Background: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic... Show moreBackground: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs.Methods: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe.Results: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life.Conclusions: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers. Show less
Guimier, A.; Achleitner, M.T.; Bellaing, A.M. de; Edwards, M.; Pontual, L. de; Mittal, K.; ... ; Doudney, K. 2021
Purpose Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death,... Show morePurpose Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants. Methods Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. Results Among the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity. Conclusion We expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided. Show less
Herbolsheimer, F.; Ungar, N.; Portegijs, E.; Dallmeier, D.; Schaap, L.; Smith, T.; ... ; Pas, S. van der 2021
BackgroundThis study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).MethodsData from the... Show moreBackgroundThis study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).MethodsData from the European Project on OSteoArthritis were used. At baseline, clinical classification criteria of the American College of Rheumatology were used to diagnose OA in older adults (65-85years). At baseline and 12-18months follow-up, frequency and duration of participation in the activities walking, cycling, gardening, light and heavy household tasks, and sports activities were assessed with the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire. Physical activity was calculated in kcal/day, based on frequency, duration, body weight and the metabolic equivalent of each activity performed. At baseline and 12-18months follow-up, pain severity was assessed using the pain subscales of the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand OA Index. Within-person pain variability was assessed using two-week pain calendars that were completed at baseline, 6months follow-up and 12-18months follow-up.ResultsOf all 669 participants, 70.0% were women. Sex-stratified multiple linear regression analyses showed that greater pain severity at baseline was cross-sectionally associated with less PA in women (Ratio=0.95, 95% CI=0.90-0.99), but not in men (Ratio=0.99, 95% CI=0.85-1.15). The longitudinal analyses showed a statistically significant inverse association between pain severity at baseline and PA at follow-up in women (Ratio=0.94, 95% CI=0.89-0.99), but not in men (Ratio=1.00, 95% CI=0.87-1.11). Greater pain variability over 12-18months was associated with more PA at follow-up in men (Ratio=1.18, 95% CI=1.01-1.38), but not in women (Ratio=0.94, 95% CI=0.86-1.03).ConclusionsGreater pain severity and less pain variability are associated with less PA in older adults with OA. These associations are different for men and women. The observed sex differences in the various associations should be studied in more detail and need replication in future research. Show less
Kampen, S.C. van; Wanner, A.; Edwards, M.; Harries, A.D.; Kirenga, B.J.; Chakaya, J.; Jones, R. 2018
