Running title: Prevention of menstrual migraine

Prevention of menstrual migraine with perimenstrual transdermal 17-beta-estradiol: a randomized, placebo-controlled, double-blind crossove

The Lost World of Administrative Law

The reality of the modern administrative state diverges considerably from the series of assumptions underlying the Administrative Procedure Act (APA) and classic judicial decisions that followed the APA reviewing agency actions. Those assumptions call for statutory directives to be implemented by one agency led by Senate-confirmed presidential appointees with decision-making authority. The implementation (in the form of a discrete action) is presumed to be through statutorily mandated procedures and criteria, with judicial review to determine whether the reasons given by the agency at the time of its action match the delegated directions. This is the lost world of administrative law, though it is what students largely still learn. Today, there are often statutory and executive directives to be implemented by multiple agencies often missing confirmed leaders, where ultimate decision-making authority may rest outside of those agencies. The process of implementation is also through mandates in both statutes and executive orders, where the final result faces limited, if any, oversight by the courts. The mismatch has consequences for the legitimacy and efficacy of the federal bureaucracy: some positive, many negative. Because we do not think a return to the lost world is possible or perhaps even desirable, we propose some possible reforms in all three branches of the federal government to strengthen the match between current realities and administrative law and to further administrative law's objectives of transparency, rule of law, and reasoned implementation of statutory mandates. We also hope that the proposed reforms can help foster the public interest goals of modern regulation, such as environmental quality or financial stability. We realize that many scholars and probably at least some judges are aware that formal administrative procedures, official records, and judicial review are only part of the dynamics of administrative governance. But administrative law, as developed by the courts and in governing statutes, has not meaningfully confronted the contemporary realities of the administrative state. It thus risks becoming irrelevant to the quality of governance

Therapy limitation in octogenarians in German intensive care units is associated with a longer length of stay and increased 30 days mortality: a prospective multicenter study

Purpose: The approach to limit therapy in very old intensive care unit patients (VIPs) significantly differs between regions. The focus of this multicenter analysis is to illuminate, whether the Clinical Frailty Scale (CFS) is a suitable tool for risk stratification in VIPs admitted to intensive care units (ICUs) in Germany. Furthermore, this investigation elucidates the impact of therapeutic limitation on the length of stay and mortality in this setting. Methods: German cohorts' data from two multinational studies (VIP-1, VIP-2) were combined. Univariate and multivariate logistic regression were used to evaluate associations with mortality. Results: 415 acute VIPs were included. Frail VIPs (CFS > 4) were older (85 [IQR 82–88] vs. 83 [IQR 81–86] years p <.001) and suffered from an increased 30-day-mortality (43.4% versus 23.9%, p <.0001). CFS was an independent predictor of 30-day-mortality in a multivariate logistic regression model (aOR 1.23 95%CI 1.04–1.46 p =.02). Patients with any limitation of life-sustaining therapy had a significantly increased 30-day mortality (86% versus 16%, p <.001) and length of stay (144 [IQR 72–293] versus 96 [IQR 47.25–231.5] hours, p =.026). Conclusion: In German ICUs, any limitation of life-sustaining therapy in VIPs is associated with a significantly increased ICU length of stay and mortality. CFS reliably predicts the outcome

Management and outcomes in critically ill nonagenarian versus octogenarian patients

Background: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (>= 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. Results: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 +/- 5 vs. 7 +/- 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)). Conclusion: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity - to effectively guide triage decisions