We determine whether an emergency department (ED)-initiated fall-prevention intervention can reduce subsequent fall-related and all-cause ED visits and hospitalizations in older adults. Methods:The Geriatric Acute and Post-acute Fall Prevention intervention was a randomized controlled trial conducted from January 2018 to October 2019. Participants at 2 urban academic EDs were randomly assigned (1:1) to an intervention or usual care arm. Intervention participants received a brief, tailored, structured, pharmacy and physical therapy consultation in the ED, with automated communication of the recommendations to their primary care physicians.Results: Of 284 study-eligible participants, 110 noninstitutionalized older adults (65 years) with a recent fall consented to participate; median age was 81 years, 67% were women, 94% were white, and 16.3% had cognitive impairment. Compared with usual care participants (n¼55), intervention participants (n¼55) were half as likely to experience a subsequent ED visit (adjusted incidence rate ratio 0.47 [95% CI 0.29 to 0.74]) and one third as likely to have fall-related ED visits (adjusted incidence rate ratio 0.34 [95% CI 0.15 to 0.76]) within 6 months. Intervention participants experienced half the rate of all hospitalizations (adjusted incidence rate ratio 0.57 [95% CI 0.31 to 1.04]), but confidence intervals were wide. There was no difference in fall-related hospitalizations between groups (adjusted incidence rate ratio 0.99 [95% CI 0.31 to 3.27]). Self-reported adherence to pharmacy and physical therapy recommendations was moderate; 73% of pharmacy recommendations were adhered to and 68% of physical therapy recommendations were followed. Conclusion:Geriatric Acute and Post-acute Fall Prevention, a postfall, in-ED, multidisciplinary intervention with pharmacists and physical therapists, reduced 6-month ED encounters in 2 urban EDs. The intervention could provide a model of care to other health care systems aiming to reduce costly and burdensome fall-related events in older adults. [

Ovarian protection from chemotoxicity is essential for reproductive health. Our objective is to determine the role of ATP-dependent, Multidrug Resistance Transporters (MDRs) in this protection. Previously we identified MDR-dependent cytoprotection from cyclophosphamide in mouse and human oocytes by use of MDR inhibitors. Here we use genetic deletions in MDR1a/b/BCRP of mice to test MDR function in ovarian somatic cells and find that mdr1a/b/bcrp−/− mice had significantly increased sensitivity to cyclophosphamide. Further, estrus cyclicity and follicle distribution in mdr1a/b/bcrp−/− mice also differed from age-matched wildtype ovaries. We found that MDR gene activity cycles through estrus and that MDR-1b cyclicity correlated with 17β-estradiol surges. We also examined the metabolite composition of the ovary and learned that the mdr1a/b/bcrp−/− mice have increased accumulation of metabolites indicative of oxidative stress and inflammation. We conclude that MDRs are essential to ovarian protection from chemotoxicity and may have an important physiological role in the ovary.

BackgroundMultidrug resistance transporters (MDRs) are transmembrane proteins that efflux metabolites and xenobiotics. They are highly conserved in sequence and function in bacteria and eukaryotes and play important roles in cellular homeostasis, as well as in avoidance of antibiotics and cancer therapies. Recent evidence also documents a critical role in reproductive health and in protecting the ovary from environmental toxicant effects. The most well understood MDRs are MDR-1 (P-glycoprotein (P-gp) also known as ABCB1) and BCRP (breast cancer resistance protein) and are both expressed in the ovary. We have previously shown that MDR-1 mRNA steady state expression changes throughout the murine estrous cycle, but expression appears to increase in association with the surge in estradiol during proestrus.MethodsHere we test the model that MDR-1 and BCRP are regulated by estrogen, the major hormonal product of the ovary. This was performed by administering 6-week-old female mice either sesame oil (vehicle control) or oral ethinyl estradiol at 1 μg, 10 μg, and 100 μg or PROGESTERONE at 0.25mg, 0.5 mg or 1 mg or a combination of both for 5 days. The mice were then sacrificed, and the ovaries were removed and cleaned. Ovaries were used for qPCR, immunoblotting, and immnunolabeling.ResultsWe found that oral ethinyl estradiol did not influence the steady state mRNA of MDR-1 or BCRP. Remarkably, the effect on mRNA levels neither increased or decreased in abundance upon estrogen exposures. Conversely, we observed less MDR-1 protein expression in the groups treated with 1 μg and 10 μg, but not 100 μg of ethinyl estradiol compared to controls. MDR-1 and BCRP are both expressed in pre-ovulatory follicles. When we tested progesterone, we found that MDR-1 mRNA increased at the dosages of 0.25 mg and 0.5 mg, but protein expression levels were not statistically significant. Combined oral ethinyl estradiol and progesterone significantly lowered both MDR-1 mRNA and protein.ConclusionsProgesterone appears to influence MDR-1 transcript levels, or steady state levels. This could have implications for better understanding how MDR-1 can be modulated during times of toxic exposure. Understanding the normal physiology of MDR-1 in the ovary will expand the current knowledge in cancer biology and reproduction.Electronic supplementary materialThe online version of this article (10.1186/s40834-018-0076-7) contains supplementary material, which is available to authorized users.