Tiotropium Respimat efficacy and safety in asthma:Relationship to age

Background: Data are limited on the differential response to long-acting bronchodilators in older versus younger adults with asthma. Objective: To determine whether the response to tiotropium Respimat differed in older versus younger patients with asthma. Methods: Post hoc analyses of 4 randomized, double-blind, placebo-controlled studies in adults with asthma were carried out. Two studies compared tiotropium Respimat 5 μg once daily with placebo, both added to high-dose inhaled corticosteroid (ICS) plus long-acting β2-agonist (ie, severe asthma). The other 2 evaluated tiotropium Respimat 2.5 or 5 μg once daily, salmeterol 50 μg twice daily, or placebo, all added to medium-dose ICS (moderate asthma). Data were analyzed in 2 pools: (1) severe and (2) moderate asthma. Efficacy end points: trough and peak FEV1; trough forced vital capacity; Asthma Control Questionnaire total score and responder percentage, all at week 24. One set of analyses was performed with age as a continuous covariate; the second was conducted in categories less than 40, 40 to 60, and more than 60 years, with treatment-by-age subgroup interaction P values obtained. Safety was analyzed in age categories. Results: Across the age categories, treatment-by-age subgroup interaction P values for trough FEV1 were.13 and.77 for patients with severe and moderate asthma, respectively, not indicating significant impact of age on overall treatment effect, with this observation replicated in the 2 continuum analyses. The other end points (including safety) were also not impacted by age. Conclusions: Once-daily tiotropium Respimat add-on to ICS or ICS/long-acting β2-agonist therapy was effective and well tolerated in patients with asthma independent of age

Tiotropium Respimat® add-on therapy to inhaled corticosteroids in patients with symptomatic asthma improves clinical outcomes regardless of baseline characteristics

BACKGROUND: Despite currently available therapies and detailed treatment guidelines, many patients with asthma remain symptomatic. Tiotropium delivered by the soft mist inhaler Respimat®, as add-on therapy to medium-dose inhaled corticosteroids (ICS), has been shown to improve lung function and asthma control in patients with symptomatic moderate asthma. OBJECTIVE: To determine whether the efficacy of tiotropium Respimat® in asthma differs by patients' study baseline characteristics. METHODS: Two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group studies (MezzoTinA-asthma®; NCT01172808 and NCT01172821) of once-daily tiotropium Respimat 5 μg and 2.5 μg add-on to ICS were conducted in patients with symptomatic asthma despite treatment with medium-dose ICS with or without additional controllers. Subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, risk of severe asthma exacerbation and Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by patients' baseline characteristics. RESULTS: In this analysis, 523 patients received placebo while 517 and 519 patients received the 5 μg and 2.5 μg dose of tiotropium Respimat, respectively. The magnitude of the improvements in lung function and asthma control, as well as the reduced risk of severe exacerbation with both doses of tiotropium Respimat versus placebo, was independent of a broad range of baseline characteristics. CONCLUSIONS: Once-daily tiotropium Respimat as add-on to ICS is a beneficial treatment option for patients with asthma who remain symptomatic despite at least medium-dose ICS, regardless of baseline characteristics

Efficacy of baricitinib in patients with moderate-to-severe rheumatoid arthritis up to 6.5 years of treatment: results of a long-term study

Objectives: To evaluate the long-term efficacy of once-daily baricitinib 4 mg or 2 mg in patients with active rheumatoid arthritis who had inadequate response (IR) to MTX, csDMARDs or bDMARDs. Methods: Data from three completed phase III studies—RA-BEAM (MTX-IR), RA-BUILD (csDMARD-IR) and RA-BEACON (bDMARD-IR)—and one completed long-term extension study (RA-BEYOND) were analysed up to 6.5 years [340 weeks (RA-BEAM) and 336 weeks (RA-BUILD and RA-BEACON)]. Low disease activity (LDA) [Simplified Disease Activity Index (SDAI) ≤11], clinical remission (SDAI ≤3.3) and physical function [Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5] were the main outcomes assessed. Completer and non-responder imputation (NRI) analyses were conducted on each population. Results: At week 340 or 336, LDA was achieved in 37%/83% of MTX-IR, 35%/83% of csDMARD-IR and 23%/73% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Remission was achieved in 20%/40% of MTX-IR, 13%/32% of csDMARD-IR and 9%/30% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. HAQ-DI ≤0.5 was reached in 31%/51% of MTX-IR, 25%/46% of csDMARD-IR and 24%/38% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Conclusion: Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP consistent with previously reported data, and was well tolerated. Trial registration: United States National Library of Medicine clinical trials database www.clinicaltrials.gov; RA-BEYOND; NCT01885078

Characteristics of patients initiating treatment with baricitinib and outcomes at follow-up: analysis of BSRBR-RA Registry data

Objectives: to describe selected baseline characteristics, continuation with baricitinib and disease activity over time in patients initiating treatment with baricitinib in a UK real-world rheumatology setting.Methods: baseline and follow-up data were analysed from baricitinib-treated patients newly recruited to the British Society for Rheumatology Biologics Registry-RA (BSRBR-RA) baricitinib cohort between 1 January 2018 and 31 March 2020. The primary objective was to evaluate continuation of baricitinib treatment in patients with at least one follow-up. Analyses were performed using the full baricitinib cohort, overall and by patient subgroup: biologic DMARD (bDMARD)/targeted synthetic (ts)DMARD-naive vs -experienced, baricitinib 4 vs 2 mg, age ≥65 vs &lt;65 years, monotherapy vs combination therapy and male vs female.Results: at baseline, the study cohort (n = 561) was 76.5% female, mean age 60.0 years, had longstanding (mean 13.1 years) and severe RA, and 54.0% had previously received a bDMARD/tsDMARD. Of 265 and 110 patients completing the 6- and 12-month follow-ups with available data, 77.7 and 69.1% remained on baricitinib at each time, respectively. In all Kaplan-Meier analyses, &gt;60% of patients remained on baricitinib at 540 days. Continuation of baricitinib therapy differed between some subgroup pairs (bDMARD/tsDMARD naive/experienced, baricitinib 2 mg/4 mg). Disease activity was lower at both follow-ups than at baseline, overall and in all subgroups.Conclusion: in the early years of real-world baricitinib use in the UK, a high proportion of patients continued with treatment at both 6 and 12 months, at which times disease activity was lower than at baseline.</p

The effect of education on the knowledge of the selected legal acts used in nursing

Wstęp. Prace nad określeniem samodzielności pielęgniarek, możliwości podnoszenia kwalifikacji zawodowych i odpowiedzialnością zawodową zaowocowały powstaniem licznych dokumentów legislacyjnych. Ich znajomość powinna stanowić jeden z elementów świadomego wykonywania zawodu pielęgniarki. Cel pracy. Celami pracy były ocena znajomości prawa medycznego przez pielęgniarki czynne zawodowo oraz określenie wpływu wykształcenia na poziom posiadanej wiedzy. Materiał i metody. Badaniami objęto 366 pielęgniarek pracujących w szpitalach wybranych miast Polski. Zastosowano sondaż diagnostyczny z użyciem autorskiego kwestionariusza ankiet. Wyniki. Średnia wieku ankietowanych wyniosła 36 lat, średnia długość stażu pracy &#8212; 14 lat. Najliczniejsza grupa pielęgniarek posiadała wykształcenie średnie (46,2%), studia pielęgniarskie na poziomie licencjackim ukończyło 30% badanych, natomiast tytuł magistra pielęgniarstwa posiadało 23,8% respondentek. Stwierdzono, że osoby, które ukończyły studia I stopnia, uzyskały znacznie więcej punktów niż pielęgniarki z wykształceniem średnim lub magisterskim. Średnia liczba punktów, jaką uzyskały w badaniu ankietowym, wyniosła 27,0 &plusmn; 5,1 punktu (p < 0,05). Wśród personelu z wykształceniem średnim oraz wyższym magisterskim średnia ta była znacznie niższa i wyniosła 25,5 punktu. Wnioski. 1. Bieżąca aktualizacja wiedzy, między innymi z zagadnień prawnych, realizowana przez pielęgniarki w czasie studiów pomostowych powoduje najlepsze przygotowanie badanych dotyczące znajomości aktów prawnych. 2. Niska znajomość zagadnień prawnych przez magistrów pielęgniarstwa może wynikać z różnych form kształcenia, w wyniku których pielęgniarki mogą uzyskać tytuł magistra, oraz długiego upływu czasu związanego z ukończeniem studiów. 3. Występuje konieczność stałego aktualizowania przez pielęgniarki wiedzy z zakresu pielęgniarstwa przez uczestniczenie w różnych formach kształcenia i dokształcania.Introduction. The work on defining the range of nurses&#8217; independence, the possibility of raising their professional qualifications and their professional responsibility resulted in numerous legislative acts. Aim of the study. The aim of this study was to assess the knowledge of medical law demonstrated by working nurses and to find out how education affects the level of their knowledge. Material and methods. The study involved 366 hospital nurses in chosen Polish towns. The study was based on a diagnostic survey using the author&#8217;s questionnaire. Results. The average age of respondents was 36 years and the average job seniority &#8212; 14 years. The most numerous group (46.2%) consisted of nurses with secondary education, 30% of respondents were bachelors and 23.8% masters of nursing. It was found that nurses with a bachelor&#8217;s degree had much better scores in the survey than those with secondary or master education. Legal acts were best known by nurses with a bachelor&#8217;s degree. The mean score that they achieved was 27.0 &plusmn; 5.1 points (p < 0.05). The mean scores obtained by nursing staff with secondary and master education were significantly lower, namely and was equal 25.5 points. Conclusions. 1. Providing updated information on legal issues during nursing studies is the best way to prepare nurses for using legal acts consciously in the future. 2. Long distance from graduating studies may be the reason of little knowledge of law regulations among nurses. 3. It is necessary that nurses continuously update their knowledge of nursing through participation in various forms of education

Effect of baricitinib on functional impairment in RA patients with moderate disease activity and an inadequate response to conventional DMARDS

Abstract for the 2020 Australian Rheumatology Association 60th Annual Scientific Meeting, 16‐19 May 2020. Aims: To assess if RA pts with moderate disease activity (MDA) benefit from improved physical function with BARI, approved for treatment of moderate-to-severe RA, to same extent as pts with high disease activity (HDA)

Cost-effectiveness of a JAK1/JAK2 inhibitor vs a biologic disease-modifying antirheumatic drug (Bdmard) in a treat-to-target strategy for rheumatoid arthritis

Background: Baricitinib is a janus kinase (JAK1/JAK2) inhibitor developed for the treatment of patients suffering from rheumatoid arthritis (RA). Treating RA to the target of remission is current common practice. Cost-effectiveness of different treat-to-target (T2T) strategies, especially ones including new treatments is important for development and preference policy for treatment centers. European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) guidelines are currently unclear about preference between a JAK1/JAK2 versus a biological disease-modifying antirheumatic drug (bDMARD). Objective: The main goal of this paper was to evaluate the cost-effectiveness of baricitinib versus first biological for methotrexate inadequate responders in a T2T strategy using a Markov model that incorporates hospital costs as well as societal costs. Costs and utilities over five years were compared between the two strategies. Methods: A Monte Carlo simulation model was developed to conduct cost–utility analysis from the societal perspective over 5 years. Health states were based on the DAS28-erythrocyte sedimentation rate (ESR) categories. Effectiveness of baricitinib was retrieved from randomized controlled trials. Effectiveness of all other treatments, health state utilities, medical costs, and productivity loss were retrieved from the Dutch RhEumatoid Arthritis Monitoring (DREAM) cohorts. Annual discount rates of 1.5% for utility and 4% for costs were used. Probabilistic sensitivity analysis was employed to incorporate uncertainty and assess robustness of the results. Results: Probabilistic sensitivity analysis results showed the baricitinib strategy yielded lower costs and higher utility over a 5-year period. Scenario analyses showed the baricitinib strategy to be cost-effective in both the moderate and severe RA populations. Conclusion: Results suggest that the use of a JAK1/JAK2 inhibitor instead of a bDMARD in a T2T approach is cost-effective in csDMARD refractory RA patients

Radiographic progression can still occur in individual patients with low or moderate disease activity in the current treat-to-target paradigm: real-world data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry

Background: The aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset < 1 year) treated according to treat-to-target (T2T) therapy. Methods: Baseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) remission. Disease activity (DAS28-ESR and C-reactive protein, CRP) were assessed at least every 3 months; X-rays of the hand and feet at inclusion, 6 months, and 1, 2, and 3 years were scored using modified Sharp/van der Heijde scoring (SHS). Between and within-person associations between time-integrated disease activity and radiographic progression over time were examined. Results: A subset of 229 out of 534 included patients were available for analysis. At the between-patient level, time-integrated DAS28-ESR scores were not significantly correlated with progression at the 6 month and 2-year follow-up and only weakly at the 1-year (Pearson’s correlation coefficient r = 0.17, P < 0.05) and 3-year follow-up (r = 0.21, P < 0.05). Individual slopes of the relationship between DAS28-ESR and progression scores in each time interval were significantly correlated over time and the slope of the first 6 months was moderately associated with this slope at later time points (r between 0.39 and 0.59; P values < 0.001). Between 15.9 to 22.7% and 16.7 to 38.5% of patients with low and moderate time-integrated disease activity, respectively, experienced relevant (ΔSHS ≥ 3) radiographic progression at the different time intervals. Analyses using CRP showed similar results. Conclusions: In early RA patients treated according to T2T, radiographic progression appears to be an individually determined disease process, driven by factors other than consistent high disease activity. For individual patients, the intra-patient relation between disease activity and cumulative radiographic damage during the first 6 months is a good indicator for this relation in later years

Safety and tolerability of once-daily tiotropium Respimat® as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma: A pooled safety analysis

Accepted manuscript (12 month embargo

Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe

Purpose: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer’s Disease. Methods: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. Results: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer’s disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-d-aspartate blocker memantine in AUH. Conclusion: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer’s Disease patients from across Europe