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The Cochrane Database of Systematic... Mar 2016Levels of physical fitness are low after stroke. It is unknown whether improving physical fitness after stroke reduces disability. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Levels of physical fitness are low after stroke. It is unknown whether improving physical fitness after stroke reduces disability.
OBJECTIVES
To determine whether fitness training after stroke reduces death, dependence, and disability and to assess the effects of training with regard to adverse events, risk factors, physical fitness, mobility, physical function, quality of life, mood, and cognitive function. Interventions to improve cognitive function have attracted increased attention after being identified as the highest rated research priority for life after stroke. Therefore we have added this class of outcomes to this updated review.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (last searched February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 1: searched February 2015), MEDLINE (1966 to February 2015), EMBASE (1980 to February 2015), CINAHL (1982 to February 2015), SPORTDiscus (1949 to February 2015), and five additional databases (February 2015). We also searched ongoing trials registers, handsearched relevant journals and conference proceedings, screened reference lists, and contacted experts in the field.
SELECTION CRITERIA
Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses. Diverse outcome measures limited the intended analyses.
MAIN RESULTS
We included 58 trials, involving 2797 participants, which comprised cardiorespiratory interventions (28 trials, 1408 participants), resistance interventions (13 trials, 432 participants), and mixed training interventions (17 trials, 957 participants). Thirteen deaths occurred before the end of the intervention and a further nine before the end of follow-up. No dependence data were reported. Diverse outcome measures restricted pooling of data. Global indices of disability show moderate improvement after cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) 0.19 to 0.84; P value = 0.002) and by a small amount after mixed training (SMD 0.26, 95% CI 0.04 to 0.49; P value = 0.02); benefits at follow-up (i.e. after training had stopped) were unclear. There were too few data to assess the effects of resistance training.Cardiorespiratory training involving walking improved maximum walking speed (mean difference (MD) 6.71 metres per minute, 95% CI 2.73 to 10.69), preferred gait speed (MD 4.28 metres per minute, 95% CI 1.71 to 6.84), and walking capacity (MD 30.29 metres in six minutes, 95% CI 16.19 to 44.39) at the end of the intervention. Mixed training, involving walking, increased preferred walking speed (MD 4.54 metres per minute, 95% CI 0.95 to 8.14), and walking capacity (MD 41.60 metres per six minutes, 95% CI 25.25 to 57.95). Balance scores improved slightly after mixed training (SMD 0.27, 95% CI 0.07 to 0.47). Some mobility benefits also persisted at the end of follow-up. The variability, quality of the included trials, and lack of data prevents conclusions about other outcomes and limits generalisability of the observed results.
AUTHORS' CONCLUSIONS
Cardiorespiratory training and, to a lesser extent, mixed training reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve the speed and tolerance of walking; some improvement in balance could also occur. There is insufficient evidence to support the use of resistance training. The effects of training on death and dependence after stroke are still unclear but these outcomes are rarely observed in physical fitness training trials. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription and identify long-term benefits.
Topics: Activities of Daily Living; Exercise Therapy; Humans; Physical Fitness; Randomized Controlled Trials as Topic; Resistance Training; Stroke; Stroke Rehabilitation; Walking
PubMed: 27010219
DOI: 10.1002/14651858.CD003316.pub6 -
The Cochrane Database of Systematic... Jan 2019Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads to right-heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left-heart disease (PH-LHD); Group 3 comprises PH as a result of lung diseases or hypoxia, or both; Group 4 includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorders. Phosphodiesterase type 5 (PDE5) inhibitors increase vasodilation and inhibit proliferation.
OBJECTIVES
To determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults and children.
SEARCH METHODS
We performed searches of CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 26 September 2018. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles.
SELECTION CRITERIA
We included randomised controlled trials that compared any PDE5 inhibitor versus placebo, or any other PAH disease-specific therapies, for at least 12 weeks. We include separate analyses for each PH group.
DATA COLLECTION AND ANALYSIS
We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were: change in WHO functional class, six-minute walk distance (6MWD), and mortality. Secondary outcomes were haemodynamic parameters, quality of life/health status, dyspnoea, clinical worsening (hospitalisation/intervention), and adverse events. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the GRADE approach and created 'Summary of findings' tables.
MAIN RESULTS
We included 36 studies with 2999 participants (with pulmonary hypertension from all causes) in the final review. Trials were conducted for 14 weeks on average, with some as long as 12 months. Two trials specifically included children.Nineteen trials included group 1 PAH participants. PAH participants treated with PDE5 inhibitors were more likely to improve their WHO functional class (odds ratio (OR) 8.59, 95% confidence interval (CI) 3.95 to 18.72; 4 trials, 282 participants), to walk 48 metres further in 6MWD (95% CI 40 to 56; 8 trials, 880 participants), and were 22% less likely to die over a mean duration of 14 weeks (95% CI 0.07 to 0.68; 8 trials, 1119 participants) compared to placebo (high-certainty evidence). The number needed to treat to prevent one additional death was 32 participants. There was an increased risk of adverse events with PDE5 inhibitors, especially headache (OR 1.97, 95% CI 1.33 to 2.92; 5 trials, 848 participants), gastrointestinal upset (OR 1.63, 95% CI 1.07 to 2.48; 5 trials, 848 participants), flushing (OR 4.12, 95% CI 1.83 to 9.26; 3 trials, 748 participants), and muscle aches and joint pains (OR 2.52, 95% CI 1.59 to 3.99; 4 trials, 792 participants).Data comparing PDE5 inhibitors to placebo whilst on other PAH-specific therapy were limited by the small number of included trials. Those PAH participants on PDE5 inhibitors plus combination therapy walked 19.66 metres further in six minutes (95% CI 9 to 30; 4 trials, 509 participants) compared to placebo (moderate-certainty evidence). There were limited trials comparing PDE5 inhibitors directly with other PAH-specific therapy (endothelin receptor antagonists (ERAs)). Those on PDE5 inhibitors walked 49 metres further than on ERAs (95% CI 4 to 95; 2 trials, 36 participants) (low-certainty evidence). There was no evidence of a difference in WHO functional class or mortality across both treatments.Five trials compared PDE5 inhibitors to placebo in PH secondary to left-heart disease (PH-LHD). The quality of data were low due to imprecision and inconsistency across trials. In those with PH-LHD there were reduced odds of an improvement in WHO functional class using PDE5 inhibitors compared to placebo (OR 0.53, 95% CI 0.32 to 0.87; 3 trials, 285 participants), and those using PDE5 inhibitors walked 34 metres further compared to placebo (95% CI 23 to 46; 3 trials, 284 participants). There was no evidence of a difference in mortality. Five trials compared PDE5 inhibitors to placebo in PH secondary to lung disease/hypoxia, mostly in COPD. Data were of low quality due to imprecision of effect and inconsistency across trials. There was a small improvement of 27 metres in 6MWD using PDE5 inhibitors compared to placebo in those with PH due to lung disease. There was no evidence of worsening hypoxia using PDE5 inhibitors, although data were limited. Three studies compared PDE5 inhibitors to placebo or other PAH-specific therapy in chronic thromboembolic disease. There was no significant difference in any outcomes. Data quality was low due to imprecision of effect and heterogeneity across trials.
AUTHORS' CONCLUSIONS
PDE5 inhibitors appear to have clear beneficial effects in group 1 PAH. Sildenafil, tadalafil and vardenafil are all efficacious in this clinical setting, and clinicians should consider the side-effect profile for each individual when choosing which PDE5 inhibitor to prescribe.While there appears to be some benefit for the use of PDE5 inhibitors in PH-left-heart disease, it is not clear based on the mostly small, short-term studies, which type of left-heart disease stands to benefit. These data suggest possible harm in valvular heart disease. There is no clear benefit for PDE5 inhibitors in pulmonary hypertension secondary to lung disease or chronic thromboembolic disease. Further research is required into the mechanisms of pulmonary hypertension secondary to left-heart disease, and cautious consideration of which subset of these patients may benefit from PDE5 inhibitors. Future trials in PH-LHD should be sufficiently powered, with long-term follow-up, and should include invasive haemodynamic data, WHO functional class, six-minute walk distance, and clinical worsening.
Topics: Adult; Child; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Numbers Needed To Treat; Phosphodiesterase 5 Inhibitors; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Walk Test
PubMed: 30701543
DOI: 10.1002/14651858.CD012621.pub2 -
Academic Psychiatry : the Journal of... Dec 2017
PubMed: 28730579
DOI: 10.1007/s40596-017-0761-x -
ELife Jul 2023Genomic analysis has shed light on how hadal snailfish have adapted to living at depths of several thousand metres.
Genomic analysis has shed light on how hadal snailfish have adapted to living at depths of several thousand metres.
Topics: Adaptation, Physiological; Perciformes; Animals
PubMed: 37436434
DOI: 10.7554/eLife.90216 -
British Journal of Sports Medicine Dec 2017Quadriceps strengthening exercises are part of the treatment of patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee pain. Blood flow... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Quadriceps strengthening exercises are part of the treatment of patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee pain. Blood flow restriction (BFR) training may provide a low-load quadriceps strengthening method to treat PFP.
METHODS
Seventy-nine participants were randomly allocated to a standardised quadriceps strengthening (standard) or low-load BFR. Both groups performed 8 weeks of leg press and leg extension, the standard group at 70% of 1 repetition maximum (1RM) and the BFR group at 30% of 1RM. Interventions were compared using repeated-measures analysis of variance for Kujala Patellofemoral Score, Visual Analogue Scale for 'worst pain' and 'pain with daily activity', isometric knee extensor torque (Newton metre) and quadriceps muscle thickness (cm). Subgroup analyses were performed on those participants with painful resisted knee extension at 60°.
RESULTS
Sixty-nine participants (87%) completed the study (standard, n=34; BFR, n=35). The BFR group had a 93% greater reduction in pain with activities of daily living (p=0.02) than the standard group. Participants with painful resisted knee extension (n=39) had greater increases in knee extensor torque with BFR than standard (p<0.01). No between-group differences were found for change in Kujala Patellofemoral Score (p=0.31), worst pain (p=0.24), knee extensor torque (p=0.07) or quadriceps thickness (p=0.2). No difference was found between interventions at 6 months.
CONCLUSION
Compared with standard quadriceps strengthening, low load with BFR produced greater reduction in pain with daily living at 8 weeks in people with PFP. Improvements were similar between groups in worst pain and Kujala score. The subgroup with painful resisted knee extension had larger improvements in quadriceps strength from BFR.
TRIAL REGISTRATION NUMBER
12614001164684.
Topics: Adult; Double-Blind Method; Exercise Therapy; Female; Humans; Male; Muscle Strength; Pain Measurement; Patellofemoral Pain Syndrome; Quadriceps Muscle; Resistance Training; Torque; Young Adult
PubMed: 28500081
DOI: 10.1136/bjsports-2016-096329 -
Physical & Occupational Therapy in... Feb 2018To provide normative reference values for the 2-minute walk test (2MWT) for children and adolescents.
AIMS
To provide normative reference values for the 2-minute walk test (2MWT) for children and adolescents.
METHODS
A population-based sample of 2,631 boys and girls (3-17 years) contributed data to this 2011 study which was part of the NIH Toolbox for the Assessment of Neurological and Behavioral Function Norming Project. The 2MWT was performed over a 50 foot (15.2 meter) out-and-back course.
RESULTS
Overall, the mean (standard deviation) distance walked by the participants was 186.2 (33.9) meters. As a general linear model demonstrated that gender (F = 11.0, p =.001) and age (F = 127.6, p <.001) affected 2MWT distance, separate norms are provided for each gender and age stratum (e.g., 3-year-old boys,16-year-old girls). Based on these findings and correlational and regression analysis, separate explanatory equations for 2MWT distance for boys and girls are provided. The separate equations for boys and girls include age, age squared, height, and body mass as variables that explain around 40% of the variance in 2MWT distance.
CONCLUSIONS
The study presents norms for the 2MWT performed by American boys and girls. The norms can be used to determine the presence of limitations in walking endurance in this population.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Reference Values; Sex Factors; Walk Test; Walking
PubMed: 28129009
DOI: 10.1080/01942638.2016.1261981 -
European Journal of Physical and... Jun 2018Stroke is a major cause of death and long-term disability across the globe. Previous studies have demonstrated the trainability of stroke survivors and documented... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Stroke is a major cause of death and long-term disability across the globe. Previous studies have demonstrated the trainability of stroke survivors and documented beneficial effects of aerobic exercises on cardiovascular fitness and gait ability.
AIM
The main aim of this study was to compare the effects of a high-intensity treadmill training (HITT) against low-intensity treadmill training (LITT) on gait ability, quality of life, cardiorespiratory fitness and cost of walking in chronic stroke subjects.
DESIGN
Randomized, controlled pilot study.
SETTING
Patients were recruited among Neurorehabilitation Unit outpatient.
POPULATION
The sample was composed of 16 subjects suffering from chronic stroke.
METHODS
Subjects were enrolled and randomly allocated either in the HITT (N.=8) or in the LITT (N.=8). Both groups performed 3-month training, 3 times per week. Subjects were evaluated before starting the training and after the end of the training by mean of clinical scales (Six-Minute Walk Test, Ten-Meter Walk Test, Health Survey Questionnaire SF-36, Stroke Impact Scale) and instrumental tests (gait analysis, VO2peak and walking energy cost).
RESULTS
Fifteen subjects completed the study and no dropouts were observed. One patient in the LITT refused to initiate the training. The HITT group produced greater improvements than LITT group on the Six-Minute Walk Test (HITT: 64.25 meters, LITT: 6 meters; p=0.005) and Ten-Meter Walk Test performances (HITT: -1.7 s, LITT: 0.6 s; P=0.007), stride length (HITT: 3.3 cm, LITT: 0.4 cm, P=0.003), step length non-paretic side (HITT: 0.5 cm, LITT: 2.4 cm, P=0.008), step length paretic side (HITT: 1.8 cm, LITT: 0.7 cm, P=0.004), cadence (HITT: 1.6 step/min, LITT: 0.6 step/min, P=0.021) and symmetry ratio (HITT: 0.04 cm, LITT: 0.01 cm, P=0.004), VO2peak (HITT: 4.6 mL/kg/min, LITT: 0.87 mL/kg/min; P=0.015) and walking energy cost at 100% of self-selected speed (HITT: -30.8 mL/kg∙km, LITT: -20 5 mL/kg∙km; P=0.021). Significant changes were found on Six-Minute Walk Test (P=0.012) and Ten-Meter Walk Test (P=0.042) performances, spatio-temporal gait parameters (stride length P=0.011, step length paretic side P=0.012, cadence P=0.037 and symmetry ratio P=0.012), VO2peak (P=0.025) and cost of walking at 100% of self-selected speed (P=0.018) in the HITT group. In the LITT no significant results were observed.
CONCLUSIONS
HITT could be considered a feasible training and led to improvement in gait ability and enhanced VO2peak and reduction in cost of walking compared to LITT.
CLINICAL REHABILITATION IMPACT
Chronic stroke survivors should be encouraged to engage regular aerobic treadmill training at medium/high intensity. HITT is safe and feasible and has positive effects on gait ability, cardiovascular fitness and cost of walking in subjects with stroke in chronic phase.
Topics: Adult; Aged; Austria; Disability Evaluation; Energy Metabolism; Exercise Test; Exercise Therapy; Female; Gait Disorders, Neurologic; Humans; Male; Middle Aged; Oxygen Consumption; Physical Fitness; Pilot Projects; Quality of Life; Stroke; Stroke Rehabilitation; Survivors; Treatment Outcome
PubMed: 27575015
DOI: 10.23736/S1973-9087.16.04224-6 -
Neuroscience Letters Apr 2019As the sites of communication between neurons, synapses depend upon precisely regulated protein-protein interactions to support neurotransmitter release and reception.... (Review)
Review
As the sites of communication between neurons, synapses depend upon precisely regulated protein-protein interactions to support neurotransmitter release and reception. Moreover, neuronal synapses typically exist great distances (i.e. up to meters) away from cell bodies, which are the sources of new proteins and the major sites of protein degradation via lysosomes. Thus, synapses are uniquely sensitive to disruptions in proteostasis, and depend upon carefully orchestrated degradative mechanisms for the clearance of dysfunctional proteins. One of the primary cellular degradative pathways is macroautophagy, hereafter referred to as 'autophagy'. Although it has only recently become a focus of research in synaptic biology, emerging studies indicate that autophagy has essential functions at the synapse throughout an organism's lifetime. This review will discuss recent findings about the roles of synaptic autophagy, as well as some of the questions and issues to be considered in this field moving forward.
Topics: Animals; Autophagy; Humans; Synapses; Synaptic Transmission; Synaptic Vesicles
PubMed: 29802916
DOI: 10.1016/j.neulet.2018.05.033 -
The Cochrane Database of Systematic... Jan 2017Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation in PH.
OBJECTIVES
To assess the efficacy and safety of exercise-based rehabilitation for people with PH. Primary outcomes were exercise capacity, adverse events during the intervention period and health-related quality of life (HRQoL). Secondary outcomes included cardiopulmonary haemodynamics, functional class, clinical worsening during follow-up, mortality and changes in B-type natriuretic peptide.
SEARCH METHODS
We searched the Cochrane Airways Specialised Register of Trials up to August 2016, which is based on regular searches of CINAHL, AMED, Embase, PubMed, MEDLINE, PsycINFO and registries of clinical trials. In addition we searched CENTRAL and the PEDro database up to August 2016 and handsearched relevant journals.
SELECTION CRITERIA
All randomised controlled trials (RCTs) focusing on exercise-based rehabilitation programmes for PH.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data independently. For binary outcomes, we calculated odds ratios and their 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included six RCTs and were able to extract data from five studies. The majority of participants were Group I pulmonary artery hypertension (PAH). Study duration ranged from three to 15 weeks. Exercise programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise training was 60.12 metres higher than control (30.17 to 90.07 metres, n = 165, 5 RCTs, low-quality evidence; minimal important difference was 30 metres), the mean peak oxygen uptake was 2.4 ml/kg/minute higher (1.4 to 3.4 ml/kg/min, n = 145, 4 RCTs, low-quality evidence) and the mean peak power in the intervention groups was 16.4 W higher (10.9 to 22.0 higher, n = 145, 4 RCTs, low-quality evidence). The mean change in HRQoL for the SF-36 physical component score was 4.63 points higher (0.80 to 8.47 points, n = 33, 2 RCTs, low-quality evidence) and for the SF-36 mental component score was 4.17 points higher (0.01 to 8.34 points; n = 33; 2 RCTs, low-quality evidence). One study reported a single adverse event, where a participant stopped exercise training due to lightheadedness.
AUTHORS' CONCLUSIONS
In people with PH, exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events. Whilst most studies reported improvements in HRQoL, these may not be clinically important. Overall, we assessed the quality of the evidence to be low. The small number of studies and lack of information on participant selection makes it difficult to generalise these results across the spectrum of people with PH.
Topics: Exercise Therapy; Exercise Tolerance; Hemodynamics; Humans; Hypertension, Pulmonary; Middle Aged; Oxygen Consumption; Quality of Life; Randomized Controlled Trials as Topic; Selection Bias; Walk Test
PubMed: 28099988
DOI: 10.1002/14651858.CD011285.pub2 -
Topics in Companion Animal Medicine Mar 2016Early and rapid identification of hypo- and hyperglycemia as well as ketosis is essential for the practicing veterinarian as these conditions can be life threatening and... (Review)
Review
Early and rapid identification of hypo- and hyperglycemia as well as ketosis is essential for the practicing veterinarian as these conditions can be life threatening and require emergent treatment. Point-of-care testing for both glucose and ketone is available for clinical use and it is important for the veterinarian to understand the limitations and potential sources of error with these tests. This article discusses the devices used to monitor blood glucose including portable blood glucose meters, point-of-care blood gas analyzers and continuous glucose monitoring systems. Ketone monitoring options discussed include the nitroprusside reagent test strips and the 3-β-hydroxybutyrate ketone meter.
Topics: Animals; Blood Glucose; Diabetes Mellitus; Ketones; Point-of-Care Systems; Veterinary Medicine
PubMed: 27451045
DOI: 10.1053/j.tcam.2016.05.005