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Biomedical subjects

Peter Finn

Publications and source records attributed to Peter Finn.

10 recordsLinked to original sources

Sub-diagnostic psychiatric comorbidity in alcoholics.

BACKGROUND: Psychiatric comorbidity in alcohol use disorders is clearly established, however most studies ignore data on psychiatric symptom counts that do not meet criteria for a diagnosis. We examined psychiatric symptom counts and psychological measures in the domains of anxiety, mood and externalizing pathology in 48 long-term abstinent alcoholics (LTAA) compared to 48 age/gender comparable light/non-drinking controls (NC). METHODS: Continuous measures of pathology (i.e., symptoms counts and psychological assessments) in each domain were compared between groups for: (1) all study participants, (2) excluding individuals with a lifetime psychiatric diagnosis in the domain, and (3) excluding individuals with a current psychiatric diagnosis in the domain. RESULTS: Psychiatric symptom counts and psychological pathology were greater in LTAA than NC. The differences between groups on these measures were not reduced by removal of individuals with lifetime or current diagnoses. CONCLUSIONS: The bulk of the difference between LTAA and NC in psychiatric illness was carried by sub-diagnostic psychopathology. In comparison to the limited view provided by using only symptomatology that meets criteria for a diagnosis, the use of continuous measures of psychiatric symptomatology and psychological abnormality yields a much more accurate picture of psychiatric illness co-occurring with alcoholism.

Alcoholism↗

Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas.

BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors have been shown to reduce colorectal adenomas but have been associated with increased cardiovascular risk. METHODS AND RESULTS: The Adenoma Prevention With Celecoxib (APC) trial studied celecoxib 200 mg twice daily and 400 mg twice daily and the Prevention of Spontaneous Adenomatous Polyps (PreSAP) trial used 400 mg once daily totest the efficacy and safety of celecoxib against placebo in reducing colorectal adenoma recurrence after polypectomy. An independent safety committee for both studies adjudicated and categorized serious cardiovascular events and then combined individual patient data from these long-term trials to improve the estimate of the cardiovascular risk and blood pressure changes associated with celecoxib compared with placebo. For adjudicated cardiovascular events, 77% and 54% in APC and PreSAP, respectively, had 37 months of follow-up. For APC and PreSAP combined, 83 patients experienced cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure. The hazard ratio for this prespecified composite end point was 2.6 (95% confidence interval [CI], 1.1 to 6.1) in patients taking 200 mg twice daily, 3.4 (95% CI, 1.5 to 7.9) in patients taking 400 mg twice daily in APC, and 1.3 (95% CI, 0.6 to 2.6) in patients taking 400 mg once daily in PreSAP (P for heterogeneity = 0.13 comparing the combined doses in APC with the dose in PreSAP). The overall hazard ratio for this composite end point was 1.9 (95% CI, 1.1 to 3.1). Both dose groups in APC showed significant systolic blood pressure elevations at 1 and 3 years (200 mg twice daily: 1 year, 2.0 mm Hg; 3 years,2.6 mm Hg; 400 mg twice daily: 1 year, 2.9 mm Hg; 3 years, 5.2 mm Hg); however, the 400 mg once daily group inPreSAP did not (P0.0001 between studies). CONCLUSIONS: Celecoxib at 200 or 400 mg twice daily or 400 mg once daily showed a nearly 2-fold-increased cardiovascular risk. The trend for a dose-related increase in cardiovascular events and blood pressure raises the possibility that lower doses or other dose intervals may be associated with less cardiovascular risk.

Adenoma↗

Brain atrophy in long-term abstinent alcoholics who demonstrate impairment on a simulated gambling task.

We recently demonstrated impairment on the Simulated Gambling Task (SGT) in long-term abstinent alcoholics (AbsAlc). Brain regions that have been shown to be necessary for intact SGT performance are the ventromedial prefrontal cortex (VMPFC) and the amygdala; patients with VMPFC or amygdalar damage demonstrate SGT impairments similar to those of substance abusing populations. We examined these brain regions, using T1-weighted MRIs, in the 101 participants from our previous study using voxel-based morphometry (VBM). VBM was performed using a modification we developed [Fein, G., Landman, B., Tran, H., Barakos, J., Moon, K., Di Sclafani, V., Shumway, R., 2006. Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs. Neuroimage] of Baron's procedure, [], in which we use skull-stripped images as input. We also restricted the analysis to a ROI consisting of the amygdala and VMPFC as defined by the Talairach Daemon resource. Compared to the controls, the AbsAlc participants had significant foci of reduced gray matter density within the amygdala. Thus, SGT decision-making deficits are associated with reduced gray matter in the amygdala, a brain region previously implicated in similar decision-making impairments in neurological samples. This structurally based abnormality may be the result of long-term alcohol abuse or dependence, or it may reflect a pre-existing factor that predisposes one to severe alcoholism. From an image analysis perspective, this work demonstrates the increased sensitivity that results from using skull-stripped inputs and from restricting the analysis to a ROI. Without both of these methodological advances, no statistically significant finding would have been forthcoming from this work.

Adult↗

Normal performance on a simulated gambling task in treatment-naive alcohol-dependent individuals.

BACKGROUND: Research suggests that substance abusers make more disadvantageous decisions on the simulated gambling task (SGT); such decisions are associated with deviance proneness and antisocial symptoms. This study examines decision making on the SGT in young adults with alcohol dependence who are treatment-naive (TxN). METHODS: A total of 116 subjects (58 controls, 58 TxNs) were tested on the SGT, where participants choose cards from 4 different decks that vary in terms of the magnitude of the immediate gain (large/small) and the magnitude of long-term loss (larger/smaller). Participants were also assessed on measures of externalizing symptoms, personality traits reflecting social deviance, neuropsychological function, and the density of the family history of alcoholism. RESULTS: Treatment-naïves did not differ from controls on measures of SGT decision making. Simulated gambling task performance was not associated with externalizing symptoms, social deviance proneness, or a familial density of alcoholism. Although TxNs had higher levels of externalizing symptoms, social deviance, and familial density of alcoholism compared with controls, these variables were only modestly elevated compared with previous samples of long-term abstinent alcohol-dependent individuals who showed decision-making deficits on the SGT. CONCLUSIONS: The results suggest that our sample of young adult TxN adults with alcohol dependence do not have global deficits in decision making as measured by the SGT, and that their poor decisions regarding their alcohol consumption are more specific to drinking.

Adult↗

Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern. METHODS: We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme. RESULTS: For all patients except those who died, 2.8 to 3.1 years of follow-up data were available. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence interval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval, 1.4 to 7.8). Similar trends were observed for other composite end points. On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug. CONCLUSIONS: Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.

Adenomatous Polyps↗

Effect of candesartan on cause-specific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure. We assessed the effect of candesartan on cause-specific mortality in patients enrolled in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program. METHODS AND RESULTS: The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure: CHARM-Alternative (n=2028; LVEF<=40% [corrected] and ACE intolerant), CHARM-Added (n=2548; LVEF<=40%, [corrected] already on ACE inhibitors), and CHARM-Preserved (n=3023; LVEF >40%). Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months. All deaths were reviewed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation. The number and rate of deaths by cause were calculated for each of the component trials and the overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of progressive heart failure. Candesartan reduced both sudden death (HR 0.85 [0.73 to 0.99], P=0.036) and death from worsening heart failure (HR 0.78 [0.65 to 0.94], P=0.008). These reductions were most apparent in the patients with LVEF<=40% [corrected]. CONCLUSIONS: Candesartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure, although this reduction was most apparent in patients with systolic dysfunction.

Aged↗

Mismatch negativity: no difference between controls and abstinent alcoholics.

BACKGROUND: A number of studies have examined the amplitude of the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. The current study examined MMN in alcoholics abstinent an average of 6.7 years (with a minimum of six months abstinence) compared to controls. This study examined the association of MMN with alcoholism family history density, with indices of the presence and severity of externalizing disorders (a risk-factor for alcoholism), and with alcohol use variables. METHODS: Electroencephalograms were gathered on 76 subjects (38 controls, 38 abstinent alcoholics) during a nonattending mismatch negativity experiment. Measures of alcoholism family history density, disinhibited personality traits, and antisocial symptoms served as measures of risk-factors known to be associated with a genetic liability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. RESULTS: There were no differences in MMN amplitude or latency between controls and abstinent alcoholics. There also were no significant associations between MMN measures and the measures of risk for alcoholism or with the severity of alcohol use or duration of abstinence. CONCLUSIONS: The results suggest that MMN is neither affected in chronic alcoholics nor associated with alcoholism vulnerability, and thus does not reflect a trait marker of alcoholism or alcoholism risk. The current results do not address effects on MMN of acute alcohol ingestion or withdrawal from alcohol.

Adult↗

Mismatch negativity: no difference between treatment-naive alcoholics and controls.

BACKGROUND: Several studies have examined the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. This study examined MMN in actively drinking treatment-naive alcohol-dependent individuals. This study examined the association of MMN with risk factors for alcoholism, postalcohol withdrawal hyperexcitability, and alcohol use variables. METHODS: Electroencephalograms were gathered on 84 subjects (42 controls and 42 treatment-naive alcohol-dependent individuals) during a nonattending MMN experiment. Alcoholism family history density, the number of externalizing disorder symptoms, and psychological indices of deviance proneness served as measures of risk factors associated with the vulnerability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. RESULTS: There were no differences in the MMN integral, amplitude, or latency between control and treatment-naive alcohol-dependent subjects. There also were no significant associations of MMN measures with any of the measures of alcoholism vulnerability, with any of the alcohol use variables, or with the prevalence or severity of symptoms of postalcohol withdrawal hyperexcitability. CONCLUSIONS: Although there is a strong association between alcohol abuse and symptoms of disinhibition and deviance proneness, the MMN response does not offer any direct physiological evidence of this phenomenon.

Adult↗

The Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales: I. Measuring sexual inhibition and excitation proneness in men.

This study involves the development and initial validation of a questionnaire measuring the propensity for sexual inhibition and excitation in men: the Sexual Inhibition Sexual Excitation Scales (SIS/SES). The underlying theoretical model postulates that sexual response and associated behavior depend on dual control mechanisms, involving excitatory and inhibitory neurophysiological systems. The scales and their discriminant and convergent validity and test-retest reliability are described. In a sample of 408 sexually functional men (mean age = 22.8 years), factor analyses identified three higher-level factors: two related to sexual inhibition and one to sexual excitation. Multigroup Confirmatory Factor Analyses revealed that the factor structure provided an acceptable fit to the data obtained in a second (N = 459; mean age = 20.9 years) and third (N = 313; mean age = 46.2 years) sample of men, with similar distributions and relationships with other measures. Theoretical issues and areas for further research, including male sexual dysfunction and risk taking, are discussed.

Adolescent↗

The Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales: II. Predicting psychophysiological response pattens.

This study evaluated the predictive value of a newly developed measure of the propensity for sexual inhibition and excitation; the Sexual Inhibition Sexual Excitation Scales (SIS/SES). Sexual, cardiovascular, and startle responses were measured in a group of 40 sexually functional men during the presentation of threatening and nonthreatening erotic films. Two levels of performance demand were created and two films were combined with a distraction task. Participants were assigned to high and low groups for each of the three SIS/SES scales. As predicted, men with high SES scores showed generally higher sexual responses. High and low SIS1 groups did not differ in their responses. Men with high and low SIS2 scores did not differ in their responses to nonthreatening stimuli; however, low SIS2 men showed greater genital response to the threatening stimuli. The findings provide support for the value of the SIS/SES scales in predicting sexual responses.

Adult↗