Post Enrollment Research Articles

Validation of PROMIS emotional distress short form scales for cervical cancer trials.

6633 Background: PROMIS is an NIH-sponsored effort to standardize the measurement of common symptoms and functional concerns of people with chronic conditions. The purpose of this study is to validate the PROMIS Emotional Distress (Depression and Anxiety) Short Forms (SFs) for use with cervical cancer patients. Methods: In a randomized psychosocial telephone counseling (PTC) trial, PROMIS measures of depression and anxiety were used alongside more traditional “legacy” measures of the same concepts. Questionnaires were administered to patients prior to randomization, four months post enrollment, and nine months post enrollment. The depression (8-item) and anxiety (7-item) SFs were evaluated in patients participating in this study, for internal consistency, concurrent validity, and responsiveness to change. SF performance results were compared to the Brief Symptom Inventory (BSI-18) subscales. Data were collapsed between PTC and usual care treatment arms for these analyses. Results: Patients showed significant improvement in depression from baseline to 4 months post study enrollment as measured by the Depression SF (p=0.003; effect size = 0.24), and BSI-Dep (p=0.041; effect size = 0.25). Internal consistency of the two PROMIS SFs were ≥0.95 at baseline (N=203), 4 months (N=165), and 9 months (N=151). The average inter-item correlation was 0.71 at the 4 month assessment for both depression and anxiety. The Depression SF T-score correlated well with the BSI-Dep (0.74), and was moderately correlated with the FACT Emotional Well-Being (EWB) subscale (-0.54), and the Perceived Stress Scale (PSS)(0.63). The Anxiety SF T-score was moderately correlated with BSI-Anx (0.60), EWB (-0.53), and PSS (0.60). Conclusions: The PROMIS Depression and Anxiety SFs reliably and validly assess cervical cancer-specific emotional distress, they capture salient features of distress in this population, and they perform as well or better than legacy measures in this gynecologic cancer population. Clinical trial information: NCT00496106.

Predictors of significant emotional distress in cervical cancer patients.

6632 Background: Cervical cancer patients experience serious quality of life (QOL) disruptions, which may include persistent emotional distress. Predictors of persistent or significant depression and anxiety are examined in this study. Methods: A randomized trial tested the efficacy of a psychosocial telephone counseling intervention designed to improve QOL and decrease emotional distress.The FACT-Cx Trial Outcome Index (FACT-Cx-TOI), depression and anxiety (PROMIS short forms) were collected at baseline (T1), 4 months (T2) and 9 months (T3) post enrollment. Multivariate linear and logistic regression models were used to identify predictors of distress at follow-up. Tested predictors included demographic information, stage, treatment assignment, and baseline FACT-Cx TOI and PROMIS scores. Results: 115 women were randomized to PTC and 89 to usual care, with 82% compliance for T2 and 75% at T3. PTC patients experienced a significantly greater reduction in depression from T1 to T2 compared to UC (p=0.014). At baseline, 45% of participants reported depression T-scores above 55 (0.5 SD above the US general population average), and 26% reported levels greater than 60 (>1 SD worse than average). PTC patients were significantly less likely to have depression scores >55 at T2, and significantly more likely to improve by ≥5 points at T2 after adjusting for baseline and disease characteristics. Participation in PTC, higher baseline depression and higher baseline TOI were significant independent predictors of improvement in depression from T1 to T2. Conclusions: Early identification of patients with poor QOL and significant depression can inform supportive care interventions, with potential to improve health outcomes. Funding Source: NCI R01 CA118136-01. Clinical trial information: NCT00496106.

Assessment of the minimum clinically important difference in quality of life in schizophrenia measured by the Quality of Well-Being Scale and disease-specific measures

This study examines the psychometric properties of the Quality of Well Being Scale (QWB), the Positive and Negative Syndrome Scale (PANSS), the Heinrich-Carpenter Quality of Life Scale (QOLS), and the Lenert PANSS-based utility measure in a cohort of patients with schizophrenia and identifies threshold values of clinically meaningful change using the Clinical Global Impressions scale (CGI), as the anchor. The correlation of these measures at baseline and change at 6 and 12 months post enrollment in a comparative effectiveness trial was evaluated in 350 veterans with schizophrenia or schizoaffective disorder. An equipercentile method was used to estimate the minimum clinically important difference (MCID) for each measure. Effect size of 0.30–0.50 for baseline quality of life associated with inpatient status supported concurrent validity. The QWB was moderately correlated with disease-specific measures. The MCID as detected by the CGI at 6 months was 0.17 for QWB, 0.15 for the Lenert utility score, 1.13 for the QOLS, and 20.2 for the PANSS. These differences were stable at 12 months. The QWB is significantly correlated with disease specific measures of health related quality of life in schizophrenia.

Medication Adherence Improvements in Employees Participating in a Pharmacist-Run Risk Reduction Program

Objective: To evaluate the medication adherence of individuals participating in a pharmacist-run employee health Cardiovascular and Diabetes Risk Reduction Program.
 Design: Retrospective analysis of medication adherence using pharmacy refill data.
 Setting: A medium sized university located in the Midwest United States and the organization's outpatient pharmacy. Participants: 38 participants ≥ 18 years of age, employed and receiving their health insurance through the organization, and have a diagnosis of hypertension, hyperlipidemia, diabetes mellitus, or a combination thereof.
 Intervention: Participation in the risk reduction program that emphasizes medication therapy management (MTM), lifestyle medicine and care coordination.
 Main Outcome Measures: The Proportion of Days Covered (PDC) and the Medication Possession Ratio (MPR).
 Results: PDC and MPR analysis showed a statistically significant improvement in medication adherence for 180 days and 360 days post enrollment versus the 180 days prior to enrollment (P<0.01). The PDC analysis demonstrated a statistically significant improvement in the number of medications that achieved a PDC ≥ 80% (high adherence) for the 180 days post enrollment versus the 180 days prior to enrollment (+30%, P<0.01). The MPR analysis showed a non-statistically significant improvement in the number of medications that achieved an MPR ≥ 80% (high adherence) pre enrollment versus post enrollment (+10%, P=0.086). The percentage of participants in the program that reached a PDC and MPR adherence rate ≥ 80% at 180 days post enrollment was 78.9% and 94.4%, respectively which exceeds that of a matched cohort that reached a PDC and MPR adherence rate ≥ 80% of 66.4% and 82.8%, respectively.
 Conclusion: Pharmacists can improve medication adherence as measured by PDC and MPR when working with employees enrolled in a novel pharmacist-run employee health risk reduction program. Medication adherence was shown to be sustainable for at least one year and was shown to be better when compared to a matched cohort of similar age, condition and region.
 
 Type: Original Research

A randomized pilot study of the Engaging Moms Program for family drug court

In response to the need for effective drug court interventions, the effectiveness of the Engaging Moms Program (EMP) versus Intensive Case Management Services (ICMS) on multiple outcomes for mothers enrolled in family drug court was investigated. In this intent-to-treat study, mothers ( N = 62) were randomly assigned to either usual drug court care or the Engaging Moms drug court program. Mothers were assessed at intake and 3, 6, 12, and 18 months following intake. Results indicated that at 18 months post drug court enrollment, 77% of mothers assigned to EMP versus 55% of mothers assigned to ICMS had positive child welfare dispositions. There were statistically significant time effects for both intervention groups on multiple outcomes including substance use, mental health, parenting practices, and family functioning. EMP showed equal or better improvement than ICMS on all outcomes. The results suggest that EMP in family drug court is a viable and promising intervention approach to reduce maternal addiction and child maltreatment.

154: Long Term Follow-Up in the AIRSAC Trial, a Multicenter Randomized Clinical Trial in Lung Transplant Recipients

Preliminary evidence from the AIRSAC trial, a multicenter randomized clinical investigation comparing sirolimus (SIR) to azathioprine (AZA) in a tacrolimus (TAC) based regimen has shown no difference in acute rejection one year post enrollment in lung transplant recipients. To determine the effect on long term outcomes, this study examines the rates of Bronchiolitis Obliterans Syndrome (BOS), re-transplantation and survival from results of the AIRSAC trial.

A phase II trial of the use of 4,4’-dihydroxybenzophenone-2,4-dinitrophenyl-hydrazone (A-007) topical gel in the treatment of high-grade squamous intraepithelial lesions (HSIL) of the cervix

5593 Background: The incidence of cervical cancer is highly correlated with cervical high grade squamous intraepithelial lesions (HSIL [CIN2/3]) and human papillomavirus (HPV) infection in men and women. Approximately 70 - 80% of sexually active adolescents and adults will become infected with HPV during their lifetime. In 2003 alone, there were 50 million cases of HPV infections in the United States. Our main objective is to determine the pathological response (complete and partial, based on independent review panel of two patho the uterine cervix of women with HSIL [CIN 2/3]. Materials and Methods: Following colposcopy, pap smear and biopsy confirmation of HSIL (CIN 2/3) and HPV infection status, women are treated with gel applied to the cervix via an intravaginal applicator once daily for 5 consecutive days of a 28-day cycle for 2 cycles. At month 4 post enrollment into the trial, all women undergo the loop electrosurgical excision procedure (LEEP) procedure and repeated virology assessment. Results: 65 patients were enrolled at 2 centers and completed treatment with A-007 and 100% (65/65) were HPV positive (81.5% by Hibrid Capture II for High Risk and 100% PCR positive). All baseline and LEEP pathological specimens will be blinded read by a panel of two independent expert pathologists. A subject will be considered a complete pathological responder (CR) when the patient has regression of HSIL (CIN 2/3) without pathological evidence of HSIL, and a partial pathological responder (PR) when she has regression of HSIL (CIN 2/3) to LSIL (CIN 1). Overall response rate is defined as the percentage of patients with CR and PR. To date, no serious adverse events (SAE) has been reported during treatment in all enrolled patients, only has been reported a moderate local and transitory itching/burning sensation during the first 5–20 minutes after application in 18% (12/65) of the cases. At this moment LEEP procedures are being scheduled for all patients and the pathological response rate as well as the HPV response rate will be available and presented at the conference. [Table: see text]

Neuropsychological performance predicts clinical recovery in bipolar patients

Background Although a number of investigations have reported cognitive deficits in patients with bipolar disorder, relatively few have focused on the relationship between these impairments and clinical outcome. Methods In order to help clarify the pattern of and extent to which cognitive deficits are present at the onset of illness and their relationship to outcome, we examined 26 bipolar patients during their first hospitalization and 20 psychiatrically healthy control subjects. All subjects completed tests of frontal/executive control, psychomotor speed and memory function at baseline and self-reports of clinical recovery (time to recover in days) at 12 months post study enrollment. Results At baseline, first episode bipolar patients demonstrated greater deficits relative to control subjects on neurocognitive measures, and a significant association was detected between time to recover and performance on a measure of frontal/executive function (interference condition of the Stroop; p = .05; derived interference: p = .04). A trend towards significance was also demonstrated between time to clinical recovery and verbal fluency ( p = .06). Conclusions These findings indicate that neuropsychological deficits are seen early in the course of bipolar disorder, prior to the effects of multiple or prolonged episodes, and may be associated with clinical outcome. Future studies are needed to determine whether changes in inhibitory processing or other cognitive function predict clinical outcome or are associated with treatment response.

Update on the Effect of a Multidisciplinary Team Clinic on Asthma Outcome for Medicaid-Eligible Inner City Children with Moderate to High-Risk Asthma

RATIONALE: To evaluate hospitalizations/ER visits, oral steroid bursts, and pulmonary function tests (PFT's) in moderate to high-risk, asthmatic children enrolled in a multidisciplinary team (MDT) clinic compared to pre-study values. METHODS: Medicaid-eligible children (5-18 years) with moderate to severe asthma were recruited from the inpatient and outpatient asthma service at Children's Hospital of Michigan. The MDT clinic involves additional resources with access to educational, psychological, pharmacological and social work components. Data is collected at six-month intervals and includes hospitalizations/ER visits, oral steroid bursts, and PFT's. RESULTS: 126 children have been enrolled in the study. 67 have completed 6 months; 54 have completed one year, and 18 have completed two years of the study. At six months the total number of hospitalizations/ER visits for the group of 67 patients was 18, compared to 50 (p = <0.001) pre-enrollment. Steroid bursts for the same group was 38 post enrollment compared to 67 (p = 0.006) pre-enrollment. At 12 months, hospitalizations/ER visits for the group of 54 was 20 versus 81 (p = <0.001) pre-enrollment, and steroid bursts was 46 versus 97 (p = 0.001) pre-enrollment. At 2 years, hospitalizations/ER visits for the group of 18 was 15 versus 49 (p = 0.715) pre-enrollment, and steroid bursts was 37 versus 55 (p = 0.255) pre-enrollment. No difference was detected in PFT results at any point. CONCLUSION: MDT clinic enrollment is shown to decrease hospitalizations and oral steroid bursts in a Medicaid eligible Pediatric population at six and twelve months. This trend also continues at the 2-year mark, however the sample size is not large enough to achieve statistical significance.

A Randomized Trial of Primary Intensive Care to Reduce Hospital Admissions in Patients with High Utilization of Inpatient Services

Randomized controlled trials of case management in primary care have been infrequent and contradictory. The aim of this study was to determine if a clinic-based ambulatory case management intervention, Primary Intensive Care (PIC), would reduce hospital utilization and total cost and/or improve health outcomes among primary care patients with a recent history of high use of inpatient services. Current patients with > or =2 hospital admissions per year in the 12-18 months prior to recruitment in an urban primary care clinic were enrolled in a randomized clinical trial. Patients were randomized to the PIC intervention or usual care. PIC patients underwent a comprehensive multidisciplinary assessment with the result being a team-generated plan. The PIC team nurse practitioner served as case manager for the 12 months of follow-up and provided services designed to implement the care plan for those in the experimental group. Health care use, function, and a medication adherence scale were measured at baseline and at 12 months. There were no significant differences when either comparing the number of admissions pre and post enrollment within groups or the followup results post intervention between groups. A similar result was noted for the number of emergency department visits. The number of clinic visits increased in the intervention group by 1.5 visits per year which was statistically significant when compared to the control group. Overall functional status, health outcomes, and the Mental Health Functional Status subscore did not change significantly in either group during the study. We were unable to detect a difference in hospital use or functional status, mental health function, or medication adherence among patients who require frequent hospital admissions using our intervention.

Maintenance Therapy with Thalidomide/Prednisone Post Autologous Stem-Cell Transplant for Patients with Multiple Myeloma Elevates D-Dimer and Possibly Factor VIII Levels.

Background: Thalidomide is commonly used for the treatment of multiple myeloma (MM). Several studies have observed that venous thromboembolism (VTE) is a complication for up to 10% of patients receiving thalidomide therapy, especially when used as combination chemotherapy as part of primary treatment. Elevated Factor VIII and D-dimer levels are well described markers of thrombin generation and for an increased risk of VTE. The purpose of this study was to assess whether MM patients allocated to receive maintenance therapy with thalidomide and prednisone (thal/pred) post stem cell transplant for MM have increased levels of Factor VIII and D-dimer as laboratory confirmation for the reported increased clinical occurrence of VTE with thalidomide therapy.Methods: This is a correlative sub-study of NCIC CTG MY.10 which is an open-label randomized multicentre trial assessing the efficacy (time to progression) of maintenance therapy with the combination of thalidomide 200mg/day and prednisone 50mg every other day compared to no maintenance therapy post stem cell transplant. No clinical outcomes are available at this time as the study is ongoing. This laboratory companion study was incorporated in MY.10 a priori. Eligible patients were registered and randomized 60–100 days post transplantation. All consenting patients had plasma samples collected and frozen at baseline and two months post study enrollment. An unmatched comparison by MY.10 treatment arm was performed to assess the change in D-dimer and Factor VIII from baseline to two months for the first 79 patients entered into the trial.Results: There were 37 patients allocated to thal/pred (28 males, 76%) and 42 on observation (29 males, 69%). The mean ages were 56.6 and 55.8 years respectively. Based on continuous log D-dimer and log Factor VIII using two-way ANOVA, the results are shown in Table 1. Since D-dimer is also reported as positive or negative (<200 or =/>200μg/l) this was also assessed and the results as shown in Table 2. D-dimer results were significantly different (Bonferroni, p = 0.05) at two months compared with baseline for patients allocated to thal/pred rather than observation alone. At two months there were also significantly more patients allocated to thal/pred who had elevated D-dimers, 13 (72%) versus 5 (28%), (Bonferroni p < 0.05). There was a trend towards higher Factor VIII levels in patients allocated to thal/pred than on observation.Conclusion: These results provide clinical laboratory evidence of thrombin activation with the use of thal/pred post autologous transplant in patients with MM, and offer a potential mechanism, as well as, potential predictive markers for the clinical observations to date that patients receiving treatment with thalidomide for MM have an increased risk of VTE.Table 1MeanUnadjustedBaseline2 monthsp-valuethal/predObservationthal/predObservaton(D-dimer μg/l)11910113775.60.03FVIII (units/ml)1.251.301.601.260.09Table 2D-dimer# ≥200(μg/l)Unadjusted p-valueNthal/predObservationPearsonExactChi-squareFisherBaseline2310 (43%)13 (57%)0.700.81At 2 months1813 (72%)5 (28%)0.010.02

Medication and health care service utilization related to depressive symptoms in older adults with psoriasis

This study examined the relationship between depressive symptoms and related medication adherence and health care costs in older adults (age > or = 65 years) with psoriasis.Prospective longitudinal cohort study over a 2-year post enrollment period in a population of older adults with psoriasis enrolled in managed care.A Medicare Health Maintenance Organization (HMO) in southeastern United States with prescription benefits.Sixty-three older adults with psoriasis using topical corticosteroids therapy and enrolled in a Medicare HMO for a 2-year continuous period.Upon enrollment, each enrollee was mailed a comprehensive health status assessment battery, which included the Center for Epidemiologic Studies Depression (CES-D) scale. Information on medication adherence (using medication possession ratio) and total health care utilization/costs following enrollment were retrieved from the Medicare HMO database.Nearly one-fifth of the patient population had depressive symptoms. Patients with psoriasis who had depressive symptoms at the time of enrollment were less likely to be adherent to topical corticosteroid medication (r= -0.29, p<0.01) and less likely to utilize health care resources as evidenced by lower health care costs (r= -0.27, p<0.05), after confounder adjustment.The prevalence of depressive symptoms in older adults with psoriasis is commonplace, with strong, yet unexplained correlations between presence of depressive symptoms and lower rates of medication and health care service use among these patients.

DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE)

The DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) was a multi-center, randomized, investigator-initiated trial. Patients enrolled in the trial had non-ischemic cardiomyopathy (LVEF <or=35%), a history of symptomatic heart failure and spontaneous arrhythmia (>10 PVCs/hr or non-sustained ventricular tachycardia defined as 3 to 15 beats at a rate of >120 bpm) on Holter monitor or telemetry within the past 6 months. All patients received standard oral medical therapy for heart failure including angiotensin converting enzyme inhibitors and beta-blockers. Patients were randomized to implantable cardioverter defibrillator (ICD) versus no ICD. Patients were followed for 2 to 3 years. The primary endpoint was total mortality. Quality of life and pharmacoeconomics analysis was also performed. A registry tracked patients who met basic inclusion criteria but were not randomized. We estimated an annual total mortality of 15% at 2 years in the treatment arm that did not receive an ICD. The ICD was expected to reduce mortality by 50%. Approximately 229 patients were required in each treatment group. Forty-five centers were included in this trial that was designed to last an estimated 4 years. Enrollment was projected to occur over 2 1/2 years with a post enrollment follow-up of 1 1/2 years.

Health Care Utilization of Chronic Inebriates

Abstract. Chronic inebriates often use emergency services, including the emergency department (ED), because they lack other resources or access to primary care. Because of their complicated medical needs, which are often exacerbated by acute intoxication and related illness or injury, a relatively small number of acutely intoxicated chronic inebriates can stretch ED resources and contribute to ED over‐crowding. Objective: In order to address this, as well as overutilization of other county services, three county programs were developed (ethnic‐ and genderspecific supportive housing; intensive street case management) to reduce emergency resource utilization while still providing a safe environment. This study determined the effectiveness of these programs. The authors hypothesized that program enrollment would reduce medical and detoxification (detox) expenditures for this patient population. Methods: Pre‐ and postprogram comparisons were made on the number of detox and medical visits, insured days, and charges. Data were retrieved (with patients written informed consent) from hospital and health plan billings and county databases. Descriptive statistics compared groups pre and post enrollment. Least‐squares regression predicted total and non‐inpatient medical charges. Results: Complete data were available for 92 of 122 patients (mean age = 47 years; 60% Native American; 93% male); seven had severe illnesses or injuries, skewing the mean. However, there were significant overall reductions in the median numbers of yearly detox visits (10 to 1) and medical visits (11 to 8), and in median medical charges (5,436 to 2,770) and total health care charges (9,297 to 5,218). The median number of days insured increased (284 to 353). By regression analysis, injury was the most important preprogram predictor of medical charges; illness drives charges post‐entry. Alcohol‐related visits added to the model before entry but disappeared post‐entry. Conclusions: These programs reduced health care use for most patients. However, serious medical illness or injury in a small number of patients contributed heavily to resource utilization.