In a large cohort of 1034 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS), the association of forced vital capacity (FVC) at baseline with (a) time to progression of 20 points i...In a large cohort of 1034 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS), the association of forced vital capacity (FVC) at baseline with (a) time to progression of 20 points in Appel ALS (AALS) score or (b) tracheostomy free survival was investigated. The median survival of ALS patients with baseline FVC < 75%was 2.91 years, compared with 4.08 years for patients with baselineFVC >75%(p < 0.001). Patients with baseline FVC < 75%progressed more rapidly (taking 8.0 months to progress 20 AALS points) compared with patients with baseline FVC >75%(10.0 months, p < 0.001). Moreover, FVC at first examination was identified as a significant predictor of survival and disease progression in both univariate and multivariate Cox regression models, after adjustment for age, sex, site of onset, diagnostic delay, riluzole therapy, and use of bilateral positive airway pressure and percutaneous endoscopic gastrostomy (p < 0.001). We conclude that a single FVC value obtained at an initial visit may serve as a clinically meaningful predictor of survival and disease progression in ALS.展开更多
The topiramate study was a 12- month randomized placebocontrolled trial in patients with ALS. Follow- up evaluation of the placebo group (n = 97) constituted a well- described cohort of patients with ALS, in whom mult...The topiramate study was a 12- month randomized placebocontrolled trial in patients with ALS. Follow- up evaluation of the placebo group (n = 97) constituted a well- described cohort of patients with ALS, in whom multiple outcome measures were assessed at 3- month intervals. During the 12- month study period, the decline of forced vital capacity (FVC% ) and ALS functional rating scale (ALSFRS) was linear, whereas the decline of maximum voluntary isometric contraction- arm (MVIC- arm) and MVIC- grip Z scores was curvilinear. Rates of FVC% and ALFRS decline, but not of MVIC- arm or MVIC- grip, were independent predictors of survival.展开更多
Mutations in the gene encoding fukutin- related protein cause limb- girdle muscular dystrophy 2I. In this multicenter retrospective analysis of 38 patients, 55.3% had cardiac abnormalities, of which 24% had developed ...Mutations in the gene encoding fukutin- related protein cause limb- girdle muscular dystrophy 2I. In this multicenter retrospective analysis of 38 patients, 55.3% had cardiac abnormalities, of which 24% had developed cardiac failure. Heterozygotes for the common C826A mutation developed cardiac involvement earlier than homozygotes. All patients initially improved while receiving standard therapy. Independent of cardiac status, forced vital capacity was below 75% in 44.4% of the patients. There was no absolute correlation between skeletal muscle weakness and cardiomyopathy or respiratory insufficiency. These complications are a primary part of this specific type of limb- girdle muscular dystrophy, with important implications for management.展开更多
Objectives: Impaired longitudinal growth and poor weight gain are common and important problems in children with cystic fibrosis. This study evaluates the hy pothesis that adjunctive growth hormone (GH) therapy augmen...Objectives: Impaired longitudinal growth and poor weight gain are common and important problems in children with cystic fibrosis. This study evaluates the hy pothesis that adjunctive growth hormone (GH) therapy augments the growth respons e to nutritional supplementation. Study design: We recruited 18 prepubertal chil dren who received enteral nutritional supplementation for at least 2 years befor e enrollment. Nine were randomly assigned to receive no GH for 1 year, followed by 1 year of GH. Nine were randomly assigned to receive 1 year of GH followed by a second year of GH. Measurements included height, weight, pulmonary function, lean tissue mass, bone mineral content, hospitalizations, outpatient antibiotic use, and caloric intake. Results: Growth hormone resulted in significant improve ment in height, weight, bone mineral content, lean tissue mass, and number of ho spitalizations. Pulmonary function was similar at baseline. Absolute forced vita l capacity and forced expiratory volume in 1 minute significantly increased in G H treatment, but there was no significant change in percent predicted pulmonary function. Caloric intake was similar in both groups during both years. Conclusio ns: These results suggest that GH is a useful for enhancing growth in children w ith cystic fibrosis receiving enteral nutritional supplementation.展开更多
Objectives: To determine whether early treatment of cystic fibrosis made possible by diagnosis after newborn screening results in improved pulmonary outcomes in adolescence. Study design: Both screening (SG) and non-s...Objectives: To determine whether early treatment of cystic fibrosis made possible by diagnosis after newborn screening results in improved pulmonary outcomes in adolescence. Study design: Both screening (SG) and non-screening groups (NSG) comprised a cohort of children from Australia previously studied at 1, 5, and 10 years of age. The groups were compared on measures of clinical status obtained during their comprehensive annual review conducted at or near the 15th birthday of the subjects. Results: Data were collected on 48 of 57 original subjects in the NSG (7 had died; 2 were lost to follow-up) and 52 of 60 original subjects in the SG (4 had died; 2 transferred out of the country; 2 were lost to follow-up). Those dying in the SG were significantly older (by 48 months, P < .05) than those in the NSG. No statistically significant differences were found between the groups in nutritional status. However, subjects in the SG displayed statistically better total Shwachman-Kulczycki scores (7.0, P ≤ .05), chest x-ray scores (2.3, P ≤ .05) and lung function (forced expiratory volume in 1 second by 12.3% , P ≤ .01; forced vital capacity by 12.6% , P ≤ .01; and mean airflow by 23.3% , P ≤ .01). Conclusions: The previously observed advantage conferred by cystic fibrosis newborn screening on clinical outcomes in infancy and childhood is still apparent in adolescence.展开更多
The rapidity of progression of amyotrophic lateral sclerosis (ALS) to death or respiratory failure impacts patients, clinicians, and clinical investigators. This study compared the abilities of various pulmonary funct...The rapidity of progression of amyotrophic lateral sclerosis (ALS) to death or respiratory failure impacts patients, clinicians, and clinical investigators. This study compared the abilities of various pulmonary function tests to predict tracheostomy-free survival. We evaluated 95 ALS patients by determining upright and supine forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, arterial partial pressure of carbon dioxide (PaCO2), and tran sdiaphragmatic sniff pressures (Pdi-sniff). Tracheostomy-free survival time was measured from the date of spirometry. Supine FVC, upright FVC,MIP,MEP, and Pdi-sniff were significantly associated with tracheostomy-free survival after controlling for non-pulmonary factors, whereas PaCO2 was not. A normal supine FVC, MIP, or MEP was highly predictive for one-year survival. These tests are well suited to predict survival for trial enrollment and patient counseling. Supine FVC’s simplicity of use and availability to ALS investigators makes it a particularly attractive predictor of one-year survival in ALS.展开更多
文摘In a large cohort of 1034 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS), the association of forced vital capacity (FVC) at baseline with (a) time to progression of 20 points in Appel ALS (AALS) score or (b) tracheostomy free survival was investigated. The median survival of ALS patients with baseline FVC < 75%was 2.91 years, compared with 4.08 years for patients with baselineFVC >75%(p < 0.001). Patients with baseline FVC < 75%progressed more rapidly (taking 8.0 months to progress 20 AALS points) compared with patients with baseline FVC >75%(10.0 months, p < 0.001). Moreover, FVC at first examination was identified as a significant predictor of survival and disease progression in both univariate and multivariate Cox regression models, after adjustment for age, sex, site of onset, diagnostic delay, riluzole therapy, and use of bilateral positive airway pressure and percutaneous endoscopic gastrostomy (p < 0.001). We conclude that a single FVC value obtained at an initial visit may serve as a clinically meaningful predictor of survival and disease progression in ALS.
文摘The topiramate study was a 12- month randomized placebocontrolled trial in patients with ALS. Follow- up evaluation of the placebo group (n = 97) constituted a well- described cohort of patients with ALS, in whom multiple outcome measures were assessed at 3- month intervals. During the 12- month study period, the decline of forced vital capacity (FVC% ) and ALS functional rating scale (ALSFRS) was linear, whereas the decline of maximum voluntary isometric contraction- arm (MVIC- arm) and MVIC- grip Z scores was curvilinear. Rates of FVC% and ALFRS decline, but not of MVIC- arm or MVIC- grip, were independent predictors of survival.
文摘Mutations in the gene encoding fukutin- related protein cause limb- girdle muscular dystrophy 2I. In this multicenter retrospective analysis of 38 patients, 55.3% had cardiac abnormalities, of which 24% had developed cardiac failure. Heterozygotes for the common C826A mutation developed cardiac involvement earlier than homozygotes. All patients initially improved while receiving standard therapy. Independent of cardiac status, forced vital capacity was below 75% in 44.4% of the patients. There was no absolute correlation between skeletal muscle weakness and cardiomyopathy or respiratory insufficiency. These complications are a primary part of this specific type of limb- girdle muscular dystrophy, with important implications for management.
文摘Objectives: Impaired longitudinal growth and poor weight gain are common and important problems in children with cystic fibrosis. This study evaluates the hy pothesis that adjunctive growth hormone (GH) therapy augments the growth respons e to nutritional supplementation. Study design: We recruited 18 prepubertal chil dren who received enteral nutritional supplementation for at least 2 years befor e enrollment. Nine were randomly assigned to receive no GH for 1 year, followed by 1 year of GH. Nine were randomly assigned to receive 1 year of GH followed by a second year of GH. Measurements included height, weight, pulmonary function, lean tissue mass, bone mineral content, hospitalizations, outpatient antibiotic use, and caloric intake. Results: Growth hormone resulted in significant improve ment in height, weight, bone mineral content, lean tissue mass, and number of ho spitalizations. Pulmonary function was similar at baseline. Absolute forced vita l capacity and forced expiratory volume in 1 minute significantly increased in G H treatment, but there was no significant change in percent predicted pulmonary function. Caloric intake was similar in both groups during both years. Conclusio ns: These results suggest that GH is a useful for enhancing growth in children w ith cystic fibrosis receiving enteral nutritional supplementation.
文摘Objectives: To determine whether early treatment of cystic fibrosis made possible by diagnosis after newborn screening results in improved pulmonary outcomes in adolescence. Study design: Both screening (SG) and non-screening groups (NSG) comprised a cohort of children from Australia previously studied at 1, 5, and 10 years of age. The groups were compared on measures of clinical status obtained during their comprehensive annual review conducted at or near the 15th birthday of the subjects. Results: Data were collected on 48 of 57 original subjects in the NSG (7 had died; 2 were lost to follow-up) and 52 of 60 original subjects in the SG (4 had died; 2 transferred out of the country; 2 were lost to follow-up). Those dying in the SG were significantly older (by 48 months, P < .05) than those in the NSG. No statistically significant differences were found between the groups in nutritional status. However, subjects in the SG displayed statistically better total Shwachman-Kulczycki scores (7.0, P ≤ .05), chest x-ray scores (2.3, P ≤ .05) and lung function (forced expiratory volume in 1 second by 12.3% , P ≤ .01; forced vital capacity by 12.6% , P ≤ .01; and mean airflow by 23.3% , P ≤ .01). Conclusions: The previously observed advantage conferred by cystic fibrosis newborn screening on clinical outcomes in infancy and childhood is still apparent in adolescence.
文摘根据在第15届欧洲呼吸学会年会上公布的一项研究结果，噻托溴铵（tiotropium bromide）（Ⅰ）加福莫特罗（formoterol）（Ⅱ）改善中度慢性阻塞性肺病（COPD）患者的肺功能的效果，优于氟替卡松丙酸盐加沙美特罗（fluticasone proprionate plus salmeterol）（Ⅱ）。与（Ⅲ）联合使用相比，（Ⅰ）加（Ⅱ）联用在改善FEV1（第1秒最大呼气量）和FVC（最大肺活量）方面显示明显的优势。
文摘The rapidity of progression of amyotrophic lateral sclerosis (ALS) to death or respiratory failure impacts patients, clinicians, and clinical investigators. This study compared the abilities of various pulmonary function tests to predict tracheostomy-free survival. We evaluated 95 ALS patients by determining upright and supine forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, arterial partial pressure of carbon dioxide (PaCO2), and tran sdiaphragmatic sniff pressures (Pdi-sniff). Tracheostomy-free survival time was measured from the date of spirometry. Supine FVC, upright FVC,MIP,MEP, and Pdi-sniff were significantly associated with tracheostomy-free survival after controlling for non-pulmonary factors, whereas PaCO2 was not. A normal supine FVC, MIP, or MEP was highly predictive for one-year survival. These tests are well suited to predict survival for trial enrollment and patient counseling. Supine FVC’s simplicity of use and availability to ALS investigators makes it a particularly attractive predictor of one-year survival in ALS.
