The last decade has witnessed developments in the CF drug pipeline which are both exciting and unprecedented, bringing with them previously unconsidered challenges. The Task Force group was brought together to consider these challenges and possible strategies to address them. Over the last 18 months, we have discussed internally and gathered views from a broad range of individuals representing patient organisations, clinical and research teams, the pharmaceutical industry and regulatory agencies. In this and the accompanying article, we discuss two main areas of focus: i) optimising trial design and delivery for speed and efficiency; ii) drug development for patients with rare CFTR mutations. We propose some strategies to tackle the challenges ahead and highlight areas where further thought is needed. We see this as the start of a process rather than the end and hope herewith to engage the wider community in seeking solutions to improved treatments for all patients with CF.

• MeSH
• cystická fibróza farmakoterapie   genetika   MeSH
• klinické zkoušky jako téma * metody   normy   MeSH
• lidé MeSH
• modulátory membránového transportu farmakologie   MeSH
• mutace MeSH
• objevování léků * metody   trendy   MeSH
• protein CFTR genetika   MeSH
• vyvíjení léků * organizace a řízení   normy   MeSH
• výzkumný projekt normy   MeSH
• zlepšení kvality MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: In the ICD Sports Safety Registry, death, arrhythmia- or shock-related physical injury did not occur in athletes who continue competitive sports after implantable cardioverter-defibrillator (ICD) implantation. However, data from non-competitive ICD recipients is lacking. This report describes arrhythmic events and lead performance in intensive recreational athletes with ICDs enrolled in the European recreational arm of the Registry, and compares their outcome with those of the competitive athletes in the Registry. METHODS: The Registry recruited 317 competitive athletes ≥ 18 years old, receiving an ICD for primary or secondary prevention (234 US; 83 non-US). In Europe, Israel and Australia only, an additional cohort of 80 'auto-competitive' recreational athletes was also included, engaged in intense physical activity on a regular basis (≥2×/week and/or ≥ 2 h/week) with the explicit aim to improve their physical performance limits. Athletes were followed for a median of 44 and 49 months, respectively. ICD shock data and clinical outcomes were adjudicated by three electrophysiologists. RESULTS: Compared with competitive athletes, recreational athletes were older (median 44 vs. 37 years; p = 0.0004), more frequently men (79% vs. 68%; p = 0.06), with less idiopathic ventricular fibrillation or catecholaminergic polymorphic ventricular tachycardia (1.3% vs. 15.4%), less congenital heart disease (1.3% vs. 6.9%) and more arrhythmogenic right ventricular cardiomyopathy (23.8% vs. 13.6%) ( p < 0.001). They more often had a prophylactic ICD implant (51.4% vs. 26.9%; p < 0.0001) or were given a beta-blocker (95% vs. 65%; p < 0.0001). Left ventricular ejection fraction, ICD rate cut-off and time from implant were similar. Recreational athletes performed fewer hours of sports per week (median 4.5 vs. 6 h; p = 0.0004) and fewer participated in sports with burst-performances ( vs. endurance) as their main sports: 4% vs. 65% ( p < 0.0001). None of the athletes in either group died, required external resuscitation or was injured due to arrhythmia or shock. Freedom from definite or probable lead malfunction was similar (5-year 97% vs. 96%; 10-year 93% vs. 91%). Recreational athletes received fewer total shocks (13.8% vs. 26.5%, p = 0.01) due to fewer inappropriate shocks (2.5% vs. 12%; p = 0.01). The proportion receiving appropriate shocks was similar (12.5% vs. 15.5%, p = 0.51). Recreational athletes received fewer total (6.3% vs. 20.2%; p = 0.003), appropriate (3.8% vs. 11.4%; p = 0.06) and inappropriate (2.5% vs. 9.5%; p = 0.04) shocks during physical activity. Ventricular tachycardia/fibrillation storms during physical activity occurred in 0/80 recreational vs. 7/317 competitive athletes. Appropriate shocks during physical activity were related to underlying disease ( p = 0.004) and competitive versus recreational sports ( p = 0.004), but there was no relation with age, gender, type of indication, beta-blocker use or burst/endurance sports. The proportion of athletes who stopped sports due to shocks was similar (3.8% vs. 7.5%, p = 0.32). CONCLUSIONS: Participants in recreational sports had less frequent appropriate and inappropriate shocks during physical activity than participants in competitive sports. Shocks did not cause death or injury. Recreational athletes with ICDs can engage in sports without severe adverse outcomes unless other reasons preclude continuation.

• MeSH
• defibrilátory implantabilní MeSH
• dospělí MeSH
• elektrická defibrilace * škodlivé účinky   přístrojové vybavení   mortalita   MeSH
• hodnocení rizik MeSH
• kompetitivní chování MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• náhlá srdeční smrt epidemiologie   prevence a kontrola   MeSH
• primární prevence MeSH
• prospektivní studie MeSH
• registrace MeSH
• rizikové faktory MeSH
• sekundární prevence MeSH
• sportovci * MeSH
• sporty * MeSH
• srdeční arytmie diagnóza   mortalita   patofyziologie   terapie   MeSH
• tělesná námaha * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

• MeSH
• lékařská praxe založená na důkazech MeSH
• lidé MeSH
• prevence sebevražd MeSH
• sebevražda MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH