Individuals' experiences in genetic counseling and predictive testing for familial amyotrophic lateral sclerosis.

As clinical genetic testing in the amyotrophic lateral sclerosis (ALS) diagnostic setting increases, the identification of at-risk family members has also expanded. No practice guidelines specifically for predictive genetic testing exist, and few studies about the psychological impacts of testing in this subgroup have occurred, limiting the ability to tailor recommendations and counseling in this community. We surveyed asymptomatic individuals at risk for inheriting an ALS-associated gene mutation. The 80-question survey was designed using a combination of validated measures (General Anxiety Disorder; FACToR; Decision Regret Scale) and original items. Ninety participants completed the survey, including those who completed predictive genetic testing (N = 42) and those who did not (N = 48). Gene positive individuals experienced greater negativity, uncertainty, and overall psychological impairment (p = 0.002; p < 0.001; p = 0.001). Individuals who had not undergone testing reported thinking about their risk multiple times per day and experiencing more decisional regret than those who tested (p = 0.006). In terms of decision-making, being prepared for potential clinical drug trials was a more important potential benefit among those who underwent testing (p = 0.026). Participants valuing preparedness for clinical drug trials supports the concept that genetic testing for ALS will increase as research in gene-targeted therapeutics progresses. This study describes factors relevant to the genetic testing decision-making process and adaptation to results from the perspective of at-risk individuals, which can ultimately guide genetic counseling practice in this population.

Randomized double-blind personalized N-of-1 clinical trial to test the safety and potential efficacy of TJ-68 for treating muscle cramps in amyotrophic lateral sclerosis (ALS): study protocol for a TJ-68 trial.

INTRODUCTION/AIMS: Muscle cramps are a common and often disabling symptom in amyotrophic lateral sclerosis (ALS), a devastating and incurable neurodegenerative disorder. To date, there are no medications specifically approved for the treatment of muscle cramps. Ameliorating muscle cramps in ALS may improve and sustain quality of life. A widely prescribed traditional Japanese (Kampo) medicine against muscle cramps, shakuyakukanzoto (TJ-68), has been studied in advanced liver disease, spinal stenosis, kidney failure, and diabetic neuropathy. The Japanese ALS Management Guideline mentions TJ-68 for difficult muscle cramps in ALS. Therefore, the rationale of our trial is to investigate the safety and effectiveness of TJ-68 in treating painful and disabling muscle cramps in people with ALS outside of Japan. Accordingly, we are conducting a randomized clinical trial to test the safety and efficacy of TJ-68 in participants with ALS reporting frequent muscle cramps using an innovative, personalized N-of-1 design. If successful, TJ-68 may be used for muscle cramps in a broader population of people with ALS. METHODS: This is a two-site, double-blind, randomized personalized N-of-1 early clinical trial with TJ-68. At least 22 participants with ALS and daily muscle cramps will receive drug or placebo for 2 weeks (one treatment period) followed by a 1-week washout in a four-period cross-over design. While the primary objective is to evaluate the safety of TJ-68, the study has 85% power to detect a one-point shift on the Visual Analog Scale for Muscle Cramps Affecting Overall Daily Activity of the Columbia Muscle Cramp Scale (MCS). Secondary outcomes include the full MCS score, a Cramp Diary, Clinical Global Impression of Changes, Goal Attainment Scale, quality of life scale and ALS functional rating scale-revised (ALSFRS-R). DISCUSSION: The study is underway. A personalized N-of-1 trial design is an efficient approach to testing medications that alleviate muscle cramps in rare disorders. If TJ-68 proves safe and efficacious then it may be used to treat cramps in ALS, and help to improve and sustain quality of life. TRIAL REGISTRATION: This clinical trial has been registered with ClinicalTrials.gov (NCT04998305), 8/9/2021.

A theory-informed, rapid cycle approach to identifying and adapting strategies to promote sustainability: optimizing depression treatment in primary care clinics seeking to sustain collaborative care (The Transform DepCare Study).

BACKGROUND: Few real-world examples exist of how best to select and adapt implementation strategies that promote sustainability. We used a collaborative care (CC) use case to describe a novel, theory-informed, stakeholder engaged process for operationalizing strategies for sustainability using a behavioral lens. METHODS: Informed by the Dynamic Sustainability Framework, we applied the Behaviour Change Wheel to our prior mixed methods to identify key sustainability behaviors and determinants of sustainability before specifying corresponding intervention functions, behavior change techniques, and implementation strategies that would be acceptable, equitable and promote key tenets of sustainability (i.e., continued improvement, education). Drawing on user-centered design principles, we enlisted 22 national and local stakeholders to operationalize and adapt (e.g., content, functionality, workflow) a multi-level, multi-component implementation strategy to maximally target behavioral and contextual determinants of sustainability. RESULTS: After reviewing the long-term impact of early implementation strategies (i.e., external technical support, quality monitoring, and reimbursement), we identified ongoing care manager CC delivery, provider treatment optimization, and patient enrollment as key sustainability behaviors. The most acceptable, equitable, and feasible intervention functions that would facilitate ongoing improvement included environmental restructuring, education, training, modeling, persuasion, and enablement. We determined that a waiting room delivered shared decision-making and psychoeducation patient tool (DepCare), the results of which are delivered to providers, as well as ongoing problem-solving meetings/local technical assistance with care managers would be the most acceptable and equitable multi-level strategy in diverse settings seeking to sustain CC programs. Key adaptations in response to dynamic contextual factors included expanding the DepCare tool to incorporate anxiety/suicide screening, triage support, multi-modal delivery, and patient activation (vs. shared decision making) (patient); pairing summary reports with decisional support and yearly onboarding/motivational educational videos (provider); incorporating behavioral health providers into problem-solving meetings and shifting from billing support to quality improvement and triage (system). CONCLUSION: We provide a roadmap for designing behavioral theory-informed, implementation strategies that promote sustainability and employing user-centered design principles to adapt strategies to changing mental health landscapes.

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Case-control study in ALS using the National ALS Registry: lead and agricultural chemicals are potential risk factors.

Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p < 0.0001) but was not associated with occupational exposure to either lead or ACs. Conclusions: Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.

Comparison of counseling methods to promote employment for HIV+ ADULTS.

BACKGROUND: Despite improved health and during a strong job market (pre-COVID-19), a substantial proportion of HIV+ adults remained unemployed. This study sought to provide time-limited counseling to promote employment goals. OBJECTIVE: To determine whether behavioral activation (BA) or supportive counseling (SC), would be more effective in promoting vocational goals (full or part-time, paid or volunteer). METHODS: The study included two groups: those with clinically significant fatigue, who were first treated with armodafinil. Once their fatigue diminished, they were enrolled in the counseling program. Those without fatigue were enrolled directly. Both BA and SC interventions were manualized, consisting of eight individual sessions plus a follow-up. RESULTS: 116 participants entered counseling, including 87 assigned to BA and 29 to SC. Of these, 79 completed counseling or found a job by session eight. By follow-up, 51%of BA versus 41%of SC participants had found jobs, a non-significant difference either clinically or statistically. CONCLUSIONS: Multiple issues contributed to difficulty in employment, including gaps in resumes, loss of contact with former colleagues, and uncertainty about career direction. Ongoing barriers included substance use, housing instability, ambivalence about forfeiting government benefits, as well as inadequately treated depression. Success in employment for about half of participants is, in this context, a reasonable outcome.

Returning to work after fatigue treatment and counseling in HIV/AIDS.

BACKGROUND: Employment rates for people with HIV/AIDS are low, compared to the general population. One widespread barrier is fatigue, accompanied by daytime sleepiness and a lack of stamina. Previous pharmacological studies have demonstrated improvement of fatigue-related symptoms without affecting work-related goal attainmentOBJECTIVE:In this pilot study, we sought to determine whether a pharmacologic-behavioral two-phase combined approach could facilitate returning to work. METHODS: HIV+ participants with fatigue were treated with armodafinil. If energy improved, 8 sessions of biweekly manualized Behavioral Activation (BA) counseling were added to medication maintenance. Outcome was assessed on a 3-point scale along with clinician and self-ratings. RESULTS: Of the 46 participants enrolled in BA, 15 (33%) did not complete all 8 sessions: 6 got jobs so they no longer needed counseling; 4 did not like BA, and 5 dropped out for reasons such as moving away or substance use relapse. Of the 46, 29 (63%) attained their vocational goal and showed significant changes on self-report scales. CONCLUSIONS: Our integrated treatment including armodafinil plus BA counseling significantly increased the success of achieving work-related goals. The two-phase medication plus counseling program was well-tolerated by participants and the manualized BA counseling was readily applied by counselors without advanced mental health training, making the method potentially feasible in community settings.

Trauma and Growth: Impact of AIDS Activism.

INTRODUCTION: Our goal was to assess the long-term impact of AIDS activism of ACT UP/New York on the current adjustment of those who were members during its peak years (1987-1992), including assessment of trauma sequelae as well as posttraumatic growth. METHODS: A 90-minute semistructured interview and 6 validated self-report scales were administered. We relied on purposive and snowball sampling to recruit potential participants. Areas covered include demographics, ACT UP participation, and psychiatric problems. Self-report scales provided approximate diagnoses of PTSD and depression, as well as coping, optimism, and related concepts. RESULTS: Participants included 102 men (40% HIV-positive) and 23 women. Seventeen percent reported current symptoms suggesting PTSD, slightly above the range in general population studies. Symptoms consistent with depression were reported by 8% overall, with higher rates for HIV+ men. Enhanced sense of self, belief in change, and empowerment were reported by 93% of respondents, independent of concurrent PTSD or depression. CONCLUSIONS: Twenty-eight years later, ACT UP study participants recall their activist days during the AIDS epidemic as the peak experience of their lives. While some continue to have symptoms of stress and depression, most found that their activism has enriched their subsequent lives.

Depressive Symptoms and Suicidal Ideation Among Symptomatic Patients With a History of Lyme Disease vs Two Comparison Groups.

BACKGROUND: Depression has been reported in 8-45% of patients with posttreatment Lyme symptoms (PTLS), but little is known about suicidal ideation in these patients. METHOD: Depression and suicidal ideation were assessed using the Beck Depression Inventory (BDI-II). Scores from the PTLS group (n = 81) were compared to those from 2 other groups: HIV+ patients being treated for fatigue (n = 70), and a nonpatient comparison group (NPCG; n = 44). ANOVA and t-tests were used to compare groups; logistic regression was used to identify the strongest correlates of suicidal ideation. RESULTS: Mean BDI-II scores fell in the mildly depressed range for PTLS and HIV+ patients, with both groups having higher depression scores than the NPCG. Suicidal ideation was reported by 19.8% of the PTLS patients and 27.1% of the HIV+ patients, a nonsignificant difference. Among those with mild or no depression, suicidal ideation was uncommon (6.5% PTLS and 11.9% HIV+). Among the patients with moderate-to-severe depression, suicidal ideation was more common (63.2% of 19 PTLS and 50% of 28 HIV+); among these, 2 with PTLS and 1 with HIV+ expressed suicidal intent. Further, 4.5% (n = 2) of the NPCG had suicidal ideation, each had scores in the moderate-to-severe depression range. Higher scores on the cognitive symptoms subscale of the BDI-II predicted greater likelihood of suicidal ideation across patient groups. CONCLUSION: As expected, suicidal ideation is increased among patients who are depressed. The fact that 1 in 5 patients with PTLS reported suicidal ideation highlights the importance of screening for depression and suicidality to optimize patient care.

Depression and wish to die in a multicenter cohort of ALS patients.

Our objective was to determine prevalence of depressive disorders and wish to die at the baseline visit of a longitudinal multisite study of patients with ALS. Structured telephone interviews were conducted with patients diagnosed in past 18 months at 16 U.S. ALS centers. Demographic, medical, psychiatric and other psychological measures were administered. Of 329 patients assessed, mean ALSFRS-R score was 36.6; 88% (289/329) had no depressive disorder, 7% (24/329) had minor depression, and 5% (16/329) had current major depressive disorder (DSM-IV criteria). Demographic, financial and employment factors were unrelated to depression, as were duration of ALS symptoms and respiratory status, although depressed patients had lower scores on the total ALSFRS-R (p = 0.004) and gross motor function (p < 0.001). Depressed patients reported less pleasure, greater suffering, weariness and anxiety, more stress, were less hopeful, felt less control over illness management, reported lower quality of life, more often had thoughts about ending their lives and hastening death (all p < 0.001). Of the 62 patients (19% of the sample) who expressed a wish to die, only 37% (23/62) were clinically depressed. In conclusion, depressive disorders are not necessarily to be expected of ALS patients. Wish to die is not always expressed in the context of depression and does not necessarily represent psychopathology as such.

Seeking a measure of clinically meaningful change in ALS.

We sought to identify a method to assess 'clinically meaningful change' perceived by patients, caregivers and clinical raters in relation to changes in ALSFRS-R scores at three-month intervals. In this five-site study, 81 patient-caregiver dyads were interviewed at baseline, three, and six months to assess changes in ALSFRS-R in relation to perceived occurrence of change, its magnitude and impact. Ratings by patients, caregivers and clinical raters were analyzed over three-month intervals within and between respondent groups. We found that patients, clinical raters, and caregivers agreed about 80% of the time about whether change occurred, and in what direction, on each of three visits. The perceived magnitude of change for the four domains measured by the ALSFRS-R was correlated with ratings of impact within respondent groups and across time. We also found moderate associations between changes in ALSFRS-R domain scores and judgments of symptom impact as rated by patient, caregiver and clinical rater. Independent measures (Quality of Life, Goal Assessment Scaling) showed no consistent correlations with ALSFRS-R change scores. In conclusion, the use of scales to assess the perceived magnitude and impact of change corresponding with the domains of the ALSFRS-R may be a step towards understanding of the clinical meaning of changes in that measure.

Japanese and American ALS patient preferences regarding TIV (tracheostomy with invasive ventilation): a cross-national survey.

Substantial disparities in TIV utilization rates among ALS patients have been observed, with rates in Japan far exceeding rates in the United States. Our objective was to elicit national preferences and their determinants. We predicted more Japanese than American patients would desire TIV, as would sicker patients, those already using non-invasive interventions, and those with more positive mood and outlook. Patients were enrolled in five U.S. states and six Japanese regions. Eligible patients completed surveys during clinic visits (U.S.) or at home (Japan). Survey responses were in multiple-choice format and took about 15 min to complete. One hundred and fifty-six Americans and 66 Japanese patients participated. Contrary to expectations, Japanese patients were more likely to oppose TIV, as were those on 24-h NIV and patients who knew someone using TIV. Most Japanese and American patients with advanced respiratory impairment were undecided or opposed to TIV, while nearly 20% in both countries were in favor. Finally, patients who favored TIV or who were undecided had more energy, greater wish to live, and more sense of control over ALS management. In conclusion, factors other than patient preferences, such as neurologist preferences, caregiver attitudes and perhaps lack of advance planning, may influence probability of TIV utilization.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Effect of armodafinil on cognition in patients with HIV/AIDS and fatigue.

Fatigue and cognitive impairment are common in HIV+ adults and may occur independently or be causally linked. This study examined whether alleviation of fatigue with armodafinil in a placebo-controlled double-blind 4-week trial had an effect on cognitive function among those with and without mild neuropsychological impairment at baseline. Sixty-one patients completed a standard battery of neuropsychological tests at study entry and Week 4: A total of 33 were randomized to armodafinil and 28 to placebo. While there was a significant effect of active medication on fatigue, cognitive performance measured by a global change score did not differ between treatment groups, or in those on active treatment with or without mild neuropsychological impairment.

Tracheostomy with invasive ventilation for ALS patients: neurologists' roles in the US and Japan.

Our objective was to determine whether substantial differences in rates of TIV utilization in the U.S. and Japan are associated with the role of the treating neurologist. Questionnaires in English and Japanese were sent to neurologists who treated ALS patients in both countries. Questions included queries about rates of TIV use in their practices, level of encouragement of TIV use, the role of the neurologist in TIV decision making, management of patient/family requests to discontinue TIV once initiated, and personal choices if neurologists themselves had ALS. Results showed that 84% of American neurologists reported fewer than 10% of their patients had TIV, compared to 32% of Japanese. Americans less often encouraged TIV use (79% of American and 36% of Japanese seldom or never suggested or encouraged TIV). Finally, neurologists were asked whether they would choose TIV for themselves in the hypothetical scenario where they had ALS: over 70% of both groups declined TIV for themselves. In conclusion, consistent with past findings, Japanese neurologists were more likely to recommend TIV and more of their patients received TIV. Both groups believed their recommendations influence patient decisions. While Americans seldom recommended TIV to patients and most would not choose TIV for themselves, Japanese neurologists' recommendations and personal choices diverged.

DHEA and cognition in HIV-positive patients with non-major depression.

BACKGROUND: Dihydroepiandrosterone (DHEA) has been investigated for its potential role in improving cognition in a number of patient populations. Treatment options are limited for HIV-associated neurocognitive disorders. OBJECTIVE: The authors tested the effect of DHEA administration on the cognitive functioning of HIV-positive subjects with non-major depression. METHOD: The neuropsychological testing data for 60 HIV-positive patients enrolled in a clinical trial for non-major depression were analyzed to determine if DHEA-treated patients demonstrated improved cognitive functioning versus placebo. RESULTS: At baseline, 80% of the sample met criteria for asymptomatic cognitive impairment. No benefit in cognitive performance was found on 16 of 17 neuropsychological measures evaluated. One measure showed a modest benefit for placebo-treated patients over DHEA. CONCLUSION: DHEA treatment was not associated with improved cognitive performance in HIV-positive patients with non-major depression.

Treatment of HIV-related fatigue with armodafinil: a placebo-controlled randomized trial.

OBJECTIVE: To evaluate the efficacy and safety of armodafinil in the treatment of fatigue in HIV+ patients, and to assess its effect on depressive symptoms and behavior once fatigue remitted. METHOD: HIV+ patients with clinically significant fatigue were treated in a placebo-controlled randomized double-blind trial for 4 weeks. Armodafinil responders and placebo non-responders or relapsers were treated openly for a total of 16 weeks with armodafinil. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement Scale, supplemented by the Fatigue Severity Scale, the Hamilton Depression Rating Scale, and the Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV RNA viral load and the SAFTEE side effects rating scale. Maximum trial dose of armodafinil was 250 mg/d. RESULTS: Seventy patients were enrolled. Attrition was 9%. In intention-to-treat analyses, fatigue response rate to armodafinil was 75% and to placebo, 26%. Armodafinil did not reduce depressive symptoms in the absence of improved energy, but of those patients with an Axis I depressive disorder at study entry whose energy improved, 82% experienced improved mood as well. Markers of immunologic suppression did not change during treatment. At 6 months, those still taking armodafinil had more energy and fewer depressive symptoms than those who were no longer taking it. CONCLUSIONS: As we found in our RCT of modafinil, armodafinil appears effective and well tolerated in treating fatigue in HIV+ patients. Side effects were minimal and most patients reported substantially improved energy and mood.

Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and to assess effect on depressive symptoms. METHOD: Patients who were HIV+ and had clinically significant fatigue (according to the Fatigue Severity Scale [FSS]) were included in a 4-week randomized, placebo-controlled, double-blind trial. This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement scale, supplemented by the FSS, Hamilton Depression Rating Scale, and Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV ribonucleic acid (RNA) viral load. Visits were weekly for 4 weeks, then biweekly, with a follow-up visit at 6 months. Maximum trial dose of modafinil was 200 mg/d. Data for this study were collected between December 2004 and December 2008. RESULTS: 115 patients were randomly assigned. In intention-to-treat analyses, fatigue response rate to modafinil was 73% and to placebo, 28%. Attrition was 9%. Modafinil did not have an effect on mood alone in the absence of improved energy. At week 4, CD4 cell counts did not change significantly; HIV RNA viral load showed a trend decline for patients taking modafinil but not for those taking placebo. At 6 months, those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil, and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load. CONCLUSIONS: Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients. Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community, its minimal side effects, and overall patient acceptance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00118378.

A prospective cohort study of neuropsychological test performance in ALS.

Our objective was to determine the prevalence and predictors of cognitive impairment in ALS, measure differences in survival among impaired and unimpaired patients, and assess changes in neuropsychological test performance over time. Fifty patients were enrolled in a prospective cohort study of neuropsychological performance. ANOVA and chi(2) tests assessed differences in clinical characteristics and neuropsychologic test results; general estimating equations assessed change in test performance; multiple regression determined which variables contributed to cognitive status; and Cox models compared survival. Thirty-six patients were categorized as cognitively normal, and 14 were impaired. Impaired patients were older at testing (p = 0.024), but no more likely to have bulbar signs. Predicators of impairment were symptom duration (p < 0.001), motor function (p < 0.001), and rate of ALS progression (p < 0.001). The Benton recognition (p < 0.001), Boston naming (p = 0.001), Wisconsin Card Sort (p = 0.001) and word generation (p = 0.001) tests contributed most strongly to cognitive status. Survival was worse in impaired patients (p = 0.027). Over time, only animal word generation declined (p = 0.016). In conclusion, 28% percent of patients were cognitively impaired. Older age and more severe ALS were associated with impairment. The strongest neuropsychological predictors of cognitive status were measures of executive, episodic memory and language function. Cognitively impaired patients had shorter survival time.

Modafinil effects on cognitive function in HIV+ patients treated for fatigue: a placebo controlled study.

Both mild cognitive impairment and fatigue are common among people with HIV/AIDS. This study examined the efficacy of modafinil for HIV+ patients who sought treatment for fatigue in a placebo-controlled double-blind 4-week trial. A battery of standard neuropsychological tests was administered at study entry and Week 4, and change in performance was compared for 59 patients receiving modafinil versus 44 patients receiving placebo. A significant effect on fatigue was observed. In addition, cognitive performance, as measured by a global change score, improved more in the modafinil than in the placebo group although the effect was not specific to any cognitive domain.