bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term worsening of different body functions in persons with progressive multiple sclerosis
Authors: Kaufmann Marco , Vaney Claude , Barin Laura , Liu Xinglu , von Wyl Viktor 
Published: October 2020

Background It is unclear whether EDSS is responsive to disability worsening in advanced MS. Objective To explore the dynamics of disability worsening in persons with advanced-stage MS (EDSS ≥5.5) using three disability worsening definitions (EDSS, Rivermead Mobility Index (RMI), 9-Hole Peg Test (9-HPT)). Methods EDSS-, RMI- and 9-HPT-based disability worsening were assessed over a minimum of two years in a cohort of 286 persons with advanced MS attending inpatient rehabilitation using Kaplan-Meier Curves and multivariable Cox regression. Furthermore, the correspondence between EDSS-, RMI- and 9-HPT-based disability worsening was analyzed. Results Disability progression was observed in 49% (9-HPT), 52% (EDSS) and 53% (RMI), with 9-HPT-based worsening slightly lagging behind. The Multiple Sclerosis Severity Score (MSSS) was the only consistent factor predicting disability worsening based on all three definitions (EDSS: hazard ratio 1.48 [1.30;1.68]; RMI: 1.12 [0.99;1.27]; 9-HPT: 1.36 [1.18;1.57]). Correspondence between EDSS and the other definitions (9-HPT and RMI) was 44.3% and 55.7% at time of EDSS progression and 65.1% and 72.5% overall, respectively. Conclusion In persons with advanced-stage MS, half still developed disability worsening in different functional systems over a median of 6 years. MSSS seems a valid predictor for disability worsening in all three outcome measures in advanced MS.
Is There Clinical Improvement Associated With Intradiscal Therapies? A Comparison Across Randomized Controlled Studies
Authors: Ju Derek G. , Kanim Linda E. , Bae Hyun W. 
Published: October 2020

Study Design: Post hoc comparison using single-site data from 4 multicenter randomized controlled trials. Objectives: Discogenic back pain is associated with significant morbidity and medical cost. Several terminated, unreported randomized controlled trials have studied the effect of intradiscal biologic injections. Here we report single-center outcomes from these trials to determine if there is clinical improvement associated with these intradiscal injections. Methods: Post hoc comparison was performed using single-site data from 4 similar multi-center randomized controlled trials. All trials evaluated an injectable therapy (growth factor, fibrin sealant, or stem cells) for symptomatic lumbar disc disease with near-identical inclusion and exclusion criteria. Demographics and patient reported outcomes were analyzed across treatment arms postinjection. Results: A total of 38 patients were treated with biologic agents and 12 were treated with control saline injections. There was a significant decrease in visual analogue score (VAS) pain for both the investigational and saline groups up to 12 months postinjection ( P < .01). There was no significant difference in VAS scores between the saline and investigational groups at 12 months. Similarly, there was significant improvement in patient-reported disability scores in both the investigational and saline groups at all time points. There were no significant differences in disability score improvement between the saline and investigational treatment groups at 12 months postinjection. Conclusions: A single-center analysis of 4 randomized controlled studies demonstrated no difference in outcomes between therapeutic intradiscal agents (growth factor, fibrin sealant, or stem cells) and control saline groups. In all groups, patient reported pain and disability scores decreased significantly. Future studies are needed to evaluate the therapeutic benefit of any intradiscal injections.
Strategic Decisions Related to Circular Business Model in a Forerunner Company: Challenges Due to Path Dependency and Lock-In
Authors: Lehtimäki Hanna , Piispanen Ville-Veikko , Henttonen Kaisa 
Published: October 2020

Circular economy (CE) entails a radical change in companies because new ways of thinking and doing business are required for value-creation opportunities. There is a lack of empirical studies on how companies themselves see and develop the CE business. Furthermore, the dynamics between the changes required when pursuing a circular business model (CBM) have not been sufficiently studied. This intensive case study examines the strategic business decisions of a forerunner company in CE over 20 years. Questions: What were the strategic decisions related to CE business model in the case company over 20 years? What internal and external factors impacted the strategic decisions and how? Theory: The theoretical framework of this study is built based on CBM strategies and capabilities in the CE business. Basis of the Case: Phenomenon. Type of the Case: An intensive case study of a forerunner company in CE. Protagonist: Not needed. Findings: First, the results of the analysis show that the company engaged in both slowing and closing resource loop business model strategies in the CE market. Second, the results of the analysis imply that the path dependency in the market was too strong, and the company was not able to break the path dependency of the closing loop strategy. Third, the results show that the case company was, however, able to challenge the path dependency and lock-in in the closing resource loop strategy with internal factors that included strategic management capabilities, such as making decisions within the current market conditions, organizational capabilities, such as developing new positions and knowledge, technological capabilities, such as investments on improving and upgrading recycling and waste management, and business model innovation capabilities. Discussions: This study contributes to a call for further research on how companies themselves see and develop CE business. This study sheds light on the ways by which path dependency and lock-in contribute to CBM innovation and can explain a CE strategy failure. Furthermore, this study provides evidence that by drawing on company-internal and company-external factors, a company can challenge path dependency and lock-in and go forward in developing the CE business despite difficulties. For the case company, it was easier to maintain the closing resource loop strategy and stay with the original core business idea of providing recycling and waste management services to construction businesses and selling waste material for energy and heat production than engaging in slowing resource loop strategy. Finally, the results of this study suggest that path dependency theory is useful in projecting future risks in CBM innovation.
The Operation Rainbow Canada Technique for Unilateral Cleft Lip Revision
Authors: White Colin , Ukani Hanif , Rai Kimit 
Published: October 2020

Background: Purpose of this article is to demonstrate the “Operation Rainbow Canada” cleft lip revision technique. This is a surgical technique used by Operation Rainbow Canada on volunteer surgical missions in developing nations. We show how to convert previous Millard or straight line cleft lip repairs to a Fisher anatomic subunit repair, placing a favourable scar along the philtrum. We show a case series of results and explain how this technique gives satisfying aesthetic results for patients seeking unilateral cleft lip revision. Methods: This technique combines the principles of the anatomic subunit repair for primary cleft lip repair as described by Fisher and the correction of the cleft nose deformity as described by McComb. We apply these 2 techniques to unilateral cleft lip revision at the same operation. Results: Patients for revision unilateral lip and nose deformities were treated with this technique over the course of several international surgical missions. There were over 90 cases of revisions performed by our group on previous repaired cleft lips. These procedures were done in India, China, and Cambodia. Conclusion: Previously repaired cleft lips can be improved by our revision procedure. We show how incorporating 2 triangular flaps to lengthen the cleft side of the repaired lip can be done in a revision setting. During lip revision, McCombs sutures can be placed to improve the aesthetic of the nose and correct the nasal alar dome.
Envelope use and reporting in randomised controlled trials: A guide for researchers
Authors: Clark Laura , Dean Alexandra , Mitchell Alex , Torgerson David J 
Published: October 2020

Introduction To produce robust evidence RCTs need to be rigorously conducted as poorly performed studies introduce bias and can mislead clinicians and policy makers. Poor allocation concealment has the largest single impact on bias in RCTs than other methodological aspects. Envelopes are frequently used as a method of allocation concealment and can be associated with increased risk of bias. This paper aims to review envelope use in RCTs published in 2017–2018 and create a guide as a reference for researchers when planning and publishing RCTs when using envelopes as an allocation concealment method. Methods RCTs that used envelopes as a form of allocation concealment that were published in BMJ, JAMA, NEJM and The Lancet in 2017 and 2018 were identified and methodological data on their envelope use extracted and authors were contacted to ascertain reasons for using envelopes in their research. Results 338 RCTs were identified that were published in 2017 and 2018. 8% (n = 29) of the RCTs published used envelopes as an allocation concealment method. 24.1% (n = 7) of studies reported envelope studies robustly with all required methodological information stated to enable an assessment of quality. Budget was the most frequent reason given for envelope use (41.7%). Discussion Only 24% of published RCTs, that used envelopes, contained robust methodological information to enable the reader to judge whether the randomisation and allocation concealment method was adequate. Conclusion RCTs are not reporting envelope use well. RCTs using envelopes should be designed and reported clearly ensuring all necessary methodological information is included.
HLA-A alleles influencing NK cell function impact AML relapse following allogeneic hematopoietic cell transplantation
Authors: van der Ploeg Kattria , Le Luduec Jean-Benoît , Stevenson Philip A. , Park Soo , Gooley Ted A. , Petersdorf Effie W. , Shaffer Brian C. , Hsu Katharine C. 
Published: October 2020

AbstractHLA-B allotypes exhibiting the Bw4 epitope trigger variable inhibitory signaling of KIR3DL1 receptor types, where strong inhibitory HLA-B and KIR3DL1 allele combinations are associated with increased risk for relapse of acute myelogenous leukemia (AML) following allogeneic hematopoietic cell transplantation (HCT). Several HLA-A allotypes also exhibit the Bw4 epitope. Studies with natural killer (NK) cell clones have demonstrated NK inhibition via KIR3DL1 by HLA-A Bw4+ allotypes, but did not delineate strengths of inhibition or hierarchies of NK education. Using primary NK cells from healthy donors, we demonstrate that HLA-A*23, HLA-A*24, and HLA-A*32 proteins are expressed at different densities and exhibit different capacities to educate and inhibit KIR3DL1-expressing NK cells in vitro. Among the HLA-A Bw4+ allotypes, HLA-A*24 and HLA-A*32 demonstrate the strongest inhibitory capacity. To determine if HLA-A allotypes with strong inhibitory capacity have similar negative impact in allogeneic HCT as HLA-B Bw4+ allotypes, we performed a retrospective analysis of 1729 patients with AML who received an allogeneic HCT from a 9/10 or 10/10 HLA allele-matched unrelated donor. Examination of the donor-recipient pairs whose Bw4 epitope was exclusively contributed from HLA-A*24 and A*32 allotypes revealed that patients with HLA-A*24 who received an allograft from a KIR3DL1+ donor experienced a higher risk of disease relapse (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P = .004) when compared with patients without a Bw4 epitope. These findings indicate that despite weak affinity interactions with KIR3DL1, common HLA-A allotypes with the Bw4 epitope can interact with KIR3DL1+ donor NK cells with clinically meaningful impact and provide additional insight to donor NK alloreactivity in HLA-matched HCT.
Observational studies assessing the pharmacological treatment of obstructive lung disease: strengths, challenges and considerations for study design
Authors: Vestbo Jørgen , Janson Christer , Nuevo Javier , Price David 
Published: October 2020

Randomised controlled trials (RCTs) are the gold standard for evaluating treatment efficacy in patients with obstructive lung disease. However, due to strict inclusion criteria and the conditions required for ascertaining statistical significance, the patients included typically represent as little as 5% of the general obstructive lung disease population. Thus, studies in broader patient populations are becoming increasingly important. These can be randomised effectiveness trials or observational studies providing data on real-world treatment effectiveness and safety data that complement efficacy RCTs.In this review we describe the features associated with the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the real-world clinical practice setting. We also discuss how RCTs and observational studies have reported opposing outcomes with several treatments and inhaler devices due to differences in study design and the variations in patients recruited by different study types. Whilst observational studies are not without weaknesses, we outline recently developed tools for defining markers of quality of observational studies. We also examine how observational studies are capable of providing valuable insights into disease mechanisms and management and how they are a vital component of research into obstructive lung disease.As we move into an era of personalised medicine, recent observational studies, such as the NOVEL observational longiTudinal studY (NOVELTY), have the capacity to provide a greater understanding of the value of a personalised healthcare approach in patients in clinical practice by focussing on standardised outcome measures of patient-reported outcomes, physician assessments, airway physiology, and blood and airway biomarkers across both primary and specialist care.
Isolated night cough in children: how does it differ from wheeze?
Authors: Jurca Maja , Goutaki Myrofora , Latzin Philipp , Gaillard Erol A. , Spycher Ben D. , Kuehni Claudia E. 
Published: October 2020

It has been postulated that some children with recurrent cough but no wheeze have a mild form of asthma (cough variant asthma), with similar risk factors and an increased risk of future wheeze.This longitudinal study compared risk factors for isolated night cough and for wheeze in the Leicester Respiratory Cohort in children aged 1, 4, 6 and 9 years and compared prognosis of children with isolated night cough, children with wheeze and asymptomatic children.We included 4101 children aged 1 year, 2854 aged 4 years, 2369 aged 6 years and 1688 aged 9 years. The prevalence of isolated night cough was 10% at age 1 year and 18% in older children. Prevalence of wheeze decreased from 35% at 1 year to 13% at 9 years. Although several risk factors were similar for cough and wheeze, day care, reflux and family history of bronchitis were more strongly associated with cough, and male sex and family history of asthma with wheeze. Over one-third of preschool children with cough continued to cough at school age, but their risk of developing wheeze was similar to that of children who were asymptomatic at earlier surveys. Wheeze tracked more strongly throughout childhood than cough.In conclusion, our study showed that only some risk factors for cough and wheeze were shared but many were not, and there was little evidence for an increased risk of future wheeze in children with isolated night cough. This provides little support for the hypothesis that recurrent cough without wheeze may indicate a variant form of asthma.
Multiple breath washout in bronchiectasis clinical trials: is it feasible?
Authors: O'Neill Katherine , Ferguson Kathryn , Cosgrove Denis , Tunney Michael M. , De Soyza Anthony , Carroll Mary , Chalmers James D. , Gatheral Timothy , Hill Adam T. , Hurst John R. , Johnson Christopher , Loebinger Michael R. , Angyalosi Gerhild , Haworth Charles S. , Jensen Renee , Ratjen Felix , Saunders Clare , Short Christopher , Davies Jane C. , Elborn J. Stuart , Bradley Judy M. 
Published: October 2020

BackgroundEvaluation of multiple breath washout (MBW) set-up including staff training, certification and central “over-reading” for data quality control is essential to determine the feasibility of MBW in future bronchiectasis studies.AimsTo assess the outcomes of a MBW training, certification and central over-reading programme.MethodsMBW training and certification was conducted in European sites collecting lung clearance index (LCI) data in the BronchUK Clinimetrics and/or i-BEST-1 studies. The blended training programme included the use of an eLearning tool and a 1-day face-to-face session. Sites submitted MBW data to trained central over-readers who determined validity and quality.ResultsThirteen training days were delivered to 56 participants from 22 sites. Of 22 sites, 18 (82%) were MBW naïve. Participant knowledge and confidence increased significantly (p<0.001). By the end of the study recruitment, 15 of 22 sites (68%) had completed certification with a mean (range) time since training of 6.2 (3–14) months. In the BronchUK Clinimetrics study, 468 of 589 (79%) tests met the quality criteria following central over-reading, compared with 137 of 236 (58%) tests in the i-BEST-1 study.ConclusionsLCI is feasible in a bronchiectasis multicentre clinical trial setting; however, consideration of site experience in terms of training as well as assessment of skill drift and the need for re-training may be important to reduce time to certification and optimise data quality. Longer times to certification, a higher percentage of naïve sites and patients with worse lung function may have contributed to the lower success rate in the i-BEST-1 study.
Validation of the Moroccan arabic version of the low anterior resection syndrome score
Authors: Essangri Hajar , Majbar Mohammed Anass , Benkabbou Amine , Amrani Laila , Mohsine Raouf , Souadka Amine 
Published: October 2020

AbstractBackgroundSphincter sparing surgery is oftentimes associated with bowel dysfunction complaints, namely the low anterior resection syndrome (LARS). The LARS questionnaire is widely used to assess this syndrome. The aim of this observational study is to translate this tool into arabic and test its psychometric properties in rectal cancer patients, in order to ease its use in clinical practice and future research.MethodsThe LARS questionnaire was translated to arabic and administered to a total of 143 patients. A subgroup of 42 patients took the test twice for test-retest reliability. Internal consistency was examined through cronbach’s alpha. The score results were correlated to the EORTC QLQ-C30 questionnaire for convergent validity assessment, while discriminant validity was established through the ability of the LARS score to differentiate patients with different clinical and pathological criteria.ResultsThe Moroccan Arabic version of the LARS score was completed by 143 patients. The internal consistency was demonstrated through a cronbach alpha score of 0.66. The agreement between the test and retest was established by a Bland Altman plot with 95% limits of agreement. 85.6% of patients remained in the same LARS category. The LARS score showed negative correlation with all five of the QLQ-C30 functional scales as well as positive correlation to the diarrhea symptom scale. The questionnaire score differed between patients according to their tumor location, chemoradiotherapy, type of mesorectal excision and anastomosis.ConclusionThe Moroccan Arabic version of the LARS score shows good psychometric properties and can be used for bowel dysfunction assessment in clinical and research settings.
Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases
Authors: Guénolé Morgan , Lucia François , Bourbonne Vincent , Dissaux Gurvan , Reygagne Emmanuelle , Goasduff Gaëlle , Pradier Olivier , Schick Ulrike 
Published: October 2020

AbstractBackgroundThe aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM).MethodsNinety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated.ResultsAfter a median follow-up of 11.9 months (range 0.7–29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53%(p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03).ConclusionSRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.