Sample size determination for longitudinal designs with binary response.

In this article, we develop appropriate statistical methods for determining the required sample size while comparing the efficacy of an intervention to a control with repeated binary response outcomes. Our proposed methodology incorporates the complexity of the hierarchical nature of underlying designs and provides solutions when varying attrition rates are present over time. We explore how the between-subject variability and attrition rates jointly influence the computation of sample size formula. Our procedure also shows how efficient estimation methods play a crucial role in power analysis. A practical guideline is provided when information regarding individual variance component is unavailable. The validity of our methods is established by extensive simulation studies. Results are illustrated with the help of two randomized clinical trials in the areas of contraception and insomnia.

Rivastigmine Transdermal Patch Treatment for Moderate to Severe Cognitive Impairment in Veterans with Traumatic Brain Injury (RiVET Study): A Randomized Clinical Trial.

Cognitive impairment is common in veterans with histories of traumatic brain injury (TBI). Cholinergic deficits have been hypothesized as contributors to this impairment. We report the effects of cholinesterase inhibitor rivastigmine transdermal patch treatment in veterans with TBI and post-traumatic memory impairment. Our objective was to evaluate the efficacy and safety of a 9.5 mg/24 h (10 cm2) rivastigmine patch in veterans of military conflicts with persistent moderate to severe memory impairment at least 12 weeks after TBI. This randomized, outpatient, double-blind, placebo-controlled 12-week trial with an exploratory double-blind phase of an additional 14 weeks was conducted at 5 VA Medical Centers, among veterans with closed, non-penetrating TBI who met or exceeded modified American Congress of Rehabilitation Medicine criteria for mild TBI with verbal memory deficits, as assessed by the Hopkins Verbal Learning Test, Revised (HVLT-R). Patients were randomized 1:1 to rivastigmine or matching placebo patches after a 1-week single-blind, placebo run-in phase. At randomization, patients received 4.6 mg/24 h rivastigmine patches or matching placebo increased to a 9.5 mg/24 h patch after 4 weeks. The primary efficacy outcome measure was the proportion of participants who had at least a five-word improvement on the HVLT-R Total Recall Index (Trials 1-3). A total of 3671 participants were pre-screened, of whom 257 (7.0%) were screened; 96 (37%) randomized, and 94 included in study analyses. Responder rates were 40.8% (20 of 49) and 51.1% (23 of 45) in the rivastigmine and placebo groups, respectively (p = 0.41). A mixed-effect model including treatment, time, and treatment-by-time interaction indicated no significant difference in treatment effect over time between the groups (p = 0.24). Overall, there were no significant differences in changes for all secondary outcomes between the rivastigmine and placebo groups. The most commonly observed adverse events were application site reactions. This trial provides the largest sample to date of veterans with TBI and post-traumatic memory deficits enrolled in a pharmacological trial. Trial Registration: clinicaltrials.gov Identifier: NCT01670526.

Amiodarone versus sotalol for atrial fibrillation.

BACKGROUND: The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring. RESULTS: Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups. CONCLUSIONS: Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

Economic Evaluation of Low-Vision Rehabilitation for Veterans With Macular Diseases in the US Department of Veterans Affairs.

Importance: Examining costs and consequences of different low-vision (LV) programs provides important information about resources needed to expand treatment options efficiently. Objective: To examine the costs and consequences of LV rehabilitation or basic LV services. Design, Setting, and Participants: The US Department of Veterans Affairs (VA) Low Vision Intervention Trial (LOVIT) II was conducted from September 27, 2010, to July 31, 2014, at 9 VA facilities and included 323 veterans with macular diseases and a best-corrected distance visual acuity of 20/50 to 20/200. Veterans were randomized to receive basic LV services that provided LV devices without therapy, or LV rehabilitation that added a therapist to LV services who provided instruction and homework on using LV devices, eccentric viewing, and environmental modification. We compared costs and consequences between these groups. Interventions: Low-vision devices without therapy and LV devices with therapy. Main Outcomes and Measures: Costs of providing basic LV services or LV rehabilitation were assessed. We measured consequences as changes in functional visual ability from baseline to follow-up 4 months after randomization using the VA Low Vision Visual Functioning Questionnaire. Visual ability was measured in dimensionless log odds units (logits). Results: Of 323 randomized patients, the mean (SD) age was 80 (10.5) years, 314 (97.2%) were men, and 292 (90.4%) were white. One hundred sixty (49.5%) received basic LV services and 163 (50.1%) received LV rehabilitation. The mean (SD) total direct health care costs per patient were similar between patients who were randomized to receive basic LV services ($1662 [$671]) or LV rehabilitation ($1788 [$864]) (basic LV services, $126 lower; 95% CI, $299 lower to $35 higher; P = .15). However, basic LV services required less time and had lower transportation costs. Patients receiving LV rehabilitation had greater improvements in overall visual ability, reading ability, visual information processing, and visual motor skill scores.

Exercise capacity in atrial fibrillation: a substudy of the Sotalol-Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T).

BACKGROUND: Therapy for chronic atrial fibrillation (AF) focuses on rate versus rhythm control, but little is known about the effects of common therapeutic interventions on exercise tolerance in AF. METHODS: Six hundred fifty-five patients with chronic AF underwent maximal exercise testing at baseline and 8 weeks, 6 months, and 1 year after randomization to sotalol, amiodarone, or placebo therapy and attempted direct current cardioversion. Analyses of baseline determinants of exercise capacity, predictors of change in exercise capacity at 6 months and 1 year, and the short- and long-term effects of cardioversion on exercise capacity were made. RESULTS: Age, obesity, and presence of symptoms accompanying AF were inversely associated with baseline exercise capacity, but these factors accounted for only 10% of the variance in exercise capacity. Patients most likely to benefit from cardioversion were those most limited initially, younger, not obese or hypertensive, and with an uncontrolled ventricular rate at baseline. Conversion to sinus rhythm (SR) resulted in significant reductions in resting (approximately 25 beat/min) and peak exercise (approximately 40 beat/min) heart rates at 6 months and 1 year (P < .001). Successful cardioversion improved exercise capacity by 15% at 8 weeks, and these improvements were maintained throughout the year. This improvement was observed both among those who maintained SR and those with intermittent AF. CONCLUSION: Cardioversion resulted in a sustained improvement in exercise capacity over the course of 1 year, and this improvement was similar between those in SR and those with SR and recurrent AF. Patients most likely to improve with treatment tended to be younger and nonobese and have the greatest limitations initially.

Outcomes of the Veterans Affairs Low Vision Intervention Trial II (LOVIT II): A Randomized Clinical Trial.

IMPORTANCE: Randomized clinical trials are needed to compare effectiveness and cost-effectiveness of different low-vision (LV) programs. OBJECTIVE: To determine the value of adding LV rehabilitation with a therapist compared with LV services without intervention. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted from September 27, 2010, to July 31, 2014, of 323 veterans with macular diseases and best-corrected distance visual acuity (BCDVAbetter-eye) of 20/50 to 20/200. Masked interviewers administered questionnaires by telephone before and after LV treatment. Using an intention-to-treat design, participants were randomized to receive LV devices with no therapy or LV devices with a rehabilitation therapist providing instruction and homework on the use of LV devices, eccentric viewing, and environmental modification. Visual ability was measured in dimensionless log odds units (logits) (0.14-logit change in visual ability corresponds to ability change expected from a 1-line change in visual acuity). INTERVENTIONS: Low-vision devices without therapy and LV devices with therapy. MAIN OUTCOMES AND MEASURES: Comparison of changes (baseline to 4 months) in overall visual ability and in 4 functional domains (reading, visual information, visual motor, and mobility) estimated from responses to the Veterans Affairs Low Vision Visual Functioning Questionnaire (higher scores indicates more ability or less difficulty in performing activities), and comparison of MNREAD changes (baseline to end of treatment) in maximum reading speed, critical print size, and reading acuity (higher number indicates lower visual acuity). RESULTS: Of the 323 participants, 314 were male (97.2%); mean (SD) age, 80 (10.5) years. Basic LV was effective in improving visual ability. However, the LV rehabilitation group improved more in all visual function domains except mobility. Differences were 0.34-logit reading (95% CI, 0.0005 to 0.69; P = .05), 0.27-logit visual information (95% CI, 0.01 to 0.53; P = .04), 0.37-logit visual motor (95% CI, 0.08 to 0.66; P = .01), and 0.27-logit overall (95% CI, 0.06 to 0.49; P = .01). For MNREAD measures, there was more improvement in reading acuity (difference, -0.11 logMAR, 95% CI, -0.15 to -0.07; P < .001) and maximum reading speed (mean increase of 21.0 words/min; 95% CI, 6.4 to 35.5; P = .005), but not critical print size for the LV rehabilitation group (-0.06 logMAR; 95% CI, -0.12 to 0.002; P = .06). In stratified analyses, the LV rehabilitation group with BCDVAbetter-eye worse than 20/63 to 20/200 improved more in visual ability (reading, visual motor, and overall). Differences were 0.56-logit reading ability (95% CI, 0.08-1.04; P = .02), 0.40-logit visual motor (95% CI, 0.03-0.78; P = .04), 0.34-logit overall (95% CI, 0.06-0.62; P = .02). There was no significant difference between treatment groups for those with BCDVAbetter-eye of 20/50 to 20/63. CONCLUSIONS AND RELEVANCE: Both basic LV alone and combined with LV rehabilitation were effective, but the added LV rehabilitation increased the effect only for patients with BCDVAbetter-eye worse than 20/63 to 20/200. Basic LV services may be sufficient for most LV patients with mild visual impairment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00958360.

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]).

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

Percutaneous coronary intervention versus coronary bypass surgery in United States veterans with diabetes.

OBJECTIVES: This study sought to determine the optimal coronary revascularization strategy in patients with diabetes with severe coronary disease. BACKGROUND: Although subgroup analyses from large trials, databases, and meta-analyses have found better survival for patients with diabetes with complex coronary artery disease when treated with surgery, a randomized trial comparing interventions exclusively with drug-eluting stents and surgery in patients with diabetes with high-risk coronary artery disease has not yet been reported. METHODS: In a prospective, multicenter study, 198 eligible patients with diabetes with severe coronary artery disease were randomly assigned to either coronary artery bypass grafting (CABG) (n = 97) or percutaneous coronary intervention (PCI) with drug-eluting stents (n = 101) and followed for at least 2 years. The primary outcome measure was a composite of nonfatal myocardial infarction or death. Secondary outcome measures included all-cause mortality, cardiac mortality, nonfatal myocardial infarction, and stroke. RESULTS: The study was stopped because of slow recruitment after enrolling only 25% of the intended sample size, leaving it severely underpowered for the primary composite endpoint of death plus nonfatal myocardial infarction (hazard ratio: 0.89; 95% confidence interval: 0.47 to 1.71). However, after a mean follow-up period of 2 years, all-cause mortality was 5.0% for CABG and 21% for PCI (hazard ratio: 0.30; 95% confidence interval: 0.11 to 0.80), while the risk for nonfatal myocardial infarction was 15% for CABG and 6.2% for PCI (hazard ratio: 3.32; 95% confidence interval: 1.07 to 10.30). CONCLUSIONS: This study was severely underpowered for its primary endpoint, and therefore no firm conclusions about the comparative effectiveness of CABG and PCI are possible. There were interesting differences in the components of the primary endpoint. However, the confidence intervals are very large, and the findings must be viewed as hypothesis generating only. (Coronary Artery Revascularization in Diabetes; NCT00326196).

The effectiveness of low-vision rehabilitation in 2 cohorts derived from the veterans affairs Low-Vision Intervention Trial.

OBJECTIVE: To evaluate the effectiveness of low-vision rehabilitation in 2 cohorts derived from the Veterans Affairs Low-Vision Intervention Trial. METHODS: In a prospective study, we observed 44 participants randomly assigned to outpatient low-vision rehabilitation who did not receive additional treatment after the trial ended at 4-month follow-up and 56 participants randomly assigned to the waiting-list control group and thereafter to standard therapy. The outcome measures included visual ability domains (reading, mobility, visual information processing, and visual motor skills) and overall visual ability estimated from difficulty ratings using the 48-item Veterans Affairs Low-Vision Visual Functioning Questionnaire. Mean visual ability scores for the treatment and control groups were compared at baseline, 4 months, and 1 year. A mixed-effects model was used to test treatment effects between groups over time. Differences in visual ability mean scores from baseline to 1 year were compared between the 2 groups. Within-group changes in visual ability were compared from baseline to 1 year, from baseline to 4 months, and from 4 months to 1 year. RESULTS: At baseline, there were no significant differences in mean visual ability scores between groups. From baseline to 4 months, the treatment effects for all visual ability domains and overall visual ability increased to a maximum in the treatment group (P< .001), whereas the mean scores (except visual motor skills) decreased in the control group (P< .01). From 4 months to 1 year, the differences became smaller. There was a loss of visual ability in reading and visual information processing (but not in visual motor skills, mobility, or overall visual ability) in the treatment group and a gain in all visual ability measures in the control group. Interactions of treatment and follow-up time in the mixed models showed the trend of treatment effects significantly changed over time from baseline to 1 year (P< .001) for all visual ability domains and overall visual ability. Both groups demonstrated improvement in visual ability from baseline to 1 year (P< .001) (except for mobility in the control group). Overall visual ability (but not other visual ability domains) improved more in the treatment group than in the control group (P= .01). CONCLUSIONS: Visual ability improved significantly in both groups from baseline to 1 year. The Low-Vision Intervention Trial treatment effect is robust and well maintained for patients with macular diseases.

Systematic electrocardioversion for atrial fibrillation and role of antiarrhythmic drugs: a substudy of the SAFE-T trial.

BACKGROUND: Energy levels for electrocardioversion in atrial fibrillation (AF) have been empiric, and the influence of antiarrhythmic therapy compared with placebo is largely unknown. OBJECTIVE: The purpose of this study was to determine systematically the energy levels for electrocardioversion in patients with persistent AF and to define the influence of antiarrhythmic therapy. METHODS: Patients (n = 665) with persistent AF were randomized to amiodarone, sotalol, or placebo. Rate control, if necessary, was achieved with digoxin, diltiazem, or verapamil. Among the 665 patients, 504 who did not achieve sinus rhythm at day 28 had electrocardioversion systematically by a prespecified four-step protocol as follows: monophasic shocks-100, 200, 360, 360 J; or biphasic shocks-150, 175, 200, 200 J sequentially. Energy levels and shock waveforms (monophasic/biphasic) for successful electrocardioversion (sinus rhythm for at least 1 minute) and use of antiarrhythmic therapy and calcium channel blockers were recorded. RESULTS: Electrocardioversion was successful in 371 (71.6%) of 504 patients: 72%, 73.5%, and 67.9% for patients assigned to amiodarone, sotalol, and placebo, respectively. Overall, after adjustments for age, body mass index (BMI), history of AF, shock waveforms, left atrial size, and ejection fraction, both amiodarone (odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.24-3.77, P <.01) and sotalol (OR: 1.92, 95% CI: 1.11-3.33, P = .02) significantly facilitated successful electrocardioversion compared with placebo. Calcium channel blockers had no effect on the success rate of electrocardioversion. Success of electrocardioversion was associated with lower BMI, AF history < or =1 year, and older age. Compared with placebo, patients taking amiodarone were significantly more likely to achieve successful electrocardioversion in step 1 (OR: 2.73, 95% CI: 1.11-6.74, P = .03) and step 3 (OR: 1.86, 95% CI: 1.00-3.44, P = .05) but not in steps 2 and 4. Sotalol was superior to placebo in step 4 (OR: 2.58, 95% CI: 1.02-6.52, P = .05) and trended in step 2 (OR: 1.7, 95% CI: 0.98-3.07, P = .06). Successful electrocardioversion was seen in 11%, 29%, 38%, and 29% in steps 1, 2, 3, and 4, respectively. Compared with monophasic shocks, biphasic shocks achieved higher success rates for step 1 (P <.001) and step 2 (P <.01), respectively. Antiarrhythmic therapy did not influence the total number of energy steps used for the patients with successful electrocardioversion. However, biphasic shocks, lower BMI, and AF duration < or =1 year were associated with less energy step used for successful cardioversion. CONCLUSION: Amiodarone and sotalol facilitated successful electrocardioversion, which could be achieved in a stepwise fashion. Upon achievement of successful electrocardioversion, amiodarone is superior to placebo, and sotalol has a lesser effect. Antiarrhythmic drugs had no effect on the total number of energy step use in patients who had successful electrocardioversion. Calcium channel blockers had no influence on the success rate in achieving sinus rhythm. Successful electrocardioversion was associated with lower BMI and AF history < or =1 year. Lower energy use was associated with biphasic shocks, lower BMI, and AF duration < or =1 year.

Outcomes of the Veterans Affairs Low Vision Intervention Trial (LOVIT).

OBJECTIVE: To evaluate the effectiveness of a low-vision rehabilitation program. METHODS: A multicenter randomized clinical trial was conducted from November 2004 to November 2006 with a 4-month follow-up. A total of 126 patients were included, 98% of whom were white and male. The patients were referred from eye or low-vision clinics and blind rehabilitation centers with a visual acuity in the better-seeing eye worse than 20/100 and better than 20/500 and were eligible for Veterans Affairs (VA) services. Telephone interviews of patients were conducted in their homes before and after participation in an outpatient low-vision program at a VA medical care facility or a (waiting list) control group. The interviewer administering questionnaires by telephone was masked to patients' assignments. Interventions included low-vision examination, counseling, and prescription and provision of low-vision devices and 6 weekly sessions provided by a low-vision therapist to teach use of assistive devices and adaptive strategies to perform daily living tasks independently. MAIN OUTCOME MEASURE: Change in patients' visual reading ability estimated from participant responses to the Veterans Affairs Low-Vision Visual Functioning Questionnaire (LV VFQ-48) reading items completed at baseline compared with 4 months after enrollment for the treatment and control groups. The secondary outcomes were changes in other visual ability domains (mobility, visual information processing, visual motor skills) and overall visual ability from baseline to 4 months estimated from VA LV VFQ-48 difficulty ratings for subsets of items. RESULTS: The treatment group demonstrated significant improvement in all aspects of visual function compared with the control group. The difference in mean changes was 2.43 logits (95% confidence interval [CI], 2.07-2.77; P < .001; effect size, 2.51) for visual reading ability; 0.84 logit (95% CI, 0.58-1.10; P < .001; effect size, 1.14) for mobility; 1.38 logits (95% CI, 1.15-1.62; P < .001; effect size, 2.03) for visual information processing; 1.51 logits (95% CI, 1.22-1.80; P < .001; effect size, 1.82) for visual motor skills; and 1.63 logits (95% CI, 1.40-1.86; P < .001; effect size, 2.51) for overall visual function. CONCLUSION: The program effectively provided low-vision rehabilitation for patients with macular diseases. APPLICATIONS TO CLINICAL PRACTICE: At least 10 hours of low-vision therapy, including a home visit and assigned homework to encourage practice, is justified for patients with moderate and severe vision loss from macular diseases. Because the waiting-list control patients demonstrated a decline in functional ability, low-vision services should be offered as early as possible. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00223756.

Economic evaluation of blind rehabilitation for veterans with macular diseases in the Department of Veterans Affairs.

PURPOSE: The Department of Veterans Affairs (VA) Low Vision Intervention Trial (LOVIT) developed an outpatient low-vision programme for patients with macular diseases providing low-vision rehabilitation comparable to VA inpatient blind rehabilitation centres (BRCs). This programme targets veterans who do not need or chose not to participate in a comprehensive inpatient blind rehabilitation programme. We examined costs and consequences using veterans in LOVIT and comparable veterans in an inpatient BRC. METHODS: We compared costs and consequences between treatment patients who participated in LOVIT, a two-site randomized clinical trial, and a sample of comparable patients who received treatment at a VA inpatient BRC. We measured consequences as the change in functional visual ability from baseline to follow-up (LOVIT: 4 months after randomization; BRC: 3 months after discharge) using the VA Low Vision Visual Functioning Questionnaire (VA LV VFQ-48). RESULTS: There were 55 LOVIT and 121 BRC patients for our analyses. Average costs were $38,627.3 higher for BRC patients ($5,054.4 +/- $404.7 SD for LOVIT vs. $43,681.7 +/- $8,853.6 SD for BRC, p < 0.0001). Thus, the BRC cost $38,627.3 per patient more than the LOVIT programme (95% CI: $17,414 to $273,482). There was a greater improvement in overall visual ability, mobility, and visual motor skill scores for BRC patients; however, there was no significant difference in improvement in reading ability or visual information processing scores. CONCLUSIONS: As VA increases outpatient blind rehabilitation services, LOVIT provides a model for expanding outpatient low-vision rehabilitation services for veterans at substantially lower costs than current inpatient BRC services.

Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation.

BACKGROUND: Many patients receiving amiodarone therapy are male. The long-term risk for amiodarone-induced thyroid dysfunction in these patients has not been systematically and prospectively investigated. The purpose of this study was to determine the extent of amiodarone-induced thyroid dysfunction in a large male cohort. METHODS: This is a substudy of a prospective randomized controlled trial (SAFE-Trial) in which amiodarone, sotalol, and placebo for persistent atrial fibrillation were evaluated. For the purpose of this substudy, sotalol and placebo groups were combined into a control group. Serial thyroid function tests were performed over 1-4.5 years. Of the 665 patients enrolled in the SAFE-Trial, 612 patients were included in this sub-study. RESULTS: Subclinical hypothyroidism, thyroid-stimulating hormone (TSH) level 4.5-10 mU/L, was seen among 25.8% of the amiodarone-treated patients and only 6.6% of controls (P <.0001). Overt hypothyroidism, TSH level >10 mU/L, was seen among 5.0% of the amiodarone-treated patients, and only 0.3% of controls (P <.001). By 6 months, 93.8% of the patients who developed TSH elevations above 10 mU/L on amiodarone had been detected. There was a trend toward a greater proportion of hyperthyroidism, defined as a TSH <0.35 mU/L, in the amiodarone group compared with the control group (5.3% vs 2.4%, P=.07). CONCLUSIONS: Hypothyroidism developed in 30.8% of older males treated with amiodarone and in only 6.9% of the controls. Hypothyroidism presented at an early stage of therapy. Hyperthyroidism occurred in 5.3% of amiodarone treated patients, and was a subclinical entity in all but 1 case.

The Veterans Affairs Low Vision Intervention Trial (LOVIT): design and methodology.

BACKGROUND: Visual impairment is a major public health problem. Vision rehabilitation programs have the potential to restore independence and improve quality of life for persons with permanent vision loss, and few have been evaluated in randomized controlled trials. PURPOSE: The Veterans Affairs (VA) Low Vision Intervention Trial is a multicenter randomized clinical trial to evaluate the effectiveness of a new outpatient low vision rehabilitation program. METHODS: 126 patients with moderate and severe vision loss due to macular diseases are randomized to low vision treatment in an outpatient setting or a usual care control group at two VA facilities in Hines, Illinois, and Salisbury, North Carolina. The primary outcome is the change in visual reading ability from baseline to four months measured with the Veterans Affairs Low Vision Visual Functioning Questionnaire-48 (VA LV VFQ-48). Secondary outcomes compare the mean change in visual ability measured with the VA LV VFQ-48 (overall ability, mobility, visual information processing, visual motor skills) for the treatment and control groups. Costs and cost effectiveness of outpatient treatment are evaluated. RESULTS: The low vision rehabilitation setting, use of a waiting list control group to address ethical issues, development of the treatment protocol, development of a vision function questionnaire for patients to self-report the difficulty they experience performing daily activities, and the use of Rasch analysis to develop and estimate this outcome measure are described. LIMITATIONS: If the new low vision rehabilitation program is proven effective, studies will be needed to determine which of the multiple aspects of the intervention are necessary and sufficient. CONCLUSIONS: The challenges of conducting clinical trials in a rehabilitation setting and use of a waiting list (deferred treatment) control group extend beyond LOVIT. The design and methods of LOVIT may be applicable to other trials of rehabilitation services and to outcomes for which reliable and valid measurement tools must be developed.

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.