Explore the vast range of titles available.

The efficacy of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency has not been substantiated by a randomised, placebo-controlled trial. CT-measured lung density is a more sensitive measure of disease progression in α1 antitrypsin deficiency emphysema than spirometry is, so we aimed to assess the efficacy of augmentation treatment with this measure. The RAPID study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial of A1PI treatment in patients with α1 antitrypsin deficiency. We recruited eligible non-smokers (aged 18–65 years) in 28 international study centres in 13 countries if they had severe α1 antitrypsin deficiency (serum concentration <11 μM) with a forced expiratory volume in 1 s of 35–70% (predicted). We excluded patients if they had undergone, or were on the waiting list to undergo, lung transplantation, lobectomy, or lung volume-reduction surgery, or had selective IgA deficiency. We randomly assigned patients (1:1; done by Accovion) using a computerised pseudorandom number generator (block size of four) with centre stratification to receive A1PI intravenously 60 mg/kg per week or placebo for 24 months. All patients and study investigators (including those assessing outcomes) were unaware of treatment allocation throughout the study. Primary endpoints were CT lung density at total lung capacity (TLC) and functional residual capacity (FRC) combined, and the two separately, at 0, 3, 12, 21, and 24 months, analysed by modified intention to treat (patients needed at least one evaluable lung density measurement). This study is registered with ClinicalTrials.gov, number NCT00261833. A 2-year open-label extension study was also completed (NCT00670007). Between March 1, 2006, and Nov 3, 2010, we randomly allocated 93 (52%) patients A1PI and 87 (48%) placebo, analysing 92 in the A1PI group and 85 in the placebo group. The annual rate of lung density loss at TLC and FRC combined did not differ between groups (A1PI −1·50 g/L per year [SE 0·22]; placebo −2·12 g/L per year [0·24]; difference 0·62 g/L per year [95% CI −0·02 to 1·26], p=0·06). However, the annual rate of lung density loss at TLC alone was significantly less in patients in the A1PI group (−1·45 g/L per year [SE 0·23]) than in the placebo group (−2·19 g/L per year [0·25]; difference 0·74 g/L per year [95% CI 0·06–1·42], p=0·03), but was not at FRC alone (A1PI −1·54 g/L per year [0·24]; placebo −2·02 g/L per year [0·26]; difference 0·48 g/L per year [–0·22 to 1·18], p=0·18). Treatment-emergent adverse events were similar between groups, with 1298 occurring in 92 (99%) patients in the A1PI group and 1068 occuring in 86 (99%) in the placebo group. 71 severe treatment-emergent adverse events occurred in 25 (27%) patients in the A1PI group and 58 occurred in 27 (31%) in the placebo group. One treatment-emergent adverse event leading to withdrawal from the study occurred in one patient (1%) in the A1PI group and ten occurred in four (5%) in the placebo group. One death occurred in the A1PI group (respiratory failure) and three occurred in the placebo group (sepsis, pneumonia, and metastatic breast cancer). Measurement of lung density with CT at TLC alone provides evidence that purified A1PI augmentation slows progression of emphysema, a finding that could not be substantiated by lung density measurement at FRC alone or by the two measurements combined. These findings should prompt consideration of augmentation treatment to preserve lung parenchyma in individuals with emphysema secondary to severe α1 antitrypsin deficiency. CSL Behring.

Generativity is defined as an individual’s concern for and actions dedicated toward the well-being of others, especially youth and subsequent generations. It is a key stage of psychological development from midlife to older age and can be a guiding concept for promoting engagement of older adults in productive and contributive activities, which benefit their well-being. This study examined the longitudinal association between generativity and higher-level functional capacity (HLFC) decline in older Japanese adults. The two-year longitudinal data of 879 older adults aged 65–84 years were analyzed. Participants’ HLFC and generativity were assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence and the Revised Japanese version of the Generativity Scale, respectively. The binary logistic regression analysis results showed that a higher generativity score was negatively associated with HLFC decline, indicating that generativity effectively prevents HLFC decline over 2 years. On adding the interaction term between generativity and sex to examine whether the protective effect of generativity differed by sex, we found that generativity was especially effective in protecting the HLFC decline in men with higher generativity. The study results highlight the importance of promoting engagement of older adults in generative activities to maintain their HLFC.

Nutritional factors, including low protein intake and poor dietary variety, affect age-associated impairment in physical performance resulting in physical frailty. This cross-sectional study investigated the association between intake frequency of major high protein foods and both physical performance and higher-level functional capacity using the food frequency score (FFS) and high protein food frequency score (PFFS) among community-dwelling older adults. The data of 1185 older adults categorized into quartiles based on FFS and PFFS were analyzed. After adjusting for covariates, FFS and PFFS were significantly associated with physical performance [FFS, usual gait speed (p for trend = 0.007); PFFS, usual gait speed (p for trend < 0.001), maximum gait speed (p for trend = 0.002), timed up and go (p for trend = 0.025)], and higher-level functional capacity [FFS (p for trend < 0.001); PFFS (p for trend < 0.001)]. After excluding PFFS data, the participants’ scores were associated with only higher-level functional capacity. Multi-regression analysis with higher-level functional capacity as the covariate showed that FFS and PFFS were significantly correlated with physical performance. Hence, improving food intake frequency, particularly that of high protein foods, and dietary variety may help maintain higher-level functional capacity and physical performance in community-dwelling older adults.

Background: Obesity is associated with increased prevalence and incidence of asthma, but the mechanism is unknown. Obesity reduces lung volumes, which can increase airway responsiveness, and increases resistive and elastic work of breathing, which can increase dyspnea. Objective: To determine if the intensity of dyspnea due to airway narrowing or if airway responsiveness is increased in obese, non-asthmatic subjects. Subjects: Twenty-three obese (BMI (body mass index) ⩾30 kg m −2 ) and 26 non-obese (BMI <30 kg m −2 ) non-asthmatic subjects, aged between 18 and 70 years. Methods: High-dose methacholine challenge was used to determine the sensitivity and the maximal response to methacholine. Respiratory system resistance (Rrs) and reactance were measured, using the forced oscillation technique, as indicators of resistive and elastic loads during challenge. Perception of dyspnea was measured by the Borg score during challenge. Static lung volumes were measured by body plethysmography. Results: Static lung volumes were reduced in the obese subjects. There were no significant differences in the sensitivity or maximal response to methacholine between obese and non-obese subjects. The magnitude of change in Rrs was similar in both groups, but obese subjects had more negative reactance after challenge ( P =0.002) indicating a greater elastic load. The intensity of dyspnea was greater in obese subjects ( P =0.03). Conclusions: Obesity reduces lung volumes, but does not alter the sensitivity or maximal response to methacholine. However, obese subjects have enhanced perception of dyspnea, associated with greater apparent stiffness of the respiratory system, and may therefore be at greater risk of symptoms.

Currently, no clinical studies have compared the inspiratory and expiratory volumes of unilateral lung or of each lobe among supine, standing, and sitting positions. In this prospective study, 100 asymptomatic volunteers underwent both low-radiation-dose conventional (supine position, with arms raised) and upright computed tomography (CT) (standing and sitting positions, with arms down) during inspiration and expiration breath-holds and pulmonary function test (PFT) on the same day. We compared the inspiratory/expiratory lung/lobe volumes on CT in the three positions. The inspiratory and expiratory bilateral upper and lower lobe and lung volumes were significantly higher in the standing/sitting positions than in the supine position (5.3–14.7% increases, all P < 0.001). However, the inspiratory right middle lobe volume remained similar in the three positions (all P > 0.15); the expiratory right middle lobe volume was significantly lower in the standing/sitting positions (16.3/14.1% decrease) than in the supine position (both P < 0.0001). The Pearson’s correlation coefficients ( r ) used to compare the total lung volumes on inspiratory CT in the supine/standing/sitting positions and the total lung capacity on PFT were 0.83/0.93/0.95, respectively. The r values comparing the total lung volumes on expiratory CT in the supine/standing/sitting positions and the functional residual capacity on PFT were 0.83/0.85/0.82, respectively. The r values comparing the total lung volume changes from expiration to inspiration on CT in the supine/standing/sitting positions and the inspiratory capacity on PFT were 0.53/0.62/0.65, respectively. The study results could impact preoperative CT volumetry of the lung in lung cancer patients (before lobectomy) for the prediction of postoperative residual pulmonary function, and could be used as the basis for elucidating undetermined pathological mechanisms. Furthermore, in addition to morphological evaluation of the chest, inspiratory and expiratory upright CT may be used as an alternative tool to predict lung volumes such as total lung capacity, functional residual capacity, and inspiratory capacity in situation in which PFT cannot be performed such as during an infectious disease pandemic, with relatively more accurate predictability compared with conventional supine CT.

Background Exercise training provides benefits for individuals with cystic fibrosis; however, the optimal program is unclear. High-intensity interval training is safe and effective for improving ‘functional capacity’ in these individuals with peak rate of O 2 uptake typically referenced. The ability to adjust submaximal rate of oxygen uptake (V̇O 2 kinetics) might be more important for everyday function because maximal efforts are usually not undertaken. Moreover, the ability of high-intensity training to accelerate V̇O 2 kinetics for individuals with cystic fibrosis could be enhanced with O 2 supplementation during training. Methods Nine individuals with cystic fibrosis completed incremental cycling to limit of tolerance followed by 8 weeks of high-intensity interval cycling (2 sessions per week x ~ 45 min per session) either with ( n  = 5; O2+) or without (AMB) oxygen supplementation (100%). Each session involved work intervals at 70% of peak work rate followed by 60 s of recovery at 35%. For progression, duration of work intervals was increased according to participant tolerance. Results Both groups experienced a significant increase in work-interval duration over the course of the intervention (O2+, 1736 ± 141 v . 700 ± 154 s; AMB, 1463 ± 598 v . 953 ± 253 s; P  = 0.000); however, the increase experienced by O2+ was greater ( P  = 0.027). During low-intensity constant-work-rate cycling, the V̇O 2 mean response time was shortened post compared to pre training (O2+, 34 ± 11 v . 44 ± 9 s; AMB, 39 ± 14 v . 45 ± 17 s; P  = 0.000) while during high-intensity constant-work-rate cycling, time to exhaustion was increased (O2+, 1628 ± 163 v . 705 ± 133 s; AMB, 1073 ± 633 v . 690 ± 348 s; P  = 0.002) and blood [lactate] response was decreased (O2+, 4.5 ± 0.9 v . 6.3 ± 1.4 mmol . L − 1 ; AMB, 4.5 ± 0.6 v . 5.2 ± 1.4 mmol . L − 1 ; P  = 0.003). These positive adaptations were similar regardless of gas inspiration during training. Conclusion Eight weeks of high-intensity interval training for patients with cystic fibrosis accelerated V̇O 2 kinetics and increased time to exhaustion. This provides some evidence that these patients may benefit from this type of exercise. Trial registration This study was retrospectively registered in the ISRTCN registry on 22/06/2019 (# ISRCTN13864650 ).

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

El objetivo de este estudio fue realizar una revisión sistemática de la literatura sobre las características de los programas de entrenamiento basados en la modalidad de intervalos de alta intensidad (HIIT, siglas en inglés) en adultos mayores, y a su vez, describir los efectos sobre la capacidad física y funcional en esta población. Se realizó una búsqueda de literatura de 5 bases de datos (DIALNET, DOAJ, Elsevier, PubMed y Web of Science). Los criterios de inclusión incluyeron estudios experimentales aplicados en personas mayores de 60 años. La escala PEDro se utilizó para la evaluación de la calidad de los estudios elegibles. La búsqueda identificó 126 artículos y se evaluaron 12 artículos en texto completo. Todos los estudios eran de buena calidad metodólogica y tenían un bajo riesgo de sesgo. En conclusión, el entrenamiento HIIT ha sido aplicado por un periodo de 6 a 16 semanas, en la modalidad “HIIT-aeróbico” con efectos positivos sobre la capacidad aeróbica y funcional de las personas mayores, además ha reducido la carga patológica en artritis reumatoidea, obesidad y/o dinapenia. === The objective of this study was to do a systematic review of the literature about the characteristics of training programs based on the high intensity interval modality (HIIT) in elderly, and at the same time, to describe the effects on physical and functional capacity in this population. A literature search of 5 databases (DIALNET, DOAJ, Elsevier, PubMed and Web of Science) was performed. The inclusion criteria included experimental studies applied in people older than 60 years. The PEDro scale was used for quality evaluation of eligible studies. The search identified 126 articles and evaluated 12 articles in full text. All studies were of good methodological quality and had a low risk of bias. In conclusion, HIIT training has been applied for a period of 6 to 16 weeks, in the “HIIT-aerobic” modality with positive effects about the aerobic and functional capacity of the elderly, it has also reduced the pathological burden in rheumatoid arthritis, obesity and / or dynapenia.

BackgroundPridopidine is a well-tolerated, oral Sigma-1 receptor (S1R) agonist. Human PET imaging shows pridopidine 45 mg bid, the dose currently evaluated in PROOF-HD, has selective and robust S1R occupancy. In preclinical HD models, S1R activation by pridopidine enhances multiple cellular processes impaired in HD, leading to neuroprotection. In the PRIDE-HD Ph2 trial, pridopidine 45 mg bid showed a beneficial effect vs placebo (Δ0.87, p=0.0032) on Total Functional Capacity (TFC) at Week 52. TFC is a regulatory-accepted, validated scale for clinical progression of HD. Post-hoc analysis shows this effect is driven by early HD patients (TFC7-13) (Δ1.16, p=0.0003). Responder analysis demonstrates that pridopidine reduced the probability of TFC worsening by 80% (p=0.002).AimEvaluate the efficacy and safety of pridopidine 45 mg bid on TFC in early HD.DesignPROOF-HD is a 65-week, double-blind, placebo-controlled, global Ph3 trial assessing pridopidine 45 mg bid in early HD patients. Primary endpoint is change from baseline to week 65 in TFC. Secondary endpoints include proportion of patients with no TFC decline and changes to week 65 in Q-Motor, Total Motor Score (TMS) and the composite UHDRS. Plasma neurofilament (NfL) levels are an exploratory endpoint. PROOF-HD completed enrollment of 499 patients ahead of schedule in Oct 2021. As of June 16th, 2022, low dropout (23/499, 4.6%) and treatment discontinuations (19/499, 3.8%) confirm pridopidine’s favorable tolerability and safety profile. In February 2022, an independent safety monitoring committee reported no safety signals of concern, and recommended PROOF-HD continue as planned. Results are expected in early 2023.