Research consent capacity varies with executive function and memory in Parkinson's disease.

BACKGROUND: We examined the association between cognitive domains and research consent capacity in PD. Our hypothesis was that research consent capacity is best predicted by executive function. METHODS: A cohort of 90 PD patients and 30 healthy older adults were administered the MacArthur Competence Assessment Tool for Clinical Research, Dementia Rating Scale-2, and the MoCA. Experts classified patients as either "capable" or "not capable" of providing informed consent to participate in two clinical trials. RESULTS: MacArthur Competence Assessment Tool for Clinical Research Reasoning scores for both clinical trial types were most associated with executive functions and delayed recall. As scores on these domains improved, the odds of an expert rating of "capable of consent" increased. CONCLUSIONS: These results extend our previous findings by demonstrating that memory and executive abilities appear closely associated with capacity when evaluated using either a structured interview or expert judgment of that interview.

Identifying expectant parents at risk for psychological distress in response to a confirmed fetal abnormality.

The aim of the study was to determine the incidence of psychological distress among expectant women carrying fetuses with prenatal diagnosed abnormalities and their partners. A 2-year retrospective medical chart review was completed of 1032 expectant mothers carrying fetuses with a confirmed anomaly, and 788 expectant fathers, who completed the CFDT Mental Health Screening Tool. Furthermore, 19.3 % of women and 13.1 % of men reported significant post-traumatic stress symptoms, and 14 % of men and 23 % of women scored positive for a major depressive disorder. Higher risk was noted among expectant parents of younger age and minority racial/ethnic status, and women with post-college level education and current or prior use of antidepressant medications. Heightened distress was noted within fetal diagnostic subgroups including neck masses, sacrococcygeal teratomas, neurological defects, and miscellaneous diagnoses. Incorporating screening tools into prenatal practice can help clinicians better identify the potential risk for psychological distress among expectant parents within high-risk fetal settings.

Why are spousal caregivers more prevalent than nonspousal caregivers as study partners in AD dementia clinical trials?

OBJECTIVES: Most Alzheimer disease (AD) caregivers are not spouses and yet most AD dementia trials enroll spousal study partners. This study examines the association between caregiver relationship to the patient and willingness to enroll in an AD clinical trial and how caregiver burden and research attitudes modify willingness. DESIGN: Interviews with 103 AD caregivers who met criteria for ability to serve as a study partner. RESULTS: A total of 54% of caregivers were spouses or domestic partners and the remaining were adult children. Willingness to enroll a patient in a clinical trial was associated with being a spouse [odds ratio (OR)=2.53, P=0.01], increasing age (OR=1.39, P=0.01), and increasing scores on the Research Attitudes Questionnaire (OR=1.39, P<0.001). No measures of caregiver burden or patient health were significant predictors of willingness. In multivariate models both research attitudes (OR=1.37, P<0.001) and being a spouse, as opposed to an adult child, (OR=2.06, P=0.048) were independently associated with willingness to participate. CONCLUSIONS: Spousal caregivers had both a higher willingness to participate and a more positive attitude toward research. Caregiver burden had no association with willingness to participate. The strongest predictor of willingness was research attitudes.

Course of depression and mortality among older primary care patients.

CONTEXT: : Depression is a treatable illness that disproportionately places older adults at increased risk for mortality. OBJECTIVE: : We sought to examine whether there are patterns of course of depression severity among older primary care patients that are associated with increased risk for mortality. DESIGN AND SETTING: : Our study was a secondary analysis of data from a practice-based randomized controlled trial within 20 primary care practices located in greater New York City, Philadelphia, and Pittsburgh. PARTICIPANTS: : The study sample consisted of 599 adults aged 60 years and older recruited from primary care settings. Participants were identified though a two-stage, age-stratified (60-74 years; older than 75 years) depression screening of randomly sampled patients. Severity of depression was assessed using the 24-item Hamilton Depression Rating Scale (HDRS). MEASUREMENTS: : Longitudinal analysis via growth curve mixture modeling was carried out to classify patterns of course of depression severity across 12 months. Vital status at 5 years was ascertained via the National Death Index Plus. RESULTS: : Three patterns of change in course of depression severity over 12 months were identified: 1) persistent depressive symptoms, 2) high but declining depressive symptoms, 3) low and declining depressive symptoms. After a median follow-up of 52.0 months, 114 patients had died. Patients with persistent depressive symptoms were more likely to have died compared with patients with a course of high but declining depressive symptoms (adjusted hazard ratio 2.32, 95% confidence interval [1.15-4.69]). CONCLUSIONS: : Persistent depressive symptoms signaled increased risk of dying in older primary care patients, even after adjustment for potentially influential characteristics such as age, smoking status, and medical comorbidity.

Prognostic factors, course, and outcome of depression among older primary care patients: the PROSPECT study.

OBJECTIVES: We sought to examine whether there are patterns of evolving depression symptoms among older primary care patients that are related to prognostic factors and long-term clinical outcomes. METHOD: Primary care practices were randomly assigned to Usual Care or to an intervention consisting of a depression care manager offering algorithm-based depression care. In all, 599 adults 60 years and older meeting criteria for major depression or clinically significant minor depression were randomly selected. Longitudinal analysis via growth curve mixture modeling was carried out to classify patients according to the patterns of depression symptoms across 12 months. Depression diagnosis determined after a structured interview at 24 months was the long-term clinical outcome. RESULTS: Three patterns of change in depression symptoms over 12 months were identified: high persistent course (19.1% of the sample), high declining course (14.4% of the sample), and low declining course (66.5% of the sample). Being in the intervention condition was more likely to be associated with a course of high and declining depression symptoms than high and persistent depression symptoms (OR = 2.53, 95% CI [1.01, 6.37]). Patients with a course of high and persistent depression symptoms were much more likely to have a diagnosis of major depression at 24 months compared with patients with a course of low and declining depression symptoms (adjusted OR = 16.46, 95% CI [7.75, 34.95]). CONCLUSION: Identification of patients at particularly high risk of persistent depression symptoms and poor long-term clinical outcomes is important for the development and delivery of interventions.

Imagery rehearsal for posttraumatic nightmares: a randomized controlled trial.

One hundred twenty-four male Vietnam War veterans with chronic, severe posttraumatic stress disorder (PTSD) were randomly assigned to imagery rehearsal (n = 61) or a credible active comparison condition (n = 63) for the treatment of combat-related nightmares. There was pre-post change in overall sleep quality and PTSD symptoms for both groups, but not in nightmare frequency. Intent-to-treat analyses showed that veterans who received imagery rehearsal had not improved significantly more than veterans in the comparison condition for the primary outcomes (nightmare frequency and sleep quality), or for a number of secondary outcomes, including PTSD. Six sessions of imagery rehearsal delivered in group format did not produce substantive improvement in Vietnam War veterans with chronic, severe PTSD. Possible explanations for findings are discussed.

Design of comprehensive Alzheimer's disease centers to address unmet national needs.

The problem of Alzheimer's disease (AD) exemplifies the challenges of dealing with a broad range of aging-related chronic disorders that require long-term, labor-intensive, and expensive care. As the baby boom generation ages and brain diseases become more prevalent, the need to confront the pending health care crisis is more urgent than ever before. Indeed, there is now a critical need to expand significantly the national effort to solve the problem of AD, with special focus on prevention. The Campaign to Prevent Alzheimer's Disease by 2020 (PAD2020) aims to create a new paradigm for planning and supporting the organization of worldwide cooperative research networks to develop new technologies for early detection and treatments of aging-related memory and motor impairments. PAD 2020 is developing an implementation plan to justify (1) increasing the federal budget for research, (2) developing novel national resources to discover new interventions for memory and motor disorders, and (3) creating innovative and streamlined decision-making processes for selecting and supporting new ideas. Since 1978 the National Institute on Aging or National Institute of Health (NIH) established an extensive national network of AD research facilities at academic institutions including AD Centers (ADCs), Consortium to Establish a Registry for AD, AD Cooperative Study (ADCS), AD Drug Discovery Program, National Alzheimer's Coordinating Center, National Cell Repository for AD, and AD Neuroimaging Initiative. However, despite the success of these programs and their critical contributions, they are no longer adequate to meet the challenges presented by AD. PAD 2020 is designed to address these changes by improving the efficiency and effectiveness of these programs. For example, the ADCs (P30s and P50s) can be enhanced by converting some into Comprehensive Alzheimer's Disease Centers (CADCs) to support not only research, but also by being demonstration projects on care/treatment, clinical trials, and education as well as by seamlessly integrating multisite collaborative studies (ADCS, AD Neuroimaging Initiative, Patient Registries, Clinical Data Banks, etc) into a cohesive structure that further enhances the original mission of the National Institute on Aging ADCs. Regional CADCs offer greater efficiency and cost savings while serving as coordinating hubs of existing ADCs, thereby offering greater economies of scale and programmatic integration. The CADCs also broaden the scope of ADC activities to include research on interventions, diagnosis, imaging, prevention trials, and other longitudinal studies that require long-term support. Thus, CADCs can address the urgent need to identify subjects at high risk of AD for prevention trials and very early in the course of AD for clinical trials of disease modification. The enhanced CADCs will allow more flexibility among ADCs by supporting collaborative linkages with other institutions and drawing on a wider expertise from different locations. This perspective article describes the University of Pennsylvania (Penn) CADC Model as an illustrative example of how an existing ADC can be converted into a CADC by better utilization of Penn academic resources to address the wide range of problems concerning AD. The intent of this position paper is to stimulate thinking and foster the development of other or alternative models for a systematic approach to the study of dementia and movement disorders.

Evaluation of the effect of cellular SMS reminders on consistency of antiretroviral therapy pharmacy pickups in HIV-infected adults in Botswana: a randomized controlled trial.

OBJECTIVE: Several studies have demonstrated that cellular phone short message service (SMS) improve antiretroviral adherence for people living with HIV in Africa, although less data are available to support using SMS reminders to improve timeliness of antiretroviral therapy (ART) pharmacy pick up. This study tested the efficacy of SMS reminders on timeliness of ART pharmacy pickups at an urban clinic in Gaborone, Botswana. DESIGN: A randomized-controlled trial evaluating the effect of SMS reminders on ART collection for patients with HIV on treatment. METHODS: One hundred and eight treatment-experienced adult patients were enrolled and randomly assigned to a control group or an intervention group. Participants in the intervention group received SMS reminders that were sent in advance of monthly ART refills that needed to be collected. The primary outcome was 100% timeliness of pharmacy ART pickups. Secondary outcomes included frequency of physician visits, CD4 cell counts and viral loads. RESULTS: Baseline characteristics in the intervention (n = 54) and control arms (n = 54) were similar. After six months, 85% of those receiving SMS reminders were 100% on time picking up monthly ART refills compared to 70% in the control group (p = 0.064). In secondary analysis, there were no significant changes in the CD4 counts and viral loads over the course of the study. CONCLUSIONS: Timeliness of ART pickup was not significantly improved by SMS reminders. Additionally, the intervention had no impact on immunologic or virologic outcomes in treatment-experienced patients.

Simvastatin causes changes in affective processes in elderly volunteers.

OBJECTIVES: To test for simvastatin-induced changes in affect and affective processes in elderly volunteers. DESIGN: Randomized, clinical trial. SETTING: The Geriatric Behavioral Psychopharmacology Laboratory at the University of Pennsylvania. PARTICIPANTS: Eighty older volunteers, average age 70, with high normal/mildly elevated serum cholesterol. INTERVENTION: Simvastatin up to 20 mg/d or placebo for 15 weeks. MEASUREMENTS: Daily diary records of positive and negative affects and of events and biweekly measures of depressive symptoms. Affect ratings were obtained using the Lawton positive and negative affect scales; independent raters coded the valences of events. RESULTS: Thirty-one of 39 subjects assigned to placebo and 33 of 41 receiving simvastatin completed the study. During biweekly assessments, four subjects on simvastatin and one on placebo experienced depressive symptoms, as manifest by Center for Epidemiological Studies Depression scale scores greater than 16 (exact P=.36). Diary data demonstrated significant effects on affective processes. For positive affect, there was a significant medication-by-time interaction that reflected decreases in positive affect in subjects receiving simvastatin, greatest in those patients whose final total cholesterol levels were below 148 mg/dL. For negative affect, there were significant medication-by-event, and medication-by-event-by-time interactions, reflecting a time-limited increase in the apparent effect of negative events. CONCLUSION: Simvastatin has statistically significant effects on affect and affective processes in elderly volunteers. The decrease in positive affect may be significant clinically and relevant to the quality of life of many patients.

Differences in Serum Human Chorionic Gonadotropin Rise in Early Pregnancy by Race and Value at Presentation.

OBJECTIVE: To assess whether variation in serum human chorionic gonadotropin (hCG) measures, used to assess early gestation viability, are associated with differences in clinical presentation and patient factors. METHOD: This retrospective cohort study included 285 women with first-trimester pain and bleeding and a pregnancy of unknown location for whom a normal intrauterine pregnancy was ultimately confirmed. Serial samples were collected at three U.S. sites and hCG changes were analyzed for differences by race, ethnicity, and clinical factors. A nonlinear, mixed-effects regression model was used assuming a random subject shift in the time axis. RESULTS: The hCG rise in symptomatic women with ongoing intrauterine pregnancy differs by patient factors and level at presentation. The 2-day minimum (first percentile) rise in hCG was faster when presenting hCG values were low and slower when presenting hCG value was high. African American women had a faster hCG rise (P<.001) compared with non-African American women. Variation in hCG curves was associated with prior miscarriage (P=.014), presentation of bleeding (P<.001), and pain (P=.002). For initial hCG values of less than 1,500, 1,500-3,000 and greater than 3,000 milli-international units/mL, the predicted 2-day minimal (first percentile) rise was 49%, 40%, and 33%, respectively. CONCLUSION: The rise of hCG levels in women with viable intrauterine pregnancies and symptoms of potential pregnancy failure varies significantly by initial value. Changes in hCG rise related to race should not affect clinical care. To limit interruption of a potential desired intrauterine pregnancy, a more conservative "cutoff" (slower rise) is needed when hCG values are high. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00194168.

Vitamin D Status in Botswana Children Under 2 Years Old With and Without Active Tuberculosis.

Additional strategies are needed to prevent and treat tuberculosis (TB). Although vitamin D may have antimycobacterial effects, it is unknown whether low vitamin D status confers a risk for active TB in African children. This case-control study assessed serum 25-hydroxyvitamin D (25(OH)D) concentration in children with and without active TB in Gaborone, Botswana. A total of 80 children under 2 years old with and without active TB, seen at hospitals and clinics in the greater Gaborone area between September 2010 and November 2012, were enrolled. Of these, 39 cases did not differ from the 41 controls in median 25(OH)D levels (P = 0.84). The 25(OH)D was < 20 ng/mL in 8/39 (21%) cases and 7/41 (17%) controls (P = 0.69, χ(2)). Univariate analyses of subject clinical characteristics (other than 25(OH)D levels) showed that any degree of weight loss was associated with a diagnosis of TB (P = 0.047). Other clinical characteristics, including age (P = 0.08) or weight below third percentile (P = 0.58), showed no association with TB. There was no significant difference in vitamin D status between children under 2 years old with and without active TB. Lower vitamin D status did not appear to be a risk factor for TB in this small Gaborone cohort.

The role of stress-induced cortisol in the relationship between depression and decreased bone mineral density.

BACKGROUND: This study was designed to test the hypothesis that cortisol mediates the relationship between bone density and depression in postmenopausal women. METHODS: Nineteen women aged 52-79 who had been assessed for bone mineral density by dual-energy x-ray absorptiometer (DEXA) were evaluated for depression and anxiety. Diurnal and stress-induced measures of salivary cortisol were obtained during the following week and at a laboratory session involving a speech task. RESULTS: Nine volunteers reported depression while 10 were never depressed. Ever depressed women had significantly lower total lumbar and right femur DEXA Z scores than never depressed (t(17) = 2.5, p = .019 and t(17) = 2.06, p = .05, respectively). Ever depressed women demonstrated a significant increase in salivary cortisol (area under the curve (AUC) = 27.83, SD = 37.64) compared to never depressed women (AUC = -13.34, SD = 19.55) (t(17) = -3.041, p = .007) during a psychological challenge. There were significant inverse relationships between salivary cortisol AUC values and bone density Z scores at every measured bone site. Mediation analyses suggest that 51 - 67% of the association between depression and bone density could be attributed to stress-induced changes in cortisol. CONCLUSIONS: Cortisol hypersecretion in response to stress may, in part, explain the impact of depression on bone density in post-menopausal women.

Association of resolution of major depression with increased natural killer cell activity among HIV-seropositive women.

OBJECTIVE: Depression is a potential risk factor for morbidity and mortality among patients with numerous medical conditions, including HIV disease, and it is also associated with decrements in immune function, such as natural killer (NK) cell activity. This study examined whether improvements in the diagnostic status of major depression are related to increases in NK cell activity among HIV-seropositive women. METHOD: HIV-seropositive women were recruited as part of a longitudinal cohort study and underwent comprehensive medical and psychiatric evaluations during a 2-year period. Fifty-seven women had complete NK cell activity and depression data measured at two time points and were examined for associations between changes in depression status and alterations in NK cell activity over time. RESULTS: Among the 57 HIV-seropositive women, improvements in the diagnostic status of depression and decreases in scores on the 17-item Hamilton Depression Rating Scale were significantly associated with increases in NK cell activity over time, as measured in lytic units. Eleven women (19.3%) had a major depression diagnosis that resolved over time, and this group also had a significant increase in cell activity measured in lytic units during this period. CONCLUSIONS: This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode. These findings support an examination of NK cell activity in assessments of the relationship between depression and morbidity and mortality in HIV disease.

Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease.

UNLABELLED: We studied the correlation of striatal dopamine transporter (DAT) imaging with anxiety and depression symptoms in Parkinson's disease (PD). METHODS: Patients with idiopathic PD (n = 76) and age-matched healthy volunteers (n = 46) underwent SPECT brain scans with (99m)Tc-TRODAT-1, a radiolabeled tropane that selectively binds to the DAT. TRODAT-1 distribution volume ratios, a reflection of DAT availability, were calculated from the SPECT scan data for 6 regions of interest (ROIs) in the caudate and putamen. The association between neuropsychiatric symptoms (anxiety, depression, and fatigue) and DAT availability was explored for both subject groups, and the impact of disease severity on this association was examined in the PD group. RESULTS: PD patients showed lower DAT availability than did healthy volunteers in all examined regions (for all ROIs, P < 0.001). In PD patients, higher individual affective measures (for anxiety, r = -0.30 and P = 0.01; and for depression, r = -0.24 and P = 0.05) and total affect scores (r = -0.31; P = 0.01) were associated with diminished left anterior putamen DAT availability. The association between total affect scores and DAT availability was present only in the subset of patients with less severe PD (r = -0.35; P = 0.04), but subjects with the highest DAT availability did not show high total affect scores. No association between neuropsychiatric measures and DAT availability was found in the controls. CONCLUSION: These preliminary findings suggest that decreased DAT availability may be necessary for but not invariably associated with the development of affective symptoms in PD. This suggestion is consistent with previous research showing a link between depression and basal ganglia impairment, particularly involving the left hemisphere, and extends this finding to include anxiety.

The relative contributions of disease label and disease prognosis to Alzheimer's stigma: A vignette-based experiment.

BACKGROUND: The classification of Alzheimer's disease is undergoing a significant transformation. Researchers have created the category of "preclinical Alzheimer's," characterized by biomarker pathology rather than observable symptoms. Diagnosis and treatment at this stage could allow preventing Alzheimer's cognitive decline. While many commentators have worried that persons given a preclinical Alzheimer's label will be subject to stigma, little research exists to inform whether the stigma attached to the label of clinical Alzheimer's will extend to a preclinical disorder that has the label of "Alzheimer's" but lacks the symptoms or expected prognosis of the clinical form. RESEARCH QUESTIONS: The present study sought to correct this gap by examining the foundations of stigma directed at Alzheimer's. It asked: do people form stigmatizing reactions to the label "Alzheimer's disease" itself or to the condition's observable impairments? How does the condition's prognosis modify these reactions? METHODS: Data were collected through a web-based experiment with N = 789 adult members of the U.S. general population (median age = 49, interquartile range, 32-60, range = 18-90). Participants were randomized through a 3 × 3 design to read one of 9 vignettes depicting signs and symptoms of mild stage dementia that varied the disease label ("Alzheimer's" vs. "traumatic brain injury" vs. no label) and prognosis (improve vs. static vs. worsen symptoms). Four stigma outcomes were assessed: discrimination, negative cognitive attributions, negative emotions, and social distance. RESULTS: The study found that the Alzheimer's disease label was generally not associated with more stigmatizing reactions. In contrast, expecting the symptoms to get worse, regardless of which disease label those symptoms received, resulted in higher levels of perceived structural discrimination, higher pity, and greater social distance. CONCLUSION: These findings suggest that stigma surrounding pre-clinical Alzheimer's categories will depend highly on the expected prognosis attached to the label. They also highlight the need for models of Alzheimer's-directed stigma that incorporate attributions about the condition's mutability.

Ascertaining Subjective Cognitive Decline: A Comparison of Approaches and Evidence for Using an Age-Anchored Reference Group.

BACKGROUND: Subjective cognitive decline (SCD) is increasingly considered promising to detect preclinical Alzheimer's disease. How SCD is ascertained is critical for determining its potential utility in identifying at-risk individuals, yet SCD measures differ along several dimensions. OBJECTIVE: We aimed to examine the extent to which reports of SCD in healthy elderly may be influenced by the characteristics of the SCD measures. We investigated variations in rates of SCD endorsement across different measures, including an open-ended question. We also examined the association of responses across measures, and the degree to which specific SCD items were associated with objective memory performance. METHODS: 99 healthy elderly completed a series of questionnaires from which 10 items examining SCD for memory and other aspects of cognition were drawn. We applied Cochran's Q tests to assess differences in rates of SCD, correlation analyses to examine association of SCD responses, and regression models to determine the association between SCD items and delayed verbal memory. RESULTS: Rates of SCD varied as a function of the assessment format, ranging from 1 to 7% for memory and 5 to 20% for concentration. SCD was lower for memory versus non-memory domains. SCD items were associated both within and across domains. The most accurate predictor of memory was memory-related SCD in comparison to others the same age. CONCLUSION: Characteristics of SCD items influence rates of endorsement. Querying SCD using an "age-anchored" question may provide the most accurate reflection of actual cognitive performance.

Risk factors for gyrA and parC mutations in Pseudomonas aeruginosa.

OBJECTIVE: The major mechanism of fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa (PSA) is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits. The objective of this study was to determine risk factors for PSA with and without gyrA or parC mutations. DESIGN: Case-case-control study SETTING: Two adult academic acute-care hospitals PATIENTS: Case 1 study participants had a PSA isolate on hospital day 3 or later with any gyrA or parC mutation; case 2 study participants had a PSA isolate on hospital day 3 or later without these mutations. Controls were a random sample of all inpatients with a stay of 3 days or more. METHODS: Each case group was compared to the control group in separate multivariate models on the basis of demographics and inpatient antibiotic exposure, and risk factors were qualitatively compared. RESULTS: Of 298 PSA isolates, 172 (57.7%) had at least 1 mutation. Exposure to vancomycin and other agents with extended Gram-positive activity was a risk factor for both cases (case 1 odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.13; OR, 1.14; 95% CI, 1.03-1.26; case 2 OR, 1.09; 95% CI, 1.03-1.14; OR, 1.13; 95% CI, 1.01-1.25, respectively). CONCLUSIONS: Exposure to agents with extended Gram-positive activity is a risk factor for isolation of PSA overall but not for gyrA/parC mutations. FQ exposure is not associated with isolation of PSA with mutations.

Who benefits from extended continuing care for cocaine dependence?

The goal of this study was to determine which cocaine dependent patients engaged in an intensive outpatient program (IOP) were most likely to benefit from extended continuing care (24 months). Participants (N=321) were randomized to: IOP treatment as usual (TAU), TAU plus Telephone Monitoring and Counseling (TMC), or TAU plus TMC plus incentives for session attendance (TMC+). Potential moderators examined were gender, stay in a controlled environment prior to IOP, number of prior drug treatments, and seven measures of progress toward IOP goals. Outcomes were: (1) abstinence from all drugs and heavy alcohol use, and (2) cocaine urine toxicology. Follow-ups were conducted at 3, 6, 9, 12, 18, and 24 months post-baseline. Results indicated that there were significant effects favoring TMC+ over TAU on the cocaine urine toxicology outcome for participants in a controlled environment prior to IOP and for those with no days of depression early in IOP. Trends were obtained favoring TMC over TAU for those in a controlled environment (cocaine urine toxicology outcome) or with high family/social problem severity (abstinence composite outcome), and TMC+ over TAU for those with high family/social problem severity or high self-efficacy (cocaine urine toxicology outcome). None of the other potential moderator effects examined reached the level of a trend. These results generally do not suggest that patients with greater problem severity or poorer performance early in treatment on the measures considered in this report will benefit to a greater degree from extended continuing care.

Cognitive impairment and PD patients' capacity to consent to research.

OBJECTIVE: To examine how cognitive impairment affects Parkinson disease (PD) patients' research consent capacity. METHODS: A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale-2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). RESULTS: Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity. CONCLUSIONS: PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity.

Towards personalizing treatment for depression : developing treatment values markers.

BACKGROUND: While 'personalized medicine' commonly refers to genetic markers or profiles associated with pharmacological treatment response, tailoring treatments to patient preferences and values is equally important. OBJECTIVE: To describe and demonstrate a method to develop 'values markers,' or profiles based on the relative importance of attributes of depression treatment. STUDY DESIGN: Discrete choice analysis was used to assess individuals' relative preferences for features of depression treatment. Preference profiles were developed using latent profile analysis. PATIENTS OR OTHER PARTICIPANTS: Eighty-six adults participating in an internet-based discrete choice questionnaire. MAIN OUTCOME MEASURE: Participants were presented with two depression scenarios representing mild and severe depression. For each scenario, they were asked to compare 18 choice sets based on the type of medication side effect (nausea, dizziness, and sexual dysfunction) and severity (mild, moderate, and severe); and for counseling frequency (once per week or every other week) and provider setting (the office of a mental health professional, primary care doctor, or spiritual counselor). RESULTS: Three profiles were identified: profile 1 was associated with a preference for counseling and an avoidance of medication side effects; profile 2 with an avoidance of strong medication side effects and for receiving counseling in medical settings; and profile 3 with a preference for medication over counseling. When presented with a severe depression scenario, there was a higher prevalence for profile 1 and patients were more likely to prefer mental health over primary care and spiritual settings. CONCLUSIONS: Values markers may provide a foundation for personalized medicine, and reflect current initiatives emphasizing patient-centered care. Next steps should assess whether values markers are predictive of treatment initiation and adherence.