Balance algorithm for cluster randomized trials

Background  

Within cluster randomized trials no algorithms exist to generate a full enumeration of a block randomization, balancing for covariates across treatment arms. Furthermore, often for practical reasons multiple blocks are required to fully randomize a study, which may not have been well balanced within blocks.     

Some behavioral effects of repeated d-amphetamine administrations

Effects of daily administrations of d-amphetamine were studied on key peck responses of pigeons maintained under a multiple fixed-interval 2-min, fixed-ratio 30-responseschedule. Under the fixed-interval schedule, a pause was followed by a transition to increasing rates of responding until food presentation. Under the fixed-ratio schedule, higher sustained rates of responding were maintained. Low to intermediate doses (0.3-1.0 mg/kg) of d-amphetamine changed the temporal patterns and occasionally increased rates of responding under the fixed-interval schedule. Higher doses decreased rates of responding under bothschedules. With daily injections of 1.0 mg/kg d-amphetamine prior to experimental sessions, the effects of this dose on rates and patterns of responding were attenuated, and d-anphetamine dose-effect curves were shifted to the right, primarily under the fixed-ratio schedule. Similar results were obtained with daily presession injections of 5.6 mg/kg d-amphetamine in a second group of pigeons, except that rates of responding under both schedules were decreased by this daily dose, and did not return completely to control values with repeated injections. In a third group of pigeons, 1.0 mg/kg d-amphetamine administered daily, after experimental sessions, did not alter dose-effect functions for d-amphetamine. In a second experiment, pigeons were trained to peck one response key when given 1.0 mg/kg d-amphetamine and a different key when given presession water injections. Increasing doses of d-amphetamine produced incresing percentages of d-amphetamine-key responses. Repeated administration of 5.6 mg/kg d-amphetamine shifted these dose-effect functions to the right one-half log unit. Results suggested that decreases in reinforcement frequency are not a necessary condition for the development of behavioral tolerance to d-amphetamine.     

A random coefficient growth curve analysis of mental development in low-birth-weight infants.

In many medical studies, longitudinal data are collected on each of a sample of patients. The objectives of such studies often are: to estimate and test bivariate or multivariate relationships within each of several groups of patients from these repeated measures data; to compare these relationships among groups; and to test for the effects of baseline covariates on the relationships. This paper illustrates the use of statistical methods for growth curve analysis recently proposed by Vonesh and Carter for achieving these goals by relating a measure of preschool cognitive development to age in four race by sex groups of low-birth-weight infants. Significant declines in Bayley's Mental Development Index (MDI) with increasing age were found in all groups. Birth-weight did not significantly influence the rate of decline but did influence the overall level of performance. Even so, in the group most comparable to Bayley's normative population, predicted MDI was near the norm even for extremely low-birth-weight infants (that is, 1000 grams). Although there is some risk of mental deficit associated with prematurity, eventual developmental delays in low-birth-weight infants frequently are acquired with age. The rate of decline in MDI was significantly associated with race and mother's education. Assumptions required for the valid application of these methods are discussed and tested in the setting of this applied problem. The assumptions appeared valid in this application. We conclude with a brief discussion of available alternatives when the assumptions are violated and point to areas for future research.     

Skin cancer in the elderly

This article discusses the relation between aging and development of nonmelanoma skin cancer. Possible age-related risk factors for development of such cancers are cumulative exposure to ultraviolet irradiation from the sun, decreased DNA repair capacity, decreased immunosurveillance, reduced melanocyte density, and altered dermal matrix. Clinical features of basal-cell carcinoma, squamous-cell carcinoma, and keratoacanthoma are discussed.     

Evaluation of Hypertensive Patients after Care Provided by Community Pharmacists in a Rural Setting

We evaluated blood pressure control, quality of life, quality of care, and satisfaction of patients who were monitored by specially trained community pharmacists in a group medical practice. After participating in an intensive skill development program, pharmacists performed in an interdisciplinary team in a rural clinic. The primary objective was assessed by evaluating outcome variables at 6 months compared with baseline in 25 patients randomly assigned to a study group. A control group of 26 patients was also evaluated to determine if outcome variables remained constant from baseline to 6 months. Systolic blood pressure was reduced in the study group (151 mm Hg baseline, 140 mm Hg at 6 mo, p<0.001) and diastolic blood pressure was significantly lower at 2, 4, and 5 months compared with baseline. Ratings from a blinded peer review panel indicated significant improvement in the appropriateness of the blood pressure regimen, going from 8.7 ± 4.7 to 10.9 ± 4.5 in the study group (p<0.01), but they did not change in the control group. Several quality of life scores improved significantly in the study group after 6 months (p<0.05). These included physical functioning (61.6 vs 70.7), physical role limitations (56.8 vs 72.8), and bodily pain (60.0 vs 71.7) at baseline and 6 months, respectively. There were no significant changes in the control group. Patient satisfaction scores were consistently higher in the study group at the end of the study. Our results indicate that when community pharmacists in a clinic setting are trained and included as members of the primary care team, significant improvements in blood pressure control, quality of life, and patient satisfaction can be achieved.     

Conservatively Treated Breast Cancer: Outcome by Histologic Subtype

Abstract: Between 1970 and 1990, 1,008 patients with early-stage breast cancer were treated by conservative surgery without axillary dissection followed by radiation therapy to the intact breast in the Department of Therapeutic Radiology at Yale-New Haven Hospital. The patient population, broken down by histologic subtype, was as follows: 761 patients presented with infiltrating ductal carcinoma, 70 patients with pure intraductal, 38 intraductal with focal invasion, 54 infiltrating lobular, 21 tubular, 17 medullary, 16 mucinous, and 29 with other various histologic subtypes. Patients were followed on a regular basis by the referring physicians and radiation oncologists. Diagnostic studies for distant metastases were performed as clinically indicated. Annual mammography was a routine component of the follow-up program. As of 3/96, with a median follow-up of 10.5 years, 83 patients developed an ipsilateral breast tumor recurrence, and 109 patients developed distant metastases resulting in an overall 10-year breast recurrence-free rate of 84%, and a 10-year distant metastasis-free rate of 78%. There were significant differences in clinical stage, pathological nodal involvement, and administration of systemic therapy between various histologic subtypes. As expected, those patients with histologies of low metastatic potential (such as intraductal, tubular, and mucinous) had significantly superior distant recurrence-free survival rates. With respect to breast relapse rates, there were no statistically significant differences in the 5- and 10-year breast recurrence-free rates between any of the histologic subtypes. Patients with intraductal carcinoma with or without focal invasion had similar breast relapse rates as those with other histologic subtypes. Patients with lobular carcinoma in situ as a histologic component also had a similar overall breast relapse-free recurrence rate. In conclusion, long-term follow-up of conservatively treated breast cancer patients demonstrates no significant differences in ipsilateral breast tumor recurrence rates between various histologic subtypes. There are no histologies which had a statistically significantly higher breast-relapse rate than infiltrating ductal carcinomas and therefore no primary histologic subtype represents a relative contraindication to breast conservation therapy.     

Effects of Pravastatin on Plasma Lipid Concentrations in Poloxamer 407-Induced Hyperlipidemic Rats

A new animal model of hyperlipidemia is being developed using the nonionic surfactant poloxamer 407 (P-407). We investigated the impact of pravastatin on P-407-induced hyperlipidemia. Twenty rats received P-407 300 mg intraperitoneally to induce hyperlipidemia, and 20 control rats received saline injection. Pravastatin was administered orally to an equal number of rats in both groups using three different regimens. A fourth group did not receive pravastatin. At 24 hours after injection, total cholesterol levels in two of the pravastatin groups were 28% and 34% lower than those in animals that did not receive pravastatin (p≤0.01). At 48 hours, triglyceride levels were significantly lower in all pravastatin groups (21–44%) versus animals not receiving pravastatin. Pravastatin diminished the effects of P-407 on lipoproteins. This new animal model may be useful in screening for investigational antihyperlipidemic agents.