Mark S. Cary

Daily ratings measures of alcohol craving during an inpatient stay define subtypes of alcohol addiction that predict subsequent risk for resumption of drinking

BACKGROUND Both depressive symptoms and alcohol craving have been postulated as important predictors of relapse in patients with addictive disorders. The purpose of this study was to examine the course of affective symptoms and cravings for alcohol use during the initial 25 days of residential treatment for middle aged and older adults addicted to alcohol and the relationship between these symptoms and recovery outcomes. METHODS 95 alcohol-dependent subjects were enrolled in this observational study. Participants completed a daily diary of alcohol craving, positive affect, and negative affect during residential treatment. Participants were interviewed 1 and 6 months after discharge to assess clinical symptoms of relapse and functioning. RESULTS Latent class analysis identified three groups of individuals for each of the three daily measures. For alcohol craving, 17 subjects reported elevated cravings during the entire treatment stay, 37 subjects reported initially elevated but then a slight improvement in craving, and 41 subjects reported relatively low craving from the time of admission to the end of residential treatment. Alcohol craving class was associated with negative affect but not positive affect. Alcohol craving class but not affective class was predictive of time to relapse to any drinking in the 6 months after residential treatment (p<0.05). CONCLUSION Results suggest that non-cue induced alcohol craving may define a subtype of alcohol dependence that is less responsive to treatment and may explain heterogeneity in treatment outcomes. These results also may suggest a role for differential treatment programming to address high states of craving for alcohol.

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.

Alcohol-related dementia: validation of diagnostic criteria.

OBJECTIVE The authors sought to validate the diagnostic criteria for alcohol-related dementia. METHODS The sample consisted of veterans consecutively admitted to a 240-bed VA Nursing Home Care Unit. Baseline and follow-up assessments included measures of cognition and functioning. The diagnosis and type of dementia was determined within 2 months of admission by a geropsychiatrist using patient interviews, chart review, and information from a structured collateral interview. Residents were followed for up to 2 years. RESULTS Data were collected on 192 of the residents, of whom, 158 (82%) were diagnosed with some form of dementia. Alcohol-related dementia (ARD) was diagnosed in 16 residents (10.1%), probable Alzheimer dementia (AD), in 26 (16.5%); vascular dementia (VD), in 46 (29.1); and mixed or dementia of undetermined origin, in 70 (44.3%). Those with ARD were less cognitively impaired and were more often unmarried. Residents with ARD demonstrated a stabilization of both cognition and functional status, whereas those with AD and VD showed a general decline in both cognition and functional status. CONCLUSION These results serve to validate the diagnostic criteria for ARD and suggest that abstinence may be of clinical value in treating patients with dementia and alcohol dependence. Further research needs to be conducted to confirm the value of abstinence.

The Role of Medical Comorbidity in Outcome of Major Depression in Primary Care The PROSPECT Study

OBJECTIVE The authors described the influence of specific medical conditions on clinical remission and response of major depression (MDD) in a clinical trial evaluating a care-management intervention among older primary-care patients. METHODS Adults age 60 years and older were randomly selected and screened for depression. Participants were randomly assigned to Usual Care or to an Intervention with a depression care-manager offering algorithm-based care for MDD. In all, 324 adults meeting criteria for MDD were included in these analyses. Remission and response was defined by a score on the Hamilton Rating Scale for Depression <10 and by a decrease from baseline of > or =50%, respectively. Medical comorbidity was ascertained through self-report. Cognitive impairment was defined by a score <24 on the Mini-Mental State Exam (MMSE). RESULTS In Usual Care, rates of remission were faster in persons who reported atrial fibrillation (AF) than in persons who did not report AF and slower in persons who reported chronic pulmonary disease than in persons who did not report chronic pulmonary disease; rates of response were less stable in persons with MMSE <24 than in those with MMSE > or =24. In the Intervention condition, none of the specific chronic medical conditions were significantly associated with outcomes for MDD. CONCLUSIONS Because disease-specific findings were observed in persons who received Usual Care but not in persons who received more intensive treatment in the Intervention condition, our results suggest that the association of medical comorbidity and treatment outcomes for MDD may be determined by the intensity of treatment for depression.

How redesigning AD clinical trials might increase study partners’ willingness to participate

Background: Timely recruiting and retaining participants into Alzheimer disease (AD) clinical trials is a challenge. We used conjoint analysis to identify how alterations in attributes of clinical trial design improve willingness to participate: risk, home visits, car service, or increased chance of receiving intervention. Method: A total of 108 study partners of patients with very mild to severe stage AD rated willingness to allow their relative to participate in eight clinical trials that varied combinations of the four attributes. Results: The highest utility was for home visits (0.89) which essentially compensated for the disutility of high risk (−0.85). The combination of home visits and car service was redundant, with almost no increase in utility over home visits alone. Seventeen percent were willing to participate in a trial with no amenities; the addition of home visits increased predicted willingness to participate to 27%; low risk, home visits, and higher chance of active treatment increased predicted willingness to 60%. The value of reducing the hassles of travel correlated well with measures of AD severity (activities of daily living r = 0.41, p < 0.001; basic activities of daily living r = 0.38, p < 0.001; Neuropsychiatric Inventory severity p = 0.24, p = 0.01; Neuropsychiatric Inventory distress r = 0.23, p < 0.02). No association was found between degree of study partner burden and willingness to tolerate risk of an intervention. Conclusion: Clinical trials that reduce travel inconvenience may offset the disincentive of study features such as the risk of intervention and may also increase willingness to participate. Redesigning trials may also help recruit patients with more severe Alzheimer disease. Shorter recruitment periods and increased retention rates may offset costs of these changes. GLOSSARY: AD = Alzheimer disease; BLUP = best linear unbiased prediction; RAQ = Research Attitude Questionnaire.

Simvastatin Causes Changes in Affective Processes in Elderly Volunteers

OBJECTIVES: To test for simvastatin‐induced changes in affect and affective processes in elderly volunteers.

Causal mediation analyses for randomized trials

In the context of randomized intervention trials, we describe causal methods for analyzing how post-randomization factors constitute the process through which randomized baseline interventions act on outcomes. Traditionally, such mediation analyses have been undertaken with great caution, because they assume that the mediating factor is also randomly assigned to individuals in addition to the randomized baseline intervention (i.e., sequential ignorability). Because the mediating factors are typically not randomized, such analyses are unprotected from unmeasured confounders that may lead to biased inference. We review several causal approaches that attempt to reduce such bias without assuming that the mediating factor is randomized. However, these causal approaches require certain interaction assumptions that may be assessed if there is enough treatment heterogeneity with respect to the mediator. We describe available estimation procedures in the context of several examples from the literature and provide resources for software code.

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.

Measuring How People View Biomedical Research: Reliability and Validity Analysis of the Research Attitudes Questionnaire

With increasing numbers of studies on research ethics and a need to improve the recruitment of research subjects, the ability to measure attitudes toward biomedical research has become important. The Research Attitudes Questionnaire is a significant predictor of the publics attitudes toward and willingness to participate in research, yet limited data are available on its psychometric properties. This study establishes the scales internal consistency and dimensionality using a large Internet-based sample from the United States. One item was removed due to a poor item-total correlation, and three additional items were removed which formed a reverse-wording measurement artifact factor. With improved internal consistency and dimensionality, the seven-item version has the advantages of shorter administration time and improved psychometric properties.

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.