Mild traumatic brain injury does not predict acute postconcussion syndrome.

BACKGROUND: The aetiology of postconcussion syndrome (PCS) following mild traumatic brain injury (mTBI) remains controversial. Identifying acute PCS (within the first 14 days after injury) may optimise initial recovery and rehabilitation, identify those at risk and increase understanding of PCS. OBJECTIVE: To examine predictors of acute outcome by investigating the relationship between preinjury psychiatric disorder, demographic factors, injury related characteristics, neuropsychological and psychological variables and acute PCS. METHODS: Prospective study of consecutive trauma admissions to a level 1 trauma hospital. The final sample comprised 90 patients with mTBI and 85 non-brain injured trauma controls. Individuals were administered a PCS checklist, and neuropsychological and psychological measures. Multiple imputation of missing data in multivariable logistic regression and bivariate logistic regressions were used to predict acute PCS at a mean of 4.90 days after injury. RESULTS: Diagnosis of acute PCS was not specific to mTBI (mTBI 43.3%; controls 43.5%). Pain was associated with acute PCS in mTBI. The strongest effect for acute PCS was a previous affective or anxiety disorder (OR 5.76, 95% CI 2.19 to 15.0). Females were 3.33 times more likely than males to have acute PCS (95% CI 1.20 to 9.21). The effect of acute post-traumatic stress and neuropsychological function on acute PCS was relatively small. Higher IQ was associated with acute PCS. CONCLUSIONS: There is a high rate of acute PCS in both mTBI and non-brain injured trauma patients. PCS was not found to be specific to mTBI. The use of the term PCS may be misleading as it incorrectly suggests that the basis of PCS is a brain injury.

Case-controlled study of nursing home residents referred for treatment of vocally disruptive behavior.

The aim of this study was to identify factors associated with vocally disruptive behavior (VDB) in nursing home patients referred to aged care services for treatment, using a case-control methodology. Characteristics of the VDB, reasons for referral, perceived causal factors, and psychotropic use were noted. Twenty-five subjects and controls were examined with the Screaming Behavior Mapping Instrument, the Cornell Scale for Depression in Dementia, the Dementia Behavior Disturbance Scale, and measures of cognition, functional capacity, social activities, and emotional reactions of nursing staff. VDB was associated with other disturbed behaviors, depression, anxiety, severe dementia, functional impairment, communication difficulties, use of psychotropic medication, social isolation, and emotional distress in the nursing staff. Reasons for referral may relate more to the stress experienced by nursing home staff in managing VDB than to specific attributes of the VDB itself.

Treatment of vocally disruptive behaviour of multifactorial aetiology.

OBJECTIVE: To describe the treatment of vocally disruptive behaviour (VDB) of multifactorial aetiology. METHOD: Three case reports were used to illustrate the treatment of multifactorial VDB. RESULTS: A biopsychosocial assessment is required to identify the different aetiologies involved and the way they interact. Acute medical and psychiatric factors may demand that interventions are introduced simultaneously rather than in succession. CONCLUSION: Successful interventions require the combination of biopsychosocial strategies tailored to the individual case with realistic goals that include the acceptance of a residual level of VDB as a reasonable outcome.

Longitudinal study of cerebral blood flow in Alzheimer's disease using single photon emission tomography.

Ten patients with probable Alzheimer's disease were assessed at baseline and a mean 2 years later using a battery of neuropsychological tests, CT scans and Tc99m-HMPAO SPECT scans. The subjects had declined significantly in their functional indices. Cerebral perfusion measures declined in the parietal lobes, left hemisphere and whole brain, but the overall decline did not reach statistical significance. The decline in brain perfusion did not correlate significantly with the decline in various indices of neuropsychological function, either globally or for specific brain regions. The index of cerebral perfusion correlated significantly with global indices of neuropsychological function at baseline but not at follow-up. No single perfusion index was a significant predictor of clinical progression of dementia.

Quinidine single dose pharmacokinetics and pharmacodynamics are unaltered by omeprazole.

Omeprazole has been shown in previous studies to inhibit the hepatic metabolism of selected drugs. Quinidine is an antiarrhythmic and antimalarial agent with a low therapeutic index. We therefore examined the effect of 40 mg omeprazole daily for one week or placebo on the pharmacokinetics and pharmacodynamics of a single 400 mg dose of quinidine in 8 healthy volunteers in a double-blind crossover study. During placebo and omeprazole treatment, there was no significant difference in area under the time-plasma quinidine concentration curve, (17.0 +/- 4.83 micrograms.h/ml, 18.6 +/- 4.43 micrograms.h/ml, respectively; P greater than 0.2) or renal clearance of quinidine (56.2 +/- 26.0 ml/min, 55.6 +/- 12.7 ml/min, respectively; P greater than 0.5). Quinidine unbound fraction in plasma (0.170 +/- 0.041 vs. 0.166 +/- 0.041 in the presence of omeprazole; P greater than 0.5) was not altered by omeprazole. Peak plasma quinidine concentration and the time this occurred did not differ. Omeprazole also had no effect on these parameters for the metabolite 3-hydroxyquinidine. There was no significant difference in the change in the corrected Q-T interval on the electrocardiogram due to quinidine (mean area under the time versus delta Q-Tc curve = 351 +/- 192 ms.h, placebo; 414 +/- 303 ms.h, omeprazole) showing that quinidine pharmacodynamics were unaltered by omeprazole. We conclude that omeprazole does not affect the pharmacokinetics of quinidine.

Oral bioavailability of omeprazole before and after chronic therapy in patients with duodenal ulcer.

1. This study investigated the mechanism of the increase in oral bioavailability of omeprazole during repeated oral dosing. Eight patients with duodenal ulcer received an i.v. dose of omeprazole before and after a 4-week course of oral omeprazole, 20 mg daily, given as enteric-coated granules. 2. AUCoral and oral bioavailability (F) increased during omeprazole treatment by 50% (P less than 0.01) and 35% (P less than 0.05), respectively. 3. There was no change in the systemic clearance of omeprazole after i.v. dosage following the course of treatment. 4. We conclude that the increased omeprazole AUC observed on repeated administration of enteric-coated granules is due to increased systemic availability rather than decreased systemic elimination. The increased availability appears to be due to increased gastrointestinal absorption rather than decreased first-pass hepatic extraction.

Effect of propranolol and verapamil on oxygen utilization, acidosis and fatigue during exercise in stable angina pectoris.

Oxygen utilization, arterial and venous blood gas levels, hemodynamic values and exercise tolerance were compared before and after administration of propranolol and verapamil in 10 patients with stable angina pectoris. During exercise, propranolol decreased cardiac output (CO) by 22%; O2 extraction was increased and O2 consumption (VO2) did not change. With verapamil treatment, CO modestly increased (7%), O2 extraction decreased and VO2 did not change. In contrast to O2 utilization, the drugs produced opposite changes in mixed venous and arterial blood gas levels. Propranolol decreased mixed venous pH, increased CO2 tension and decreased the pH of arterial blood. Verapamil increased venous pH and decreased CO2 tension; pH of arterial blood did not change. The drugs yielded similar levels of antianginal efficacy, but patients exercised longer during verapamil therapy and were less fatigued. The hemodynamic and metabolic differences suggest that muscle perfusion during exercise influences the onset of fatigue and may help determine the choice of therapy.

Propranolol steady-state pharmacokinetics are unaltered by omeprazole.

In a randomised double-blind cross-over study, 8 normal subjects received propranolol 80 mg twice daily with omeprazole 20 mg or identical placebo each morning. Propranolol kinetics were measured on day 8 of both treatment periods. Areas under the propranolol concentration/time curves were not significantly increased by omeprazole treatment: off treatment mean 787.6, on treatment 802.5 ng-1.ml.h. Maximum and minimum steady-state propranolol concentrations were similarily unaffected. Omeprazole also failed to increase the clinical effect of propranolol, as assessed by exercise tests on Day 8 of treatment. We conclude that omeprazole in the dose likely to be used for peptic ulcer has no significant effect on the kinetics or action of propranolol.

Beta-adrenergic stimulation of the failing ventricle: a double-blind, randomized trial of sustained oral therapy with prenalterol.

Eleven patients with severe left ventricular impairment (mean ejection fraction 24%) and moderate impairment of exercise tolerance underwent a double-blind, placebo-controlled, cross-over trial of the orally administered beta-agonist prenalterol. Exercise hemodynamics and tolerance were measured during bicycle and treadmill exercise after 2 weeks of therapy with placebo or prenalterol. Cardiac index, ejection fraction, and stroke work index were not improved and exercise duration and peak oxygen consumption were not significantly different during the two treatments. During prenalterol treatment heart rate during exercise was consistently reduced. These results show that prolonged therapy with prenalterol does not improve hemodynamics or exercise tolerance and is associated with a diminished heart rate response to exercise.

Effects of intravenous verapamil on the haemodynamic response to exercise in patients with angina pectoris.

The effects of intravenous Verapamil (V) on exercise haemodynamics and ventricular function were compared in 13 patients with stable effort angina. Intravascular pressures, thermodilution cardiac output and radionuclide ejection fraction were measured simultaneously at rest and during exercise. At rest Verapamil produced systemic vasodilation. During exercise at identical workloads compared to control, Verapamil increased cardiac index (CI) and decreased AVO2 difference. Pulmonary artery wedge pressure was lower. Ejection fraction was higher (control-55 +/- 11% vs V-64 +/- 11%) as the disproportionate increase in end systolic volume relative to the end diastolic volume was prevented. Verapamil is effective in exercise induced angina and alters haemodynamics primarily through its vasodilating properties associated with an increased CI.