Select Dietary Supplement Ingredients for Preserving and Protecting the Immune System in Healthy Individuals: A Systematic Review.

Immune health products represent approximately 10% of all US dietary supplement sales. Claims made on products to support or boost the immune system are attractive to the otherwise healthy consumer who may or may not be experiencing certain life stressors. The purpose of this systematic review is to critically evaluate the purported benefits and/or potential harms of select dietary supplement ingredients frequently listed on the labels of products having immune health or related market claims. With a focus on resilience, research questions were related to whether dietary supplement ingredients are efficacious in preserving and protecting immune health in healthy individuals; and when faced with a stressor, whether taking a supplement prophylactically can assist in maintaining health and resisting or bouncing back more quickly. Thirty-nine randomized controlled studies involving populations including children, adults and seniors exposed to stressors, such as air travel, intense exercise, academic stress, and/or exposure to winter weather, met eligibility criteria. The studies included eight of the 27 supplement ingredients identified through a market-driven scoping review. Those ingredients used in single ingredient products were echinacea, elderberry, garlic, vitamin A, vitamin C, vitamin D, vitamin E, and zinc. Whereas some studies may point to evidence for benefit, specific gaps preclude the authors from making firm statements with regard to the overall evidence-base for these products and ingredients and in answering the research questions. As we move toward a vision of health promotion and resilience rather than a sole focus on disease prevention and treatment, further work in this area of dietary supplements is of utmost importance.

Analysis of Select Dietary Supplement Products Marketed to Support or Boost the Immune System.

Importance: Cold, flu, and immunity dietary supplement product sales have skyrocketed since the start of the COVID-19 pandemic. Supporting or boosting the immune system has become an important reason for using dietary supplements, and many consumers are purchasing products through online platforms. Objectives: To examine whether select dietary supplement products advertised as supporting or boosting the immune system are accurately labeled according to the Supplement Facts label of listed ingredients and to qualitatively describe the product labels' characteristics in terms of claims made. Design, Setting, and Participants: In this case series, 30 featured immune health dietary supplements were selected and purchased from Amazon.com in May 2021. Product analysis was performed using liquid chromatography-mass spectrometry. The list of ingredients detected through analysis for each product was compared with the ingredients on the product's Supplement Facts label to determine whether the product's label was accurate. Claims made on product labels were also evaluated by using the Operation Supplement Safety Scorecard's set of questions to describe the labels' characteristics. Results: A total of 30 select dietary supplement products were evaluated. Thirteen of the 30 products had accurate labels based on the product analysis. Of the 17 products with inaccurate labels, 13 had ingredients listed on the labels that were not detected through analysis, such that their labels were misbranded. Nine products had substances detected that were not claimed on the product labels, some of which may be considered adulterated. Five were misbranded and contained additional components not claimed on the label. No product had third-party certification seals present on the packaging. Ten of the 13 products with accurate labels received a score of 4 or more when applying the Operation Supplement Safety Scorecard, meaning the product was "likely okay/less risky." Conclusions and Relevance: In this case series study, most of the products tested had inaccurate labels and claims that were inconsistent with requirements the US Food and Drug Administration has put forward for dietary supplements. Quality control measures seem to be insufficient for most of these select products, and claims made on labels may be misleading consumers who purchase products.

Relative safety and quality of various dietary supplement products U.S. Service Members ask about.

CONTEXT: The purpose of this project was to determine types of dietary supplement products U.S. Service Members frequently ask about and identify risks associated with select products that consumers should be aware of when considering their use. METHODS: Forty-one dietary supplement products frequently asked about through the Operation Supplement Safety's (OPSS.org) Ask-the-Expert portal were selected. Product analysis was performed to verify whether select products were accurately labeled and to identify any risky ingredients contained in these products. Operation Supplement Safety Risk Assessment Scorecard criteria were additionally used as a screening tool to assess a product's relative safety potential. RESULTS: Among the select dietary supplements, 12 (29.3%) were marketed as pre-workout products; 14 (34.1%) for weight loss; four (9.8%) for male enhancement/testosterone boosters; and 11 (26.8%) as body building supplements. Eleven (26.8%) products had accurate labels; only eight of these had accurate labels plus no risky ingredients listed on the labels. Twenty-six (63.4%) products were misbranded; 10 (24.4%) were adulterated, and six (14.6%) were both misbranded and adulterated. Risky ingredients appeared on 23 (56%) of all product labels. Eight of these 23 products also had additional risky ingredients not listed on the labels but detected through analysis. According to the Scorecard based on label claims, 35 (85.4%) received a rating of "no-go/risky". CONCLUSIONS: U.S. Service Members and the public at large should be aware that dietary supplements may contain risky ingredients and know how to identify ingredients on the label to evaluate potential risk.

Prioritized research recommendations and potential solutions: addressing gaps surrounding dietary supplement ingredients for boosting brain health and optimizing cognitive performance.

In the market of dietary supplements, a low level of certainty exists in the state of the science, coupled with not always knowing what is in the product. Together these issues make weighing benefits/risks difficult and hinder the ability to guide evidence-based practice decisions. The authors sought to identify priorities and develop potential solutions to address research gaps so that information disseminated, can ultimately, be relied upon, when trying to make appropriate and safe decisions. Using a modified-Delphi process, 8 panelists reviewed evidence, provided from systematic review, on dietary supplement ingredients for brain health, and prioritized gaps identified and offered potential solutions. Research gaps specific to dietary supplements research included the need for quality testing of products, the question of bioavailability and absorption of ingredients, and optimal composition and standardization of supplements under investigation. Other gaps related to populations studied; a general sense of bias towards focusing research on diseased rather than maintaining or optimizing performance in healthy populations. Additionally, the lack of uniform cognitive performance measures and metrics used across research is a gap, as well as whether the metrics are accurate representations of or even generalizable to "real-life" participants wishing to optimize their performance. Methodological quality and ethical concerns in the conduct and reporting of science encompass all issues. If resources map to potential solutions outlined in this paper, then these proposed next steps offered will help facilitate meaningful research, move evidence into practice recommendations, and ultimately develop better decision-making tools for consumers to trust and rely upon for making safe supplement decisions.

Dietary Supplement Ingredients for Optimizing Cognitive Performance Among Healthy Adults: A Systematic Review.

Background: Dietary supplements promoted for brain health and enhanced cognitive performance are widely available. Claims made for these products are directed not only to the elderly wishing to prevent or mitigate cognitive decline, but also young healthy populations looking to boost their cognitive performance. It is unclear whether these claims made on product bottles and through advertising match the science. Objectives: To explore the evidence on the efficacy and safety of single dietary supplement ingredients frequently marketed with claims of enhanced cognitive performance among healthy adults. Design: A systematic review. Results: Nine of 54 dietary supplement ingredients identified through a scoping review met the eligibility criteria with at least 3 published studies identified per ingredient, yielding 69 unique publications. Ingredients evaluated included Bacopa monnieri, choline, creatine, omega-3 fatty acids, Ginkgo biloba, ginseng, Rhodiola rosea, tyrosine, and valerian root, all in supplement form and compared with a placebo, at various serving sizes and durations of use. Conclusions: The low level of certainty in the state of the science, coupled with not always knowing what is in a dietary supplement product, make weighing risks and benefits difficult; these data hinder the ability to develop recommendations about using such ingredients for consumers interested in boosting their cognitive performance. Whereas certain trends regarding promising serving sizes or duration for use, are pointed to in this synthesis, when combined, studies are inconsistent and imprecise, and many are methodologically flawed. Potential solutions to address research gaps are offered, for future research next steps, which is needed to strengthen the evidence and inform decisions.

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives.

The increased utilization of metrology resources and expanded application of its' approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects.

Be in the Know: Dietary Supplements for Cognitive Performance.

Dietary supplements promoted for brain health and enhanced cognitive performance are becoming increasingly popular. Special Operations Forces (SOF) is likely a prime target for this market as they strive to continually optimize and then sustain their high level of performance at all times. When a dietary supplement hits the market, it is considered safe until it is proven otherwise; yet the majority have not been analyzed for quality or tested for safety. The authors describe issues related to products marketed for brain health and cognitive enhancement and focus on products brought to our attention by the operational communities. The overwhelming majority of product labels were found to be misbranded and some were found to contain prohibited ingredients and drugs. The problematic ingredients in these products are introduced. The Operation Supplement Safety scorecard algorithm is demonstrated as a tool to quickly screen a product for potential safety; it can be used in real-time when considering the use of any dietary supplement product. These resources are available to help SOF medical assets evaluate whether a product's claims may be deceiving and potentially harmful to the health or career of Operators.

A Public Health Issue: Dietary Supplements Promoted for Brain Health and Cognitive Performance.

Background: Dietary supplements targeting brain health have quickly emerged in the marketplace as cognitive performance becomes an important public health issue. While manufacturers are required to report the exact ingredients and formulations listed on the Supplement Facts labels of products, many reports have indicated such labels are not always truthful, and the content of some products is inconsistent with the ingredients listed on the Supplement Facts label. Objectives: To identify dietary supplement products and ingredients marketed for brain health and cognitive performance and perform analyses of select products to verify whether purported claims are truthful and product labels accurate. Design: A scoping review was performed to identify products and ingredients. Products were selected for content analysis, investigated for scientific-sounding claims made, and assessed using an educational tool for potential red flags when reading Supplement Facts labels. Results: Twelve products were selected from the 650 products being marketed for brain health and queried about by Service Members. Eight (67%) had at least one ingredient listed on the Supplement Facts label not detected through analysis. Compounds not reported on the label were detected in 10 (83%) products. Scientific-sounding claims made are not supported by science and red flags are presented. Conclusions: There are dietary supplements targeting brain health being marketed to consumers that should be considered adulterated and misbranded. Advertisements and product labels may be deceiving and could put the public at risk. Education is required so that the public can recognize red flags while the U.S. Food and Drug Administration works to "modernize" the current regulations for dietary supplements.

The scoop on brain health dietary supplement products containing huperzine A.

Context: Public health concerns are emerging surrounding huperzine A commonly found in dietary supplements. We sought to determine the actual content of products claiming to contain huperzine A and whether the ingredients on the supplement facts labels matched the analyses.Methods: We identified and analyzed 22 dietary supplement products listing huperzine A on product labels. We found these products were listed in Natural Medicines and Dietary Supplement Databases and being queried by Military Service Members for enhanced mental focus, alertness and energy. Analyses were conducted by using Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry.Results: Sixteen (73%) products had at least one ingredient claimed on the supplement facts label not detected through analysis. Compounds not reported on the label were detected in 16 (73%) products analyzed. Nine products (41%) listed ingredients not meeting the regulations for being a dietary supplement ingredient according to the FDA. Ingredients of most concern detected include stimulants: demelverine, 1,5-dimethylhexylamine, 1,3-dimethylhexylamine, N-phenethyl dimethylamine, halostachine, higenamine, noopept, ß-PEA, vinpocetine, sulbutiamine; and hordenine, currently on the FDA advisory list. Quantitative analysis showed the presence of huperzine A in the range from detected under the limits of quantification (DUL) to 267.1 µg/serving. Only two supplements showed huperzine A content within 10% of the declared amount.Conclusions: In a study of dietary supplements claiming to contain huperzine A, we found products that had at least one ingredient claimed on the supplement facts label not detected through analysis. Moreover, some ingredients not on the label could be dangerous and likely do not meet the definition of a dietary supplement ingredient according to the FDA. Quantitative analysis of huperzine A showed the amount detected was not in line with what appeared on the product label. Consumers should be aware of deceptive label claims and warned not to purchase products containing potentially dangerous ingredients.

Conditional Recommendations for Specific Dietary Ingredients as an Approach to Chronic Musculoskeletal Pain: Evidence-Based Decision Aid for Health Care Providers, Participants, and Policy Makers.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular for a wide range of pain conditions, decisions to use supplements are often driven by information that is not evidence-based. This work evaluates whether the current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. A decision table was constructed to make evidence-informed judgments across factors required for decision-making, and recommendations were made for practice and self-care use. RESULTS: Nineteen dietary ingredients were included. Conditional evidence-based recommendations were made for the use of avocado soybean unsaponifiables, capsaicin, curcuma, ginger, glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D. In these cases, desirable effects outweighed undesirable effects, but there was uncertainty about the trade-offs, either because the evidence was low quality or because benefits and downsides were closely balanced. CONCLUSIONS: The evidence showed that certain dietary ingredients, when taken as part of a balanced diet and/or as a supplement (e.g., pill, tablet, capsule, cream), may alleviate musculoskeletal pain with no to minimal risk of harm. This finding emphasizes and reinforces the critical importance of shared decision-making between Operators and their health care providers.

Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use. RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations. CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.

Dietary Ingredients Requiring Further Research Before Evidence-Based Recommendations Can Be Made for Their Use as an Approach to Mitigating Pain.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular, decisions are often driven by information that is not evidence-based. This work evaluates whether current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. Grading of Recommendations, Assessment, Development and Evaluation was used to determine confidence in the effect estimates. The committee used a decision table to make evidence-informed judgments across decision-making factors and recommendations for practice and self-care use. RESULTS: Nineteen dietary ingredients were assessed. No recommendations were given for boswellia, ginger, rose hip, or s-adenosyl-L-methionine (SAMe); specifically, although ginger can be obtained via food, no recommendation is provided for use as a supplement due to unclear research. Further, there were insufficient strong research on boswellia and SAMe and possible compliance issues (i.e., high number of capsules required daily) associated with rose hip. CONCLUSIONS: No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative. Research recommendations are provided to enhance the quality and body of evidence for the most promising ingredients. Clinicians and those with chronic pain can rely on evidence-based recommendations to inform their decisions.

Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain: A Systematic Review and Meta-Analysis for an Appropriateness Panel.

BACKGROUND: Mobilization and manipulation therapies are widely used by patients with chronic nonspecific neck pain; however, questions remain around efficacy, dosing, and safety, as well as how these approaches compare to other therapies. OBJECTIVES: Based on published trials, to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic nonspecific neck pain. STUDY DESIGN: A systematic literature review and meta-analysis. METHODS: We identified studies published between January 2000 and September 2017, by searching multiple electronic databases, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation and/or mobilization therapies to sham, no treatment, each other, and other active therapies, or when combined as multimodal therapeutic approaches. We assessed risk of bias by using the Scottish Intercollegiate Guidelines Network criteria. When possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation was applied to determine the confidence in effect estimates. This project was funded by the National Center for Complementary and Integrative Health under award number U19AT007912 and ultimately used to inform an appropriateness panel. RESULTS: A total of 47 randomized trials (47 unique trials in 53 publications) were included in the systematic review. These studies were rated as having low risk of bias and included a total of 4,460 patients with nonspecific chronic neck pain who were being treated by a practitioner using various types of manipulation and/or mobilization interventions. A total of 37 trials were categorized as unimodal approaches and involved thrust or nonthrust compared with sham, no treatment, or other active comparators. Of these, only 6 trials with similar intervention styles, comparators, and outcome measures/timepoints were pooled for meta-analysis at 1, 3, and 6 months, showing a small effect in favor of thrust plus exercise compared to an exercise regimen alone for a reduction in pain and disability. Multimodal approaches appeared to be effective at reducing pain and improving function from the 10 studies evaluated. Health-related quality of life was seldom reported. Some 22/47 studies did not report or mention adverse events. Of the 25 that did, either no or minor events occurred. LIMITATIONS: The current evidence is heterogeneous, and sample sizes are generally small. CONCLUSIONS: Studies published since January 2000 provide low-moderate quality evidence that various types of manipulation and/or mobilization will reduce pain and improve function for chronic nonspecific neck pain compared to other interventions. It appears that multimodal approaches, in which multiple treatment approaches are integrated, might have the greatest potential impact. The studies comparing to no treatment or sham were mostly testing the effect of a single dose, which may or may not be helpful to inform practice. According to the published trials reviewed, manipulation and mobilization appear safe. However, given the low rate of serious adverse events, other types of studies with much larger sample sizes would be required to fully describe the safety of manipulation and/or mobilization for nonspecific chronic neck pain. KEY WORDS: Chronic neck pain, nonspecific, chiropractic, manipulation, mobilization, systematic review, meta-analysis, appropriateness.

Dietary Supplements for Musculoskeletal Pain: Science Versus Claims.

Special Operations Forces (SOF) face unique challenges that manifest themselves both mentally and physically. The extremes of training and combat can affect the readiness to perform at peak levels, especially when confronted with musculoskeletal pain. Many SOF Operators turn to dietary supplements in hopes of gaining an edge. Although some supplements are now being marketed for pain, decisions to use these products need to be driven by information that is evidence based. We describe SOF-specific evidence-based recommendations for the use of dietary ingredients for pain that emerged from a rigorous scientific evaluation. These recommendations are compared with the label claims made in the commercial market by companies selling products to combat musculoskeletal pain. This information can be used by the SOF medical community to assist Operators in making informed decisions when considering or selecting dietary supplements for maintaining and optimizing performance.

Manipulation and mobilization for treating chronic low back pain: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Mobilization and manipulation therapies are widely used to benefit patients with chronic low back pain. However, questions remain about their efficacy, dosing, safety, and how these approaches compare with other therapies. PURPOSE: The present study aims to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic low back pain. STUDY DESIGN/SETTING: This is a systematic literature review and meta-analysis. OUTCOME MEASURES: The present study measures self-reported pain, function, health-related quality of life, and adverse events. METHODS: We identified studies by searching multiple electronic databases from January 2000 to March 2017, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation or mobilization therapies with sham, no treatment, other active therapies, and multimodal therapeutic approaches. We assessed risk of bias using Scottish Intercollegiate Guidelines Network criteria. Where possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was applied to determine the confidence in effect estimates. This project is funded by the National Center for Complementary and Integrative Health under Award Number U19AT007912. RESULTS: Fifty-one trials were included in the systematic review. Nine trials (1,176 patients) provided sufficient data and were judged similar enough to be pooled for meta-analysis. The standardized mean difference for a reduction of pain was SMD=-0.28, 95% confidence interval (CI) -0.47 to -0.09, p=.004; I2=57% after treatment; within seven trials (923 patients), the reduction in disability was SMD=-0.33, 95% CI -0.63 to -0.03, p=.03; I2=78% for manipulation or mobilization compared with other active therapies. Subgroup analyses showed that manipulation significantly reduced pain and disability, compared with other active comparators including exercise and physical therapy (SMD=-0.43, 95% CI -0.86 to 0.00; p=.05, I2=79%; SMD=-0.86, 95% CI -1.27 to -0.45; p<.0001, I2=46%). Mobilization interventions, compared with other active comparators including exercise regimens, significantly reduced pain (SMD=-0.20, 95% CI -0.35 to -0.04; p=.01; I2=0%) but not disability (SMD=-0.10, 95% CI -0.28 to 0.07; p=.25; I2=21%). Studies comparing manipulation or mobilization with sham or no treatment were too few or too heterogeneous to allow for pooling as were studies examining relationships between dose and outcomes. Few studies assessed health-related quality of life. Twenty-six of 51 trials were multimodal studies and narratively described. CONCLUSION: There is moderate-quality evidence that manipulation and mobilization are likely to reduce pain and improve function for patients with chronic low back pain; manipulation appears to produce a larger effect than mobilization. Both therapies appear safe. Multimodal programs may be a promising option.

Methodological approach to moving nutritional science evidence into practice.

The Metabolically Optimized Brain study explored nutritional science believed to be ready to place into practice to help improve US service members' cognitive performance and, thereby, optimize mission-readiness. A transparent, step-wise, research approach was used for informing evidence-based decisions among and for various, diverse stakeholders. A steering committee and subject-matter experts convened to devise the protocol and independent systematic reviews were performed to determine the quality of the evidence for nutritional science in 4 areas relevant to military populations: (1) caffeinated foods and beverages; (2) omega-3 polyunsaturated fatty acids; (3) plant-based foods and beverages or their phytochemical constituents; and (4) whole dietary patterns. A research expert panel was asked to then recommend future research directions and solutions likely to benefit warfighters. An implementation expert panel further considered how to apply sound nutritional science in a cost-effective manner. This article summarizes the methodological processes, high-level results, global research recommendations, and priorities for implementation. Specific results of the individual dietary interventions, as well as recommendations for moving this field of research and practice forward, are detailed throughout the current supplement.

Scientific Evaluation and Review of Claims in Health Care (SEaRCH): A Streamlined, Systematic, Phased Approach for Determining "What Works" in Healthcare.

BACKGROUND: Answering the question of "what works" in healthcare can be complex and requires the careful design and sequential application of systematic methodologies. Over the last decade, the Samueli Institute has, along with multiple partners, developed a streamlined, systematic, phased approach to this process called the Scientific Evaluation and Review of Claims in Health Care (SEaRCH™). The SEaRCH process provides an approach for rigorously, efficiently, and transparently making evidence-based decisions about healthcare claims in research and practice with minimal bias. METHODS: SEaRCH uses three methods combined in a coordinated fashion to help determine what works in healthcare. The first, the Claims Assessment Profile (CAP), seeks to clarify the healthcare claim and question, and its ability to be evaluated in the context of its delivery. The second method, the Rapid Evidence Assessment of the Literature (REAL©), is a streamlined, systematic review process conducted to determine the quantity, quality, and strength of evidence and risk/benefit for the treatment. The third method involves the structured use of expert panels (EPs). There are several types of EPs, depending on the purpose and need. Together, these three methods-CAP, REAL, and EP-can be integrated into a strategic approach to help answer the question "what works in healthcare?" and what it means in a comprehensive way. DISCUSSION: SEaRCH is a systematic, rigorous approach for evaluating healthcare claims of therapies, practices, programs, or products in an efficient and stepwise fashion. It provides an iterative, protocol-driven process that is customized to the intervention, consumer, and context. Multiple communities, including those involved in health service and policy, can benefit from this organized framework, assuring that evidence-based principles determine which healthcare practices with the greatest promise are used for improving the public's health and wellness.

Is Hyperbaric Oxygen Therapy Effective for Traumatic Brain Injury? A Rapid Evidence Assessment of the Literature and Recommendations for the Field.

OBJECTIVE: This systematic review examines the efficacy of hyperbaric oxygen (HBO2) for traumatic brain injury (TBI) to make evidence-based recommendations for its application and future research. METHODS: A comprehensive search was conducted to identify studies through 2014. Methodological quality was assessed and synthesis and interpretation of relevant data was performed. RESULTS: Twelve randomized trials were included. All mild TBI studies demonstrated minimal bias and no statistically significant differences between HBO2 and sham arms. Statistically significant improvement occurred over time within both groups. Moderate-to-severe TBI studies were of mixed quality, with majority of results favoring HBO2 compared with "standard care." The placebo analysis conducted was limited by lack of details. CONCLUSIONS: For mild TBI, results indicate HBO2 is no better than sham treatment. Improvements within both HBO2 and sham groups cannot be ignored. For acute treatment of moderate-to-severe TBI, although methodology appears flawed across some studies, because of the complexity of brain injury, HBO2 may be beneficial as a relatively safe adjunctive therapy if feasible. Further research should be considered to resolve the controversy surrounding this field, but only if methodological flaws are avoided and bias minimized.