Biomedical subjects

Robert J Gallop

Publications and source records attributed to Robert J Gallop.

9 recordsLinked to original sources

PubMed2006

A mixed effects Markov model for repeated binary outcomes with non-ignorable dropout.

In many areas of research, repeated binary measures often represent a two-state stochastic process, where individuals can transition among two states. In a behavioural or physical disability setting, individuals can flow from susceptible or subthreshold state, to an infectious or symptomatic state, and back to a subthreshold state. Quite often the transition among the states happens in continuous time but is observed at discrete, irregularly spaced timepoints which may be unique to each individual. Methods for analyses of such data are typically based on the Markov assumption. Cook (Biometrics 1999; 55:915-920) introduced a conditional Markov model that accommodates the subject-to-subject variation in the model parameters with random effects. We extend this model by adding a non-ignorable dropout component to the model. Specification of the distribution of the random effects is made to guarantee a closed form expression of the marginal likelihood. This methodology is illustrated by applications to a data set from a parasitic field infection survey, a data set from a cocaine treatment study, and a data set from an aging study. Simulations suggest that the shared parameter model is robust with respect to at least one alternative non-ignorable model.

Activities of Daily Living↗

PubMed2006

Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia.

Recent molecular genetics studies implicate neuregulin 1 (NRG1) and its receptor erbB in the pathophysiology of schizophrenia. Among NRG1 receptors, erbB4 is of particular interest because of its crucial roles in neurodevelopment and in the modulation of N-methyl-D-aspartate (NMDA) receptor signaling. Here, using a new postmortem tissue-stimulation approach, we show a marked increase in NRG1-induced activation of erbB4 in the prefrontal cortex in schizophrenia. Levels of NRG1 and erbB4, however, did not differ between schizophrenia and control groups. To evaluate possible causes for this hyperactivation of erbB4 signaling, we examined the association of erbB4 with PSD-95 (postsynaptic density protein of 95 kDa), as this association has been shown to facilitate activation of erbB4. Schizophrenia subjects showed substantial increases in erbB4-PSD-95 interactions. We found that NRG1 stimulation suppresses NMDA receptor activation in the human prefrontal cortex, as previously reported in the rodent cortex. NRG1-induced suppression of NMDA receptor activation was more pronounced in schizophrenia subjects than in controls, consistent with enhanced NRG1-erbB4 signaling seen in this illness. Therefore, these findings suggest that enhanced NRG1 signaling may contribute to NMDA hypofunction in schizophrenia.

Animals↗

PubMed2006

Two-year randomized controlled trial and follow-up of dialectical behavior therapy vs therapy by experts for suicidal behaviors and borderline personality disorder.

CONTEXT: Dialectical behavior therapy (DBT) is a treatment for suicidal behavior and borderline personality disorder with well-documented efficacy. OBJECTIVE: To evaluate the hypothesis that unique aspects of DBT are more efficacious compared with treatment offered by non-behavioral psychotherapy experts. DESIGN: One-year randomized controlled trial, plus 1 year of posttreatment follow-up. SETTING: University outpatient clinic and community practice. PARTICIPANTS: One hundred one clinically referred women with recent suicidal and self-injurious behaviors meeting DSM-IV criteria, matched to condition on age, suicide attempt history, negative prognostic indication, and number of lifetime intentional self-injuries and psychiatric hospitalizations. INTERVENTION: One year of DBT or 1 year of community treatment by experts (developed to maximize internal validity by controlling for therapist sex, availability, expertise, allegiance, training and experience, consultation availability, and institutional prestige). MAIN OUTCOME MEASURES: Trimester assessments of suicidal behaviors, emergency services use, and general psychological functioning. Measures were selected based on previous outcome studies of DBT. Outcome variables were evaluated by blinded assessors. RESULTS: Dialectical behavior therapy was associated with better outcomes in the intent-to-treat analysis than community treatment by experts in most target areas during the 2-year treatment and follow-up period. Subjects receiving DBT were half as likely to make a suicide attempt (hazard ratio, 2.66; P = .005), required less hospitalization for suicide ideation (F(1,92) = 7.3; P = .004), and had lower medical risk (F(1,50) = 3.2; P = .04) across all suicide attempts and self-injurious acts combined. Subjects receiving DBT were less likely to drop out of treatment (hazard ratio, 3.2; P < .001) and had fewer psychiatric hospitalizations (F(1,92) = 6.0; P = .007) and psychiatric emergency department visits (F(1,92) = 2.9; P = .04). CONCLUSIONS: Our findings replicate those of previous studies of DBT and suggest that the effectiveness of DBT cannot reasonably be attributed to general factors associated with expert psychotherapy. Dialectical behavior therapy appears to be uniquely effective in reducing suicide attempts.

Adaptation, Psychological↗

PubMed2006

Seeking safety therapy for adolescent girls with PTSD and substance use disorder: a randomized controlled trial.

This randomized, controlled trial evaluated a manualized psychotherapy, Seeking Safety (SS), for posttraumatic stress disorder (PTSD) and substance use disorder (SUD) in adolescent females. To our knowledge, no prior study has evaluated any psychotherapy designed for this population. SS was compared to treatment as usual (TAU) for 33 outpatients, at intake, end-of-treatment, and 3 months follow-up. SS evidenced significantly better outcomes than TAU in a variety of domains at posttreatment, including substance use and associated problems, some trauma-related symptoms, cognitions related to SUD and PTSD, and several areas of pathology not targeted in the treatment (e.g., anorexia, somatization). Effect sizes were generally in the moderate to high range. Some gains were sustained at follow-up. SS appears a promising treatment for this population, but needs further study and perhaps additional clinical modification.

Adaptation, Psychological↗

PubMed2005

The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients.

OBJECTIVE: Although cocaine-dependent patients are frequently referred to 12-step self-help groups, little research has examined the benefits of 12-step group attendance in this population. Moreover, the distinction between attending meetings and actively participating in 12-step activities has not typically been examined. METHOD: In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, 487 cocaine-dependent outpatients were recruited at five sites for a randomized controlled trial of 24-week behavioral treatments. Study data were examined to see whether self-help attendance or active participation were related to subsequent drug use. RESULTS: Twelve-step group attendance did not predict subsequent drug use. However, active 12-step participation in a given month predicted less cocaine use in the next month. Moreover, patients who increased their 12-step participation during the first 3 months of treatment had significantly less cocaine use and lower ASI Drug Use Composite scores in the subsequent 3 months. Finally, Individual Drug Counseling, based on a 12-step model, and increasing levels of 12-step participation each offered discrete benefits. CONCLUSIONS: Results suggest that active 12-step participation by cocaine-dependent patients is more important than meeting attendance, and that a combination of Individual Drug Counseling and active 12-step participation is effective for these patients.

Adult↗

PubMed2005

Aberrant intracellular calcium signaling in olfactory neurons from patients with bipolar disorder.

OBJECTIVE: The authors examined the feasibility of using olfactory receptor neurons from living patients to test whether calcium signaling is altered in a neuronal cell population in bipolar disorder. METHOD: Ratiometric fluorescence photomicroscopy was used to assess basal and stimulus-induced changes in intracellular calcium levels in biopsy-derived olfactory receptor neurons from seven euthymic patients with bipolar disorder who were medication-free, 10 euthymic patients with bipolar disorder who were treated with mood stabilizers, and 17 age- and sex-matched comparison subjects without bipolar disorder. RESULTS: Olfactory receptor neurons from the seven medication-free patients responded to stimuli predominantly with decreases in intracellular calcium, unlike those from the seven matched healthy subjects. Olfactory receptor neurons from patients treated with mood stabilizers were less likely to respond to stimulation than olfactory receptor neurons from medication-free patients. CONCLUSIONS: This study demonstrates the feasibility of using olfactory receptor neurons to examine alterations in intracellular signaling in neuronal cells from living patients. Our results, although based on a small number of subjects, suggest that altered intracellular calcium signaling in olfactory receptor neurons may be a trait of bipolar disorder.

Anticonvulsants↗

PubMed2004

The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication.

BACKGROUND: A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo. METHOD: Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John's wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John's wort or placebo were treated with an antidepressant for 24 weeks. RESULTS: During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John's wort extract, 5 (29.4%) relapsed. CONCLUSIONS: The subjects who did not respond to St. John's wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.

Adult↗

PubMed2002

Cardiopulmonary bypass for bilateral sequential lung transplantation in patients with chronic obstructive pulmonary disease without adverse effect on lung function or clinical outcome.

OBJECTIVE: The use of cardiopulmonary bypass in lung transplantation remains controversial. Previous studies have concluded that cardiopulmonary bypass is deleterious, but these studies were confounded by the inclusion of patients with different diagnoses undergoing single- and double-lung transplantation with elective or emergency use of bypass. The goal of this study was to determine whether cardiopulmonary bypass has deleterious effects on lung function or clinical outcome by analyzing the cases of patients with a single disease entity and elective use of bypass for bilateral sequential lung transplantation. METHODS: A retrospective review of 50 patients with chronic obstructive pulmonary disease who underwent bilateral sequential lung transplantation was performed. Fourteen patients who underwent elective cardiopulmonary bypass for 218.3 +/- 75.4 minutes were compared to 36 control patients. RESULTS: After the operation, the bypass and nonbypass groups were not significantly different with respect to median duration of mechanical ventilation (1 day vs 1 day, P =.76), median stay in the intensive care unit (4 days vs 4 days, P =.44), median hospital stay (15.5 days vs 16 days, P =.74), mean increase in serum creatinine level (1.4 +/- 1.9 mg/dL vs 0.9 +/- 1.0 mg/dL, P =.33), and mean ratio of Pao(2) to fraction of inspired oxygen at 1 hour (376.6 +/- 123 vs 357.0 +/- 218, P =.75), at 24 hours (309.9 +/- 92 vs 350.6 +/- 122, P =.26), and at 48 hours (335.0 +/- 144 vs 316.2 +/- 120, P =.64). Late outcome markers compared between the bypass and nonbypass groups were the following: 1-year percentage predicted forced expiratory volume in 1 second (76.1% +/- 17.0% vs 85.3% +/- 21.7%, P =.24), 30-day mortality (7.1% vs 8.3%, P >.999), 1-year survival (85.7% vs 80.1%, P =.66), 3-year survival (64.3% vs 58.3%, P =.70), and the prevalence of bronchiolitis obliterans syndrome (0% vs 36.1%, P =.01). CONCLUSION: Cardiopulmonary bypass appears to have no deleterious effect on early lung function or clinical outcome. We hope that this pilot study removes some of the unwarranted fear of the use of bypass in lung transplantation for chronic obstructive pulmonary disease.

Analysis of Variance↗

PubMedDate not supplied

Determination of threshold conditions for a non-linear stochastic partnership model for heterosexually transmitted diseases with stages.

When comparing the performance of a stochastic model of an epidemic at two points in a parameter space, a threshold is said to have been crossed when at one point an epidemic develops with positive probability; while at the other there is a tendency for an epidemic to become extinct. The approach used to find thresholds in this paper was to embed a system of ordinary non-linear differential equations in a stochastic process, accommodating the formation and dissolution of marital partnerships in a heterosexual population, extra-marital sexual contacts, and diseases such as HIV/AIDS with stages. A symbolic representation of the Jacobian matrix of this system was derived. To determine whether this matrix was stable or non-stable at a particular parameter point, the Jacobian was evaluated at a disease-free equilibrium and its eigenvalues were computed. The stability or non-stability of the matrix was then determined by checking if all real parts of the eigenvalues were negative. By writing software to repeat this process for a selected set of points in the parameter space, it was possible to develop search engines for finding points in the parameter space where thresholds were crossed. The results of a set of Monte Carlo simulation experiments were reported which suggest that, by combining the stochastic and deterministic paradigms within a single formulation, it was possible to obtain more informative interpretations of simulation experiments than if attention were confined solely to either paradigm.

Acquired Immunodeficiency Syndrome↗