Lifestyle intervention for adults with spinal cord injury: Results of the USC-RLANRC Pressure Ulcer Prevention Study.

CONTEXT/OBJECTIVE: Medically serious pressure injuries (MSPrIs), a common complication of spinal cord injury (SCI), have devastating consequences on health and well-being and are extremely expensive to treat. We aimed to test the efficacy of a lifestyle-based intervention designed to reduce incidence of MSPrIs in adults with SCI. DESIGN: A randomized controlled trial (RCT), and a separate study wing involving a nonrandomized standard care control group. SETTING: Rancho Los Amigos National Rehabilitation Center, a large facility serving ethnically diverse, low income residents of Los Angeles County. PARTICIPANTS: Adults with SCI, with history of one or more MSPrIs over the past 5 years: N=166 for RCT component, N=66 in nonrandomized control group. INTERVENTIONS: The Pressure Ulcer Prevention Program, a 12-month lifestyle-based treatment administered by healthcare professionals, largely via in-home visits and phone contacts. OUTCOME MEASURES: Blinded assessments of annualized MSPrI incidence rates at 12 and 24 months, based on: skin checks, quarterly phone interviews with participants, and review of medical charts and billing records. Secondary outcomes included number of surgeries and various quality-of-life measures. RESULTS: Annualized MSPrI rates did not differ significantly between study groups. At 12 months, rates were .56 for intervention recipients, .48 for randomized controls, and .65 for nonrandomized controls. At follow-up, rates were .44 and .39 respectively for randomized intervention and control participants. CONCLUSIONS: Evidence for intervention efficacy was inconclusive. The intractable nature of MSPrI threat in high-risk SCI populations, and lack of statistical power, may have contributed to this inability to detect an effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT01999816.

A Retrospective Review of Infants Receiving Sildenafil.

OBJECTIVE: The purpose of the study was to assess mortality in an infant population receiving sildenafil. METHODS: A retrospective review of hospitalized infants at Children's Hospital Los Angeles who received sildenafil between 2008 and 2012 was conducted. Patient characteristics, comorbidities, and treatment characteristics were analyzed. Primary outcome was mortality at discharge. Sildenafil dosage ranges were based on the Sildenafil in Treatment-Naïve Children, Aged 1-17 Years, With Pulmonary Arterial Hypertension trial and were categorized as small (<1.5 mg/kg/day), medium (1.5-3.75 mg/kg/day), large (3.76-7.5 mg/kg/day), and very large (>7.5 mg/kg/day). RESULTS: A total of 147 infants were studied. A total of 82% of patients had severe pulmonary hypertension. Our data revealed 29% mortality at discharge. Mortality increased with increasing sildenafil dosage: 14% (small), 19% (medium), 49% (large), and 90% (very large). On multivariate analysis of sildenafil dosage, other pulmonary hypertension therapies, presence of persistent cardiac shunts, and duration of sildenafil, odds of dying were significantly higher with combined high and very high sildenafil dosage groups compared with combined low and medium dosage groups (OR, 13.2; CI, 4.4-39.5; p < 0.0001). CONCLUSION: Sildenafil was given to critically ill infants with multiple risk factors for mortality. Although higher doses cannot be causally related to mortality, there appears to be no added benefit by escalating the sildenafil dose.

Lower-limb dynamics and clinical outcomes for habitually shod runners who transition to barefoot running.

OBJECTIVES: Recent investigations have revealed lower vertical loading rates and knee energy absorption amongst experienced barefoot runners relative to those who rear-foot strike (RFS). Although this has led to an adoption of barefoot running amongst many recreational shoe runners, recent investigations indicate that the experienced barefoot pattern is not immediately realized. Therefore, the purpose this investigation was to quantify changes in lower-extremity dynamics and clinical outcomes measures for habitually shod runners who perform a transition to barefoot running. DESIGN & PARTICIPANTS: We examined lower-extremity dynamics and clinical outcomes for 26 RFS shod runners who performed an 8-10 week transition to barefoot running. SETTING: Runners were evaluated at the University of Southern California's Musculoskeletal Biomechanics Research Laboratory. MAIN OUTCOME MEASURES: Foot-strike patterns, vertical load rates, and joint energetics were evaluated before and after the transition using inverse dynamics. Clinical assessments were conducted throughout the transition by two licensed clinicians. RESULTS: Eighteen of the 26 runners successfully completed the transition: 7 maintained a RFS, 8 adopted a mid-foot strike (MFS), and 3 adopted a forefoot strike (FFS) during novice barefoot running. Following the transition, novice MFS/FFS runners often demonstrated reversions in strike-patterns and associated reductions in ankle energetics. We report no change in loading rates and knee energy absorption across transition time points. Importantly, there were no adverse events other than transient pain and soreness. CONCLUSIONS: These findings indicate that runners do not innately adopt the biomechanical characteristics thought to lower injury risk in-response to an uninstructed barefoot running transition.

Prevalence of Lens Opacities in Adult Chinese Americans: The Chinese American Eye Study (CHES).

Purpose: We determined the age- and sex-specific prevalence of posterior subcapsular (PSC), nuclear, cortical, and mixed lens opacities in a population-based sample of Chinese-American adults. Methods: A population-based sample of Chinese-Americans 50 years and older, from 10 census tracts in Monterey Park, CA, USA, underwent a detailed interview and a comprehensive clinical examination that included assessment of different types of lens opacities by the slit-lamp-based Lens Opacities Classification System II (LOCS II). All lens changes (including pseudophakia/aphakia), PSC, nuclear, and/or cortical opacities, were evaluated and graded. Results: Of the 5782 eligible subjects, 4582 (79.2%) Chinese Americans aged 50 years and older completed a comprehensive eye examination. Of the participants with LOCS II grading (n = 4234/4582, 92%), 3.0% had PSC opacities, 38.1% had nuclear opacities, and 23.4% had cortical opacities. The prevalence of all lens changes was 48.0% for all age groups and was higher by 10-year increasing age groups (P < 0.0001). The prevalence of visual impairment in the better-seeing eye with cortical only, nuclear only, PSC only, and mixed opacities was 3.9%, 5.0%, 14.3%, and 9.4%, respectively. A total of 454 (9.9%) individuals had undergone cataract extraction in at least one eye. Conclusions: Chinese Americans have a high prevalence of visual impairment associated with lens opacities, and a high prevalence of nuclear opacities. Public health policies and programs designed to improve cataract detection and treatment could help reduce the burden of visual impairment in Chinese Americans.

Prevalence and Causes of Visual Impairment and Blindness in Chinese American Adults: The Chinese American Eye Study.

IMPORTANCE: Visual impairment (VI) and blindness continue to be major public health problems worldwide. Despite previously published studies on VI in Chinese and other racial/ethnic populations, there are no data specific to Chinese American adults. OBJECTIVES: To determine the age- and sex-specific prevalence and causes of VI and blindness in adult Chinese Americans and to compare the prevalence to other racial/ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: In this population-based, cross-sectional study of 10 US Census tracts in the city of Monterey Park, California, 4582 Chinese American adults 50 years and older underwent complete ophthalmologic examinations, including measurement of presenting and best-corrected visual acuity (BCVA) for distance using the Early Treatment Diabetic Retinopathy Study protocol from February 1, 2010, through October 31, 2013. MAIN OUTCOMES AND MEASURES: Age-specific prevalence and causes of VI and blindness for presenting and BCVA. RESULTS: Of the 5782 eligible adults, 4582 (79.2%) completed an in-clinic eye examination. Of the 4582 participants, most were born in China (3149 [68.7%]), female (2901 [63.3%]), and married (3458 [75.5%]). The mean (SD) age was 61 (9) years. The prevalence of presenting VI was 3.0% (95% CI, 2.5%-3.5%), with 60.0% of this prevalence being attributed to uncorrected refractive error. The overall age-adjusted prevalence for VI (BCVA of ≤20/40 in the better eye) was 1.2% (95% CI, 0.9%-1.5%). The overall age-adjusted prevalence of blindness (BCVA of ≤20/200 in the better-seeing eye) was 0.07% (95% CI, 0%-0.2%). The prevalence of VI and blindness was higher in older Chinese Americans compared with younger. The primary causes of VI were cataracts and myopic retinopathy; the primary cause of blindness was myopic retinopathy. CONCLUSIONS AND RELEVANCE: The prevalence of VI in Chinese Americans is similar to that of non-Hispanic white and Latino individuals in the United States and similar to or lower than the prevalence previously reported for Chinese adults from non-US studies. The prevalence of blindness is lower than that noted in other US or non-US studies. Myopic retinopathy is a frequent cause of VI and blindness in Chinese Americans that has not been commonly observed in other racial/ethnic groups. Because myopia frequently develops at a young age, Chinese Americans should be educated regarding the importance of regular screening of preschool and school-aged children to reduce the development and progression of myopia.

Prevalence of Diabetic Retinopathy in Adult Chinese American Individuals: The Chinese American Eye Study.

IMPORTANCE: Chinese American individuals are a fast-growing segment of people in the United States, but the burden and effect of diabetic complications on this group of people is not fully understood. OBJECTIVE: To determine the age- and sex-specific prevalence of diabetic retinopathy (DR) overall and by severity, duration of diabetes, and treatment history in adult Chinese American individuals. DESIGN, SETTING, AND PARTICIPANTS: The Chinese American Eye Study (CHES), a population-based, cross-sectional study, was conducted from February 2010 to October 2013 for 10 census tracts in Monterey Park, California. This analysis, conducted between February 16, 2010, and October 9, 2013, included 4582 Chinese residents 50 years and older. MAIN OUTCOMES AND MEASURES: Prevalence of nonproliferative DR, proliferative DR, and macular edema, as well as stereoscopic fundus photography of 7 standard Early Treatment Diabetic Retinopathy Study fields. RESULTS: Of the 4582 survey participants, most were first-generation immigrants from China (68.7%) and female (63%). In total, 736 participants (16.1%) were identified as having type 2 diabetes. Fundus photographs were gradable for 665 (90.4%) of these participants. The reproducibility of DR grading was evaluated throughout study and showed moderate to excellent agreement (weighted κ = 0.78-0.97). Diabetic retinopathy was present in 35.8% of people with diabetes (95% CI, 32.1%-39.6%). The estimated prevalence of severe nonproliferative DR and proliferative DR was 1.7% (95% CI, 0.8%-2.9%) and 2.4% (95% CI, 1.4%-3.9%), respectively. Macular edema was observed among 4.5% of people with diabetes (95% CI, 3.0%-6.4%), and clinically significant macular edema was observed among 2.0% (95% CI, 1.1%-3.3%). The prevalence of DR was higher (56%) among participants with a longer duration of diabetes (≥15 years; P < .001). The prevalence of visual impairment (best-corrected visual acuity worse than 20/40 in the better-seeing eye) among participants with diabetes was higher than those without diabetes (6.7% vs 2.2% = difference of 4.5%; 95% CI, 3.9%-5.1%). The primary causes of visual impairment in participants with diabetes were cataracts (38% of participants; 95% CI, 36.6%-39.4%) followed by macular edema (7% of participants; 95% CI, 6.3%-7.7%). CONCLUSIONS AND RELEVANCE: Data from CHES and this study indicate that the prevalence of DR in the Chinese American Eye Study Group is relatively lower than studies of Chinese individuals residing in rural northern China or Latino individuals from Los Angeles County, California.

Prevalence of Age-Related Macular Degeneration in Chinese American Adults: The Chinese American Eye Study.

IMPORTANCE: Population-based prevalence estimates of age-related macular degeneration (AMD) need to be determined to assess its burden among Chinese Americans, the fastest growing racial group in the United States. OBJECTIVE: To determine the age- and sex- specific prevalence of AMD among Chinese Americans. DESIGN: The Chinese American Eye Study (CHES) was conducted in a general urban community of 10 census tracts in Monterey Park, California. A total of 4582 Chinese American adults aged 50 years or older participated in this population-based, cross-sectional study from February 16, 2010, through October 9, 2013, and underwent an interview as well as comprehensive clinical and eye examinations, including detailed retinal photography of both eyes. Fundus photographs were graded for drusen and retinal pigment epithelium abnormalities and were evaluated for AMD. MAIN OUTCOMES AND MEASURES: The prevalence of early and advanced AMD, drusen, geographic atrophy, and neovascular AMD were determined by using a modified Wisconsin Age-Related Maculopathy Grading Scale (a 6-level scale: 10, no AMD; 60, advanced AMD). RESULTS: Of the 4582 participants completing both the home survey and clinical examination, 4172 individuals (91.1%) had at least 1 gradable photograph. A total of 1526 (36.6%) participants were men, and the mean (SD) age was 61.2 (8.8) years. When examined by 10-year age groups, the prevalence of early AMD ranged from 5.8% (n = 119) in participants aged 50 to 59 years to 17.6% (n = 37) in those 80 years or older, retinal pigment epithelium abnormalities from 4.1% (n = 85) to 7.2% (n = 16), large drusen (≥125 µm) from 9.8% to 32.4%, soft drusen from 27.6% (n = 567) to 58.6% (n = 123), and soft indistinct drusen from 3.7% (n = 76) to 15.2% (n = 32). The prevalence of advanced AMD ranged from 0.2% (n = 3) in participants aged 50 to 59 years to 1.0% (n = 2) in those 80 years or older. Of the 14 cases of advanced AMD, 85.7% (95% CI, 57.2%-98.2%; n = 12) were neovascular AMD and 14.3% (95% CI, 2.0%-42.8%; n = 2) were geographic atrophy. Acute macular degeneration was more common in men (10.9% [9.3%-12.5%]; n = 166) than women (5.8% [4.9%-6.7%]; n = 154) in this cohort. CONCLUSIONS AND RELEVANCE: Data from CHES suggest that Chinese Americans have a lower prevalence of early and advanced AMD compared with non-Hispanic white individuals. The prevalence of early AMD, advanced AMD, and large drusen was higher among Chinese Americans in CHES than among the Chinese population living in urban/rural China but lower than that in urban-dwelling Taiwanese.

Age-Related Macular Degeneration and Quality of Life in Latinos: The Los Angeles Latino Eye Study.

IMPORTANCE: This study found evidence of a threshold effect in which the presence of bilateral soft drusen and depigmentation of retinal pigment epithelium was associated with substantially low health-related quality of life (HRQoL) in adult Latinos from the United States. OBJECTIVE: To assess the association of general and vision-specific HRQoL with age-related macular degeneration (AMD), overall and by bilaterality and severity, in adult Latinos. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, population-based study included 4876 participants from the general urban community in 6 US Census tracts in La Puente, California. The data for these analyses were collected as part of a population-based study of ocular diseases in adult Latinos in the Los Angeles Latino Eye Study from February 1, 2000, through May 31, 2003. The analysis was performed from November 2010 to February 2011. Additional analyses were performed in June 2014. MAIN OUTCOMES AND MEASURES: Mean-adjusted HRQoL scores and effect sizes. RESULTS: Of the 4876 participants included in the analysis, 4402 (90.3%) had no AMD, and 474 (9.7%) had any AMD, with 453 having early (9.3%) and 21 (0.4%) having late stages of the disease. The mean (SD) age of the cohort was 54.8 (10.7) years. Of the 4876 participants, 2001 (41.0%) were male and 2875 (59.0%) were female. In this cohort of Latinos, participants with AMD had lower vision-specific HRQoL scores. General HRQoL was assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey and self-reported vision-related HRQoL by the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Composite NEI-VFQ-25 scores were 59.5 (95% CI, 50.8-68.1) for those with late-stage AMD and 79.4 (95% CI, 72.5-86.1) for those with early-stage AMD, compared with participants without AMD 80.7 (95% CI, 73.9-82.4); P < .001. Several lesions of early AMD were associated with lower NEI-VFQ-25 composite scores and 8 to 10 individual scales. Large effect sizes and lower mean scores were observed for those with late AMD lesions, overall and specifically for geographic atrophy and neovascular AMD, compared with those without AMD. With the use of concatenated bilateral severity levels for AMD, decreases in the NEI-VFQ-25 composite and individual scale scores were observed at the transition from a unilateral to bilateral severity level of 40, which corresponds to having bilateral soft drusen (>125 µm in diameter with drusen area ≥196 350 µm2) and depigmentation of retinal pigment epithelium (slope of -19.17 for the NEI-VFQ-25 composite score). Measures of general health, as assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey, were not affected in this cohort. CONCLUSIONS AND RELEVANCE: In this study of adult Latinos, early AMD lesions are associated with lower self-reported, vision-specific HRQoL but not general HRQoL. Severity and bilaterality of AMD are associated with measurably lower HRQoL scores, with the largest difference in scores occurring for individuals with both eyes affected. A concatenated approach to incorporate bilateral severity might be more useful and provide better insight into the association of AMD and HRQoL.

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.

BACKGROUND: Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. METHODS: A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17ß-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. RESULTS: After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. CONCLUSIONS: Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).

Clinical improvements in adopted children with fetal alcohol spectrum disorders through neurodevelopmentally informed clinical intervention: A pilot study.

Research on early intervention for young children (infants and toddlers) with fetal alcohol spectrum disorders (FASD), particularly children with comorbid maltreatment experiences, is limited. Existing research has primarily focused on structuring environments to be responsive to the needs experienced by children with FASD rather than improving their functioning. The purpose of this study is to present outcomes from an early psychosocial intervention with 10 adopted, maltreated young children diagnosed with FASD, aged 10-53 months (M = 35 months), and their adoptive parents. The potential for early, targeted interventions to improve developmental outcomes for children with prenatal alcohol exposure was examined, as well as improving the skills of and reducing stress experienced by their adoptive parents. Based on the outcomes of a neurodevelopmentally informed assessment protocol, the 10 children whose data are presented were recommended to receive a range of regulatory, somatosensory, relational, and cognitive enrichments. As part of their treatment, children and caregivers received Child-Parent Psychotherapy (CPP), and caregivers (here, adoptive parents) also received Mindful Parenting Education (MPE). Related-samples Wilcoxon signed-rank tests indicated that scores of several measures of child developmental functioning improved from pre- to post-intervention and that parents' caregiving skills improved while their caregiving stress decreased. Reliable change analyses indicated that change observed from pre- to post-intervention was reliable. The promise of using neurodevelopmentally informed assessment strategies to sequence interventions for young children with diverse neurodevelopmental insults is discussed.

Effect of a Task-Oriented Rehabilitation Program on Upper Extremity Recovery Following Motor Stroke: The ICARE Randomized Clinical Trial.

IMPORTANCE: Clinical trials suggest that higher doses of task-oriented training are superior to current clinical practice for patients with stroke with upper extremity motor deficits. OBJECTIVE: To compare the efficacy of a structured, task-oriented motor training program vs usual and customary occupational therapy (UCC) during stroke rehabilitation. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, pragmatic, single-blind randomized trial among 361 participants with moderate motor impairment recruited from 7 US hospitals over 44 months, treated in the outpatient setting from June 2009 to March 2014. INTERVENTIONS: Structured, task-oriented upper extremity training (Accelerated Skill Acquisition Program [ASAP]; n = 119); dose-equivalent occupational therapy (DEUCC; n = 120); or monitoring-only occupational therapy (UCC; n = 122). The DEUCC group was prescribed 30 one-hour sessions over 10 weeks; the UCC group was only monitored, without specification of dose. MAIN OUTCOMES AND MEASURES: The primary outcome was 12-month change in log-transformed Wolf Motor Function Test time score (WMFT, consisting of a mean of 15 timed arm movements and hand dexterity tasks). Secondary outcomes were change in WMFT time score (minimal clinically important difference [MCID] = 19 seconds) and proportion of patients improving ≥25 points on the Stroke Impact Scale (SIS) hand function score (MCID = 17.8 points). RESULTS: Among the 361 randomized patients (mean age, 60.7 years; 56% men; 42% African American; mean time since stroke onset, 46 days), 304 (84%) completed the 12-month primary outcome assessment; in intention-to-treat analysis, mean group change scores (log WMFT, baseline to 12 months) were, for the ASAP group, 2.2 to 1.4 (difference, 0.82); DEUCC group, 2.0 to 1.2 (difference, 0.84); and UCC group, 2.1 to 1.4 (difference, 0.75), with no significant between-group differences (ASAP vs DEUCC: 0.14; 95% CI, -0.05 to 0.33; P = .16; ASAP vs UCC: -0.01; 95% CI, -0.22 to 0.21; P = .94; and DEUCC vs UCC: -0.14; 95% CI, -0.32 to 0.05; P = .15). Secondary outcomes for the ASAP group were WMFT change score, -8.8 seconds, and improved SIS, 73%; DEUCC group, WMFT, -8.1 seconds, and SIS, 72%; and UCC group, WMFT, -7.2 seconds, and SIS, 69%, with no significant pairwise between-group differences (ASAP vs DEUCC: WMFT, 1.8 seconds; 95% CI, -0.8 to 4.5 seconds; P = .18; improved SIS, 1%; 95% CI, -12% to 13%; P = .54; ASAP vs UCC: WMFT, -0.6 seconds, 95% CI, -3.8 to 2.6 seconds; P = .72; improved SIS, 4%; 95% CI, -9% to 16%; P = .48; and DEUCC vs UCC: WMFT, -2.1 seconds; 95% CI, -4.5 to 0.3 seconds; P = .08; improved SIS, 3%; 95% CI, -9% to 15%; P = .22). A total of 168 serious adverse events occurred in 109 participants, resulting in 8 patients withdrawing from the study. CONCLUSIONS AND RELEVANCE: Among patients with motor stroke and primarily moderate upper extremity impairment, use of a structured, task-oriented rehabilitation program did not significantly improve motor function or recovery beyond either an equivalent or a lower dose of UCC upper extremity rehabilitation. These findings do not support superiority of this program among patients with motor stroke and primarily moderate upper extremity impairment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00871715.

Impaired coronary artery distensibility is an endothelium-dependent process and is associated with vulnerable plaque composition.

Coronary endothelial-dependent microvascular dysfunction, an early reversible stage of coronary artery disease (CAD), is associated with poor clinical outcome. The current study investigated whether coronary artery distensibility index (CDI) is associated with: (i) coronary endothelial-dependent microvascular dysfunction and (ii) vulnerable plaque composition among subjects with non-obstructive CAD. Seventy-four subjects with non-obstructive CAD (luminal stenosis <30%) were studied. In 20 subjects with and without coronary endothelial-dependent microvascular dysfunction, coronary flow reserve (CFR) of target segment during intracoronary (IC) infusion of acetylcholine (Ach) and bolus injection of adenosine as well as CDI at rest of corresponding target segment were measured. In 54 subjects, plaque compositions and CDI at rest of 154 non-obstructive coronary segments as well as proximal segment without disease were measured by intravascular ultrasound (IVUS). CDI was defined as: [(Early-diastolic cross-sectional-area (CSA) - End-diastolic CSA of target segment)/(end-diastolic CSA of target segment × coronary-pulse-pressure) × 10(3) ]. There is a direct association between endothelial dysfunction and impaired CDI of a coronary segment both in the given coronary segment and corresponding microvessels in which a strong agreement between CDI and CFR Ach (r(2)  = 0·85, P = 0·0001) was observed. Multivariable regression-analysis showed that CDI was an independent predictor of the vulnerable plaque characteristics. The risk of impaired CDI was 125% higher in segments with necrotic core and 60% higher in segments with fibrofatty components as compared to normal segments (P = 0·001). In conclusions, the current study reveals that impaired CDI is an endothelial-dependent process of both given coronary segment and corresponding microvessels and is associated with vulnerable plaque composition.

Life span exercise among elite intercollegiate student athletes.

BACKGROUND: Despite prominent public attention, data on life span health and exercise outcomes among elite, competitive athletes are sparse and do not reflect the diversity of modern athletes. HYPOTHESIS: Life span exercise behavior differs between National Collegiate Athletic Association (NCAA) student athletes and a nonathlete control group. Sustained exercise is associated with improved cardiopulmonary health outcomes. STUDY DESIGN: Cross-sectional, descriptive epidemiology study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 496 students and alumni (age range, 17-84 year) at a large, NCAA Division I university, including student athletes and an age- and sex-matched nonathlete control group, completed anonymous, self-report health and exercise questionnaires. Age-stratified, cross-sectional analysis evaluated previous week's total exercise volume (ExVol), self-rated exercise importance (ExImp), and compliance with American College of Sports Medicine (ACSM) exercise guidelines for healthy adults. The association of ACSM guideline compliance with lifetime cardiopulmonary health outcomes was also assessed. RESULTS: Current student athletes reported significantly greater ExVol (P < 0.001. Cohen d = 0.99, probability of clinically important difference [pCID] >99.5%), ExImp (P < 0.001, d = 1.96, pCID = 96%), and likelihood of compliance with ACSM guidelines (odds ratio [OR], 95% confidence interval [CI] = 30.6, 11.0-84.6) compared with nonathletes. No significant differences were found between alumni student athletes and nonathletes. Alumni student athletes demonstrated substantially lower ExVol (P < 0.001, d = -0.94, pCID >99.5%) and guideline compliance (OR = 0.09, 95% CI = 0.05-0.19) compared with current student athletes, whereas nonathletes had similar exercise behavior across the life span. Among alumni, ACSM guideline compliance was associated with significant attenuation of cardiopulmonary health concerns (P = 0.02, d = -0.50, pCID = 14%) independent of intercollegiate athletic participation. CONCLUSION: Although current NCAA Division I student athletes demonstrated significant, clinically important differences in exercise behavior compared with nonathletes, no group differences were evident later in life. Irrespective of collegiate athletic status, healthy exercise behavior among alumni was associated with cardiopulmonary health benefits. CLINICAL RELEVANCE: To realize life span health benefits, it is imperative that student athletes maintain consistent patterns of healthy exercise beyond retirement from competitive sports.

The Trojan Lifetime Champions Health Survey: development, validity, and reliability.

CONTEXT: Self-report questionnaires are an important method of evaluating lifespan health, exercise, and health-related quality of life (HRQL) outcomes among elite, competitive athletes. Few instruments, however, have undergone formal characterization of their psychometric properties within this population. OBJECTIVE: To evaluate the validity and reliability of a novel health and exercise questionnaire, the Trojan Lifetime Champions (TLC) Health Survey. DESIGN: Descriptive laboratory study. SETTING: A large National Collegiate Athletic Association Division I university. PATIENTS OR OTHER PARTICIPANTS: A total of 63 university alumni (age range, 24 to 84 years), including former varsity collegiate athletes and a control group of nonathletes. INTERVENTION(S): Participants completed the TLC Health Survey twice at a mean interval of 23 days with randomization to the paper or electronic version of the instrument. MAIN OUTCOME MEASURE(S): Content validity, feasibility of administration, test-retest reliability, parallel-form reliability between paper and electronic forms, and estimates of systematic and typical error versus differences of clinical interest were assessed across a broad range of health, exercise, and HRQL measures. RESULTS: Correlation coefficients, including intraclass correlation coefficients (ICCs) for continuous variables and κ agreement statistics for ordinal variables, for test-retest reliability averaged 0.86, 0.90, 0.80, and 0.74 for HRQL, lifetime health, recent health, and exercise variables, respectively. Correlation coefficients, again ICCs and κ, for parallel-form reliability (ie, equivalence) between paper and electronic versions averaged 0.90, 0.85, 0.85, and 0.81 for HRQL, lifetime health, recent health, and exercise variables, respectively. Typical measurement error was less than the a priori thresholds of clinical interest, and we found minimal evidence of systematic test-retest error. We found strong evidence of content validity, convergent construct validity with the Short-Form 12 Version 2 HRQL instrument, and feasibility of administration in an elite, competitive athletic population. CONCLUSIONS: These data suggest that the TLC Health Survey is a valid and reliable instrument for assessing lifetime and recent health, exercise, and HRQL, among elite competitive athletes. Generalizability of the instrument may be enhanced by additional, larger-scale studies in diverse populations.

Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis.

OBJECTIVE: This study aims to present methods and baseline data from the Early versus Late Intervention Trial with Estradiol (ELITE), the only clinical trial designed to specifically test the timing hypothesis of postmenopausal hormone therapy (HT). The timing hypothesis posits that HT effects depend on the temporal initiation of HT relative to time since menopause. METHODS: ELITE is a randomized, double-blind, placebo-controlled trial with a 2 × 2 factorial design. Six hundred forty-three healthy postmenopausal women without cardiovascular disease were randomized to oral estradiol or placebo for up to 6 to 7 years according to time since menopause (<6 or ≥10 y). Carotid artery intima-media thickness (CIMT) and cardiac computed tomography were conducted to determine HT effects on subclinical atherosclerosis across menopause strata. RESULTS: Participants in the early and late postmenopausal strata were well-separated by mean age (55.4 vs 65.4 y) and median time since menopause (3.5 vs 14.3 y). Expected risk factors (age, blood pressure, and body mass index) were associated with CIMT at baseline in both strata. In the early postmenopausal group, but not in the late postmenopausal group, we observed significant associations between CIMT and factors that may play a role in the responsiveness of atherosclerosis progression according to timing of HT initiation. These include low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sex hormone-binding globulin, and serum total estradiol. CONCLUSIONS: The ELITE randomized controlled trial is timely and unique. Baseline data indicate that ELITE is well-positioned to test the HT timing hypothesis in relation to atherosclerosis progression and coronary artery disease.

Holistic life-span health outcomes among elite intercollegiate student-athletes.

CONTEXT: Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. OBJECTIVE: To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs). DESIGN: Cross-sectional study. SETTING: A large Division I university. PATIENTS OR OTHER PARTICIPANTS: Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. MAIN OUTCOME MEASURE(S): Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. RESULTS: Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. CONCLUSIONS: The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable cardiopulmonary health, and differences in life-span psychosocial health and HRQL profiles compared with NAs. These data provide timely evidence regarding a compelling public issue and highlight the need for further study of life-span health among modern athletes.

Comparison of robustness to outliers between robust poisson models and log-binomial models when estimating relative risks for common binary outcomes: a simulation study.

BACKGROUND: To estimate relative risks or risk ratios for common binary outcomes, the most popular model-based methods are the robust (also known as modified) Poisson and the log-binomial regression. Of the two methods, it is believed that the log-binomial regression yields more efficient estimators because it is maximum likelihood based, while the robust Poisson model may be less affected by outliers. Evidence to support the robustness of robust Poisson models in comparison with log-binomial models is very limited. METHODS: In this study a simulation was conducted to evaluate the performance of the two methods in several scenarios where outliers existed. RESULTS: The findings indicate that for data coming from a population where the relationship between the outcome and the covariate was in a simple form (e.g. log-linear), the two models yielded comparable biases and mean square errors. However, if the true relationship contained a higher order term, the robust Poisson models consistently outperformed the log-binomial models even when the level of contamination is low. CONCLUSIONS: The robust Poisson models are more robust (or less sensitive) to outliers compared to the log-binomial models when estimating relative risks or risk ratios for common binary outcomes. Users should be aware of the limitations when choosing appropriate models to estimate relative risks or risk ratios.

Visual function assessment in simulated real-life situations in HIV-infected subjects.

Visual function abnormalities are common in people living with HIV disease (PLWH) without retinitis, even after improvement in immune status. Abnormalities such as reduced contrast sensitivity, altered color vision, peripheral visual field loss, and electrophysiological changes are related to a combination of retinal dysfunctions, involving inner and outer retinal structures. The standard protocol for testing vision performance in clinical practice is the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. However, this method poorly correlates with activities of daily living that require patients to assess visual stimuli in multiple light/contrast conditions, and with limited time. We utilized a novel interactive computer program (Central Vision Analyzer) to analyze vision performance in PLWH under a variety of light/contrast conditions that simulate stressful and real-world environments. The program tests vision in a time-dependent way that we believe better correlates with daily living activities than the non-timed ETDRS chart. We also aimed to correlate visual scores with retinal neuro-fiber layer thickness on optical coherence tomography. Here we show that visual acuity is more affected in PLWH in comparison to HIV-seronegative controls in varying contrast and luminance, especially if the nadir CD4+ T-cell count was lower than 100 cells/mm3. Visual impairment reflects the loss of retinal nerve fiber layer thickness especially of the temporal-inferior sector. In PLWH the ETDRS chart test led to better visual acuity compared to the Central Vision Analyzer equivalent test, likely because patients had indefinite time to guess the letters. This study confirms and strengthens the finding that visual function is affected in PLWH even in absence of retinitis, since we found that the HIV serostatus is the best predictor of visual loss. The Central Vision Analyzer may be useful in the diagnosis of subclinical HIV-associated visual loss in multiple light/contrast conditions, and may offer better understanding of this entity called "neuroretinal disorder".

Implementing trials of complex interventions in community settings: the USC-Rancho Los Amigos pressure ulcer prevention study (PUPS).

BACKGROUND: Randomized trials of complex, non-pharmacologic interventions implemented in home and community settings, such as the University of Southern California (USC)-Rancho Los Amigos National Rehabilitation Center (RLANRC) Pressure Ulcer Prevention Study (PUPS), present unique challenges with respect to (1) participant recruitment and retention, (2) intervention delivery and fidelity, (3) randomization and assessment, and (4) potential inadvertent treatment effects. PURPOSE: We describe the methods employed to address the challenges confronted in implementing PUPS. In this randomized controlled trial, we are assessing the efficacy of a complex, preventive intervention in reducing the incidence of, and costs associated with, the development of medically serious pressure ulcers in people with spinal cord injury. METHODS: Individuals with spinal cord injury recruited from RLANRC were assigned to either a 12-month preventive intervention group or a standard care control group. The primary outcome is the incidence of serious pressure ulcers with secondary endpoints including ulcer-related surgeries, medical treatment costs, and quality of life. These outcomes are assessed at 12 and 24 months after randomization. Additionally, we are studying the mediating mechanisms that account for intervention outcomes. RESULTS: PUPS has been successfully implemented, including recruitment of the target sample size of 170 participants, assurance of the integrity of intervention protocol delivery with an average 90% treatment adherence rate, and enactment of the assessment plan. However, implementation has been replete with challenges. To meet recruitment goals, we instituted a five-pronged approach customized for an underserved, ethnically diverse population. In intervention delivery, we increased staff time to overcome economic and cultural barriers to retention and adherence. To ensure treatment fidelity and replicability, we monitored intervention protocol delivery in accordance with a rigorous plan. Finally, we have overcome unanticipated assessment and design concerns related to (1) determining pressure ulcer incidence/severity, (2) randomization imbalance, and (3) inadvertent potential control group contamination. LIMITATIONS: We have addressed the most daunting challenges encountered in the recruitment, assessment, and intervention phases of PUPS. Some challenges and solutions may not apply to trials conducted in other settings. CONCLUSIONS: Overcoming challenges has required a multifaceted approach incorporating individualization, flexibility, and persistence, as well as the ability to implement needed mid-course corrections.

Apriori feasibility testing of randomized clinical trial design in patients with cleft deformities and Class III malocclusion.

OBJECTIVES: To assess the feasibility of randomizing treatment (surgical vs. non-surgical) for correction of a Class III malocclusion (underbite) resulting from an earlier repair of cleft lip and palate. MATERIALS AND METHODS: Surveys about willingness to accept randomized treatment during adolescence were mailed to the parents of cleft lip and palate patients under the care of Children's Hospital Los Angeles between 2005 and 2010. The inclusion criteria were patients with cleft lip and palate, Class III malocclusion due to maxillary deficiency, and absence of medical and cognitive contraindications to treatment. RESULTS: Out of 287 surveys, 82 (28%) were completed and returned; 47% of the subjects held a strong treatment preference (95% CI, 35-58%), while 30% were willing to accept randomization (95% CI, 20-41%). Seventy-eight percent would drop out of a randomized trial if dissatisfied with the assigned treatment (95% CI, 67-86%). The three most commonly cited reasons for being unwilling to accept random treatment assignment were 1) the desire for doctors to choose the best treatment, 2) the desire for parents to have input on treatment, and 3) the desire to correct the underbite as early as possible. CONCLUSION: Based on this study, parents and patients would be unwilling to accept a randomly assigned treatment and would not remain in an assigned group if treatment did not meet expectations. This highlight the limitations associated with randomization trials involving surgical modalities and provide justification for other research models (e.g., cohort studies) to compare two treatment options when randomization is not feasible.