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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.

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.)

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.

In May 2014, the U.S. National Institutes of Health (NIH) announced that it will ensure that investigators account for sex as a biological variable (SABV) in NIH-funded preclinical research as part of the agency's rigor and transparency initiative. Herein, I describe in more detail the rationale behind the SABV policy component and provide additional detail about policy goals. In short, studying both sexes is a guiding principle in biomedical research that will expand knowledge toward turning discovery into health. NIH expects that considering SABV in preclinical research will help to build a knowledge base that better informs the design of clinical research and trials in humans. Integrating the practice of studying both sexes in preclinical research will, over time, expand our currently incomplete knowledge base that plays a critical role in informing the development of sex- and gender-appropriate medical care for women and men., (© FASEB.)

Given the recent National Institutes of Health proposal for balanced use of male and female cells and animals in preclinical studies, we explored whether sex bias exists in skin research. We surveyed 802 dermatological research articles from 2012 through 2013. No information about the sex of studied cells or animals was provided in 60% of papers. Among keratinocytes of known sex, 70% were male. Few studies compared male versus female cells or animals. Disclosure of sex and comparative studies contribute to our understanding of the biologic basis of sex differences. Addressing sex-specific differences in preclinical research informs subsequent clinical trial design and promotes individualized therapy., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) awards higher deficit scores for infarcts in the dominant hemisphere when compared with otherwise similar infarcts in the nondominant hemisphere. This has been shown to adversely affect stroke recognition, therapeutic decisions, and outcome. However, factors modifying the association between infarct side and deficit severity are incompletely understood. Thus, we sought to determine whether age and age-related leukoaraiosis alter the relation between NIHSS deficit score and the side and volume of infarction., Methods: We studied 238 patients with supratentorial, nonlacunar ischemic infarcts prospectively included in our stroke registry between January 2013 and January 2014. NIHSS deficit severity was assessed at the time of presentation. Infarct volumes were assessed by manual planimetry on diffusion-weighted imaging. Leukoaraiosis burden was graded on fluid-attenuated inversion recovery images according to the Fazekas scale and dichotomized to none-to-mild (0-2) versus severe (3-6). Multivariable linear regression with backward elimination was used to identify independent predictors of the admission NIHSS., Results: Left-hemispheric infarction (P<0.001), severe leukoaraiosis (P=0.001), their interaction term (P=0.005), infarct volume (P<0.001), and sex (P=0.013) were independently associated with the NIHSS deficit. Analysis of the individual NIHSS components showed that severe leukoaraiosis was associated with an increase of the lateralizing components of the NIHSS in patients with right-hemispheric infarction (P<0.05)., Conclusions: Severe leukoaraiosis substantially attenuates the classic hemispheric lateralization of the NIHSS deficit by relating to greater NIHSS scores of components that are typically assigned to left hemisphere function., (© 2015 American Heart Association, Inc.)

Background and Purpose: The 15-item National Institutes of Health Stroke Scale (NIHSS) has been critiqued for its complexity and variability, and shortened versions have been proposed. This study aimed to compare the measurement properties of the original version with 3 shortened versions with 11, 8, and 5 items, respectively., Methods: Analyses were performed using data from an international, double-blind randomized controlled trial investigating the efficacy of MLC601 on stroke recovery in patients with ischemic stroke of intermediate severity (Chinese Medicine Neuroaid Efficacy on Stroke recovery [CHIMES]). To compare discriminative ability and responsiveness to change, the effect sizes of the NIHSS scores in relation to modified Rankin Scale, mini-mental status examination, and Barthel index were estimated using regression analysis., Results: For both discriminative ability and responsiveness to change, the original version exhibited a larger effect size (0.55 and 0.84) in relation to modified Rankin Scale than the other 3 shortened versions (0.35-0.46 and 0.74-0.78)., Conclusions: The original 15-item NIHSS retained information that made it more discriminative and responsive to change than the shortened versions. We recommend future clinical researchers to use the full version NIHSS to evaluate patients' stroke severity., Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00554723., (© 2015 American Heart Association, Inc.)

Introduction: The National Institutes of Health Stroke Scale (NIHSS), the most commonly used tool to quantify neurological deficit in acute stroke, was initially developed in English. We present our experience in developing and validating an Arabic version of the NIHSS (arNIHSS)., Results: In 6months, 137 patients were recruited (mean age±standard deviation 62±12years; 48 women). For interrater agreement, weighted kappa value ranged from 0.36 to 0.66 and intraclass correlation coefficient (ICC) for the whole scale was excellent at 0.95 (95% confidence interval [CI] 0.94-0.97). For intrarater agreement, weighted kappa ranged from 0.52 to 1.0 and the ICC was 0.94 (95% CI 0.87-0.98). The construct validity of the arNIHSS is demonstrated by its correlation with the DWI-ASPECT and the 3months mRS score (Spearman correlation -0.46 and 0.58 respectively; P<0.001 for both)., Conclusion: We developed and validated a culturally adapted Arabic version of the NIHSS. Further validation in other Arab countries is recommended., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The National Institutes of Health Stroke Scale (NIHSS) is purported to be associated with long-term outcomes. This study determined the concurrent validity of the NIHSS with the Stroke Impact Scale (SIS), a previously validated measure of health status in chronic stroke survivors., Methods: The NIHSS and the SIS were administered to 147 subjects before participation in a multicenter, randomized, controlled trial. A Spearman's rho was used to determine correlations between NIHSS total score and (1) SIS physical dimension scores, (2) SIS overall perception of recovery scores, and (3) the SIS activities and independent activities of daily living (ADL/IADL) scores. SIS score variation and medians between subjects who scored a zero versus a nonzero on the NIHSS was also assessed., Results: There was no association between total NIHSS scores and SIS physical dimension scores, SIS overall perception of recovery scores, and SIS ADL/IADL scores (P = -.036, P = .782; P = -.039, P = .640; P = -.054, P = .520; respectively). Lastly, significant variation and similar median scores on the SIS were found between those scoring a zero on the NIHSS versus those who did not score a zero., Conclusions: The NIHSS has no association with health status in chronic stroke and lacks association with measures of impairment and functional limitation. From these findings, we conclude that the NIHSS has poor validity to discern long-term poststroke outcomes and is not associated with health status. Because of possible limitation in the NIHSS's ability to accurately determine outcomes in this population, we recommend restriction of its use to the acute stage of recovery., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Patients increasingly consult online resources for healthcare information. The American Medical Association (AMA) and National Institutes of Health (NIH) recommend that online education resources be written between a 3rd- and 7th-grade level. This study assesses whether online health information abides by these guidelines., Methods: Ten pediatric ophthalmology conditions were entered into a commonly used search engine, Google.com, and analyzed using 10 validated readability scales. Scientific articles and articles written on patient forums were excluded. The 10 conditions--amblyopia, cataract, conjunctivitis, corneal abrasion, nystagmus, retinoblastoma, retinopathy of prematurity, strabismus, stye, and glaucoma--were also searched and analyzed separately from widely used websites, including Wikipedia and WebMD, as well as those of professional societies, including the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) and the American Optometric Association (AOA)., Results: The majority of articles were written above recommended guidelines. All scales showed that the 100 articles were written at a mean grade-level of 11.75 ± 2.72. Only 12% of articles were written below a 9th-grade level and only 3% met recommended criteria. The articles accrued separately from Wikipedia, WebMD, AAPOS, and AOA also had average grade levels above the recommended guidelines., Conclusions: The readability of online patient education material exceeds NIH and AMA guidelines. This disparity can adversely affect caregiver comprehension of such resources and contribute to poor decision making. Pediatric ophthalmology online articles are generally written at a level too high for average caregiver comprehension. Revision of articles can increase satisfaction, improve outcomes, and facilitate the patient-ophthalmologist relationship., (Published by Elsevier Inc.)

Chronic graft versus host disease (cGvHD) is the most common cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated the impact of NIH classification on outcome of patients at our center. Primary endpoint was overall survival at 5 years. Two hundred one patients with cGVHD according to NIH were included. Platelets <100,000/μl on day of diagnosis of cGvHD (HR 2.97, 95 % CI 1.7-5.3, p < 0.001), female donor (HR 1.78, 95 % CI 1.0-3.2, p = 0.05), and reduced intensity conditioning (HR 1.95, 95 % CI 1.0-3.8, p = 0.05) impacted overall survival. Non-relapse mortality (NRM) was higher for patients with low vs. high platelets: 26 % (95 % CI 14-40) vs. 6 % (95 % CI 2-10), p < 0.001, and tended to be higher for female vs. male donor: 14 % (95 % CI 7-23) vs. 7 % (95 % CI 3-13), p = 0.08. Relapse tended to be higher for recipients of reduced intensity conditioning (RIC) vs. myeloablative conditioning (MAC): 33 % (95 % CI 23-43) vs. 20 % (95 % CI 10-31), p = 0.06. After excluding patients with myeloma and lymphoma, IgG serum levels at diagnosis of cGvHD of 122 patients were correlated with survival. IgG levels above normal were associated with worse 2-year overall survival (OS), p = 0.04, compared to normal or low IgG levels. Platelet count at diagnosis remains the most valid prognostic factor for survival of patients with cGvHD even in the era of NIH grading. High IgG level at diagnosis of cGVHD represents a potential negative prognostic parameter that deserves further investigation.

Background: The present study aimed to evaluate the relation between the National Institutes of Health Stroke Scale (NIHSS) score and the presence of laryngeal penetration and/or laryngotracheal aspiration in ischemic stroke patients and to verify what factors are predictors of the occurrence of pneumonia in the evaluated patients., Methods: This was an observational study of ischemic stroke in the acute or subacute phases. Neurologic examination included anamnesis, Bamford classification, and application of the NIHSS. Speech therapy evaluation was carried out after clinical stabilization of the patient, and all individuals who were considered dysphagic were sent for examination by means of videofluoroscopic recordings. The parameters observed in the objective examination were the presence of laryngeal penetration and/or laryngotracheal aspiration. The pneumonia data were obtained in accordance with local protocols, which were based on international guidelines. The relation of laryngeal penetration and laryngotracheal aspiration with the NIHSS score was assessed by the Mann-Whitney U test, and predictors for the occurrence of pneumonia were analyzed by multiple logistic regression using semiautomatic backward selection. Significance was set at P less than .05., Results: The relations between laryngeal penetration and the NIHSS score and between laryngotracheal aspiration and the NIHSS score were not statistically significant. The predictors for pneumonia occurrence in the ischemic stroke patients with a clinical diagnosis of dysphagia were age (P = .002; odds ratio [OR], 1.12) and NIHSS score (P = .04; OR, 1.17), whereas laryngeal penetration of liquid (P = .065; OR, 3.70) tended to correlate with pneumonia but not significantly., Conclusions: There was no relation between the NIHSS score and laryngeal penetration or laryngotracheal aspiration, and the principal predictors of pneumonia in dysphagic patients after ischemic stroke were advanced age and neurologic severity., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Fatigue is a complex, multidimensional condition. Although it is often associated with depression, it is not known whether it has a distinct network from depression or whether it can be clinically evaluated, separately. This study describes preliminary findings in the development of a brief, clinician-administered instrument to measure fatigue in the context of depressive disorders using items from existing clinician-administered depression and mania scales., Methods: Based on items from prior fatigue measurements, items were selected from the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale, and Structured Interview Guide for HDRS with Atypical Depression. The final items composed the NIH-Brief Fatigue Inventory (NIH-BFI). Responses from 89 depressed adults collected pre- and post-antidepressant therapy (ADT) determined the reliability and consistency of the NIH-BFI using Cronbach's alpha and principal components analysis (PCA). Correlations of the NIH-BFI and fatigue items from other scales before and after ADT explored validity., Results: The 7-item NIH-BFI had Cronbach alphas ranging from 0.81 to 0.88 and PCA indicating a single dimension. The NIH-BFI score was strongly correlated (r = 0.73, p < 0.001) with fatigue items from Beck Depression Index, with MADRS without fatigue items (r = 0.77, p < 0.001), and HDRS without fatigue items (pre: r = 0.69, p < 0.001)., Conclusions: Preliminary findings show support for internal consistency reliability and validity of the NIH-BFI, a clinician-administered measure of fatigue. Further testing in other clinical populations is recommended to obtain additional information on reliability and validity. The NIH-BFI provides a method for clinician-rated fatigue that may be a separate from depression., (Published by Elsevier Ltd.)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) provides a reliable, quantitative measure of ischemic stroke severity and is predicted by the infarct size. We sought to determine whether leukoaraiosis severity affects the association between infarct size and NIHSS., Methods: NIHSS and diffusion-weighted imaging-defined infarct volumes from 312 prospectively enrolled patients with supratentorial, ischemic strokes were analyzed. Leukoaraiosis severity was graded according to the Fazekas scale and conceptually defined as absent (0; n=44), mild (1-2; n=106), moderate (3-4; n=105), and severe (5-6; n=57). ANCOVA was used to describe the effect of leukoaraiosis on the association between infarct volume and NIHSS. Multivariable linear regression models were constructed to assess whether the association of leukoaraiosis and infarct volume on NIHSS was independent of other clinically relevant covariates., Results: Overall, there was a significant correlation between the infarct volume and NIHSS (r=0.591; P<0.001). This correlation significantly attenuated with increasing leukoaraiosis severity from r=0.786 (P<0.001; absent leukoaraiosis) to r=0.498 (P<0.001; severe leukoaraiosis) and as shown by ANCOVA (P<0.001). Leukoaraiosis (coefficient, 0.107; 95% confidence interval, 0.036-0.179; P=0.016) and infarct volume (coefficient, 0.360; 95% confidence interval, 0.305-0.416; P<0.001) were independently associated with a greater NIHSS deficit in the fully adjusted multivariable model., Conclusions: Leukoaraiosis significantly modulates the association between infarct volume and NIHSS. The clinical implications of these findings need further exploration in prospective studies but may be relevant to mitigate outcome differences in patients with stroke by aiding treatment decisions that rely on the NIHSS., (© 2015 American Heart Association, Inc.)

Objective: To evaluate the methodologic quality of 3 primary open-angle glaucoma (POAG) clinical practice guidelines (CPGs)., Design: The CPGs were assessed with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument., Participants: Four authors (A.M.W., C.M.W., B.K.Y., D.J.W.) performed independent assessments of POAG CPGs., Methods: POAG CPGs published by the American Academy of Ophthalmology (AAO), Canadian Ophthalmological Society (COS), and National Institute for Health and Care Excellence (NICE) were appraised using the AGREE II instrument's 6 domains (Scope and Purpose, Stakeholder Involvement, Rigor of Development, Clarity of Presentation, Applicability, and Editorial Independence) and Overall Assessment score summarizing guideline quality across all domains., Results: Scores ranged from 28% to 85% for the AAO CPG, 51% to 96% for the COS CPG, and 55% to 97% for the NICE CPG. Intraclass correlation coefficients for the reliability of mean scores for the AAO, COS, and NICE CPGs were 0.89, 0.86, and 0.74; 95% CIs were 0.80 to 0.95, 0.74 to 0.93, and 0.51 to 0.87, respectively. The strongest domains were Scope and Purpose (AAO, COS, NICE) and Clarity of Presentation (COS, NICE). The weakest domains were Stakeholder Involvement (AAO, COS) and Editorial Independence (AAO, COS, NICE)., Conclusions: Future POAG CPGs can be improved by addressing potential conflicts of interest within the development group, ensuring transparency of guideline development methodology, and involving all relevant stakeholders in guideline development and review., (Published by Elsevier Inc.)

Social scientific and public health literature on National Institutes of Health-funded HIV behavioural prevention science often assumes that this body of work has a strong biomedical epistemological orientation. We explore this assumption by conducting a systematic content analysis of all NIH-funded HIV behavioural prevention grants for men who have sex with men between 1989 and 2012. We find that while intervention research strongly favours a biomedical orientation, research into the antecedents of HIV risk practices favours a sociological, interpretive and structural orientation. Thus, with respect to NIH-funded HIV prevention science, there exists a major disjunct in the guiding epistemological orientations of how scientists understand HIV risk, on the one hand, and how they engineer behaviour change in behavioural interventions, on the other. Building on the extant literature, we suggest that the cause of this disjunct is probably attributable not to an NIH-wide positivist orientation, but to the specific standards of evidence used to adjudicate HIV intervention grant awards, including randomised controlled trials and other quantitative measures of intervention efficacy., (© 2015 The Authors. Sociology of Health & Illness © 2015 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.)

Importance: Patients are increasingly using the Internet to supplement finding medical information, which can be complex and requires a high level of reading comprehension. Online ophthalmologic materials from major ophthalmologic associations should be written at an appropriate reading level., Objectives: To assess ophthalmologic online patient education materials (PEMs) on ophthalmologic association websites and to determine whether they are above the reading level recommended by the American Medical Association and National Institutes of Health., Design, Setting, and Participants: Descriptive and correlational design. Patient education materials from major ophthalmology websites were downloaded from June 1, 2014, through June 30, 2014, and assessed for level of readability using 10 scales. The Flesch Reading Ease test, Flesch-Kincaid Grade Level, Simple Measure of Gobbledygook test, Coleman-Liau Index, Gunning Fog Index, New Fog Count, New Dale-Chall Readability Formula, FORCAST scale, Raygor Readability Estimate Graph, and Fry Readability Graph were used. Text from each article was pasted into Microsoft Word and analyzed using the software Readability Studio professional edition version 2012.1 for Windows., Main Outcomes and Measures: Flesch Reading Ease score, Flesch-Kincaid Grade Level, Simple Measure of Gobbledygook grade, Coleman-Liau Index score, Gunning Fog Index score, New Fog Count, New Dale-Chall Readability Formula score, FORCAST score, Raygor Readability Estimate Graph score, and Fry Readability Graph score., Results: Three hundred thirty-nine online PEMs were assessed. The mean Flesch Reading Ease score was 40.7 (range, 17.0-51.0), which correlates with a difficult level of reading. The mean readability grade levels ranged as follows: 10.4 to 12.6 for the Flesch-Kincaid Grade Level; 12.9 to 17.7 for the Simple Measure of Gobbledygook test; 11.4 to 15.8 for the Coleman-Liau Index; 12.4 to 18.7 for the Gunning Fog Index; 8.2 to 16.0 for the New Fog Count; 11.2 to 16.0 for the New Dale-Chall Readability Formula; 10.9 to 12.5 for the FORCAST scale; 11.0 to 17.0 for the Raygor Readability Estimate Graph; and 12.0 to 17.0 for the Fry Readability Graph. Analysis of variance demonstrated a significant difference (P < .001) between the websites for each reading scale., Conclusions and Relevance: Online PEMs on major ophthalmologic association websites are written well above the recommended reading level. Consideration should be given to revision of these materials to allow greater comprehension among a wider audience.

Objective: The purpose of this study was to determine the reading level of frequently used patient information pamphlets and documents in the field of urogynecology., Methods: Urogynecology pamphlets were identified from a variety of sources. Readability was determined using 4 different accepted formulas: the Flesch-Kincaid Grade Level, the simple measure of gobbledygook Index, the Coleman-Liau Index, and the Gunning Fog index. The scores were calculated using an online calculator (http://www.readability-score.com). Descriptive statistics were used for analysis. The average of the 4 scores was calculated for each pamphlet. Subsequently, Z-scores were used to standardize the averages between the reading scales., Results: Of the 40 documents reviewed, only a single pamphlet met the National Institutes of Health-recommended reading level. This document was developed by the American Urological Association and was specifically designated as a "Low-Literacy Brochure." The remainder of the patient education pamphlets, from both industry-sponsored and academic-sponsored sources, consistently rated above the recommended reading level for maximum comprehension., Conclusions: The majority of patient education pamphlets, from both industry-sponsored and academic-sponsored sources, are above the reading level recommended by the National Institutes of Health for maximum patient comprehension. Future work should be done to improve the educational resources available to patients by simplifying the verbiage in these documents.

Background and Purpose: National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed may prove useful both clinically and for research studies. We aimed to validate the NIHSS item profiles in an acute cohort., Methods: We conducted a retrospective analysis on pooled data from randomized clinical trials. We applied the latent class analysis probabilities of profile membership developed from the derivation study to obtain symptom grouping, a-NIHSS item profiles. We implemented an independent latent class analysis to derive secondary symptom grouping, b-NIHSS item profiles. Validation was performed by assessing the associations with outcomes and evaluating both sets of NIHSS item profiles' discrimination and calibration to the data. The outcomes evaluated included modified Rankin Scale (mRS; using the full distribution and dichotomized, mRS, 0-1) at day 90 and mortality by 90 days., Results: We identified 10 271 patients. Ordinal analysis of mRS confirmed increased odds of better outcome across the profiles in a stepwise manner, adjusted for age and thrombolysis treatment, for each set of NIHSS item profiles. Similar patterns were observed for mRS 0 to 1, and inverse patterns were seen for mortality. The c-statistics of a-NIHSS and b-NIHSS item profiles for mRS 0 to 1 were similar at 0.71 (95% confidence interval, 0.70-0.72) and for mortality, 0.74 (0.73-0.75) and 0.75 (0.73-0.76), respectively. Calibration was good., Conclusions: These NIHSS item profiles identified using latent class analysis offer a reliable approach to capture the true response patterns that are associated with functional and outcome and mortality post stroke. This approach has the potential to enhance the clinical value of the overall NIHSS score., (© 2014 American Heart Association, Inc.)