Objective This study proposes a method for self-report health questionnaires to adjust test-retest reliability for changes during the test-retest interval based on an external measure, and to ...distinguish such changes from random response errors. Methods In our application, eighty participants completed the Symptoms of Illness Checklist (SIC) on two occasions, two weeks apart, immediately before interviews given on each occasion by one of two physicians in a crossover design. The physician interview scores served as external measures, and structural equation modeling was used to estimate the parameters of a model that corrected for the occasion-specific effect of participants' responses using information from the interviews. Results Correcting for changes in symptoms during the test-retest interval increased SIC test-retest reliability from .744 to .804 and significantly improved model fit $(X_{diff}^2 (1)\, = \,30.78,\,p\, < \,.001)$. Conclusions The results suggest methods that can improve the evaluation of self-report health questionnaire test-retest reliability by identifying changes using an external measure, and distinguishing these from random response errors; these increased the estimated SIC test-retest reliability and indicated that the SIC was indeed able to measure changes over the studied time interval. This method can be applied across a broad range of questionnaires.
Over the years numerous papers have presented the effectiveness of various machine learning methods in analyzing drug discovery biological screening data. The predictive performance of models ...developed using these methods has traditionally been evaluated by assessing performance of the developed models against a portion of the data randomly selected for holdout. It has been our experience that such assessments, while widely practiced, result in an optimistic assessment. This paper describes the development of a series of ensemble-based decision tree models, shares our experience at various stages in the model development process, and presents the impact of such models when they are applied to vendor offerings and the forecasted compounds are acquired and screened in the relevant assays. We have seen that well developed models can significantly increase the hit-rates observed in HTS campaigns.
ABSTRACT
Aims The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine ...dependence.
Design A multi‐arm, modified blinded, placebo‐controlled design was used.
Setting The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU).
Participants Participants met criteria for cocaine dependence during a 2‐week screening period.
Intervention Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study.
Measurements Urine benzoylecgonine (BE) concentrations, self‐report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period.
Findings None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end‐point compared to the placebo group. Significant within‐group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self‐reported cocaine use declined over the study period. Overall, the active medications were well tolerated.
Conclusions This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.
The purpose of this study was to determine the incidence and significance of aneurysm enlargement, with or without treatment, in relation to the primary end points of rupture, surgical conversion, ...aneurysm-related death, and survival following endovascular repair.
Aneurysm (AAA) size changes and clinical outcome of all patients treated from 1997 through 1998 during the Phase II AneuRx multicenter clinical trial of endovascular AAA repair were reviewed. Aneurysm dimensions and the presence or absence of endoleak were determined by an independent core laboratory, with enlargement or shrinkage defined as a diameter change of 5 mm or more compared with baseline.
Among 383 patients (89% men, 11% women, age 73 ± 9 years), with a mean device implant time of 36 ± 11 months (median = 39 months), aneurysm diameter decreased from 5.7 ± 1.0 at baseline to 5.2 ± 1.0 at 3 years (
P = .0001). A total of 46 patients (12%) experienced AAA enlargement, 199 patients (52%) had no change in AAA diameter, and 138 patients (36%) had a decrease in AAA diameter of 5 mm or more. Significant risk factors for enlargement included age (enlargement patients were 4 years older on average than patients with aneurysms that decreased in size;
P = .002) and the presence of an endoleak (
P < .001). Among patients with endoleak at any time, 17% had aneurysm enlargement, whereas only 2% of patients without endoleak had aneurysm enlargement (
P < .001). Patients with enlargement were more likely to undergo secondary endovascular procedures and surgical conversions (
P < .001). Twenty patients (43%) with enlargement underwent treatment, and 26 patients were untreated. There were two deaths following elective surgical conversion and one death in a patient with untreated enlargement and a type I endoleak. Three aneurysms ruptured: one with enlargement, one with no change, and one with a decrease in aneurysm size; all three aneurysms were larger than 6.5 cm. Kaplan-Meier analysis showed that freedom from rupture at 3 years was 98% with enlargement, 99% with no change, and 99% with decrease in AAA size (log-rank test, not significant). Freedom from AAA death at 3 years was 93% in patients with enlargement, 99% in no increase, and 99% in decrease (
P = .005). Survival at 3 years was 86% with increase, 82% with no change, and 93% with decrease (
P = .02).
Aneurysm enlargement following endovascular repair was not associated with an increased risk of aneurysm rupture or decrease in patient survival during a 3-year observation period. Aneurysm size rather than enlargement may be a more meaningful predictor of rupture. Close follow-up and a high re-intervention rate (43%) may account for the low risk of rupture in patients with enlargement. The long-term significance of aneurysm enlargement following endovascular repair remains to be determined.
Measurements of standing balance were determined for 92 children and adolescents, 5-18 years old, while they stood on a force plate with eyes open or eyes closed. The measurements included ...center-of-pressure calculations for path length per second, average radial displacement, anterior-posterior and mediolateral amplitudes, area per second, mean frequency of sway, Brownian random motion measure of short-term diffusion coefficient, and long-term scaling exponent. All balance parameters improved from youngest to oldest subjects, and the parameters improved when measured with the subjects' eyes open compared with closed. The mean values for data from three trials varied by only 5% when compared with the mean values from 10 trials. Data from this study suggest that force-plate center-of-pressure data can be used to determine differences in standing balance between children and adolescents of different ages and those with movement and balance abnormalities.
To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in ...patients with obstructive sleep apnea.
Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy.
Sleep clinics and laboratories at 5 university medical centers and community-based hospitals.
Target enrollment is 1100 randomly assigned subjects across 5 clinical centers.
Active versus sham (subtherapeutic) CPAP.
A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life.
The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.
To assess the utility of geriatric targeting criteria in predicting survival and health care utilization in a cohort of hospitalized older veterans.
A prospective cohort study assessing geriatric ...targeting criteria, e.g., polypharmacy, falls, or confusion, with respect to adverse outcomes at 12 months.
A Tertiary Care VA Medical Center.
507 acutely hospitalized male veterans aged 65 years or more.
Survival status, nursing home placement, and total hospital days during 12 months following hospital admission.
Patients who had a higher number of targeting criteria at admission showed a significantly increasing trend toward death (P < or = .001), nursing home placement (P < or = .01), and longer hospital stays (P < or = .01) at 12 months. In univariate analyses, weight loss (relative hazard 3.8, 95% CI 2.4, 5.9), appetite loss (relative hazard 3.3, 95% CI 1.9, 5.8), depression (relative hazard 2.5, 95% CI 1.4, 4.5), falls (relative hazard 2.2, 95% CI 1.2, 4.1), confusion (relative hazard 2.2, 95% CI 1.2, 4.0), and socioeconomic problems (relative hazard 1.6, 95% CI 1.0, 2.5) predicted death. Polypharmacy (OR 3.4, 95% CI 1.3, 8.8), confusion (OR 4.4, 95% CI 1.5, 13.0), and prolonged bedrest (OR 7.6, 95% CI 1.5, 39.3) predicted nursing home placement. Confusion (Beta 12.0, 95% CI 2.9, 21.3), falls (Beta 14.2, 95% CI 4.2, 24.3), and prolonged bedrest (Beta 22.4, 95% CI 3.9, 41.0) predicted total hospital days. In multivariate analyses, weight loss, depression, and socioeconomic problems predicted death; confusion and polypharmacy predicted nursing home placements; and falls predicted total hospital days.
This prospective cohort study of hospitalized older veterans demonstrated geriatric targeting criteria as predictors of adverse hospital outcomes. Our findings suggest screening acutely hospitalized patients using chart abstracted geriatric targeting criteria is useful in identifying patients at risk for adverse outcomes of hospitalization.
The most prevalent serious drug toxicity in the United States is increasingly recognized as gastrointestinal (GI) pathology associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). ...The incidence of serious GI events (hospitalization or death) associated with NSAID use was therefore prospectively analyzed in patients with rheumatoid arthritis (RA) and patients with osteoarthritis.
The study consisted of 2,747 patients with RA and 1,091 patients with osteoarthritis. The yearly hospitalization incidence during NSAID treatment was 1.58% in RA patients and was similar in all five populations studied. The hazard ratio of patients taking NSAIDs to those not taking NSAIDs was 5.2. The incidence in osteoarthritis may be less. The risk of GI-related death in RA patients was 0.19% per year with NSAIDs. Multivariate analyses assessing risk factors for serious GI events were performed in the 1,694 (98 with an event) RA patients taking NSAIDs at the predictive visit. The main risk factors were higher age, use of prednisone, previous NSAID GI side effects, prior GI hospitalization, level of disability, and NSAID dose. A rule is presented that allows estimation of the risk for the individual patient with RA.
Knowledge of the risk factors for NSAID-associated gastropathy and their inter-relationships provides a tool for identification of the patient at high risk and for initiation of appropriate therapeutic action.
To determine survivorship in Wegener's granulomatosis (WG) in a well-defined multicenter cohort.
Follow-up was obtained for 77 of the 85 patients enrolled in the 1990 American College of Rheumatology ...vasculitis classification study.
There were 28 deaths (10 females and 18 males) among the 77 patients available for follow-up. Standardized mortality ratios (SMR) were calculated with mortality data from the general population and from this group of patients with WG (an SMR of 1 indicates that expected and observed survival are identical). Overall survivorship among patients with WG was substantially reduced in this cohort (SMR = 4.685 ± 0.65; for females SMR = 6.814 ± 1.571; for males SMR = 3.998 ± 0.69).
The life expectancy of patients with WG is reduced compared with the general population.
This paper considers an index to assess the success of blinding with application to a clinical trial of disulfiram. The index increases as the success of blinding increases, accounts for uncertain ...responses, and is scaled to an interval of 0⋅0 to 1⋅0, 0⋅0 being complete lack of blinding and 1⋅0 being complete blinding.
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