It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

• MeSH
• chronicko-progresivní roztroušená skleróza * epidemiologie   etiologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• recidiva MeSH
• rizikové faktory MeSH
• roztroušená skleróza * epidemiologie   etiologie   MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Austrálie MeSH

BACKGROUND AND OBJECTIVES: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. METHODS: This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. RESULTS: A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). DISCUSSION: The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different therapies. These results suggest that untreated intervals should be minimized after stopping antitrafficking therapies (natalizumab and fingolimod). CLASSIFICATION OF EVIDENCE: This study provides Class III that disease reactivation occurs within months of discontinuation of MS disease-modifying therapies. The risk of disease activity is reduced by commencement of a subsequent therapy.

• MeSH
• fingolimod hydrochlorid terapeutické užití   MeSH
• imunosupresiva škodlivé účinky   MeSH
• lidé MeSH
• natalizumab terapeutické užití   MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   epidemiologie   MeSH
• retrospektivní studie MeSH
• roztroušená skleróza * chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To compare the clinical effectiveness of high- and low-efficacy treatments in patients with recently active and inactive secondary progressive multiple sclerosis (SPMS) after accounting for therapeutic lag. METHODS: Patients treated with high-efficacy (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferon beta, glatiramer acetate, teriflunomide) therapies after SPMS onset were selected from MSBase and Observatoire Français de la Sclérose en Plaques (OFSEP), 2 large observational cohorts. Therapeutic lag was estimated for each patient from their demographic and clinical characteristics. Propensity score was used to match patients treated with high- and low-efficacy therapies. Outcomes after the period of therapeutic lag was disregarded were compared in paired, pairwise-censored analyses. RESULTS: One thousand patients were included in the primary analysis. Patients with active SPMS treated with high-efficacy therapy experienced less frequent relapses than those on low-efficacy therapy (hazard ratio [HR] 0.7, p = 0.006). In patients with inactive SPMS, there was no evidence for a difference in relapse frequency between groups (HR 0.8, p = 0.39). No evidence for a difference in the risk of disability progression was observed. CONCLUSION: In treated patients with SPMS, high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active but not those with inactive SPMS. However, more potent therapies do not offer an advantage in reducing disability progression in this patient group. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active SPMS, although we did not find a difference in disability progression between patients treated with high- and low-efficacy therapy.

• MeSH
• chronicko-progresivní roztroušená skleróza * farmakoterapie   MeSH
• glatiramer acetát terapeutické užití   MeSH
• lidé MeSH
• natalizumab MeSH
• relabující-remitující roztroušená skleróza * MeSH
• roztroušená skleróza * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

AIM: This study aimed to assess safety and outcomes of patients, 2 years after implantation with the HeartMate 3 Left Ventricular Assist System. METHODS AND RESULTS: This study included 50 adults with New York Heart Association (NYHA) class IIIB or IV symptoms or American College of Cardiology/American Heart Association stage D heart failure with an ejection fraction ≤25% and a cardiac index ≤2.2 L/min/m2 without inotropes, or inotrope-dependent with optimal medical management, or listed for heart transplant. The median duration of left ventricular assist device support was 694 days (range: 19-833 days). At baseline, cardiac index was 1.8 ±0.5 L/min/m2 , 58% of patients were receiving inotropes, and 92% were INTERMACS profiles 2-4. At 2 years, Kaplan-Meier survival was 74 ±6%, 5 (10%) patients were transplanted, and 32 patients (64%) remain with support. Adverse event rates include bleeding requiring surgery (16%), gastrointestinal bleeding (20%), driveline infection (24%), ischaemic stroke (16%), haemorrhagic stroke (8%), right heart failure (14%), and outflow graft thrombosis (2%). Notably, no haemolysis, pump thrombosis, or pump malfunction events occurred. At 2 years, 47% of patients remained in NYHA class I and 41% in NYHA class II (P <0.0001). From baseline to 2 years, the mean six-minute walk distance increased from 239 m to 347 m (P <0.0001), and the mean EQ-5D quality of life score improved from 48.2 to 70.6 (P < 0.0001). CONCLUSIONS: Two years post-HeartMate 3 implantation, results show expected and acceptable survival, enhanced haemocompatibility, improved patient functional status and quality of life. This corroborates the success of HeartMate 3 since its first-in-man implantation case in Germany. ClinicalTrials.gov: NCT02170363.

• MeSH
• časové faktory MeSH
• design vybavení MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• podpůrné srdeční systémy * MeSH
• prospektivní studie MeSH
• srdeční komory patofyziologie   MeSH
• srdeční selhání mortalita   patofyziologie   terapie   MeSH
• tepový objem fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Austrálie MeSH
• Evropa MeSH
• Kanada MeSH
• Kazachstán MeSH
• Spojené státy americké MeSH

BACKGROUND: Transcatheter Aortic Valve Implantation (TAVI) is commonly used to deploy new bioprosthetic valves inside degenerated surgically implanted aortic valves in high risk patients. The three scoring systems used to assess risk of postprocedural mortality are: Logistic EuroSCORE (LES), EuroSCORE II (ES II), and Society of Thoracic Surgeons (STS). OBJECTIVE: The purpose of this study is to analyze the accuracy of LES, ES II, and STS in estimating all-cause mortality after transcatheter aortic valve-in-valve (ViV) implantations, which was not assessed before. METHODS: Using the Valve-in-Valve International Data (VIVID) registry, a total of 1,550 patients from 110 centers were included. The study compared the observed 30-day overall mortality vs. the respective predicted mortalities calculated by risk scores. The accuracy of prediction models was assessed based on calibration and discrimination. RESULTS: Observed mortality at 30 days was 5.3%, while average expected mortalities by LES, ES II and STS were 29.49 (± 17.2), 14.59 (± 8.6), and 9.61 (± 8.51), respectively. All three risk scores overestimated 30-day mortality with ratios of 0.176 (95% CI 0.138-0.214), 0.342 (95% CI 0.264-0.419), and 0.536 (95% CI 0.421-0.651), respectively. 30-day mortality ROC curves demonstrated that ES II had the largest AUC at 0.722, followed by STS at 0.704, and LES at 0.698. CONCLUSIONS: All three scores overestimated mortality at 30 days with ES II showing the highest predictability compared to LES and STS; and therefore, should be recommended for ViV procedures. There is a need for a dedicated scoring system for patients undergoing ViV interventions.

• MeSH
• aortální chlopeň patofyziologie   chirurgie   MeSH
• bioprotézy * MeSH
• časové faktory MeSH
• chirurgická náhrada chlopně škodlivé účinky   přístrojové vybavení   mortalita   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• metody pro podporu rozhodování * MeSH
• prediktivní hodnota testů MeSH
• protézy - design MeSH
• registrace MeSH
• rizikové faktory MeSH
• selhání protézy * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční chlopně umělé * MeSH
• transkatetrální implantace aortální chlopně škodlivé účinky   přístrojové vybavení   mortalita   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH

OBJECTIVES: The objective of this study was to describe the operative experience and 30-day outcomes of patients implanted with the HeartMate 3 Left Ventricular Assist System (LVAS) during the Conformité Européenne (CE) Mark clinical trial. METHODS: Adult patients met inclusion and exclusion criteria defining advanced-stage heart failure and included the indications of bridge to transplant and destination therapy. Operative parameters, outcomes, adverse events, physical status and quality-of-life parameters were assessed in the first 30 days after LVAS implant. RESULTS: Fifty patients were implanted with the HeartMate 3 at 10 centres in 6 countries. The 30-day survival rate was 98%. The median operative and cardiopulmonary bypass times were 200 (range: 95-585) min and 84 (range: 47-250) min, respectively. Patients required transfusion with packed red blood cells (3.6 ± 2.3 units), fresh frozen plasma (6.5 ± 5 units) and platelets (2 ± 1 units). Six patients (12%) required reoperation for postoperative bleeding and 10 patients (20%) did not require blood transfusion. The median intensive care time was 6 days (range: 1-112 days) and the total hospital stay was 28 days (range: 14-116 days). The most common adverse events were bleeding (15, 30%), arrhythmia (14, 28%) and infection (10, 20%). There were 2 (4%) strokes. CONCLUSIONS: The 30-day outcomes following implantation of the HeartMate 3 demonstrates excellent survival with low adverse event rates. The LVAD performed as intended with no haemolysis or device failure. CLINICALTRIALSGOV IDENTIFIER: NCT02170363. HeartMate 3™ CE Mark Clinical Investigation Plan (HM3 CE Mark).

• MeSH
• časové faktory MeSH
• celosvětové zdraví MeSH
• délka pobytu trendy   MeSH
• design vybavení MeSH
• incidence MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• podpůrné srdeční systémy * MeSH
• pooperační komplikace epidemiologie   chirurgie   MeSH
• prospektivní studie MeSH
• reoperace MeSH
• srdeční komory patofyziologie   chirurgie   MeSH
• srdeční selhání mortalita   patofyziologie   chirurgie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH