Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Optimal adaptive sequential designs for crossover bioequivalence studies.

In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70-143% within each of two ranges of intra-subject coefficient of variation (10-30% and 30-55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at ≥ 80%, their average sample sizes were similar to or less than those of conventional single stage designs.

Correlates of quality of life for individuals with dementia living at home: the role of home environment, caregiver, and patient-related characteristics.

OBJECTIVES: To examine prevalence of modifiable risk factors and their contribution to patient quality of life (QoL) as rated by dementia patients and family caregivers. DESIGN: Cross-sectional. SETTING: Home environment. PARTICIPANTS: 88 patients and their caregivers. MEASUREMENTS: Modifiable characteristics of home environments, patients, and caregivers were observed or obtained through interview. Demographics and ratings of patients' QoL were obtained from patients and caregivers. RESULTS: Patients had mean Mini-mental Status Examination (MMSE) score = 17.7 ± 4.6, (range: 10-28) on an average 7.7 ± 2.4 neuropsychiatric behaviors, 6.0 ± 3.1 health conditions and moderate functional challenges; 70.7% (N = 58) had fall risk; 60.5% (N = 52) had sleep problems at least once weekly; and 42.5% (N = 37) had pain. An average of 8.1 ± 5.2 home hazards and 5.4 ± 4.1 adaptations were observed; 51.7% had unmet device/navigation needs. Patients' and caregivers' QoL ratings were unrelated to MMSE; and patients' self-rated QoL was higher than rated by caregivers. Number of health conditions and unmet device/navigation needs were inversely associated with patient self-rated QoL, and number of health conditions, frequency of behaviors, and level of negative communications were inversely associated with caregiver's assessment of patient QoL. Positive endorsement of caregiving was positively associated with caregiver's appraisal of patient QoL. Other factors were unrelated. CONCLUSIONS: Most patients lived at home with high fall risk, unmanaged behavioral symptoms, pain, sleep disturbances, environmental challenges, and multiple hazards. Except for health, factors associated with lower QoL differed for patients and caregivers. Results suggest need to improve QoL by addressing modifiable risk factors and tailoring interventions to patient and caregiver perspectives.

A home-based intervention to reduce depressive symptoms and improve quality of life in older African Americans: a randomized trial.

BACKGROUND: Effective care models for treating older African Americans with depressive symptoms are needed. OBJECTIVE: To determine whether a home-based intervention alleviates depressive symptoms and improves quality of life in older African Americans. DESIGN: Parallel, randomized trial stratified by recruitment site. Interviewers assessing outcomes were blinded to treatment assignment. (ClinicalTrials.gov: NCT00511680). SETTING: A senior center and participants' homes from 2008 to 2010. PATIENTS: African Americans aged 55 years or older with depressive symptoms. INTERVENTION: A multicomponent, home-based intervention delivered by social workers or a wait-list control group that received the intervention at 4 months. MEASUREMENTS: Self-reported depression severity at 4 months (primary outcome) and depression knowledge, quality of life, behavioral activation, anxiety, function, and remission at 4 and 8 months. RESULTS: Of 208 participants (106 and 102 in the intervention and wait-list groups, respectively), 182 (89 and 93, respectively) completed 4 months and 160 (79 and 81, respectively) completed 8 months. At 4 months, participants in the intervention group showed reduced depression severity (difference in mean change in Patient Health Questionnaire-9 score from baseline, -2.9 [95% CI, -4.6 to -1.2]; difference in mean change in Center for Epidemiologic Studies Depression Scale score from baseline, -3.7 [CI, -5.4 to -2.1]); improved depression knowledge, quality of life, behavioral activation, and anxiety (P < 0.001); and improved function (P = 0.014) compared with wait-list participants. More intervention than wait-list participants entered remission at 4 months (43.8% vs. 26.9%). After treatment, control participants showed benefits similar in magnitude to those of participants in the initial intervention group. Those in the initial intervention group maintained benefits at 8 months. LIMITATION: The study had a small sample, short duration, and differential withdrawal rate. CONCLUSION: A home-based intervention delivered by social workers could reduce depressive symptoms and enhance quality of life in most older African Americans. PRIMARY FUNDING SOURCE: National Institute of Mental Health.

Phenotypic parameters predict time to normalization in infants with hypogammaglobulinemia.

PURPOSE: Infants with recurrent infection may be found to have hypogammaglobulinemia without impaired specific antibody responses. Many will be diagnosed with transient hypogammaglobulinemia of infancy. METHODS: This study used a parametric survival analysis of 100 infants with hypogammaglobulinemia to predict time to normalization. RESULTS: Aggregate initial immunoglobulins (IgG + IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution: median time to resolution for the infants in the lowest quartile of aggregate levels (≤81 % of age-adjusted lower limits) was greater than 5 years, with 34 % resolving in 3 years. For infants in the highest quartile (≥130 % of age-adjusted lower limits), the median was 9.9 months, with 77 % resolving in 3 years (P = 0.008). Initial IgG level, as a percentage of age-adjusted normal, also predicted resolution: the median time in the lowest quartile (≤78 % of age-adjusted lower limits) was greater than 5 years, with 36 % resolving in 3 years. In the highest quartile (≥128 %), the median time was 14.5 months, with 70 % resolving in 3 years (P = 0.010). Male sex was associated with more rapid resolution. The median time in males was 13 months, with 73 % resolution in 3 years. The median time in females was greater than 5 years, with 32 % resolution in 3 years. CONCLUSIONS: These results suggest that if a term infant presents with hypogammaglobulinemia, protective specific antibody titers, and an absence of other known immune deficiency, initial immunoglobulin levels and sex may predict time to normalization.

Identification of and beliefs about depressive symptoms and preferred treatment approaches among community-living older African Americans.

OBJECTIVE: To examine older African American's recognition of and beliefs about depressive symptoms, preferred symptom management strategies, and factors associated with willingness to use mental health treatments. Differences between the depressed and nondepressed and men and women were examined. DESIGN: Cross-sectional survey. SETTING: Home, senior center. PARTICIPANTS: A total of 153 senior center members (56 male, 97 female) 55 years and older. MEASUREMENTS: Using a depression vignette, participants indicated if the person was depressed and their endorsement of items reflecting beliefs, stigma, symptom management, and willingness to use treatments (yes/no). A 9-item Patient Health Questionnaire assessed current symptomatology. RESULTS: Overall, 24.2% reported depressive symptoms (≥5); 88.2% correctly identified the person in the vignette as depressed. Most (≥75%) endorsed active symptom management strategies, preference for treatment in physician and therapist offices, and willingness to take medications, seek therapy, see doctor, and attend support groups; less than 33% viewed depression as stigmatizing, whereas 48% viewed depression as normal aging. Logistic regressions revealed lower education, higher physical function, and feeling okay if community knew of depression diagnosis were associated with willingness to see physician if feeling depressed; being married and believing antidepressant medications are beneficial were related to willingness to use medications. Different associations emerged for depressed/nondepressed and men and women. CONCLUSIONS: Overall, this older African American sample had positive attitudes and beliefs and endorsed traditional treatment modalities suggesting that beliefs alone are unlikely barriers to underutilization of mental health services. Because different factors were associated with willingness to seek physician help and use medications and factors differed for depressed/nondepressed and by sex, interventions should be tailored.

Primary and secondary reference materials for procedures to test the quality of medicines and foods.

At present a complex global patchwork of private and public monographs and reference materials is variously available to help ensure the quality of medicines and foods. The relationship of these monographs and reference materials, one to another, frequently is inconsistently understood and documented.This article considers the complexity of monographs and reference materials with a focus on qualifying one reference material relative to another.

Development of a performance verification test for USP apparatus 4.

PURPOSE: To evaluate salicylic acid tablets as a candidate reference material in a Performance Verification Test (PVT) when a USP performance test for dissolution (General Chapter <711>) relies on USP Apparatus 4 (flow-through cell). METHODS: We developed a dissolution procedure relying on Apparatus 4 and salicylic acid tablets. Thereafter, a designed experiment was conducted to identify operational variables that significantly affect salicylic acid dissolution in this apparatus. RESULTS: Four variables (size of glass beads, cell temperature, flow rate, level of deaeration) and one combination effect (deaeration/bead size) were significant for mean percent dissolved. Two variables (tablet orientation, level of deaeration) were significant for standard deviation results, but these effects were less pronounced than those for mean percent dissolved results. Three variables (analyst, tester manufacturer, amount of glass beads) had no statistically significant effects on either the mean or standard deviation of the responses. CONCLUSIONS: The proposed PVT is capable of probing effects of changes in several critical operational parameters of Apparatus 4. Salicylic acid tablets were shown to be a suitable reference material for the PVT. The PVT using salicylic acid tablets satisfies important aspects of a PVT.

Additional results for 'Sequential design approaches for bioequivalence studies with crossover designs'.

In 2008, this group published a paper on approaches for two-stage crossover bioequivalence (BE) studies that allowed for the reestimation of the second-stage sample size based on the variance estimated from the first-stage results. The sequential methods considered used an assumed GMR of 0.95 as part of the method for determining power and sample size. This note adds results for an assumed GMR = 0.90. Two of the methods recommended for GMR = 0.95 in the earlier paper have some unacceptable increases in Type I error rate when the GMR is changed to 0.90. If a sponsor wants to assume 0.90 for the GMR, Method D is recommended. Copyright © 2011 John Wiley & Sons, Ltd.

Establishing new acceptance limits for dissolution performance verification of USPC apparatus 1 and 2 using USPC prednisone tablets reference standard.

PURPOSE: On 1 March 2010, the US Pharmacopeial Convention released into commerce Lot P1I300 of its Prednisone Tablets Reference Standard for use in periodic performance verification testing (PVT) of dissolution Apparatus 1 and 2. This report presents the collaborative study data, development of the acceptance limits, and results from supporting work for this Lot. METHODS: The collaborative study involved 25 collaborators who provided data for Apparatus 1 and 31 who provided data for Apparatus 2. These limits are for the geometric mean and percent coefficient of variation (%CV) instead of per-individual results as for prior lots. Stability of results and sensitivity to test performance parameters were also studied. RESULTS: To determine new PVT acceptance limits, the authors calculated geometric mean and variance components as percent coefficient of variation. The move to the geometric mean and %CV criteria brings the acceptance criteria in line with current accepted statistics and provides a more realistic assessment of the system's performance. Results for Apparatus 1 are stable over time, but for Apparatus 2, the mean decreases over time. Acceptance criteria are adjusted for this trend. Lot P1 demonstrates sensitivity to test performance parameters (vessels and degassing). CONCLUSIONS: Apparatus 1 results are stable over time. Those in Apparatus 2 show a decrease over time in the geometric mean but show no trend in variability. The current tablets are shown to remain sensitive to two operational parameters, degassing and vessel dimensions, not covered by mechanical calibration. The new acceptance limits for Lot P1 are based on geometric mean and %CV for Prednisone Tablets Reference Standard Lot P1I300. The limits better control variability than the prior per-individual-result limits.

Measurement science for food and drug monographs: toward a global system.

This article continues USP's public dialogs about applications of modern measurement science (metrology) to public or private specifications (monographs) of food and drug articles. An objective of the discussion is to promote understanding of traceability and uncertainty of measurement results. Adoption of modern metrologic principles helps ensure that a measurement of one or more property values (attributes) of a food or drug article are acceptable without regard to when (time), where (space), or how (technology) the measurement was conducted. The approach is applicable to both in-process and end-product measurements and facilitates and supports understanding of manufacturing and measurement variability relative to acceptance criteria. Application of modern metrologic principles to measurement of food and drug articles expands opportunities to ensure availability of good quality food and drugs in national and international markets.

A biobehavioral home-based intervention and the well-being of patients with dementia and their caregivers: the COPE randomized trial.

CONTEXT: Optimal treatment to postpone functional decline in patients with dementia is not established. OBJECTIVE: To test a nonpharmacologic intervention realigning environmental demands with patient capabilities. DESIGN, SETTING, AND PARTICIPANTS: Prospective 2-group randomized trial (Care of Persons with Dementia in their Environments [COPE]) involving patients with dementia and family caregivers (community-living dyads) recruited from March 2006 through June 2008 in Pennsylvania. INTERVENTIONS: Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits; obtained blood and urine samples; and trained families in home safety, simplifying tasks, and stress reduction. Control group caregivers received 3 telephone calls and educational materials. MAIN OUTCOME MEASURES: Functional dependence, quality of life, frequency of agitated behaviors, and engagement for patients and well-being, confidence using activities, and perceived benefits for caregivers at 4 months. RESULTS: Of 284 dyads screened, 270 (95%) were eligible and 237 (88%) randomized. Data were collected from 209 dyads (88%) at 4 months and 173 (73%) at 9 months. At 4 months, compared with controls, COPE patients had less functional dependence (adjusted mean difference, 0.24; 95% CI, 0.03-0.44; P = .02; Cohen d = 0.21) and less dependence in instrumental activities of daily living (adjusted mean difference, 0.32; 95% CI, 0.09-0.55; P = .007; Cohen d = 0.43), measured by a 15-item scale modeled after the Functional Independence Measure; COPE patients also had improved engagement (adjusted mean difference, 0.12; 95% CI, 0.07-0.22; P = .03; Cohen d = 0.26), measured by a 5-item scale. COPE caregivers improved in their well-being (adjusted mean difference in Perceived Change Index, 0.22; 95% CI, 0.08-0.36; P = .002; Cohen d = 0.30) and confidence using activities (adjusted mean difference, 0.81; 95% CI, 0.30-1.32; P = .002; Cohen d = 0.54), measured by a 5-item scale. By 4 months, 64 COPE dyads (62.7%) vs 48 control group dyads (44.9%) eliminated 1 or more caregiver-identified problems (chi(2/1) = 6.72, P = . 01). CONCLUSION: Among community-living dyads, a nonpharmacologic biobehavioral environmental intervention compared with control resulted in better outcomes for COPE dyads at 4 months. Although no group differences were observed at 9 months for patients, COPE caregivers perceived greater benefits. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00259454.

Change in criteria for USP dissolution performance verification tests.

The US Pharmacopeial Convention has been evaluating its performance verification tests (PVT) for several years. These tests help ensure the integrity of the US Pharmacopeia performance test when a dissolution procedure, as described in General Chapter Dissolution <711>, is relied upon to test a nonsolution orally administered dosage form. One result of the evaluation is a change in the PVT criterion from one based on individual tablet results to one based on the mean and variability of a set of tablets. This paper describes the new PVT and its criterion and how its acceptance limits are derived from results of a collaborative study, explains a two-stage option for the test, and presents operating characteristics.

Variation in response to a home intervention to support daily function by age, race, sex, and education.

BACKGROUND: Functional difficulty is associated with increased frailty and poor life quality, with the oldest old, women, African Americans, and less educated persons at greatest risk of disablement. This study examines whether these at-risk groups benefit differentially from an in-home intervention previously found to effectively reduce functional difficulties. METHODS: Three hundred nineteen community-living, functionally vulnerable adults 70 years old or older were randomized to usual care or an intervention involving occupational and physical therapy home instruction in problem solving, device use, energy conservation, safety, fall recovery, balance, and muscle strengthening. Outcome measures at 6 and 12 months included difficulty level in ambulation, instrumental (IADLs) and activities of daily living (ADLs), self-efficacy, and fear of falling. RESULTS: At 6 months, for ADLs, individuals > or =80 years (p =.022), women (p =.036), and less educated persons (p =.028) improved compared to their control group counterparts. For mobility, women (p =.048) and the oldest participants (p =.001) improved relative to their counterparts. For self-efficacy, women (p =.036) benefited more than men. For fear of falling, less educated persons improved more than their counterparts (p =.001). A similar pattern was found at 12 months. For IADLs, whites improved more than non-whites at 12 months. CONCLUSIONS: Treatment benefits varied by specific participant characteristics, with individuals at greatest disability risk being most responsive to the intervention. Both white and minority participants benefited similarly except in IADL functioning. Future research should control for participant characteristics, identify underlying mechanisms for variation in treatment effects, and tailor treatment to patient characteristics and desired outcomes.

Metrologic approaches to setting acceptance criteria: unacceptable and unusual characteristics.

Decisions regarding acceptance criteria in regulatory or compendial contexts are among the most difficult to make. Acceptance criteria aid in the identification, on the one hand, of materials with unacceptable characteristics that should not pass the tests and procedures or, on the other hand, of unusual characteristics that indicate materials that are unlikely to pass the tests and procedures. For relatively complex procedures metrological approaches can differentiate between intra- and inter-laboratory variation and clarify unacceptable and unusual data. Such testing requires collaborative studies in which each participating laboratory essentially compares itself to the other laboratories in the collaborative study. Laboratories that use the reference standard established by the collaborative study are conducting a performance verification test in which they compare their capabilities to those of laboratories in the collaborative study. This paper considers aspects of a series of complex issues involving unacceptable/unusual characteristics primarily in the context of USP's work but with implications for manufacturing science via considerations of process capability and Quality by Design and to measurement science. Ultimately, acceptance criteria support the availability of good quality, safe, and effective medicines for patients and consumers.

Sequential design approaches for bioequivalence studies with crossover designs.

The planning of bioequivalence (BE) studies, as for any clinical trial, requires a priori specification of an effect size for the determination of power and an assumption about the variance. The specified effect size may be overly optimistic, leading to an underpowered study. The assumed variance can be either too small or too large, leading, respectively, to studies that are underpowered or overly large. There has been much work in the clinical trials field on various types of sequential designs that include sample size reestimation after the trial is started, but these have seen only little use in BE studies. The purpose of this work was to validate at least one such method for crossover design BE studies. Specifically, we considered sample size reestimation for a two-stage trial based on the variance estimated from the first stage. We identified two methods based on Pocock's method for group sequential trials that met our requirement for at most negligible increase in type I error rate.

Depressive symptoms in older African-American and white adults with functional difficulties: the role of control strategies.

OBJECTIVES: To examine whether control-oriented strategies buffer effects of functional difficulties on depressive symptoms over time in older African-American and white adults with disability. DESIGN: Community-based, prospective study. SETTING: Baseline and 12-month data from a randomized trial. PARTICIPANTS: One hundred twenty-nine African-American and 151 white older adults with 12-month data from 319 participants in the trial. MEASUREMENTS: Data were obtained for functional difficulties, the extent that respondents reported using control (cognitive and behavioral) strategies to enhance and maintain independence, and baseline and 12-month depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D). RESULTS: African Americans reported greater baseline functional difficulty (P=.009), fewer depressive symptoms (P=.002) and higher control strategy use (P=.001) than whites. Functional difficulty was associated with depressive symptoms for both groups at baseline and 12 months. Living alone for whites and low spirituality for African Americans predicted higher 12-month depressive symptom scores. African Americans with baseline functional difficulty and high strategy use had lower 12-month depression than those with similar difficulty levels but low strategy use (P=.04 for interaction), representing a 28.5-point CES-D score differential. Control strategies did not buffer the function-depression relationship over time for whites. CONCLUSION: Control-oriented strategies moderated the experience of depressive symptomatology over time for African Americans with disability but not for whites. This may explain the paradox of greater functional disparities but less reported emotional distress in African Americans than whites. Results suggest that the use and benefits of adaptive resources to attain functional goals and determinants of depression differ by race. Depression prevention programs should be modified to be suitable for different cultural groups.

Predictors of adherence to a skill-building intervention in dementia caregivers.

BACKGROUND: Treatment adherence is a widely recognized problem in health services but understudied in caregiver intervention research. This study examines caregiver sociodemographic and psychological characteristics, patient illness severity, and treatment implementation factors as predictors of caregiver adherence to a skills training intervention to help families manage dementia care problems at home. METHODS: The sample consisted of 105 caregivers randomized to the Home Environmental Skill-Building Program at the Philadelphia site of the National Institutes of Health (NIH) Resources for Enhancing Alzheimer's Caregiver Health (REACH I). The intervention, implemented by occupational therapists, consisted of education, problem solving, communication, environmental and task simplification techniques, and home modifications. Adherence was measured by a proportion score representing the percentage of strategies used by participants compared to the total number of strategies prescribed during intervention (Strategy Use). RESULTS: Regression analysis with intraclass correlation adjustment for interventionist effects revealed that caregivers with better physical health (p <.001), greater treatment exposure (p <.001), more problem areas addressed (p =.012), and for whom more active therapeutic techniques (role play) were used (p =.004) demonstrated greater adherence. Other caregiver characteristics, patient cognitive impairment, and troublesome behaviors were not significantly related to caregiver adherence. CONCLUSIONS: Modifiable caregiver and treatment implementation factors, including active engagement of caregivers, were associated with adherence, whereas patient characteristics were not. Caregivers with poor health may be at risk for not benefiting from intervention, suggesting that efforts, including instruction in preventive care and allocating time to attend to their own health care needs, be directed towards improving their health.

Validity of the walking scale for spinal cord injury and other domains of function in a multicenter clinical trial.

OBJECTIVE: To demonstrate criterion (concurrent and predictive) and construct validity of the Walking Index for Spinal Cord Injury (WISCI) scale and other walking measures in the Spinal Cord Injury Locomotor Trial (SCILT). DESIGN: Prospective multicenter clinical trial of a walking intervention for patients with acute traumatic spinal cord injury (SCI). PARTICIPANTS/ METHODS: Body weight-supported treadmill training was compared to overground mobility training in 146 patients with incomplete SCI (C4 to L3) enrolled within 8 weeks of onset and treated for 12 weeks. Primary outcome measures were the Functional Independence Measure (FIM), 50-foot walking speed (50FW-S), and 6-minute walking distance (6MW-D), tested 3, 6, and 12 months after entry. Secondary measures were the Lower Extremity Motor Score (LEMS), Berg Balance Scale (BBS), WISCI, and FIM locomotor score (LFIM), assessed at 6 centers by blinded observers. Data for the 2 arms were combined since no significant differences in outcomes had been found. RESULTS: Correlations with WISCI at 6 months were significant with BBS (r = .90), LEMS (r = .85), LFIM (r = .89), FIM (r = .77), 50FW-S (r = .85), and 6MW-D ( r = .79); similar correlations occurred at 3 and 12 months. Correlations of change scores from baseline WISCI were significant for change scores from baseline of LEMS/BBS/LFIM. Correlation of baseline LEMS and WISCI at 12 months were most significant (r = .73). The R(2) of baseline LEMS explained 57% of variability of WISCI levels at 3 months. CONCLUSION: Concurrent validity of the WISCI scale was supported by significant correlations with all measures at 3, 6, and 12 months. Correlation of change scores supports predictive validity. The LEMS at baseline was the best predictor of the WISCI score at 12 months and explained most of the variance, which supported both predictive and construct validity. The combination of the LEMS, BBS, WISCI, 50FW-S, and LFIM appears to encompass adequate descriptors for outcomes of walking trials for incomplete SCI.

Light therapy for seasonal affective disorder with blue narrow-band light-emitting diodes (LEDs).

BACKGROUND: While light has proven an effective treatment for Seasonal Affective Disorder (SAD), an optimal wavelength combination has not been determined. Short wavelength light (blue) has demonstrated potency as a stimulus for acute melatonin suppression and circadian phase shifting. METHODS: This study tested the efficacy of short wavelength light therapy for SAD. Blue light emitting diode (LED) units produced 468 nm light at 607 microW/cm2 (27 nm half-peak bandwidth); dim red LED units provided 654 nm at 34 microW/cm2 (21 nm half-peak bandwidth). Patients with major depression with a seasonal pattern, a score of > or =20 on the Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version (SIGH-SAD) and normal sleeping patterns (routine bedtimes between 10:00 pm and midnight) received 45 minutes of morning light treatment daily for 3 weeks. Twenty-four patients completed treatment following random assignment of condition (blue vs. red light). The SIGH-SAD was administered weekly. RESULTS: Mixed-effects analyses of covariance determined that the short wavelength light treatment decreased SIGH-SAD scores significantly more than the dimmer red light condition (F = 6.45, p = .019 for average over the post-treatment times). CONCLUSIONS: Narrow bandwidth blue light at 607 microW/cm2 outperforms dimmer red light in reversing symptoms of major depression with a seasonal pattern.