Dataset Information

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

ABSTRACT:

Objective

To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI).

Methods

PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI.

Results

A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57-1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78-1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96-4.66).

Conclusions

Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC4608716 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

Zeng Yunhui Y Zhang Yujie Y Ma Junpeng J Xu Jianguo J

PloS one 20151016 10

<h4>Objective</h4>To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI).<h4>Methods</h4>PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. ...[more]

PMID: 26473361

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Project description:Background and aims: There is a gap in knowledge regarding effective rehabilitation service delivery in the post-acute phase after traumatic brain injury (TBI). Recently, Gutenbrunner et al. proposed a classification system for health-related rehabilitation services (International Classification System for Service Organization in Health-related Rehabilitation, ICSO-R) that could be useful for contrasting and comparing rehabilitation services. The ICSO-R describes the dimensions of Provision (i.e., context of delivered services), Funding (i.e., sources of income and refunding), and Delivery (i.e., mode, structure and intensity) at the meso-level of services. We aim to: -Provide an overview of randomized, controlled trials (RCTs) with rehabilitation service relevance provided to patients with moderate and severe TBI in the post-acute phase using the ICSO-R as a framework; and -Evaluate the extent to which the provision, funding and delivery dimensions of rehabilitation services were addressed and differed between the intervention arms in these studies. Materials and methods: A systematic literature search was performed in OVID MEDLINE, EMBASE, CINHAL, PsychINFO, and CENTRAL, including multidisciplinary rehabilitation interventions with RCT designs and service relevance targeting moderate and severe TBI in the post-acute phase. Results: 23 studies with 4,644 TBI patients were included. More than two-thirds of the studies were conducted in a hospital-based rehabilitation setting. The contrast in Context between the intervention arms often co-varied with Resources. The funding of the services was explicitly described in only one study. Aspects of the Delivery dimension were described in all of the studies, and the Mode of Production, Intensity, Aspects of Time and Peer Support were contrasted in the intervention arms in several of the studies. A wide variety of outcome measures were applied often covering Body function, as well as the Activities and Participation domains of the International Classification of Functioning, Disability, and Health (ICF). Conclusion: Aspects of service organization and resources as well as delivery may clearly influence outcome of rehabilitation. Presently, lack of uniformity of data and collection methods, the heterogeneity of structures and processes of rehabilitation services, and a lack of common outcome measurements make comparisons between the studies difficult. Standardized descriptions of services by ICSO-R, offer the possibility to improve comparability in the future and thus enhance the relevance of rehabilitation studies.

Project description:Background: This systematic review aimed to evaluate the effectiveness (functional outcomes and clinical symptoms) and safety (incidence of adverse events) of herbal medicine (HM) as monotherapy or adjunctive therapy to conventional treatment (CT) for traumatic brain injury (TBI). Methods: We comprehensively searched 14 databases from their inception until July 2019. Randomized controlled trials (RCTs) using HM as monotherapy or adjunctive therapy to treat TBI patients were included. The primary outcome was functional outcomes, consciousness state, morbidity, and mortality. Meta-analysis was performed to calculate a risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs), when appropriate data were available. Methodological quality of RCTs and the strength of evidence were also assessed. Results: Thirty-seven RCTs with 3,374 participants were included. According to meta-analysis, HM as a monotherapy (RR 1.29, 95% CI: 1.21-1.37) or an adjunctive therapy to CT (RR 1.21, 95% CI: 1.16-1.27) showed significantly better total effective rate based on clinical symptoms, compared to CT alone. Subgroup analysis showed that HM had significantly improved post-concussion syndrome, dizziness, headache, epilepsy, and mild TBI, but not traumatic brain edema, compared to CT. Moreover, HM combined with CT had significantly improved post-concussion syndrome, mental disorder, headache, epilepsy, and mild TBI-like symptoms, but not cognitive dysfunction and posttraumatic hydrocephalus, compared to CT alone. When HM was combined with CT, functional outcomes such as activities of daily living and neurological function were significantly better than in patients treated using CT alone. In terms of the incidence of adverse events, HM did not differ from either CT (RR 0.88, 95% CI: 0.33-2.30) or placebo (RR 2.29, 95% CI: 0.83-6.32). However, HM combined with CT showed better safety profile than CT alone (RR 0.64, 95% CI: 0.44-0.93). Most studies had a high risk of performance bias, and the quality of evidence was mostly rated "very low" to "moderate," mostly because the included studies had a high risk of bias and imprecise quantitative synthesis results. Conclusion: The current evidence suggests that there is insufficient evidence for recommending HM for TBI in clinical practice. Therefore, further larger, high-quality, rigorous RCTs should be conducted.

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Project description:Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. RCTs were identified through comprehensive database and other searches. Key characteristics, outcomes, risk of bias, and analysis approach were extracted. Data were narratively synthesized, with a focus on robust (multi-center, low risk of bias, n?>?100) RCTs, and three-dimensional graphical figures also were used to explore relationships between RCT characteristics and findings. A total of 207 RCTs were identified. The 191 completed RCTs enrolled 35,340 participants (median, 66). Most (72%) were single center and enrolled less than 100 participants (69%). There were 26 robust RCTs across 18 different interventions. For 74% of 392 comparisons across all included RCTs, there was no significant difference between groups. Positive findings were broadly distributed with respect to RCT characteristics. Less than one-third of RCTs demonstrated low risk of bias for random sequence generation or allocation concealment, less than one-quarter used covariate adjustment, and only 7% employed an ordinal analysis approach. Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients.

Project description:To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric traumatic brain injury.National Library of Medicine PubMed literature review.The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of traumatic brain injury is summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult traumatic brain injury is reviewed.Progesterone is a pleiotropic agent with beneficial effects on secondary injury cascades that occur after traumatic brain injury, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after traumatic brain injury in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human phase II trials of progesterone for adult traumatic brain injury have been published, and two multicenter phase III trials are underway.The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of traumatic brain injury. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, and statue epilepticus).

Dataset Information

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

Objective

Methods

Results

Conclusions

Publications

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

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