The Precose Resolution of Optimal Titration to Enhance Current Therapies (PROTECT) study is an ongoing Phase IV clinical trial designed to assess the effectiveness, tolerability, and safety of acarbose tablets in patients with type II diabetes when the dosage is slowly titrated upward. This multicenter, open-label, 28-week trial will enroll approximately 7,000 type II diabetic patients. The present report describes the interim results for 2,139 patients who completed the trial as of November 1, 1996. Patients with type II diabetes enrolled in the study were inadequately controlled either with diet alone or with a sulfonylurea. The dosage of acarbose was titrated from 25 mg three times a day (TID) to 100 mg TID based on tolerability and efficacy. Efficacy of glycemic control was assessed by changes in glycated hemoglobin A1c (Hb A1c) and 1-hour postprandial plasma glucose (PPG) levels. Tolerability and safety were determined by patient reports of treatment-emergent adverse events and by review of laboratory tests. The PROTECT study confirms the previously demonstrated efficacy and safety of acarbose in improving glycemic control in patients with type II diabetes regardless of a patient's age, body weight, ethnic background, time since diagnosis, or severity of disease. mean 1-hour PPG levels declined throughout the entire treatment period, with a mean decrease from baseline of -47 mg/dL at the end of treatment. Hb A1c, the most reliable indicator of long-term glycemic control, decreased over the course of treatment, resulting in a mean decrease of -0.7% (P < 0.001). Although all patient types enrolled in the study responded positively to therapy, certain subgroups responded particularly well, such as those patients diagnosed with the disease less than 1 year ago, those treated with acarbose as monotherapy, and those with higher baseline Hb A1c levels. Adverse events were experienced by 36% of all patients and consisted primarily of gastrointestinal disturbances (flatulence, diarrhea, abdominal pain). Moderate renal insufficiency (serum creatinine levels between 1.5 and 2 mg/dL) was present in 259 patients, and no patients developed serum hepatic transaminase levels more than twice the normal range.

Acarbose↗

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Measurement scales and the age-complexity hypothesis.

The influences of the measurement scale on interpretations of age-related slowing are discussed. Although the customary practice is to describe performances as response latencies (sec/response), a plausible alternative is to describe performances as response speeds (responses/sec). Different scales may lead to contradictory conclusions because nonlinear transformations of time (such as speed) reduce or remove age x complexity interactions. Reconciliation is difficult because choice of measure appears more dependent on theoretical than psychometric considerations. Certain assumptions of cognitive theory require that untransformed response latencies serve as the dependent measure, whereas those of behavioral-learning approaches suggest scales that give increasing weight to latency reductions.

Aging↗

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Behavioral slowing and neuropsychological signs in a sample of active older men.

The neuropsychological test profiles of older men (62+) enrolled in a continuing education program differed from those of a comparison group of younger men, but fell well within the normal range. These findings ran counter to the assumption that characteristic and easily observed signs of brain dysfunction are a necessary accompaniment of old age. The further finding that the older men also were slower on digit symbol coding, a standard task used to measure behavioral slowing, was contrary to the hypothesis that slowing in the elderly reflects a developmental sequence of central nervous impairment, at least insofar as such impairment can be measured by neuropsychological tests. The good health and active lifestyles of the older sample may have played a role in forestalling neuropsychological signs otherwise seen among individuals their ages.

Adult↗

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Progress in ovarian cancer research: proceedings of the 5th Biennial Ovarian Cancer Research Symposium.

Ovarian cancer remains the most lethal gynecological malignancy. The 5th Biennial Symposium overviewed the progress of ovarian cancer research over the last few years. Molecularly based technologies have allowed the identification of multiple biomarkers to aid in ovarian cancer diagnosis and treatment. Furthermore, data analysis systems evaluating the behavior of these markers have been designed. Therapeutic use of ovarian cancer protein markers has been fueled by the development of animal models that more closely simulate the pathogenesis of ovarian cancer, and multiple new therapies are being developed that may have impact against the disease. Finally, the design of clinical trials both for ovarian cancer treatment and prevention are key in advancing the science of ovarian cancer into the clinic. The need for strategies that would optimize patient participation in clinical trials is paramount.

Biomarkers, Tumor↗

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Estimation of organ transport function for recirculating indicator dilution curves.

The transport function of an indicator through an organ allows the calculation of important physiological parameters, but its estimation, especially in the presence of recirculation, can be difficult. In this paper, we estimate the transport function of 3H-mannitol (an extracellular tracer of glucose) in the human leg skeletal muscle. To do so, an indicator bolus is administered into the femoral artery and its recirculating dilution curves are nonuniformly sampled in both the femoral artery and the femoral vein. A new deconvolution-based method is used to simultaneously estimate the indicator transport function and the organ plasma flow. Subsequently, the indicator mean transit time and distribution volume are calculated. The reliability of the method is assessed by Monte Carlo simulation. The ability to estimate parameters, like mean transit time and extracellular distribution volume, is critical to the study of pathophysiologic states such as diabetes, insulin resistance, and hypertension.

Bias↗

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