cardiovascular-agents and Central-Nervous-System-Diseases

There are several challenging statistical problems identified in the regulatory review of large cardiovascular (CV) clinical outcome trials and central nervous system (CNS) trials. The problems can be common or distinct due to disease characteristics and the differences in trial design elements such as endpoints, trial duration, and trial size. In schizophrenia trials, heavy missing data is a big problem. In Alzheimer trials, the endpoints for assessing symptoms and the endpoints for assessing disease progression are essentially the same; it is difficult to construct a good trial design to evaluate a test drug for its ability to slow the disease progression. In CV trials, reliance on a composite endpoint with low event rate makes the trial size so large that it is infeasible to study multiple doses necessary to find the right dose for study patients. These are just a few typical problems. In the past decade, adaptive designs were increasingly used in these disease areas and some challenges occur with respect to that use. Based on our review experiences, group sequential designs (GSDs) have borne many successful stories in CV trials and are also increasingly used for developing treatments targeting CNS diseases. There is also a growing trend of using more advanced unblinded adaptive designs for producing efficacy evidence. Many statistical challenges with these kinds of adaptive designs have been identified through our experiences with the review of regulatory applications and are shared in this article.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Central Nervous System Diseases; Clinical Trials as Topic; Humans; Research Design; Treatment Outcome

Uncaria species (Gouteng in Chinese) have been used as a plant medicine to treat ailments of cardiovascular and central nervous systems. As the main alkaloid constituent of Uncaria species, isorhynchophylline has drawn extensive attention toward antihypertensive and neuroprotective activities in recent years. Isorhynchophylline mainly acts on cardiovascular and central nervous systems diseases including hypertension, brachycardia, arrhythmia, and sedation, vascular dementia, and amnesia. Isorhynchophylline also has effects on anticoagulation, inhibition vascular smooth muscle cell apoptosis and proliferation, anti-multidrug resistant of lung cells, anti-endotoxemic, and antispasmodic. The active mechanisms are related to modulation on calcium ion channel, protection neural and neuroglial cells against β-amyloid(25-35)-induced neurotoxicity and via inducing autophagy. As a candidate drug of several cardiovascular and central nervous systems diseases, isorhynchophylline will attract scientists to pursue the potential related pharmacological effects and its mechanism with new technologies. But relatively few clinical application of isorhynchophylline has been conducted on its pharmacological activities. It requires more in vivo validations and further investigations of antihypertensive and neuroprotective mechanisms of isorhynchophylline.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Diseases; Humans; Indole Alkaloids; Neuroprotective Agents; Oxindoles; Phytotherapy; Plant Extracts; Uncaria

To evaluate whether use of certain medications with potential urological effects is associated with development of incident urinary incontinence in community-resident older women.. Longitudinal cohort study.. Pittsburgh, PA, and Memphis, TN.. Nine hundred fifty-nine healthy black and white women aged 65 and older enrolled in the Health, Aging and Body Composition Study without baseline (Year 1) self-reported urinary incontinence.. Use of alpha blockers, anticholinergics, central nervous system medications (opioids, benzodiazepines, antidepressants, antipsychotics), diuretics (thiazide, loop, potassium sparing), and estrogen (all dosage forms) was determined during Year 3 interviews. Self-reported incident (≥ weekly) incontinence in during the previous 12 months was assessed at Year 4 interviews.. Overall, 20.5% of these women reported incident incontinence at Year 4 (3 years from baseline). The most common medication used with potential urological activity was a thiazide diuretic (24.3%), followed by estrogen (22.2%); alpha blockers were the least commonly used (2.3%). Multivariable logistic regression analyses revealed that current users of alpha blockers (adjusted odds ratio (AOR)=4.98, 95% confidence interval (CI)=1.96-12.64) and estrogen (AOR=1.60, 95% CI=1.08-2.36) had a greater risk of urinary incontinence than nonusers. There was no greater risk (P>.05) of urinary incontinence with the current use of anticholinergics, central nervous system medications, or diuretics. No statistically significant race-by-medication use interactions were found (all P>.05).. These results corroborate earlier reports that, in elderly women, use of alpha blockers or estrogens is associated with risk of self-reported incident urinary incontinence.

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Central Nervous System Diseases; Female; Follow-Up Studies; Humans; Incidence; Prognosis; Retrospective Studies; Risk Factors; Surveys and Questionnaires; Time Factors; United States; Urinary Incontinence; Urodynamics

The records of 268 patients were used to assess the effects of five disease/drug complexes on the number of postinsertion visits in complete denture wearers. The data were analyzed with SAS and BMDP computer packages. The results showed a statistically significant increase in the number of postinsertion visits in patients who had central nervous system or psychiatric disorders. Practitioners are alerted to consider the ergonomic implications at the outset of treatment.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Central Nervous System Diseases; Chi-Square Distribution; Dental Care for Aged; Dental Care for Chronically Ill; Denture Retention; Denture, Complete; Diabetes Complications; Diabetes Mellitus; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Masticatory Muscles; Mental Disorders; Metabolic Diseases; Middle Aged; Mouth Diseases; Movement; Office Visits; Pain; Prosthesis Fitting; Respiratory Tract Diseases; Retrospective Studies; Xerostomia

Topics: Cardiovascular Agents; Central Nervous System Diseases; Muscle Relaxants, Central; Muscle Spasticity; Spasm; Syndrome

Topics: Cardiovascular Agents; Central Nervous System Diseases; Humans; Muscle Relaxants, Central; Muscle Spasticity; Syndrome