13 research outputs found
Respiratory function in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a 1.5-year natural history study
INTRODUCTION: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) are rare neuromuscular diseases with respiratory impairment from a young age. Prospective natural history studies are needed for prevalence estimations, respiratory characterization, optimizing clinical care and selecting outcome measures for trial readiness.METHODS: Our prospective 1.5-year natural history study included spirometry (forced vital capacity (FVC); difference between upright and supine vital capacity (dVC)), respiratory muscle strength tests (sniff nasal inspiratory pressure (SNIP)) (age≥5 years), and diaphragm ultrasound (thickness; thickening; echogenicity; all ages).RESULTS: Twenty-six LAMA2-MD patients (M = 8, median 21 [9; 31] years) and 11 SELENON-RM patients (M = 8, 20 [10; 33] years) were included. At baseline, 17 (85 %) LAMA2-MD (FVC%: 59 % [33; 68]) and all SELENON-RM patients (FVC%: 34 % [31; 46]) had an impaired respiratory function (FVC%<80 %). Nine (35 %) LAMA2-MD and eight (73 %) SELENON-RM patients received mechanical ventilation at baseline, and two additional SELENON-RM patients started during follow-up. Contrarily to LAMA2-MD, SELENON-RM patients had severe diaphragm atrophy (diaphragm thickness z-score: 2.5 [-3.1; -2.1]) and dysfunction (diaphragm thickness ratio: 1.2 [1.0; 1.7]; dVC: 30 % [7.7; 41]). SNIP was low in both neuromuscular diseases and correlated with motor function. In SELENON-RM, respiratory function decreased during follow-up.CONCLUSION: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials.CLINICAL TRIAL NUMBER: NCT04478981.</p
Respiratory function in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a 1.5-year natural history study
INTRODUCTION: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) are rare neuromuscular diseases with respiratory impairment from a young age. Prospective natural history studies are needed for prevalence estimations, respiratory characterization, optimizing clinical care and selecting outcome measures for trial readiness.METHODS: Our prospective 1.5-year natural history study included spirometry (forced vital capacity (FVC); difference between upright and supine vital capacity (dVC)), respiratory muscle strength tests (sniff nasal inspiratory pressure (SNIP)) (age≥5 years), and diaphragm ultrasound (thickness; thickening; echogenicity; all ages).RESULTS: Twenty-six LAMA2-MD patients (M = 8, median 21 [9; 31] years) and 11 SELENON-RM patients (M = 8, 20 [10; 33] years) were included. At baseline, 17 (85 %) LAMA2-MD (FVC%: 59 % [33; 68]) and all SELENON-RM patients (FVC%: 34 % [31; 46]) had an impaired respiratory function (FVC%<80 %). Nine (35 %) LAMA2-MD and eight (73 %) SELENON-RM patients received mechanical ventilation at baseline, and two additional SELENON-RM patients started during follow-up. Contrarily to LAMA2-MD, SELENON-RM patients had severe diaphragm atrophy (diaphragm thickness z-score: 2.5 [-3.1; -2.1]) and dysfunction (diaphragm thickness ratio: 1.2 [1.0; 1.7]; dVC: 30 % [7.7; 41]). SNIP was low in both neuromuscular diseases and correlated with motor function. In SELENON-RM, respiratory function decreased during follow-up.CONCLUSION: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials.CLINICAL TRIAL NUMBER: NCT04478981.</p
Cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma:prospective real-world data from the DRUG Access Protocol
Background: The DRUG Access Protocol provides patients with cancer access to registered anti-cancer drugs that are awaiting reimbursement in the Netherlands and simultaneously collects prospective real-world data (RWD). Here, we present RWD from PD-1 blocker cemiplimab in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (laCSCC; mCSCC). Methods: Patients with laCSCC or mCSCC received cemiplimab 350 mg fixed dose every three weeks. Primary endpoints were objective clinical benefit rate (CBR), defined as objective response (OR) or stable disease (SD) at 16 weeks, physician-assessed CBR, defined as clinician's documentation of improved disease or SD based on evaluation of all available clinical parameters at 16 weeks, objective response rate (ORR), and safety, defined as grade ≥ 3 treatment related adverse events (TRAEs) occurring up to 30 days after last drug administration. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Findings: Between February 2021 and December 2022, 151 patients started treatment. Objective and physician-assessed CBR were 54.3% (95% CI, 46.0–62.4) and 59.6% (95% CI, 51.3–67.5), respectively. ORR was 35.1% (95% CI, 27.5–43.3). After a median follow-up of 15.2 months, median DoR was not reached. Median PFS and OS were 12.2 (95% CI, 7.0-not reached) and 24.2 months (95% CI, 18.8-not reached), respectively. Sixty-eight TRAEs occurred in 29.8% of patients. Most commonly reported TRAE was a kidney transplant rejection (9.5%). Interpretation: Cemiplimab proved highly effective and safe in this real-world cohort of patients with laCSCC or mCSCC, confirming its therapeutic value in the treatment of advanced CSCC in daily clinical practice. Funding: The DRUG Access Protocol is supported by all participating pharmaceutical companies: Bayer, Janssen, Lilly, Merck, Novartis, Roche, and Sanofi.</p
Cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma:prospective real-world data from the DRUG Access Protocol
Background: The DRUG Access Protocol provides patients with cancer access to registered anti-cancer drugs that are awaiting reimbursement in the Netherlands and simultaneously collects prospective real-world data (RWD). Here, we present RWD from PD-1 blocker cemiplimab in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (laCSCC; mCSCC). Methods: Patients with laCSCC or mCSCC received cemiplimab 350 mg fixed dose every three weeks. Primary endpoints were objective clinical benefit rate (CBR), defined as objective response (OR) or stable disease (SD) at 16 weeks, physician-assessed CBR, defined as clinician's documentation of improved disease or SD based on evaluation of all available clinical parameters at 16 weeks, objective response rate (ORR), and safety, defined as grade ≥ 3 treatment related adverse events (TRAEs) occurring up to 30 days after last drug administration. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Findings: Between February 2021 and December 2022, 151 patients started treatment. Objective and physician-assessed CBR were 54.3% (95% CI, 46.0–62.4) and 59.6% (95% CI, 51.3–67.5), respectively. ORR was 35.1% (95% CI, 27.5–43.3). After a median follow-up of 15.2 months, median DoR was not reached. Median PFS and OS were 12.2 (95% CI, 7.0-not reached) and 24.2 months (95% CI, 18.8-not reached), respectively. Sixty-eight TRAEs occurred in 29.8% of patients. Most commonly reported TRAE was a kidney transplant rejection (9.5%). Interpretation: Cemiplimab proved highly effective and safe in this real-world cohort of patients with laCSCC or mCSCC, confirming its therapeutic value in the treatment of advanced CSCC in daily clinical practice. Funding: The DRUG Access Protocol is supported by all participating pharmaceutical companies: Bayer, Janssen, Lilly, Merck, Novartis, Roche, and Sanofi.</p
The Study on Relationship between the Traits of Leaders and the Performance of the Leaders under Different Organizational Cultures
Regarded leader’s traits as independent variables, performance as dependent variables, organizational culture as control variables, this paper found that under the innovation-orientation culture, the tuition type of perception type, risking-taking , and artistic subscale significantly and positively correlated with performance. Under the support-orientation culture, the affiliation motive and the ability of understanding diction have a significantly positive correlation with performance. Under rule-orientation culture, the power motive, the conventional subscale, and the ability of analyzing datum have a significantly positive correlation with performance. Thus, the hypothesis of the leader’s trait theories based on context proposed in this paper is validated. Key words: traits, organizational culture, leadership Résumé: En considérant les traits de leaders comme variables indépendantes, la performance comme variable dépendante, la culture organisationnelle comme variable de controle, l’article présent trouve que, sous la culture d’innovation-orientation, le type de frais scolaires du type de perception, le risque-recette et le subscale artistique se rapportent significativement et catégoriquement à la performance. Sous la culture de support-orientation, le motif d’affiliation et l’aptitude de compréhension du langage a une corrélation évidente avec la performance. Sous la culture de règle-orientaion, la force motrice, le subscale conventionnel et la capacité d’analyse des données a un lien effectif avec la performance. Ce faisant, les hypothèses des théories de triats de leaders basées sur le contexte dans l’article s’avèrent fondées. Mots-Clés: traits, culture organisationnelle, directio
High-quality colonoscopy: using Textbook Process as a composite quality measure
Background: High-quality colonoscopy is fundamental to good patient outcomes. Textbook Outcome has proven to be a feasible multidimensional measure for quality assurance between surgical centers. In this study, we sought to establish Textbook Process (TP) as a new composite measure for the optimal colonoscopy process and assessed how frequently TP was attained in clinical practice and the variation in TP between endoscopists. Methods: To reach consensus on the definition of TP, international expert endoscopists completed a modified Delphi consensus process. Then, the achievement of TP was applied to clinical practice. Prospectively collected data in two endoscopy services were retrospectively evaluated. Data on colonoscopies performed for symptoms or surveillance between 01-01-2018 and 31-07-2021 were analyzed. Results: The Delphi consensus process was completed by 20 of 27 invited experts (74.1%). TP was defined as a colonoscopy fulfilling the following items: explicit colonoscopy indication, successful cecal intubation, adequate bowel preparation, adequate withdrawal time, acceptable patient comfort score, provision of post-polypectomy surveillance recommendations in line with guidelines, and the absence of the use of reversal agents, early adverse events, readmissions and mortality. In the two endoscopy services studied, TP was achieved in 5.962 of 8.227 (72.5%) colonoscopies. Of 48 endoscopists performing colonoscopy, attainment of TP varied significantly, ranging from 41.0% to 89.1% per endoscopist. Conclusion: This study proposes a new composite measure for colonoscopy: Textbook Process. TP gives a comprehensive summary of performance and demonstrates significant variation between endoscopists, illustrating the potential benefit of TP as measure in future quality assessment programs