Recently Published Projects

Objectives: Review question What are the existing methods for identifying epilepsy surgery targets? What are the results and how do they compare to the current gold standard (trained experts)? What is the quality of method validation, considering the patient cohort, ground truth reference, and validation metrics? Does the study provide source code and data to replicate the results?

Objectives: Main Points • Overall, evidence from January 2000 to May 2024 was insufficient and inconclusive across populations to determine the average daily dietary protein and indispensable amino acid requirements across populations. • For most populations, one or two studies of higher methodological rigor examined protein or indispensable amino acid requirement estimates. When more than two studies were available, different designs and/or methods to calculate the estimate requirements were used, making comparisons between studies difficult. • We identified a critical need for the development of a single standardized and validated method to assess protein and amino acid requirement estimates. Future studies, using this new method, should focus on population groups including infants, children, adolescents, pregnant people, and lactating people where protein intake is essential for appropriate growth and development. Background and Purpose Protein is essential for the growth, development, function, and maintenance of human health.1 Protein is a complex structure made up of various amino acids; some amino acids are considered “indispensable” because the body cannot produce them and therefore, they must be consumed in the diet. The current Dietary Reference Intakes (DRIs) for protein and amino acids were established in 2005.2 This report reviews the evidence on the average daily dietary protein and individual indispensable amino acid intake requirement of apparently healthy individuals by life stage and sex. We considered evidence published since the current DRIs were set and our findings will serve as a key reference for future updates to the DRIs for protein and amino acids. Methods The methods for this systematic review followed the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews, which we describe in the full report. Our searches covered publication dates from January 2000 through May 2024. We included randomized and nonrandomized controlled trials, prospective cohort, and nested case-control studies that investigated total protein and amino acid requirements using a variety of methods (i.e., nitrogen balance, indicator amino acid oxidation, etc.). We extracted data, assessed risk of bias, narratively summarized and synthesized results, and evaluated the strength of the evidence supporting the conclusions. Full details on the methods are contained in the full report (https://effectivehealthcare.ahrq.gov/products/dietary-protein-intake/protocol) of this review. Results We identified 11,408 studies, of which 68 articles reporting on 66 unique studies were eligible for the review and 45 studies were assessed as low or moderate risk of bias and therefore included in the synthesis of results. Overall, the evidence was insufficient to draw conclusions for average daily dietary protein and indispensable amino acid requirements. Estimated requirements for protein and indispensable amino acids varied both by population and by method used to calculate the requirement. For most populations, one or two studies of higher methodological rigor were available for both protein and amino acid requirements. For infants, six studies examined requirements for isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine using the indicator amino acid oxidation method. Both males and females were studied for all requirements except valine where only males were studied. For children and adolescents, seven studies examined requirements for protein, lysine, methionine, phenylalanine, and total branched chain amino acids using the indicator amino acid oxidation method. Both males and females were studied for all requirements except phenylalanine, for which the sex of participants was not reported. For pregnant people, four studies examined requirements for protein, lysine, and phenylalanine using the direct amino acid oxidation and indicator amino acid oxidation methods. For adults aged 19-50 years, 16 studies examined requirements for protein, leucine, lysine, methionine, phenylalanine, threonine, and valine using the indicator amino acid oxidation, 24-hour indicator amino acid oxidation/24-hour indicator amino acid balance, nitrogen balance and plasma amino acid response methods. Only males were studied for all requirements except lysine, where one study enrolled only females. For adults aged 51>70 years, six studies examined requirements for protein, leucine, and phenylalanine using the direct amino acid oxidation, indicator amino acid oxidation, and nitrogen balance methods. Even when more than two studies were available for protein or amino acids, they used different designs and/or methods to calculate the requirement estimates, making synthesis impossible. Studies without a protein or amino acid requirement estimate (k=6) reported outcomes such as growth, nitrogen balance, leucine oxidation, phenylalanine oxidation, rate of 13CO2 released from tracer oxidation (F13CO2), and 24-hour whole body lysine balance and oxidation. Strengths and Limitations The current systematic review has several strengths and limitations. One strength is that we captured a wide array of methodologies used to calculate protein and amino acid requirements, which expands on the previous evidence used to inform the 2005 DRIs. We also included a range of populations, from infants to older adults and pregnant people. And we performed risk of bias assessments and graded the strength of evidence, which provides context about the methodological rigor and confidence in the findings of the included studies. However, our review is limited by our decision not to capture or review evidence on the protein content of human milk, which was used in the previous DRIs to determine the requirements. We made this decision to avoid duplicating other ongoing efforts by the U.S. federal government to document the nutrient composition of human milk.3-6 Also, since our review sought to examine on the quantity of dietary protein, we did not examine how protein quality impacts requirements. Implications and Conclusions Our review expands on the previous evidence used to inform the 2005 DRIs and offers valuable insights for future research. We found very few studies for protein or indispensable amino acids across all populations. Overall, evidence from January 2000 to May 2024 is inconclusive across populations to determine the average daily dietary protein and indispensable amino acid requirements. This field critically needs a single standardized and validated method to assess protein and amino acid requirement estimates with future studies focused specifically on life stages where protein intake is vital to growth and development and older adults.

Objectives: DMain Points • Research conducted since 2000 on the association between dietary protein intake and bone disease, kidney disease, and sarcopenia risks is insufficient and inconclusive. Improving this evidence base will require more robust long-term studies. • To assess chronic disease risk, studies used intermediate markers, including surrogate markers for bone, kidney disease, and sarcopenia diagnostic components. However, these markers may not fully represent the conditions’ presence and progression. Sarcopenia’s absence as a study endpoint marks a significant research gap for older adults. • Varied methods and outcome measures made it hard to compare results across studies. • A notable research gap regarding the impact of dietary protein intake on bone health in children and adolescents highlights the urgent need for further investigation. Background and Purpose Since the publication of the protein Dietary Reference Intakes (DRIs) in 2005, no update has been made.1 Protein is essential for optimal growth, development, function, and maintenance of human health.2 It significantly influences bone health across all life stages and is essential for the development of peak bone mass in children and adolescents.3,4 In adults, dietary protein has a complex effect on bone health, described as both beneficial5,6 and potentially harmful.7,8 The relationship between protein intake and kidney health is still under debate, particularly in those without existing kidney issues.9-13 For sarcopenia, protein is considered potentially important in slowing its progression, underscoring protein’s role in addressing age-related health concerns.14,15 This report reviews the association between dietary protein intake and bone disease, kidney disease, and sarcopenia risks, aiming to inform updates to the protein DRIs, including a new reference value for chronic disease risk reduction. Methods Following the Agency for Healthcare Research and Quality's guidelines, our systematic review (PROSPERO registration CRD42023446621) assessed literature from January 2000 to May 2024, searching MEDLINE®, Embase®, AGRICOLA, and citations of reviews and original research. We included randomized and non-randomized trials, prospective cohorts, and nested case-controls in healthy individuals, exploring dietary protein intake without exercise. We assessed risk of bias using Cochrane Risk of Bias 2.0 and Risk Of Bias In Non-randomized Studies - of Exposure, extracted data, qualitatively synthesized findings from studies rated as low to moderate risk of bias (studies less prone to biases affecting the robustness of their findings), and evaluated the strength of evidence. For further details on the methods, see the full report [include a hyperlink/URL to the full report on the AHRQ website]. Results Of 11,015 identified studies, 82 articles detailing 81 distinct studies met our inclusion criteria. Among these, 13 studies rated as low to moderate risk of bias were synthesized. This analytic set included five bone disease studies (3 randomized controlled trials in adults [2 low and 1 moderate risk of bias], 1 prospective cohort study in adults [moderate risk of bias], and 1 randomized controlled trial in children and adolescents [low risk of bias and the only eligible child study]); one kidney disease study (1 randomized controlled trial [moderate risk of bias]); and nine sarcopenia studies (9 randomized controlled trials [7 low and 2 moderate risk of bias]). The evidence was insufficient to address the Key Questions, with only a few studies rated as low to moderate risk of bias. Particularly scarce was the literature pertaining to children and adolescents. A single study assessing dietary protein's association with bone disease risk in children and adolescents showed mixed results on bone health measures such as turnover markers, and lumbar spine bone mineral density, content, and bone area. Additionally, just one study informed dietary protein's association with adult kidney disease risk, and it reported no significant effects on kidney function, assessed by creatinine clearance. Findings on the effects of protein intake on adult bone disease were inconsistent, showing both no difference and benefit on outcomes such as bone turnover markers, bone mineral density of the lumbar spine, total hip, and femoral neck, as well as total body bone mineral density and content. Similarly, the studies on sarcopenia risk showed inconsistent results regarding muscle mass, physical performance, and muscle strength. The variety of outcome measures, the differences in dietary protein intake levels, and sparse outcome data distribution across studies made it challenging to synthesize and compare findings. Furthermore, studies used established intermediate markers to evaluate disease risk, such as surrogate markers for bone and kidney health and diagnostic components of sarcopenia, instead of direct chronic condition outcomes. Strengths and Limitations Our systematic review had several strengths, including a unique emphasis on multiple chronic diseases, and the inclusion of all relevant outcomes. Additionally, our review is notable for examining the relationship between dietary protein intake and bone disease risk in children and adolescents, and for isolating the effects of protein intake without exercise. However, our exclusion of pre-2000 studies might have missed crucial foundational research, though this is unlikely to significantly affect our findings. Further, by focusing only on studies rated low to moderate risk of bias, we limited the size of our body of evidence, but including high risk of bias studies would likely have lessened the robustness of our findings and the strength of evidence. Our review identifies evidence base limitations, including reliance on recognized intermediate markers for bone and kidney disease and sarcopenia, which may not fully reflect the presence and progression of chronic diseases, diverse outcome measurement methods with inherent limitations, the absence of sarcopenia as a study endpoint, lack of randomized controlled trials, and the challenges in assessing risk of bias, particularly in non-randomized studies, such as prospective cohort studies. These limitations could pose challenges in accurately assessing health effects. Implications and Conclusions Studies conducted since 2000 on the association between dietary protein intake and the risks of bone disease, kidney disease, and sarcopenia have yielded unclear yet potentially significant findings. Ambiguities stem from study limitations, lack of studies on vital demographics such as children and adolescents for bone health, varying protein intake levels in studies, and inconsistent outcome measures across studies. This underlines the crucial need for more comprehensive, high quality, long-term research to strengthen the evidence base. Such improvements will be essential for assessing dietary protein’s impact on these chronic conditions.

Objectives: JHU EPC systematic review project as part of EPC VI

Objectives: Objectives: (1) Summarize reported barriers and facilitators to the receipt of clinical preventive services among people with disabilities; (2) Evaluate the literature on the effectiveness of interventions to improve receipt of preventive services among people with disabilities. Data Sources: Electronic databases (Ovid®, MEDLINE®, PsycINFO®, Embase®, the Cochrane Central Register of Controlled Trials, and EBSCO CINAHL Plus) from 1990, through April 23, 2024. Review Methods: Following the Agency for Healthcare Research and Quality Methods Guide (https://effectivehealthcare.ahrq.gov/products/collections/cer-methods-guide), the methods and protocol were determined a priori. We used independent dual review to determine inclusion of studies related to 20 preventive services with Grade A or Grade B recommendations by the U.S. Preventive Services Task Force. We assessed general quality (studies of barriers/facilitators) or risk of bias (effectiveness studies) using study design-specific criteria. Barriers/facilitators were classified into seven general categories (environment-level, person-level, provider-level, healthcare system-level, accessibility of healthcare facility, accessible communication, and policy-level). Barriers/facilitators and interventions were described and presented for each preventive service according to general types of disability (physical, cognitive/intellectual/developmental, sensory, serious psychiatric/mental illness). Due to high methodological/clinical heterogeneity of studies and limited available data, we did not assign strength of evidence ratings or conduct meta-analyses. Results: Of 11,472 references, we included 68 studies – 54 on barriers/facilitators; 16 on the effectiveness of interventions. Evidence was lacking for most preventive services and generally limited to one or two types of disability for any given preventive service. Studies on barriers/facilitators pertained to 10 preventive services; studies on the effectiveness of interventions pertained to 8 preventive services. Most evidence was for two preventive services – breast cancer screening and cervical cancer screening. For breast and cervical cancer screening, studies reported on most categories of barriers/facilitators and included all types of disability; for other preventive services, fewer studies reported fewer categories of barriers/facilitators and fewer types of disability. Limited evidence from three trials found various educational and health advocacy interventions to be associated with increased rates of breast and cervical cancer screening among women with physical disabilities, cognitive/intellectual/developmental disabilities, and serious mental illness. Conclusions: We found limited evidence on barriers and facilitators to receipt of most preventive services among people with disabilities, and especially limited evidence on interventions to improve receipt of those services. Most studies were related to breast and cervical cancer screening. The lack of studies for most preventive services and types of disability underscores the need for research to address substantial gaps in the evidence.