The Six-Minute Walk Test (6MWT) is increasingly being used as a functional outcome measure for chronic pediatric conditions. Knowledge about its measurement properties is needed to determine whether ...it is an appropriate test to use.
The purpose of this study was to systematically review all published clinimetric studies on the 6MWT in chronic pediatric conditions.
The databases MEDLINE, EMBASE, CINAHL, PEDro, and SPORTDiscus were searched up to February 2012.
Studies designed to evaluate measurement properties of the 6MWT in a chronic pediatric condition were included in the systematic review.
The methodological quality of the included studies and the measurement properties of the 6MWT were examined.
A best evidence synthesis was performed on 15 studies, including 9 different chronic pediatric conditions. Limited evidence to strong evidence was found for reliability in various chronic conditions. Strong evidence was found for positive criterion validity of the 6MWT with peak oxygen uptake in some populations, but negative criterion validity was found in other populations. Construct validity remained unclear in most patient groups because of methodological flaws. Little evidence was available for responsiveness and measurement error. Studies showed large variability in test procedures despite existing guidelines for the performance of the 6MWT.
Unavailability of a specific checklist to evaluate the methodological quality of clinimetric studies on performance measures was a limitation of the study.
Evidence for measurement properties of the 6MWT varies largely among chronic pediatric conditions. Further research is needed in all patient groups to explore the ability of the 6MWT to measure significant and clinically important changes. Until then, changes measured with the 6MWT should be interpreted with caution. Future studies or consensus regarding modified test procedures in the pediatric population is recommended.
Background
Physical exercise training might improve muscle and cardiorespiratory function in spinal muscular atrophy (SMA). Optimization of aerobic capacity or other resources in residual muscle ...tissue through exercise may counteract the muscle deterioration that occurs secondary to motor neuron loss and inactivity in SMA. There is currently no evidence synthesis available on physical exercise training in people with SMA type 3.
Objectives
To assess the effects of physical exercise training on functional performance in people with SMA type 3, and to identify any adverse effects.
Search methods
On 8 May 2018, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, and LILACS. On 25 April 2018 we searched NHSEED, DARE, and ClinicalTrials.gov and WHO ICTRP for ongoing trials.
Selection criteria
We included randomized controlled trials (RCTs) or quasi‐RCTs lasting at least 12 weeks that compared physical exercise training (strength training, aerobic exercise training, or both) to placebo, standard or usual care, or another type of non‐physical intervention for SMA type 3. Participants were adults and children from the age of five years with a diagnosis of SMA type 3 (Kugelberg‐Welander syndrome), confirmed by genetic analysis.
Data collection and analysis
We used standard Cochrane methodological procedures.
Main results
We included one RCT that studied the effects of a six‐month, home‐based, combined muscle strength and recumbent cycle ergometry training program versus usual care in 14 ambulatory people with SMA. The age range of the participants was between 10 years and 48 years. The study was evaluator‐blinded, but personnel and participants could not be blinded to the intervention, which placed the results at a high risk of bias. Participants performed strength training as prescribed, but 50% of the participants did not achieve the intended aerobic exercise training regimen. The trial used change in walking distance on the six‐minute walk test as a measure of function; a minimal detectable change is 24.0 m. The change from baseline to six months' follow‐up in the training group (9.4 m) was not detectably different from the change in the usual care group (‐0.14 m) (mean difference (MD) 9.54 m, 95% confidence interval (CI) ‐83.04 to 102.12; N = 12). Cardiopulmonary exercise capacity, assessed by the change from baseline to six months' follow‐up in peak oxygen uptake (VO2max) was similar in the training group (‐0.12 mL/kg/min) and the usual care group (‐1.34 mL/kg/min) (MD 1.22 mL/kg/min, 95% CI ‐2.16 to 4.6; N = 12). A clinically meaningful increase in VO2max is 3.5 mL/kg/min.
The trial assessed function on the Hammersmith Functional Motor Scale ‐ Expanded (HFMSE), which has a range of possible scores from 0 to 66, with an increase of 3 or more points indicating clinically meaningful improvement. The HFMSE score in the training group increased by 2 points from baseline to six months' follow‐up, with no change in the usual care group (MD 2.00, 95% CI ‐2.06 to 6.06; N = 12). The training group showed a slight improvement in muscle strength, expressed as the manual muscle testing (MMT) total score, which ranges from 28 (weakest) to 280 (strongest). The change from baseline in MMT total score was 6.8 in the training group compared to ‐5.14 in the usual care group (MD 11.94, 95% CI ‐3.44 to 27.32; N = 12).
The trial stated that training had no statistically significant effects on fatigue and quality of life. The certainty of evidence for all outcomes was very low because of study limitations and imprecision. The study did not assess the effects of physical exercise training on physical activity levels. No study‐related serious adverse events or adverse events leading to withdrawal occurred, but we cannot draw wider conclusions from this very low‐certainty evidence.
Authors' conclusions
It is uncertain whether combined strength and aerobic exercise training is beneficial or harmful in people with SMA type 3, as the quality of evidence is very low. We need well‐designed and adequately powered studies using protocols that meet international standards for the development of training interventions, in order to improve our understanding of the exercise response in people with SMA type 3 and eventually develop exercise guidelines for this condition.
On the occasion of the 13th International Conference on Osteogenesis imperfecta in August 2017 an expert panel was convened to develop an international consensus paper regarding physical ...rehabilitation in children and adolescents with Osteogenesis imperfecta. The experts were chosen based on their clinical experience with children with osteogenesis imperfecta and were identified by sending out questionnaires to specialized centers and patient organizations in 26 different countries. The final expert-group included 16 representatives (12 physiotherapists, two occupational therapists and two medical doctors) from 14 countries. Within the framework of a collation of personal experiences and the results of a literature search, the participating physiotherapists, occupational therapists and medical doctors formulated 17 expert-statements on physical rehabilitation in patients aged 0-18 years with osteogenesis imperfecta.
To assess the prevalence of fatigue, pain, anxiety, and depression in adults with Duchenne muscular dystrophy (DMD), and to analyze their relationship with health-related quality of life.
...Cross-sectional study.
Home of participants.
Adults (N=80) with DMD.
Not applicable.
Fatigue was assessed with the Fatigue Severity Scale; pain with 1 item of the Medical Outcomes Study 36-Item Short-Form Health Survey and by interview; and anxiety and depression by using the Hospital Anxiety and Depression Scale. Health-related quality of life was assessed using the World Health Organization Quality of Life Scale-Brief Version. Associations between these conditions and quality of life were assessed by means of univariate and multivariate logistic regression analyses.
Symptoms of fatigue (40.5%), pain (73.4%), anxiety (24%), and depression (19%) were frequently found. Individuals often had multiple conditions. Fatigue was related to overall quality of life and to the quality-of-life domains of physical health and environment; anxiety was related to the psychological domain.
Fatigue, pain, anxiety, and depression, potentially treatable symptoms, occur frequently in adults with DMD and significantly influence health-related quality of life.
Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural ...history of lung function in SMA has, however, not been studied in much detail.
We analysed 2098 measurements of lung function from 170 treatment-naïve patients with SMA types 1c-4, aged 4-74 years. All patients are participating in an ongoing population-based prevalence cohort study. We measured Forced Expiratory Volume in 1 s (FEV
), Forced Vital Capacity (FVC), and Vital Capacity (VC). Longitudinal patterns of lung function were analysed using linear mixed-effects and non-linear models. Additionally, we also assessed postural effects on results of FEV
and FVC tests. In early-onset SMA types (1c-3a), we observed a progressive decline of lung function at younger ages with relative stabilisation during adulthood. Estimated baseline values were significantly lower in more severely affected patients: %FEV
ranged from 42% in SMA type 1c to 100% in type 3b, %FVC 50 to 109%, and %VC 44 to 96%. Average annual decline rates also differed significantly between SMA types, ranging from - 0.1% to - 1.4% for FEV
, - 0.2% to - 1.4% for FVC, and + 0.2% to - 1.7% for VC. In contrast to SMA types 1c-3a, we found normal values for all outcomes in later-onset SMA types 3b and 4 throughout life, although with some exceptions and based on limited available data. Finally, we found no important differences in FVC or FEV
values measured in either sitting or supine position.
Our data illustrate the longitudinal course of lung function in patients with SMA, which is characterised by a progressive decline in childhood and stabilisation in early adulthood. The data do not support an additional benefit of measuring FEV
or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.
The low-salinity effect (LSE) in carbonate rock has been less explored in comparison to sandstone rock. Laboratory experiments have shown that brine composition and (somewhat reduced) salinity can ...have a positive impact on oil recovery in carbonates. However, the mechanism leading to improved oil recovery in carbonate rock is not well understood. Several studies showed that a positive low-salinity flooding (LSF) effect might be associated with dissolution of rock; however, because of equilibration, dissolution may not contribute at reservoir scale, which would make LSF for carbonate rock less attractive for field applications. This raises now the question whether calcite dissolution is the primary mechanism of the LSF effect. In this paper, we aim to first demonstrate the positive response of carbonate rock to low salinity and then to gain insight into the underlying mechanism(s) specific to carbonate rock. We followed a similar methodology as in sandstone rock Mahani H. ; Berg S. ; Ilic D. ; Bartels W.-B. ; Joekar-Niasar V. Kinetics of low-salinity-flooding effect. SPE J. 2015, 20 (1), 8−20 , DOI: 10.1021/ef5023847 using a model system comprised of carbonate surfaces obtained from crushed carbonate rocks. Wettability alteration upon exposure to low-salinity brine was examined by continuous monitoring of the contact angle. Furthermore, the effective surface charge at oil–water and water–rock interfaces was quantified via ζ-potential measurements. Mineral dissolution was addressed both experimentally and with geochemical modeling using PHREEQC. Two carbonate rocks with different mineralogy were investigated: limestone and Silurian dolomite. Four types of brines were used: high-salinity formation water (FW), seawater (SW), 25× diluted seawater (25dSW), and 25× diluted seawater equilibrated with calcite (25dSWEQ). It was observed that, by switching from FW to SW, 25dSW, and 25dSWEQ, the limestone surface became less oil-wet. The results with SW and 25dSWEQ suggest that the LSE occurs even in the absence of mineral dissolution, because no dissolution is expected in SW and none in 25dSWEQ. The wettability alteration to a less oil-wetting state by low salinity is consistent with the ζ-potential data of limestone, indicating that, at lower salinities, the charges at the limestone–brine interface become more negative, indicative of a weaker electrostatic adhesion between the oil–brine and rock–brine interfaces, thus recession of the three-phase contact line. In comparison to limestone, a smaller contact angle reduction was observed with dolomite. This is again consistent with the ζ-potential of dolomite, generally showing more positive charges at higher salinities and less decrease at lower salinities. This implies that oil detachment from the dolomite surface requires a larger reduction of adhesion forces at the contact line than limestone. Our study concludes that surface charge change is likely to be the primary mechanism, which means that there is a positive LSE in carbonates without mineral dissolution.
To determine construct validity and test-retest reliability of Endurance Shuttle Tests as outcome measures for fatigability of remaining motor functions in children and adults with Spinal Muscular ...Atrophy (SMA) across the severity spectrum.
We assessed the Endurance Shuttle - Nine Hole Peg Test (ESNHPT), - Box and Block Test (ESBBT) and - Walk Test (ESWT) in 61 patients with SMA types 2-4, 25 healthy controls (HC) and 15 disease controls (DC). Convergent validity, discriminative validity and test-retest reliability were investigated. Additionally, we compiled the Endurance Shuttle Combined Score (ESTCS) by selecting the most relevant endurance test of each individual. 54, 70 and 73% of patients with SMA demonstrated increased fatigability on the ESNHPT, ESBBT and the ESWT. Endurance response in SMA was characterized by a decrease in muscle strength, an increase in muscle fatigue and an increase in motor adaptions, thereby confirming convergent validity. Patients with SMA showed increased drop-out rates and a shorter endurance time compared to HC and DC demonstrating good discriminative validity. Test-retest reliability was moderate to excellent (ICC's ranging from .78 to .91) with a trend towards better performance on retest. The ESTCS increased sample size and drop-out rate up to 100 and 85%.
Fatigability is an important additional dimension of physical impairments across the severity spectrum in children and adults with SMA. The EST's are reliable and valid to document fatigability of walking, proximal- and distal arm function in SMA and thus are promising outcome measures for use in clinical trials.
To determine the value of a continuous repetitive task to detect and quantify fatigability as additional dimension of impaired motor function in patients with hereditary proximal spinal muscular ...atrophy (SMA).
In this repeated measure case-control study 52 patients with SMA types 2-4, 17 healthy and 29 disease controls performed five consecutive rounds of the Nine-Hole Peg test to determine the presence of fatigability. We analysed differences in test performance and associations with disease characteristics. Five patients with SMA type 2 (22%) and 1 disease control (3%) could not finish five rounds due to fatigue (p = 0.01). Patients with SMA type 2 performed the test significantly more slowly than all other groups (p < 0.005) and disease controls were slower than healthy controls (p < 0.05). Patients with SMA type 2 performed round five 27% slower than round one, while healthy controls performed round five 14% faster than round one (p = 0.005). There was no difference between SMA type 3a, type 3b/4 or disease controls and healthy controls (p > 0.4). Time needed to complete each round during the five-round task increased in 15 patients with SMA type 2 (65%), 4 with type 3a (36%), 4 with type 3b/4 (22%), 9 disease controls (31%) and 1 healthy control (6%). There was no effect of age at disease onset or disease duration in SMA type 2 (p = 0.39). Test-retest reliability was high.
Fatigability of remaining arm function is a feature of SMA type 2 and can be determined with continuous repetitive tasks.
Respiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract ...infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life.
We measured maximal expiratory and inspiratory pressure (PE
and PI
), Sniff Nasal inspiratory pressure (SNIP), peak expiratory flow (PEF), and peak cough flow (PCF) in treatment-naïve patients with SMA. We used mixed-models to analyze natural history patterns.
We included 2172 measurements of respiratory muscle function from 80 treatment-naïve patients with SMA types 1c-3b. All outcomes were lower in the more severe phenotypes. Significant differences in PEF were present between SMA types from early ages onwards. PEF decline was linear (1-2%/year). PEF reached values below 80% during early childhood in types 1c-2, and during adolescence in type 3a. PE
and PI
were severely lowered in most patients throughout life, with PE
values abnormally low (i.e. < 80 cmH
O) in virtually all patients. The PE
/PI
ratio was < 1 throughout life in all SMA types, indicating that expiratory muscles were most affected. All but SMA type 3b patients had a lowered PCF. Patients with types 2b and 3a had PCF levels between 160 and 270 L/min, those with type 2a around 160 L/min and patients with type 1c well below 160 L/min. Finally, SNIP was low in nearly all patients, most pronounced in more severely affected patients.
There are clear differences in respiratory muscle strength and its progressive decline between SMA types. We observed lower outcomes in more severe SMA types. Particularly PEF may be a suitable outcome measure for the follow-up of respiratory strength in patients with SMA. PEF declines in a rather linear pattern in all SMA types, with clear differences at baseline. These natural history data may serve as a reference for longer-term treatment efficacy assessments.
Spinal Muscular Atrophy (SMA) is characterized by progressive and predominantly proximal and axial muscle atrophy and weakness. Respiratory muscle weakness results in impaired cough with recurrent ...respiratory tract infections, nocturnal hypoventilation, and may ultimately lead to fatal respiratory failure in the most severely affected patients. Treatment strategies to either slow down the decline or improve respiratory muscle function are wanting.
The aim of this study is to assess the feasibility and efficacy of respiratory muscle training (RMT) in patients with SMA and respiratory muscle weakness.
The effect of RMT in patients with SMA, aged ≥ 8 years with respiratory muscle weakness (maximum inspiratory mouth pressure PImax ≤ 80 Centimeters of Water Column cmH2O), will be investigated with a single blinded randomized sham-controlled trial consisting of a 4-month training period followed by an 8-month open label extension phase.
The RMT program will consist of a home-based, individualized training program involving 30-breathing cycles through an inspiratory and expiratory muscle training device. Patients will be instructed to perform 10 training sessions over 5-7 days per week. In the active training group, the inspiratory and expiratory threshold will be adjusted to perceived exertion (measured on a Borg scale). The sham-control group will initially receive RMT at the same frequency but against a constant, non-therapeutic resistance. After four months the sham-control group will undergo the same intervention as the active training group (i.e., delayed intervention). Individual adherence to the RMT protocol will be reviewed every two weeks by telephone/video call with a physiotherapist.
We hypothesize that the RMT program will be feasible (good adherence and good acceptability) and improve inspiratory muscle strength (primary outcome measure) and expiratory muscle strength (key secondary outcome measure) as well as lung function, patient reported breathing difficulties, respiratory infections, and health related quality of life (additional secondary outcome measures, respectively) in patients with SMA.
RMT is expected to have positive effects on respiratory muscle strength in patients with SMA. Integrating RMT with recently introduced genetic therapies for SMA may improve respiratory muscle strength in this patient population.
Retrospectively registered at clinicaltrial.gov: NCT05632666.
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