Reliability, validity, and responsiveness of the lower extremity measure for patients with a hip fracture.

BACKGROUND: The purpose of this study was to determine whether currently published outcome measures of physical function would be suitable for use for older adults with a hip fracture. The measures that were considered were the Musculoskeletal Function Assessment (MFA) Instrument, the Older Americans' Resources and Services (OARS) Multidimensional Functional Assessment Questionnaire physical function subscale, the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36). Following suggestions by an expert panel and patient interviews, the MFA was not tested further. The TESS was modified and renamed the Lower Extremity Measure (LEM). METHODS: Forty-three community-dwelling patients with a hip fracture completed the LEM, OARS, and SF-36 in the hospital so that the prefracture status could be obtained; they were then followed prospectively at six weeks and at six months. All patients were interviewed twice in the hospital to assess the reliability of the LEM (intraclass correlation coefficient = 0.85). To establish criterion validity, the measures were compared with the Timed Up and Go (TUG) test at six weeks. We tested a number of hypotheses to determine construct validity. RESULTS: Only the LEM scores were significantly correlated with the TUG scores (r = -0.53, p = 0.03). The LEM scores were significantly correlated with the SF-36 subscale scores and the OARS scores. Patients with at least one comorbidity had a lower mean prefracture LEM score (90.0 +/- 9.7) than patients with no comorbidity (96.9 +/- 8.1) (p = 0.02). Patients who had used no walking aids before the fracture had a higher mean prefracture LEM score than those who had used a cane (95.5 +/- 5.8 compared with 85.5 +/- 12.7; p = 0.0007). Both the LEM and the SF-36 scores changed significantly between all of the time-periods (p < 0.05). Measures of responsiveness indicated that the LEM was the best measure for detecting changes in physical function. CONCLUSIONS: The LEM can detect clinically important changes in physical function over time in patients with a hip fracture and would be most useful for clinical trials or cohort studies. Orthopaedists who are currently utilizing the SF-36 can be reassured that the physical function subscale is a valid measure for patients with a hip fracture.

Antianginal efficacy and safety of controlled-delivery diltiazem QD versus an equivalent dose of immediate-release diltiazem TID.

Controlled-delivery once-daily diltiazem (qd), 180 mg and 360 mg, was assessed in two multicenter, randomized, double-blind, placebo-controlled trials using a 3 x 3 Latin square design. Both studies compared the controlled-delivery dosage form to the same total daily dose of immediate-release diltiazem administered three times daily (tid) and to placebo. The primary measure of efficacy was the time to termination of the exercise tolerance test (ETT) at 2, 8, and 24 hours after the morning dose. There were no significant differences in time to ETT termination between the qd and tid formulations at any time, except at 24 hours with 180 mg qd versus 60 mg tid. The comparison to placebo showed that diltiazem 180 mg qd, 360 mg qd, and 120 mg tid significantly lengthened the time to ETT termination (p < 0.05) at all time points, while diltiazem 60 mg tid did not differ from placebo at any time point. The qd formulation also increased the time to 1-mm ST-segment depression and reduced the number of angina attacks and the amount of nitroglycerin used when compared to placebo. No new or unusual adverse events were noted. Diltiazem controlled-release capsules administered once daily are safe and effective for the treatment of patients with chronic stable angina.

Diltiazem pharmacokinetics in elderly volunteers after single and multiple doses.

In young healthy volunteers diltiazem does not have linear kinetics between single and multiple doses. Elimination half-life increases and gives AUC's and Cmax higher than those predicted from single dose data. Kinetics of diltiazem were assessed in 16 healthy elderly after a single 60 mg dose and in 24 healthy elderly after 60 mg every 8 h for 7 days. Thirteen participants completed both studies. Elimination half-life, AUC0-24, AUC0-infinity, and Cmax were (mean +/- SE) 7.4 (1.2) h, 349 (34) ng/ml.h, 392 (44) ng/ml.h, and 43 (5) ng/ml respectively after a single dose. After multiple doses elimination half-life, AUC0-48, AUC0-infinity, Cmax and Cmin were respectively 5.7 (0.3) h, 974 (107) ng/ml.h, 1022 (108) ng/ml.h, 102 (7) ng/ml and 43 (5) ng/ml. Exploratory statistics on the 13 volunteers common to both studies showed that the ratio of AUC desacetyl-diltiazem (DAD)/AUC diltiazem rose between single and multiple doses while elimination half-life of both diltiazem and N-desmethyl-diltiazem (MA), tmax, and AUC MA/AUC diltiazem were not affected. The conclusion of this study is that elimination half-life of diltiazem does not increase in elderly between single and multiple doses, possibly due to an increased biotransformation into DAD.

Diltiazem pharmacokinetics in elderly volunteers after single and multiple doses.

In young healthy volunteers diltiazem does not have linear kinetics between single and multiple doses. Elimination half-life increases and gives AUC's and Cmax higher than those predicted from single dose data. Kinetics of diltiazem were assessed in 16 healthy elderly after a single 60 mg dose and in 24 healthy elderly after 60 mg every 8 h for 7 days. Thirteen participants completed both studies. Elimination half-life, AUC0-24, AUC0-infinity, and Cmax were (mean +/- SE) 7.4 (1.2) h, 349 (34) ng/ml.h, 392 (44) ng/ml.h, and 43 (5) ng/ml respectively after a single dose. After multiple doses elimination half-life, AUC0-48, AUC0-infinity, Cmax and Cmin were respectively 5.7 (0.3) h, 974 (107) ng/ml.h, 1022 (108) ng/ml.h, 102 (7) ng/ml and 43 (5) ng/ml. Exploratory statistics on the 13 volunteers common to both studies showed that the ratio of AUC desacetyl-diltiazem (DAD)/AUC diltiazem rose between single and multiple doses while elimination half-life of both diltiazem and N-desmethyl-diltiazem (MA), tmax, and AUC MA/AUC diltiazem were not affected. The conclusion of this study is that elimination half-life of diltiazem does not increase in elderly between single and multiple doses, possibly due to an increased biotransformation into DAD.

Early nonhemorrhagic cardiac tamponade complicating acute myocardial infarction: a case report and review of the literature.

Pericarditis and small pericardial effusions frequently occur following acute myocardial infarction (AMI). A case is reported in which nonhemorrhagic cardiac tamponade complicated AMI within three days of the acute event. In such cases the placement of a pericardial drainage catheter may obviate the need for repeated pericardiocentesis.

Two-dimensional echocardiographic detection of left pulmonary artery aneurysm following Potts' anastomosis.

The two-dimensional echocardiographic detection of left pulmonary artery aneurysm following a Pott's anastomosis in a patient with tetralogy of Fallot is described. The diagnosis was confirmed at angiography and surgery.

Pharmacokinetic and pharmacodynamic studies with prazosin in chronic heart failure.

The correlation between the plasma concentration of prazosin and the effects on supine and standing systemic blood pressure and heart rate was examined at 1/2, 1, 2, 4, and 8 hr after single oral doses of 0.5, 1, 2, and 4 mg in 8 patients with severe refractory heart failure due to coronary heart disease. Despite wide between-patient and within-patient variation in the plasma concentration, the grouped results showed a significant linear relationship between dose, peak concentration, and area under the time-concentration curve. Time of maximum plasma concentration (2 hr) and half-life in plasma (5.6 hr) were similar after all four doses. Compared to the reported pharmacokinetic profile of the drug in normal subjects, the plasma clearance of the drug in these patients in heart failure was substantially reduced. In the recumbent posture there were reductions in systolic and diastolic blood pressure without consistent changes in heart rate after all doses of prazosin. A clear dose-response effect of the drug on both variables only became apparent during standing, when there was a significant correlation between dose, the postural fall in systolic and diastolic blood pressure, and the increase in heart rate. Three of the 8 patients were unable to tolerate more than 1 mg prazosin due to postural hypotension.