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.).

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.

Body-weight-supported treadmill rehabilitation after stroke.

BACKGROUND: Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. METHODS: We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. RESULTS: At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). CONCLUSIONS: Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

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.

Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE): a randomized controlled trial protocol.

BACKGROUND: Residual disability after stroke is substantial; 65% of patients at 6 months are unable to incorporate the impaired upper extremity into daily activities. Task-oriented training programs are rapidly being adopted into clinical practice. In the absence of any consensus on the essential elements or dose of task-specific training, an urgent need exists for a well-designed trial to determine the effectiveness of a specific multidimensional task-based program governed by a comprehensive set of evidence-based principles. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) Stroke Initiative is a parallel group, three-arm, single blind, superiority randomized controlled trial of a theoretically-defensible, upper extremity rehabilitation program provided in the outpatient setting.The primary objective of ICARE is to determine if there is a greater improvement in arm and hand recovery one year after randomization in participants receiving a structured training program termed Accelerated Skill Acquisition Program (ASAP), compared to participants receiving usual and customary therapy of an equivalent dose (DEUCC). Two secondary objectives are to compare ASAP to a true (active monitoring only) usual and customary (UCC) therapy group and to compare DEUCC and UCC. METHODS/DESIGN: Following baseline assessment, participants are randomized by site, stratified for stroke duration and motor severity. 360 adults will be randomized, 14 to 106 days following ischemic or hemorrhagic stroke onset, with mild to moderate upper extremity impairment, recruited at sites in Atlanta, Los Angeles and Washington, D.C. The Wolf Motor Function Test (WMFT) time score is the primary outcome at 1 year post-randomization. The Stroke Impact Scale (SIS) hand domain is a secondary outcome measure.The design includes concealed allocation during recruitment, screening and baseline, blinded outcome assessment and intention to treat analyses. Our primary hypothesis is that the improvement in log-transformed WMFT time will be greater for the ASAP than the DEUCC group. This pre-planned hypothesis will be tested at a significance level of 0.05. DISCUSSION: ICARE will test whether ASAP is superior to the same number of hours of usual therapy. Pre-specified secondary analyses will test whether 30 hours of usual therapy is superior to current usual and customary therapy not controlled for dose. TRIAL REGISTRATION: www.ClinicalTrials.gov Identifier: NCT00871715

Characterizing and identifying risk for falls in the LEAPS study: a randomized clinical trial of interventions to improve walking poststroke.

BACKGROUND AND PURPOSE: Better understanding of fall risk poststroke is required for developing screening and prevention programs. This study characterizes falls in the Locomotor Experience Applied Post-Stroke (LEAPS) randomized clinical trial, describes the impact of 2 walking recovery interventions on falls, and examines the value of clinical assessments for predicting falls. METHODS: Community-dwelling ambulatory stroke survivors enrolled in LEAPS were assessed 2 months poststroke. Falls were monitored until 12 months poststroke and participants were characterized as multiple or injurious (M/I); single, noninjurious; or nonfallers. Incidence and time to M/I falls were compared across interventions (home exercise and locomotor training initiated 2 months [early-LTP] or 6 months [late-LTP] poststroke). Predictive value of 2-month clinical assessments for falls outcome was assessed. RESULTS: Among the 408 participants, 36.0% were M/I, 21.6% were single, noninjurious, and 42.4% were nonfallers. Most falls occurred at home in the first 3 months after assessment. Falls incidence was highest for those with severe walking impairment who received early-LTP (P=0.025). Berg Balance Scale score ≤ 42/56 was the single best predictor of M/I falls. CONCLUSIONS: As individuals with stroke improve in walking capacity, risk for M/I falls remains high. Individuals walking <0.4 m/s are at higher risk for M/I falls if they receive early-LTP training. Berg Balance Scale score at 2 months poststroke is useful for informing falls risk, but it cannot account for the multifactorial nature of the problem. Falls prevention in stroke will require multifactorial risk assessment and management provided concomitantly with exercise interventions to improve mobility. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00243919.

Risk factors for incident cortical, nuclear, posterior subcapsular, and mixed lens opacities: the Los Angeles Latino eye study.

PURPOSE: To identify sociodemographic and biological risk factors associated with the 4-year incidence of nuclear, cortical, posterior subcapsular (PSC), and mixed lens opacities. DESIGN: Population-based, longitudinal study. PARTICIPANTS: We included 4658 Latinos ≥40 years from 6 census tracts in Los Angeles, California. METHODS: Participants underwent an interview and detailed eye examination, including best-corrected visual acuity and slit-lamp assessment of lens opacities using the Lens Opacities Classification System II (LOCS II) at baseline and again 4 years later. Each opacity type was defined in persons with a LOCS II score of ≥2. Univariate and forward stepwise logistic regression analyses were used to identify independent baseline risk factors associated with 4-year incidence of nuclear only, cortical only, PSC only, and mixed (when >1 opacity type developed in a person) lens opacities. These comprised 4 mutually exclusive groups, and were based on person rather than eye. MAIN OUTCOME MEASURES: Odds ratios for independent risk factors associated with 4-year incidence of nuclear-only, cortical-only, PSC-only, and mixed lens opacities. RESULTS: Of the 3471 participants with gradable lenses in the same eye at baseline and 4-year follow-up, 200 (5.8%) had incident nuclear-only opacities, 151 (4.1%) had incident cortical-only opacities, 16 (0.5%) had incident PSC-only lens opacities, and 88 (2.5%) had mixed lens opacities. Independent baseline risk factors for incident nuclear-only lens opacities included older age, current smoking, and presence of diabetes. Independent risk factors for incident cortical-only lens opacities included older age and having diabetes at baseline. Female gender was an independent risk factor for incident PSC-only lens opacities. Older age and presence of diabetes at baseline examination were independent risk factors for incident mixed lens opacities. Specifically, in diabetics, higher levels of hemoglobin A1c was associated with greater risk for 4-year incident nuclear-only, cortical-only and mixed lens opacities. CONCLUSIONS: Improved diabetic control and smoking prevention may reduce the risk of developing lens opacities. Understanding both modifiable and nonmodifiable risk factors provides insight into the development of lens opacification.

Risk factors for cortical, nuclear, posterior subcapsular, and mixed lens opacities: the Los Angeles Latino Eye Study.

PURPOSE: To identify sociodemographic and biological risk factors associated with having cortical, nuclear, posterior subcapsular (PSC), and mixed lens opacities. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 5945 Latinos aged ≥ 40 years from 6 census tracts in Los Angeles, California. METHODS: Participants underwent an interview and detailed eye examination, including best-corrected visual acuity and slit-lamp assessment of lens opacities using the Lens Opacities Classification System II. Univariate and stepwise logistic regression analyses were used to identify independent risk factors associated with each type of lens opacity. MAIN OUTCOME MEASURES: Odds ratios for sociodemographic and biological risk factors associated with cortical only, nuclear only, PSC only, and mixed lens opacities. RESULTS: Of the 5945 participants with gradable lenses, 468 had cortical only lens opacities, 217 had nuclear only lens opacities, 27 had PSC only opacities, and 364 had mixed lens opacities. Older age, higher hemoglobin A(1c), and history of diabetes mellitus were independent risk factors for cortical only lens opacities. Older age, smoking, and myopic refractive error were independent risk factors for nuclear only lens opacities. Higher systolic blood pressure and history of diabetes were independent risk factors for PSC lens opacities. Older age, myopic refractive error, history of diabetes, higher systolic blood pressure, female gender, and presence of large drusen were independent risk factors for mixed lens opacities. CONCLUSIONS: The modifiable and non-modifiable risk factors identified in this study provide insight into the mechanisms related to the development of lens opacification. Improved glycemic control, smoking cessation and prevention, and blood pressure control may help to reduce the risk of having lens opacities and their associated vision loss.

Baseline risk factors that predict the development of open-angle glaucoma in a population: the Los Angeles Latino Eye Study.

OBJECTIVE: To determine which baseline sociodemographic, lifestyle, anthropometric, clinical, and ocular risk factors predict the development of open-angle glaucoma (OAG) in an adult population. DESIGN: A population-based, prospective cohort study. PARTICIPANTS: A total of 3772 self-identified Latinos aged ≥40 years from Los Angeles, California, who were free of OAG at baseline. METHODS: Participants from the Los Angeles Latino Eye Study had standardized study visits at baseline and 4-year follow-up with structured interviews and a comprehensive ophthalmologic examination. We defined OAG as the presence of an open angle and a glaucomatous visual field abnormality and/or evidence of glaucomatous optic nerve damage in ≥1 eye. Multivariate logistic regression with stepwise selection was performed to determine which potential baseline risk factors independently predict the development of OAG. MAIN OUTCOME MEASURES: Odds ratios for various risk factors. RESULTS: Over the 4-year follow-up, 87 participants developed OAG. The baseline risk factors that predict the development of OAG include older age (odds ratio [OR] per decade, 2.19; 95% confidence interval [CI], 1.74-2.75; P<0.001), higher intraocular pressure (IOP; OR per mmHg, 1.18; 95% CI, 1.10-1.26; P<0.001), longer axial length (OR per mm, 1.48; 95% CI, 1.22-1.80; P<0.001), thinner central cornea (OR per 40 µm thinner, 1.30; 95% CI, 1.00-1.70; P = 0.050), higher waist-to-hip ratio (OR per 0.05 higher, 1.21; 95% CI, 1.05-1.39; P = 0.007) and lack of vision insurance (OR, 2.08; 95% CI, 1.26-3.41; P = 0.004). CONCLUSIONS: Despite a mean baseline IOP of 14 mmHg in Latinos, higher IOP is an important risk factor for developing OAG. Biometric measures suggestive of less structural support such as longer axial length and thin central corneal thickness were identified as important risk factors. Lack of health insurance reduces access to eye care and increases the burden of OAG by reducing the likelihood of early detection and treatment of OAG. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Value of measuring muscle performance to assess changes in lean mass with testosterone and growth hormone supplementation.

We hypothesized that treatment with testosterone (T) and recombinant human growth hormone (rhGH) would increase lean mass (LM) and muscle strength proportionally and an in a linear manner over 16 weeks. This was a multicenter, randomized, controlled, double-masked investigation of T and rhGH supplementation in older (71 ± 4 years) community-dwelling men. Participants received transdermal T at either 5 or 10 g/day as well as rhGH at 0, 3.0 or 5.0 µg/kg/day for 16 weeks. Body composition was determined by dual-energy X-ray absorptiometry (DEXA) and muscle performance by composite one-repetition maximum (1-RM) strength and strength per unit of lean mass (muscle quality, MQ) for five major muscle groups (upper and lower body) at baseline, week 8 and 17. The average change in total LM at study week 8 compared with baseline was 1.50 ± 1.54 kg (P < 0.0001) in the T only group and 2.64 ± 1.7 (P < 0.0001) in the T + rhGH group and at week 17 was 1.46 ± 1.48 kg (P < 0.0001) in the T only group and 2.14 ± 1.96 kg (P < 0.0001) in the T + rhGH group. 1-RM strength improved modestly in both groups combined (12.0 ± 23.9%, P < 0.0001) at week 8 but at week 17 these changes were twofold greater (24.7 ± 31.0%, P < 0.0001). MQ did not significantly change from baseline to week 8 but increased for the entire cohort, T only, and T + rhGH groups by week 17 (P < 0.001). Despite sizeable increases in LM measurements at week 8, tests of muscle performance did not show substantive improvements at this time point.

Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: a randomized controlled trial.

BACKGROUND AND PURPOSE: Although epidemiological and experimental studies suggest that dietary intake of soy may be cardioprotective, use of isoflavone soy protein (ISP) supplementation as a primary preventive therapy remains unexplored. We determined whether ISP reduces subclinical atherosclerosis assessed as carotid artery intima-media thickness progression. METHODS: In a double-blind, placebo-controlled trial, 350 postmenopausal women 45 to 92 years of age without diabetes and cardiovascular disease were randomized to 2 evenly divided daily doses of 25 g soy protein containing 91 mg aglycon isoflavone equivalents or placebo for 2.7 years. RESULTS: Overall, mean (95% CI) carotid artery intima-media thickness progression rate was 4.77 (3.39-6.16) µm/year in the ISP group and 5.68 (4.30-7.06) µm/year in the placebo group. Although carotid artery intima-media thickness progression was reduced on average by 16% in the ISP group relative to the placebo group, this treatment effect was not statistically significant (P=0.36). Among the subgroup of women who were randomized within 5 years of menopause, ISP participants had on average a 68% lower carotid artery intima-media thickness progression rate than placebo participants 2.16 (-1.10 to 5.43) versus 6.79 (3.56-10.01) µm/year (P=0.05). ISP supplementation had a null effect on women who were >5 years beyond menopause when randomized. There were no major adverse events from ISP supplementation. CONCLUSIONS: ISP supplementation did not significantly reduce subclinical atherosclerosis progression in postmenopausal women. Subgroup analysis suggests that ISP supplementation may reduce subclinical atherosclerosis in healthy young (median age, 53 years) women at low-risk for cardiovascular disease who were <5 years postmenopausal. These first trial results of their kind warrant further investigation.

Risk factors for four-year incident visual impairment and blindness: the Los Angeles Latino Eye Study.

PURPOSE: To identify independent risk factors for incident visual impairment (VI) and monocular blindness. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 4658 Latinos aged 40 years in the Los Angeles Latino Eye Study (LALES). METHODS: A detailed history and comprehensive ophthalmologic examination was performed at baseline and at the 4-year follow-up on 4658 Latinos aged ≥40 years from Los Angeles, California. Incident VI was defined as best-corrected visual acuity (BCVA) of <20/40 and >20/200 in the better-seeing eye at the 4-year follow-up examination in persons who had a BCVA of ≥20/40 in the better-seeing eye at baseline. Incident monocular blindness was defined as BCVA of ≤20/200 in 1 eye at follow-up in persons who had a BCVA >20/200 in both eyes at baseline. Sociodemographic and clinical risk factors identified at the baseline interview and examination and associated with incident VI and loss of vision were determined using multivariable regression. Odds ratios (ORs) were calculated for those variables that were independently associated with VI and monocular blindness. MAIN OUTCOME MEASURES: Odds ratios for various risk factors for incident VI and monocular blindness. RESULTS: Independent risk factors for incident VI were older age (70-79 years, OR 4.8; ≥80 years OR 17.9), unemployment (OR 3.5), and diabetes mellitus (OR 2.2). Independent risk factors for monocular blindness were being retired (OR 3.4) or widowed (OR 3.7) and having diabetes mellitus (OR 2.1) or any ocular disease (OR 5.6) at baseline. Persons with self-reported excellent/good vision were less likely to develop VI or monocular blindness (OR 0.4-0.5). CONCLUSIONS: Our data highlight that older Latinos and Latinos with diabetes mellitus or self-reported eye diseases are at high risk of developing vision loss. Furthermore, being unemployed, widowed, or retired confers an independent risk of monocular blindness. Interventions that prevent, treat, and focus on the modifiable factors may reduce the burden of vision loss in this fastest growing segment of the US population.

Severity of diabetic retinopathy and health-related quality of life: the Los Angeles Latino Eye Study.

OBJECTIVE: To assess the impact of diabetic retinopathy (DR) and its severity on health-related quality of life (HRQOL) in a population-based sample of Latinos with type 2 diabetes mellitus (DM). DESIGN: Cross-sectional population-based study, the Los Angeles Latino Eye Study (LALES). PARTICIPANTS: We included 1064 LALES participants with DM. METHODS: We measured HRQOL by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the Medical Outcomes Study 12-item Short Form Health Survey (SF-12). We assessed DR by masked standardized grading of stereoscopic photographs from 7 standard fields. Severity of DR in eyes was graded using a modified Airlie House classification. The severity scores from each eye were then concatenated to create a single per person grade ranging from 1 (no DR in either eye) to 15 (bilateral PDR). Multiple linear regression analyses were performed to determine the independent relationship between severity of DR and HRQOL after adjusting for covariates. MAIN OUTCOME MEASURES: Scores on the NEI-VFQ-25 and SF-12. RESULTS: More severe DR was associated with worse HRQOL scores on all of the NEI-VFQ-25 and SF-12 subscales (P<0.05). Individuals with DR from grade 2 (minimum nonproliferative diabetic retinopathy [NPDR]) through grade 8 (unilateral moderate NPDR) show a modest decline in HRQOL. However, the decline becomes significantly steeper between steps 8 (unilateral moderate NPDR) and 9-15 (bilateral moderate NPDR to bilateral PDR). The domains with the most significant impact were for vision-related daily activities, dependency, and mental health. CONCLUSIONS: Greater severity of DR was associated with lower general and vision-specific HRQOL. Persons with bilateral moderate NPDR had the most substantial decrease in quality of life compared with those with less severe DR. The prevention of incident DR and, more important, its progression from unilateral to bilateral NPDR is likely to have a positive impact on a person's HRQOL and should be considered an important goal in management of individuals with DM.

The impact of change in visual field on health-related quality of life the los angeles latino eye study.

PURPOSE: To assess the impact of change in visual field (VF) on change in health-related quality of life (HRQoL) at the population level. DESIGN: Prospective cohort study. PARTICIPANTS: Three thousand one hundred seventy-five Los Angles Latino Eye Study participants. METHODS: Objective measures of VF and visual acuity and self-reported HRQoL were collected at baseline and at the 4-year follow-up. Analysis of covariance was used to evaluate mean differences in change of HRQoL across severity levels of change in VF and to test for effect modification by covariates. MAIN OUTCOME MEASURES: General and vision-specific HRQoL. RESULTS: Of 3175 participants, 1430 (45%) showed a change in VF (≥1 decibel [dB]) and 1715 (54%) reported a clinically important change (≥5 points) in vision-specific HRQoL. Progressive worsening and improvement in the VF were associated with increasing losses and gains in vision-specific HRQoL for the composite score and 10 of its 11 subscales (all P(trend)<0.05). Losses in VF of more than 5 dB and gains of more than 3 dB were associated with clinically meaningful losses and gains in vision-specific HRQoL, respectively. Areas of vision-specific HRQoL most affected by greater losses in VF were driving, dependency, role-functioning, and mental health. The effect of change in VF (loss or gain) on mean change in vision-specific HRQoL varied by level of baseline vision loss (in VF, visual acuity, or both) and by change in visual acuity (all P(interaction)<0.05). Those with moderate or severe VF loss at baseline and with a more than 5 dB loss in VF during the study period had a mean loss of vision-specific HRQoL of 11.3 points, whereas those with no VF loss at baseline had a mean loss of 0.97 points. Similarly, with a more than 5 dB loss in VF and baseline visual acuity impairment (mild or severe), there was a loss in vision-specific HRQoL of 10.5 points, whereas with no visual acuity impairment at baseline, there was a loss of vision-specific HRQoL of 3.7 points. CONCLUSIONS: Both losses and gains in VF produce clinically meaningful changes in vision-specific HRQoL. In the presence of pre-existing vision loss (VF and visual acuity), similar levels of VF change produce greater losses in QOL.

Risk factors for astigmatism in preschool children: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

OBJECTIVE: To evaluate risk factors for astigmatism in a population-based sample of preschool children. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Population-based samples of 9970 children ages 6 to 72 months from Los Angeles County, California, and Baltimore, Maryland. METHODS: A cross-sectional study of children participating in the Multiethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study was completed. Data were obtained by clinical examination or by in-person interview. Odds ratios and 95% confidence intervals (CI) were calculated to evaluate potential associations between clinical, behavioral, or demographic factors and astigmatism. MAIN OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with astigmatism. RESULTS: Participants with myopia (≤-1.0 diopters) were 4.6 times as likely to have astigmatism (95% CI, 3.56-5.96) than those without refractive error, whereas participants with hyperopia (≥+2.00 diopters) were 1.6 times as likely (95% CI, 1.39-1.94). Children 6 to <12 months of age were approximately 3 times as likely to have astigmatism than children 5 to 6 years of age (95% CI, 2.28-3.73). Both Hispanic (OR, 2.38) and African-American (OR, 1.47) children were as likely to have astigmatism than non-Hispanic white children. Furthermore, children whose mothers smoked during pregnancy were 1.46 times (95% CI, 1.14-1.87) as likely to have astigmatism than children whose mothers did not smoke. CONCLUSIONS: In addition to infancy, Hispanic and African-American race/ethnicity and correctable/modifiable risk factors such as myopia, hyperopia, and maternal smoking during pregnancy are associated with a higher risk of having astigmatism. Although the prevalence of smoking during pregnancy is typically low, this association may suggest etiologic pathways for future investigation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Risk factors associated with childhood strabismus: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

OBJECTIVE: To investigate risk factors associated with esotropia or exotropia in infants and young children. DESIGN: Population-based cross-sectional prevalence study. PARTICIPANTS: Population-based samples of 9970 children 6 to 72 months of age from California and Maryland. METHODS: Participants were preschool African-American, Hispanic, and non-Hispanic white children participating in the Multi-Ethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study. Data were obtained by parental interview and ocular examination. Odd ratios and 95% confidence intervals were calculated to evaluate the association of demographic, behavioral, and clinical risk factors with esotropia and exotropia. MAIN OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with esotropia or exotropia diagnosis based on cover testing. RESULTS: In multivariate logistic regression analysis, esotropia was associated independently with prematurity, maternal smoking during pregnancy, older preschool age (48-72 months), anisometropia, and hyperopia. There was a severity-dependent association of hyperopia with the prevalence of esotropia, with ORs increasing from 6.4 for 2.00 diopters (D) to less than 3.00 D of hyperopia, to 122.0 for 5.00 D or more of hyperopia. Exotropia was associated with prematurity, maternal smoking during pregnancy, family history of strabismus, female sex, astigmatism (OR, 2.5 for 1.50 to <2.50 D of astigmatism, and 5.9 for ≥2.5 D of astigmatism), and anisoastigmatism in the J0 component (OR, ≥2 for J0 anisoastigmatism of ≥0.25 D). CONCLUSIONS: Prematurity and maternal smoking during pregnancy are associated with a higher risk of having esotropia and exotropia. Refractive error is associated in a severity-dependent manner to the prevalence of esotropia and exotropia. Because refractive error is correctable, these risk associations should be considered when developing guidelines for the screening and management of refractive error in infants and young children. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk factors for decreased visual acuity in preschool children: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

OBJECTIVE: To investigate risk factors associated with unilateral or bilateral decreased visual acuity (VA) in preschool children. DESIGN: Population-based, cross-sectional prevalence study. PARTICIPANTS: Population-based samples of 6504 children ages 30 to 72 months from California and Maryland. METHODS: Participants were preschool African-American, Hispanic, and non-Hispanic white children from Los Angeles, California, and Baltimore, Maryland. Data were obtained by a parental interview and a detailed ocular examination. Logistic regression models were used to evaluate the independent associations between demographic, behavioral, and clinical risk factors with unilateral and bilateral decreased VA. MAIN OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with interocular difference (IOD) in VA of ≥2 lines with ≤20/32 in the worse eye, or bilateral decreased VA <20/40 or <20/50 if <48 months of age. RESULTS: In multivariate logistic regression analysis, 2-line IOD with a VA of ≤20/32 was independently associated with Hispanic ethnicity (OR, 2.05), esotropia (OR, 8.98), spherical equivalent (SE) anisometropia (ORs ranging between 1.5 and 39.7 for SE anisometropia ranging between 0.50 to <1.00 diopters [D] and ≥2.00 D), and aniso-astigmatism in J0 or J45 (ORs ranging between 1.4 and ≥5.3 for J0 or J45 differences ranging between 0.25 to <0.50 D and ≥1.00 D). Bilateral decreased VA was independently associated with lack of health insurance (OR, 2.9), lower primary caregiver education (OR, 1.7), astigmatism (OR, 2.3 and 17.6 for astigmatism 1.00 to <2.00 D and ≥2.00 D), and SE hyperopia ≥4.00 D (OR, 10.8). CONCLUSIONS: Anisometropia and esotropia are risk factors for IOD in VA. Astigmatism and high hyperopia are risk factors for bilateral decreased VA. Guidelines for the screening and management of decreased VA in preschool children should be considered in light of these risk associations. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Risk factors for hyperopia and myopia in preschool children the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

PURPOSE: To describe the risk factors associated with hyperopia and myopia among children 6 to 72 months of age. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Population-based samples of 9970 children 6 to 72 months of age from Los Angeles County, California, and Baltimore, Maryland. METHODS: Participants were preschool African-American, Hispanic, and non-Hispanic white children (n = 9770) from Los Angeles, California, and Baltimore, Maryland. Parental questionnaires and a comprehensive eye examination were administered. Demographic, behavioral, and clinical risk factors associated with hyperopia (≥2.00 diopters [D]) and myopia (≤-1.00 D) were determined. MAIN OUTCOME MEASURES: Odds ratios (ORs) for risk factors associated with myopia and hyperopia. RESULTS: Compared with non-Hispanic whites, African-American (OR, 6.0) and Hispanic (OR, 3.2) children were more likely to be myopic. Children 6 to 35 months of age were more likely to be myopic compared with those 60 to 72 months of age (OR, ≥1.7). Compared with African-American children, non-Hispanic white (OR, 1.63) and Hispanic (OR, 1.49) children were more likely to be hyperopic. Children whose parents had health insurance (OR, 1.5) and those with a history of maternal smoking during pregnancy (OR, 1.4) were more likely to have hyperopia. Astigmatism of 1.5 D or more at any axis was associated with myopia (OR, 4.37) and hyperopia (OR, 1.43). CONCLUSIONS: Children in specific racial or ethnic groups and age groups are at higher risk of having myopia and hyperopia. Cessation of maternal smoking during pregnancy may reduce the risk of hyperopia in these children. Given that both myopia and hyperopia are risk factors for the development of amblyopia and strabismus, these risk factors should be considered when developing guidelines for screening and intervention in preschool children. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Durability of the effects of testosterone and growth hormone supplementation in older community-dwelling men: the HORMA Trial.

OBJECTIVES: To determine the durability of anabolic effects and adverse events (AEs) after stopping testosterone and growth hormone supplementation in older men. DESIGN: Secondary analysis of a double-masked, randomized controlled trial of testosterone gel (5 or 10 g/daily) plus rhGH (0, 3 or 5 µg/kg/day) with follow-up of outcomes 3 months later. PARTICIPANTS: A total of 108 community-dwelling 65- to 90-year-old men. MEASUREMENTS: Testosterone and IGF-1 levels, body composition (DEXA), 1-repetition maximum (1-RM) strength, stair-climbing power, quality-of-life (QOL) and activity questionnaires, AEs. RESULTS: Despite improvements in body composition during treatment, residual benefits 3 months later (week 28) were variable. For participants with improvements exceeding their week-17 median changes, benefits were sustained at week 28 for lean body mass (1·45 ± 1·63 kg, 45% of week-17 values, P < 0·0001 vs baseline), appendicular skeletal muscle mass (ASMM, 0·71 ± 1·01 kg, 42%, P < 0·0001), total fat (-1·06 ± 2·18 kg, 40%, P < 0·0001) and trunk fat (-0·89 ± 1·42 kg, 50%, P < 0·0001); retention of ASMM was associated with greater week-16 protein intake (P = 0·01). For 1-RM strength, 39%-43% of week-17 improvements (P ≤ 0·05) were retained and associated with better week-17 strength (P < 0·0001), change in testosterone from week 17-to 28 (P = 0·004) and baseline PASE (P = 0·04). Framingham 10-year cardiovascular risks were low (~14%), did not worsen and improved by week 28 (P = 0·0002). The hypothalamic-pituitary-gonadal axis recovered completely. CONCLUSIONS: Durable improvements in muscle mass, strength and fat mass were retained 3 months after discontinuing hormone supplementation in participants with greater than median body composition changes during treatment, but not in others with smaller gains. AEs largely resolved after intervention discontinuation. Additional strategies may be needed to sustain or augment muscle mass and strength gains achieved during short-term hormone therapy.

Recruitment and retention of African American and Latino preadolescent females into a longitudinal biobehavioral study.

OBJECTIVE: Addressing recruitment challenges faced by researchers when the intended participants are young individuals from minority communities is crucial to prevent increases in study costs, prolonged length of the study, and loss of generalizability that may occur due to the resulting higher attrition rates. This article focuses on understanding the differences in census-tract level income, education, and socioeconomic status of young Latina and African American female participants and non-participants during the first 26 months of recruitment (June 2006-August 2008) in a longitudinal biobehavioral study. DESIGN: The Transitions Study examines the psychological and physiological determinants influencing the decrease in physical activity during puberty among Latina and African American girls aged 8 to 11 years within the greater Los Angeles area. Recruitment and retention through five main steps in the process were examined: telephone contact, telephone screening, consent, clinical screening, and baseline overnight visit. RESULTS: As of August 2008, the recruitment pool consisted of 110 African Americans (17.8%) and 373 Latinas (60.4%); of these, only 40 Latinas and 11 African American girls completed the final step into the study. African Americans were less willing to provide their phone numbers, but more likely to be reached at initial phone contact than Latino families. CONCLUSIONS: Understanding the heterogeneity within minority populations, population characteristics, through careful and timely analyses, could be used to adjust recruitment and retention strategies in a study involving minority youth.