Psychometric testing of two new patient-reported outcome instruments for the evaluation of treatment for hypogonadism.

AIM: The aim of this study was to perform psychometric testing and estimate minimal important change (MIC) of two new patient-reported outcome (PRO) instruments - Sexual Arousal, Interest and Drive Scale (SAID) and Hypogonadism Energy Diary (HED). METHODS: New PRO instruments were administered immediately after screening (Time 1, test-retest subset only) and immediately prior to both randomisation (Time 2) and end-point (Time 3) to men participating in a randomised clinical trial comparing the effect of testosterone solution 2% (TS) and placebo on serum total testosterone. Psychometric analyses included reliability, validity and responsiveness. Total scores for both PRO instruments were transformed to a 0-100 scale. RESULTS: Study participants (n = 694) were 80% age ≤ 65 years, 79% White, with mean baseline testosterone = 202 ng/dl. Clinicians identified 86% subjects as having low sex drive, 86% with low energy and 76% with both symptoms. Reliability analyses for SAID and HED yielded reliability coefficients > 0.70. SAID scores discriminated between men having low sex drive (n = 553) and those who did not (n = 80) (34.5 vs. 42.8, p < 0.001). HED scores discriminated between men having low energy (n = 541) and those who did not (n = 64) (48.9 vs. 60.2, p < 0.001). In the men randomised to TS (vs. placebo), SAID and HED detected effect sizes of 0.61 (vs. 0.39) and 0.68 (vs. 0.48), respectively. MIC estimates for SAID and HED were approximately 10 and 8, respectively. CONCLUSIONS: This study provided evidence of the reliability, validity and responsiveness of SAID and HED as measures of sex drive and energy, respectively, making them potentially useful for evaluation of hypogonadal treatment.

Detecting a thienopyridine effect by platelet reactivity assessment and its implications for risk stratification.

BACKGROUND: On-treatment platelet reactivity (OTR) is a predictor of clinical outcomes in patients receiving thienopyridine therapy. OBJECTIVE: To assess whether point-of-care platelet reactivity testing can discriminate between patients who have and have not received a thienopyridine. PATIENTS/METHODS: This was an analysis of a randomized, multicenter, pharmacodynamic trial. Subjects with coronary artery disease treated with aspirin were randomly assigned to clopidogrel 75 mg daily or prasugrel 10 mg daily for 7 days. Platelet reactivity assessment with the VerifyNow P2Y12 test was performed before study drug admistration and 24 h after the final dose. Optimal cut-offs for a detectable drug effect were identified by the use of receiver operating characteristic curve analysis. RESULTS: A total of 54 subjects were enrolled and completed the study. The c-statistic for the identification of a thienopyridine effect was highly significant (0.93, P < 0.001), including for the clopidogrel and prasugrel groups considered separately (P < 0.001 for both). The optimal cut-off was < 213 P2Y12 reaction units (PRU), which provided a sensitivity of 80% and a specificity of 98%. This cut-off provided a sensitivity of 58% and a specificity of 100% for a clopidogrel effect, and a sensitivity of 100% and specificity of 96% for a prasugrel effect. CONCLUSIONS: OTR of < 213 PRU is highly specific for exposure to either clopidogrel or prasugrel. This may be useful in the management of thienoypridine-treated patients who require surgery. Furthermore, this diagnostic cut-off is similar to levels of OTR that have been associated with ischemic events in thienopyridine-treated patients, supporting the contention that a lack of drug effect is the mechanistic basis for the prognostic relationship between OTR and clinical outcomes.

Relevance of routine admission electrocardiograms for psychiatric patients.

OBJECTIVE: To make clinically relevant recommendations for electrocardiogram (ECG) testing among psychiatric patients, the study examined the practice of ordering ECGs for this population. METHODS: The records of 4,045 patients consecutively admitted for psychiatric care to seven community teaching hospitals over one year were examined. The frequency of ECG orders was documented, and abnormal ECG results were grouped into two categories: relevant to psychiatric treatment (ischemia or conduction defects) and incidental to treatment (minor abnormalities and screening abnormalities). For those with abnormalities, additional cardiac follow-up data were recorded. Associations between ECG results and patients' characteristics were analyzed. RESULTS: ECGs were performed for 2,857 (71 percent) of first admissions, of which 2,225 (78 percent) showed neither relevant nor screening abnormalities. Eighteen percent of those tested had relevant abnormalities, most commonly a first-degree atrioventricular block or some evidence of a myocardial infarction. ECG screening abnormalities were found for another 4 percent, primarily left ventricular hypertrophy (3 percent), but no follow-up occurred for 46 percent of these patients. Among patients under 40 years of age, 8 percent had relevant abnormalities, and 3 percent had screening abnormalities. Among patients without apparent cardiac risk, 10 percent had relevant and 3 percent had screening abnormalities. More than half the patients who had a second or third admission during the year had a repeat ECG, even when previous ECGs were normal. CONCLUSIONS: Routine ECG is not an effective treatment or screening tool in this population, and substantial cost savings could result from more selective testing, particularly among young patients, those at low risk, and those with repeat admissions.

Enteral feeding tube placement success with intravenous metoclopramide administration in ICU patients.

OBJECTIVE: The purpose of this study was to determine if intravenous push metoclopramide would facilitate immediate transpyloric passage of a small-bore feeding tube without fluoroscopy or endoscopy. DESIGN: Prospective, randomized trial. PATIENTS: One hundred five medical and surgical ICU patients at a community teaching hospital. INTERVENTIONS: Patients were randomized to receive 10 mg of metoclopramide 10 min before tube insertion or no medication. MEASUREMENT: Successful placement was stated as radiologically verified transduodenal tube location. RESULTS: A 54% success rate was shown with administration of the drug with 46% success for the control. Chi square analysis of the success rate showed no significant relationship between administration of metoclopramide and successful tube placement (p = 0.38). Increasing years of physician training was the only variable associated with successful placement (p = 0.003). No association was found between successful tube placement and presence of endotracheal tube, tracheostomy, or cervical immobility, nor any interaction of metoclopramide with these variables. CONCLUSION: Intravenous metoclopramide, 10 mg, administered 10 min prior to intubation with a small-bore feeding tube (10F), was ineffective in facilitating transpyloric intubation.

Randomized comparison of gastric pH control with intermittent and continuous intravenous infusion of famotidine in ICU patients.

OBJECTIVE: To compare gastric pH control using intravenous famotidine as a primed, continuous infusion versus intermittent infusion. METHODS: In a prospective, double-blind study, 40 ICU patients at risk for stress ulceration were randomly assigned to receive either famotidine 20 mg intravenous bolus followed by 1.67 mg/h infusion or famotidine 20 mg intravenously every 12 h. Intraluminal gastric pH was recorded at baseline and every 4 h using a glass electrode. Clinical outcome indicators were also monitored. Subjects were studied for a minimum of 24 h and a maximum of 6 days. Continuous variables were analyzed by ANOVA and nominal variables by Fisher's exact test (alpha = 0.05). RESULTS: Nineteen patients were randomized to the continuous infusion group, and 21 were randomized to the intermittent group. Using gastric pH greater than 4.0 as an endpoint, the continuous group exhibited better pH control, both in terms of percentage of total measurements (83% versus 63%, p < 0.001) and time spent above pH 4.0 (91% versus 76%, p < 0.01). Similar results were found at pH greater than 5.0 (78% versus 56% for all measurements for the continuous and bolus groups, respectively (p < 0.001), and 88% versus 72% for the time spent above pH 5.0 (p < 0.01). Clinical outcomes, including evidence for gastrointestinal bleeding and hospital mortality, did not differ significantly between groups. CONCLUSION: Famotidine infusion at 1.67 mg/h, when preceded by a bolus dose of 20 mg, provides a greater and more sustained increase in gastric pH than intermittent administration of famotidine 20 mg every 12 h.

Complete heart block and torsade de pointes associated with thioridazine poisoning.

A 72-year-old woman attempted suicide with thioridazine 3000 mg and 60 tablets of acetaminophen 325 mg plus codeine 30 mg. She was semicomatose and had persistent third-degree atrioventricular block, progressive hypotension, and an episode of torsade de pointes. Heart block, arrhythmias, and hypotension resolved within 48 hours, and the patient recovered without adverse sequelae.

Nasointestinal tube placement with a pH sensor feeding tube.

Radiographic confirmation of enteral feeding tube placement is a common practice representing considerable expense and causing delay in the initiation of enteral nutrition therapy. We evaluated an enteral feeding tube with a pH sensor, which allows immediate verification of the location of the tube by assessment of the pH upon insertion. Insertion pHs were obtained for 24 intensive care unit patients requiring feeding tube placement. Placement was verified radiographically and compared with expected location on the basis of the pH profile. The radiograph and the insertion pH profile were in agreement in 87.5% (21 of 24) of the cases. Concomitant use of histamine blockers did not affect the ability of the pH sensor to detect placement accurately (Fisher's Exact Test, p 5.71) Use of these pH measurements eliminates the need for radiographic documentation of placement, provides a savings for the patient, and may be beneficial in promoting enteral feedings in critically ill patients.

Sinus arrest associated with continuous-infusion cimetidine.

The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.

Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial.

Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.

Treatment of urokinase-related anaphylactoid reaction with intravenous famotidine.

OBJECTIVE: We describe our experience with an anaphylactoid reaction to urokinase and the treatment used. We also discuss the use of histamine H1- and H2-blockers in combination for the treatment of allergic anaphylactoid reactions. DESIGN: Case report. SETTING: Hospital. PARTICIPANTS: Observation of a patient who had a pulmonary embolism. INTERVENTION: During the use of urokinase, in treatment of a pulmonary embolism, the patient developed an anaphylactoid reaction that did not respond to diphenhydramine or hydrocortisone. Famotidine was administered. RESULTS: Abatement of urticaria and normalization of vital signs were obtained soon after famotidine was given. Completion of thrombolysis took place. CONCLUSIONS: Further investigation of the use of H1- and H2-blocking agents in the presence of anaphylactoid reactions to thrombolytic agents should be performed. Consideration of intravenous famotidine for the treatment of anaphylactoid-type reactions to urokinase is suggested.

Hemodynamic status during famotidine infusion.

Histamine H2 antagonists, which reduce gastric acid secretion, are often used in the intensive care setting for the prophylaxis of stress ulcers. This double-blind, placebo-controlled study evaluated hemodynamic parameters in 11 stable, critically ill patients receiving famotidine. Repeated-measures ANOVA demonstrated that famotidine had no significant effect on baseline hemodynamic measurements and that there was no significant difference in hemodynamic values following the famotidine infusion as compared with NaCl 0.9% placebo (p greater than 0.05).

Fatal intrapartum pulmonary embolus during tocolysis.

Intrapartum pulmonary embolus, especially in association with hypercapnea, is an extremely dangerous situation requiring immediate detection and aggressive management. The predisposing factors of obesity and bed rest must be assessed, with strong consideration given to the use of prophylactic heparin.