Association of Initial Maximal Motor Ability With Long-term Functional Outcome in Patients With COL6-Related Dystrophies.

OBJECTIVE: To accurately categorize the phenotypes of individuals with collagen VI-related dystrophies (COL6-RDs) during the first years of life to predict long-term motor function and pulmonary function, to provide phenotype-specific anticipatory care, and to improve clinical trial readiness. METHODS: This retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD. RESULTS: We studied 119 patients with COL6-RD from Spain (n = 54) and the United States (n = 65). The early maximal motor milestones of ability to rise from the floor unassisted and ability to climb 4 steps without holding onto a railing demonstrated reliability in distinguishing between 3 COL6-RD phenotypic subgroups: (1) Ullrich congenital muscular dystrophy, (2) intermediate COL6-RD, and (3) Bethlem myopathy. Long-term motor function and pulmonary function are strongly correlated with the maximal motor ability achieved during the first years of life. Maximal motor capacity can predict other disease-relevant events such as the age at loss of ambulation and the need for the initiation of nocturnal noninvasive ventilation. CONCLUSION: This work proposes a prospective phenotypic classification for COL6-RDs that will enable an accurate prediction of a patient's COL6-RD phenotype during the first years of life. The ability to establish a patient's COL6-RD phenotypic classification early will enable a more accurate prognosis of future motor and pulmonary function, thus improving anticipatory clinical care, and it will be instrumental in aiding the design of future clinical trials by allowing early stratification of trial cohorts.

Effectiveness of a multidisciplinary BIOPSYCHOSOCIAL intervention for non-specific SUBACUTE low back pain in a working population: a cluster randomized clinical trial.

BACKGROUND: Low back pain (LBP) is a multifactorial condition with individual and societal impact that affects populations globally. Current guidelines for the treatment of LBP recommend pharmacological and non-pharmacological strategies. The aim of this study was to compare usual clinical practice with the effectiveness of a biopsychosocial multidisciplinary intervention in reducing disability, severity of pain and improving quality of life in a working population of patients with subacute (2-12 weeks), non-specific LBP. METHODS: Longitudinal cluster randomized clinical trial conducted in 39 Primary Health Care Centres (PHCC) of Barcelona, with patients aged 18-65 years (n = 501; control group = 239; 26 PHCC, intervention group = 262; 13 PHCC). The control group received usual clinical care. The intervention group received usual clinical care plus a biopsychosocial multidisciplinary intervention, which consisted of physiotherapy, cognitive-behavioural therapy and medication. The main outcomes were changes in the Roland Morris Disability Questionnaire (RMDQ), and the minimal clinically important differences. Secondary outcomes were changes in the McGill Pain (MGPQ) and Quality of Life (SF-12) questionnaires. Assessment was conducted at baseline, 3 and 12 months. Analysis was by intention-to-treat and analyst-blinded. Multiple imputations were used. RESULTS: Of the 501 enrolled patients, 421 (84%) provided data at 3 months, and 387 (77.2%) at 12 months. Mean age was 46.8 years (SD: 11.5) and 64.7% were women. In the adjusted analysis of the RMDQ outcome, only the intervention group showed significant changes at 3 months (- 1.33 points, p = 0.005) and at 12 months (- 1.11 points, p = 0.027), but minimal clinically important difference were detected in both groups. In the adjusted analysis of the RMDQ outcome, the intervention group improvement more than the control group at 3 months (- 1.33 points, p = 0.005) and at 12 months (- 1.11 points, p = 0.027). The intervention group presented a significant difference. Both groups presented a minimal clinically important difference, but more difference in the intervention group. The intervention group presented significant differences in the MGPQ scales of current pain intensity and VAS scores at 3 months. No statistically significant differences were found in the physical and mental domains of the SF-12. CONCLUSIONS: A multidisciplinary biopsychosocial intervention in a working population with non-specific subacute LBP has a small positive impact on disability, and on the level of pain, mainly at short-term, but no difference on quality of life. TRIAL REGISTRATION: ISRCTN21392091 (17 oct 2018) (Prospectively registred).

Identification of serum microRNAs as potential biomarkers in Pompe disease.

OBJECTIVE: To analyze the microRNA profile in serum of patients with Adult Onset Pompe disease (AOPD). METHODS: We analyzed the expression of 185 microRNAs in serum of 15 AOPD patients and five controls using microRNA PCR Panels. The expression levels of microRNAs that were deregulated were further studied in 35 AOPD patients and 10 controls using Real-Time PCR. Additionally, the skeletal muscle expression of microRNAs which showed significant increase levels in serum samples was also studied. Correlations between microRNA serum levels and muscle function test, spirometry, and quantitative muscle MRI were performed (these data correspond to the study NCT01914536 at ClinicalTrials.gov). RESULTS: We identified 14 microRNAs that showed different expression levels in serum samples of AOPD patients compared to controls. We validated these results in a larger cohort of patients and we found increased levels of three microRNAs, the so called dystromirs: miR-1-3p, miR-133a-3p, and miR-206. These microRNAs are involved in muscle regeneration and the expression of these was increased in patients' muscle biopsies. Significant correlations between microRNA levels and muscle function test were found. INTERPRETATION: Serum expression levels of dystromirs may represent additional biomarkers for the follow-up of AOPD patients.

Assessment of disease progression in dysferlinopathy: A 1-year cohort study.

OBJECTIVE: To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year. METHODS: One hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis. RESULTS: The functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint. CONCLUSION: Certain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials. CLINICALTRIALSGOV IDENTIFIER: NCT01676077.

Accuracy for optical diagnosis of colorectal polyps in clinical practice.

BACKGROUND: Optical diagnostic involves predicting polyp histopathology from its endoscopic characteristics. It is only recommended for diminutive polyps ( < or = 5 mm) and for predictions made with high confidence. OBJECTIVES: To evaluate the accuracy of optical imaging in clinical practice and to assess if optical diagnosis is useful for predicting future colonoscopy surveillance intervals without waiting for histopathological analysis. METHODS: consecutive > 18 years patients were enrolled in this prospective study. Colonoscopies were performed by five expert endoscopists who previously participated in an ex-vivo training. Colonoscopes CF-H180AL and CF-Q180AL were used together with Exera II (Olympus Medical System, Tokyo, Japan) processors. Each polyp was characterized in real time using white light and Narrow Band Imaging. Accuracy of optical diagnosis (S, E, NPV, PPV) and correlation between surveillance interval based on optical diagnosis and histopathological analysis were calculated. RESULTS: 311 colon polyps < 10 mm (216 diminutive) in 195 patients were analyzed. Accuracy of optical diagnostics for predictions made with high confidence: Diminutive polyps(sensitivity 0.59, specificity 0.92, NPV 0.48); polyps < 10 mm (sensitivity 0.73, specificity 0.88, NPV 0.50). An optical diagnosis based surveillance recommendation was given to 90 patients. Concordance with histopathology based recommendation was 92.2% according to the European guideline and 93.3% according to the ESGE guideline. CONCLUSIONS: Optical diagnostics can be used to predict future surveillance intervals immediately after colonoscopy. However, in this study, based on clinical practice, the accuracy of optical imaging is below the recommended standards.

Does "responsive insertion technology" improve practice of colonoscopy? Results of a randomized study.

OBJECTIVE. During colonoscopy, advancing the endoscope can sometimes be difficult due to the appearance of loops or bends in the insertion tube. Therefore, research continues toward improving colonoscope technology. The aim of this study is to compare the use of colonoscopes equipped with "responsive insertion technology" (RIT) versus regular non-RIT colonoscopes. MATERIALS AND METHODS. Prospective, comparative and randomized trials that included patients submitted to colonoscopy. In group I, RIT colonoscopes were used, while in group II, colonoscopies with variable stiffness but without the other components of the RIT technology were used. Demographic variables and variables related to colonoscopy, as well as the pain perceived by the patient and the difficulty in performing endoscopy were recorded. RESULTS. A total of 122 patients were included in group I and 120 patients in group II. The cecal intubation rate was similar in both groups. The use of the RIT colonoscopes was associated with a lower cecal intubation time (4.4 ± 2.0 vs. 5.4 ± 3.5, p = 0.005) and a lower difficulty in performing examinations for both the endoscopist (19.1 ± 20.0 vs. 27.7 ± 22.2, p = 0.002) and the nursing staff (20.8 ± 17.0 vs. 26.3 ± 19.6, p = 0.04). No significant differences were found between both groups in the need for ancillary maneuvers or in the pain perceived by the patient. CONCLUSIONS. RIT colonoscopes allow cecal intubation in a shorter time compared to variable stiffness colonoscopes, and are associated with a greater level of ease of the procedure.

Study protocol of effectiveness of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.

BACKGROUND: Non-specific low back pain is a common cause for consultation with the general practitioner, generating increased health and social costs. This study will analyse the effectiveness of a multidisciplinary intervention to reduce disability, severity of pain, anxiety and depression, to improve quality of life and to reduce the incidence of chronic low back pain in the working population with non-specific low back pain, compared to usual clinical care. METHODS/DESIGN: A Cluster randomised clinical trial will be conducted in 38 Primary Health Care Centres located in Barcelona, Spain and its surrounding areas. The centres are randomly allocated to the multidisciplinary intervention or to usual clinical care. Patients between 18 and 65 years old (n = 932; 466 per arm) and with a diagnostic of a non-specific sub-acute low back pain are included. Patients in the intervention group are receiving the recommendations of clinical practice guidelines, in addition to a biopsychosocial multidisciplinary intervention consisting of group educational sessions lasting a total of 10 hours. The main outcome is change in the score in the Roland Morris disability questionnaire at three months after onset of pain. Other outcomes are severity of pain, quality of life, duration of current non-specific low back pain episode, work sick leave and duration, Fear Avoidance Beliefs and Goldberg Questionnaires. Outcomes will be assessed at baseline, 3, 6 and 12 months. Analysis will be by intention to treat. The intervention effect will be assessed through the standard error of measurement and the effect-size. Responsiveness of each scale will be evaluated by standardised response mean and receiver-operating characteristic method. Recovery according to the patient will be used as an external criterion. A multilevel regression will be performed on repeated measures. The time until the current episode of low back pain takes to subside will be analysed by Cox regression. DISCUSSION: We hope to provide evidence of the effectiveness of the proposed biopsychosocial multidisciplinary intervention in avoiding the chronification of low back pain, and to reduce the duration of non-specific low back pain episodes. If the intervention is effective, it could be applied to Primary Health Care Centres. TRIAL REGISTRATION: ISRCTN21392091.