Chavezmattingly8486

Costly and lengthy clinical trials hinder the development of safe and effective treatments for postmenopausal osteoporosis. To reduce the expense associated with these trials, we established a mechanistic disease-drug trial model for postmenopausal osteoporosis that can predict phase 3 trial outcome based on short-term bone turnover marker data. To this end, we applied a previously developed model for tibolone to bisphosphonates using zoledronic acid as paradigm compound by (1) linking the mechanistic bone cell interaction model to bone turnover markers as well as bone mineral density in lumbar spine and total hip, (2) employing a mechanistic disease progression function, and (3) accounting for zoledronic acid's mechanism of action. Once developed, we fitted the model to clinical trial data of 581 postmenopausal women receiving (1) 5-mg zoledronic acid in year 1 and saline in year 2, (2) 5-mg zoledronic acid in year 1 and year 2, or (3) placebo (saline), calcium (500 mg), and vitamin D (400 IU). All biomarker data was fitted reasonably well, with no apparent bias or model misspecification. Age, years since menopause, and body mass index at baseline were identified as significant covariates. In the future, the model can be modified to explore the link between short-term biomarkers and fracture risk.Every woman, if she lives long enough, will transition into menopause, and as the US population ages, women will be spending more time in a postmenopausal state than before. For postmenopausal women, the decision to initiate menopausal hormone therapy should be individualized. A thorough evaluation of the patient's cardiovascular, venous thromboembolic, cancer, and fracture risk should be considered along with the woman's quality of life. Hormone therapy exerts its therapeutic effects on vasomotor symptoms, the skeleton, and the genitourinary system independent of age since menopause and these benefits are lost once hormone therapy is stopped. Here we review the pharmacologic properties dose, formulation, mode of administration, timing of initiation, and duration of hormonal therapies in regard to optimizing benefit and minimizing risk to the patient. This discussion will focus on the effects of common hormonal therapies including estrogen (local and systemic), progesterone, estrogen receptor agonist/antagonist, and local dehydroepiandrosterone and include a brief review of compounded bioidentical hormone therapy.This systematic review evaluates the efficacy of intravaginal diazepam in treating chronic pelvic pain and sexual dysfunction associated with high-tone pelvic floor dysfunction. A literature search was conducted in Medline and Web of Science, including articles from the database's inception to July 2019. The search identified 126 articles, and 5 articles met study inclusion criteria 2 observational reviews and 3 small randomized, controlled trials (RCTs) evaluating intravaginal diazepam for high-tone pelvic floor dysfunction. Z-VAD-FMK Caspase inhibitor The 2 observational studies identified subjective reports of improvement in sexual function for a majority of women, 96% and 71%, in each study. However, there were no statistical differences between Female Sexual Function Index (FSFI) and Visual Analog Scale (VAS) scores for pain identified. One RCT found no significant changes between groups in median FSFI or VAS scores, and a second RCT found no significant changes between groups in 100-mm VAS scores. The third RCT demonstrated that compared with placebo, treatment with transcutaneous electrical nerve stimulation and intravaginal diazepam for women with vestibulodynia and high-tone pelvic floor dysfunction yielded significant differences in reduction of dyspareunia (P ≤ .05), ability to relax pelvic floor muscles after contraction (P ≤.05), and current perception threshold values at a 5-Hz stimulation related to C fibers (P less then .05), but no significant changes in 10-cm VAS scores. Intravaginal diazepam may be helpful in women with a specific diagnosis of high-tone pelvic floor dysfunction, but more and larger studies are needed to confirm these potential effects.The prevalence of rheumatoid arthritis (RA) is higher in females than in males. With the development of new treatment options and strategies such as biologics, we found it worthwhile to identify whether males and females warrant different treatment regimens to ensure the best clinical response. Our meta-analysis included 11 clinical trials of RA patients in support of the Food and Drug Administration's approval of 6 biological products. We evaluated the data of American College of Rheumatology 20 (ACR20) 24 or 26 weeks after treatment. Logistic regression models were applied to compute the odds ratio (OR) of treatment responses between sexes. The ORs of ACR20 response rates in males and females were similar across all studies and not significantly different in overall studies (OR, 1.05; 95% confidence interval, 0.96-1.16) analyzed with a fixed-effects model. Further analyses on the 7 ACR20 subcomponents showed high heterogeneity among studies (Q statistic P 95%), with no observed clinically meaningful sex-related difference. Thus, our meta-analysis did not find significant difference in ACR20 response rates between male and female RA patients treated with biologics at approved dosing regimens. This result supports the current clinical practice of not requiring sex-dependent treatment regimens for RA patients.Oral contraceptives (OCs) are the most widely used form of birth control among women of childbearing potential. Knowledge of potential drug-drug interactions (DDIs) with OCs becomes imperative to provide information on the medication to women of childbearing potential and enable their inclusion in clinical trials, especially if the new molecular entity is a teratogen. Although a number of DDI guidance documents are available, they do not provide recommendations for the design and conduct of OC DDI studies. The evaluation of DDI potential of a new molecular entity and OCs is particularly challenging because of the availability of a wide variety of combinations of hormonal contraceptives, different doses of the ethinyl estradiol, and different metabolic profiles of the progestin component. The aim of this review is to comprehensively discuss factors to be considered such as pharmacokinetics (PK), pharmacodynamics (PD), choice of OC, and study population for the conduct of in vivo OC DDI studies. In this context, metabolic pathways of OCs, the effect of enzyme inhibitors and inducers, the role of sex hormone-binding globulin in the PK of progestins, current evidence on OC DDIs, and the interpretation of PD end points are reviewed.