A “Metamorphosis” in Our Approach to Treatment Is Not Likely to Result From a Meta-Analysis of the Use of Therapeutic Hypothermia in Severe Traumatic Brain Injury*

Wallisch, Jessica; Kochanek, Patrick M.

doi:10.1097/ccm.0000000000002240

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…The TBI field has seen similar lack of translation across all ages for TH treatments. Though a recent meta-analysis performed in 2017 suggested that TH provides an 18% reduction in mortality and 35% improvement in neurologic outcome for adults, 27 this was highly contested by those involved in the field, as all the high-quality trials in both adult and pediatric TBI have failed to show benefit 28 …”

Section: Normal Physiological Variations Should Guide Experimental Dementioning

confidence: 99%

Disease-directed engineering for physiology-driven treatment interventions in neurological disorders

Wood

Nance

2019

APL Bioengineering

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Neurological disease is killing us. While there have long been attempts to develop therapies for both acute and chronic neurological diseases, no current treatments are curative. Additionally, therapeutic development for neurological disease takes 15 years and often costs several billion dollars. More than 96% of these therapies will fail in late stage clinical trials. Engineering novel treatment interventions for neurological disease can improve outcomes and quality of life for millions; however, therapeutics should be designed with the underlying physiology and pathology in mind. In this perspective, we aim to unpack the importance of, and need to understand, the physiology of neurological disease. We first dive into the normal physiological considerations that should guide experimental design, and then assess the pathophysiological factors of acute and chronic neurological disease that should direct treatment design. We provide an analysis of a nanobased therapeutic intervention that proved successful in translation due to incorporation of physiology at all stages of the research process. We also provide an opinion on the importance of keeping a high-level view to designing and administering treatment interventions. Finally, we close with an implementation strategy for applying a disease-directed engineering approach. Our assessment encourages embracing the complexity of neurological disease, as well as increasing efforts to provide system-level thinking in our development of therapeutics for neurological disease.

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Section: Normal Physiological Variations Should Guide Experimental Dementioning

confidence: 99%

Disease-directed engineering for physiology-driven treatment interventions in neurological disorders

Wood

Nance

2019

APL Bioengineering

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“…Although the current literature including systematic reviews and meta-analyses does not support the routine use of hypothermia for the management of severe TBI in pediatric and adult patients, more recent studies suggest that specific patient populations may benefit from this experimental treatment. [ 59 60 61 62 63 64 65 66 67 ] Over the last several years, there have been reports suggesting various explanations for the lack of efficacy of therapeutic hypothermia with severe TBI. [ 68 ] Furthermore, considerable work has continued using preclinical TBI models to more clearly define the most critical factors that may be important when designing clinical trials for the use of therapeutic hypothermia.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

Dietrich

Bramlett

2017

Brain Circ

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Traumatic brain injury (TBI) is a worldwide medical problem, and currently, there are few therapeutic interventions that can protect the brain and improve functional outcomes in patients. Over the last several decades, experimental studies have investigated the pathophysiology of TBI and tested various pharmacological treatment interventions targeting specific mechanisms of secondary damage. Although many preclinical treatment studies have been encouraging, there remains a lack of successful translation to the clinic and no therapeutic treatments have shown benefit in phase 3 multicenter trials. Therapeutic hypothermia and targeted temperature management protocols over the last several decades have demonstrated successful reduction of secondary injury mechanisms and, in some selective cases, improved outcomes in specific TBI patient populations. However, the benefits of therapeutic hypothermia have not been demonstrated in multicenter randomized trials to significantly improve neurological outcomes. Although the exact reasons underlying the inability to translate therapeutic hypothermia into a larger clinical population are unknown, this failure may reflect the suboptimal use of this potentially powerful therapeutic in potentially treatable severe trauma patients. It is known that multiple factors including patient recruitment, clinical treatment variables, and cooling methodologies are all important in yielding beneficial effects. High-quality multicenter randomized controlled trials that incorporate these factors are required to maximize the benefits of this experimental therapy. This article therefore summarizes several factors that are important in enhancing the beneficial effects of therapeutic hypothermia in TBI. The current failures of hypothermic TBI clinical trials in terms of clinical protocol design, patient section, and other considerations are discussed and future directions are emphasized.

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Staying Cool in Space: A Review of Therapeutic Hypothermia and Potential Application for Space Medicine

Rosahl

Covarrubias

et al. 2022

Therapeutic Hypothermia and Temperature Management

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A “Metamorphosis” in Our Approach to Treatment Is Not Likely to Result From a Meta-Analysis of the Use of Therapeutic Hypothermia in Severe Traumatic Brain Injury*

Cited by 3 publications

References 21 publications

Disease-directed engineering for physiology-driven treatment interventions in neurological disorders

Disease-directed engineering for physiology-driven treatment interventions in neurological disorders

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

Staying Cool in Space: A Review of Therapeutic Hypothermia and Potential Application for Space Medicine

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