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1.  Assessment of Anxiety and Depression in Primary Care: Value of a Four-Item Questionnaire 
Standard questionnaires (eg, Primary Care Evaluation of Mental Disorders [PRIME-MD], Hopkins Symptom Checklist [HSCL]) can be used to assess anxiety and depression in patients. However, such survey tools are typically lengthy and are therefore not used often in primary care.
To determine the value of a four-item anxiety and depression screening questionnaire as a diagnostic assessment tool in family practice.
Two self-administered patient questionnaires—PRIME-MD and 25-item HSCL—were provided to a random sample of adult patients at three family practices in Philadelphia, Pa. A subset of patients who endorsed at least one of four anxiety and depression stem items in the PRIME-MD questionnaire were interviewed using the PRIME-MD clinician evaluation guide. The HSCL anxiety and depression clusters were used as the standard measures of emotional symptomatology. Sensitivity and specificity for the four stem items to detect evidence of anxiety or mood disorders were established using the structured interview as the diagnostic gold standard.
A total of 211 patients participated in the present study. Lowest levels of emotional symptomatology were seen in patients who did not endorse any of the stem items, while highest levels were seen in patients who endorsed anxiety and depression items. Findings were statistically significant (P<.0001). Endorsement of at least three of the four stem items differentiated best between patients with and without an anxiety or mood disorder (P<.001), achieving high sensitivity (78%) and specificity (95%).
A four-item screening tool based on PRIME-MD anxiety and depression stem questions can alert family physicians to potential anxious or depressive symptomatology in the patient and the need for continued evaluation and possible treatment.
PMCID: PMC4566952  PMID: 19369508
2.  Measuring Outcome in the Treatment of Cocaine Dependence 
Little in known about the extent to which outcome measures used in studies of the treatment of cocaine dependence are associated with longer-term use and with broader measures of clinical improvement. The current study examined reductions in use, and abstinence-oriented measures, in relation to functioning and longer-term clinical benefits in the treatment of cocaine dependence.
Overall drug use, cocaine use, and functioning in a number of addiction-related domains for 487 patients diagnosed with DSM-IV cocaine dependence and treated with one of four psychosocial interventions in the NIDA Cocaine Collaborative Treatment Study were assessed monthly during 6 months of treatment and at 9, 12, 15, and 18 month follow-up.
Measures of during-treatment reduction in use were moderately correlated with drug and cocaine use measures 12 months, but showed non-significant or small correlations with measures of functioning at 12 months. Highest correlations were evident for abstinence measures (maximum consecutive days abstinence and completely abstinent) during treatment in relation to sustained (3 month) abstinence at 12 months. Latent class analysis of patterns of change over time revealed that most patients initially (months 1 to 4 of treatment) either became abstinent immediately or continued to use every month. Over the couse of follow-up, patients either maintained abstinence or used regularly – intermittent use was less common.
There were generally small associations between various measures of cocaine use and longer-term clinical benefits, other than abstinence was associated with continued abstinence. No one method of measuring outcome of treatment of cocaine dependence appears superior to others.
PMCID: PMC4564116  PMID: 26366427
Cocaine Dependence; Psychosocial Treatment; Patterns of Change; Abstinence; Relapse
3.  Psychotherapy Credibility Ratings: Patient Predictors of Credibility and the Relation of Credibility to Therapy Outcome 
Very little is known about what factors may influence credibility ratings. The current investigation examined the relation between credibility ratings for adult psychotherapies and a variety of patient factors as well as the relation between credibility ratings and subsequent symptom change. A pooled study database that included studies evaluating the efficacy of cognitive and psychodynamic therapies for a variety of disorders was used. For all studies, a 3-item credibility scale was administered at session 2. Early symptom change, expectation of improvement, demographic characteristics, clinical measures, and functioning and interpersonal measures were used to predict credibility at session 2. We found that early symptom improvement was significantly associated with higher credibility ratings at session 2; higher ages, higher levels of education, and lower expectations of improvement were associated with lower credibility ratings at session 2; and credibility ratings predicted subsequent symptom improvement.
PMCID: PMC4560353  PMID: 24219179
4.  Effect of Exenatide, Sitagliptin, or Glimepiride on β-Cell Secretory Capacity in Early Type 2 Diabetes 
Diabetes Care  2014;37(9):2451-2458.
Agents that augment GLP-1 effects enhance glucose-dependent β-cell insulin production and secretion and thus are hoped to prevent progressive impairment in insulin secretion characteristic of type 2 diabetes (T2D). The purpose of this study was to evaluate GLP-1 effects on β-cell secretory capacity, an in vivo measure of functional β-cell mass, early in the course of T2D.
We conducted a randomized controlled trial in 40 subjects with early T2D who received the GLP-1 analog exenatide (n = 14), the dipeptidyl peptidase IV inhibitor sitagliptin (n = 12), or the sulfonylurea glimepiride (n = 14) as an active comparator insulin secretagogue for 6 months. Acute insulin responses to arginine (AIRarg) were measured at baseline and after 6 months of treatment with 5 days of drug washout under fasting, 230 mg/dL (glucose potentiation of arginine-induced insulin release [AIRpot]), and 340 mg/dL (maximum arginine-induced insulin release [AIRmax]) hyperglycemic clamp conditions, in which AIRmax provides the β-cell secretory capacity.
The change in AIRpot was significantly greater with glimepiride versus exenatide treatment (P < 0.05), and a similar trend was notable for the change in AIRmax (P = 0.1). Within each group, the primary outcome measure, AIRmax, was unchanged after 6 months of treatment with exenatide or sitagliptin compared with baseline but was increased with glimepiride (P < 0.05). α-Cell glucagon secretion (AGRmin) was also increased with glimepiride treatment (P < 0.05), and the change in AGRmin trended higher with glimepiride than with exenatide (P = 0.06).
After 6 months of treatment, exenatide or sitagliptin had no significant effect on functional β-cell mass as measured by β-cell secretory capacity, whereas glimepiride appeared to enhance β- and α-cell secretion.
PMCID: PMC4140159  PMID: 24969577
5.  Do supervisors and independent judges agree on evaluations of therapists’ adherence and competence? 
The current study examined the agreement between supervisors’ and independent judges’ evaluations of therapist adherence and competence in three treatments of cocaine dependence: supportive expressive therapy (SE), cognitive therapy CT), and individual drug counseling (IDC). We used data from The National Institute on Drug Abuse Collaborative Cocaine Treatment Study (N=295). Trained and experienced supervisors and independent judges rated treatment fidelity. At the therapist level of analysis, the agreement between supervisors’ and independent judges’ ratings was weak for SE competence, CT adherence, and CT competence. Moderate relations were found for IDC adherence and competence. Supervisors consistently rated adherence and competence more positively than judges in CT and IDC. The potential bias in supervisors’ ratings is discussed.
PMCID: PMC4550095  PMID: 22900944
adherence; competence; cognitive therapy; supportive expressive therapy; drug counseling
6.  The Effectiveness of Clinician Feedback in the Treatment of Depression in the Community Mental Health System 
We describe the development and evaluation of a clinician feedback intervention for use in community mental health settings. The Community Clinician Feedback System (CCFS) was developed in collaboration with a community partner to meet the needs of providers working in such community settings.
The CCFS consists of weekly performance feedback to clinicians as well as a clinical feedback report that assists clinicians with patients who are not progressing as expected. Patients in the randomized sample (N=100) were pre-dominantly female African-Americans, with a mean age of 39.
Satisfaction ratings of the CCFS indicate that the system was widely accepted by clinicians and patients. An HLM analysis comparing rates of change across conditions controlling for baseline gender, age, and racial group indicated a moderate effect in favor of the feedback condition for symptom improvement (t(94) = 2.41, p = .017, d = .50). Thirty-six percent of feedback patients compared to only 13% of patients in the no feedback condition demonstrated clinically significant change across treatment (χ2(1) = 6.13, p = .013).
These results indicate that our CCFS is acceptable to providers and patients of mental health services, and has the potential to improve the effectiveness of services for clinically meaningful depression in the community mental health setting.
PMCID: PMC4516646  PMID: 26052874
feedback; psychotherapy; community mental health; depression
7.  Mapping the Trajectory of Socioeconomic Disparity in Working Memory: Parental and Neighborhood Factors 
Child development  2014;85(4):1433-1445.
Working memory (WM) is positively correlated with socioeconomic status (SES). It is not clear, however, if SES predicts the rate of WM development over time nor whether SES effects are specific to family rather than neighborhood SES. A community sample of children (n = 316) enrolled between ages 10 and 13 completed four annual assessments of WM. Lower parental education, but not neighborhood disadvantage, was associated with worse WM performance. Neither measure of SES was associated with the rate of developmental change. Consequently the SES disparity in WM is not a developmental lag which narrows nor an accumulating effect that becomes more pronounced. Rather, the relation between family SES and WM originates earlier in childhood and is stable though adolescence.
PMCID: PMC4107185  PMID: 24779417
8.  Combined Medication and CBT for Generalized Anxiety Disorder with African American Participants: Reliability and Validity of Assessments and Preliminary Outcomes 
Behavior therapy  2014;45(4):495-506.
Using data from a study of combined cognitive behavioral therapy (CBT) and venlafaxine XR in the treatment of generalized anxiety disorder (GAD), the current article examines the reliability and convergent validity of scales, and preliminary outcomes, for African American compared to European American patients. Internal consistency and short-term stability coefficients for African Americans (n=42) were adequate and similar or higher compared to those found for European Americans (n=164) for standard scales used in GAD treatment research. Correlations among outcome measures among African Americans were in general not significantly different for African Americans compared to European Americans. A subset of patients with DSM-IV–diagnosed GAD (n = 24 African Americans; n = 52 European Americans) were randomly selected to be offered the option of adding 12 sessions of CBT to venlafaxine XR treatment. Of those offered CBT, 33.3% (n = 8) of the African Americans, and 32.6% (n = 17) of the European Americans accepted and attended at least one CBT treatment session. The outcomes for African Americans receiving combined treatment were not significantly different from European Americans receiving combined treatment on primary or secondary efficacy measures.
PMCID: PMC4260926  PMID: 24912462
Generalized Anxiety Disorder; Cognitive-Behavioral Therapy; venlafaxine; combined treatment; African American
9.  School-Based Prevention of Depressive Symptoms: A Randomized Controlled Study of the Effectiveness and Specificity of the Penn Resiliency Program 
The authors investigated the effectiveness and specificity of the Penn Resiliency Program (PRP; J. E. Gillham, L. H. Jaycox, K. J. Reivich, M. E. P. Seligman, & T. Silver, 1990), a cognitive–behavioral depression prevention program. Children (N = 697) from 3 middle schools were randomly assigned to PRP, Control (CON), or the Penn Enhancement Program (PEP; K. J. Reivich, 1996; A. J. Shatté, 1997), an alternate intervention that controls for nonspecific intervention ingredients. Children’s depressive symptoms were assessed through 3 years of follow-up. There was no intervention effect on average levels of depressive symptoms in the full sample. Findings varied by school. In 2 schools, PRP significantly reduced depressive symptoms across the follow-up relative to both CON and PEP. In the 3rd school, PRP did not prevent depressive symptoms. The authors discuss the findings in relation to previous research on PRP and the dissemination of prevention programs.
PMCID: PMC4469032  PMID: 17295559
depression; prevention; children; adolescence
10.  Evaluation of a group cognitive-behavioral depression prevention program for young adolescents: A randomized effectiveness trial 
Depression is a common psychological problem in adolescence. Recent research suggests that group cognitive-behavioral interventions can reduce and prevent symptoms of depression in youth. Few studies have tested the effectiveness of such interventions when delivered by school teachers and counselors (as opposed to research team staff).
We evaluated the effectiveness of the Penn Resiliency Program for adolescents (PRP-A), a school-based group intervention that targets cognitive behavioral risk factors for depression. We randomly assigned 408 middle school students (ages 10-15) to one of three conditions: PRP-A, PRP-AP (in which adolescents participated in PRP-A and parents were invited to attend a parent intervention component), or a school-as-usual control. Adolescents completed measures of depression and anxiety symptoms, cognitive style, and coping at baseline, immediately after the intervention, and at 6-month follow-up.
PRP-A reduced depression symptoms relative to the school as usual control. Baseline levels of hopelessness moderated intervention effects. Among participants with average and high levels of hopelessness, PRP (A and AP) significantly improved depression symptoms, anxiety symptoms, hopelessness, and active coping relative to control. Among participants with low baseline hopelessness, we found no intervention effects. PRP-AP was not more effective than PRP-A alone. We found no intervention effects on clinical levels of depression or anxiety.
These findings suggest that cognitive-behavioral interventions can be beneficial when delivered by school teachers and counselors. These interventions may be most helpful to students with elevated hopelessness.
PMCID: PMC4469079  PMID: 22889296
11.  Heterogeneous Phenotypes of Acute Respiratory Distress Syndrome after Major Trauma 
Rationale: Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that can develop at various times after major trauma.
Objectives: To identify and characterize distinct phenotypes of ARDS after trauma, based on timing of syndrome onset.
Methods: Latent class analyses were used to identify patterns of ARDS onset in a cohort of critically ill trauma patients. Identified patterns were tested for associations with known ARDS risk factors and associations were externally validated at a separate institution. Eleven plasma biomarkers representing pathophysiologic domains were compared between identified patterns in the validation cohort.
Measurements and Main Results: Three patterns of ARDS were identified; class I (52%) early onset on Day 1 or 2, class II (40%) onset on Days 3 and 4, and class III (8%) later onset on Days 4 and 5. Early-onset ARDS was associated with higher Abbreviated Injury Scale scores for the thorax (P < 0.001), lower lowest systolic blood pressure before intensive care unit admission (P = 0.003), and a greater red blood cell transfusion requirement during resuscitation (P = 0.030). In the external validation cohort, early-onset ARDS was also associated with a higher Abbreviated Injury Scale score for the thorax (P = 0.001) and a lower lowest systolic blood pressure before intensive care unit enrollment (P = 0.006). In addition, the early-onset phenotype demonstrated higher plasma levels of soluble receptor for advanced glycation end-products and angiopoietin-2.
Conclusions: Degree of hemorrhagic shock and severity of thoracic trauma are associated with an early-onset phenotype of ARDS after major trauma. Lung injury biomarkers suggest a dominant alveolar–capillary barrier injury pattern in this phenotype.
PMCID: PMC4225810  PMID: 24712298
acute respiratory distress syndrome; critical illness; phenotype; trauma; hemorrhagic shock
12.  The Associations Among Improvement and Alliance Expectations, Alliance During Treatment, and Treatment Outcome for Major Depressive Disorder 
To examine the associations between treatment/outcome expectations, alliance before and during treatment, and the impact of alliance on symptomatic improvement.
153 depressed patients randomized to dynamic supportive-expressive psychotherapy (SET), antidepressant medication (ADM) or placebo (PBO) + clinical management completed ratings of treatment expectations, therapeutic alliance (CALPAS, WAI-S) and depressive symptoms (HAM-D).
Pretreatment expectations of the therapeutic alliance were significantly related to alliance later in therapy but did not differ across treatments and did not predict outcome. Alliance development over time differed between treatments; it increased more in SET than in PBO. After controlling for prior symptom improvement, early alliance predicted subsequent depression change.
Expectations of alliance and of treatment outcome/improvement measured prior to treatment onset, predicted subsequent alliance.
PMCID: PMC3988465  PMID: 24392793
Alliance; Depression; Expectation; Psychodynamic Psychotherapy; Medication; Placebo
13.  Extreme Non-response to Acute Phase Cognitive Therapy for Depression: An Attempt to Replicate and Extend 
Behavior therapy  2013;45(3):300-313.
As with other interventions for major depressive disorder (MDD), cognitive therapy (CT) results in treatment failure for about half of all participants. In 2007, Coffman and colleagues in Seattle studied this topic by identifying a group of patients who demonstrated an extremely poor response to CT (i.e. post-treatment BDI score ≥ 31). They called these patients “extreme non-responders” (ENR) and described the pre-treatment characteristics that predicted response status.
In the current study, we attempt a replication of the Seattle study with a larger sample of adults with recurrent MDD (N=473) who received a 16–20 session (12–14 week) course of CT.
The rate of ENR in this large sample was only 6.3% (30/473), compared to 22.2% (10/45) in the Seattle sample. Four pre-treatment measures of symptom severity and functioning differed significantly among ENR and non-ENR participants. In each case, higher symptoms or poorer functioning were associated with ENR status. However, the combination of these factors in a regression model did not predict actual ENR status with the high degree of sensitivity or specificity observed in the Seattle study.
These findings suggest that extreme non-response to cognitive therapy is not as common as previously described and, although poor outcomes are associated with pre-treatment clinical status, it is difficult to predict post-treatment symptom severity with a high degree of accuracy across different research samples.
PMCID: PMC4221276  PMID: 24680227
cognitive therapy (CT); major depressive disorder (MDD); non-response; predictors of response
14.  Effect of Cognitive Therapy With Antidepressant Medications vs Antidepressants Alone on the Rate of Recovery in Major Depressive Disorder 
JAMA psychiatry  2014;71(10):1157-1164.
Antidepressant medication (ADM) is efficacious in the treatment of depression, but not all patients achieve remission and fewer still achieve recovery with ADM alone.
To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in major depressive disorder (MDD).
A total of 452 adult outpatients with chronic or recurrent MDD participated in a trial conducted in research clinics at 3 university medical centers in the United States. The patients were randomly assigned to ADM treatment alone or CT combined with ADM treatment. Treatment was continued for up to 42 months until recovery was achieved.
Antidepressant medication with or without CT.
Blind evaluations of recovery with a modified version of the 17-item Hamilton Rating Scale for Depression and the Longitudinal Interval Follow-up Evaluation.
Combined treatment enhanced the rate of recovery vs treatment with ADM alone (72.6% vs 62.5%; t451 = 2.45; P = .01; hazard ratio [HR], 1.33; 95% CI, 1.06–1.68; number needed to treat [NNT], 10; 95% CI, 5–72). This effect was conditioned on interactions with severity (t451 = 1.97; P = .05; NNT, 5) and chronicity (χ2 = 7.46; P = .02; NNT, 6) such that the advantage for combined treatment was limited to patients with severe, nonchronic MDD (81.3% vs 51.7%; n = 146; t145 = 3.96; P = .001; HR, 2.34; 95% CI, 1.54–3.57; NNT, 3; 95% CI, 2–5). Fewer patients dropped out of combined treatment vs ADM treatment alone (18.9% vs 26.8%; t451 = −2.04; P = .04; HR, 0.66; 95% CI, 0.45–0.98). Remission rates did not differ significantly either as a main effect of treatment or as an interaction with severity or chronicity. Patients with comorbid Axis II disorders took longer to recover than did patients without comorbid Axis II disorders regardless of the condition (P = .01). Patients who received combined treatment reported fewer serious adverse events than did patients who received ADMs alone (49 vs 71; P = .02), largely because they experienced less time in an MDD episode.
Cognitive therapy combined with ADM treatment enhances the rates of recovery from MDD relative to ADMs alone, with the effect limited to patients with severe, nonchronic depression.
TRIAL REGISTRATION Identifier: NCT00057577
PMCID: PMC4315327  PMID: 25142196
15.  Comparative effectiveness of cognitive and dynamic therapies for major depressive disorder in a community mental health setting: study protocol for a randomized non-inferiority trial 
BMC psychology  2014;2(1):47.
There is substantial evidence that cognitive therapy is an effective intervention for the treatment of major depressive disorder. Although dynamic psychotherapies have been widely studied and are commonly practiced worldwide, there are few randomized comparisons of cognitive therapy and dynamic therapy for major depressive disorder.
We are completing data collection on a randomized non-inferiority trial comparing the effectiveness of cognitive therapy and short-term dynamic psychotherapy in the treatment of major depressive disorder in the community mental health setting. Therapists employed in the community setting have been recruited for training in either short-term dynamic psychotherapy or cognitive therapy. Patients seeking services at the community site who meet criteria for major depressive disorder based on a blind independent diagnostic interview are randomized to 16 sessions of treatment. All patients are assessed at baseline and months 1, 2, 4, and 5 utilizing a comprehensive battery.
This study adds to the growing literature evaluating the effectiveness of short-term dynamic psychotherapy for specific diagnostic groups. These results will have implications for the dissemination of effective interventions for major depressive disorder in community mental health settings.
Trial registration
This trial is registered at, a service of the United States National Institute of Health. NIH Identifier: NCT01207271. Registered 21 September 2010.
PMCID: PMC4270014  PMID: 25566391
Dynamic therapy; Cognitive therapy; Non-inferiority trial; Community mental health
16.  Group Process in the single-gender Women's Recovery Group compared with mixed-gender Group Drug Counseling 
Journal of groups in addiction & recovery  2013;8(4):10.1080/1556035X.2013.836867.
Enhanced affiliation among members is thought to provide increased support for women in single-gender compared with mixed-gender group therapy for substance use disorders (SUDs) and to provide a potential mechanism of action for its efficacy. In a Stage I trial of single-gender versus mixed-gender group therapy for SUDs we examined affiliative statements made by members in two group treatments, single-gender Women's Recovery Group (WRG) and mixed-gender Group Drug Counseling (GDC). Twenty-eight WRG and 17 GDC group therapy tapes were coded and compared for five types of affiliative statements. Three types of affiliative statements (agreement, supportive, and completing a thought) were highly correlated and were more frequent in WRG than GDC (D=0.882, p=0.27). In GDC, women were more likely to provide an affiliative statement to a male group member than any other combination of directionality (p<0.01). Compared with mixed-gender, single-gender group therapy for SUDs may enhance support through greater frequency of affiliative statements.
PMCID: PMC3840539  PMID: 24294145
Treatment for women; Women-only programs; Mixed-gender programs; Treatment outcomes; Group Therapy
17.  Differential Change in Specific Depressive Symptoms during Antidepressant Medication or Cognitive Therapy 
Behaviour research and therapy  2013;51(7):392-398.
Cognitive therapy and antidepressant medications are effective treatments for depression, but little is known about their relative efficacy in reducing individual depressive symptoms. Using data from a recent clinical trial comparing cognitive therapy, antidepressant medication, and placebo in the treatment of moderate-to-severe depression, we examined whether there was a relative advantage of any treatment in reducing the severity of specific depressive symptom clusters. The sample consisted of 231 depressed outpatients randomly assigned to: cognitive therapy for 16 weeks (n=58); paroxetine treatment for 16 weeks (n=116); or pill placebo for 8 weeks (n=57). Differential change in five subsets of depressive symptoms was examined: mood, cognitive/suicide, anxiety, typical-vegetative, and atypical-vegetative symptoms. Medication led to a greater reduction in cognitive/suicide symptoms relative to placebo by 4 weeks, and both active treatments reduced these symptoms more than did placebo by 8 weeks. Cognitive therapy reduced the atypical-vegetative symptoms more than placebo by 8 weeks and more than medications throughout the trial. These findings suggest that medications and cognitive therapy led to different patterns of response to specific symptoms of depression and that the general efficacy of these two well-validated treatments may be driven in large part by changes in cognitive or atypical-vegetative symptoms.
PMCID: PMC3711944  PMID: 23644038
Cognitive Therapy; Antidepressant Medication; Paroxetine; Symptom Reduction; Treatment for Depression
18.  IL1RN Coding Variant Is Associated with Lower Risk of Acute Respiratory Distress Syndrome and Increased Plasma IL-1 Receptor Antagonist 
Rationale: Acute respiratory distress syndrome (ARDS) behaves as a complex genetic trait, yet knowledge of genetic susceptibility factors remains incomplete.
Objectives: To identify genetic risk variants for ARDS using large scale genotyping.
Methods: A multistage genetic association study was conducted of three critically ill populations phenotyped for ARDS. Stage I, a trauma cohort study (n = 224), was genotyped with a 50K gene-centric single-nucleotide polymorphism (SNP) array. We tested SNPs associated with ARDS at P < 5 × 10−4 for replication in stage II, a trauma case–control population (n = 778). SNPs replicating their association in stage II (P < 0.005) were tested in a stage III nested case–control population of mixed subjects in the intensive care unit (n = 2,063). Logistic regression was used to adjust for potential clinical confounders. We performed ELISA to test for an association between ARDS-associated genotype and plasma protein levels.
Measurements and Main Results: A total of 12 SNPs met the stage I threshold for an association with ARDS. rs315952 in the IL1RN gene encoding IL-1 receptor antagonist (IL1RA) replicated its association with reduced ARDS risk in stages II (P < 0.004) and III (P < 0.02), and was robust to clinical adjustment (combined odds ratio = 0.81; P = 4.2 × 10−5). Plasma IL1RA level was associated with rs315952C in a subset of critically ill subjects. The effect of rs315952 was independent from the tandem repeat variant in IL1RN.
Conclusions: The IL1RN SNP rs315952C is associated with decreased risk of ARDS in three populations with heterogeneous ARDS risk factors, and with increased plasma IL1RA response. IL1RA may attenuate ARDS risk.
PMCID: PMC3707367  PMID: 23449693
functional genetic polymorphism; acute lung injury; acute respiratory distress syndrome; IL-1 receptor antagonist; replication
19.  Prevention of Depression in at-risk Adolescents: Longer-term Effects 
JAMA psychiatry  2013;70(11):1161-1170.
Adolescent offspring of depressed parents are at high risk for experiencing depressive disorders themselves.
To determine whether the positive effects of a group cognitive-behavioral prevention (CBP) program extended to longer term (multi-year) follow-up.
Design, Setting, and Participants
A four-site, randomized, controlled trial enrolled 316 adolescent (ages 13-17 years) offspring of parents with current and/or prior depressive disorders; adolescents had histories of depression, current elevated depressive symptoms, or both.
The CBP program consisted of 8 weekly, 90-minute group sessions followed by 6 monthly continuation sessions. Adolescents were randomly assigned to either the CBP program or usual care (UC).
Main Outcome Measure
The primary outcome was a probable or definite episode of depression (Depression Symptom Rating score ≥; 4) for at least 2 weeks through the month 33 follow-up evaluation.
Over the 33-month follow-up period, youths in the CBP condition had significantly fewer onsets of depressive episodes compared to those in UC. Parental depression at baseline significantly moderated the intervention effect. When parents were not depressed at intake, CBP was superior to UC (NNT ratio=6), whereas when parents were actively depressed at baseline, average onset rates between CBP and UC were not significantly different. A three-way interaction among intervention, baseline parental depression, and site indicated that the impact of parental depression on intervention effectiveness varied across sites.
The CBP program showed significant sustained effects compared to usual care in preventing the onset of depressive episodes in at-risk youth over a nearly three-year period. Important next steps will be to strengthen the CBP intervention to further enhance its preventive effects, improve intervention outcomes when parents are currently depressed, and conduct larger implementation trials to test the broader public health impact of the CBP program for preventing depression in youth.
PMCID: PMC3978119  PMID: 24005242
depression; prevention; children; adolescents
20.  Preventing adolescents’ externalizing and internalizing symptoms: Effects of the Penn Resiliency Program 
This study reports secondary outcome analyses from a past study of the Penn Resiliency Program (PRP), a cognitive-behavioral depression prevention program for middle-school aged children. Middle school students (N = 697) were randomly assigned to PRP, PEP (an alternate intervention), or control conditions. Gillham et al., (2007) reported analyses examining PRP’s effects on average and clinical levels of depression symptoms. We examine PRP’s effects on parent-, teacher-, and self-reports of adolescents’ externalizing and broader internalizing (depression/anxiety, somatic complaints, and social withdrawal) symptoms over three years of follow-up. Relative to no intervention control, PRP reduced parent-reports of adolescents’ internalizing symptoms beginning at the first assessment after the intervention and persisting for most of the follow-up assessments. PRP also reduced parent-reported conduct problems relative to no-intervention. There was no evidence that the PRP program produced an effect on teacher- or self-report of adolescents’ symptoms. Overall, PRP did not reduce symptoms relative to the alternate intervention, although there is a suggestion of a delayed effect for conduct problems. These findings are discussed with attention to developmental trajectories and the importance of interventions that address common risk factors for diverse forms of negative outcomes.
PMCID: PMC3952879  PMID: 24634897
adolescence; prevention intervention; conduct problems; internalizing symptoms
21.  A tutorial on count regression and zero-altered count models for longitudinal substance use data 
Critical research questions in the study of addictive behaviors concern how these behaviors change over time - either as the result of intervention or in naturalistic settings. The combination of count outcomes that are often strongly skewed with many zeroes (e.g., days using, number of total drinks, number of drinking consequences) with repeated assessments (e.g., longitudinal follow-up after intervention or daily diary data) present challenges for data analyses. The current article provides a tutorial on methods for analyzing longitudinal substance use data, focusing on Poisson, zero-inflated, and hurdle mixed models, which are types of hierarchical or multilevel models. Two example datasets are used throughout, focusing on drinking-related consequences following an intervention and daily drinking over the past 30 days, respectively. Both datasets as well as R, SAS, Mplus, Stata, and SPSS code showing how to fit the models are available on a supplemental website.
PMCID: PMC3513584  PMID: 22905895
22.  An Independent Randomized Clinical Trial of Multisystemic Therapy with Non-Court-Referred Adolescents with Serious Conduct Problems 
Journal of consulting and clinical psychology  2013;81(6):10.1037/a0033928.
Adolescent conduct problems exact serious social as well as personal costs, and effective treatments are essential. One of the most widely disseminated and effective programs for the treatment of serious conduct problems in adolescents is Multisystemic Therapy (MST). However, most evaluations of MST have involved the developers of MST. The purpose of the present study was to conduct an independent evaluation of MST, with non-court-referred adolescents with conduct problems.
Participants were 164 adolescents aged 11 to 18 years who were recruited from self-contained behavior intervention classrooms in public schools. Adolescents and their families were randomly assigned to receive MST or services as usual. Outcome measures assessed conduct problems, school functioning, and court records of criminal behavior. Participants were followed for 18 months after baseline using parent, adolescent, and teacher reports; arrest data were collected for 2.5 years post-baseline.
Two of four primary outcome measures focused on externalizing problems showed significant treatment effects favoring MST. Several secondary and intervention targets pertaining to family functioning and parent psychopathology showed positive effects of MST, and no negative effects were identified.
Results provide some further support for the effectiveness of MST, although smaller effect sizes than previous studies also suggest the complexity of successful dissemination, particularly to non-court-referred populations.
PMCID: PMC3830634  PMID: 23937347
multisystemic therapy; MST; delinquency; antisocial behavior; non-court-referred
23.  Process Predictors of the Outcome of Group Drug Counseling 
This study examined the relation of process variables to the outcome of group drug counseling, a commonly used community treatment, for cocaine dependence.
Videotaped group drug counseling sessions from 440 adult patients (23% female, 41% minority) were rated for member alliance, group cohesion, participation, self-disclosure, positive and non-positive feedback and advice, during the 6-month treatment of cocaine dependence. Average, session-level, and slopes of process scores were evaluated. Primary outcomes were monthly cocaine use (days using out of 30), next session cocaine use, and duration of sustained abstinence from cocaine. Secondary outcomes were endorsement of 12-step philosophy and beliefs about substance abuse.
More positive alliances (with counselor) were associated with reductions in days using cocaine per month and next-session cocaine use, and increases in endorsement of 12-step philosophy. Patient self-disclosure about the past and degree of participation in the group were generally not predictive of group drug counseling outcomes. More advice from counselor and other group members were consistently associated with poorer outcomes in all categories. Individual differences in changes in process variables over time (linear slopes) were generally not predictive of treatment outcomes.
Some group behaviors widely believed to be associated with outcome, such as self-disclosure and participation, were not generally predictive of outcomes of group drug counseling, but alliance with the group counselor was positively associated, and advice giving negatively associated, with the outcome of treatments for cocaine dependence.
PMCID: PMC3565014  PMID: 23106760
group drug counseling; cocaine dependence; predictors; process ratings
24.  Predictors and moderators of outcomes of HIV/STD sex risk reduction interventions in substance abuse treatment programs: a pooled analysis of two randomized controlled trials 
The objective of the current study was to examine predictors and moderators of response to two HIV sexual risk interventions of different content and duration for individuals in substance abuse treatment programs.
Participants were recruited from community drug treatment programs participating in the National Institute on Drug Abuse Clinical Trials Network (CTN). Data were pooled from two parallel randomized controlled CTN studies (one with men and one with women) each examining the impact of a multi-session motivational and skills training program, in comparison to a single-session HIV education intervention, on the degree of reduction in unprotected sex from baseline to 3- and 6- month follow-ups. The findings were analyzed using a zero-inflated negative binomial (ZINB) model.
Severity of drug use (p < .01), gender (p < .001), and age (p < .001) were significant main effect predictors of number of unprotected sexual occasions (USOs) at follow-up in the non-zero portion of the ZINB model (men, younger participants, and those with greater severity of drug/alcohol abuse have more USOs). Monogamous relationship status (p < .001) and race/ethnicity (p < .001) were significant predictors of having at least one USO vs. none (monogamous individuals and African Americans were more likely to have at least one USO). Significant moderators of intervention effectiveness included recent sex under the influence of drugs/alcohol (p < .01 in non-zero portion of model), duration of abuse of primary drug (p < .05 in non-zero portion of model), and Hispanic ethnicity (p < .01 in the zero portion, p < .05 in the non-zero portion of model).
These predictor and moderator findings point to ways in which patients may be selected for the different HIV sexual risk reduction interventions and suggest potential avenues for further development of the interventions for increasing their effectiveness within certain subgroups.
PMCID: PMC3929547  PMID: 24433412
HIV prevention intervention; Skills building; Randomized controlled trial; Predictors; Moderators
25.  Dialectical Behavior Therapy (DBT) Applied to College Students: A Randomized Clinical Trial 
College counseling centers (CCCs) are increasingly being called upon to treat highly distressed students with complex clinical presentations. This study compared the effectiveness of Dialectical Behavior Therapy (DBT) for suicidal college students to an optimized control condition, and analyzed baseline global functioning as a moderator.
The intent-to-treat (ITT) sample included 63 college students between the ages of 18 and 25 who were suicidal at baseline, reported at least one lifetime non-suicidal self-injurious (NSSI) act or suicide attempt, and met three or more borderline personality disorder (BPD) diagnostic criteria. Participants were randomly assigned to DBT (n = 31) or an optimized Treatment as Usual (O-TAU) control condition (n = 32). Treatment was provided by trainees, supervised by experts in both treatments. Both treatments lasted 7–12 months and included both individual and group components. Assessments were conducted at pretreatment, 3-months, 6-months, 9-months, 12-months, and 18-months (follow-up).
Mixed effects analyses (ITT sample) revealed that DBT, compared to the control condition, showed significantly greater decreases in suicidality, depression, number of NSSI events (if participant had self-injured), BPD criteria, and psychotropic medication use, and significantly greater improvements in social adjustment. Most of these treatment effects were observed at follow-up. No treatment differences were found for treatment dropout. Moderation analyses showed that DBT was particularly effective for suicidal students who were lower functioning at pretreatment.
DBT is an effective treatment for suicidal, multi-problem college students. Future research should examine the implementation of DBT in CCCs in a stepped care approach.
PMCID: PMC3514574  PMID: 22730955

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