Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept

BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110

New proglacial meteorology and river stage observations from Inglefield Land and Pituffik, NW Greenland

Meltwater runoff from the Greenland ice sheet (GrIS) is an important contributor to global sea level rise, but substantial uncertainty exists in its measurement and prediction. Common approaches for estimating ice sheet runoff are in situ gauging of proglacial rivers draining the ice sheet and surface mass balance (SMB) modeling. To obtain hydrological and meteorological data sets suitable for both runoff stage characterization and, pending the establishment of stage–discharge curves, SMB model evaluation, we established an automated weather station (AWS) and a cluster of traditional and experimental river stage sensors on the Minturn River, the largest proglacial river draining Inglefield Land, NW Greenland. Secondary installations measuring river stage were installed in the Fox Canyon River and North River at Pituffik Space Base, NW Greenland. Proglacial runoff at these sites is dominated by supraglacial processes only, uniquely advantaging them for SMB studies. The three installations provide rare hydrological time series and an opportunity to evaluate experimental measurements of river stage from a harsh, little-studied polar region. The installed instruments include submerged vented and non-vented pressure transducers, a bubbler sensor, experimental bank-mounted laser rangefinders, and time-lapse cameras. The first 3 years of observations (2019 to 2021) from these stations indicate (a) a meltwater runoff season from late June to late August/early September that is roughly synchronous throughout the region; (b) the early onset (∼ 23 June to 8 July) of a strong diurnal runoff signal in 2019 and 2020, suggesting minimal meltwater storage in snow and/or firn; (c) 1 d lagged air temperature that displays the strongest correlation with river stage; (d) river stage that correlates more strongly with ablation zone albedo than with net radiation; and (e) the late-summer rain-on-ice events appear to trigger the region's sharpest and largest floods. The new gauging stations provide valuable in situ hydrological observations that are freely available through the PROMICE network (https://promice.org/weather-stations/, last access: 14 September 2023).</p

Acceptability, Feasibility and Preliminary Evaluation of a Novel, Personalised, Home based Physical Activity Intervention for Chronic Heart Failure (Active-at-Home-HF)::A Pilot Study

Purpose: Less than 10% of heart failure patients in the UK participate in cardiac rehabilitation programmes. The present pilot study evaluated feasibility, acceptability and physiological effects of a novel, personalised, home-based physical activity intervention in chronic heart failure. Methods: Twenty patients (68±7 years old, 20% females) with stable chronic heart failure due to reduced left ventricular ejection fraction (31±8 %) participated in a single group, pilot study assessing the feasibility and acceptability of a 12-week personalised home-based physical activity intervention aiming to increase daily number of steps by 2000 from baseline (Active-at-Home-HF). Patients completed cardiopulmonary exercise testing with non-invasive gas exchange and haemodynamic measurements and quality of life questionnaire pre- and post-intervention. Patients were supported weekly via telephone and average weekly step count data collected using pedometers. Results: 43 patients were screened and 20 recruited into the study. Seventeen patients (85%) completed the intervention, and 15 (75%) achieved the target step count. Average step count per day increased significantly from baseline to 3 weeks by 2546 (5108±3064 to 7654±3849 P=0.03, n=17), and was maintained until week 12 (9022±3942). Following completion of the intervention, no adverse events were recorded, quality of life improved by 4 points (26±18 vs. 22±19). Peak exercise stroke volume increased by 19% (127±34 vs 151±34 m/beat, P=0.05), while cardiac index increased by 12% (6.8±1.5 vs. 7.6±2.0 L/min/m2, P=0.19). Workload and oxygen consumption at anaerobic threshold also increased by 16% (49±16 vs. 59±14 watts, P=0.01) and 10% (11.5±2.9 vs. 12.8±2.2 ml/kg/min, P=0.39). Conclusion: The Active-at-Home-HF intervention is feasible, acceptable and effective for increasing physical activity in CHF. It may lead to improvements in quality of life, exercise tolerance and haemodynamic function

Conformation-regulated mechanosensory control via titin domains in cardiac muscle

The giant filamentous protein titin is ideally positioned in the muscle sarcomere to sense mechanical stimuli and transform them into biochemical signals, such as those triggering cardiac hypertrophy. In this review, we ponder the evidence for signaling hotspots along the titin filament involved in mechanosensory control mechanisms. On the way, we distinguish between stress and strain as triggers of mechanical signaling events at the cardiac sarcomere. Whereas the Z-disk and M-band regions of titin may be prominently involved in sensing mechanical stress, signaling hotspots within the elastic I-band titin segment may respond primarily to mechanical strain. Common to both stress and strain sensor elements is their regulation by conformational changes in protein domains

Home care in Europe: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Health and social services provided at home are becoming increasingly important. Hence, there is a need for information on home care in Europe. The objective of this literature review was to respond to this need by systematically describing what has been reported on home care in Europe in the scientific literature over the past decade.</p> <p>Methods</p> <p>A systematic literature search was performed for papers on home care published in English, using the following data bases: Cinahl, the Cochrane Library, Embase, Medline, PsycINFO, Sociological Abstracts, Social Services Abstracts, and Social Care Online. Studies were only included if they complied with the definition of home care, were published between January 1998 and October 2009, and dealt with at least one of the 31 specified countries. Clinical interventions, instrument developments, local projects and reviews were excluded. The data extracted included: the characteristics of the study and aspects of home care 'policy & regulation', 'financing', 'organisation & service delivery', and 'clients & informal carers'.</p> <p>Results</p> <p>Seventy-four out of 5,133 potentially relevant studies met the inclusion criteria, providing information on 18 countries. Many focused on the characteristics of home care recipients and on the organisation of home care. Geographical inequalities, market forces, quality and integration of services were also among the issues frequently discussed.</p> <p>Conclusions</p> <p>Home care systems appeared to differ both between and within countries. The papers included, however, provided only a limited picture of home care. Many studies only focused on one aspect of the home care system and international comparative studies were rare. Furthermore, little information emerged on home care financing and on home care in general in Eastern Europe. This review clearly shows the need for more scientific publications on home care, especially studies comparing countries. A comprehensive and more complete insight into the state of home care in Europe requires the gathering of information using a uniform framework and methodology.</p

Rehabilitation needs for older adults with stroke living at home: perceptions of four populations

<p>Abstract</p> <p>Background</p> <p>Many people who have suffered a stroke require rehabilitation to help them resume their previous activities and roles in their own environment, but only some of them receive inpatient or even outpatient rehabilitation services. Partial and unmet rehabilitation needs may ultimately lead to a loss of functional autonomy, which increases utilization of health services, number of hospitalizations and early institutionalization, leading to a significant psychological and financial burden on the patients, their families and the health care system. The aim of this study was to explore partially met and unmet rehabilitation needs of older adults who had suffered a stroke and who live in the community. The emphasis was put on needs that act as obstacles to social participation in terms of personal factors, environmental factors and life habits, from the point of view of four target populations.</p> <p>Methods</p> <p>Using the focus group technique, we met four types of experts living in three geographic areas of the province of Québec (Canada): older people with stroke, caregivers, health professionals and health care managers, for a total of 12 groups and 72 participants. The audio recordings of the meetings were transcribed and NVivo software was used to manage the data. The process of reducing, categorizing and analyzing the data was conducted using themes from the Disability Creation Process model.</p> <p>Results</p> <p>Rehabilitation needs persist for nine capabilities (e.g. related to behaviour or motor activities), nine factors related to the environment (e.g. type of teaching, adaptation and rehabilitation) and 11 life habits (e.g. nutrition, interpersonal relationships). The caregivers and health professionals identified more unmet needs and insisted on an individualized rehabilitation. Older people with stroke and the health care managers had a more global view of rehabilitation needs and emphasized the availability of resources.</p> <p>Conclusion</p> <p>Better knowledge of partially met or unmet rehabilitation needs expressed by the different types of people involved should lead to increased attention being paid to education for caregivers, orientation of caregivers towards resources in the community, and follow-up of patients' needs in terms of adjustment and rehabilitation, whether for improving their skills or for carrying out their activities of daily living.</p