Multimethod assessment of baseline depression and relationship to hepatitis C treatment discontinuation.

Objective The primary study objective is to determine which measures of depression are associated with early discontinuation of hepatitis C virus infection treatment and to determine which measure best characterizes the depression that develops during treatment. Methods Seventy-eight treatment-naïve subjects who initiated pegylated interferon/ribavirin treatment for hepatitis C virus infection were included. Baseline depression was assessed with the Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the Hamilton Depression Rating Scale, and the Beck Depression Inventory-II. The latter two measures were repeated at treatment weeks 12 and 24. Results Depression scores, as measured by the three instruments, lacked adequate consistency. Baseline depression as measured by the Beck Depression Inventory-II, but not by the other scales, was associated with early treatment discontinuation at weeks 12 and 24. Changes in depression during treatment were restricted to somatic symptoms. Of those who completed treatment, those who were not depressed at baseline tended to demonstrate significant depression increases during treatment. Conclusion The Beck Depression Inventory-II is recommended to assess depression prior to hepatitis C virus infection treatment. Somatic symptoms of depression should be monitored during treatment. Baseline depression as measured by the Beck Depression Inventory-II was associated with early treatment discontinuation. The Beck Depression Inventory-II, Structured Interview for DSM-IV, and Hamilton Depression Rating Scale yielded results that were not consistent with each other in this sample. Future research should focus on standardizing depression assessment in medically ill populations to identify measures that predict treatment discontinuation.

Comparison of conventional and nonconventional strictureplasties in Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: The Heineke-Mikulicz and Finney techniques are conventional strictureplasties that have been used to manage short (<10 cm) and medium-length (>10 cm and <20 cm) strictures from Crohn's disease. Nonconventional strictureplasty techniques have emerged to facilitate bowel conservation for atypical strictures. These techniques include the modified Finney, combined Heineke-Mikulicz and Finney, modified Heineke-Mikuliczs, Michelassi, and modifications of it and others. OBJECTIVE: The aim of this study is to compare conventional vs nonconventional strictureplasties with respect to short-term complications and long-term results. DATA SOURCES AND STUDY SELECTION: A MEDLINE search was performed using "Crohn's disease", "surgical therapy", "strictureplasty", "complications", "reoperation", and "recurrence" as medical subject headings. Studies conducted between 1975 and June 31, 2010 were found via PubMed, Ovid, Embase, and Cochrane databases and categorized into 3 groups. These groups consist of centers performing conventional strictureplasties, nonconventional strictureplasties, or both. Studies with at least 3 patients were reviewed. INTERVENTIONS: A mixed-effects meta-analysis for each outcome was performed by use of Supermix software by SSI Scientific Software International. MAIN OUTCOME MEASURES: We focused on immediate and long-term complication rates among the groups. The 6 immediate complications include small-bowel obstructions, sepsis, other infections, reoperations, early postoperative GI bleeds, and other early complications. The 5 long-term complications include recurrent strictures, small-bowel obstructions, reoperations, carcinoma, and deaths. RESULTS: We reviewed 32 studies with 1616 patients who underwent 4538 strictureplasties. One thousand one hundred fifty-seven patients underwent conventional strictureplasties with an early complication rate of 15%; 459 patients underwent nonconventional strictureplasties with an early complication rate of 8%. A late complication rate of 29% for the conventional strictureplasty group and 17% for the nonconventional strictureplasty group was noted. LIMITATIONS: We are limited by the data published with the inherent risk of finding and analyzing mostly articles with positive results. CONCLUSION: The nonconventional strictureplasty techniques were noninferior to the conventional strictureplasty procedures with respect to all prespecified outcomes.

Engagement in Trauma-Specific CBT for Youth Post-9/11.

Treatment participation was examined among youth enrolled in an evaluation of cognitive behavioral therapy (CBT) for trauma following the 9/11 World Trade Center disaster. Staff at nine agencies serving a predominantly low-income ethnically diverse population were trained to deliver CBT and structured engagement strategies. Four hundred and forty-five youth ages 5-19 were eligible for CBT, and 417 (94%) received at least one treatment session. Pretreatment and treatment show rates and overall dose were examined. Treatment participation rates were higher than those typically reported in community studies of children's mental health services. Regression analyses indicated variability across sites in treatment show rates with the highest rates at where services were delivered in schools. However, sites, demographic factors and trauma symptoms accounted for a small amount of variance in treatment participation overall. The study suggests structured engagement strategies, linked to evidence-based treatments may improve treatment participation for youth.

Adolescent-adult discrepancies on the eating disorder examination: a function of developmental stage or severity of illness?

OBJECTIVE: Across studies, adolescents score lower on measures of eating disorder pathology than adults, but it is unclear whether such findings reflect discrepancies inherent to site/study or true developmental differences. The aim of this study was to determine whether age predicts subscale and diagnostic scores of the Eating Disorder Examination (EDE) in adolescents and adults with anorexia nervosa (AN) admitted to a single research center within the same period of time. METHOD: The sample consisted of 16 adolescent and 20 adult consecutive admissions to parallel, age-specific, research-based AN treatment programs. Participants completed a baseline evaluation at admission that included the EDE, depression measures, and global assessment of functioning scales. RESULTS: Age significantly predicted EDE scores in univariate regression analyses. However, in multivariate models that included severity indices of general and specific psychopathology as covariates, age was no longer a significant predictor of severity of eating disorder symptoms. DISCUSSION: This study adds to the growing body of data showing lower scores on the EDE for adolescents with AN relative to their adult counterparts, while eliminating potential site confounds. Results indicate that the higher adult scores may be carried in part by a more overall severe and chronic general clinical profile.

Post-approval drug safety surveillance.

Following the drug-approval process, concerns remain regarding the safety of new drugs that are introduced into the marketplace. In the case of rare adverse events, the number of subjects that are treated in randomized controlled trials is invariably inadequate to determine the safety of the new pharmaceutical. Identifying safety signals for new and/or existing drugs is a major priority in the protection of public health. Unfortunately, design, analysis, and available data are often quite limited for detecting in a timely fashion any potentially harmful effects of drugs. In this review, we examine a variety of approaches for determining the possibility of adverse drug reactions. Our review includes spontaneous reports, meta-analysis of randomized controlled clinical trials, ecological studies, and analysis of medical claims data. We consider both experimental design and analytic problems as well as potential solutions. Many of these methodologies are then illustrated through application to data on the possible relationship between taking antidepressants and increased risk of suicidality.

Using Non-experimental Data to Estimate Treatment Effects.

While much psychiatric research is based on randomized controlled trials (RCTs), where patients are randomly assigned to treatments, sometimes RCTs are not feasible. This paper describes propensity score approaches, which are increasingly used for estimating treatment effects in non-experimental settings. The primary goal of propensity score methods is to create sets of treated and comparison subjects who look as similar as possible, in essence replicating a randomized experiment, at least with respect to observed patient characteristics. A study to estimate the metabolic effects of antipsychotic medication in a sample of Florida Medicaid beneficiaries with schizophrenia illustrates methods.

Preventive services use among women seen by gynecologists, general medical physicians, or both.

OBJECTIVE: To estimate how preventive services and counseling differ for women seen by general medical physicians and gynecologists, and whether seeing both types of physicians had a greater impact on delivery of gender-specific and gender-neutral preventive care than by either type of physician alone. METHODS: Using data from the 2000 National Health Interview Survey, we studied the association of provider type with Pap tests, tobacco use screening, and exercise and diet counseling among women 18-64 years (n=7,317), and these services along with clinical breast examinations, mammograms, and colon cancer screening among women aged 50-64 years (n=1,551). We modeled care using multivariable logistic regression and used propensity score techniques to limit selection bias from choice of provider. RESULTS: In the study sample, 15% were seen by general medical physicians, 62% by gynecologists, and 23% by both. Overall rates of gender-specific services (Pap test, clinical breast examination, mammography) were high (88-95%), whereas gender-neutral services were low (23-53%). Patients of gynecologists only were more likely to have Pap tests (adjusted relative risk [RR] 1.26, 95% confidence interval [CI] 1.24-1.27), tobacco use screening (adjusted RR 1.08, 95% CI 1.02-1.14), mammography (adjusted RR 1.25, 95% CI 1.20-1.28), and clinical breast examination (adjusted RR 1.25, 95% CI 1.19-1.29). In general, combined gynecologist and general care did not increase the likelihood of preventive care. Propensity score analyses confirmed these results. CONCLUSION: Patients of gynecologists receive more preventive services compared with patients of general medical physicians, although rates of gender-neutral services were low regardless of provider type. These findings validate gynecologists' roles as providers of basic preventive care services but demonstrate that considerable room exists to improve delivery of preventive care to women.

Relationship between antidepressants and suicide attempts: an analysis of the Veterans Health Administration data sets.

OBJECTIVE: In late 2006, a U.S. Food and Drug Administration advisory committee recommended that the 2004 black box warning regarding suicidality in pediatric patients receiving antidepressants be extended to include young adults. This study examined the relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system. METHOD: The authors analyzed data on 226,866 veterans who received a diagnosis of depression in 2003 or 2004, had at least 6 months of follow-up, and had no history of depression from 2000 to 2002. Suicide attempt rates overall as well as before and after initiation of antidepressant therapy were compared for patients who received selective serotonin reuptake inhibitors (SSRIs), new-generation non-serotonergic-specific (non-SSRI) antidepressants (bupropion, mirtazapine, nefazodone, and venlafaxine), tricyclic antidepressants, or no antidepressant. Age group analyses were also performed. RESULTS: Suicide attempt rates were lower among patients who were treated with antidepressants than among those who were not, with a statistically significant odds ratio for SSRIs and tricyclics. For SSRIs versus no antidepressant, this effect was significant in all adult age groups. Suicide attempt rates were also higher prior to treatment than after the start of treatment, with a significant relative risk for SSRIs and for non-SSRIs. For SSRIs, this effect was seen in all adult age groups and was significant in all but the 18-25 group. CONCLUSIONS: These findings suggest that SSRI treatment has a protective effect in all adult age groups. They do not support the hypothesis that SSRI treatment places patients at greater risk of suicide.

Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents.

OBJECTIVE: In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression. METHOD: The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings. RESULTS: SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979. CONCLUSIONS: In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents.

A comparison of medication side effect reports by panic disorder patients with and without concomitant cognitive behavior therapy.

OBJECTIVE: The authors assessed whether adding cognitive behavior therapy (CBT) to imipramine for patients with panic disorder decreased the severity of side effects and dropouts from side effects. METHOD: Data were analyzed for 172 panic disorder patients who were randomly assigned to receive imipramine alone, imipramine plus CBT, or placebo. Mixed-effects models were used to assess longitudinal differences among the treatment groups with respect to side effect burden and dropout rates during the acute, maintenance, and follow-up phases of treatment. RESULTS: Patients treated with imipramine plus CBT experienced less severe fatigue/weakness, dry mouth, and sweating and had a lower rate of dropout due to side effects compared with those treated with imipramine only. CONCLUSIONS: The addition of CBT to medication treatment with imipramine was associated with less severe side effects and fewer dropouts due to perceived side effects than treatment with imipramine alone.

Simulation of the Syst-Eur randomized control trial using a primary care electronic medical record was feasible.

OBJECTIVE: To determine the validity of outcome research using a primary care practice database by comparing a randomized controlled trial (RCT) with a simulated one. STUDY DESIGN AND SETTING: A cohort from the United Kingdom General Practice Research Database (GPRD) was used to simulate the Systolic Hypertension in Europe (Syst-Eur) trial, a study of antihypertensive therapy of isolated systolic hypertension, by replicating all aspects of that RCT (selection criteria, study time frame, treatment, and outcomes) except randomization. RESULTS: The exposed and unexposed groups in the GPRD study exhibited similar baseline characteristics. Stroke, the primary RCT outcome, decreased significantly in both the RCT (incidence rate ratio IRR = 0.58) and the GPRD study (IRR = 0.68). Myocardial infarction decreased nonsignificantly but similarly in both studies (RCT IRR = 0.70; GPRD IRR = 0.74). With the GPRD study extended for 3 years more, myocardial infarction decreased significantly, comparable to findings from the Systolic Hypertension in the Elderly Program (SHEP), another RCT similar to Syst-Eur. CONCLUSIONS: The findings support the potential value of clinical databases to investigate treatment effectiveness. RCT simulation using the GPRD may be the most feasible way to assess observational study validity in comparison to RCTs. The extended GPRD study shows the feasibility of using a simulated study to supplement the results of an RCT of limited duration.

Use of Peer Staff in a Critical Time Intervention for Frequent Users of a Psychiatric Emergency Room.

Project Connect, a clinical demonstration program developed in consultation with the New York State Office of Mental Health, adapted critical time intervention for frequent users of a large urban psychiatric emergency room (ER). Peer staff provided frequent users with time-limited care coordination. Participants increased their use of outpatient services over 12 months, compared with a similar group not enrolled in the program. For persons with significant general medical, psychiatric, and social needs, provision of this intervention alone is unlikely to reduce reliance on ERs, especially among homeless individuals.

Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy.

CONTEXT: Reduced cortisol levels have been linked with vulnerability to posttraumatic stress disorder (PTSD) and the risk factor of parental PTSD in adult offspring of Holocaust survivors. OBJECTIVE: The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001 during pregnancy. DESIGN: Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-yr-old babies at awakening and at bedtime. RESULTS: Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters. CONCLUSIONS: The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD.

Multiple Family Groups for Children with Disruptive Behavior Disorders: Child Outcomes at 6-Month Follow-Up.

This paper reports on the 6-month follow-up outcomes of an effectiveness study testing a multiple family group (MFG) intervention for clinic-referred youth (aged 7-11) with disruptive behavior disorders (DBDs) and their families in socioeconomically disadvantaged families compared to services-as-usual (SAU) using a block comparison design. The settings were urban community-based outpatient mental health agencies. Clinic-based providers and family partner advocates facilitated the MFG intervention. Parent-report measures targeting child behavior, social skills, and impairment across functional domains (i.e., relationships with peers, parents, siblings, and academic progress) were assessed across four timepoints (baseline, mid-test, post-test, and 6-month follow-up) using mixed effects regression modeling. Compared to SAU participants, MFG participants reported significant improvement at 6-month follow-up in child behavior, impact of behavior on relationship with peers, and overall impairment/need for services. Findings indicate that MFG may provide longer-term benefits for youth with DBDs and their families in community-based settings. Implications within the context of a transforming healthcare system are discussed.

Independent evaluator knowledge of treatment in a multicenter comparative treatment study of panic disorder.

The purpose of this study was to examine independent evaluators' (IEs) blindness to treatment condition during a Multicenter Comparative Treatment Study of Panic Disorder. IEs were 15 doctoral- and masters-level clinicians in psychology, social work, and medicine. They conducted three post-treatment assessments with each patient. Immediately after each assessment interview, IEs completed a form indicating which of the five possible treatments they believed the patient had received and any specific information that provided IEs with information about a patient's treatment condition. These forms were completed for 170 patients. Analyses were conducted to determine the accuracy of guesses about treatment condition by IEs during post-treatment assessments, the relationship between accuracy of IE guessing and actual treatment assignment, the relationship between accurate guessing and outcome ratings, and contributors to the breaking of the blind. A significant relationship was found between IE guesses and actual treatment at all three assessment points, across individual IEs, treatment sites, and IE professional affiliations. IEs were no more accurate in their guessing about patients taking medication than those receiving behavior therapy. Patients and project staff inadvertently provided information to IEs that enhanced the rates of accurate guessing. Implications of these findings on interpretation of the treatment study are discussed, and recommendations are made for improving blindness procedures.

Bias due to sample selection in propensity score matching for a supportive housing program evaluation in New York City.

OBJECTIVES: Little is known about influences of sample selection on estimation in propensity score matching. The purpose of the study was to assess potential selection bias using one-to-one greedy matching versus optimal full matching as part of an evaluation of supportive housing in New York City (NYC). STUDY DESIGN AND SETTINGS: Data came from administrative data for 2 groups of applicants who were eligible for an NYC supportive housing program in 2007-09, including chronically homeless adults with a substance use disorder and young adults aging out of foster care. We evaluated the 2 matching methods in their ability to balance covariates and represent the original population, and in how those methods affected outcomes related to Medicaid expenditures. RESULTS: In the population with a substance use disorder, only optimal full matching performed well in balancing covariates, whereas both methods created representative populations. In the young adult population, both methods balanced covariates effectively, but only optimal full matching created representative populations. In the young adult population, the impact of the program on Medicaid expenditures was attenuated when one-to-one greedy matching was used, compared with optimal full matching. CONCLUSION: Given covariate balancing with both methods, attenuated program impacts in the young adult population indicated that one-to-one greedy matching introduced selection bias.

Impact of hepatitis C treatment initiation on adherence to concomitant medications.

Our study investigated whether initiating hepatitis C virus (HCV) treatment affected adherence to concomitant medications. Mixed-effects linear regression was used to analyze data from 57 patients (29 co-infected with HIV) in a prospective study of HCV treatment-naïve patients initiating HCV treatment. Adherence was assessed using structured self-report at the time of treatment initiation, and at 12 weeks and 24 weeks into treatment. There was no change in adherence to concomitant medications over the first 24 weeks of HCV treatment. There was a significant interaction effect such that the change in adherence to concomitant medications between baseline and 12 weeks differed between the HIV-infected and HIV-uninfected patients. Adherence to concomitant medications in the HIV-infected patients was found to decrease, whereas adherence in the HIV-uninfected patients was found to increase. HIV-infected patients may be more at risk for adherence problems in the first 12 weeks of HCV treatment as compared to HIV-uninfected patients.

Using claims data to generate clinical flags predicting short-term risk of continued psychiatric hospitalizations.

OBJECTIVE: As health information technology advances, efforts to use administrative data to inform real-time treatment planning for individuals are increasing, despite few empirical studies demonstrating that such administrative data predict subsequent clinical events. Medicaid claims for individuals with frequent psychiatric hospitalizations were examined to test how well patterns of service use predict subsequent high short-term risk of continued psychiatric hospitalizations. METHODS: Medicaid claims files from New York and Pennsylvania were used to identify Medicaid recipients ages 18-64 with two or more inpatient psychiatric admissions during a target year ending March 31, 2009. Definitions from a quality-improvement initiative were used to identify patterns of inpatient and outpatient service use and prescription fills suggestive of clinical concerns. Generalized estimating equations and Markov models were applied to examine claims through March 2011, to see what patterns of service use were sufficiently predictive of additional hospitalizations to be clinically useful. RESULTS: A total of 11,801 individuals in New York and 1,859 in Pennsylvania identified met the cohort definition. In both Pennsylvania and New York, multiple recent hospitalizations, but not failure to use outpatient services or failure to fill medication prescriptions, were significant predictors of high risk of continued frequent hospitalizations, with odds ratios greater than 4.0. CONCLUSIONS: Administrative data can be used to identify individuals at high risk of continued frequent hospitalizations. Payers and system administrators could use such information to authorize special services (such as mobile outreach) for such individuals to promote service engagement and prevent rapid rehospitalizations.

Donepezil treatment of older adults with cognitive impairment and depression (DOTCODE study): clinical rationale and design.

Treatment strategies for patients with depression and cognitive impairment (DEP-CI), who are at high risk to develop a clinical diagnosis of dementia, are not established. This issue is addressed in the donepezil treatment of cognitive impairment and depression (DOTCODE) pilot clinical trial. The DOTCODE study is the first long-term treatment trial that assesses differences in conversion to dementia and cognitive change in DEP-CI patients using a study design of open antidepressant medication plus add-on randomized, double-blind, placebo-controlled treatment with the acetylcholinesterase inhibitor donepezil. In Phase 1, DEP-CI patients receive optimized antidepressant treatment for 16 weeks. In Phase 2, antidepressant treatment is continued with the addition of randomized, double-blind treatment with donepezil or placebo. The total study duration for each patient is 78 weeks (18 months). Eighty DEP-CI outpatients (age 55 to 95 years) are recruited: 40 at New York State Psychiatric Institute/Columbia University and 40 at Duke University Medical Center. The primary outcome is conversion to a clinical diagnosis of dementia. The secondary outcomes are cognitive change scores in Selective Reminding Test (SRT) total recall and the modified Alzheimer's Disease Assessment Scale (ADAS-cog). Other key assessments include the 24-item Hamilton Depression Rating Scale and antidepressant response; Clinical Global Impression (CGI) for depression, cognition, and global status; neuropsychological test battery for diagnosis; informant report of functional abilities (Pfeffer FAQ); and Treatment Emergent Symptom Scale (TESS) for somatic side effects. Apolipoprotein E ε4 status, odor identification deficits, and MRI entorhinal/hippocampal cortex atrophy at baseline are evaluated as neurobiological moderators of donepezil treatment effects.