scholarly journals Comparative effectiveness of surgery in traumatic acute subdural and intracerebral haematoma: study protocol for a prospective observational study within CENTER-TBI and Net-QuRe

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e033513 ◽  
Author(s):  
Thomas A. Van Essen ◽  
Victor Volovici ◽  
Maryse C. Cnossen ◽  
Angelos Kolias ◽  
Iris Ceyisakar ◽  
...  
Keyword(s):  
Observational Study ◽  
Surgical Management ◽  
Decompressive Craniectomy ◽  
Sensitivity Analyses ◽  
Treatment Preference ◽  
Secondary Outcome ◽  
Intracerebral Haematoma ◽  
Primary Analysis ◽  
Acute Subdural Haematoma ◽  
Acute Surgery

IntroductionControversy exists about the optimal treatment for patients with a traumatic acute subdural haematoma (ASDH) and an intracerebral haematoma/contusion (t-ICH). Treatment varies largely between different regions. The effect of this practice variation on patient outcome is unknown. Here, we present the protocol for a prospective multicentre observational study aimed at comparing the effectiveness of different treatment strategies in patients with ASDH and/or t-ICH. Specifically, the aims are to compare (1) an acute surgical approach to an expectant approach and (2) craniotomy to decompressive craniectomy when evacuating the haematoma.Methods and analysisPatients presenting to the emergency room with an ASDH and/or an t-ICH are eligible for inclusion. Standardised prospective data on patient and injury characteristics, treatment and outcome will be collected on 1000 ASDH and 750 t-ICH patients in 60–70 centres within two multicentre prospective observational cohort studies: the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and Neurotraumatology Quality Registry (Net-QuRe). The interventions of interest are acute surgery, defined as surgery directly after the first CT at presentation versus late or no surgery and craniotomy versus decompressive craniectomy. The primary outcome measure is the Glasgow Outcome Score-Extended at 6 months. Secondary outcome measures include in-hospital mortality, quality of life and neuropsychological tests. In the primary analysis, the effect of treatment preference (eg, proportion of patients in which the intervention under study is preferred) per hospital will be analysed with random effects ordinal regression models, adjusted for casemix and stratified by study. Such a hospital-level approach reduces confounding by the indication. Sensitivity analyses will include propensity score matching, with treatment defined on patient level. This study is designed to determine the best acute management strategy for ASDH and t-ICH by exploiting the existing between-hospital variability in surgical management.Ethics and disseminationEthics approval was obtained in all participating countries. Results of surgical management of ASDH and t-ICH/contusion will separately be submitted for publication in a peer-reviewed journal.Trial registration numberNCT02210221and NL 5761.

scholarly journals Mindfulness-based and acceptance-based programmes in the treatment of obsessive–compulsive disorder: a study protocol for a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e050329
Author(s):  
Johannes Julian Bürkle ◽  
Johannes Caspar Fendel ◽  
Stefan Schmidt
Keyword(s):  
Systematic Review ◽  
Depressive Symptoms ◽  
Obsessive Compulsive Disorder ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

IntroductionCognitive–behavioural therapy (CBT) with exposure and response prevention is the recommended standard for the treatment of obsessive–compulsive disorder (OCD). However, a high proportion of patients refuse this treatment, do not respond or relapse shortly after treatment. Growing evidence suggests that mindfulness-based and acceptance-based programmes (MABPs) are an effective option for the treatment of OCD. This systematic review and meta-analysis will examine the effectiveness of MABPs in treating OCD. We also aimed to explore potential moderators of the programmes’ effectiveness.Methods and analysisWe will systematically search MEDLINE, Embase, PsycINFO, PSYINDEX, Web of Science, CINAHL and Cochrane Register of Controlled Trials (no language restrictions) for studies that evaluate the effect of MABPs on patients with OCD. We will conduct backward and forward citation searches of included studies and relevant reviews and contact corresponding authors. The primary outcome will be pre-post intervention change in symptom severity. A secondary outcome will be change in depressive symptoms. Two reviewers will independently screen the records, extract the data and rate the methodological quality of the studies. We will include both controlled and uncontrolled trials. Randomised controlled trials will be meta-analysed, separately assessing between-group effects. A second meta-analysis will assess the within-group effect of all eligible studies. We will explore moderators and sources of heterogeneity such as the specific programme, study design, changes in depressive symptoms, hours of guided treatment, control condition and prior therapy (eg, CBT) using metaregression and subgroup analyses. We will perform sensitivity analyses using follow-up data. A narrative synthesis will also be pursued. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of the evidence.Ethics and disseminationEthical approval is not required. Results will be published in peer-reviewed journals and presented at international conferences.

scholarly journals Survival in elderly glioblastoma patients treated with bevacizumab-based regimens in the United States

2018 ◽  
Vol 5 (4) ◽  
pp. 251-261 ◽  
Author(s):  
Jessica Davies ◽  
Irmarie Reyes-Rivera ◽  
Thirupathi Pattipaka ◽  
Stephen Skirboll ◽  
Beatrice Ugiliweneza ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Lower Risk ◽  
Karnofsky Performance Status ◽  
The United States ◽  
Cox Proportional Hazards Model ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Risk Of Death ◽  
Initial Surgery ◽  
The Impact

AbstractBackgroundThe efficacy of bevacizumab (BEV) in elderly patients with glioblastoma remains unclear. We evaluated the effect of BEV on survival in this patient population using the Survival, Epidemiology, and End Results (SEER)-Medicare database.MethodsThis retrospective, cohort study analyzed SEER-Medicare data for patients (aged ≥66 years) diagnosed with glioblastoma from 2006 to 2011. Two cohorts were constructed: one comprised patients who had received BEV (BEV cohort); the other comprised patients who had received any anticancer treatment other than BEV (NBEV cohort). The primary analysis used a multivariate Cox proportional hazards model to compare overall survival in the BEV and NBEV cohorts with initiation of BEV as a time-dependent variable, adjusting for potential confounders (age, gender, Charlson comorbidity index, region, race, radiotherapy after initial surgery, and diagnosis of coronary artery disease). Sensitivity analyses were conducted using landmark survival, propensity score modeling, and the impact of poor Karnofsky Performance Status.ResultsWe identified 2603 patients (BEV, n = 597; NBEV, n = 2006). In the BEV cohort, most patients were Caucasian males and were younger with fewer comorbidities and more initial resections. In the primary analysis, the BEV cohort showed a lower risk of death compared with the NBEV cohort (hazard ratio, 0.80; 95% confidence interval, 0.72–0.89; P < .01). The survival benefit of BEV appeared independent of the number of temozolomide cycles or frontline treatment with radiotherapy and temozolomide.ConclusionBEV exposure was associated with a lower risk of death, providing evidence that there might be a potential benefit of BEV in elderly patients with glioblastoma.

scholarly journals Guidelines for performing Mendelian randomization investigations

2020 ◽  
Vol 4 ◽  
pp. 186 ◽  
Author(s):  
Stephen Burgess ◽  
George Davey Smith ◽  
Neil M. Davies ◽  
Frank Dudbridge ◽  
Dipender Gill ◽  
...  
Keyword(s):  
Statistical Methods ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Data Sources ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Data Presentation ◽  
Journal Editors ◽  
Robust Statistical Methods

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into nine sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 18 months.

Transoral Dermoid Cyst Excision: A Multicenter Prospective Observational Study

2018 ◽  
Vol 159 (6) ◽  
pp. 981-986 ◽  
Author(s):  
Jin Pyeong Kim ◽  
Dong Kun Lee ◽  
Jeong Hwan Moon ◽  
Jung Je Park ◽  
Seung Hoon Woo
Keyword(s):  
Observational Study ◽  
Oral Cavity ◽  
Dermoid Cyst ◽  
Prospective Observational Study ◽  
University Hospital ◽  
Secondary Outcome ◽  
Transoral Surgery ◽  
Cyst Excision ◽  
Surgery Group ◽  
Multicenter Prospective Observational Study

Objective Transoral surgery is becoming a preferred technique because it does not leave any scar after surgery. However, transoral surgery for a dermoid cyst of the oral cavity is not standardized yet, due to the anatomic complexity of this region. The aim of this study was to evaluate the safety and efficacy of a transoral dermoid cyst excision. Study Design Multicenter prospective observational study. Setting University hospital. Subjects and Methods This study was designed as a 4-year prospective multicenter evaluation of dermoid cyst excisions within the floor of mouth. Clinical outcomes and complications related to procedures were evaluated among patients. The primary outcome was the efficacy of the procedure, and the secondary outcome was cosmetic satisfaction of each procedure. Results Twenty-one patients underwent transoral dermoid cyst excisions, and 22 underwent transcervical excisions. In the transoral surgery group, the mean size of the dermoid cyst was 5.35 cm (95% CI, 4.79-5.91), and in the transcervical surgery group, it was 6.19 cm (95% CI, 5.67-6.71). There was no significant differences with respect to overall demographic characteristics between the groups. However, the duration of the operation was shorter with the transoral group than with the transcervical group ( P = .001), and cosmetic satisfaction was much better in the transoral group ( P < .001). Conclusion Transoral dermoid cyst excision is a potentially safe and effective method that can lead to easy and quick removal of an oral cavity dermoid cyst, with excellent cosmetic outcomes.

Analysis of the effect of crossover from placebo (PBO) to darolutamide (DARO) on overall survival (OS) benefit in the ARAMIS Trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 240-240
Author(s):  
Neal D. Shore ◽  
Karim Fizazi ◽  
Teuvo Tammela ◽  
Murilo Luz ◽  
Manuel Philco Salas ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Safety Profile ◽  
Final Analysis ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Secondary Endpoints ◽  
The Impact

240 Background: DARO is a structurally distinct androgen receptor inhibitor approved for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) based on significantly prolonged metastasis-free survival compared with PBO (median 40.4 vs 18.4 months; hazard ratio [HR] 0.41; 95% confidence interval [CI] 0.34–0.50; P < 0.0001) and a favorable safety profile in the phase III ARAMIS trial. Following unblinding at the primary analysis, crossover from PBO to DARO was permitted for the subsequent open-label treatment phase. Sensitivity analyses were performed to assess the effect of PBO–DARO crossover on OS benefit. Methods: Patients (pts) with nmCRPC receiving androgen deprivation therapy were randomized 2:1 to DARO (n = 955) or PBO (n = 554). In addition to OS, secondary endpoints included times to pain progression, first cytotoxic chemotherapy, first symptomatic skeletal event, and safety. The OS analysis was planned to occur after approximately 240 deaths, and secondary endpoints were evaluated in a hierarchical order. Iterative parameter estimation (IPE) and rank-preserving structural failure time (RPSFT) analyses were performed as pre-planned sensitivity analyses to adjust for the treatment effect of PBO–DARO crossover. The IPE method used a parametric model for the survival times and iteratively determined the model parameter describing the magnitude of the treatment effect, whereas a grid search and non-parametric log-rank test were used for the RPSFT analysis. The IPE and RPSFT analyses both generated a Kaplan–Meier curve for the PBO arm that predicts what would have been observed in the absence of PBO–DARO crossover. Results: After unblinding, 170 pts (30.7% of those randomized to PBO) crossed over from PBO to DARO; median treatment duration from unblinding to the final data cut-off was 11 months. Final analysis of the combined double-blind and open label periods was conducted after 254 deaths (15.5% of DARO and 19.1% of PBO pts) and showed a statistically significant OS benefit for DARO vs PBO (HR 0.69; 95% CI 0.53–0.88; P = 0.003). Results from the IPE (HR 0.66; 95% CI 0.51–0.84; P < 0.001) and RPSFT (HR 0.68; 95% CI 0.51–0.90; P = 0.007) analyses were similar to those from the intention-to-treat population, showing that the impact of PBO–DARO crossover was small. Additional analyses accounting for the effect of PBO–DARO crossover will be presented. The safety profile of DARO continued to be favorable at the final analysis, and discontinuation rates at the end of the double-blind period remained unchanged from the primary analysis (8.9% with DARO and 8.7% with PBO). Conclusions: Early treatment with DARO in men with nmCRPC is associated with significant improvement in OS regardless of pts crossing over from PBO to DARO. The safety profile of DARO remained favorable at the final analysis. Clinical trial information: NCT02200614.

Rib Fractures in Geriatric Patients: An Observational Study of Surgical Management

2019 ◽  
Vol 4 (1) ◽  
pp. 23
Author(s):  
JoyDowden Hughes ◽  
MichelleJ Berning ◽  
AlexanderS Hunt ◽  
BrianD Kim ◽  
Mariela Rivera ◽  
...  
Keyword(s):  
Observational Study ◽  
Surgical Management ◽  
Geriatric Patients ◽  
Rib Fractures

scholarly journals Cost-effectiveness analysis of cinacalcet for haemodialysis patients with moderate-to-severe secondary hyperparathyroidism in China: evaluation based on the EVOLVE trial

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e034123
Author(s):  
Lin Liu ◽  
Dongsheng Hong ◽  
Kuifen Ma ◽  
Bin Wu ◽  
Xiaoyang Lu
Keyword(s):  
Cost Effectiveness ◽  
Willingness To Pay ◽  
Secondary Hyperparathyroidism ◽  
Treatment Effect ◽  
Conventional Therapy ◽  
Pharmacoeconomic Evaluation ◽  
Sensitivity Analyses ◽  
Secondary Outcome ◽  
Life Years ◽  
The Cost

ObjectiveAs the cost-effectiveness evaluation of cinacalcet and conventional therapy in China has not been reported, the objective of this study was to make a pharmacoeconomic evaluation of cinacalcet specific to the Chinese healthcare setting in patients with moderate-to-severe secondary hyperparathyroidism (SHPT) undergoing dialysis.DesignsData from Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events trial were used for this analysis. A semi-Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs in cinacalcet plus conventional therapy (cinacalcet strategy) compared with conventional therapy (standard strategy), in patients with moderate-to-severe SHPT undergoing dialysis. Treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and covariate-adjusted ITT analysis were used as the main analyses. Model sensitivity to variations in individual inputs and overall decision uncertainty were assessed through probabilistic sensitivity analyses.Primary and secondary outcome measuresIncremental cost-effectiveness ratio (ICER) as measured by cost per QALY gained.ResultsThe ICER for cinacalcet strategy was US$44 400 per QALY gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 46.2% chance of the ICER being below a willingness-to-pay threshold of US$26 508. Treatment effects from unadjusted ITT analysis yielded an ICER of US$87 210 per QALY. The model was most sensitive to the treatment effect on mortality.ConclusionsExisting evidence does not support the cost-effectiveness of cinacalcet strategy in patients with moderate-to-severe SHPT undergoing dialysis when applying a willingness-to-pay threshold of US$26 508 per QALY, whether it is using the treatment effect from covariate-adjusted ITT analysis or unadjusted ITT analysis.

scholarly journals Comparable Efficacy and Better Safety of Double β-Lactam Combination Therapy versus β‑Lactam plus Aminoglycoside in Gram-Negative Bacteria in Randomized, Controlled Trials

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Yuanyuan Jiao ◽  
Bartolome Moya ◽  
Mong-Jen Chen ◽  
Alexandre P. Zavascki ◽  
Hsinyin Tsai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Response ◽  
Risk Ratio ◽  
Sensitivity Analyses ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Randomized Controlled

ABSTRACTThere is a great need for efficacious therapies against Gram-negative bacteria. Double β-lactam combination(s) (DBL) are relatively safe, and preclinical data are promising; however, their clinical role has not been well defined. We conducted a metaanalysis of the clinical and microbiological efficacy of DBL compared to β-lactam plus aminoglycoside combinations (BLAG). PubMed, Embase, ISI Web of Knowledge, and Cochrane Controlled Trials Register database were searched through July 2018. We included randomized controlled clinical trials that compared DBL with BLAG combinations. Clinical response was used as the primary outcome and microbiological response in Gram-negative bacteria as the secondary outcome; sensitivity analyses were performed forPseudomonas aeruginosa,Klebsiellaspp., andEscherichia coli. Heterogeneity and risk of bias were assessed. Safety results were classified by systems and organs. Thirteen studies evaluated 2,771 cases for clinical response and 665 cases for microbiological response in various Gram-negative species. DBL achieved slightly, but not significantly, better clinical response (risk ratio, 1.05; 95% confidence interval [CI], 0.99 to 1.11) and microbiological response in Gram-negatives (risk ratio, 1.11; 95% CI, 0.99 to 1.25) compared with BLAG. Sensitivity analyses by pathogen showed the same trend. No significant heterogeneity across studies was found. DBL was significantly safer than BLAG regarding renal toxicity (6.6% versus 8.8%,P = 0.0338) and ototoxicity (0.7 versus 3.1%,P = 0.0137). Other adverse events were largely comparable. Overall, empirically designed DBL showed comparable clinical and microbiological responses across different Gram-negative species, and were significantly safer than BLAG. Therefore, DBL should be rationally optimized via the latest translational approaches, leveraging mechanistic insights and newer β-lactams for future evaluation in clinical trials.

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