity, but lead to an unsuspected high frequency of grade 3 liver toxicity. The phase II recommended dose of AA combined to goserelin and SRT is 750 mg., Competing Interests: CONFLICTS OF INTEREST This study was funded by Janssen.

Background: Palbociclib, a CDK4-6 inhibitor, combined with endocrine therapy (ET) is a new standard of treatment for Hormone Receptor-positive Metastatic Breast Cancer. We present the first real-life efficacy and tolerance data of palbociclib plus fulvestrant in this population., Methods: From November 2015 to November 2016, patients receiving in our institution palbociclib + fulvestrant according to the Temporary Authorization for Use were prospectively analyzed., Results: 60 patients were treated accordingly; median age was 61 years; 50 patients (83.3%) had visceral metastasis, and 10 (16.7%) had bone-only disease. Patients had previously received a median of 5 (1-14) lines of treatment, including ET (median 3) and chemotherapy (median 2); 28 (46.7%) received previously fulvestrant and all everolimus. With a median follow-up of 10.3 months, median progression-free survival (mPFS) was 5.8 months (95% CI 3.9-7.3). Patients pretreated with fulvestrant had a similar PFS of 6.4 months (HR 1.00; 95% CI 0.55-1.83; P = 1.00). The most common AEs (adverse events) were neutropenia (93%), anemia (65%), and thrombocytopenia (55%)., Conclusion: In this heavily pretreated population including everolimus, fulvestrant plus palbociclib provides an mPFS of 5.8 months with the same magnitude of benefit for fulvestrant-pretreated patients.

Background and Aims: Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication., Design: Systematic review with direct and network meta-analysis of double-blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non-abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data., Setting: Thirty-two RCTs., Participants: A total of 6036 patients., Measurements: The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes., Findings: No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10; I 2  = 0%], baclofen (SMD = -1.00, 95% CI = -1.80, -0.19; one study) and topiramate (SMD = -0.77, 95% CI = -1.12, -0.42; I 2  = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor., Conclusions: There is currently no high-grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes., (© 2017 Society for the Study of Addiction.)

There is a long-standing and very active debate regarding which psychotherapeutic intervention should be used in depressive disorders. However, the effects of psychotherapies may result majorly from non-specific factors rather than from specific factors related to the type of psychotherapeutic intervention. We performed a systematic review and meta-analysis on aggregated data to understand how the effects of different psychotherapies are impacted by non-specific factors. We included randomized controlled trials that assessed the efficacy of psychotherapeutic interventions in the treatment of adult depressive disorders. The primary outcome was the change in depression score from baseline to the latest follow-up visit (i.e. response). A meta-regression was performed to predict response according to the type of intervention and non-specific factors (e.g. number of treatment sessions, length of follow-up, therapeutic allegiance of the investigator). The main analysis included 214 study arms from 84 trials. The effects of psychotherapies compared to the waiting list control condition failed to remain significant after adjusting for non-specific factors. Response increased with the number of treatment sessions (β = 0.03, 95% CI [0.01; 0.04]) and the length of follow-up (β = 0.01, 95% CI [0.00; 0.02]). Response also improved in case of presumed therapeutic allegiances among investigators (β = 0.29, 95% CI [0.07; 0.52]). Response to psychotherapies seems to be closely related to non-specific effects. The development of a well-designed trial that controls for non-specific factors might help disentangle the effects of psychotherapies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nalmefene was the first treatment approved by the European Medicines Agency for reducing alcohol consumption in adult patients with alcohol dependence. It is often presented as a paradigm shift in therapeutics, but major issues limit the interpretation of the evidence supporting its use. The randomised trials submitted provided no evidence of harm reduction, the differences on consumption outcomes were of questionable clinical relevance, the target population was defined a posteriori and the drug was compared to a placebo although naltrexone was already used off-label. No post-approval randomised study is currently designed to clearly address these issues. In addition, nalmefene trials have been uncritically cited, even in guidelines. This experience reveals weaknesses in drug evaluations in alcohol dependence, which call for changes. We propose to dispense with alcohol consumption as a surrogate outcome, to consider comparative effectiveness issues, and to recommend randomised post-approval studies in case of controversial approval.

Background: Pulmonary artery catheters (PACs) are frequently used for monitoring patient temperatures in the intensive care unit. Nevertheless, data regarding the accuracy of these measurements are lacking, and few data testify to the accuracy of temperatures recorded after the PAC has been in place for several days. The absolute values of such measurements are relevant for critical care because patient temperatures are often used as diagnostic criteria for sepsis and antibiotic therapy. We thus hypothesized that the Edwards Lifesciences PAC would accurately measure blood temperature. To test our hypothesis, we compared temperature measurements obtained from PACs inserted in patients for different lengths of time with measurements of a reference platinum resistance thermometer (PRT)., Methods: PACs were removed and analyzed in 39 patients in whom PACs were inserted for 0 to 5 days. The PACs were placed in calibration baths, and 10 consecutive measurements at each of 7 different temperatures were obtained (36°C, 36.5°C, 37°C, 38°C, 38.3°C, 39°C, and 40°C). The temperature measurements obtained using PACs were compared with measurements obtained using a PRT. Bland-Altman statistical analyses were performed. Outliers, defined as PAC temperature measurements that varied more than ±0.3°C from PRT measurements, were identified. We considered a catheter unfit for clinical diagnostic or therapeutic use if ≥15% of data pairs were outliers., Results: A total of 2730 data pairs were analyzed. Overall, the bias was -0.15°C; the precision was +0.13°C; and the limits of agreement were -0.45°C to +0.13°C. The bias and limits of agreement did not differ according to the age of the catheter or the temperature tested. One hundred fourteen data pairs (4.2% [95% confidence interval, 2.0%-6.4%]), involving 13 PACs and mostly from 4 PACs, were outliers., Conclusions: We conclude that temperature measurements obtained using the Edwards Lifesciences PACs are thus sufficiently accurate to be used for clinical temperature monitoring in critically ill patients.

Background: Nalmefene is a recent option in alcohol dependence treatment. Its approval was controversial. We conducted a systematic review and meta-analysis of the aggregated data (registered as PROSPERO 2014:CRD42014014853) to compare the harm/benefit of nalmefene versus placebo or active comparator in this indication., Methods and Findings: Three reviewers searched for published and unpublished studies in Medline, the Cochrane Library, Embase, ClinicalTrials.gov, Current Controlled Trials, and bibliographies and by mailing pharmaceutical companies, the European Medicines Agency (EMA), and the US Food and Drug Administration. Double-blind randomized clinical trials evaluating nalmefene to treat adult alcohol dependence, irrespective of the comparator, were included if they reported (1) health outcomes (mortality, accidents/injuries, quality of life, somatic complications), (2) alcohol consumption outcomes, (3) biological outcomes, or (4) treatment safety outcomes, at 6 mo and/or 1 y. Three authors independently screened the titles and abstracts of the trials identified. Relevant trials were evaluated in full text. The reviewers independently assessed the included trials for methodological quality using the Cochrane Collaboration tool for assessing risk of bias. On the basis of the I2 index or the Cochrane's Q test, fixed or random effect models were used to estimate risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% CIs. In sensitivity analyses, outcomes for participants who were lost to follow-up were included using baseline observation carried forward (BOCF); for binary measures, patients lost to follow-up were considered equal to failures (i.e., non-assessed patients were recorded as not having responded in both groups). Five randomized controlled trials (RCTs) versus placebo, with a total of 2,567 randomized participants, were included in the main analysis. None of these studies was performed in the specific population defined by the EMA approval of nalmefene, i.e., adults with alcohol dependence who consume more than 60 g of alcohol per day (for men) or more than 40 g per day (for women). No RCT compared nalmefene with another medication. Mortality at 6 mo (RR = 0.39, 95% CI [0.08; 2.01]) and 1 y (RR = 0.98, 95% CI [0.04; 23.95]) and quality of life at 6 mo (SF-36 physical component summary score: MD = 0.85, 95% CI [-0.32; 2.01]; SF-36 mental component summary score: MD = 1.01, 95% CI [-1.33; 3.34]) were not different across groups. Other health outcomes were not reported. Differences were encountered for alcohol consumption outcomes such as monthly number of heavy drinking days at 6 mo (MD = -1.65, 95% CI [-2.41; -0.89]) and at 1 y (MD = -1.60, 95% CI [-2.85; -0.35]) and total alcohol consumption at 6 mo (SMD = -0.20, 95% CI [-0.30; -0.10]). An attrition bias could not be excluded, with more withdrawals for nalmefene than for placebo, including more withdrawals for safety reasons at both 6 mo (RR = 3.65, 95% CI [2.02; 6.63]) and 1 y (RR = 7.01, 95% CI [1.72; 28.63]). Sensitivity analyses showed no differences for alcohol consumption outcomes between nalmefene and placebo, but the weight of these results should not be overestimated, as the BOCF approach to managing withdrawals was used., Conclusions: The value of nalmefene for treatment of alcohol addiction is not established. At best, nalmefene has limited efficacy in reducing alcohol consumption.

There is a long-standing polemic concerning the usefulness of antidepressants in the treatment of major depressive disorder. In this paper, we propose to highlight some aspects of this controversy by exploring the mutual influence of psychopharmacology and trial methodologies. Indeed, antidepressant efficacy, if not proved, was accepted before antidepressant randomised controlled trials (RCTs) were run. While RCTs became a gold standard to meet the requirements of the regulatory bodies, methodological tools were required to measure outcomes and to test whether antidepressants provide statistically significant benefits as compared with a placebo. All these methodological options have nonetheless introduced fuzziness in our interpretation of study results, in terms of clinical meaningfulness and in terms of transposability to a real life settings. Additionally, selective publication raises concerns about the published literature, and results in many paradoxes. Instead of providing easy answers, the application of the RCT paradigm in MDD raises numerous questions. This is probably in the nature of all scientific studies, but it can be in contradiction with clinicians' expectations, who want to be sure that the treatment will (or will not) work for their individual patients., (© 2015 Société Française de Pharmacologie et de Thérapeutique.)

Aim: Breast-conserving surgery with radiation therapy is the primary treatment for ductal carcinoma in situ (DCIS). Re-excision is indicated when clear resection margins have not been achieved, although in some cases the procedure may be unnecessary as there is no residual tumor. The purpose of our three-Center retrospective study was to identify predictors of positive re-excision findings following breast-conserving surgery for DCIS., Patients and Methods: A total of 285 patients underwent re-excision following conservative treatment for DCIS between 01/01/08 and 12/31/13 at three breast-cancer referral Centers. We conducted a retrospective, comparative review of the factors that differentiated patients with a residual tumor from those without. The study was based on clinical, radiological, surgical and pathological criteria., Results: A total of 180 patients (63%) had residual tumor after conservative treatment. Six factors were predictive on univariate analysis: young age (p=0.025), non-menopausal status (p=0.016), absence of preoperative biopsy (p=0.0029), high nuclear grade (p=0.0181), lesion size >30 mm (p=0.032), and positive surgical margins (p=0.0016). Four factors remained independently predictive on multivariate analysis: non-menopausal status (p=0.0017), high nuclear grade (p=0.0031), lesion size >30 mm (p=0.012) and positive surgical margins (p=0.0013). We calculated a 93% probability of positive re-excision findings if all four factors were combined. On the other hand, if none of the factors were present, the rate fell to 18%., Conclusion: In cases of DCIS, where risk factors for both involved lumpectomy margins and recurrence are carefully studied, knowledge of the risk factors for residual tumor can help guide therapeutic choices., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)