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1.
Ann Clin Transl Neurol ; 8(5): 1086-1095, 2021 05.
Article in English | MEDLINE | ID: mdl-33788421

ABSTRACT

OBJECTIVE: To estimate muscle oxygen uptake and quantify fatigue during exercise in ambulatory individuals with spinal muscular atrophy (SMA) and healthy controls. METHODS: Peak aerobic capacity (VO2peak ) and workload (Wpeak ) were measured by cardiopulmonary exercise test (CPET) in 19 ambulatory SMA patients and 16 healthy controls. Submaximal exercise (SME) at 40% Wpeak was performed for 10 minutes. Change in vastus lateralis deoxygenated hemoglobin, measured by near-infrared spectroscopy, determined muscle oxygen uptake (ΔHHb) at rest and during CPET and SME. Dual energy X-ray absorptiometry assessed fat-free mass (FFM%). Fatigue was determined by percent change in workload or distance in the first compared to the last minute of SME (FatigueSME ) and six-minute walk test (Fatigue6MWT ), respectively. RESULTS: ΔHHb-PEAK, ΔHHb-SME, VO2peak , Wpeak , FFM%, and 6MWT distance were lower (P < 0.001), and Fatigue6MWT and FatigueSME were higher (P < 0.001) in SMA compared to controls. ΔHHb-PEAK correlated with FFM% (r = 0.50) and VO2peak (r = 0.41) only in controls. Only in SMA, Fatigue6MWT was inversely correlated with Wpeak (r = -0.69), and FatigueSME was inversely correlated with FFM% (r = -0.55) and VO2peak (r = -0.69). INTERPRETATION: This study provides further support for muscle mitochondrial dysfunction in SMA patients. During exercise, we observed diminished muscle oxygen uptake but no correlation with aerobic capacity or body composition. We also observed increased fatigue which correlated with decreased aerobic capacity, workload, and body composition. Understanding the mechanisms underlying diminished muscle oxygen uptake and increased fatigue during exercise in SMA may identify additional therapeutic targets that rescue symptomatic patients and mitigate their residual disease burden.


Subject(s)
Exercise/physiology , Fatigue/metabolism , Mitochondrial Myopathies/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy, Spinal/metabolism , Oxygen Consumption/physiology , Absorptiometry, Photon , Adolescent , Adult , Child , Exercise Test , Fatigue/etiology , Female , Humans , Male , Middle Aged , Mitochondrial Myopathies/complications , Muscle, Skeletal/diagnostic imaging , Muscular Atrophy, Spinal/complications , Spectroscopy, Near-Infrared , Young Adult
2.
Vasc Med ; 21(1): 33-40, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26608733

ABSTRACT

Despite high morbidity and mortality associated with peripheral artery disease (PAD), it remains under-diagnosed and under-treated. The objective of this study was to develop a screening metric to identify undiagnosed patients at high risk of developing PAD using administrative data. Commercial claims data from 2010 to 2012 were utilized to develop and internally validate a PAD screening metric. Medicare data were used for external validation. The study population included adults, aged 30 years or older, with new cases of PAD identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis/procedure codes or the Healthcare Common Procedure Coding System (HCPCS) codes. Multivariate logistic regression was conducted to determine PAD risk factors used in the development of the screening metric for the identification of at-risk PAD patients. The cumulative incidence of PAD was 6.6%. Sex, age, congestive heart failure, hypertension, chronic renal insufficiency, stroke, diabetes, acute myocardial infarction, transient ischemic attack, hyperlipidemia, and angina were significant risk factors for PAD. A cut-off score of ⩾20 yielded sensitivity, specificity, positive predictive value, negative predictive value, and c-statistics of 83.5%, 60.0%, 12.8%, 98.1%, and 0.78, respectively. By identifying patients at high risk for developing PAD using only administrative data, the use of the current pre-screening metric could reduce the number of diagnostic tests, while still capturing those patients with undiagnosed PAD.


Subject(s)
Administrative Claims, Healthcare , Data Mining/methods , Mass Screening/methods , Peripheral Arterial Disease/epidemiology , Adult , Aged , Aged, 80 and over , Algorithms , Chi-Square Distribution , Databases, Factual , Female , Humans , Logistic Models , Male , Medicare , Middle Aged , Multivariate Analysis , Odds Ratio , Peripheral Arterial Disease/diagnosis , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk Factors , United States/epidemiology , Workflow
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