STUDY DESIGN.Concurrent prospective randomized and observational cohort studies.
OBJECTIVE.To assess the 8-year outcomes of surgery versus nonoperative care.
SUMMARY OF BACKGROUND DATA.Although ...randomized trials have demonstrated small short-term differences in favor of surgery, long-term outcomes comparing surgical with nonoperative treatment remain controversial.
METHODS.Surgical candidates with imaging-confirmed lumbar intervertebral disc herniation meeting Spine Patient Outcomes Research Trial eligibility criteria enrolled into prospective randomized (501 participants) and observational cohorts (743 participants) at 13 spine clinics in 11 US states. Interventions were standard open discectomy versus usual nonoperative care. Main outcome measures were changes from baseline in the SF-36 Bodily Pain and Physical Function scales and the modified Oswestry Disability Index-AAOS/Modems version assessed at 6 weeks, 3 months, and 6 months, and annually thereafter.
RESULTS.Advantages were seen for surgery in intent-to-treat analyses for the randomized cohort for all primary and secondary outcomes other than work status; however, with extensive nonadherence to treatment assignment (49% patients assigned to nonoperative therapy receiving surgery versus 60% of patients assigned to surgery) these observed effects were relatively small and not statistically significant for primary outcomes (bodily pain, physical function, Oswestry Disability Index). Importantly, the overall comparison of secondary outcomes was significantly greater with surgery in the intent-to-treat analysis (sciatica bothersomeness P > 0.005, satisfaction with symptoms P > 0.013, and self-rated improvement P > 0.013) in long-term follow-up. An as-treated analysis showed significant surgical treatment effects for primary outcome measures (mean change, surgery vs. nonoperative care; treatment effect; 95% confidence interval)bodily pain (45.3 vs. 34.4; 10.9; 7.7 to 14); PF (42.2 vs. 31.5; 10.6; 7.7 to 13.5); and Oswestry Disability Index (−36.2 vs. −24.8; −11.3; −13.6 to −9.1).
CONCLUSION.Carefully selected patients who underwent surgery for a lumbar disc herniation achieved greater improvement than nonoperatively treated patients; there was little to no degradation of outcomes in either group (operative and nonoperative) from 4 to 8 years.Level of Evidence2
Objective:
The aim of this study was to validate a novel pictorial-based Longshi Scale for evaluating a patient’s disability by healthcare professionals and non-professionals.
Design:
Prospective ...study.
Setting:
Rehabilitation departments from a grade A, class 3 public hospital, a grade B, class 2 public hospital, and a private hospital and seven community rehabilitation centers.
Subjects:
A total of 618 patients and 251 patients with functional disabilities were recruited in a two-phase study, respectively.
Main measures:
Outcome measure: pictorial scale of activities of daily living (ADLs, Longshi Scale). Reference measure: Barthel Index. The Spearman correlation coefficient was used to analyze the validity of Longshi Scale against Barthel Index.
Results:
In phase 1 study, from March 2016 to August 2016, the results demonstrated that the Longshi Scale was both reliable and valid (intraclass correlation coefficient based on two-way random effect (ICC2,1) = 0.877–0.974 for intra-rater reliability; ICC2,1 = 0.928–0.979; κ = 0.679–1.000 for inter-rater reliability; intraclass correlation coefficient based on one-way random effect (ICC1,1) = 0.921–0.984 for test–retest reliability and Spearman correlation coefficient = 0.836–0.899). In the second phase, in March 2018, results further demonstrated that the Longshi Scale had good inter-rater and intra-rater reliability among healthcare professionals and non-professionals including therapists, interns, and personal care aids (ICC1,1 = 0.822–0.882 on Day 1; ICC1,1 = 0.842–0.899 on Day 7 for inter-rater reliability). In addition, the Longshi Scale decreased assessment time significantly, compared with the Barthel Index assessment (P < 0.01).
Conclusion:
The Longshi Scale could potentially provide an efficient way for healthcare professionals and non-professionals who may have minimal training to assess the ADLs of functionally disabled patients.
The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National ...Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with multiple sclerosis (MS). One of the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful in MS. This article addresses the history, application, and psychometric properties of one such MSOAC metric of ambulation or walking namely, the timed 25-foot walk (T25FW). The T25FW has strong reliability over both brief and long periods of time in MS across a large range of disability levels. The outcome of walking speed from the T25FW has obvious real-world relevance and has correlated strongly with other measures of walking and lower extremity function. The T25FW is responsive for capturing intervention effects in pharmacological and rehabilitation trials and has an established value for capturing clinically meaningful change in ambulation. Directions for future research involve validating clinically meaningful improvements on the T25FW as well as determining whether 20% change is clinically meaningful across the disability spectrum. Researchers might further consider synchronizing accelerometers and motion sensors with the T25FW for capturing walking speed in everyday life and the patient’s real environment.
Global developmental delay and intellectual disability are relatively common pediatric conditions. This report describes the recommended clinical genetics diagnostic approach. The report is based on ...a review of published reports, most consisting of medium to large case series of diagnostic tests used, and the proportion of those that led to a diagnosis in such patients. Chromosome microarray is designated as a first-line test and replaces the standard karyotype and fluorescent in situ hybridization subtelomere tests for the child with intellectual disability of unknown etiology. Fragile X testing remains an important first-line test. The importance of considering testing for inborn errors of metabolism in this population is supported by a recent systematic review of the literature and several case series recently published. The role of brain MRI remains important in certain patients. There is also a discussion of the emerging literature on the use of whole-exome sequencing as a diagnostic test in this population. Finally, the importance of intentional comanagement among families, the medical home, and the clinical genetics specialty clinic is discussed.
IMPORTANCE: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data ...collection from the acute to chronic phases of recovery after msTBI. OBJECTIVE: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. DESIGN, SETTING, AND PARTICIPANTS: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. EXPOSURES: Moderate or severe TBI. MAIN OUTCOMES AND MEASURES: The Glasgow Outcome Scale–Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. RESULTS: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men 78.2%; median interquartile range age, 35.5 25-53 years) and moderate TBI (n = 122; 98 men 80.3%; median interquartile range age, 38 25-53 years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 19.3%) and 1 in 3 with moderate TBI (23 of 71 32%) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. CONCLUSIONS AND RELEVANCE: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.
OBJECTIVE:To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348).
METHODS:Alemtuzumab-treated patients ...received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale EDSS score increase ≥1.5 if baseline EDSS = 0), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease baseline score ≥2.0), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs).
RESULTS:Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0–5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2–4, remaining low in year 5 (years 1–5−0.59%, −0.25%, −0.19%, −0.15%, and −0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined.
CONCLUSIONS:Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses.
CLINICALTRIALS.GOV IDENTIFIER:NCT00530348; NCT00930553.
CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
OBJECTIVEDepression is common in multiple sclerosis (MS), but its impact on disability worsening has not yet been determined. We explored the risk of disability worsening associated with depression ...in a nationwide longitudinal cohort.
METHODSThis retrospective cohort study used linked data from 3 Swedish nationwide registriesthe MS Register, National Patient Register, and Prescribed Drug Register. Two incident cohorts were developedcohort 1 included all registered cases of MS in the MS Registry (2001–2014) with depression defined as ≥1 ICD-10 code for depression; and cohort 2 comprised all cases of MS in the MS Registry (2005–2014) with depression defined as ≥1 prescription filled for an antidepressant. Cox regression models were used to compare the risk of reaching sustained disability milestone scores of 3.0, 4.0, and 6.0 on the Expanded Disability Status Scale (EDSS) between persons with MS with and without depression.
RESULTSCohort 1 included 5,875 cases; 502 (8.5%) had depression. Cohort 2 had 3,817 cases; 1,289 (33.8%) were prescribed an antidepressant. Persons with depression were at a significantly higher risk of reaching sustained EDSS scores of 3.0, 4.0, and 6.0, with hazard ratios of 1.50 (95% confidence interval CI 1.20–1.87), 1.79 (95% CI 1.40–2.29), and 1.89 (95% CI 1.38–2.57), respectively. A similar increased risk among persons exposed to antidepressants was observed, with hazard ratios of 1.37 (95% CI 1.18–1.60), 1.93 (95% CI 1.61–2.31), and 1.86 (95% CI 1.45–2.40) for sustained EDSS scores of 3.0, 4.0, and 6.0, respectively.
CONCLUSIONPersons with MS and comorbid depression had a significantly increased risk of disability worsening. This finding highlights the need for early recognition and appropriate treatment of depression in persons with MS.
Objective
Spontaneous recovery is an important determinant of upper extremity recovery after stroke and has been described by the 70% proportional recovery rule for the Fugl–Meyer motor upper ...extremity (FM‐UE) scale. However, this rule is criticized for overestimating the predictability of FM‐UE recovery. Our objectives were to develop a longitudinal mixture model of FM‐UE recovery, identify FM‐UE recovery subgroups, and internally validate the model predictions.
Methods
We developed an exponential recovery function with the following parameters: subgroup assignment probability, proportional recovery coefficient
r
k, time constant in weeks
τ
k, and distribution of the initial FM‐UE scores. We fitted the model to FM‐UE measurements of 412 first‐ever ischemic stroke patients and cross‐validated endpoint predictions and FM‐UE recovery cluster assignment.
Results
The model distinguished 5 subgroups with different recovery parameters (
r1 = 0.09,
τ1 = 5.3,
r2 = 0.46,
τ2 = 10.1,
r3 = 0.86,
τ3 = 9.8,
r4 = 0.89,
τ4 = 2.7,
r5 = 0.93,
τ5 = 1.2). Endpoint FM‐UE was predicted with a median absolute error of 4.8 (interquartile range IQR = 1.3–12.8) at 1 week poststroke and 4.2 (IQR = 1.3–9.8) at 2 weeks. Overall accuracy of assignment to the poor (subgroup 1), moderate (subgroups 2 and 3), and good (subgroups 4 and 5) FM‐UE recovery clusters was 0.79 (95% equal‐tailed interval ETI = 0.78–0.80) at 1 week poststroke and 0.81 (95% ETI = 0.80–0.82) at 2 weeks.
Interpretation
FM‐UE recovery reflects different subgroups, each with its own recovery profile. Cross‐validation indicates that FM‐UE endpoints and FM‐UE recovery clusters can be well predicted. Results will contribute to the understanding of upper limb recovery patterns in the first 6 months after stroke. ANN NEUROL 2020;87:383–393 Ann Neurol 2020;87:383–393
The modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability, is the most widely employed outcome scale in acute stroke trials. The scale's original development ...preceded the advent of modern clinimetrics, but substantial subsequent work has been performed to enable the mRS to meet robust contemporary scale standards. Prior research and consensus recommendations have focused on modernizing 2 aspects of the mRS: operationalized assignment of scale scores and statistical analysis of scale distributions. Another important characteristic of the mRS still requiring elaboration and specification to contemporary clinimetric standards is the Naming of scale outcomes. Recent clinical trials have used a bewildering variety, often mutually contradictory, of rubrics to describe scale states. Understanding of the meaning of mRS outcomes by clinicians, patients, and other clinical trial stakeholders would be greatly enhanced by use of a harmonized, uniform set of labels for the distinctive mRS outcomes that would be used consistently across trials. This statement advances such recommended rubrics, developed by the Stroke Therapy Academic Industry Roundtable collaboration using an iterative, mixed-methods process. Specific guidance is provided for health state terms (eg, Symptomatic but Nondisabled for mRS score 1; requires constant care for mRS score 5) and valence terms (eg, excellent for mRS score 1; very poor for mRS score 5) to employ for 23 distinct numeric mRS outcomes, including: all individual 7 mRS levels; all 12 positive and negative dichotomized mRS ranges, positive and negative sliding dichotomies; and utility-weighted analysis of the mRS.
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