Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor

Prevenció; Atac d'angioedema; Inhibidor C1Prevención; Ataque de angioedema; Inhibidor C1Prevention; Angioedema attack; C1 inhibitorBACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used. RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo. CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456)

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: a prospective cohort study

Background: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). Methods: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. Results: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. Conclusions: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Mapping Fashion in the \u27City by the Sea\u27: Shopping Districts in Newport, Rhode Island

Newport, Rhode Island is internationally recognized for both its prime location on Narragansett Bay and its storied history. Nicknamed the ‘City by the Sea,’ it is famous for its world-class sailing, colonial New England architecture, Gilded Age mansions, trendy restaurants and bars, and nearby beaches. Cultural tourism is a multi-million dollar business for Rhode Island, especially for Newport, where shopping is fourth on the list of revenue generators. The relationship of an American resort city’s geographical setting, built environment, and cultural heritage to its fashion retail sector has not been explored. Acknowledging that fashion contributes to a city’s image, the authors review Newport’s history, provide a profile of Newport today, map Newport’s nine shopping districts, and analyze Newport’s fashion retail sector on the various streets, squares, wharves, and piers. Such an analysis may prove useful to retailers in other resort cities—both small independent boutique owners and national chain stores—as well as city planners and tourism boards

Symmetries and the identity of physical states

The paper proposes a combined account of identity for physical states and direct empirical significance for symmetries according to which symmetry-related state variables designate distinct physical states if and only if the symmetry that relates them has direct empirical significance. Strengthening an earlier result, I show that, given this combined account, the local gauge symmetries in our leading contemporary theories of particle physics do not have any direct empirical significance

Measuring Patient Compliance With Remote Monitoring Following Discharge From Hospital After Major Surgery (DREAMPath): Protocol for a Prospective Observational Study

BACKGROUND: The incidence of major surgery is on the rise globally, and more than 20% of patients are readmitted to hospital following discharge from hospital. During their hospital stay, patients are monitored for early detection of clinical deterioration, which includes regularly measuring physiological parameters such as blood pressure, heart rate, respiratory rate, temperature, and pulse oximetry. This monitoring ceases upon hospital discharge, as patients are deemed clinically stable. Monitoring after discharge is relevant to detect adverse events occurring in the home setting and can be made possible through the development of digital technologies and mobile networks. Smartwatches and other technological devices allow patients to self-measure physiological parameters in the home setting, and Bluetooth connectivity can facilitate the automatic collection and transfer of this data to a secure server with minimal input from the patient. OBJECTIVE: This paper presents the protocol for the DREAMPath (Domiciliary Recovery After Medicalization Pathway) study, which aims to measure compliance with a multidevice remote monitoring kit after discharge from hospital following major surgery. METHODS: DREAMPath is a single-center, prospective, observational, cohort study, comprising 30 patients undergoing major intracavity surgery. The primary outcome is to assess patient compliance with wearable and interactive smart technology in the first 30 days following discharge from hospital after major surgery. Secondary outcomes will explore the relation between unplanned health care events and physiological data collected in the study, as well as to explore a similar relationship with daily patient-reported outcome measures (Quality of Recovery-15 score). Secondary outcomes will be analyzed using appropriate regression methods. Cardiopulmonary exercise testing data will also be collected to assess correlations with wearable device data. RESULTS: Recruitment was halted due to COVID-19 restrictions and will progress once research staff are back from redeployment. We expect that the study will be completed in the first quarter of 2022. CONCLUSIONS: Digital health solutions have been recently made possible due to technological advances, but urgency in rollout has been expedited due to COVID-19. The DREAMPath study will inform readers about the feasibility of remote monitoring for a patient group that is at an increased risk of acute deterioration. TRIAL REGISTRATION: ISRCTN Registry ISRCTN62293620; https://www.isrctn.com/ISRCTN62293620. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30638