Can an Emergency Department-Initiated Intervention Prevent Subsequent Falls and Health Care Use in Older Adults? A Randomized Controlled Trial.

STUDY OBJECTIVE: 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 (n=55), intervention participants (n=55) 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.

PRECISE-DAPT and ARC-HBR Predict in-Hospital Outcomes in Patients Who Underwent Percutaneous Coronary Intervention.

Bleeding events result in morbidity and mortality in patients who underwent percutaneous coronary intervention (PCI). There are limited data on the predicting bleeding complications in patients who underwent stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) and Academic Research Consortium for High Bleeding Risk (ARC-HBR) scores' ability to predict in-hospital outcomes in patients who underwent PCI. Consecutive patients who underwent PCI at tertiary centers from January 2016 to March 2018 were identified and the bleeding risk scores were calculated. The primary end point was the National Cardiovascular Data Registry-defined in-hospital bleeding stratified by low versus high predicted bleeding risk. The major and net adverse cardiovascular events were also examined. The discriminatory ability of the risk models was determined using receiver operating characteristic curves. Among 3,659 patients studied, the in-hospital major bleeding was 3.3% (n = 121). The patients characterized as high bleeding risk by either criterion had significantly higher bleeding rates than those meeting the low-risk criteria (ARC-HBR 5.4% vs 3.3%, p <0.001; PRECISE-DAPT 5.8% vs 2.4%, p <0.001), and higher major adverse cardiovascular events and net adverse clinical events. These risk estimates showed moderate and similar predictive ability (ARC-HBR high-risk area under the receiver operating characteristic curve [AUC] 0.62, PRECISE-DAPT ≥25 AUC 0.61, p = 0.49), with no incremental benefit to adding the estimates (AUC 0.60). The subgroup analysis revealed that women had higher bleeding rates than men (5.53% vs 2.39%, p <0.001); however, the predictive ability of the criteria were similar in women and men. The patients identified as having a high bleeding risk by the PRECISE-DAPT and the ARC-HBR criteria before PCI are at high risk for in-hospital bleeding and adverse outcomes independent of gender. The 2 scores have moderate predictive ability for bleeds. Further study is needed to determine strategies to reduce risk in this population.

Predictors of In-Hospital De-Escalation of P2Y12 Inhibitors to Clopidogrel in Patients With Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention.

BACKGROUND: Ticagrelor or prasugrel are recommended to reduce ischemic events in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, in clinical practice, patients are often switched from a potent P2Y12 inhibitor to clopidogrel prior to or at discharge ('de-escalation'). We sought to assess the incidence and predictors of de-escalation. METHODS: Consecutive patients who received either a ticagrelor or prasugrel loading dose for AMI PCI at two tertiary centers between Jan 2015-Mar 2019 who survived to discharge were included. Data were obtained from the electronic health record and institutional NCDR CathPCI data. Patients who were de-escalated to clopidogrel were compared with those who remained on potent P2Y12 inhibitors through the time of discharge. RESULTS: Of the1818 patients in the cohort, 1146 (63%) were de-escalated. Patients in the de-escalation group were older, more often Black, had lower prevalence of co-morbidities, less often had private insurance, and had less complex PCI. After adjustment, older age remained positively associated (OR 1.2, CI 1.08-1.34, p = .001) and Caucasian race (OR 0.5, CI 0.33-0.77, p = .002), prior MI (OR 0.7, CI 0.5-0.97, p = .032), bifurcation lesion (OR 0.71, CI 0.53-0.95, p = .019), and greater number of stents (OR 0.82, CI 0.75-0.91, p = .0001) were negatively associated with de-escalation. In de-escalated patients, the rationale was not documented in 75.9% of cases. CONCLUSIONS: De-escalation occurred frequently in patients with AMI and was associated with both non-clinical and clinical factors. Medical decision making was poorly documented and represent an area for improvement.

Ovarian hormones modulate multidrug resistance transporters in the ovary.

BACKGROUND: Multidrug 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. METHODS: Here 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. RESULTS: We 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. CONCLUSIONS: Progesterone 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.

Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology.

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 17ß-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.