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Physical and functional assessment of the elderly stroke patient.

A functionally oriented approach to acute stroke care should take place in parallel with traditional medical management, since the medical care provided during the first days and weeks after a stroke affects the patient's ultimate disability status. The components of the functionally oriented approach include a comprehensive history and physical examination, through which information is obtained on current disabilities and abilities, risk factors for common poststroke complications, psychologic and social resources, and environmental barriers that preclude maximal functioning.

Affect↗

Self-reported sleep quality and quality of life for individuals with chronic pain conditions.

OBJECTIVE: To determine the sleep quality and quality of life for individuals with degenerative spinal disease or failed back surgery syndrome. DESIGN: Cross-sectional survey design utilizing standardized instruments. Data were analyzed with use of hierarchical stepwise multiple regression analyses. PATIENTS: One hundred sixty-seven individuals with degenerative spinal disease or postlaminectomy syndrome who presented to a tertiary care outpatient patient pain center. OUTCOME MEASURES: The Center for Epidemiological Studies Depression Index measured depressive symptomatology. A modified Pittsburgh Sleep Quality Index (PSQI) measured sleep quality. The arithmetic average of least and usual VAS ratings of pain measured everyday pain. A visual analog scale rating of highest pain during the past 2 weeks measured highest pain. The Epworth Sleepiness Scale measured daytime sleepiness. The Medical Outcome Study-Short Form-Health Survey (SF-36) measured the mental health and general health components of quality of life. RESULTS: Higher overall sleep quality and lower sleep latency primarily were related to higher ratings of physical functioning and shorter duration of pain. Ratings of the highest pain, but not everyday pain, were independent predictors of overall sleep quality and sleep latency. Daytime sleepiness was associated with younger age and depressed mood. Pain was not associated independently with daytime sleepiness. The quality of life related to mental functioning was associated positively with depressed mood and with the interaction of pain and depressed mood. None of the variables in the model (i.e., pain intensity, sleep quality, depression, and demographic variables) predicted quality of life related to overall general health. CONCLUSIONS: These data suggest that physical functioning, duration of pain, and age may be more important than pain intensity and depressed mood in contributing to decreased overall sleep quality and sleep latency. The contribution of physical functioning was particularly strong and should be included in subsequent studies of sleep, pain, and mood. The SF-36 should be compared to pain-specific quality-of-life measures to further evaluate the usefulness of this instrument with outpatients with chronic nonmalignant pain conditions.

Adult↗

Evaluation of a Hebrew version of the revised and expanded Arthritis Impact Measurement Scales (AIMS2) in patients with fibromyalgia.

OBJECTIVE: To validate a translated version of the revised and expanded Arthritis Impact Measurement Scales (AIMS2) to be used by Hebrew speaking populations. METHODS: The AIMS2 was translated into Hebrew and administered to 66 women with fibromyalgia (FM) along with the Hebrew versions of the Fibromyalgia Impact Questionnaire (FIQ) and the Quality of Life (QOL) Scale. All subjects were asked about the presence and severity (assessed by visual analog scale) of FM symptoms (pain, fatigue, anxiety, etc.); a count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were measured by dolorimetry. Test-retest reliability was assessed by Pearson correlation coefficients, and internal consistency was evaluated with Cronbach's alpha coefficient of reliability. Construct validity was tested by correlating the AIMS2 items with measures of symptom severity, count of tender points, tenderness thresholds, physical functioning measured by FIQ, and with a score of QOL. RESULTS: Test-retest reliability coefficients ranged from 0.84 to 0.99, and Cronbach's alpha coefficients from 0.74 to 0.93. Significant moderate to high correlations were obtained between the AIMS2 subscales (except self-care) and measures of physical functioning, quality of life, severity of FM symptoms, and number of tender points. CONCLUSION: The AIMS2 is a reliable and valid instrument for measuring health status and physical functioning in Israeli women with FM.

Evaluation Studies as Topic↗

Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes.

B cell linker protein (BLNK) is a SLP-76-related adaptor protein essential for signal transduction from the BCR. To identify components of BLNK-associated signaling pathways, we performed a phosphorylation-dependent yeast two-hybrid analysis using BLNK probes. Here we report that the serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1), which is activated upon antigen-receptor stimulation and which has been implicated in the regulation of MAP kinase pathways, interacts physically and functionally with BLNK in B cells and with SLP-76 in T cells. This interaction requires Tyr(379) of HPK1 and the Src homology 2 (SH2) domain of BLNK/SLP-76. Via homology modeling, we defined a consensus binding site within ligands for SLP family SH2 domains. We further demonstrate that the SH2 domain of SLP-76 participates in the regulation of AP-1 and NFAT activation in response to T cell receptor (TCR) stimulation and that HPK1 inhibits AP-1 activation in a manner partially dependent on its interaction with SLP-76. Our data are consistent with a model in which full activation of HPK1 requires its own phosphorylation on tyrosine and subsequent interaction with adaptors of the SLP family, providing a mechanistic basis for the integration of this kinase into antigen receptor signaling cascades.

Adaptor Proteins, Signal Transducing↗

Physical and functional properties of airway secretions in cystic fibrosis--therapeutic approaches.

The airway secretions which line the respiratory tract form a biphasic layer composed of an aqueous 'sol' layer and a more superficial 'gel' layer. In the sol layer, also described as the 'periciliary' layer or 'airway surface fluid', the cilia beat and relax. The lubricant sol layer enables the gel mucus present at the tips of the cilia to be transported by the ciliary beating of the ciliated cells. Due to difficulties with sampling, little is known about the physical and biochemical properties of the sol layer. The gel layer is composed of high molecular weight glycoproteins (mucins) linked with proteins and lipids. They form a gel network with a high water content (95%) and rheologic and physical properties (viscoelasticity, adhesivity) adapted in normal conditions to protect the airway mucosa, particularly through mucociliary transport. The adhesive properties of mucus, which are influenced by its lipid composition and degree of hydration, are very important in controlling the efficacy of mucus transport through ciliary activity and coughing. An intermediate viscosity and elasticity is required for optimal mucociliary transport. In obstructive airway diseases, either of genetic origin, such as cystic fibrosis (CF), or acquired (acute or chronic bronchitis), and particularly during inflammatory and infectious episodes, mucus dehydration is associated with an increase in secreted or transudated molecules and with marked augmentation of DNA content. These abnormalities contribute to the increased viscosity and adhesivity of the airway secretions and are responsible for their abnormally low transport rate by ciliary activity and for inefficient cough clearance. In view of these alterations in the physical and functional properties of CF airway secretions, pharmacologic approaches should aim to rehydrate the mucus and to restore normal mucociliary or cough transport by stimulating chloride ion secretion (i.e. using UTP or ATP associated with amiloride in order to block sodium ion and water reabsorption). During acute episodes of infection, recombinant human DNase (rhDNase) may rapidly prevent mucus stasis by improving its rheologic properties. Lubrication of the mucus at the sol phase interface by 'surfactant' therapy may also represent a very promising therapeutic perspective to reduce the hyperviscosity and hyperadhesivity of airway secretions.

Cilia↗

A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding.

VP40, the putative matrix protein of both Ebola and Marburg viruses, possesses a conserved proline-rich motif (PY motif) at its N terminus. We demonstrate that the VP40 protein can mediate its own release from mammalian cells, and that the PY motif is important for this self-exocytosis (budding) function. In addition, we used Western-ligand blotting to demonstrate that the PY motif of VP40 can mediate interactions with specific cellular proteins that have type I WW-domains, including the mammalian ubiquitin ligase, Nedd4. Single point mutations that disrupted the PY motif of VP40 abolished the PY/WW-domain interactions. Significantly, the full-length VP40 protein was shown to interact both physically and functionally with full-length Rsp5, a ubiquitin ligase of yeast and homolog of Nedd4. The VP40 protein was multiubiquitinated by Rsp5 in a PY-dependent manner in an in vitro ubiquitination assay. These data demonstrate that the VP40 protein of Ebola virus possesses a PY motif that is functionally similar to those described previously for Gag and M proteins of specific retroviruses and rhabdoviruses, respectively. Last, these studies imply that VP40 likely plays an important role in filovirus budding, and that budding of retroviruses, rhabdoviruses, and filoviruses may proceed via analogous mechanisms.

Amino Acid Motifs↗

Assessing the validity of the SF-36 General Health Survey.

Our objective was to assess the validity of the SF-36 General Health Survey against the Social Maladjustment Schedule (SMS) and two questionnaire measures, the Social Problem Questionnaire and the Nottingham Health Profile (NHP) in a random subsample of 206 men and women from the Whitehall II study, a longitudinal survey of health and disease amongst 10,308 London-based civil servants. We found that social functioning on the SF-36 correlated significantly with social contacts, total satisfaction and total management scores on the SMS, and social isolation and emotional reactions on the NHP. General mental health on the SF-36 was associated with marriage, social contacts, leisure scores, total satisfaction and total management scores on the SMS, and emotional reactions, energy level and social isolation on the NHP. Conversely, physical functioning and physical role limitations were generally not associated with the SMS but were associated with physical abilities and pain on the NHP. In conclusion, this study offers evidence of the discriminant validity of the general mental health and physical functioning scales of the SF-36. We also found moderate construct and criterion validity for the social functioning scale of the SF-36 and considerable overlap between the general mental health and social functioning scales.

Activities of Daily Living↗

Physical and functional association of human protein O-mannosyltransferases 1 and 2.

A defect of protein O-mannosylation causes congenital muscular dystrophy with brain malformation and structural eye abnormalities, so-called Walker-Warburg syndrome. Protein O-mannosylation is catalyzed by protein O-mannosyltransferase 1 (POMT1) and its homologue, POMT2. Coexpression of POMT1 and POMT2 is required to show O-mannosylation activity. Here we have shown that POMT1 forms a complex with POMT2 and the complex possesses protein O-mannosyltransferase activity. Results indicate that POMT1 and POMT2 associate physically and functionally in vivo. Recently, three mutations were reported in the POMT1 gene of patients who showed milder phenotypes than typical Walker-Warburg syndrome. We coexpressed these mutant POMT1s with POMT2 and found that none of them had any activity. However, all POMT1 mutants, including previously identified POMT1 mutants, coprecipitated with POMT2. These results indicate that the mutant POMT1s could form heterocomplexes with POMT2 but that such complexes are insufficient for enzymatic activity.

Abnormalities, Multiple↗

Involvement of the retinoblastoma protein in brown and white adipocyte cell differentiation: functional and physical association with the adipogenic transcription factor C/EBPalpha.

We investigated the expression of the retinoblastoma protein (pRB) in adipocytes and its possible interaction with the adipogenic transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) in controlling the acquisition of the terminally differentiated adipocyte phenotype. The pRB was expressed (as measured by immunoblotting and/or immunofluorescence) in mice brown and white adipose tissue and in cultured adipocytes that showed lipid accumulation and expressed specific differentiation markers such as aP2 (measured using a specific cDNA probe) and in the case of brown adipocytes UCP-1 (measured using specific antibodies), but was undetectable in proliferative undifferentiated preadipocytes. Transient transfection experiments revealed a functional interaction between pRB and C/EBPalpha affecting transcription from the ucp-1 gene promoter. Thus, in immortalized brown adipocytes, co-transfection of both a C/EBPalpha and a pRB expression vectors maximally enhanced the expression of reporter chloramphenicol acetyltransferase driven by the ucp-1 promoter. Interestingly, C/EBPalpha inhibited reporter gene expression in CHO cells in an effect that was also potentiated in the presence of pRB. A positive effect of pRB on transcription from the ucp-1 promoter could be detected in C/EBPalpha-/-fibroblasts only after forced to overexpress C/EBPalpha, suggesting that the effect of pRB is dependent on its interaction with C/EBPalpha. We also found evidence that pRB and C/EBPalpha can directly bind to each other in vitro. Our results show that the expression of pRB is restricted to differentiated adipocytes, and provide evidence of a physical and functional interaction between pRB and C/EBPalpha that affects the transcriptional activity of the later on a brown adipocyte-specific gene.

3T3 Cells↗

Psychosocial counseling to improve quality of life in HIV infection.

Psychosocial interventions such as cognitive behavioral stress management (CBSM), may enhance coping and social support which contribute to an improvement of quality of life factors such as emotional functioning, social functioning, and sense of well-being, for HIV-infected men during several phases of HIV spectrum disease. These phases include the acutely stressful period immediately following notification of HIV+ status, the adjustment period following this news, and the process of dealing with chronic symptomatic HIV infection. Normalization of some aspects of immunological status were found to accompany some of these psychosocial changes in the short-run. Longer-term follow-up indicated relationships between psychosocial factors and improved immunological status and physical functioning up to 2 years later. Factors such as an increased use of active coping strategies, including relaxation exercises, use of more functional appraisals and elicitation of social support, and decreased use of denial/avoidance coping strategies, may be key predictors of longer-term emotional well-being, social functioning, and physical functioning in HIV-infected populations. Special issues need to be addressed in emerging models of quality of life assessment in HIV populations. For example, the way resurgence of stigmatization and self-doubt affects sense of identity and well-being need to be addressed in quality of life research as well as in psychosocial interventions. Loss of employment and its financial and existential consequences are also factors which impact sense of self and well-being, and need to be addressed both in research as well as in interventions. The effect of repeated HIV-related bereavements upon an individual's social network and the emotional, social, and physical sequelae of bereavement have implications for HIV quality of life research as well. Quality of survival time has become a paramount issue in the context of HIV spectrum disease. Examining the relationships among coping strategies, social support, emotional well-being, realistic appraisals of one's functioning in comparison to their aspirations, and the influence of psychosocial functioning on disease course are central missions of our research program.

Adult↗

Off-the-shelf orthopedic footwear for people with rheumatoid arthritis.

OBJECTIVES: To assess the effectiveness of off-the-shelf orthopedic footwear for people with rheumatoid arthritis (RA) reporting chronic foot pain, in terms of self-reported pain and physical function, as well as objectively measured gait variables using an electric footswitch walkway. METHODS: A small, randomized, controlled trial followed by a larger repeated measures analysis was used. RESULTS: The control group (n = 15) demonstrated no significant changes over a 2-month period in pain, physical function, or gait scores. In contrast, after supply of the footwear both the original footwear group (n = 15) and the control group demonstrated significant improvements, with small to large effect sizes, in weight-bearing pain scores, physical function, gait velocity, and gait stride length without increases in use of arthritis medications or walking aids. CONCLUSION: These data suggest that off-the-shelf orthopedic footwear is beneficial for people with RA even when subjects were unselected on basis of age, sex, disease duration, or disability as measured by the Stanford Health Assessment Questionnaire.

Activities of Daily Living↗

Impact of different adjuvant therapy strategies on quality of life in breast cancer survivors.

Little is known about the long-term effects of adjuvant therapy on quality of life, sexual functioning and symptoms in breast cancer survivors. Between January 1996 and June 1997, we surveyed 1098 women who had been diagnosed with early stage breast cancer between 1 and 5 years earlier. The breast cancer survivors were recruited in two large metropolitan centers in the USA. They completed a survey battery that contained standardized measures of health-related quality of life (HRQL), depression, body image, sexual functioning, and symptoms. A total of 1096 had usable responses for these analyses. In this sample, n = 356 had received tamoxifen (TAM) alone, n = 180 received chemotherapy (CHEM) alone, n = 395 received CHEM + TAM, and n = 265 received no adjuvant therapy (NO RX). There were significant differences in the mean age of each group, with the TAM group being the oldest (mean 62.6 years) and the CHEM group being the youngest (mean 46.8 years). Both age and time since diagnosis were controlled for in all statistical analyses. We found no significant differences in global quality of life among the four treatment groups. For the MOS-SF-36, there were no significant differences on the subscale scores except for the physical functioning subscale (p = 0.0002); the NO RX group had the highest functioning. There were no significant differences in depression scores among the four treatment groups. The MOS-SF-36 physical functioning composite score differed by treatment group (p = 0.012); the NO RX group had a physical functioning composite score that was at the mean for a normal healthy population of women, while those in the adjuvant treatment groups scored slightly lower. The mental health composite score was not significantly different among the four treatment groups and approximated scores from the normal population of healthy women. There were no differences in body image scores among the four treatment groups; however, sexual functioning scores did differ (p = 0.0078) with patients receiving chemotherapy (either alone or with tamoxifen) experiencing more problems. Hot flashes, night sweats, and vaginal discharge differed by treatment (p = 0.0001); all symptoms were reported more often in breast cancer survivors on tamoxifen. Vaginal dryness and pain with intercourse also differed significantly by adjuvant treatment, occurring more often in survivors treated with chemotherapy. Overall, breast cancer survivors function at a high level, similar to healthy women without cancer. However, compared to survivors with no adjuvant therapy, those who received chemotherapy have significantly more sexual problems, and those treated with tamoxifen experience more vasomotor symptoms.

Breast Neoplasms↗

Physical and functional interactions between protein tyrosine phosphatase alpha, PI 3-kinase, and PKCdelta.

The somatostatin analogue, TT-232 inhibits cell proliferation and induces apoptosis in a variety of tumor cells both in vivo and in vitro. While the early transient activation of Erk/MAPK was found to be important for the induction of cell cycle arrest, the signaling pathway leading to the activation of Erk/MAPK had not been fully established. Here we present evidence that activation of the Erk/MAPK pathway by TT-232 involves PI 3-kinase, PKCdelta and the protein tyrosine phosphatase alpha (PTPalpha). We show a physical interaction of PI 3-kinase and PKCdelta with PTPalpha and show that the tyrosine phosphatase plays a role in the activation of MAPK. In this process, PTPalpha Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60(c-src). Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232.

Animals↗

Exercise and chronic kidney disease: current recommendations.

Patients with chronic kidney disease (CKD) are inactive and have reduced physical functioning and performance. Aerobic exercise interventions have been shown to increase maximal oxygen consumption in selected patients. In addition, preliminary evidence, although mixed, suggests that aerobic exercise training can improve blood pressure control, lipid profiles and mental health in this population. A few larger studies are now available showing that aerobic training can also improve physical functioning and performance. The impact on survival or hospitalisation has not been determined. Resistance exercise training, although less studied, appears to increase muscle strength and size and may also improve functioning. There have been several reports of successful combined exercise interventions, but the designs have not allowed evaluation of the relative benefits of aerobic and resistance training on physical functioning. Despite the evidence that exercise is safe and beneficial in patients with CKD, dialysis patients remain inactive, and exercise assessment, counselling and training is not widely offered to patients with CKD. Studies of the barriers to patient participation in exercise and to provider assessment and recommendations are needed so that more widely generalisable interventions can be developed. However, in the interim, patients should be encouraged to participate in moderate physical activity to meet the US Surgeon General's recommendations. Patients who are weak can benefit from strength-training interventions. Resistance and aerobic exercise programmes should be initiated at relatively low intensity in patients with CKD and progressed as slowly as tolerated in order to avoid injury and discontinuation of exercise. For patients on haemodialysis, incorporation of exercise into the dialysis session may increase patient participation and tolerance of exercise.

Exercise↗

The influence of discordance in pain assessment on the functional status of patients with chronic nonmalignant pain.

BACKGROUND: Chronic pain is a frequent cause of suffering and disability that seriously affects patients' quality of life and imposes a staggering socioeconomic toll on society. Little is known about the impact of patient-physician disagreement (discordance) regarding the assessment of chronic pain on patients' quality of life in primary care settings. This study evaluates the role of discordance and other potentially modifiable factors that affect the quality of life and functional status of chronic pain patients. METHODS: We evaluated 436 patient-physician encounters at 12 academic medical centers in the United States. We surveyed chronic nonmalignant pain patients to understand their pain perceptions. We concurrently surveyed their physicians about their perceptions of their patient's pain in primary care settings. RESULTS: More than 50% of physicians disagreed with their patient's pain. Thirty-nine percent of primary care physicians underestimated their patient's pain. In the multivariate analysis, this discordance was associated with poor physical functioning and worse bodily pain (P < 0.018 and P < 0.001 respectively). Patients with chronic, nonmalignant pain have reductions in physical function and bodily pain domains of the SF-36 compared to age-matched populations. Depression and obesity represented other associations. CONCLUSION: Patients with chronic nonmalignant pain have poor physical functioning and worse bodily pain. Discordance, obesity, and depression are other modifiable factors. Prospective studies are needed to design interventions. However, a multifaceted approach appears to represent the best opportunity to reduce the pain and suffering of this challenging population.

Chronic Disease↗

Rehabilitation, aging and chronic renal disease.

Restorative management of the disabled elderly requires knowledge about realistic functional expectations, in addition to knowledge about a patient's particular disease. Health outlook, especially sense of control, should also be assessed because rehabilitation depends on the patient's active participation. A comparison of 349 older end-stage renal disease (ESRD) patients on chronic dialysis and 354 similar-age persons selected as a control group showed that significantly compromised physical function and health outlook were reported by the dialysis patients compared with the control group. Increasing exercise capacity and participation in dialysis self-care activity are recommended ways to improve physical functioning and health outlook among ESRD patients. Individuals who cannot perform strenuous activity can improve in level of fitness; improvements in anemia and muscle strength are key variables. Clinical application of therapeutic and rehabilitative strategies to improve physical function and health outlook in the geriatric renal patient is greatly needed.

Activities of Daily Living↗

Physical and functional interactions between Escherichia coli MutY glycosylase and mismatch repair protein MutS.

Escherichia coli MutY and MutS increase replication fidelity by removing adenines that were misincorporated opposite 7,8-dihydro-8-oxo-deoxyguanines (8-oxoG), G, or C. MutY DNA glycosylase removes adenines from these mismatches through a short-patch base excision repair pathway and thus prevents G:C-to-T:A and A:T-to-G:C mutations. MutS binds to the mismatches and initiates the long-patch mismatch repair on daughter DNA strands. We have previously reported that the human MutY homolog (hMYH) physically and functionally interacts with the human MutS homolog, hMutSalpha (Y. Gu et al., J. Biol. Chem. 277:11135-11142, 2002). Here, we show that a similar relationship between MutY and MutS exists in E. coli. The interaction of MutY and MutS involves the Fe-S domain of MutY and the ATPase domain of MutS. MutS, in eightfold molar excess over MutY, can enhance the binding activity of MutY with an A/8-oxoG mismatch by eightfold. The MutY expression level and activity in mutS mutant strains are sixfold and twofold greater, respectively, than those for the wild-type cells. The frequency of A:T-to-G:C mutations is reduced by two- to threefold in a mutS mutY mutant compared to a mutS mutant. Our results suggest that MutY base excision repair and mismatch repair defend against the mutagenic effect of 8-oxoG lesions in a cooperative manner.

Binding Sites↗

Cardiorespiratory training for people with stroke.

RATIONALE: Low levels of cardiorespiratory fitness are common after stroke and are associated with post-stroke disability and increased risk of secondary stroke. Cardiorespiratory training interventions aim to increase cardiorespiratory fitness, improve physical function, reduce disability, and help prevent future strokes. Clinical guidelines recommend exercise as part of lifestyle modification for secondary prevention, and strongly recommend exercise for rehabilitation. This review is one of three reviews that were originally a single review on physical fitness training for stroke. OBJECTIVES: The primary objective of this review was to determine whether cardiorespiratory training after stroke has an effect on death, disability, adverse events, risk factors, fitness, walking, and indices of physical function when compared to a non-exercise control. SEARCH METHODS: In April 2025, we searched nine bibliographic databases and two trials registers to identify studies for inclusion in the review. We checked reference lists, tracked citations, and contacted experts. ELIGIBILITY CRITERIA: We included randomised controlled trials comparing cardiorespiratory training interventions with usual care, no intervention, or a non-exercise intervention in people with stroke. OUTCOMES: Our critical outcomes were death, disability, adverse events, risk factors, fitness, walking, and indices of physical function, assessed at the end of the intervention and the end of the longest follow-up. RISK OF BIAS: We used the Cochrane RoB 1 tool to assess the risk of bias in the included studies. SYNTHESIS METHODS: The studies evaluated different comparisons (e.g. cardiorespiratory training versus no intervention/waiting list control or versus attention control or versus usual care), which we synthesised into a single comparison: cardiorespiratory training versus control. We used random-effects meta-analysis on arm-level data (risk difference (RD) for dichotomous data, and mean difference (MD) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs)). For outcome data that we did not meta-analyse, we followed Synthesis Without Meta-analysis (SWiM) guidance. We used GRADE to assess the certainty of the evidence for critical outcomes. INCLUDED STUDIES: We included 53 studies (2672 participants, with an average age of 61.9 years). Most studies recruited ambulatory participants in the early subacute (7 days to 3 months) or chronic (> 6 months) phases of recovery. Exercise duration recommendations were met in 49 studies, and frequency recommendations in 48. Twenty-eight studies lacked balanced exposure between groups. Programme duration was 12 weeks or more in 16 studies (maximum: 24 weeks). Sixteen studies had a post-intervention follow-up period (12 weeks to 12 months from baseline). One study planned a six-month follow-up but did not report it. SYNTHESIS OF RESULTS: Cardiorespiratory training does not increase or decrease deaths at the end of intervention (RD 0.00, 95% CI -0.01 to 0.01; 36 studies, 1563 participants; high-certainty evidence) or the end of follow-up (RD -0.00, 95% CI -0.02 to 0.02; 10 studies, 713 participants; high-certainty evidence). Cardiorespiratory training may improve indices of disability slightly at the end of intervention (SMD 0.35, 95% CI 0.12 to 0.57; 17 studies, 1073 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressed using the Barthel Index (0 to 20), the equivalent effect is MD 1.68, 95% CI 0.59 to 2.74. It is unclear if the effect is clinically meaningful (the minimal clinically important difference (MCID) is +1.85). The effect is unclear at the end of follow-up (SMD -0.14, 95% CI -0.36 to 0.08; 5 studies, 347 participants; low-certainty evidence). Cardiorespiratory training does not increase or decrease the incidence of secondary cardiovascular or cerebrovascular events at the end of intervention (RD -0.00, 95% CI -0.03 to 0.02; 8 studies, 544 participants; high-certainty evidence) and probably does not affect them at the end of follow-up (RD -0.02, 95% CI -0.08 to 0.04; 4 studies, 412 participants; moderate-certainty evidence). It is very uncertain whether cardiorespiratory training affects systolic blood pressure (mmHg) at the end of intervention (MD -2.12, 95% CI -5.81 to 1.57; 9 studies, 535 participants; very low-certainty evidence) (MCID -2 mmHg) or follow-up (MD 0.93, 95% CI -4.30 to 6.16; 3 studies, 155 participants; very low-certainty evidence); the 95% CIs include the MCID. Cardiorespiratory training probably results in a slight improvement in cardiorespiratory fitness (VO2 ml/kg/min) at the end of intervention (MD 2.37, 95% CI 1.39 to 3.36; 13 studies, 608 participants; moderate-certainty evidence); it is unclear if the effect is clinically meaningful (MCID +3.5 ml/kg/min). The effect may be similar at the end of follow-up (MD 2.76, 95% CI 1.36 to 4.16; 5 studies, 237 participants; low-certainty evidence). Subgroup analysis favoured longer interventions. Cardiorespiratory training probably results in a slight increase in comfortable walking speed (metres per second) at the end of intervention (MD 0.08, 95% CI 0.04 to 0.12; 16 studies, 647 participants; moderate-certainty evidence), but the effect is not clinically meaningful (MCID +0.13). The effect is unclear at the end of follow-up (MD 0.02, 95% CI -0.05 to 0.10; 3 studies, 182 participants; low-certainty evidence). Cardiorespiratory training may improve indices of balance at the end of intervention (SMD 0.31, 95% CI 0.15 to 0.47; 18 studies, 772 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressing using the Berg Balance Scale, the equivalent effect is MD 2.09, 95% CI 1.10 to 3.07; and it is unclear if it is clinically meaningful (MCID of +2). The effect is unclear at the end of follow-up (MD 0.90, 95% CI -1.32 to 3.12; 6 studies, 253 participants; low-certainty evidence). Overall, our certainty about the evidence is limited for most outcomes by imprecision (small number of studies and participants) or risks of bias (e.g. imbalanced exposure doses) or both. AUTHORS' CONCLUSIONS: Cardiorespiratory training after stroke does not affect mortality or the incidence of secondary events at the end of the aerobic exercise training programme or end of follow-up. It may increase fitness, reduce disability, increase walking speed, and improve balance at the end of intervention, but it is unclear if these improvements are clinically meaningful. Further well-designed randomised trials are needed to fully understand the potential benefits and long-term effects of cardiorespiratory training and the optimal exercise prescription. FUNDING: No dedicated funding REGISTRATION: Protocol (and previous versions) available via DOI 10.1002/14651858.CD003316.

Humans↗