Behavioral mediators of treatment effects in the weight loss maintenance trial.

BACKGROUND: The Weight Loss Maintenance Trial tested strategies for maintenance of weight loss. Personal contact was superior to interactive technology and self-directed conditions. PURPOSE: We aimed to identify behavioral mediators of the superior effect of personal contact vs. interactive technology and of personal contact vs. self-directed arms. METHODS: Overweight/obese adults at risk for cardiovascular disease (n = 1,032) who lost at least 4 kg were randomized to personal contact, interactive technology, or self-directed. After 30 months, 880 participants had data on weight and behavioral strategies. RESULTS: Reported increase of intake of fruits and vegetables and physical activity and more frequent self-weighing met criteria as mediators of the better outcome of personal contact vs. interactive technology. Increased intake of fruits and vegetables, more frequent self-weighing, and decreased dessert consumption were mediators of the difference between personal contact vs. self-directed. CONCLUSION: Inducing changes in the identified behaviors might yield better outcomes in future weight loss maintenance trials.

ONJ in two dental practice-based research network regions.

The incidence of osteonecrosis of the jaw (ONJ) in the population is low, but specifics are unknown. Potential risk factors include bisphosphonate treatment, steroid treatment, osteoporosis, and head/neck radiation. This Dental Practice-Based Research Network study estimated ONJ incidence and odds ratios from bisphosphonate exposure and other risk factors using a key word search and manual chart reviews of electronic records for adults aged > or = 35 years enrolled during 1995-2006 in 2 large health care organizations. We found 16 ONJ cases among 572,606 cohort members; 7 additional cases were identified through dental plan resources. Among 23 cases (0.63 per 100,000 patient years), 20 (87%) had at least 1 risk factor, and 6 (26%) had received oral bisphosphonates. Patients with oral bisphosphonates were 15.5 (CI, 6.0-38.7) more likely to have ONJ than non-exposed patients; however, the sparse number of ONJ cases limits firm conclusions and suggests that the absolute risks for ONJ from oral bisphosphonates is low.

Efficacy of chlorhexidine varnish for the prevention of adult caries: a randomized trial.

The Prevention of Adult Caries Study, an NIDCR-funded multicenter, double-blind, randomized clinical trial, enrolled 983 adults (aged 18-80 yrs) at high risk for developing caries (20 or more intact teeth and 2 or more lesions at screening) to test the efficacy of a chlorhexidine diacetate 10% weight per volume (w/v) dental coating (CHX). We excluded participants for whom the study treatment was contraindicated or whose health might affect outcomes or ability to complete the study. Participants were randomly assigned to receive either the CHX coating (n = 490) or a placebo control (n = 493). Coatings were applied weekly for 4 weeks and a fifth time 6 months later. The primary outcome (total net D(1-2)FS increment) was the sum of weighted counts of changes in tooth surface status over 13 months. We observed no significant difference between the two treatment arms in either the intention-to-treat or per-protocol analyses. Analysis of 3 protocol-specified secondary outcomes produced similar findings. This trial failed to find that 10% (w/v) chlorhexidine diacetate coating was superior to placebo coating for the prevention of new caries (Clinicaltrials.gov registration number NCT00357877).

Impact of sleep, screen time, depression and stress on weight change in the intensive weight loss phase of the LIFE study.

BACKGROUND: The LIFE study is a two-phase randomized clinical trial comparing two approaches to maintaining weight loss following guided weight loss. Phase I provided a nonrandomized intensive 6-month behavioral weight loss intervention to 472 obese (body mass index 30-50) adult participants. Phase II is the randomized weight loss maintenance portion of the study. This paper focuses on Phase I measures of sleep, screen time, depression and stress. METHODS: The Phase I intervention consisted of 22 group sessions led over 26 weeks by behavioral counselors. Recommendations included reducing dietary intake by 500 calories per day, adopting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and increasing physical exercise to at least 180 min per week. Measures reported here are sleep time, insomnia, screen time, depression and stress at entry and post-weight loss intervention follow-up. RESULTS: The mean weight loss for all participants over the intensive Phase I weight loss intervention was 6.3 kg (s.d. 7.1). Sixty percent (N=285) of participants lost at least 4.5 kg (10 lbs) and were randomized into Phase II. Participants (N=472) attended a mean of 73.1% (s.d. 26.7) of sessions, completed 5.1 (s.d. 1.9) daily food records/week, and reported 195.1 min (s.d. 123.1) of exercise per week. Using logistic regression, sleep time (quadratic trend, P=0.030) and lower stress (P=0.024) at entry predicted success in the weight loss program, and lower stress predicted greater weight loss during Phase I (P=0.021). In addition, weight loss was significantly correlated with declines in stress (P=0.048) and depression (P=0.035). CONCLUSION: Results suggest that clinicians and investigators might consider targeting sleep, depression and stress as part of a behavioral weight loss intervention.

ONJ in two dental practice-based research network regions.

The incidence of osteonecrosis of the jaw (ONJ) in the population is low, but specifics are unknown. Potential risk factors include bisphosphonate treatment, steroid treatment, osteoporosis, and head/neck radiation. This Dental Practice-Based Research Network study estimated ONJ incidence and odds ratios from bisphosphonate exposure and other risk factors using a key word search and manual chart reviews of electronic records for adults aged ≥ 35 yrs enrolled during 1995-2006 in two large health-care organizations. We found 16 ONJ cases among 572,606 cohort members; seven additional cases were identified through dental plan resources. Among 23 cases (0.63 per 100,000 patient years), 20 (87%) had at least one risk factor, and six (26%) had received oral bisphosphonates. Patients with oral bisphosphonates were 15.5 (CI, 6.0-38.7) more likely to have ONJ than non-exposed patients; however, the sparse number of ONJ cases limits firm conclusions and suggests that the absolute risks for ONJ from oral bisphosphonates is low.

Effects of fluoxetine on the polysomnogram in outpatients with major depression.

This study investigated the effects of open-label fluoxetine (20 mg/d) on the polysomnogram (PSG) in depressed outpatients (n = 58) who were treated for 5 weeks, after which dose escalation was available (< or = 40 mg/d), based on clinical judgment. Thirty-six patients completed all 10 weeks of acute phase treatment and responded (HRS-D < or = 10). PSG assessments were conducted and subjective sleep evaluations were gathered at baseline and at weeks 1, 5, and 10. Of the 36 subjects who completed the acute phase, 17 were reevaluated after 30 weeks on continuation phase treatment and 13 after approximately 7 weeks (range 6-8 weeks) following medication discontinuation. Acute phase treatment in responders was associated with significant increases in REM latency, Stage 1 sleep, and REM density, as well as significant decreases in sleep efficiency, total REM sleep, and Stage 2 sleep. Conversely, subjective measures of sleep indicated a steady improvement during acute phase treatment. After fluoxetine was discontinued, total REM sleep and sleep efficiency were found to be increased as compared to baseline.

Toward a generalizable model of symptoms in major depressive disorder.

BACKGROUND: This study has two goals: 1) to establish a generalizable model of the symptoms observed in outpatients with major depressive disorder (MDD); and 2) to compare symptom coverage of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) to that of the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). METHODS: A factor analysis of IDS-C, IDS-SR, HDRS, and BDI items was carried out on 324 adult outpatients with MDD. Patients with coexisting Axis I or III illness or those taking psychotropic medication were excluded. RESULTS: Ten primary factors were identified, six of which were substantially intercorrelated, defining a second-order factor of general depression severity. Schmid-Leiman orthogonalization identified the symptoms most associated with general severity. CONCLUSIONS: The IDS provided more complete factors coverage than did the HDRS or BDI and thus may be more useful in research on symptom profiles.

Recurrence of major depressive disorder in hospitalized children and adolescents.

OBJECTIVE: To evaluate the outcome of a sample of children and adolescents hospitalized with major depressive disorder (MDD) and to assess different duration and severity criteria to define recovery and recurrence. METHOD: Fifty-nine of 70 children and adolescents were reevaluated 1 to 5 years later, and the intervening course of depression and other disorders was assessed using the Kiddie-Longitudinal interval Follow-up Evaluation (K-LIFE). RESULTS: Ninety-eight percent of subjects had recovered from their index MDD episode within 1 year of their initial evaluation, but 61% had at least one recurrence during the follow-up period. Of those with recurrences, 47.2% had a recurrence within 1 year and 69.4% by 2 years from the offset of the index episode. Changing the criteria for recovery by increasing the length of time required to define recovery resulted in decreases in the number of episodes of recurrence reported. CONCLUSION: MDD in children and adolescents is often an episodic disorder. Difference in definitions of recovery and recurrence affect the data reported. Consistent definitions of remission, recovery, relapse, and recurrence are needed. These data suggest that recovery may be defined after two consecutive months without symptoms and that episodes of MDD may be briefer, but more frequent, in children and adolescents than in adults.

Effects of four normalizing methods on data analytic results in functional brain imaging.

Functional brain imaging data may contain large individual differences in information about whole brain and regional levels of activity, and it is common to remove these differences using arithmetic transformation (normalization) prior to statistical analysis. As no single transformation is widely accepted, we examine the effects of four normalizing methods (ratioing, residuals from regressions on global cerebral blood flow, Z scores, and subject residual profiles) on 1) profile shape, 2) correlations between regions, 3) correlations between subjects, and 4) analysis of variance results. These effects are evaluated using an empirical data set consisting of regional cerebral blood flow values from 22 regions of interest in 46 depressed adults and 48 age-matched normal controls obtained by 133Xe single photon emission computed tomography. Results show that normalization method has substantial but different effects on characteristics of the data and statistical results. The rationing method appears to be an optimal choice for most analyses.

The effects of extended evaluation on depressive symptoms in children and adolescents.

A sample of 137 child and adolescent outpatients with major depressive disorder were examined to identify baseline clinical characteristics that predicted symptom severity at the end of a 3-week evaluation period and to determine whether change in symptom severity between week 1 and week 2 predicted symptom severity at week three. Subjects underwent three consecutive weekly evaluations prior to being considered for entry into a double-blind, placebo-controlled treatment trial of fluoxetine. Results indicated that the combination of age, social functioning, family history, Children's Depressive Rating Scale-Revised (CDRS-R) (Poznanski et al. (1985) Psychopharmacol. Bull. 21, 979-989) total score at visit one, and percent change in symptom severity between visit one and visit two were predictors of symptom severity at visit three. These findings suggest that (1) subjects should not be excluded from randomized controlled clinical treatment trials based solely on improvement of symptom severity between visits and (2) an extended evaluation period is warranted, especially for adolescents whose symptom severity tends to fluctuate from week to week.

The Inventory of Depressive Symptomatology (IDS): psychometric properties.

The psychometric properties of the 28- and 30-item versions of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) are reported in a total of 434 (28-item) and 337 (30-item) adult out-patients with current major depressive disorder and 118 adult euthymic subjects (15 remitted depressed and 103 normal controls). Cronbach's alpha ranged from 0.92 to 0.94 for the total sample and from 0.76 to 0.82 for those with current depression. Item total correlations, as well as several tests of concurrent and discriminant validity are reported. Factor analysis revealed three dimensions (cognitive/mood, anxiety/arousal and vegetative) for each scale. Analysis of sensitivity to change in symptom severity in an open-label trial of fluoxetine (N = 58) showed that the IDS-C and IDS-SR were highly related to the 17-item Hamilton Rating Scale for Depression. Given the more complete item coverage, satisfactory psychometric properties, and high correlations with the above standard ratings, the 30-item IDS-C and IDS-SR can be used to evaluate depressive symptom severity. The availability of similar item content for clinician-rated and self-reported versions allows more direct evaluations of these two perspectives.

A curbstone consult to applicants for National Institute of Mental Health grant support.

With research budgets tight and review procedures being streamlined, applicants for research funds, especially newer investigators, may become disheartened. This article provides advice that we believe improves the quality of a written application. We detail ideas for how to develop applications that are complete and most easily understood by reviewers. Important elements include: a focus on selected, specific critical hypotheses that have both clinical and theoretical significance, documenting feasibility, establishing reliable effect sizes, providing specific analyses for each hypothesis, and writing a clear, well-articulated, "reader-friendly" application. In addition, we emphasize the value of collegial review and critique of the application prior to submission. We believe this "curbstone" advice will facilitate a well-reasoned review and if funds are available, eventual funding.

Can state and trait variables be disentangled? A methodological framework for psychiatric disorders.

The goal of this study is to propose conceptual and operational definitions of "state" and "trait", and a methodological approach to document empirically the state and trait aspects of a characteristic. An example using real data related to rapid eye movement latency for patients with major depressive disorder is presented to model the application of this method.

Aberrant behaviors of young boys with fragile X syndrome.

To determine whether aberrant behaviors described in boys with fragile X syndrome distinguish them from other boys with developmental disabilities, we asked the primary caregivers of 55 boys with fragile X and 57 matched controls to complete five behavioral questionnaires. Twenty-one items distinguished the groups. Principal components analysis (PCA) yielded five behavioral clusters: abnormal language, tactile defensiveness, poor self-control, poor eye contact/shyness, and hand flapping. Boys with fragile X were found times more likely to have both tactile defensiveness and abnormal language. The presence of these abnormal behaviors in boys with developmental delays warrants further assessment for fragile X.

Regional cerebral blood flow alterations in unipolar depression.

Forty-seven symptomatic inpatients and outpatients with major depression (13 nonendogenous, 23 endogenous, and 11 psychotic by Research Diagnostic Criteria) were compared with 138 normal control subjects. Absolute regional cerebral blood flow (rCBF, ml/minute/100 g) was measured with 133Xe single photon emission computed tomography. Flow ratios (region of interest/global flow) and residual scores (the difference between patient flow ratios and expected normal flow ratios, as derived from the control population) were also computed. Results revealed significant age x region x depression subtype interactions for absolute, ratio, and residual flow data. Consequently, a test of group means (or analysis of covariance) could not be used to examine between-group differences. Multiple regression analyses were employed to study the effects of age on rCBF. This analysis revealed that different, though sometimes overlapping, regions exhibited different age effects on rCBF in different depressive subtypes. Thus, diagnostic-subtype-dependent age effects on rCBF precluded comparisons of mean values within or across regions for subject groups, but distinguished between symptomatic depressed patients and control subjects and among patient groups. Possible causes of such effects include variations in duration of illness or medication history or sensitization phenomena.

Tridimensional Personality Questionnaire and serotonin in bulimia nervosa.

To determine the relationship between Tridimensional Personality Questionnaire (TPQ) scales and bulimia nervosa, TPQ scores of 27 bulimic women, age range 21-59, were compared with values for an age-matched sample of 128 normal control women drawn from the national norming sample by Przybeck. Scores for Novelty Seeking and Harm Avoidance were significantly higher, while scores for Reward Dependence were significantly lower for the bulimic women. A stepwise regression model of severity of purging on TPQ selected Novelty Seeking and a composite depression score, with Novelty Seeking being the stronger of the two predictors. Whole blood serotonin levels did not relate to TPQ scores or to purging frequency.

Low plasma gamma-aminobutyric acid levels in male patients with depression.

Plasma levels of gamma-aminobutyric acid (GABA) were significantly lower in males with primary unipolar major depressive disorder than in healthy controls. Although the difference in means between control and symptomatic depressed patient groups was small, the distribution of plasma GABA in the depressed patients was markedly different from controls. Forty percent of depressed patients had plasma GABA levels below those of controls. Plasma GABA levels correlated positively with duration of illness, and negatively with age at onset of the mood disorder and the total Endogenomorphic Symptom Score on the Hamilton Rating Scale. Plasma GABA levels may be a biochemical marker of vulnerability to depression, as opposed to a consequence of the illness. A low GABA condition in depression fits and complements the prevailing biogenic amine hypotheses of depression.

Does learned resourcefulness predict response to cognitive therapy in depressed outpatients?

Thirty-seven unipolar, nonpsychotic, outpatients with major depression were treated with cognitive therapy in an ongoing study designed to identify which depressions respond to cognitive therapy. Pretreatment levels of learned resourcefulness, assessed by Rosenbaum's (1980) Self Control Schedule (SCS), were used to predict response to cognitive therapy (according to the 17-item Hamilton Rating Scale for Depression and the 21-item Beck Depression Inventory). Pretreatment SCS scores did not predict response to cognitive therapy according to either measure.

A randomized, double-blind, placebo-controlled trial of trazodone hydrochloride in chronic low back pain syndrome.

A 6-week placebo-controlled trial evaluated the efficacy of trazodone hydrochloride for the relief of chronic low back pain. Forty-two subjects (22 trazodone, 20 placebo) with a 20.3-year average history of back pain were titrated to an average dose of trazodone 201 mg or placebo 238 mg and evaluated daily on a Visual Analogue Scale of pain intensity, at 2-week intervals on an observer rating of pain behavior while walking, and before and after the trial on the Beck Depression Inventory, the Sickness Impact Profile, and a solid state microcomputer (Vitalog) that measured physical activity. Trazodone blood levels and urine toxicology screens were also obtained. There were no significant differences between groups in treatment effect. The results of this study require confirmation by longer trials with larger, less chronic, more homogeneous samples at higher doses with follow-up assessments.