The COPD Assessment Test (CAT) contains eight items (cough, phlegm, chest tightness, breathlessness, limited activities, confidence leaving home, sleeplessness and energy). The current study aimed 1) ...to better understand the impact of the respiratory and non-respiratory CAT item scores on the CAT total score; and 2) to determine the impact of pulmonary rehabilitation (PR) on CAT items and CAT total score.
CAT total score of ≥10 or ≥ 18 points was used to classify patients as highly symptomatic, a decrease of 2 points was considered as clinically relevant improvement. 'Cough', 'phlegm', 'chest tightness', 'breathlessness' were defined as respiratory items; ≥3 points on each item was defined as highly symptomatic.
In total, 497 clinically stable patients (55% male, age 64.0 (57.5-71.0) years, FEV
46.0 (32.0-63.0)% predicted, CAT total score 22.0 (17.5-26.0) points) were included. 95% had CAT score ≥ 10 points and 75% ≥18 points. Respectively, 45% and 54% of subjects scored high on 3 or 4 of the respiratory CAT items. Following PR, 220 patients (57.7%) reported an improved health status as assessed by CAT total score (- 3.0 (- 7.0-1.0) points). Change in CAT item scores ranged from 0.0 (- 1.0-0.0) to - 1.0 (- 2.0-0.0) points) with best improvements in 'energy' (- 1.0 (- 2.0-0.0)points).
A substantial number of patients classified as highly symptomatic did not report a high level of respiratory symptoms, indicating that non-respiratory symptoms impact on disease classification and treatment algorithm. The impact of PR on CAT item scores varied by individual item.
Netherlands National Trial Register ( NTR3416 ). Registered 2 May 2012.
Grass pea (Lathyrus sativus L.) is a rich source of protein cultivated as an insurance crop in Ethiopia, Eritrea, India, Bangladesh, and Nepal. Its resilience to both drought and flooding makes it a ...promising crop for ensuring food security in a changing climate. The lack of genetic resources and the crop's association with the disease neurolathyrism have limited the cultivation of grass pea. Here, we present an annotated, long read-based assembly of the 6.5 Gbp L. sativus genome. Using this genome sequence, we have elucidated the biosynthetic pathway leading to the formation of the neurotoxin, β-L-oxalyl-2,3-diaminopropionic acid (β-L-ODAP). The final reaction of the pathway depends on an interaction between L. sativus acyl-activating enzyme 3 (LsAAE3) and a BAHD-acyltransferase (LsBOS) that form a metabolon activated by CoA to produce β-L-ODAP. This provides valuable insight into the best approaches for developing varieties which produce substantially less toxin.
Chronic obstructive pulmonary disease (COPD) is an umbrella term that covers many clinical subtypes with clearly different pulmonary and extra-pulmonary characteristics, but with persistent airflow ...limitation in common. This insight has led to the development of a more personalised approach in bronchodilator therapy, prevention of exacerbations, and advanced treatments (such as non-invasive ventilation and lung volume reduction techniques). However, systemic manifestations and comorbidities of COPD also contribute to different clinical phenotypes and warrant an individualised approach as part of integrated disease management. Alterations in bodyweight and composition, from cachexia to obesity, demand specific management. Psychological symptoms are highly prevalent, and thorough diagnosis and treatment are necessary. Moreover, prevention of exacerbations requires interventions beyond the lungs, including treatment of gastro-oesophageal reflux disease, reduction of cardiovascular risks, and management of dyspnoea and anxiety. In this Review, we discuss the management of COPD beyond the respiratory system and propose treatment strategies on the basis of the latest research and best practices.
Abstract A more profound investigation about the responses in activity levels following pulmonary rehabilitation (PR) in patients with COPD is needed. We aimed to describe groups of patients with ...COPD according to patterns of change in physical activity and sedentary behaviour following PR. 90 patients with COPD (60% male; mean age 67 ± 8; median FEV1 47 (32–62) %pred) completed a comprehensive PR programme. A triaxial accelerometer was used to assess the time in sedentary behaviour, light activities and moderate-to-vigorous physical activity (MVPA). Additionally, exercise capacity, quality of life, and symptoms of anxiety and depression were assessed before and after PR. Six groups with different patterns of change in physical activity and sedentary behaviour were identified. The two most prevalent patterns were represented by good responders (increase in physical activity and reduction in sedentary behaviour, 34%) and poor responders (decrease in physical activity and increase in sedentary behaviour, 30%). Good responders had greater improvements in six-minute walk distance (6MWD) and symptoms of depression than poor responders ( P < 0.05 for all). Strong correlation was found between changes in sedentary behaviour and changes in light activities ( rs = −0.89; P < 0.0001). Changes in 6MWD correlated fairly with changes in sedentary behaviour ( rs = −0.26), light activities ( rs = 0.25), and MVPA ( rs = 0.24); P < 0.05 for all. Different patterns of change in activity levels following PR can be found in patients with COPD. Focusing on light physical activities might be a potential strategy to make patients less sedentary, but for this to be achieved prior (or at least parallel) improvements in functional capacity seem to be necessary.
Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most ...prevalent FGIDs, affecting up to 16-26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity. These findings come to challenge the traditional view of FGIDs as pure functional disorders, and relate the origin to a tangible organic substrate. The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and intraepithelial lymphocytes in the intestine of FGIDs. It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns in FGIDs, postoperative ileus, food allergy and inflammatory bowel disease. This review will discuss the role of mucosal mast cells in the gastrointestinal tract with a specific focus on recent advances in disease mechanisms and clinical management in irritable bowel syndrome and functional dyspepsia.
Mast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the ...effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS.
60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers.
Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen.
This study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H(1) receptor antagonism remains to be further investigated. Trial Registration Number NTR39, ISRCTN22504486.
The aim of the present study was to profile a multidimensional response to pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD).Dyspnoea, exercise performance, ...health status, mood status and problematic activities of daily life were assessed before and after a 40-session pulmonary rehabilitation programme in 2068 patients with COPD (mean forced expiratory volume in 1 s of 49% predicted). Patients were ordered by their overall similarity concerning their multidimensional response profile, which comprises the overall response on MRC dyspnoea grade, 6MWD, cycle endurance time, Canadian Occupational Performance Measure performance and satisfaction scores, Hospital Anxiety and Depression Scale anxiety and depression, and St George's Respiratory Questionnaire total score, using a novel non-parametric regression technique.Patients were clustered into four groups with distinct multidimensional response profiles: n=378 (18.3%; "very good responder"), n=742 (35.9%; "good responder"), n=731 (35.4%; "moderate responder"), and n=217 (10.5%; "poor responder"). Patients in the "very good responder" cluster had higher symptoms of dyspnoea, number of hospitalisations <12 months, worse exercise performance, worse performance and satisfaction scores for problematic activities of daily life, more symptoms of anxiety and depression, worse health status, and a higher proportion of patients following an inpatient PR programme compared to the other three clusters.A multidimensional response outcome needs to be considered to study the efficacy of pulmonary rehabilitation services in patients with COPD, as responses to regular outcomes are differential within patients with COPD.
The assessment of gaps and steps in acetabular fractures is challenging. Data from various imaging techniques to enable accurate quantification of acetabular fracture displacement are limited. The ...aim of this study was to assess the accuracy of pelvic radiographs, intraoperative fluoroscopy, and computed tomography (CT) in detecting gaps and step-offs in acetabular fractures. Sixty patients, surgically treated for acetabular fractures, were included. Five observers (5400 measurements) measured the gaps and step-offs on radiographs and CT scans. Intraoperative fluoroscopy images were reassessed for the presence of gaps and/or step-offs. Preoperatively, 25% of the gaps and 40% of the step-offs were undetected on radiographs compared to CT. Postoperatively, 52% of the gaps and 80% of the step-offs were missed on radiographs compared to CT. Radiograph analysis led to a significantly smaller gap and step-off compared to the CT measurements, an underestimation by a factor of two. Approximately 70% of the residual gaps and step-offs was not detected using intraoperative fluoroscopy. Gaps and step-offs that exceed the critical cut-off indicating worse prognosis often remained undetected on radiographs compared to CT scans. Less-experienced observers tend to overestimate gaps and step-offs compared to the more-experienced observers. In acetabular fracture treatment, gaps and step-offs were often undetected and underestimated on radiographs and intraoperative fluoroscopy in comparison with CT scans. This means that CT is superior to radiographs in detecting acetabular fracture displacement, which is clinically relevant for patient counselling regarding treatment decisions and prognosis.
To avoid delay in oncological treatment, a 6-weeks norm for time to treatment has been agreed on in The Netherlands. However, the impact of the COVID-19 pandemic on health systems resulted in reduced ...capacity for regular surgical care. In this study, we investigated the impact of the COVID-19 pandemic on time to treatment in surgical oncology in The Netherlands.
A population-based analysis of data derived from five surgical audits, including patients who underwent surgery for lung cancer, colorectal cancer, upper gastro-intestinal, and hepato-pancreato-biliary (HPB) malignancies, was performed. The COVID-19 cohort of 2020 was compared to the historic cohorts of 2018 and 2019. Primary endpoints were time to treatment initiation and the proportion of patients whose treatment started within 6 weeks. The secondary objective was to evaluate the differences in characteristics and tumour stage distribution between patients treated before and during the COVID-19 pandemic.
A total of 14,567 surgical cancer patients were included in this study, of these 3292 treatments were started during the COVID-19 pandemic. The median time to treatment decreased during the pandemic (26 vs. 27 days,
< 0.001) and the proportion of patients whose treatment started within 6 weeks increased (76% vs. 73%,
< 0.001). In a multivariate logistic regression analysis, adjusting for patient characteristics, no significant difference in post-operative outcomes between patients who started treatment before or after 6 weeks was found. Overall, the number of procedures performed per week decreased by 8.1% during the pandemic. This reduction was most profound for patients with stage I lung carcinoma and colorectal carcinoma. There were fewer patients with pulmonary comorbidities in the pandemic cohort (11% vs. 13%,
= 0.003).
Despite pressure on the capacity of the healthcare system during the COVID-19 pandemic, a larger proportion of surgical oncological patients started treatment within six weeks, possibly due to prioritisation of cancer care and reductions in elective procedures. However, during the pandemic, a decrease in the number of surgical oncological procedures performed in The Netherlands was observed, especially for patients with stage I disease.
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