Showing 7 ideas for tag "oxygen"

Goal 2: Reduce Human Disease

Anemia, oxygen delivery, and red blood cell transfusion

In neonatal, pediatric, and adult patients with critical illness, what is the best means to identify: (1) the degree to which anemia contributes to insufficient oxygen (O2) delivery and (2) the likelihood that O2 delivery will be improved by red blood cell (RBC) transfusion?

These questions are most relevant to critically ill populations that exhibit unique physiology, including those with low cardiac output (cardiac... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

In the critically ill, RBC transfusion is indicated to improve O2 delivery. Although RBC transfusion increases hemoglobin concentration (Hb) and thereby blood O2 content, it does not necessarily follow that O2 delivery to tissues is likewise increased. Current approaches to transfusion decision making in critical care settings maintain an ‘adequate’ RBC mass well above a level that may limit tissue O2 delivery. With improved understanding of vascular signaling and gas transport by RBCs and of the array of defects comprising the RBC ‘storage lesion’, we appreciate that this strategy must be balanced by consideration that: (1) donor and recipient RBCs do not exhibit similar physiology and (2) RBC transfusion may cause harm (beyond transfusion reactions and transmission of infection) – and that this harm appears progressive with: transfusion volume, frequency and donor exposure. As such, ‘restrictive’ Hb thresholds for RBC transfusion are appreciated to be at least non-inferior to ‘liberal’ Hb thresholds for a broad array of conditions. A paradigm shift is emerging in approach to the critically ill, with re-consideration of the ‘Hb trigger’ strategy, itself. Ideally, the decision to transfuse should be based upon individual and context-specific consideration of the degree to which anemia contributes to tissue O2 delivery.

Feasibility and challenges of addressing this CQ or CC

We need to identify specific physiologic endpoints linked to outcomes as well as determine the appropriate thresholds for these goals. We must improve current means to assess functionality of the circulating RBC mass and its specific relationship to tissue O2 delivery in both humans and animal models. Approaches to resolve this gap could be conducted in the following areas during the next 3-5 years (studies may be independent or ancillary to clinical transfusion trials). Examples include but are not limited to the following: (1) clinical and translational research studies examining physiologic tolerance of acute and chronic anemia in the critically ill populations; (2) basic and clinical research exploring accuracy, precision and reliability of novel approaches to quantify and monitor O2 consumption and delivery (global/regional). Investigations should also determine the relationship of these measures to clinically relevant patient outcomes, both global (mortality, ventilator dependence, length of stay, etc.) and organ-specific; and (3) studies evaluating the process of transfusion decision making in the setting of critical illness.

Name of idea submitter and other team members who worked on this idea Nareg Roubinian, MD and Naomi Luban, MD for the 2015 NHLBI State of the Science in Transfusion Medicine.

Voting

40 net votes
54 up votes
14 down votes
Active

Goal 3: Advance Translational Research

The effect of continuous LTOT in COPD targeting fixed oxygen flow rates vs. oxygen saturation on patient-reported outcomes

What is the comparative effectiveness of prescribing continuous LTOT in COPD that targets fixed oxygen flow rates vs. oxygen saturation on patient-reported outcomes (symptom frequency, activities of daily living, quality of life, sleep quality, exacerbations)?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Amelia Mutso, PhD, collaborator with COPD Foundation

Voting

13 net votes
16 up votes
3 down votes
Active

Goal 3: Advance Translational Research

Develop alternatives for patients for whom routine red cell transfusion is unavailable or impractical

There is a compelling need to advance research to understand the physiology governing the safety and efficacy of hemoglobin-based oxygen therapeutics functioning outside the red cell.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Adequate numbers of red blood cells are required to sustain human life. Neurocognitive deficits and mortality in acutely anemic humans increase significantly at a hemoglobin level of below 5 g/dL even in the absence of significant cardiovascular disease. At extremely low hemoglobin levels, alternative treatments (supplemental or hyperbaric oxygen, sedation, muscle paralysis and mechanical ventilation) are of only limited benefit and are not without risk. Several classes of patients cannot be routinely transfused with red blood cells. These classes of patients for whom blood is not an option would include patients who will not accept transfusion for religious or personal reasons, patients who due to multiple prior transfusions have developed red cell antibodies without the option for compatible red cells, and massive trauma patients needing treatment in a remote location. The development of cell-free hemoglobin-based oxygen carriers, stable at room temperature and not requiring cross-matching prior to transfusion as a red cell substitute, has been a sought after goal for several decades, yet to date all attempts have met with failure during clinical trials. There is a compelling need to advance research to understand the physiology governing the safety and efficacy of hemoglobin-based oxygen therapeutics functioning outside the red cell.

Feasibility and challenges of addressing this CQ or CC

Multiple physiologic insults and adverse events seen with earlier modified hemoglobins, compared to banked red blood cells, have been described and are now better, but not completely, understood. Advances in hemoglobin modification could allow for successful use in a variety of clinical scenarios with life-saving results. Additional clinical indications could be investigated and established, such as identification of clinical situations where additional oxygen delivery could modulate the effects of chronic ischemic conditions. In addition, the hemoglobin molecule could be modified to deliver additional therapeutic benefit.

Name of idea submitter and other team members who worked on this idea Office of Blood Research and Review, CBER, FDA

Voting

8 net votes
13 up votes
5 down votes
Active

Goal 3: Advance Translational Research

Use of symptoms vs spirometry in increasing patient and provider adherence to guidelines

What is the comparative effectiveness of using symptoms vs. spirometry in increasing patient and provider adherence to COPD treatment guidelines and patient-reported outcomes (symptom frequency, activities of daily living, quality of life, sleep quality, exacerbations)?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

COPD is underdiagnosed. The lack of recognition of COPD risk by physicians and patients themselves is well known, with many undiagnosed COPD patients presenting for the first time with late stage COPD. Currently used cut-points based on a fixed ratio of FEV1/FVC may overestimate the number of elderly patients with COPD, particularly with mild disease, because of changes in lung volumes with aging. It has been suggested that using a cut-point based on the normal distribution of FEV1/FVC values may decrease the misclassification rate. Other strategies have been proposed for risk assessment as adjuncts to diagnostic classification (e.g., Fragoso et al. J Am Geriatr Soc 2008, 56:1014-1020). Pertinent references: Guideline #1 in Qaseem et al., strong recommendation, moderate-quality evidence; GOLD, 2008 and the 2005 American Thoracic Society/European Respiratory Society Task Force Report, standards for the diagnosis and management of patients with COPD.
Although there are ample guidance to help providers identify and evaluate patients likely to have earlier stage COPD, few are referred to spirometric testing. Subsequent spirometry provides a good working yield of true positives, which is frequently superior to pre-test probabilities of other, more complex and expensive medical tests commonly ordered for other conditions (colonoscopy,lung cancer), why is it so much more difficult to provide spirometry? COPD will remain undertreated as long as it remains underdiagnosed.

Name of idea submitter and other team members who worked on this idea Helene Gussin, PhD

Voting

9 net votes
12 up votes
3 down votes
Active

Goal 2: Reduce Human Disease

Making It Real: Affordable Physiologically Relevant In Vitro Environments

We have done the best we can to mimic the human internal environment in vitro for the discovery, testing, and validation of therapeutics, but there is a critical need to do better. The use of more complex cell-based in vitro models is the result of the recognition of how little predictive power there is in current experimental conditions, even with animal models. With an in vitro environment that goes beyond temperature... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Physiologically relevant in vitro environments could potentially impact research on every tissue type, disease, and intervention, including transfusion-based treatments. Basic research, drug-testing, and translational medicine would all be fundamentally altered. Individualized medicine, cellular therapies, and regenerative medicine could all benefit from in vitro conditions that best support the care of the patient's cells and guide those cells in the direction needed for effective treatment.

Feasibility and challenges of addressing this CQ or CC

Research and Industry are in the early stages of developing the techniques and know-how needed to address the technical challenges in establishing human-relevant in vitro environments. We already have the technology to control in vitro oxygen and other critical gas components. Mimicking cell-cell interactions and variable cell states such as states of differentiation or stress are areas under active research. Computational and analytical techniques are being developed that can gain insight from large data sets. More of a challenge may be assessing distant effects like metabolism of drugs by the liver or potential drug and cellular interactions with the external environment. However, making a human-predictive in vitro environment affordable is the challenge that could define success or failure of any particular approach. It is feasible within the next ten years to have truly predictive in vitro environments for drug cellular therapy development.

Voting

-4 net votes
10 up votes
14 down votes
Active