A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry.

OBJECTIVE: Our purpose was to evaluate the subclinical occurrence of heparin-induced osteoporosis in pregnancy, by means of bone densitometry. STUDY DESIGN: A prospective, consecutive cohort of 14 pregnant women requiring heparin therapy and 14 pregnant controls matched for age, race, and smoking status was identified by 20 weeks' gestation at a university medical center. Proximal femur bone density measurements were taken at baseline, immediately post partum, and 6 months post partum in the cases and controls. Vertebral measurements were also obtained on both groups immediately post partum and 6 months post partum. Bone density as a function of heparin dosing and duration was examined. Nonparametric statistical tests were used for all comparisons. RESULTS: Five of 14 cases (36%) had a > or = 10% decrease from the baseline proximal femur measurements to immediate postpartum values versus none of the 14 matched controls (p = 0.04). Mean proximal femur bone density measurements also decreased in the cases (p = 0.01); this difference continued to be statistically significant 6 months post partum (p = 0.03). No dose-response relationship could be demonstrated. CONCLUSION: Heparin adversely affected bone density in about one third of exposed patients.

Research consent forms: continued unreadability and increasing length.

Consent forms are often long and incomprehensible. The authors studied 88 consecutive research consent forms generated at the Denver Veterans Administration Medical Center, evaluating the reading levels of the forms using the Fry Readability Scale and recording the numbers of lines of text. The mean grade reading level required for comprehension was 13.4 years of schooling. Twenty-two percent of all text passages scored were at the postgraduate level of readability. This difficult readability level has not improved since the forms were last tested in 1982. The mean length of the forms was 84.6 lines. Also found was a 58% increase in the length of forms since 1982, a factor known to impair comprehension. These factors, poor readability and increasing length, may make many consent forms incomprehensible. It is recommended that investigators be brief, use plain English, and write consent forms at appropriate reading levels, and receive training on how to obtain valid consent.

The natural history of medication compliance in a drug trial: limitations of pill counts.

To assess medication compliance over time, we prospectively performed pill counts among 121 ambulatory hypertensive subjects for less than or equal to 12 months. Prescribed regimens consisted of pinacidil or hydralazine administered four times a day and of secondary drugs administered up to twice daily. Surreptitious pill counts occurred every 1 to 12 weeks. Among a middle-aged subject group that had been selected for high rates of compliance, we observed mean compliance rates that approximated 100%. We noted marked intrasubject and intersubject variability for any one medication, between medications, and over time. From baseline blood pressures (+/- SE) of 155.5 +/- 1.9/97.3 +/- 1.0 mm Hg, subsequent mean blood pressures varied by compliance subgroup: "hypocompliers" (less than 80%), 151.3/91.0 mm Hg; "hypercompliers" (greater than or equal to 120%), 147.6/91.4 mm Hg; and "eucompliers" (80% to 119%), 143.3/88.5 mm Hg (systolic blood pressure: F1,52 = -220.9, NS; diastolic blood pressure: F1,52 = -121.4, NS). We concluded that weekly pill counts indicated marked intersubject and intrasubject variability, obscured by long-term averages; that compliance lapses appeared to be random; and that excessive medication-taking was the most consistent with "pill dumping."

Pill count measures of compliance in a drug trial: variability and suitability.

To evaluate pill counts as a compliance measure for drug trials, we followed 121 ambulatory hypertensives selected for good compliance over less than or equal to 12 months. The medication regimens consisted of either pinacidil or hydralazine as monotherapy or with propranolol and/or hydrochlorothiazide. Pill counts for the two primary drugs were obtained at each of the 20 return visits. The population was characterized by chronic uncomplicated hypertension and sociodemographic diversity; mean age was 53 years. Despite excellent average weekly pill counts (overall mean compliance rate [+/- SD] = 96.0 +/- 13.2%), we observed large intersubject and intrasubject variance in weekly pill count assessment: individuals' mean standard deviation = 13.7% (range = 0%-86%) and mean coefficient of variation = 0.138 (range = 0.001-0.410). By pill count, 35% of individuals exhibited greater than 110% compliance on at least 1 visit. We conclude that (a) pill count variability is large, even among highly selected subjects, (b) traditional reports of overall pill counts are suboptimal, and (c) pill counts may unreliably measure medication-taking behavior because "supranormal" compliance by this method is improbable but common.

A double-blind, randomized, controlled trial comparing pinacidil to hydralazine in essential hypertension.

Pinacidil is a direct vasodilator with good absorption, a half-life of 2 to 4 hours, and side effects similar to those of other vasodilators. We hypothesized that controlled-release pinacidil would be comparable to or better than hydralazine for blood pressure control and side effects. A double-blind, randomized trial comparing pinacidil with hydralazine when combined with hydrochlorothiazide or propranolol to control side effects or the diastolic blood pressure was performed. Pinacidil decreased systolic and diastolic blood pressure from 156/100 mm Hg to 132/81 mm Hg. The increase in heart rate and weight with both drugs was controlled with the additional drugs. There was 1/17 successes on monotherapy with both drugs. When combined with other drugs there were 15/18 successes with hydralazine and 16/20 successes with pinacidil. Side effects were typical of vasodilators. Both drugs acutely increased plasma norepinephrine and epinephrine during chronic therapy.

Effect of a sustained-release formulation of trimazosin in mild to moderate hypertension.

A single-blind study was conducted to evaluate the blood pressure (BP) reduction and side effects of a sustained-release (SR) formulation of trimazosin in patients with mild to moderate hypertension. Eighteen individuals (age, 21-65 yr; mean diastolic BP, greater than 95 mm Hg) with essential hypertension were enrolled into the study. Each patient's dose was titrated to a range of 150-900 mg/d, with polythiazide added as necessary to achieve BP control. Four hours following the maximum titrated dose of trimazosin, mean standing and supine diastolic BPs were significantly lower than baseline readings. Supine systolic BP and supine and standing heart rate were not significantly lower than baseline. At 24 hours after administration of the maximum dose, there were no significant differences in heart rate of BP compared with baseline readings. Five of 16 patients responded to trimazosin therapy alone. Of the 11 treatment failures with trimazosin alone, five were therapeutic failures and six discontinued because of side effects. Only two of these 11 patients achieved satisfactory results with the combination therapy. Trimazosin SR acutely lowers BP three to six hours after administration. It appears to have a duration of action longer than six hours, but it is not sustained for 24 hours. The proportion of patients failing to respond in this sample was very high and suggests that for similar patients, the drug does not appear to be a very useful antihypertensive agent.