Feasibility of Prone Positioning for Brain-injured Patients with Severe Acute Respiratory Distress Syndrome: A Systematic Review and Pilot Study (ProBrain).

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.

Local budesonide therapy in the management of persistent hyposmia in suspected non-severe COVID-19 patients: Results of a randomized controlled trial.

OBJECTIVES: Consequences of COVID-19 on olfactory functions remained unclear during the pandemic. We assessed the efficacy of local budesonide in addition to olfactory rehabilitation when managing non-severe COVID-19 patients with persistent hyposmia. METHODS: A multicentric, randomized, superiority trial was conducted (ClinicalTrials.gov NCT04361474). The experimental group (EG) received budesonide and physiological saline nasal irrigations administered via three syringes of 20 ml in each nasal cavity in the morning and evening for 30 days. The control group (CG) received a similar protocol without budesonide. Patients were included if they were >18 years old, with a SARS-CoV-2 infection and presenting an isolated hyposmia persisting 30 days after symptom onset. The primary endpoint was the percentage of patients with improvement of more than two points on the ODORATEST score after 30 days of treatment. RESULTS: In total, 123 patients were included and randomized (EG: 62 vs CG: 61). Two patients from the EG met the primary endpoint with no statistical difference between the two groups (P = 0.5). CONCLUSION: To our knowledge, this is the first study evaluating local budesonide for COVID-19 related hyposmia treatment even though previous trials were performed with other local corticosteroids. Local budesonide efficacy was not demonstrated for persistent hyposmia related to COVID-19.

Attachment patterns, self-compassion, and coping strategies in patients with chronic pain.

Introduction: In the recent year's literature, attachment insecurity is described as a vulnerability factor among patients with chronic pain, associated with poor pain coping, anxiety, depression, catastrophizing, greater pain intensity, and disability. Self-compassion, on the other hand, is described as a protective factor, associated with lower levels of negative affect, catastrophizing, depression, and anxiety in patients with chronic pain. Methods: In this study, we aim to explore the association between attachment, self-compassion quality, and coping strategies, in patients with chronic pain. Thus, 134 eligible patients with chronic pain were recruited at the certified Evaluation and Treatment Pain Center of the A. de Rothschild Foundation in Paris. We used a sociodemographic questionnaire, the Relationship Scale Questionnaire (RSQ-RC), the Self-Compassion Scale, and the Brief COPE. Results: Results supported our principal hypothesis; securely attached participants reported a significantly higher global self-compassion score compared with insecurely attached ones. Secure attachment and higher self-compassion levels were positively correlated with functional coping strategies and negatively correlated with dysfunctional ones. Discussion: Attachment patterns may be the basis of someone's ability to be compassionate to himself and to cope adequately with a difficult situation, such as a chronic pain condition. An attachment-informed approach to pain management could offer a better understanding of the complexity of this clinical condition and potentially provide appropriate support for both patients and health professionals, aiming to improve the effectiveness of interventions.

Prophylactic levosimendan in patients with low ejection fraction undergoing coronary artery bypass grafting: A pooled analysis of two multicentre randomised controlled trials.

OBJECTIVES: To assess the effect of preoperative levosimendan on mortality at day 90 in patients with left ventricular ejection fraction (LVEF) ≤ 40%, and to investigate a possible differential effect between patients undergoing isolated coronary artery bypass grafting (CABG) versus CABG combined with valve replacement surgery. DESIGN: Pooled analysis of two multicentre randomised controlled trials (RCT) investigating prophylactic levosimendan versus placebo prior to CABG surgery on mortality at day 90 in patients with LVEF ≤ 40%. A meta-analysis of all RCT investigating the same issue was also conducted. RESULTS: A cohort of 1084 patients (809 isolated CABG, and 275 combined surgery) resulted from the merging of LEVO-CTS and LICORN databases. Seventy-two patients were dead at day 90. The mortality at day 90 was not different between levosimendan and placebo (Hazard Ratio (HR): 0.73, 95% CI: 0.41-1.28, p = 0.27). However, there was a significant interaction between the type of surgery and the study drug (p = 0.004). We observed a decrease in mortality at day 90 in the isolated CABG subgroup (HR: 0.39, 95% CI: 0.19-0.82, p = 0.013), but not in the combined surgery subgroup (HR: 1.73, 95% CI: 0.77-3.92, p = 0.19). The meta-analysis of 6 RCT involving 1441 patients confirmed the differential effect on mortality at day 30 between the 2 subgroups. CONCLUSIONS: Preoperative levosimendan did not reduce mortality in a mixed surgical population with LV dysfunction. However, the subgroup of patients undergoing isolated CABG had a reduction in mortality at day 90, whereas there was no significant effect in combined surgery patients. This finding requires confirmation with a specific prospective trial.

Evaluation of a uniplanar pupil expansion ring in small-pupil cataract surgery: a feasibility study.

PURPOSE: The aim of this study was to evaluate the effectiveness of a disposable uniplanar pupil expansion device in small-pupil cataract surgery. METHODS: This is a feasibility study carried out at the Rothschild Foundation, Paris, France. Patients undergoing routine cataract surgery with a dilated pupil size < 6 mm, and who agreed to participate in the study were included. The trial enrolled 25 patients, of whom 21 proceeded to cataract surgery using the pupil expansion device to be evaluated. The pupil diameter was measured at defined stages during the cataract surgery, which was performed by a single surgeon, in a single center setting. The 1st generation Bhattacharjee pupil expansion ring was used if the preoperative pupil size was < 6 mm. Intraoperative and postoperative adverse events were recorded. RESULTS: Pupil size immediately after the Bhattacharjee ring implantation was ≥ 6 mm for 15 eyes (71.4%). The mean dilated pupil size before ring insertion was 4.5 ± 0.8 mm (range 2.5-5.8 mm), and the mean pupil size after ring insertion was 6.1 ± 0.3 mm (range 5.9-6.8 mm). Mean pupil size following removal of the ring was 4.2 ± 0.8 mm (range 2.5-5.4 mm). Two adverse events occurred during the surgeries: 1 Bhattacharjee ring broke prior to implantation, and 1 implanted Bhattacharjee ring was unstable and removed before the end of the surgery. No postoperative adverse event was recorded. CONCLUSIONS: The Bhattacharjee ring is an effective pupil expansion device, which facilitates stable pupil expansion during cataract surgery. This study was registered as a clinical trial at clinicaltrials.gov under the number NCT02434588.

Daily Telephone Call During the COVID-19 Pandemic: Perceptions of Families and Providers.

BACKGROUND: In intensive care units (ICUs), the quality of communication with families is a key point in the caregiver-patient-family relationship. During the COVID-19 pandemic, hospital visits were prohibited, and many ICUs implemented a daily telephone call strategy to ensure continuity of communication with patients' families. OBJECTIVE: To assess how family members and health care providers perceived this communication strategy. METHODS: The study was conducted in a 45-bed ICU during the COVID-19 pandemic. Communication with families consisted of a single daily telephone call from the senior physician in charge of the patient to the patient's surrogate decision maker. Satisfaction was qualitatively assessed via an anonymous online questionnaire with open-ended questions. RESULTS: Participants completed 114 questionnaires. Forty-six percent of surrogate decision makers stated that the key medical messages were understandable, but 57% of other family members expressed that the frequency of information delivery was insufficient. Fifty-six percent of the physicians described the practice as functional for the organization of the unit. Among health care providers other than physicians, 55% felt that not having to interact with families decreased their emotional load and 50% mentioned saving time and the absence of task interruptions as positive aspects. CONCLUSION: Fixed-time, daily telephone calls in the ICU allowed satisfactory transmission of information between physicians and surrogate decision makers, as perceived by both parties. However, the telephone-based communication strategy could still be improved.

Vascular origin in acute transient visual disturbance: A prospective study.

BACKGROUND AND PURPOSE: This study was undertaken to validate a clinical score of vascular origin in patients with acute transient visual disturbances (TVDs) without diplopia. METHODS: We conducted a prospective study in an ophthalmology emergency department and a transient ischemic attack (TIA) clinic. Patients underwent clinical evaluation including a tailored questionnaire, brain, vascular, and ophthalmologic investigations, and 3-month follow-up. TVDs were classified according to vascular or nonvascular origin by three independent experts based on all clinical, cerebrovascular, and ophthalmologic investigations, but blind to the questionnaire results. A clinical score was derived based on clinical variables independently associated with a vascular origin, and was externally validated in an independent cohort. RESULTS: An ischemic origin of TVD was found in 45% (67/149) of patients in the derivation cohort. Age and six questions were independently associated with an ischemic origin. A nine-point score (≥70 years old = 2; monocular visual loss = 2; black or white vision = 1; single episode = 1; lack of headache = 2; diffuse, constricted, altitudinal, or lateralized visual loss pattern on drawings = 1) showed good discriminative power in identifying ischemic origin (c-statistic = 0.82) and was replicated in the validation cohort (n = 130, 25% of ischemic origin, c-statistic = 0.75). With a score ≥ 4, sensitivity was 85% (95% confidence interval = 68-95) and specificity was 52% (95% confidence interval = 41-62). In both cohorts, ophthalmologic evaluation found a vascular cause in 4% and was noncontributive in 85%. After 3 months, no patients had a stroke, TIA, or retinal infarct. CONCLUSIONS: Our score may assist in predicting a vascular origin of TVD. Ophthalmologic evaluation, when not readily available, should not delay the neurovascular evaluation.

Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial.

BACKGROUND: High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target. METHODS: We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100-129 mm Hg) or a standard care systolic blood pressure target group (130-185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24-36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites. FINDINGS: Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24-36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60-1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group. INTERPRETATION: An intensive systolic blood pressure target of 100-129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24-36 h as compared with a standard care systolic blood pressure target of 130-185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion. FUNDING: French Health Ministry.

Automated weaning from mechanical ventilation: Results of a Bayesian network meta-analysis.

PURPOSE: Mechanical ventilation (MV) weaning is a crucial step. Automated weaning modes reduce MV duration but the question of the best automated mode remains unanswered. Our objective was to compare the major automated modes for MV weaning in critically ill and post-operative adult patients. MATERIAL AND METHODS: We conducted a network Bayesian meta-analysis to compare different automated modes. We searched MEDLINE, EMBASE and Cochrane central registry for randomized control trials comparing automated weaning modes either to another automated mode or to standard-of-care. The primary outcome was the duration of MV weaning extracted from the original trials. RESULTS: 663 articles were screened and 26 trials (2097patients) were included in the final analysis. All automated modes included in the study (ASV°, Intellivent ASV, Smartcare, Automode°, PAV° and MRV°) outperformed standard-of-care but no automated mode reduced the duration of mechanical ventilation weaning as compared to others in the network meta-analysis. CONCLUSION: Compared to standard weaning practice, all automated modes significantly reduced the duration of MV weaning in critically ill and post-operative adult patients. When cross-compared using a network meta-analysis, no specific mode was different in reducing the duration of MV weaning. The study was registered in PROSPERO (CRD42015024742).

Blood Pressure Target in Acute Stroke to Reduce HemorrhaGe After Endovascular Therapy: The Randomized BP TARGET Study Protocol.

Background: High systolic blood pressure (BP) is associated with an increased risk of intracranial hemorrhage (ICH) in patients undergoing reperfusion therapy. However, there are no data from randomized trials to guide BP management after reperfusion following endovascular therapy (EVT) for patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO). The objective is to evaluate if BP control with a target of 100-129 mmHg systolic BP ("tight" SBP control) can reduce ICH as compared to 130-185 mmHg ("usual" SBP control) in AIS participants after reperfusion by EVT. Methods: The BP TARGET trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial. AIS participants with LVO experiencing successful reperfusion are randomly assigned, in a 1:1 ratio, to have a "tight" SBP control (100-129 mmHg) or a conservative SBP control (130-185 mmHg) during the following 24-36 h. The primary outcome is the rate of ICH (either symptomatic or asymptomatic) on follow-up CT scan at 24-36 h. Secondary outcomes include the rate of the symptomatic ICH, the overall distribution of the modified Rankin Scale (mRS) at 90 days, favorable outcome (90-day mRs 0-2), infarct volume at follow-up CT scan at 24-36 h, change in National Institute of Health Stroke Scale at 24 h, and all-cause mortality at 90 days. Conclusion: This is the first randomized trial directly comparing the efficacy of different SBP targets after EVT reperfusion. This prospective trial aims to determine whether a "tight" SBP control after EVT reperfusion can reduce the risk of ICH.

Correction to: Three randomized controlled trials evaluating the impact of "spin" in health news stories reporting studies of pharmacologic treatments on patients'/caregivers' interpretation of treatment benefit.

Figure 3 in the original article [1] is incorrect; labels for secondary outcomes have been shifted and do not correspond to the numbers reported in the table (Additional file 8). The corrected version can be seen ahead. This figure should be used over the figure 3 seen in the original article. This error does not affect the results, interpretation, or conclusion.

Three randomized controlled trials evaluating the impact of "spin" in health news stories reporting studies of pharmacologic treatments on patients'/caregivers' interpretation of treatment benefit.

BACKGROUND: News stories represent an important source of information. We aimed to evaluate the impact of "spin" (i.e., misrepresentation of study results) in health news stories reporting studies of pharmacologic treatments on patients'/caregivers' interpretation of treatment benefit. METHODS: We conducted three two-arm, parallel-group, Internet-based randomized trials (RCTs) comparing the interpretation of news stories reported with or without spin. Each RCT considered news stories reporting a different type of study: (1) pre-clinical study, (2) phase I/II non-RCT, and (3) phase III/IV RCT. For each type of study, we identified news stories reported with spin that had earned mention in the press. Two versions of the news stories were used: the version with spin and a version rewritten without spin. Participants were patients/caregivers involved in Inspire, a large online community of more than one million patients/caregivers. The primary outcome was participants' interpretation assessed by one specific question "What do you think is the probability that 'treatment X' would be beneficial to patients?" (scale, 0 [very unlikely] to 10 [very likely]). RESULTS: For each RCT, 300 participants were randomly assigned to assess a news story with spin (n = 150) or without spin (n = 150), and 900 participants assessed a news story. Participants were more likely to consider that the treatment would be beneficial to patients when the news story was reported with spin. The mean (SD) score for the primary outcome for abstracts reported with and without spin for pre-clinical studies was 7.5 (2.2) versus 5.8 (2.8) (mean difference [95% CI] 1.7 [1.0-2.3], p < 0.001); for phase I/II non-randomized trials, 7.6 (2.2) versus 5.8 (2.7) (mean difference 1.8 [1.0-2.5], p < 0.001); and for phase III/IV RCTs, 7.2 (2.3) versus 4.9 (2.8) (mean difference 2.3 [1.4-3.2], p < 0.001). CONCLUSIONS: Spin in health news stories reporting studies of pharmacologic treatments affects patients'/caregivers' interpretation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03094078 , NCT03094104 , NCT03095586.

Node-making process in network meta-analysis of nonpharmacological treatment are poorly reported.

OBJECTIVE: To identify methods to support the node-making process in network meta-analyses (NMAs) of nonpharmacological treatments. STUDY DESIGN AND SETTING: We proceeded in two stages. First, we conducted a literature review of guidelines and methodological articles about NMAs to identify methods proposed to lump interventions into nodes. Second, we conducted a systematic review of NMAs of nonpharmacological treatments to extract methods used by authors to support their node-making process. MEDLINE and Google Scholar were searched to identify articles assessing NMA guidelines or methodology intended for NMA authors. MEDLINE, CENTRAL, and EMBASE were searched to identify reports of NMAs including at least one nonpharmacological treatment. Both searches involved articles available from database inception to March 2016. From the methodological review, we identified and extracted methods proposed to lump interventions into nodes. From the systematic review, the reporting of the network was assessed as long as the method described supported the node-making process. RESULTS: Among the 116 articles retrieved in the literature review, 12 (10%) discussed the concept of lumping or splitting interventions in NMAs. No consensual method was identified during the methodological review, and expert consensus was the only method proposed to support the node-making process. Among 5187 references for the systematic review, we included 110 reports of NMAs published between 2007 and 2016. The nodes were described in the introduction section of 88 reports (80%), which suggested that the node content might have been a priori decided before the systematic review. Nine reports (8.1%) described a specific process or justification to build nodes for the network. Two methods were identified: (1) fit a previously published classification and (2) expert consensus. CONCLUSION: Despite the importance of NMA in the delivery of evidence when several interventions are available for a single indication, recommendations on the reporting of the node-making process in NMAs are lacking, and reporting of the node-making process in NMAs seems insufficient.

Interpretation of health news items reported with or without spin: protocol for a prospective meta-analysis of 16 randomised controlled trials.

INTRODUCTION: We aim to compare the interpretation of health news items reported with or without spin. 'Spin' is defined as a misrepresentation of study results, regardless of motive (intentionally or unintentionally) that overemphasises the beneficial effects of the intervention and overstates safety compared with that shown by the results. METHODS AND ANALYSIS: We have planned a series of 16 randomised controlled trials (RCTs) to perform a prospective meta-analysis. We will select a sample of health news items reporting the results of four types of study designs, evaluating the effect of pharmacological treatment and containing the highest amount of spin in the headline and text. News items reporting four types of studies will be included: (1) preclinical studies; (2) phase I/II (non-randomised) trials; (3) RCTs and (4) observational studies. We will rewrite the selected news items and remove the spin. The original news and rewritten news will be appraised by four types of populations: (1) French-speaking patients; (2) French-speaking general public; (3) English-speaking patients and (4) English-speaking general public. Each RCT will explore the interpretation of news items reporting one of the four study designs by each type of population and will include a sample size of 300 participants. The primary outcome will be participants' interpretation of the benefit of treatment after reading the news items: (What do you think is the probability that treatment X would be beneficial to patients? (scale, 0 (very unlikely) to 10 (very likely)).This study will evaluate the impact of spin on the interpretation of health news reporting results of studies by patients and the general public. ETHICS AND DISSEMINATION: This study has obtained ethics approval from the Institutional Review Board of the Institut national de la santé et de la recherche médicale (INSERM) (registration no: IRB00003888). The description of all the steps and the results of this prospective meta-analysis will be available online and will be disseminated as a published article. On the completion of this study, the results will be sent to all participants. PROSPERO REGISTRATION NUMBER: CRD42017058941.

Comparative efficacy and safety of second-line treatments for advanced non-small cell lung cancer with wild-type or unknown status for epidermal growth factor receptor: a systematic review and network meta-analysis.

BACKGROUND: Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis. METHODS: MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the US Food and Drug Administration website, as well as other sources, were searched for available reports up to June 6, 2017. Two reviewers independently selected published and unpublished reports of RCTs comparing any second-line treatments, extracted data and assessed the risk of bias of all included trials. We performed a Bayesian network meta-analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response (ObR), the number of serious adverse events, and quality of life. RESULTS: We included 102 RCTs involving 36,058 patients (62% male, median age 61 years, 81% with stage IV cancer, 80% smokers, and 92% with performance status 0-1). We revealed a differential reporting of outcomes between efficacy and safety outcomes. Half of the trials reported safety outcomes and less than 20% quality of life. For OS, nivolumab was more effective than docetaxel (hazard ratio (HR) 0.69, 95% credible interval (CrI) 0.56-0.83), pemetrexed (0.67, 0.52-0.83), erlotinib (0.68, 0.53-0.86), and gefitinib (0.66, 0.53-0.83). Pembrolizumab, atezolizumab, and pemetrexed plus erlotinib were also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib. For PFS, erlotinib plus cabozantinib was more effective than docetaxel (HR 0.39, 95% CrI 0.18-0.84), pemetrexed (0.38, 0.18-0.82), erlotinib (0.37, 0.18-0.78), and gefitinib (0.38, 0.18-0.82). Cabozantinib and pemetrexed plus erlotinib were also significantly more effective than the four recommended treatments. For ObR, no treatment was significantly more effective. The effectiveness of the four recommended treatments was similar and they were ranked among the 25 less-effective treatments. For safety, evidence is insufficient to draw certain conclusions. CONCLUSIONS: Nivolumab, pembrolizumab, atezolizumab, and pemetrexed plus erlotinib may be the most effective second-line treatments for NSCLC in terms of OS. The four recommended treatments seem to have relatively poor performance. However, the impact on life expectancy of immunotherapy versus other treatments should be further explored by future analyses, and more trials comparing the novel treatments are needed to reduce uncertainty in these results. TRIAL REGISTRATION: Registration number: PROSPERO ( CRD42015017592 ).

Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review.

BACKGROUND: Fecal microbiota transplantation (FMT) could be a novel treatment option for several chronic diseases associated with altered gut microbiota. PURPOSE: To examine the conduct and reporting of studies assessing FMT. DATA SOURCES: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science from inception to 31 January 2017. STUDY SELECTION: Two reviewers independently examined titles and abstracts to identify all English-language reports of human clinical studies assessing the safety or efficacy of FMT. DATA EXTRACTION: Three reviewers independently assessed study types and characteristics and the reporting of important methodological components of the FMT intervention. DATA SYNTHESIS: Most (84%) of the 85 published reports found addressed the use of FMTs for Clostridium difficile infection or inflammatory bowel disease, and most (87%) were non-randomized controlled trials. Important methodological components that were not reported in published studies included the following: eligibility criteria for donors (47%), materials used for collecting stools and the period of collection (96%), methods used for conservation of stools (76%), the amount and type of stools used (for example, fresh or frozen), and duration of stool conservation (67%). Many (58%) did not report an analysis of microbiota composition. LIMITATIONS: Lack of universal consensus regarding the most important methodological components of FMT and inability to assess the actual conduct of studies and whether the publication process affected the completeness of reporting. CONCLUSION: Key components of FMT interventions, which are necessary to replicate and understand study findings about efficacy and safety, are poorly reported. PRIMARY FUNDING SOURCE: No specific funding.

Impact of searching clinical trial registries in systematic reviews of pharmaceutical treatments: methodological systematic review and reanalysis of meta-analyses.

Objective To evaluate the impact of searching clinical trial registries in systematic reviews.Design Methodological systematic review and reanalyses of meta-analyses.Data sources Medline was searched to identify systematic reviews of randomised controlled trials (RCTs) assessing pharmaceutical treatments published between June 2014 and January 2015. For all systematic reviews that did not report a trial registry search but reported the information to perform it, the World Health Organization International Trials Registry Platform (WHO ICTRP search portal) was searched for completed or terminated RCTs not originally included in the systematic review.Data extraction For each systematic review, two researchers independently extracted the outcomes analysed, the number of patients included, and the treatment effect estimated. For each RCT identified, two researchers independently determined whether the results were available (ie, posted, published, or available on the sponsor website) and extracted the data. When additional data were retrieved, we reanalysed meta-analyses and calculated the weight of the additional RCTs and the change in summary statistics by comparison with the original meta-analysis.Results Among 223 selected systematic reviews, 116 (52%) did not report a search of trial registries; 21 of these did not report the information to perform the search (key words, search date). A search was performed for 95 systematic reviews; for 54 (57%), no additional RCTs were found and for 41 (43%) 122 additional RCTs were identified. The search allowed for increasing the number of patients by more than 10% in 19 systematic reviews, 20% in 10, 30% in seven, and 50% in four. Moreover, 63 RCTs had results available; the results for 45 could be included in a meta-analysis. 14 systematic reviews including 45 RCTs were reanalysed. The weight of the additional RCTs in the recalculated meta-analyses ranged from 0% to 58% and was greater than 10% in five of 14 systematic reviews, 20% in three, and 50% in one. The change in summary statistics ranged from 0% to 29% and was greater than 10% for five of 14 systematic reviews and greater than 20% for two. However, none of the changes to summary effect estimates led to a qualitative change in the interpretation of the results once the new trials were added.Conclusions Trial registries are an important source for identifying additional RCTs. The additional number of RCTs and patients included if a search were performed varied across systematic reviews.

Comparison of central adjudication of outcomes and onsite outcome assessment on treatment effect estimates.

BACKGROUND: Assessment of events by adjudication committees (ACs) is recommended in multicentre randomised controlled trials (RCTs). However, its usefulness has been questioned. OBJECTIVES: The aim of this systematic review was to compare 1) treatment effect estimates of subjective clinical events assessed by onsite assessors versus by AC, and 2) treatment effect estimates according to the blinding status of the onsite assessor as well as the process used to select events to adjudicate. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, PsycINFO, CINAHL and Google Scholar (25 August 2015 as the last updated search date), using a combination of terms to retrieve RCTs with commonly used terms to describe ACs. SELECTION CRITERIA: We included all reports of RCTs and the published RCTs included in reviews and meta-analyses that reported the same subjective outcome event assessed by both an onsite assessor and an AC. DATA COLLECTION AND ANALYSIS: We extracted the odds ratio (OR) from onsite assessment and the corresponding OR from AC assessment and calculated the ratio of the odds ratios (ROR). A ratio of odds ratios < 1 indicated that onsite assessors generated larger effect estimates in favour of the experimental treatment than ACs. MAIN RESULTS: Data from 47 RCTs (275,078 patients) were used in the meta-analysis. We excluded 11 RCTs because of incomplete outcome data to calculate the OR for onsite and AC assessments. On average, there was no difference in treatment effect estimates from onsite assessors and AC (combined ROR: 1.00, 95% confidence interval (CI) 0.97 to 1.04; I(2) = 0%, 47 RCTs). The combined ROR was 1.00 (95% CI 0.96 to 1.04; I(2) = 0%, 35 RCTs) when onsite assessors were blinded; 0.76 (95% CI 0.48 to 1.12, I(2) = 0%, two RCTs) when AC assessed events identified independently from unblinded onsite assessors; and 1.11 (95% CI 0.96 to 1.27, I(2) = 0%, 10 RCTs) when AC assessed events identified by unblinded onsite assessors. However, there was a statistically significant interaction between these subgroups (P = 0.03) AUTHORS' CONCLUSIONS: On average, treatment effect estimates for subjective outcome events assessed by onsite assessors did not differ from those assessed by ACs. Results of subgroup analysis showed an interaction according to the blinded status of onsite assessors and the process used to submit data to AC. These results suggest that the use of ACs might be most important when onsite assessors are not blinded and the risk of misclassification is high. Furthermore, research is needed to explore the impact of the different procedures used to select events to adjudicate.