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Purpose: We sought to understand physiotherapists’ and physiotherapist assistants’ perspectives on using three physical function measures in the intensive care unit (ICU) setting: the Activity Measure for Post-Acute Care Inpatient Mobility Short Form, the Johns Hopkins Highest Level of Mobility scale, and the Functional Status Score for the Intensive Care Unit. Method: A six-item questionnaire was developed and administered to physiotherapists and physiotherapist assistants working in adult ICUs at one U.S. teaching hospital. A single semi-structured focus group was conducted with seven physiotherapists, recruited using purposive sampling to include participants with a range of clinical experience. Results: Of 22 potential participants, 18 physiotherapists and 2 physiotherapist assistants completed the questionnaire. Seven physiotherapists participated in the focus group. The questionnaire found favourable perspectives on the use of the three physical function measures in clinical practice, and the focus group identified five themes related to clinicians’ experience with using them: (1) ease of scoring, (2) usefulness in inter-professional communication, (3) general ease of use, (4) responsiveness to change in physical function, and (5) generalizability across patients. Conclusions: The most frequently discussed themes in this study were ease of scoring and usefulness in inter-professional communication, highlighting their importance in designing and selecting physical function measures for clinical use in the ICU setting.

Background A multicentre randomised trial demonstrated improved outcomes for intensive care unit (ICU) patients using early, goal-directed mobility implemented by nurses. Objectives The aim of the study was to evaluate barriers to nursing mobility, using a validated survey, during an ongoing quality improvement (QI) project (2019) in a medical ICU and determine changes from the pre-QI (2017) baseline. Methods Nurses, nurse practitioners, physician assistants, and clinical technicians completed the 26-item Patient Mobilization Attitudes and Beliefs Survey for the ICU (PMABS-ICU). An overall score and three subscale scores (knowledge, attitudes, behaviour), each ranging from 0 to 100, were calculated; higher scores indicated greater barriers. Results Seventy-five (93% response rate) nurses, eight (100%) nurse practitioners and physician assistants, and 11 (100%) clinical technicians completed the PMABS-ICU. For all respondents (N = 94), the mean (standard deviation) overall PMABS-ICU score was 32 (8) and the knowledge, attitudes and behaviour subscale scores were 22 (11), 33 (11), and 34 (8), respectively. Among all respondents completing the survey in both 2017 and 2019 (N = 46), there was improvement in the mean (95% confidence interval) overall score [−3.1 (−5.8, −0.5); p = .022] and in the knowledge [−5.1 (−8.9, −1.3); p = .010] and attitudes [−3.9 (−7.3, −0.6); p = .023] subscale scores. Among all respondents (N = 48) taking the PMABS-ICU for the first time in 2019 compared with those taking the survey before the QI project in 2017 (N = 99), there was improvement in the mean (95% confidence interval) overall score [−3.8 (−6.5, −1.1); p = .007] and in the knowledge [−6.9 (−11.0, –2.7); p = .001] and attitude [−4.3 (−8.1, –0.5); p = .027] subscale scores. Conclusions Using a validated survey administered to ICU nurses and other staff, before and during a structured QI project, there was a decrease in perceived barriers to mobility. Reduced barriers among those taking the survey for the first time during the QI project compared with those taking the survey before the QI project suggests a positive culture change supporting early, goal-directed mobility implemented by nurses.

Importance: Identifying cognitive impairment in adults in acute care is essential so that providers can address functional deficits and plan for safe discharge. Occupational therapy practitioners play an essential role in screening for, evaluating, and treating cognitive impairment. Objective: To test and compare the psychometrics and feasibility of three cognitive screens and select the ideal screen for use in acute care. Design: Prospective mixed methods. Setting: Acute care hospital. Participants: Fifty adults. Outcomes and Measures: We examined the interrater reliability, administration time, and usability of the Brief Cognitive Assessment Tool Short Form (BCAT–SF), the Activity Measure for Post-Acute Care “6-Clicks” Applied Cognitive Inpatient Short Form (AM-PAC ACISF), and the Montreal Cognitive Assessment (MoCA). We compared the construct validity, sensitivity, and specificity of the BCAT–SF and AM-PAC ACISF with those of the MoCA. Results: Interrater reliability was good to excellent; ICCs were .98 for the MoCA, .97 for the BCAT–SF, and .86 for the AM-PAC ACISF. The BCAT–SF and the AM-PAC ACISF both had 100% sensitivity, and specificity was 74% for the BCAT–SF and 98% for the AM-PAC ACISF. The optimal cutoff score for cognitive impairment on the AM-PAC ACISF was Conclusions and Relevance: Each screen demonstrated acceptable reliability and construct validity. The AM-PAC ACISF had the optimum mix of performance and feasibility for the fast-paced acute care setting. What This Article Adds: Early identification of cognitive impairment using the AM-PAC ACISF can allow for timely occupational therapy intervention in acute care settings.

BackgroundPrior acute respiratory distress syndrome (ARDS) trials have identified hypoinflammatory and hyperinflammatory subphenotypes, with distinct differences in short-term outcomes. It is unknown if such differences extend beyond 90 days or are associated with physical, mental health or cognitive outcomes.Methods568 patients in the multicentre Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo were included and assigned a subphenotype. Among 6-month and 12-month survivors (N=232 and 219, respectively, representing 243 unique survivors), subphenotype status was evaluated for association with a range of patient-reported outcomes (eg, mental health symptoms, quality of life). Patient subsets also were evaluated with performance-based tests of physical function (eg, 6 min walk test) and cognition.FindingsThe hyperinflammatory versus hypoinflammatory subphenotype had lower overall 12-month cumulative survival (58% vs 72%, pInterpretationComparing the hyperinflammatory versus hypoinflammatory ARDS subphenotype, there was no significant difference in survival beyond 90 days and no consistent findings of important differences in 6-month or 12-month physical, cognitive and mental health outcomes. These findings, when considered with prior results, suggest that inflammatory subphenotypes largely reflect the acute phase of illness and its short-term impact.

BACKGROUND: With an increasing number of follow-up studies of acute respiratory failure survivors, there is need for a better understanding of participant retention and its reporting in this field of research. Hence, our objective was to synthesize participant retention data and associated reporting for this field. METHODS: Two screeners independently searched for acute respiratory failure survivorship studies within a published scoping review to evaluate subject outcomes after hospital discharge in critical illness survivors. RESULTS: There were 21 acute respiratory failure studies (n = 4,342 survivors) over 47 follow-up time points. Six-month follow-up (range: 2–60 months) was the most frequently reported time point, in 81% of studies. Only 1 study (5%) reported accounting for loss to follow-up in sample-size calculation. Retention rates could not be calculated for 5 (24%) studies. In 16 studies reporting on retention across all time points, retention ranged from 32% to 100%. Pooled retention rates at 3, 6, 12, and 24 months were 85%, 89%, 82%, and 88%, respectively. Retention rates did not significantly differ by publication year, participant mean age, or when comparing earlier (3 months) versus each later follow-up time point (6, 12, or 24 months). CONCLUSIONS: Participant retention was generally high but varied greatly across individual studies and time points, with 24% of studies reporting inadequate data to calculate retention rate. High participant retention is possible, but resources for optimizing retention may help studies retain participants. Improved reporting guidelines with greater adherence would be beneficial.

Background and Objectives: Impaired physical functioning is common and long lasting after an intensive care unit (ICU) admission. The 6-minute walk test (6MWT) is a validated and widely used test of functional capacity. This systematic review synthesizes existing data in order to: (1) evaluate 6-minute walk distance (6MWD) in meters over longitudinal follow-up after critical illness, (2) compare 6MWD between acute respiratory distress syndrome (ARDS) versus non-ARDS survivors, and (3) evaluate patient- and ICU-related factors associated with 6MWD. Data Sources: Five databases (PubMed, EMBASE, Cumulative Index of Nursing and Allied Health Literature, PsychINFO, and Cochrane Controlled Trials Registry) were searched to identify studies reporting 6MWT after hospital discharge in survivors from general (ie, nonspeciality) ICUs. The last search was run on February 14, 2018. Databases were accessed via Johns Hopkins University Library. Data Extraction and Synthesis: Pooled mean 6MWD were reported, with separate linear random effects models used to evaluate associations of 6MWD with ARDS status, and patient- and ICU-related variables. Twenty-six eligible articles on 16 unique participant groups were included. The pooled mean (95% confidence interval [CI]) 6MWD results at 3- and 12-months post discharge were 361 (321-401) and 436 (391-481) meters, respectively. There was a significant increase in 6MWD at 12 months compared to 3 months ( P = .017). In ARDS versus non-ARDS survivors, the mean (95% CI) 6MWD difference over 3-, 6-, and 12-month follow-up was 73 [13-133] meters lower. Female sex and preexisting comorbidity also were significantly associated with lower 6MWD, with ICU-related variables having no consistent associations. Conclusions: Compared to initial assessment at 3 months, significant improvement in 6MWD was reported at 12 months. Female sex, preexisting comorbidity, and ARDS (vs non-ARDS) were associated with lower 6MWT results. Such factors warrant consideration in the design of clinical research studies and in the interpretation of patient status using the 6MWT.

Rationale: Increasingly, patients are surviving acute respiratory failure (ARF), prompting the need to better understand standardized outcome measures commonly used during ARF follow-up studies. Objectives: Investigate standardized outcome measures (patient-reported physical and mental health measures, and cognitive testing) compared with findings from semistructured, qualitative interviews. Methods: As part of two ARF multicenter follow-up studies, standardized outcome measures were obtained, followed by qualitative evaluation via an in-depth, semistructured interview conducted and coded by two independent researchers. Qualitative interviews revealed the following post-ARF survivorship themes: physical impairment; anxiety, depression, and post-traumatic stress disorder symptoms; and cognitive impairment. Scores from standardized measures related to these themes were compared for ARF survivors reporting versus not reporting these themes in their qualitative interviews. Results: Of 59 invited ARF survivors, 48 (81%) completed both standardized outcome measures and qualitative interviews. Participants’ median (interquartile range) age was 53 (43–64) years; 54% were female, and 88% were living independently before hospitalization. The two independent reviewers classifying the presence or absence of themes from the qualitative interviews had excellent agreement (κ = 0.80). There were significantly worse scores on standardized outcome measures for survivors reporting (vs. not reporting) physical and mental health impairments in their qualitative interviews. However, standardized cognitive test scores did not differ between patients reporting versus not reporting cognitive impairments in their qualitative interviews. Conclusions: These findings support the use of recommended, commonly used standardized outcome measures for physical and mental health impairments in ARF survivorship research. However, caution is needed in interpreting self-reported cognitive function compared with standardized cognitive testing.

BackgroundThe study aimed to synthesize participant retention-related data for longitudinal follow-up studies of survivors from trauma intensive care units (ICUs).MethodsWithin a published scoping review evaluating ICU patient outcomes after hospital discharge, two screeners independently searched for trauma ICU survivorship studies.ResultsThere were 11 trauma ICU follow-up studies, all of which were cohort studies. Twelve months (range: 1–60 months) was the most frequent follow-up time point for assessment (63% of studies). Retention rates ranged from 54% to 94% across time points and could not be calculated for two studies (18%). Pooled retention rates at 3, 6, and 12 months were 75%, 81%, and 81%, respectively. Mean patient age (OR 0.85 per 1-year increase, 95% CI 0.73 to 0.99, p=0.036), percent of men (OR 1.07, 95% CI 1.04 to 1.10, p=0.002), and publication year (OR 0.89 per 1-year increase, 95% CI 0.82 to 0.95, p=0.007) were associated with retention rates. Early (3-month) versus later (6-month, 12-month) follow-up time point was not associated with retention rates.DiscussionPooled retention rates were >75%, at 3-month, 6-month, and 12-month time points, with wide variability across studies and time points. There was little consistency with reporting participant retention methodology and related data. More detailed reporting guidelines, with better author adherence, will help improve reporting of participant retention data. Utilization of existing research resources may help improve participant retention.Level of evidenceLevel III: meta-analyses (post-hoc analyses) of a prior scoping review.

Objective Examine the inter-rater reliability of the activity measure for post-acute care (AM-PAC) inpatient mobility short form (IMSF) when completed by physical therapists (PTs), during routine clinical practice, in a variety of patients with critical illness. Methods A prospective observational evaluation at single, large academic hospital in the United States. Patients (n = 76) in surgical, medical and neurological intensive care units (ICUs) were evaluated as part of routine clinical practice using the AM-PAC IMSF administered by eight PTs with at least 6 months of experience using this tool. One of two reference rater PTs observed the physical therapy session, and simultaneously scored the AM-PAC IMSF. The reference rater and clinical PTs were blinded to each other's scores with a minimum of 10 assessments completed by each clinical PT. Bland-Altman plots were constructed and intra-class correlation coefficients (ICC) were computed using a random intercept (physical therapy session) model. Results Eighty one assessments (five patients assessed twice) were scored by both a clinical PT and reference rater PT (total assessments = 162). Bland-Altman plots revealed a mean difference in AM-PAC IMSF scoring of 0.0 (95% limits of agreement: -3.0 to +3.0), with an ICC (95% confidence interval) of 0.957 (0.947-0.964). The ICC (95% confidence interval) for patients in surgical, medical and neurological ICUs was very similar: 0.949 (0.927-0.959), 0.963 (0.946-0.971) and 0.936 (0.886-0.955), respectively. Conclusions The AM-PAC IMSF demonstrates excellent reliability compared with reference rater PTs when performed by PTs during clinical care across surgical, medical and neurological ICUs.

Purpose: Early mobilization in the intensive care unit (ICU) can improve patient outcomes but has perceived barriers to implementation. As part of an ongoing structured quality improvement project to increase mobilization of medical ICU patients by nurses and clinical technicians, we adapted the existing, validated Patient Mobilization Attitudes & Beliefs Survey (PMABS) for the ICU setting and evaluated its performance characteristics and results. Materials and Methods: The 26-item PMABS adapted for the ICU (PMABS-ICU) was administered as an online survey to 163 nurses, clinical technicians, respiratory therapists, attending and fellow physicians, nurse practitioners, and physician assistants in one medical ICU. We evaluated the overall and subscale (knowledge, attitude, and behavior) scores and compared these scores by respondent characteristics (clinical role and years of work experience). Results: The survey response rate was 96% (155/163). The survey demonstrated acceptable discriminant validity and acceptable internal consistency for the overall scale (Cronbach α: 0.82, 95% confidence interval: 0.76-0.85), with weaker internal consistency for all subscales (Cronbach α: 0.62-0.69). Across all respondent groups, the overall barrier score (range: 1-100) was relatively low, with attending physicians perceiving the lowest barriers (median [interquartile range]: 30 [28-34]) and nurses perceiving the highest (37 [31-40]). Within the first 10 years of work experience, greater experience was associated with a lower overall barrier score (−0.8 for each additional year; P = 0.02). Conclusions: In our medical ICU, across 6 different clinical roles, there were relatively low perceived barriers to patient mobility, with greater work experience over the first 10 years being associated with lower perceived barriers. As part of a structured quality improvement project, the PMABS-ICU may be valuable in assisting to identify specific perceived barriers for consideration in designing mobility interventions for the ICU setting.

Objectives The objective of this study was to elicit feedback on consensus methodology used for core outcome set (COS) development. Study Design and Setting An online survey of international Delphi panelists participating in a recent COS for clinical research studies evaluating acute respiratory failure (ARF) survivors was conducted. Panelists represented 14 countries (56% outside the United States). Results Seventy (92%) panelists completed the survey, including 32 researchers, 19 professional association representatives, 4 research funding representatives, and 15 ARF survivors/caregiver members. Among respondents, 91% reported that the time required to participate was appropriate and 96% were not bothered by reminders for timely response. Attributes of measurement instruments and voting results from previous rounds were evaluated differently across stakeholder groups. When measurement properties were explained in the stem of the survey question, 59 (84%) panelists (including 73% of survivors/families) correctly interpreted information about an instrument's reliability. Without a reminder in the stem, only 20 (29%) panelists (including 38% of researchers) correctly identified properties of a COS. Conclusion This international Delphi panel, including >20% patients/caregivers, favorably reported on feasibility of the methodology. Providing all panelists pertinent information/reminders about the project's objective at each voting round is important to informed decision making across all stakeholder groups.

Background:A decline in physical functioning is common during an intensive care unit (ICU) stay. The Functional Status Score for the Intensive Care Unit (FSS-ICU) is a performance-based measure designed to evaluate aspects of physical functioning in the ICU setting. While existing data support valid

Survivors of acute respiratory distress syndrome (ARDS) experience severe muscle wasting. Upper arm anthropometrics can provide a quick, non-invasive estimate of muscle status, but its accuracy is unknown. This study examines the accuracy of upper arm percent muscle area (UAMA) with reference measures of lean mass from dual energy X-ray absorptiometry (DXA). Data are from 120 ARDS survivors participating in a multicenter national study. Receiver operating characteristic (ROC) curves, by patient sex, demonstrated that UAMA did no better than chance in discriminating low appendicular skeletal muscle mass identified using DXA findings (c-statistics, 6 months: 0.50–0.59, 12 months: 0.54–0.57). Modest correlations of UAMA with DXA measures (whole-body: r = 0.46–0.49, arm-specific: r = 0.50–0.51, p

We aimed to characterize anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms over 5-year follow-up after acute respiratory distress syndrome (ARDS) and determine risk factors for prolonged psychiatric morbidity. This prospective cohort study enrolled patients from 13 medical and surgical intensive care units in four hospitals, with follow-up at 3, 6, 12, 24, 36, 48, and 60 months post-ARDS. Trained research staff administered the Hospital Anxiety and Depression Scale (HADS) (scores ≥ 8 on anxiety and depression subscales indicating substantial symptoms) and the Impact of Event Scale-Revised (IES-R, scores ≥ 1.6 indicating substantial PTSD symptoms) at each follow-up visit. Of 196 consenting survivors, 186 (95%) completed HADS and IES-R assessments; 96 (52%) had any continuous or recurring (prolonged) symptoms, and 71 (38%), 59 (32%), and 43 (23%) had prolonged anxiety, depression, and PTSD symptoms, respectively (median total durations 33–39 months, 71–100% of observed follow-up time). Prolonged psychiatric symptoms tended to co-occur across domains; the most common morbidity pattern involved substantial symptoms in all three domains. Worse pre-ARDS mental health, including prior depression and psychological distress in the period immediately preceding ARDS, was strongly associated with prolonged post-ARDS psychiatric morbidity across symptom domains. Clinically significant and long-lasting symptoms of anxiety, depression, and PTSD are common in the first 5 years after ARDS. In-hospital screening of psychiatric history, including recent anxiety and depression symptoms, may be useful for long-term mental health treatment planning after ARDS.

Research evaluating acute respiratory failure (ARF) survivors' outcomes after hospital discharge has substantial heterogeneity in terms of the measurement instruments used, creating barriers to synthesizing study data.To identify a minimum set of core outcome measures that are essential to include in all clinical research studies evaluating ARF survivors after discharge.We conducted a three-round modified Delphi consensus process with 77 participants (47% female, 55% outside the United States), including clinical researchers from more than 16 countries across six continents, patients/caregivers, clinicians, and research funders. Participants reviewed standardized information on measure instruments for seven consensus-derived outcomes plus one recommended outcome.Response rates were 91 to 97% across the three rounds. Among 75 measurement instruments evaluated, the following met a priori consensus criteria: EQ-5D and 36-item Short Form Health Survey version 2 (optional) for the "satisfaction with life and personal enjoyment" and "pain" outcomes, and both the Hospital Anxiety and Depression Scale and the Impact of Events Scale-Revised for the "mental health" outcome. No measures reached consensus for the following outcomes: cognition, muscle and/or nerve function, physical function, and pulmonary function. All measures considered for pulmonary function met consensus criteria for exclusion. The following measures did not reach the threshold for consensus but achieved the highest scores for their respective outcomes: the Montreal Cognitive Assessment (cognition), manual muscle testing and handgrip dynamometry (muscle and/or nerve function), and 6-minute-walk test (physical function).This Core Outcome Measurement Set is recommended for use in all clinical research evaluating ARF survivors after hospital discharge. In the future, researchers should evaluate measures for outcomes not reaching consensus.

To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival.Longitudinal prospective cohort study over 5 years of follow-up.Thirteen ICUs in four hospitals in Baltimore, MD.One hundred fifty-six acute respiratory distress syndrome survivors.None.Strength was evaluated with standardized manual muscle testing using the Medical Research Council sum score (range, 0-60; higher is better), with post-ICU weakness defined as sum score less than 48. Muscle strength was assessed at hospital discharge and at 3, 6, 12, 24, 36, and 48 months after acute respiratory distress syndrome. At discharge, 38% of patients had muscle weakness. Every one point increase in sum score at discharge was associated with improved survival (hazard ratio [95% CI], 0.96 [0.94-0.98]), with similar findings longitudinally (0.95 [0.93-0.98]). Having weakness at discharge was associated with worse 5-year survival (1.75 [1.01-3.03]), but the association was attenuated (1.54 [0.82-2.89]) when evaluated longitudinally over follow-up. Persisting and resolving trajectories of muscle weakness, occurring in 50% of patients during follow-up, were associated with worse survival (3.01 [1.12-8.04]; and 3.14 [1.40-7.03], respectively) compared to a trajectory of maintaining no muscle weakness.At hospital discharge, greater than one third of acute respiratory distress syndrome survivors had muscle weakness. Greater strength at discharge and throughout follow-up was associated with improved 5-year survival. In patients with post-ICU weakness, both persisting and resolving trajectories were commonly experienced and associated with worse survival during follow-up.

Background The Johns Hopkins Highest Level of Mobility (JH-HLM) scale is used to document the observed mobility of hospitalized patients, including those patients in the intensive care unit (ICU) setting. Objective To evaluate the inter-rater reliability of the JH-HLM, completed by physical therapists, across medical, surgical, and neurological adult ICUs at a single large academic hospital. Methods The JH-HLM is an ordinal scale for documenting a patient’s highest observed level of activity, ranging from lying in bed (score = 1) to ambulating > 250 feet (score = 8). Eighty-one rehabilitation sessions were conducted by eight physical therapists, with 1 of 2 reference physical therapist rater simultaneously observing the session and independently scoring the JH-HLM. The intraclass correlation coefficient was used to determine the inter-rater reliability. Results A total of 77 (95%) of 81 assessments had perfect agreement. The overall intraclass correlation coefficient for inter-rater reliability was 0.98 (95% confidence interval: 0.96, 0.99), with similar scores in the medical, surgical, and neurological ICUs. A Bland–Altman plot revealed a mean difference in JH-HLM scoring of 0 (limits of agreement: −0.54 to 0.61). Conclusion The JH-HLM has excellent inter-rater reliability as part of routine physical therapy practice, across different types of adult ICUs.

Delayed hospital discharges for patients needing rehabilitation in a postacute setting can exacerbate hospital-acquired mobility loss, prolong functional recovery, and increase costs. Systematic measurement of patient mobility by nurses early during hospitalization has the potential to help identify which patients are likely to be discharged to a postacute care facility versus home. To test the predictive ability of this approach, a machine learning classification tree method was applied retrospectively to a diverse sample of hospitalized patients (N = 805) using training and validation sets. Compared with patients discharged to home, patients discharged to a postacute facility were older (median, 64 vs 56 years old) and had lower mobility scores at hospital admission (median, 32 vs 41). The final decision tree accurately classified the discharge location for 73% (95%CI:67%-78%) of patients. This study emphasizes the value of systematically measuring mobility in the hospital and provides a simple decision tree to facilitate early discharge planning.

This cohort study examines whether use of a mobility assessment tool in hospitalized patients with impaired mobility is associated with discharge to a postacute facility.

Rapid muscle wasting occurs during acute respiratory failure, resulting in muscle weakness and functional impairments. This study examines survivors' body composition in the year after acute respiratory distress syndrome and tests associations of patient characteristics, hospital exposures, and survivors' strength and physical functioning with whole body percent lean mass.Prospective cohort study with 6- and 12-month follow-up.National study enrolling patients from five study centers.Acute respiratory distress syndrome survivors (n = 120).None.Lean and fat mass from dual energy x-ray absorptiometry. On average, survivors gained whole body total mass (+1.4 kg; 0.1-2.7) and fat mass (+1.2 kg; 0.2-2.2) and maintained lean mass (+0.2 kg; -0.4 to 0.8) between 6 and 12 months. Proportionally, percent fat mass increased and percent lean mass decreased for the whole body, trunk, and legs (p0.05). Greater whole body percent lean mass was associated with younger age, male sex, and lower baseline body mass index, but not other patient characteristics or ICU/hospital exposures. Greater percent lean mass was also significantly associated with gait speed and 6-minute walk distance, but not volitional strength or self-reported functional status.In the first year after acute respiratory distress syndrome, patients gained fat mass and maintained lean mass. We found no association of whole body percent lean mass with commonly hypothesized hospital risk factors. Direct measurement of body composition and performance-based functional measures may be helpful for understanding functional recovery in ICU survivors.

Vitamin D plays an important role in the mineral and bone disorder seen in chronic kidney disease (CKD). Deficiency of 25-hydroxyvitamin D (25OHD) is highly prevalent in the adult CKD population.The prevalence and determinants of 25OHD deficiency (defined as a level20 ng/ml) were examined longitudinally in 506 children in the CKiD cohort. Predictors of secondary hyperparathyroidism and the determinants of 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were also evaluated.Deficiency of 25OHD was observed in 28 % of the cohort at enrollment. Significant predictors of 25OHD deficiency were older age, non-white race, higher body mass index, assessment during winter, less often than daily milk intake, non-use of nutritional vitamin D supplement and proteinuria. Lower values of glomerular filtration rate (GFR), serum 25OHD, calcium and higher levels of FGF23 were significant determinants of secondary hyperparathyroidism. Lower GFR, low serum 25OHD, nephrotic-range proteinuria, and high FGF23 levels were significant determinants of serum 1,25(OH)2 D levels.Deficiency of 25OHD is prevalent in children with CKD and is associated with potentially modifiable risk factors such as milk intake, nutritional vitamin D supplement use, and proteinuria. 25OHD deficiency is a risk factor for secondary hyperparathyroidism and decreased serum 1,25(OH)2D in children with CKD.

Knowledge-related barriers to safely implement early rehabilitation programs in intensive care units (ICUs) may be overcome via targeted education. The purpose of this study was to evaluate the effectiveness of an interactive educational session on short-term knowledge of clinical decision-making for safe rehabilitation of patients in ICUs.A case-based teaching approach, drawing from published safety recommendations for initiation of rehabilitation in ICUs, was used with a multidisciplinary audience. An audience response system was incorporated to promote interaction and evaluate knowledge before vs. after the educational session.Up to 175 audience members, of 271 in attendance (129 (48%) physical therapists, 51 (19%) occupational therapists, 31 (11%) nursing, 14 (5%) physician, 46 (17%) other), completed both the pre- and post-test questions for each of the six unique patient cases. In four of six patient cases, there was a significant (p 0.001) increase in identifying the correct answer regarding initiation of rehabilitation activities. This learning effect was similar irrespective of participants' years of experience and clinical discipline.An interactive, case-based, educational session may be effective for increasing short-term knowledge, and identifying knowledge gaps, regarding clinical decision-making for safe rehabilitation of patients in ICUs. Implications for Rehabilitation Lack of knowledge regarding the safety considerations for early rehabilitation of ICU patients is a barrier to implementing early rehabilitation. Interactive educational formats, such as the use of audience response systems, offer a new method of teaching and instantly assessing learning of clinically important information. In a small study, we have shown that an interactive, case-based educational format may be used to effectively teach clinical decision-making for the safe rehabilitation of ICU patients to a diverse audience of clinicians.

BackgroundThere is heterogeneity among the outcomes evaluated in studies of survivors of acute respiratory failure (ARF).AimTo evaluate the importance of specific outcome domains to acute respiratory distress syndrome (ARDS) survivors, their family members and clinical researchers.MethodsNineteen outcome domains were identified from the National Institutes of Health’s Patient Reported Outcomes Measurement Information System; WHO’s International Classification of Functioning, Disability, and Health; Society of Critical Care Medicine’s Post-Intensive Care Syndrome (PICS); as well as patient, clinician and researcher input. We surveyed ARDS survivors, family members and critical care researchers, 279 respondents in total, using a 5-point scale (strongly disagree, disagree, neutral, agree and strongly agree) to rate the importance of measuring each domain in studies of ARF survivors’ postdischarge outcomes.Measurements and main resultsAt least 80% of patients and family members supported (ie, rated ‘agree’ or ‘strongly agree’) that 15 of the 19 domains should be measured in all future studies. Among researchers, 6 of 19 domains were supported, with researchers less supportive for all domains, except survival (95% vs 72% support). Overall, four domains were supported by all groups: physical function, cognitive function, return to work or prior activities and mental health.ConclusionPatient, family and researcher groups supported inclusion of outcome domains that fit within the PICS framework. Patients and family members also supported many additional domains, emphasising the importance of including patients/family, along with researchers, in consensus processes to select core outcome domains for future research studies.

Chronic kidney disease (CKD) is associated with increased incidence of cardiac dysfunction. Recent animal studies have demonstrated that elevated levels of ceramides cause dilated lipotoxic cardiomyopathy. We hypothesized ceramides are increased in children with CKD and associated with abnormal cardiac structure and function.Ceramide levels were determined in 93 children aged 1-16 years enrolled in the Chronic Kidney Disease in Children (CKiD) study and compared to levels from 24 healthy controls. Complete demographic, clinical, and laboratory information, and ceramide measurements were analyzed cross-sectionally. Echocardiography was performed to determine cardiac structure and function.Very long-chain C24:0 ceramides were the most abundant species in both control (56 %) and CKD subjects (55 %), followed by C24:1 (controls 19 %, CKD 23 %) and C22:0 (controls 19 %, CKD 13 %). Total serum ceramide levels were significantly higher in CKD children versus controls (p0.001). Ceramide metabolites lactosylceramide, C24:0L, and C16:0L were significantly higher in CKD subjects than controls (p0.001). The proportion of C24:0L was dramatically higher in CKD (59 %) versus control (17 %) subjects (p0.001). In adjusted multivariate analyses, higher log10C24:0L and log10C16:0L were significant predictors of lower shortening fraction and mid-wall shortening.Ceramide levels are increased in children with CKD. Our study identified lactosylceramides as an independent predictor of lower systolic function in these children.

To examine the reliability, validity, responsiveness, and minimal important difference of the 4-m gait speed test in acute respiratory distress syndrome survivors.Secondary analyses of data from two longitudinal follow-up studies of acute respiratory distress syndrome survivors. Test-retest and inter-rater reliability, construct validity (convergent, discriminant, and known group), predictive validity, and responsiveness were examined. The minimal important difference was estimated using anchor- and distribution-based approaches.A national multicenter prospective study (ARDSNet Long-Term Outcome Study) and a multisite prospective study in Baltimore, MD (Improving Care of Acute Lung Injury Patients).Acute respiratory distress syndrome survivors with 4-m gait speed assessment up to 60 months after acute respiratory distress syndrome (ARDSNet Long-Term Outcome Study, n = 184; Improving Care of Acute Lung Injury Patients, n = 122).Not applicable.Four-meter gait speed was assessed at 6- and 12-month follow-up (ARDSNet Long-Term Outcome Study) and 36-, 48-, and 60-month follow-up (Improving Care of Acute Lung Injury Patients). Excellent test-retest (intraclass correlation, 0.89-0.99 across studies and follow-up) and inter-rater (intraclass correlation, 0.97) reliability were found. Convergent validity was supported by moderate-to-strong correlations (69% of 320.40) with other physical function measures. Discriminant validity was supported by weak correlations (86% of 280.30) with mental health measures. Survivors with impaired versus nonimpaired measures of muscle strength and pulmonary function had significantly slower 4-m gait speed (all but one p0.05). Furthermore, 4-m gait speed significantly predicted future hospitalization and health-related quality of life. Gait speed changes were consistent with reported changes in function, supporting responsiveness. The estimated 4-m gait speed minimal important difference was 0.03-0.06 m/s.The 4-m gait speed is a reliable, valid, and responsive measure of physical function in acute respiratory distress syndrome survivors. The estimated minimal important difference will facilitate sample size calculations for clinical studies evaluating the 4-m gait speed test in acute respiratory distress syndrome survivors.

Objective This study will estimate distribution-based minimal important difference (MID) for the Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) subscales, and the Impact of Event Scale-Revised (IES-R) in survivors of acute respiratory failure (ARF). Methods Secondary analyses of data from two US and three UK studies of ARF survivors (total N =1223). HADS-D and HADS-A were used to assess depression and anxiety symptoms. IES-R assessed post-traumatic stress disorder symptoms. Standard error of measurement, minimal detectable change 90 , 0.5 standard deviation (S.D.), and 0.2 S.D. were used to estimate MID for the combined sample, by studies, 6- and 12-month follow-ups, country and mental health condition. Results Overall, MID estimates converged to 2.0–2.5 for the HADS-A, 1.9–2.3 for the HADS-D and 0.17–0.18 for the IES-R. MID estimates were comparable across studies, follow-up, country and mental health condition. Conclusion Among ARF survivors, 2.0–2.5 is a reasonable range for the MID for both HADS subscales, and 0.2 is reasonable for IES-R. Until anchor-based MIDs for these instruments are available, these distribution-based estimates can help researchers plan future studies and interpret the clinical importance of findings in ARF patient populations.

Objective To prospectively assess the association of the metabolic syndrome in childhood with adult metabolic syndrome and type 2 diabetes mellitus (T2DM) 25 to 30 years later. Study design Data from the National Heart Lung and Blood Institute Lipid Research Clinics (LRC) Princeton Prevalence Study (1973-1976) and the Princeton Follow-up Study (PFS, 2000-2004) were used. Body mass index (BMI = kg/m 2 ) was used as the obesity measure in childhood because waist circumference was not measured at the LRC. The adult T2DM status of participants and their parents was obtained by participant report or fasting blood glucose ≥126 mg/dL. A logistic analysis for clustered samples was used to predict adult metabolic syndrome and T2DM, taking into account sibling correlations in the cohort. Pediatric metabolic syndrome, age at PFS, sex, race, change in BMI percentile, parental history of diabetes, and the interaction of pediatric metabolic syndrome and parental diabetes were explanatory variables. Results Ages ranged from 5 to 19 years in the LRC and from 30 to 48 years in the PFS. Pediatric metabolic syndrome, parental diabetes, age at follow-up, and change in age-specific BMI percentile were significant predictors of metabolic syndrome in adulthood, and pediatric metabolic syndrome, age at follow-up, black race, and parental diabetes were significant predictors of T2DM. Conclusions Evaluating 5- to 19-year-old children for metabolic syndrome and family history of diabetes could identify children at increased risk of adult metabolic syndrome and T2DM, allowing prospective primary prevention of these outcomes.

Objective To compare treatment, sex, and visit differences in beverage choice and calcium intake in the Dietary Intervention Study in Children, to compare the relationship of other beverages to milk consumption, and document whether or not the dietary intervention affected choice of beverage and milk type over time. Design Data from the Dietary Intervention Study in Children, a randomized, controlled, multicenter, clinical trial with five sets of three 24-hour recalls. Subjects Six hundred fifty-three children from six clinics started the study at age 8 to 10 years. Participants had serum low-density lipoprotein cholesterol levels between the 80th and 98th percentiles of age, and were followed for a median of 7.3 years. Intervention Children were randomized to a total fat- and saturated fat-modified dietary intervention or usual care. Main Outcome Measures Volume and percent of total energy from soft drinks, fruit-flavored drinks, fruit juice, and milk, calcium intake in milligrams and per 1,000 kcal, and percent reduced-fat and skim milk consumed. Statistical Analyses General Estimating Equations methodology was used to adjust for treatment, sex, and visit differences. Results The intervention group consumed more reduced-fat or skim milk than the usual care group. The intervention group also reported a greater increase in calcium per 1,000 kcal than those in the usual care group due to nonbeverage sources. Consumption of soft drinks increased over the course of the study, whereas total milk consumption decreased sharply. Conclusions With nutrition education, children can make changes in the type of milk consumed, and in the quantity of dietary calcium consumed.

Diet reportedly alters serum sex hormone concentrations in adults, but little is known about the influence of diet during puberty on these hormones.We aimed to determine whether an intervention to lower fat intake during adolescence alters serum sex hormone concentrations and progression through puberty.In 1990-1997, we conducted an ancillary study to the Dietary Intervention Study in Children, a multicenter, randomized, controlled clinical trial to test the safety and efficacy of a cholesterol-lowering dietary intervention in children.Healthy, prepubertal, 8 to 10 yr olds with elevated low-density lipoprotein cholesterol were randomized to usual care or a behavioral intervention. Of 362 randomized Dietary Intervention Study in Children boys, 354 participated in the ancillary study. Eighty-four percent of boys attended last visits when their median time on trial was 7.1 yr.The behavioral intervention continued throughout the duration of the trial and promoted a diet with 28% energy from total fat, less than 8% from saturated fat, 9% or less from polyunsaturated fat, and less than 75 mg cholesterol per 1000 kcal.The main outcome measure for boys formulated before study initiation was non-SHBG bound testosterone concentration. Secondary outcomes included serum total testosterone, dihydrotestosterone, androstenedione, estradiol, estrone, SHBG, and Tanner stage.There were no significant treatment group differences in boys' serum hormone levels, SHBG, or Tanner stages at any individual visit or over the course of the trial when evaluated by longitudinal models.Modest reductions in total fat, saturated fat, and possibly energy intake do not alter progression through puberty or serum sex hormone concentrations in adolescent boys.

OBJECTIVE Irritability is a significant component in the clinical manifestation of major depressive disorder (MDD). The Sheehan Irritability Scale (SIS) was developed to assess irritability-related symptoms in patients with psychiatric disorders. Data from a phase 2 clinical trial (June 2008-July 2009) was utilized to evaluate the psychometric properties of the SIS. The trial population included patients diagnosed with MDD, according to DSM-IV and confirmed via the MINI diagnostic scale, who had inadequate response to citalopram. METHOD The secondary analyses included 586 patients from the United States and India. Data from the SIS, depression severity measures (17-item Hamilton Depression Rating Scale [HDRS-17], Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]), and other measures (Sheehan Disability Scale [SDS], Clinical Global Impressions-Severity of Illness scale [CGI-S]) were used in the psychometric evaluation. All statistical tests used a significance level of .05 unless otherwise noted. RESULTS Internal consistency (0.92-0.99) and test-retest reliability (0.83 to 0.98) were excellent. Concurrent validity was demonstrated through strong correlations between the SIS total score and HDRS-17, QIDS-SR, SDS, CGI-S, and MADRS scores. SIS total scores were significantly different by clinical severity level (P < .001). Minimally important difference estimates suggest that a 7- to 8-point change in the SIS total score may be clinically meaningful. CONCLUSIONS The SIS has excellent reliability, acceptable validity, and good responsiveness, making the SIS appropriate for use in clinical research and practice. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00692445.

OBJECTIVE—Age at onset of type 2 diabetes has decreased during the past 20 years, especially in black women. Studies of factors associated with insulin resistance and hyperglycemia in preadolescent and adolescent populations are essential to understanding diabetes development. RESEARCH DESIGN AND METHODS—The National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study (NGHS) is a 10-year cohort study of the development of obesity in black and white girls. Two NGHS centers examined the associations of obesity, puberty, and race with fasting insulin, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR; a calculated index of insulin resistance) measures at 9–10 years of age (baseline) and 10 years later. RESULTS—Black girls had greater baseline and year-10 BMI than white girls, with a greater 10-year incidence of obesity. BMI-insulin correlations were positive in both black and white girls at both visits, but insulin remained higher in black girls after controlling for BMI. In black girls, insulin and HOMA-IR were higher in the prepubertal period (before the emergence of racial differences in BMI), increased more during puberty, and decreased less with its completion. Baseline BMI predicted year-10 glucose and the development of impaired fasting glucose (IFG) in black girls. In white girls, the rate of BMI increase during follow-up predicted these outcomes. The 10-year incidence of diabetes in black girls was 1.4%. CONCLUSIONS—Black-white differences in insulin resistance are not just a consequence of obesity, but precede the pubertal divergence in BMI. The development of IFG appears to be a function of the rate of increase of BMI in white girls and early obesity in black girls.

Aims The aim of this study was to investigate the association of left ventricular mass (LVM) with coronary atherosclerosis and myocardial infarction (MI). Methods and results Patients ( n = 338) underwent 320 × 0.5 mm detector row coronary computed tomography (CT) angiography, invasive coronary angiography (ICA), and single-photon emission CT (SPECT) myocardial perfusion imaging. Quantitative coronary atheroma volume was obtained from the CT images for the entire coronary tree (19-segment model) with an arterial contour detection algorithm. Normalized total atheroma volume (NormTAV) was analysed to reflect quantitative total atheroma volume. LVM was measured on myocardial CT images and indexed to height to the power of 2.7 (LVMi). Patients with obstructive coronary artery disease (CAD) were defined as those with ≥50% diameter stenosis by quantitative ICA. Abnormal perfusion defect was defined as ≥1 abnormal myocardial segment by SPECT. The association of LVMi with coronary atherosclerosis and myocardial perfusion defect on SPECT at the patient level was determined with uni- and multivariable linear and logistic regression analyses. Obstructive CAD was present in 60.0% of enrolled patients. LVMi was independently associated with abnormal summed rest score [SRS; odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03–1.09] and summed stress score (OR, 1.04; 95% CI, 1.01–1.07). An increase in LVMi was also independently associated with that in NormTAV (coefficient, 10.44; 95% CI, 1.50–19.39) and SRS ≥1 (OR, 1.05; 95% CI, 1.01–1.10), even after adjusting for cardiovascular risk factors in patients without previous MI. Conclusions LVM was independently associated with the presence of coronary artery atherosclerosis and MI.

Objective. Diets reduced in fat and cholesterol are recommended for children over 2 years of age, yet long-term safety and efficacy are unknown. This study tests the long-term efficacy and safety of a cholesterol-lowering dietary intervention in children. Methods. Six hundred sixty-three children 8 to 10 years of age with elevated low-density lipoprotein cholesterol (LDL-C) were randomized to a dietary intervention or usual care group, with a mean of 7.4 years' follow-up. The dietary behavioral intervention promoted adherence to a diet with 28% of energy from total fat, Results. Reductions in dietary total fat, saturated fat, and cholesterol were greater in the intervention than in the usual care group throughout the intervention period. At 1 year, 3 years, and at the last visit, the intervention compared with the usual care group had 4.8 mg/dL (.13 mmol/L), 3.3 mg/dL (.09 mmol/L), and 2.0 mg/dL (.05 mmol/L) lower LDL-C, respectively. There were no differences at any data collection point in height or serum ferritin or any differences in an adverse direction in red blood cell folate, serum retinol and zinc, sexual maturation, or body mass index. Conclusion. Dietary fat modification can be achieved and safely sustained in actively growing children with elevated LDL-C, and elevated LDL-C levels can be improved significantly up to 3 years. Changes in the usual care group's diet suggest that pediatric practices and societal and environmental forces are having positive public health effects on dietary behavior during adolescence.

Background The Dietary Intervention Study in Children (DISC) is a multicenter, randomized, controlled clinical trial designed to examine the efficacy and safety of a dietary intervention to reduce serum LDL cholesterol (LDL-C) in children with elevated LDL-C. Methods and Results The effects of dietary intake of fat and cholesterol and of sexual maturation and body mass index (BMI) on LDL-C were examined in a 3-year longitudinal study of 663 boys and girls (age 8 to 10 years at baseline) with elevated LDL-C levels. Multiple linear regression was used to predict LDL-C at 3 years. For boys, LDL-C decreased by 0.018 mmol/L for each 10 mg/4.2 MJ decrease in dietary cholesterol ( P P P P Conclusions In pubertal children, sexual maturation, BMI, dietary intervention (in girls), and dietary cholesterol (in boys) were significant in determining LDL-C. Sexual maturation was the factor associated with the greatest difference in LDL-C. Clinicians screening for dyslipidemia or following dyslipidemic children should be aware of the powerful effects of pubertal change on measurements of lipoproteins.

In adult patients with CKD, hypertension is linked to the development of left ventricular hypertrophy, but whether this association exists in children with CKD has not been determined conclusively. To assess the relationship between BP and left ventricular hypertrophy, we prospectively analyzed data from the Chronic Kidney Disease in Children cohort. In total, 478 subjects were enrolled, and 435, 321, and 142 subjects remained enrolled at years 1, 3, and 5, respectively. Echocardiograms were obtained 1 year after study entry and then every 2 years; BP was measured annually. A linear mixed model was used to assess the effect of BP on left ventricular mass index, which was measured at three different visits, and a mixed logistic model was used to assess left ventricular hypertrophy. These models were part of a joint longitudinal and survival model to adjust for informative dropout. Predictors of left ventricular mass index included systolic BP, anemia, and use of antihypertensive medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Predictors of left ventricular hypertrophy included systolic BP, female sex, anemia, and use of other antihypertensive medications. Over 4 years, the adjusted prevalence of left ventricular hypertrophy decreased from 15.3% to 12.6% in a systolic BP model and from 15.1% to 12.6% in a diastolic BP model. These results indicate that a decline in BP may predict a decline in left ventricular hypertrophy in children with CKD and suggest additional factors that warrant additional investigation as predictors of left ventricular hypertrophy in these patients.

Autonomic nervous system dysfunction and sympathetic nervous system over-activity play important roles in the development of hypertension associated with chronic kidney disease (CKD). In adults, increased blood pressure variability (BPV) appears to be directly related to sympathetic over-activity with increased risk of end-organ damage and cardiovascular events. Decreased heart rate variability (HRV) has been observed in adults with CKD, and is an independent predictor of mortality.The purpose of this study was to evaluate BPV and HRV in pediatric patients enrolled in the Chronic Kidney Disease in Children Study. Ambulatory blood pressure monitoring data were available for analysis of 215 person-visits from 144 children that were not receiving antihypertensive medications.BPV and HRV were determined by standard deviation and coefficient of variation for heart rate and systolic and diastolic blood pressure for each patient averaged for wake/sleep periods during 24-h monitoring. Uniformly lower values were displayed during sleep versus wake periods: BPV was 20 % lower during sleep (p 0.001) and HRV was 30 % lower during sleep (p 0.001). A significant increase in systolic BPV was observed in hypertensive children compared to children with normal blood pressure (6.9 %, p = 0.009). Increased diastolic BPV was detected among hypertensive children during sleep period compared to children with normal blood pressure (11.5 %, p = 0.008). There was a significant decrease in HRV in hypertensive compared to normotensive children (-8.2 %, p = 0.006).These findings are similar to those in adult patients and may underscore childhood origin and natural progression of adverse cardiovascular outcomes in adults with CKD.

The Severity Classification for AIDS Hospitalizations (SCAH) was applied to a longitudinal person-based data set of Maryland adult residents diagnosed with acquired immunodeficiency syndrome (AIDS) between 1983 and 1989 to predict long-term survival. In contrast to other AIDS severity measures, SCAH can be applied to administrative data bases for analyses of large populations. Although SCAH was created to predict inpatient mortality using cross-sectional hospital discharge data, the models used in this study show SCAH stage at first AIDS hospitalization to predict long-term survival in persons with AIDS, even after adjusting for sociodemographic and treatment variables. Additional models in the study show SCAH stage at first hospitalization has a strong association with inpatient length of stay and associated charges, making it useful for health care resource planning.

OBJECTIVE. The goal was to assess the association of metabolic syndrome in childhood with adult cardiovascular disease 25 years later.METHODS. Data from the National Heart, Lung, and Blood Institute Lipid Research Clinics Princeton Prevalence Study (1973–1976) and the Princeton Follow-up Study (2000–2004) were used. BMI was used as the obesity measure in childhood, because waist circumference was not measured in the Lipid Research Clinics study. The adult cardiovascular disease status of participants and their parents was obtained through participant report. A logistic analysis was used to predict adult cardiovascular disease; pediatric metabolic syndrome, age at the Princeton Follow-up Study, gender, race, and parental history of cardiovascular disease were potential explanatory variables.RESULTS. Ages ranged from 6 to 19 years in the Lipid Research Clinics study and from 30 to 48 years in the Princeton Follow-up Study. There were 17 cases of cardiovascular disease in the analysis cohort in the Princeton Follow-up Study. Pediatric metabolic syndrome and age at follow-up assessment were significant predictors of cardiovascular disease. Pediatric metabolic syndrome and changes in age-specific BMI percentile from childhood to adulthood were significant predictors of adult metabolic syndrome.CONCLUSIONS. Evaluating children for metabolic syndrome could identify patients at increased risk of adult cardiovascular disease, making targeted interventions possible.

OBJECTIVE. The goal was to determine the diagnostic utility of the National Cholesterol Education Program pediatric guidelines.METHODS. With the use of pediatric lipid data from the Cincinnati Clinic of the Lipid Research Clinics Prevalence Study and lipid and cardiovascular disease data collected for the same subjects as adults in the Princeton Follow-up Study, the sensitivity and specificity of the National Cholesterol Education Program pediatric guidelines were calculated overall and according to age. Furthermore, whether use of parental cardiovascular disease history during childhood influenced the sensitivity and specificity was assessed.RESULTS. Overall sensitivities were 43% to 46% and specificities were 82% to 86% for total and low-density lipoprotein cholesterol levels. There was considerable variation in sensitivities according to age, with the lowest sensitivities at ages 14 to 16 years and the highest sensitivities at ages 5 to 10 years and 17 to 19 years. Results were similar whether or not the population was restricted to children with a positive parental history of cardiovascular disease.CONCLUSIONS. Results of our analyses suggest that the sensitivity and specificity for evaluating total cholesterol or low-density lipoprotein cholesterol levels that are elevated in adulthood are not improved by selecting children with a positive parental history. These data also show the strong role that age (particularly the pubertal years between 10 and 15 years of age) plays in lipid measurements for children and adolescents. Continued prospective and longitudinal studies designed with age as well as other risk parameters are needed to determine the best guidelines for clinical screening in the future.

Background. The metabolic syndrome, associated with increased risk of type 2 diabetes mellitus and cardiovascular disease, begins to develop during adolescence. Objective. We sought to identify early predictors of the presence of the syndrome at the ages of 18 and 19 years in black and white girls. Methods. Using longitudinal data on participants from 2 centers in the National Heart, Lung, and Blood Institute Growth and Health Study, a 10-year cohort study, we applied cutoffs from the Adult Treatment Panel III to document changes in the prevalence of abnormal syndrome elements and the syndrome in girls aged 9 and 10 years, when cases were rare, and those aged 18 and 19 years, when prevalence had reached 3%. Longitudinal regression models identified early predictors for the presence of the syndrome. Results. Only 1 girl of each race had ≥3 factors at ages 9 and 10 (0.2%), but 20 black girls (3.5%) and 12 white girls (2.3%) had the syndrome 10 years later. Low high-density lipoprotein cholesterol was prevalent throughout the period in both black and white girls. The prevalence of other variables was low at enrollment but increased during follow-up, except for abnormal triglyceride levels in black girls, which remained low throughout follow-up. In multivariate models, early measures of waist circumference and triglyceride level were significant predictors for development of the syndrome. Conclusion. The strong association of central adiposity with the development of the metabolic syndrome suggests that early interventions aimed at managing preteen obesity could reduce risk of developing the syndrome.

Adolescent girls with polycystic ovary syndrome (PCOS) have increased levels of factors constituting the metabolic syndrome: centripetal obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and hyperinsulinemia. Given the strong association reported between early, persistent obesity and development of metabolic syndrome 10 years later in girls, we speculated that if adolescent girls without PCOS had obesity measures similar to girls with PCOS, they would exhibit similar metabolic syndrome-cardiovascular disease risk factors. Within this context, we compared 37 adolescent girls with PCOS and 2 samples of normal, regularly cycling adolescent girls (controls) of similar ages, selected from the Cincinnati Clinic of the National Heart, Lung, and Blood Institute Growth and Health Study. The first sample included 157 controls selected using a stratified random sample based on age. As expected, girls with PCOS had higher body mass index (BMI), waist circumference, insulin, systolic blood pressure (SBP) and diastolic blood pressure, triglycerides (TGs), lower HDL-C, and higher low-density lipoprotein cholesterol (LDL-C) and free testosterone (FT) than controls. A second sample consisted of girls matched one to one with girls with PCOS for BMI and age. Comparisons of group differences were not significant for insulin, lipids, or blood pressure; girls with PCOS had a trend toward higher values for waist circumference (median, 92.7 vs 87.5 cm; P = .07) and much higher median FT (4.25 vs 1.42 ng/mL, P = .0001). After matching for BMI and age, by conditional regression analysis, we showed that the groups were not differentiated (P > .15) by insulin, HDL-C, LDL-C, TG, SBP, or diastolic blood pressure, but were differentiated by higher FT (P = .0024) and waist circumference (P = .0024) in PCOS than in controls. Prospective longitudinal analyses of NHGS controls showed that changes in BMI from ages 9 to 10 years to ages 15 to 16 years were positively associated with changes in waist circumference (P < .0001), LDL-C (P = .01), TG (P = .008), and SBP (P = .002). These findings suggest that if adolescent girls achieve adiposity equal to girls with PCOS, they then acquire major components of the metabolic syndrome, and excluding high FT and waist circumference, comparable increased cardiovascular disease risk.

Age at onset of type 2 diabetes has decreased during the past 20 years, especially in black women. Studies of factors associated with insulin resistance and hyperglycemia in preadolescent and adolescent populations are essential to understanding diabetes development.The National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study (NGHS) is a 10-year cohort study of the development of obesity in black and white girls. Two NGHS centers examined the associations of obesity, puberty, and race with fasting insulin, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR; a calculated index of insulin resistance) measures at 9-10 years of age (baseline) and 10 years later.Black girls had greater baseline and year-10 BMI than white girls, with a greater 10-year incidence of obesity. BMI-insulin correlations were positive in both black and white girls at both visits, but insulin remained higher in black girls after controlling for BMI. In black girls, insulin and HOMA-IR were higher in the prepubertal period (before the emergence of racial differences in BMI), increased more during puberty, and decreased less with its completion. Baseline BMI predicted year-10 glucose and the development of impaired fasting glucose (IFG) in black girls. In white girls, the rate of BMI increase during follow-up predicted these outcomes. The 10-year incidence of diabetes in black girls was 1.4%.Black-white differences in insulin resistance are not just a consequence of obesity, but precede the pubertal divergence in BMI. The development of IFG appears to be a function of the rate of increase of BMI in white girls and early obesity in black girls.

Background: Results of several studies have suggested that diet during adolescence may influence the risk of breast cancer in adulthood. We evaluated whether an intervention to lower fat intake among adolescent girls altered their serum concentrations of sex hormones that, in adults, are related to breast cancer development. Methods: We conducted an ancillary hormone study among 286 of the 301 girls who participated between 1988 and 1997 in the Dietary Intervention Study in Children, in which healthy, prepubertal, 8- to 10year-olds with elevated low-density lipoprotein cholesterol were randomly assigned to usual care or to a behavioral intervention that promoted a low-fat diet. Median time on the intervention was 7 years. Blood samples collected before randomization and at the year 1, year 3, year 5, and last visits were assayed to determine the girls’ serum levels of sex hormones. All P values are two-sided. Results: At the year 5 visit, girls in the intervention group had 29.8% (95% confidence interval [CI] = 5.4% to 47.9%; P = .02) lower estradiol, 30.2% (95% CI = 7.0% to 47.7%; P = .02) lower nonsex hormone binding globulin-bound estradiol, 20.7% (95% CI = 4.7% to 34.0%; P = .02) lower estrone, and 28.7% (95% CI = 5.1% to 46.5%; P = .02) lower estrone sulfate levels during the follicular phase of the menstrual cycle and 27.2% (95% CI = 5.7% to 53.1%; P = .01) higher testosterone levels during the luteal phase of the menstrual cycle than did girls in the usual care group. At the last visit, the luteal phase progesterone level was 52.9% (95% CI = 20.0% to 72.3%) lower for girls in the intervention group than for girls in the usual care group (P = .007). Conclusion: Modest reductions in fat intake during puberty are associated with changes in sex hormone concentrations that are consistent with alterations in the function of the hypothalamic–pituitary–ovarian axis. Whether these changes influence breast cancer risk is currently unknown. [J Natl Cancer Inst 2003;95:132–41]

Concern has been raised about the adequacy of radioimmunoassays to measure steroid sex hormones in population studies. We compared steroid sex hormone measurements in serum by radioimmunoassay with mass spectrometry. Four male and four female serum pools with known relative concentrations of steroid sex hormones were measured multiple times by both methods. Because measurements are expected to increase linearly with concentration for each sex, we examined whether the linear regressions of hormone measurements on concentration were the same for radioimmunoassay and mass spectrometry. Estradiol, estrone, androstenedione, testosterone, and dehydroepiandrosterone sulfate were measured in female pools; testosterone, dihydrotestosterone, androstenedione, and dehydroepiandrosterone sulfate were measured in male pools. Regression slopes for radioimmunoassay and mass spectrometry measurements were comparable for all hormones except androstenedione, which had a steeper slope when measured by mass spectrometry (Por = 0.02). Intercepts for radioimmunoassay and mass spectrometry were similar and close to zero for estradiol, androstenedione, dehydroepiandrosterone sulfate, and in male samples, testosterone. For testosterone in female samples, estrone, and dihydrotestosterone, radioimmunoassay and mass spectrometry intercepts differed significantly. Standard deviations of individual measurements by radioimmunoassay and mass spectrometry differed by hormone and serum concentration; neither method consistently measured hormone concentrations with less variability. Our findings suggest that although absolute concentrations may differ for some hormones, radioimmunoassay and mass spectrometry can yield similar estimates of between subject differences in serum concentrations of most steroid sex hormones commonly measured in population studies. Relative power of studies using radioimmunoassay and mass spectrometry will depend on the hormones measured and their serum concentrations.

In a previous report (Kimball and Friedman, Am J Epidemiol, 1992;135:1279-86), linear models for relating health outcomes to alcohol consumption were proposed for differentiating between beverage type effects and beverage preference effects. The models were applied to data relating serum high density lipoprotein cholesterol to alcohol consumption. In this report, those models are extended to the nonlinear case and are applied to data from the 1982 Maryland Hypertension Survey relating systolic blood pressure to alcohol consumption.