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The progress of developmental research demands reliable measurement techniques, yet inconsistency persist across laboratories, subfields, and settings. To address this, the NIH Toolbox for Neurological and Behavioral Function (NIHTB)® has been extended to create a universal assessment for developmental and pediatric communities: The NIH Infant and Toddler ("Baby") Toolbox. Currently undergoing norming in a sample of 2550 children demographically representative of the 2020 U.S. census, the Baby Toolbox is slated for release in late 2024. This paper introduces the Baby Toolbox, details its objectives, development, and technological innovations, describes plans for reliability and norming, and invites researchers to consider the Baby Toolbox in the future studies. Ultimately, this initiative stands to enhance cross-study comparability and advance comprehensive developmental evaluation., (© 2024 The Author(s). Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

The NIH Toolbox Cognitive Battery (NIHTB-CB) was developed as a common-metric, computerized cognitive screener for research. Although extensively normed and validated in Americans of different ethnicities, there is little data on how generalizable such results would be when used outside of the United States. The objective of this study was to assess measurement invariance (MI) of the NIHTB-CB across Jamaican and African-American samples and determine appropriateness of comparisons across groups. Multi-group confirmatory factor analyses using a single-factor model were conducted using five tests of fluid cognitive abilities from the NIHTB-CB, which assess working memory, episodic memory, processing speed, and executive function. MI was tested sequentially for configural, metric and scalar invariance. 125 Jamaican and 154 American adults of African descent were included. The Jamaican mean age was 31.6 ± 8.6 years (57% males) compared to 43.5 ± 15.5 years (25% males) for the African-American group. The Jamaicans had on average 11.3 ± 2.7 years of education compared to 13.9 ± 2.6 years for the African-Americans. We found metric and configural invariance across both samples but not scalar invariance. These findings suggest that the single factor emerging from the NIHTB-CB measures the same construct, i.e. fluid cognitive ability, in both groups and hence the battery is appropriate for assessments within cultures. However, lack of scalar invariance indicates that direct cross-cultural comparisons of performance levels should be interpreted with caution, also suggesting that U.S. normative standards are not generalizable to the Jamaican population.

Objective: Researchers and practitioners can detect cognitive improvement or decline within a single examinee by applying a reliable change methodology. This study examined reliable change through test-retest data from the English-language National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) normative sample., Method: Participants included adults (n = 138; age: M ± SD = 54.8 ± 20.0, range: 18-85; 51.4% men; 68.1% White) who completed test-retest assessments about a week apart on five fluid cognition tests, providing raw scores, age-adjusted standard scores (SS), and demographic-adjusted T-scores (T)., Results: The Fluid Cognition Composite (SS: ICC = 0.87; T-score: ICC = 0.84) and the five fluid cognition tests had good test-retest reliability (SS: ICC range = 0.66-0.85; T-score: ICC range = 0.64-0.86). The lower and upper bounds of 70%, 80%, and 90% confidence intervals (CIs) were calculated around change scores, which serve as cutoffs for determining reliable change. Using T-scores, 90% CI, and adjustment for practice effects, 32.3% declined on one or more tests, 9.7% declined on two or more tests, 36.6% improved on one or more tests, and 5.4% improved on two or more tests., Conclusions: It was common for participants to show reliable change on at least one test score, but not two or more test scores. Per an 80% CI, test-retest difference scores beyond these cutoffs would indicate reliable change: Dimensional Change Card Sort (SS ≥ 14/T ≥ 10), Flanker (SS ≥ 12/T ≥ 8), List Sorting (SS ≥ 14/T ≥ 10), Picture Sequence Memory (SS ≥ 19/T ≥ 13), Pattern Comparison (SS ≥ 11/T ≥ 8), and Fluid Cognition Composite (SS ≥ 10/T ≥ 7). The reliable change cutoffs could be applied in research or practice to detect within-person change in fluid cognition at the individual level., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Identify which NIH Toolbox Cognition Battery (NIHTB-CB) subtest(s) best differentiate healthy controls (HC) from those with amnestic mild cognitive impairment (aMCI) and compare the discriminant accuracy between a model using a priori "Norm Adjusted" scores versus "Unadjusted" standard scores with age, sex, race/ethnicity, and education controlled for within the model. Racial differences were also examined., Methods: Participants were Black/African American (B/AA) and White consensus-confirmed (HC = 96; aMCI = 62) adults 60-85 years old that completed the NIHTB-CB for tablet. Discriminant function analysis (DFA) was used in the Total Sample and separately for B/AA ( n = 80) and White participants ( n = 78)., Results: Picture Sequence Memory (an episodic memory task) was the highest loading coefficient across all DFA models. When stratified by race, differences were noted in the pattern of the highest loading coefficients within the DFAs. However, the overall discriminant accuracy of the DFA models in identifying HCs and those with aMCI did not differ significantly by race (B/AA, White) or model/score type (Norm Adjusted versus Unadjusted)., Conclusions: Racial differences were noted despite the use of normalized scores or demographic covariates-highlighting the importance of including underrepresented groups in research. While the models were fairly accurate at identifying consensus-confirmed HCs, the models proved less accurate at identifying White participants with an aMCI diagnosis. In clinical settings, further work is needed to optimize computerized batteries and the use of NIHTB-CB norm adjusted scores is recommended. In research settings, demographically corrected scores or within model correction is suggested.

The United States (U.S.) National Institutes of Health-funded Environmental influences on Child Health Outcomes (ECHO)-wide Cohort was established to conduct high impact, transdisciplinary science to improve child health and development. The cohort is a collaborative research design in which both extant and new data are contributed by over 57,000 children across 69 cohorts. In this review article, we focus on two key challenging issues in the ECHO-wide Cohort: data collection standardization and data harmonization. Data standardization using a Common Data Model and derived analytical variables based on a team science approach should facilitate timely analyses and reduce errors due to data misuse. However, given the complexity of collaborative research designs, such as the ECHO-wide Cohort, dedicated time is needed for harmonization and derivation of analytic variables. These activities need to be done methodically and with transparency to enhance research reproducibility. IMPACT: Many collaborative research studies require data harmonization either prior to analyses or in the analyses of compiled data. The Environmental influences on Child Health Outcomes (ECHO) Cohort pools extant data with new data collection from over 57,000 children in 69 cohorts to conduct high-impact, transdisciplinary science to improve child health and development, and to provide a national database and biorepository for use by the scientific community at-large. We describe the tools, systems, and approaches we employed to facilitate harmonized data for impactful analyses of child health outcomes., (© 2024. The Author(s).)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established., Methods: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ., Results: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR 2 0.368 and adjusted odds ratio 0.79 [0.75-0.84], P <0.001 for mRS score 0-2; aR 2 0.444 and adjusted odds ratio 0.84 [0.8-0.86] for ordinal mRS). For predicting mRS score of 0-2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14-20], P <0.001), followed by percent change in NIHSS (sensitivity 79%, specificity 58.5%; adjusted odds ratio 4.55 [2.85-7.69], P <0.001)., Conclusions: Twenty-four-hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

Objectives: The National Institutes of Health Stroke Scale (NIHSS) has not been validated to diagnose aphasia in the stroke population. We therefore examined the diagnostic accuracy of NIHSS for detecting aphasia in acute ischemic stroke., Methods: Consecutive patients with acute first-ever ischemic stroke were included prospectively in Lund Stroke Register Study at Skåne University Hospital, Sweden. Exclusion criteria were: (a) non-native Swedish; (b) obtundation (c) dementia or psychiatric diagnosis. Patients were assessed with NIHSS item 9 (range 0-3, where 1-3 indicate aphasia) by a NIHSS certified research nurse in the acute phase after stroke onset (median 3 days). Within 24 h after this assessment, a speech therapist evaluated the patients' language function with the comprehensive language screening test (LAST, range 0-15 where 0-14 indicates aphasia). Data were analyzed using LAST as 'reference standard'., Results: We examined 221 patients. Among these, 23% (n = 50) had aphasia according to NIHSS (distribution of scores 0, 1, 2, 3 were n = 171, n = 29, n = 12, n = 9) compared to 26% (n = 58) with aphasia according to LAST (score ≤14; median = 11). Assuming LAST as reference standard, NIHSS gave 16 false negatives (NIHSS item 9 = 0) for aphasia (LAST scores range 8-14), and 8 false positives (NIHSS item 9 score = 1) for aphasia, yielding a sensitivity of 72% (0.59-0.83) and a specificity of 95% (0.91-0.98)., Conclusions: When using NIHSS for screening and diagnosing aphasia in adults with acute ischemic stroke, patients with severe aphasia can be detected, however, some mild aphasias might be misclassified. Given the 72% sensitivity, absence of aphasia on the NIHSS should not be used to guide stroke treatment., (© 2020 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Introduction: Faculty training awards are an important means of advancing early career faculty in research. The National Institutes of Health (NIH) Building Interdisciplinary Research Careers in Women's Health (BIRCWH) is a long-running K12 career development program and has been integral in promoting the research success of faculty nationally. We surveyed BIRCWH program directors to understand factors likely to influence long-term research careers and funding success., Materials and Methods: We developed an online survey containing open-ended questions about individual and programmatic attributes and activities that promote success in achieving independent research funding. Domains of interest included: 1) strategies for funding success; 2) traits for predicting success; 3) groups considered vulnerable to attrition; and 4) existing resources and means of support., Results: Fifteen institutions (75%) were included in the final analysis. Passion for research, persistence, resilience, and strong mentorship relationships were identified by all directors as factors important to scholar success. Responses also revealed an important pattern: program directors attributed attrition either to individual or organizational characteristics. This distinction has meaningful consequences for framing efforts to diminish attrition. Faculty who were clinicians, women, parents and underrepresented minorities were identified as vulnerable to attrition from the research careers. Common perceived challenges in these groups included isolation/feeling alienated, juggling numerous priorities, inadequate research time, lack of role models, and work-life balance issues., Conclusion: K12 BIRCWH directors identified persistence and resilience and developing community, networks, and other support opportunities as elements of scholar success. Programs and mentors can help early career faculty by teaching skills and providing tools they can use to maximize the value of these opportunities and expand their mentees' research relationships. Our study also highlights the importance of social factors, particularly isolation, on clinicians, women, and minoritized scholars on career success., (Copyright © 2020. Published by Elsevier Inc.)

Aims: Sustained heavy alcohol consumption is associated with a range of neurocognitive deficits. Yet, past research centers on a severe profile of alcohol use disorder (AUD), with persons recruited from in-patient settings. The current project aims to compare neurocognitive performance between individuals seeking AUD outpatient treatment with healthy comparisons while considering the association between performance, disorder severity, and sex., Methods: Enrollment included two matched groups (N = 125; 34 % female): 77 treatment-seeking individuals with AUD; 48 healthy comparison individuals with low drinking patterns. Neurocognitive performance on NIH Toolbox subtests measuring attention, inhibition, episodic memory, working memory, language, and processing speed were compared across groups. Within the AUD group, analyses examined the relationship between performance, disorder severity, recent alcohol consumption, and sex., Results: AUD group did not perform significantly lower than healthy comparisons on neurocognition subtests assessed. Within AUD group, females displayed significantly higher processing speeds than males (p = .007). Disorder severity and alcohol consumption were not significantly related to performance. However, a significant interaction between disorder severity and sex emerged (p = .010), with higher severity associated with poorer performance in males but not females, on a subtest measuring attention and inhibition., Conclusions: Effect of heavy alcohol use on neurocognitive performance was not detected in this outpatient AUD sample. Weaknesses in domains of attention and inhibition may be correlated with AUD severity among males, but not females. Further research on AUD severity and sex in understanding individual differences in neurocognition is warranted, particularly using novel tools for large scale phenotyping, such as the NIH Toolbox., (Copyright © 2020. Published by Elsevier B.V.)

Background: The etiology of myeloproliferative neoplasms (MPN) is obscure, and no previous studies have evaluated the role of diet., Methods: In the NIH-AARP Diet and Health Study, a prospective cohort of 463,049 participants ages 50 to 71 years at baseline (1995-1996), we identified 490 MPN cases after a median follow-up of 15.5 years, including 190 with polycythemia vera (PV) and 146 with essential thrombocythemia (ET). We examined possible associations between various dietary factors and the risk of MPN as a group, as well as PV and ET, using multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) and adjust for potential confounding variables., Results: An increased risk was observed between fruit consumption and the risk of MPN overall (third tertile vs. first tertile, HR = 1.32; 95% CI, 1.04-1.67; P trend = 0.02) and PV (third tertile vs. first tertile, HR = 2.00; 95% CI, 1.35-2.95; P trend < 0.01). Increased risk of PV was also observed among those with high intake of sugar (HR = 1.77; 95% CI, 1.12-2.79), sugar from natural sources (HR = 1.77; 95% CI, 1.16-2.71), sugar from natural beverage sources (HR = 1.57; 95% CI, 1.08-2.29), and fructose (HR = 1.84; 95% CI, 1.21-2.79)., Conclusions: The intake of fat and protein did not appear to influence PV risk-neither did meat or vegetable consumption. None of the dietary factors studied was associated with the risk of ET. The role of sugar intake in the etiology of PV in older individuals warrants further investigation., Impact: Our results indicate that high sugar intake is associated with an increased risk of polycythemia vera., (©2020 American Association for Cancer Research.)

The representation of women and scientists from underrepresented groups (URGs), including Black/African Americans, Hispanic/Latinx, Pacific Islanders, and American Indians, diminishes as individuals advance in their careers from training to senior leadership positions. Correcting this imbalance requires integrated strategies to achieve inclusive excellence within the scientific workforce reflected by creating and sustaining environments, in which diverse talent thrives. The National Institutes of Health (NIH) Scientific Workforce Diversity office has led the charge to develop and implement evidence-informed interventions toward achieving this goal that undergirds NIH's mission to improve the nation's health. Past and current efforts aiming to enhance workforce diversity but targeted to individuals are necessary but insufficient for lasting change. Thus, NIH-funded institutions should develop and prioritize integrated, systems-targeted efforts as foundational components of a well-supported, productive workforce. At the heart of these endeavors is institutional accountability that ties progress toward inclusive excellence to institutional values and reward systems., (© 2020 Federation of American Societies for Experimental Biology.)

Background: Clinical governance of medical mobile apps is challenging, and there is currently no standard method for assessing the quality of such apps. In 2018, the National Institute for Health and Care Excellence (NICE) developed a framework for assessing the required level of evidence for digital health technologies (DHTs), as determined by their clinical function. The framework can potentially be used to assess mobile apps, which are a subset of DHTs. To be used reliably in this context, the framework must allow unambiguous classification of an app's clinical function., Objective: The objective of this study was to determine whether mobile health apps could be reliably classified using the NICE evidence standards framework for DHTs., Methods: We manually extracted app titles, screenshots, and content descriptions for all apps listed on the National Health Service (NHS) Apps Library website on July 12, 2019; none of the apps were downloaded. Using this information, 2 mobile health (mHealth) researchers independently classified each app to one of the 4 functional tiers (ie, 1, 2, 3a, and 3b) described in the NICE digital technologies evaluation framework. Coders also answered contextual questions from the framework to identify whether apps were deemed to be higher risk. Agreement between coders was assessed using Cohen κ statistic., Results: In total, we assessed 76 apps from the NHS Apps Library. There was classification agreement for 42 apps. Of these, 0 apps were unanimously classified into Tier 1; 24, into Tier 2; 15, into Tier 3a; and 3, into Tier 3b. There was disagreement between coders in 34/76 cases (45%); interrater agreement was poor (Cohen κ=0.32, 95% CI 0.16-0.47). Further investigation of disagreements highlighted 5 main explanatory themes: apps that did not correspond to any tier, apps that corresponded to multiple tiers, ambiguous tier descriptions, ambiguous app descriptions, and coder error., Conclusions: The current iteration of the NICE evidence standards framework for DHTs did not allow mHealth researchers to consistently and unambiguously classify digital health mobile apps listed on the NHS app library according to their functional tier., (©Khine Nwe, Mark Erik Larsen, Natalie Nelissen, David Chi-Wai Wong. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.06.2020.)

In response to a policy of the National Institutes of Health and requirements in the revised Common Rule, a protocol for a multisite study must be reviewed by a single institutional review board (IRB), rather than by the IRB at each study site. The goal of the single IRB approach is to increase the efficiency of IRB review of multisite research without jeopardizing protections for research subjects. Yet the extent to which these joint goals are being achieved is unclear. To better understand how single IRBs function, we recruited academic, government, and commercial single IRBs (N = 49) to participate in a study involving observation of protocol review meetings and/or interviews with their members, chairs, and administrators. Twenty (40.8%) agreed to participate, of which 50% agreed to both interviews and observation. While 81.8% (9/11) of academic and 50% (4/8) of government single IRBs participated in some way, only 23.3% (7/30) of commercial single IRBs did so. The four largest commercial single IRBs declined to participate. Because evaluation of single IRBs is important to inform development, implementation, monitoring, and refinement of federal policies, single IRBs should be encouraged to participate in research that examines how they function., (© 2020 by The Hastings Center. All rights reserved.)

This article describes the origins and drafting of the Belmont Report by members of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

Given its outsized influence as a core document in bioethics, it is worth reminding ourselves of the historical context in which the Belmont Report came to be. This article examines the societal forces that helped bring about the Belmont Report and that shaped its conception of ethical research. A product of a public investigation that included many nonscientists and espoused philosophical principles, the Report internalized a growing call in the late 1960s for oversight over the research enterprise, which had long been the private realm of physician-investigators. Belmont helped bring about a regulatory and oversight apparatus to the research enterprise, as well as a language and discipline of bioethics that added a multidisciplinary set of voices and decision-makers to discussions of what constitutes ethical research. Because it reflected the spirit of protectionism engendered by events of the 1960s and 1970s, Belmont also helped emphasize the importance of informed consent and the protection of vulnerable populations. But because the Report was a product of its time, contingent on historical developments and highly publicized events, it is not necessarily responsive to new factors that now condition the research enterprise.

Study Design: Prospective cohort study., Objective: To analyze responsiveness and minimal clinically important change (MCIC) of the US National Institutes of Health (NIH) minimal dataset for chronic low back pain (CLBP)., Summary of Background Data: The NIH minimal dataset is a 40-item questionnaire developed to increase use of standardized definitions and measures for CLBP. Longitudinal validity of the total minimal dataset and the subscale Impact Stratification are unknown., Methods: Total outcome scores on the NIH minimal dataset, Dutch Language Version, were calculated ranging from 0 to 100 points with higher scores representing worse functioning. Responsiveness and MCIC were determined with an anchor-based method, calculating the area under the receiver operating characteristics (ROC) curve (AUC) and by determining the optimal cut-off point. Smallest detectable change (SDC) was calculated as a parameter of measurement error., Results: In total 223 patients with CLBP were included. Mean total score on the NIH minimal dataset was 44 ± 14 points at baseline. The total outcome score was responsive to change with an AUC of 0.84. MCIC was 14 points with a sensitivity of 72% and specificity 82%, and SDC was 23 points. Mean total score on Impact Stratification (scale 8-50) was 34.4 ± 7.4 points at baseline, with an AUC of 0.91, an MCIC of 7.5 with a sensitivity 96% of and specificity of 78%, and an SDC of 14 points., Conclusion: The longitudinal validity of the NIH minimal dataset is adequate. An improvement of 14 points in total outcome score and 7.5 points in Impact Stratification can be interpreted as clinically important in individual patients. However, MCIC depends on baseline values and the method that is chosen to determine the optimal cut-off point. Furthermore, measurement error is larger than the MCIC. This means that individual change scores should be interpreted with caution., Level of Evidence: 2.

Background/aims: Obtaining ethical approval from multiple institutional review boards is a long-standing challenge to multi-site clinical trials and often leads to significant delays in study activation and enrollment. As of 25 January 2018, the National Institutes of Health began requiring use of a single institutional review board for US multi-site trials. To learn more and further inform the research and regulatory communities around aspects of transitioning to single institutional review board review, this study evaluated the efficiency, resource use, and user perceptions of a nascent institutional review board reliance model (Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance)., Methods: This research was embedded within the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure trial-a multi-site trial of two influenza vaccine formulations. In the first year of the trial, a sample of sites agreed to use the developing Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance model and participated in its evaluation. In keeping with a least burdensome approach, short surveys were developed and obtained from each reporting entity (relying sites, non-relying site, lead site, and reviewing institutional review board). Data regarding time to institutional review board approval and site activation, costs, and user perceptions of reliant review were self-reported and collected via the survey form. Quantitative and qualitative analyses were performed, with costs analyzed as actual versus estimated due to the lack of established baseline cost data., Results: A total of 13 sites ceded review and received institutional review board approval. Mean time to approval was substantially faster in sites that ceded review using the Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance model versus the site that did not cede review (81 vs 121 days). The mean time to approval was also faster than published averages for academic medical centers (81 vs 103 days). Time to first enrollment was faster for ceding sites versus the non-ceding site, and also faster than published averages (126 vs 149 and 169 days, respectively). Costs were higher than estimates for local institutional review board review and approval. Nearly half (47%) the stakeholders reported being very satisfied or satisfied with the reliance experience, although many noted the challenge related to institutional culture change., Conclusion: Implementation of a single institutional review board represents a shift in practice and culture for many institutions. Evaluation of the reliance arrangements for this study highlights both the potential of, and challenges for, institutions as they transition to single institutional review board review. Although efficiencies were observed for study start-up, we anticipate a learning curve as institutions and research teams implement necessary process and resource changes to adapt to single institutional review board oversight. Findings may inform research teams but are, however, limited by the relatively small number of sites and lack of a control group.

Objectives: To provide recommendations for the selection of comparators for randomized controlled trials of health-related behavioral interventions., Study Design and Setting: The National Institutes of Health Office of Behavioral and Social Science Research convened an expert panel to critically review the literature on control or comparison groups for behavioral trials and to develop strategies for improving comparator choices and for resolving controversies and disagreements about comparators., Results: The panel developed a Pragmatic Model for Comparator Selection in Health-Related Behavioral Trials. The model indicates that the optimal comparator is the one that best serves the primary purpose of the trial but that the optimal comparator's limitations and barriers to its use must also be taken into account., Conclusion: We developed best practice recommendations for the selection of comparators for health-related behavioral trials. Use of the Pragmatic Model for Comparator Selection in Health-Related Behavioral Trials can improve the comparator selection process and help resolve disagreements about comparator choices., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cognition is an important outcome in many clinical trials. The NIH Toolbox-Cognition Battery (NIHTB-CB) is a computerized cognitive assessment designed for clinical research that is administered in-person. Here, we evaluated the equivalency of a novel videoconference protocol for administering the NIHTB-CB. Since our protocol required repeated assessments, we further explored the NIHTB-CB's practice effect., Materials and Methods: Twenty-five healthy participants completed the NIHTB-CB under two separate conditions 4 weeks apart. The standard condition followed the recommended administration protocol, whereas the videoconference condition had the examiner and participant in separate rooms but able to communicate over videoconference. A linear mixed-model analysis was performed to explore the fixed effect of testing condition and time on NIHTB-CB performance., Results: Across all three NIHTB-CB composite scores (total, fluid, and crystallized cognition), no significant fixed effect of administration condition was found. A significant practice effect was observed for the fluid and total cognition composite scores over a 29.0 (±2.1) day test-retest interval., Conclusions: Our novel videoconference protocol for the NIHTB-CB is equivalent to the standard protocol in healthy participants, and may provide a solution for researchers seeking to engage study participants at remote sites. If the NIHTB-CB is used longitudinally to monitor patients, corrections for repeated measures may be required.

The NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is focused on developing new tools and neurotechnologies to transform our understanding of the brain, and neuroethics is an essential component of this research effort. Coordination with other brain projects around the world will help maximize success., (Published by Elsevier Inc.)

Two hundred patients with severe and/or life-threatening disease were recruited form the NIH Clinical Center and participated in the validation of the NIH-HEALS, which included exploratory factor analysis, principal component analysis, reliability, convergent validity, and divergent validity analyses. Item-reducing principal components analysis and internal consistency and split-half reliability demonstrated excellent internal consistency and split-half reliability (Cronbach's alpha = 0.89, split-half reliability = 0.95). Exploratory factor analysis revealed a three-factor structure, namely Connection (including religious, spiritual, and interpersonal), Reflection & Introspection, and Trust & Acceptance. Seven items were not retained. Convergent and divergent validity of 35-item NIH-HEALS against other validated measures of healing and spirituality provided strong evidence for its validity. As predicted, the Healed factor of the Self-Integration Scale (SIS), and Meaning, Peace, and Faith factors of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being-12 Scale (FACIT-SP12) were all positively and significantly correlated with the NIH-HEALS and its three factors. Divergent validity was also confirmed by the significant negative correlation between the NIH-HEALS and the Codependent factor on the SIS. Confirmatory Factor Analyses revealed good model fit by GFI (0.96), adjusted GFI (0.95), SRMR (0.077), and RMSEA (0.065), supporting the use of the NIH-HEALS with 35 items., Competing Interests: The authors have declared that no competing interests exist.

Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what healthy brain development looks like. A large longitudinal study beginning in early adolescence could help us understand the normal variability in adolescent brain and cognitive development and tease apart the many factors that influence it. Recent advances in neuroimaging, informatics, and genetics technologies have made it feasible to conduct a study of sufficient size and scope to answer many outstanding questions. At the same time, several Institutes across the NIH recognized the value of collaborating in such a project because of its ability to address the role of biological, environmental, and behavioral factors like gender, pubertal hormones, sports participation, and social/economic disparities on brain development as well as their association with the emergence and progression of substance use and mental illness including suicide risk. Thus, the Adolescent Brain Cognitive Development study was created to answer the most pressing public health questions of our day., (Published by Elsevier Ltd.)

The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues., (Published by Elsevier Inc.)

Study Design: Translation and cultural adaptation of the National Institutes of Health (NIH) Task Force's minimal dataset., Objective: The purpose of this study was to evaluate validity and reliability of the Farsi version of NIH Task Force's recommended multidimensional minimal dataset for research on chronic low back pain (CLBP)., Summary of Background Data: Considering the high treatment cost of CLBP and its increasing prevalence, NIH Pain Consortium developed research standards (including recommendations for definitions, a minimum dataset, and outcomes' report) for studies regarding CLBP. Application of these recommendations could standardize research and improve comparability of different studies in CLBP., Methods: This study has three phases: translation of dataset into Farsi and its cultural adaptation, assessment of pre-final version of dataset's comprehensibility via a pilot study, and investigation of the reliability and validity of final version of translated dataset. Subjects were 250 patients with CLBP. Test-retest reliability, content validity, and convergent validity (correlations among different dimensions of dataset and Farsi versions of Oswestry Disability Index, Roland Morris Disability Questionnaire, Fear-Avoidance Belief Questionnaire, and Beck Depression Inventory-II) were assessed., Results: The Farsi version demonstrated good/excellent convergent validity (the correlation coefficient between impact dimension and ODI was r = 0.75 [P < 0.001], between impact dimension and Roland-Morris Disability Questionnaire was r = 0.80 [P < 0.001], and between psychological dimension and BDI was r = 0.62 [P < 0.001]). The test-retest reliability was also strong (intraclass correlation coefficient value ranged between 0.70 and 0.95) and the internal consistency was good/excellent (Chronbach's alpha coefficients' value for two main dimensions including impact dimension and psychological dimension were 0.91 and 0.82 [P < 0.001], respectively). In addition, its face validity and content validity were acceptable., Conclusion: The Farsi version of minimal dataset for research on CLBP is a reliable and valid instrument for data gathering in patients with CLBP. This minimum dataset can be a step toward standardization of research regarding CLBP., Level of Evidence: 3.

Despite advances in our understanding of the pathophysiology and the management of pulmonary arterial hypertension (PAH), significant therapeutic gaps remain for this devastating disease. Yet, few innovative therapies beyond the traditional pathways of endothelial dysfunction have reached clinical trial phases in PAH. Although there are inherent limitations of the currently available models of PAH, the leaky pipeline of innovative therapies relates, in part, to flawed preclinical research methodology, including lack of rigour in trial design, incomplete invasive hemodynamic assessment, and lack of careful translational studies that replicate randomized controlled trials in humans with attention to adverse effects and benefits. Rigorous methodology should include the use of prespecified eligibility criteria, sample sizes that permit valid statistical analysis, randomization, blinded assessment of standardized outcomes, and transparent reporting of results. Better design and implementation of preclinical studies can minimize inherent flaws in the models of PAH, reduce the risk of bias, and enhance external validity and our ability to distinguish truly promising therapies form many false-positive or overstated leads. Ideally, preclinical studies should use advanced imaging, study several preclinical pulmonary hypertension models, or correlate rodent and human findings and consider the fate of the right ventricle, which is the major determinant of prognosis in human PAH. Although these principles are widely endorsed, empirical evidence suggests that such rigor is often lacking in pulmonary hypertension preclinical research. The present article discusses the pitfalls in the design of preclinical pulmonary hypertension trials and discusses opportunities to create preclinical trials with improved predictive value in guiding early-phase drug development in patients with PAH, which will need support not only from researchers, peer reviewers, and editors but also from academic institutions, funding agencies, and animal ethics authorities., (© 2018 American Heart Association, Inc.)

The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Study Design: Validation study with cross-sectional and longitudinal measurements., Objective: To translate the US National Institutes of Health (NIH)-minimal dataset for clinical research on chronic low back pain into the Dutch language and to test its validity and reliability among people with chronic low back pain., Summary of Background Data: The NIH developed a minimal dataset to encourage more complete and consistent reporting of clinical research and to be able to compare studies across countries in patients with low back pain. In the Netherlands, the NIH-minimal dataset has not been translated before and measurement properties are unknown., Methods: Cross-cultural validity was tested by a formal forward-backward translation. Structural validity was tested with exploratory factor analyses (comparative fit index, Tucker-Lewis index, and root mean square error of approximation). Hypothesis testing was performed to compare subscales of the NIH dataset with the Pain Disability Index and the EurQol-5D (Pearson correlation coefficients). Internal consistency was tested with Cronbach α and test-retest reliability at 2 weeks was calculated in a subsample of patients with Intraclass Correlation Coefficients and weighted Kappa (κω)., Results: In total, 452 patients were included of which 52 were included for the test-retest study., Validity: factor analysis for structural validity pointed into the direction of a seven-factor model (Cronbach α = 0.78). Factors and total score of the NIH-minimal dataset showed fair to good correlations with Pain Disability Index (r = 0.43-0.70) and EuroQol-5D (r = -0.41 to -0.64). Reliability: test-retest reliability per item showed substantial agreement (κω=0.65). Test-retest reliability per factor was moderate to good (Intraclass Correlation Coefficient = 0.71)., Conclusion: The Dutch language version measurement properties of the NIH-minimal were satisfactory., Level of Evidence: N/A.

Introduction: The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function Cognition Battery is comprised of seven cognitive tests, including two tests measuring crystallized cognitive ability (i.e., vocabulary and reading) and five tests measuring fluid cognitive functioning (i.e., working memory, memory, speed of processing, and executive functioning). This study presents comprehensive base rate tables for the frequency of low scores in adults and older adults from the normative sample., Methods: Participants were 843 adults, ages 20-85, from the NIH Toolbox standardization sample who completed all seven cognition tests. Rates of low scores were derived for standard age-adjusted and fully-demographically-adjusted scores at multiple cut-scores. Base rates were stratified by education, crystallized intellectual ability, and cognitive domain., Results: Using the five demographically-adjusted fluid cognitive test scores, 45.9% of adults obtained one or more scores at or below the 16th percentile, and 16.8% obtained one or more score at or below the 5th percentile, which is consistent with findings from other neurocognitive test batteries., Discussion: Based on the study findings, nearly 50% of adults in the general population would meet psychometric criteria for a diagnosis of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) Mild Neurocognitive Disorder (MND). We developed new psychometric criteria for identifying MND using the NIH Toolbox Cognition Battery that reduce the false positive rate. Knowing these multivariate normative base rates will help researchers and clinicians interpret NIH Toolbox scores in people with neurodevelopmental, psychiatric, medical, neurological, and neurodegenerative disorders that affect cognitive functioning., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cognition, psychological well-being, stress, functional status, and pain are all priority outcomes of interest to oncology nurses. However, it can be challenging to choose an instrument for clinical assessment or for use in research projects that assess these constructs. The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function was created for measuring emotional health and cognitive, motor, and sensory function. The toolbox can be a potentially useful resource for clinicians and nurse researchers.

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple clinical selection strategies., Methods: Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry (January 2012-May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery)., Results: Among 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.8-5.3). All 3 face-arm-speech-time test (FAST) items identified LAVO with high sensitivity. Addition of the item gaze to the original FAST score (G-FAST) or high scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with an NIHSS threshold of ≥6, the prehospital stroke scales performed similarly or even better without losing sensitivity., Conclusions: Simple modification of the face-arm-speech-time score or evaluating the NIHSS symptom profile may help to stratify patients' risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers. Prospective validation in the prehospital setting is required., (© 2017 American Heart Association, Inc.)

In June 2015, the National Institutes of Health (NIH) released a Guide notice (NOT-OD-15-102) that highlighted the expectation of the NIH that the possible role of sex as a biologic variable be factored into research design, analyses, and reporting of vertebrate animal and human studies. Anticipating these guidelines, the NIH Office of Research on Women's Health, in October 2014, convened key stakeholders to discuss methods and techniques for integrating sex as a biologic variable in preclinical research. The workshop focused on practical methods, experimental design, and approaches to statistical analyses in the use of both male and female animals, cells, and tissues in preclinical research. Workshop participants also considered gender as a modifier of biology. This article builds on the workshop and is meant as a guide to preclinical investigators as they consider methods and techniques for inclusion of both sexes in preclinical research and is not intended to prescribe exhaustive/specific approaches for compliance with the new NIH policy.-Miller, L. R., Marks, C., Becker, J. B., Hurn, P. D., Chen, W.-J., Woodruff, T., McCarthy, M. M., Sohrabji, F., Schiebinger, L., Wetherington, C. L., Makris, S., Arnold, A. P., Einstein, G., Miller, V. M., Sandberg, K., Maier, S., Cornelison, T. L., Clayton, J. A. Considering sex as a biological variable in preclinical research., (© FASEB.)

Background and Purpose: We compared baseline characteristics and outcomes at 3 months between patients with minor anterior circulation infarction (ACI) versus minor posterior circulation infarction (PCI), including the influence of large vessel disease on outcomes., Methods: This study is an analysis of a prospective multicenter registry database in South Korea. Eligibility criteria were patients with ischemic stroke admitted within 7 days of stroke onset, lesions in either anterior or posterior circulation, and National Institutes of Health Stroke Scale score of ≤4 at baseline. Patients were divided into 4 groups for further analysis: minor ACI with and without internal carotid artery/middle cerebral artery large vessel disease and minor PCI with and without vertebrobasilar large vessel disease., Results: A total of 7178 patients (65.2±12.6 years) were analyzed in this study, and 2233 patients (31.1%) had disability (modified Rankin Scale score 2-6) at 3 months. Disability was 32.3% in minor PCI and 30.3% in minor ACI (P=0.07), and death was 1.3% and 1.5%, respectively (P=0.82). In a multivariable logistic regression analysis, minor PCI was significantly associated with disability at 3 months when compared with minor ACI (odds ratio, 1.23; 95% confidence interval, 1.09-1.37; P<0.001). In pairwise comparisons, minor PCI with vertebrobasilar large vessel disease was independently associated with disability at 3 months, compared with the other 3 groups., Conclusions: Our study showed that minor PCI exhibited more frequent disability at 3 months than minor ACI. Especially, the presence of vertebrobasilar large vessel disease in minor PCI had a substantially higher risk of disability. Our results suggest that minor PCI with vertebrobasilar large vessel disease could require more meticulous care and are important targets for further study., (© 2016 American Heart Association, Inc.)

The recently implemented National Institutes of Health policy requiring that grant applicants consider sex as a biological variable in the design of basic and preclinical animal research studies has prompted considerable discussion within the neuroscience community. Here, we present reasons to be optimistic that this new policy will be valuable for neuroscience, and we suggest some ways for neuroscientists to think about incorporating sex as a variable in their research., (Copyright © 2016 the authors 0270-6474/16/3611817-06$15.00/0.)

Background: In acute stroke, it is crucial to assess for intracranial large-vessel occlusion and site of occlusion. The National Institutes of Health Stroke Scale score (NIHSSS) is the frequently used clinical tool to predict the site of arterial occlusion. In this study we aimed to determine the following: (1) if there is a correlation between the site of occlusion and the NIHSSS at presentation (bNIHSSS); and (2) if there is a bNIHSSS cutoff which can distinguish proximal occlusions (PO) from distal occlusions (DO)., Methods: Up to 313 patients from CLOTBUST data bank with demonstrable intracranial arterial occlusion and having received intravenous recombinant tissue plasminogen activator (rt-PA) were included. Occlusions were classified as PO (terminal internal carotid artery, M1 segment of middle cerebral artery [M1 MCA], and basilar artery) or DO (M2 MCA, anterior cerebral artery, posterior cerebral artery, and vertebral artery)., Results: By univariate analysis, bNIHSSS, thrombolysis in brain ischemia (TIBI) flow grade before rt-PA, degree of recanalization after rt-PA, and modified Rankin Scale score at 3 months were significantly different between various sites of occlusion. By univariate analysis, a higher bNIHSSS, lower TIBI flow grade, and lower ASPECTS (Alberta Stroke Program Early CT Score) differentiated PO from DO. Lower TIBI flow grade and higher bNIHSSS differentiated PO from DO by logistic regression analysis. No single NIHSSS cutoff with acceptable sensitivity and specificity could be derived to differentiate PO from DO., Conclusions: Although NIHSSS are higher in PO, there is no satisfactory NIHSSS cutoff which differentiates PO from DO. A vascular imaging or transcranial doppler should be obtained to determine the site of arterial occlusion in acute stroke., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The benefits of intravenous tissue-type plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) are time dependent. Because emergency rooms quickly initiate a stroke alert with more severe symptoms, we hypothesized that patients with lower National Institutes of Health Stroke Scale (NIHSS) scores, indicating a less severe stroke, would have longer door-to-needle (DTN) times compared to patients with higher NIHSS scores., Methods: Data obtained from the 19-hospital Providence Stroke Registry were used to identify AIS patients who received IV-tPA within 4.5 hours of last-known-well. NIHSS scores were obtained prior to tPA administration at the time of emergency department presentation and categorized as low-NIHSS (score = 0-5) or high-NIHSS (score = 6-42) strokes. Median DTN times were collected for both groups as the primary outcome variable. Linear mixed-effects regression models were used to assess the effect of NIHSS scores on DTN and its 2 components: door-to-CT (DCT) and CT-to-needle (CTN) times., Results: We identified 692 AIS patients who received IV-tPA within 4.5 hours of last-known-well, with 198 patients presenting with low-NIHSS strokes and 494 patients with high-NIHSS strokes. In multivariable analysis, median DTN time was estimated to be 18% higher for low-NIHSS strokes than high-NIHSS strokes after adjusting for covariates (P < .001). Median DCT times were also higher for low-NIHSS (19 minutes) compared to high-NIHSS (11 minutes) strokes after adjusting for covariates (P < .001), whereas CTN times were unchanged (P = .055)., Conclusion: In AIS patients receiving IV-tPA in a telestroke network, lower NIHSS scores were associated with longer DTN and DCT times., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Simple clinical scores to predict large vessel occlusion (LVO) in acute ischemic stroke would be helpful to triage patients in the prehospital phase. We assessed the ability of various combinations of National Institutes of Health Stroke Scale (NIHSS) subitems and published stroke scales (i.e., RACE scale, 3I-SS, sNIHSS-8, sNIHSS-5, sNIHSS-1, mNIHSS, a-NIHSS items profiles A-E, CPSS1, CPSS2, and CPSSS) to predict LVO on CT or MR arteriography in 1085 consecutive patients (39.4 % women, mean age 67.7 years) with anterior circulation strokes within 6 h of symptom onset. 657 patients (61 %) had an occlusion of the internal carotid artery or the M1/M2 segment of the middle cerebral artery. Best cut-off value of the total NIHSS score to predict LVO was 7 (PPV 84.2 %, sensitivity 81.0 %, specificity 76.6 %, NPV 72.4 %, ACC 79.3 %). Receiver operating characteristic curves of various combinations of NIHSS subitems and published scores were equally or less predictive to show LVO than the total NIHSS score. At intersection of sensitivity and specificity curves in all scores, at least 1/5 of patients with LVO were missed. Best odds ratios for LVO among NIHSS subitems were best gaze (9.6, 95 %-CI 6.765-13.632), visual fields (7.0, 95 %-CI 3.981-12.370), motor arms (7.6, 95 %-CI 5.589-10.204), and aphasia/neglect (7.1, 95 %-CI 5.352-9.492). There is a significant correlation between clinical scores based on the NIHSS score and LVO on arteriography. However, if clinically relevant thresholds are applied to the scores, a sizable number of LVOs are missed. Therefore, clinical scores cannot replace vessel imaging.

In the midst of the recent Ebola outbreak, scientific developments involving infection challenge experiments on nonhuman primates (NHPs) sparked hope that successful treatments and vaccines may soon become available. Yet these studies pose a stark ethical quandary. On the one hand, they represent an important step in developing novel therapies and vaccines for Ebola and the Marburg virus, with the potential to save thousands of human lives and to protect whole communities from devastation; on the other hand, they intentionally expose sophisticated animals to severe suffering and a high risk of death. Other studies that infect NHPs with a lethal disease in order to test interventions that may prove beneficial for humans pose the same ethical difficulty. Some advocates have argued that all research on primates should be phased out, and ethicists have questioned whether a moral justification of primate research is possible. A 2010 European Union directive banned virtually all research on great apes, and 2013 guidelines from the National Institutes of Health (NIH), based upon recommendations in an influential 2011 Institute of Medicine (IOM) report, eliminated most biomedical research with chimpanzees in the United States. But studies involving other NHPs face no comparable restrictions. Should research on NHPs other than great apes be subject to tighter restrictions than it currently is? In this article, we explore this general question in the context of one particular type of biomedical research: infection challenge studies. We advocate a presumptive prohibition on infection challenge experiments in NHPs, but we also argue that exceptions to this prohibition are permissible, subject to strict substantive and procedural safeguards, when necessary to avert substantial loss of human life or severe morbidity for a substantial number of people., (© 2016 The Hastings Center.)

In June 2015, the National Institutes of Health (NIH) of the USA published a new funding guideline entitled "Consideration of Sex as a Biological Variable in NIH-funded Research". This guideline is part of the NIH policy to enhance quality and generalizability of health research. Its core element is the classification of sex as a key element of rigorous study designs. The requirement is that sex be defined as a biological variable, and taking the potentially relevant sex/gender related anatomical and physiological characteristics into account. In Germany, the "Guidelines and recommendations to assure good epidemiological practice" (GEP) of 1998 specify that the study design and research methods are to be designed so that sex/gender-specific aspects of the research question can be adequately detected. Mostly health research is restricted to the categorization of the study population into men and women and to the consideration of the sex/gender variable (man*woman) in the analyses. Research in accordance with the NIH guideline as well as with the German GEP needs to investigate differences and similarities between men and women, and also to look for factors that explain in what way being a man or a woman poses a risk or is protective against the development of diseases. This scientific basis is essential for the development and implementation of sex/gender equitable prevention, health promotion and health care, which in turn enables statutory health insurances to take sex/gender differences into account regarding the medical services they provide. The latter is a consequence of the current legal position in Germany, which is based on the Prevention law that was passed in 2015. In addition to the categorical sex/gender variable (man*woman), there is therefore the need to analytically differentiate between the dimensions sex (the biological factors) and gender (the socio-cultural ascriptions) as well as their interaction. For conceptual clarity, this paper proposes that the terms sex and/or gender be used only where the biological and/or socio-cultural aspects of being a man or a woman are explicitly taken into account. For the common sex/gender variable man*woman (based on self-reports, register data etc.) the term Survey sex (German: Erhebungsgeschlecht) can be used. Further, the establishment of a Federal Institute "Geschlecht und Gesundheit - Sex/Gender and Health" is recommended., (© Georg Thieme Verlag KG Stuttgart · New York.)

In May 2014, Dr. Francis Collins, the director of U.S. National Institutes of Health (NIH), and Dr. Janine Clayton, the director of the U.S. National Institutes of Health Office of Research on Women's Health, published a commentary in the journal Nature announcing new policies to ensure that preclinical research funded by the NIH considers both males and females. While these policies are still developing, they have already generated great interest by the scientific community and triggered both criticism and applause. This review provides a description and interpretation of the NIH guidelines, and it traces the history that led to their implementation. As expected, this NIH initiative generated some anxiety in the scientific community. The use of female animals in the investigation of basic mechanisms is perceived to increase variability in the results, and the use of both sexes has been claimed to slow the pace of scientific discoveries and to increase the cost at a time characterized by declining research support. This review discusses issues related to the study of sex as a biological variable (SABV) in alcohol studies and provides examples of how researchers have successfully addressed some of them. A practical strategy is provided to include both sexes in biomedical research while maintaining control of the research direction. The inclusion of sex as an important biological variable in experimental design, analysis, and reporting of preclinical alcohol research is likely to lead to a better understanding of alcohol pharmacology and the development of alcohol use disorder, may promote drug discovery for new pharmacotherapies by increasing scientific rigor, and may provide clinical benefit to women's health. This review aims to promote the understanding of the NIH's SABV guidelines and to provide alcohol researchers with a theoretical and practical framework for working with both sexes in preclinical research., (Copyright © 2016 by the Research Society on Alcoholism.)

Background: The National Institutes of Health (NIH) recommend that health materials be written at a grade 6-7 reading level, which has generally not been achieved in online reading materials. Up to the present time, there have not been any assessments focused on the reading level of online educational materials across the most popular consumer Web sites for common internal medicine diagnoses. In this study, we examined the readability of open-access online health information for 9 common internal medicine diagnoses., Methods: Nine of the most frequently encountered inpatient and ambulatory internal medicine diagnoses were selected for analysis. In November and December 2014, these diagnoses were used as search terms in Google, and the top 5 Web sites across all diagnoses and a diagnosis-specific site were analyzed across 5 validated reading indices., Results: On average, the lowest reading grade-level content was provided by the NIH (10.7), followed by WebMD (10.9), Mayo Clinic (11.3), and diagnosis-specific Web sites (11.5). Conversely, Wikipedia provided content that required the highest grade-level readability (14.6). The diagnoses with the lowest reading grade levels were chronic obstructive pulmonary disease (10.8), followed by diabetes (10.9), congestive heart failure (11.7), osteoporosis (11.7) and hypertension (11.7). Depression had the highest grade-level readability (13.8)., Discussion: Despite recommendations for patient health information to be written at a grade 6-7 reading level, our examination of online educational materials pertaining to 9 common internal medicine diagnoses revealed reading levels significantly above the NIH recommendation. This was seen across both diagnosis-specific and general Web sites. There is a need to improve the readability of online educational materials made available to patients. These improvements have the potential to greatly enhance patient awareness, engagement, and physician-patient communication., (Published by Elsevier Inc.)

Both bipolar disorder and borderline personality disorder (BPD) are serious mental health disorders resulting in significant psychosocial morbidity, reduced health-related quality of life, and excess mortality. Yet research on BPD has received much less funding from the National Institute of Health (NIH) than has bipolar disorder during the past 25 years. Why hasn't the level of NIH research funding for BPD been commensurate with the level of psychosocial morbidity, mortality, and health expenditures associated with the disorder? In the present article, the author illustrates how the bipolar disorder research community has done a superior job of "marketing" their disorder. Studies of underdiagnosis, screening, diagnostic spectra, and economics are reviewed for both bipolar disorder and BPD. Researchers of bipolar disorder have conducted multiple studies highlighting the problem with underdiagnosis, developed and promoted several screening scales, published numerous studies of the operating characteristics of these screening measures, attempted to broaden the definition of bipolar disorder by advancing the concept of the bipolar spectrum, and repeatedly demonstrated the economic costs and public health significance of bipolar disorder. In contrast, researchers of BPD have almost completely ignored each of these four issues and research efforts. Although BPD is as frequent as (if not more frequent than) bipolar disorder, as impairing as (if not more impairing than) bipolar disorder, and as lethal as (if not more lethal than) bipolar disorder, it has received less than one-tenth the level of funding from the NIH and has been the focus of many fewer publications in the most prestigious psychiatric journals. The researchers of BPD should consider adopting the strategy taken by researchers of bipolar disorder before the diagnosis is eliminated in a future iteration of the DSM or the ICD.