Disability Outcomes In Patients Research Articles

Risk factors for neurological disability outcomes in patients under extracorporeal membrane oxygenation following cardiac arrest: An observational study

ObjectivesThis study aimed to identify factors associated with neurological and disability outcomes in patients who underwent ECMO following cardiac arrest. MethodsThis retrospective, single-center, observational study included adult patients who received ECMO treatment for in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) between February 2016 and March 2020. Factors associated with neurological and disability outcomes in these patients who underwent ECMO were assessed. SettingHamad General Hospital, Qatar. Main outcome measuresNeurological disability outcomes were assessed using the Modified Rankin Scale (mRS) and the Cerebral Performance Category (CPC) scale. ResultsAmong the 48 patients included, 37 (77 %) experienced OHCA, and 11 (23 %) had IHCA. The 28-day survival rate was 14 (29.2 %). Of the survivors, 9 (64.3 %) achieved a good neurological outcome, while 5 (35.7 %) experienced poor neurological outcomes. Regarding disability, 5 (35.7 %) of survivors had no disability, while 9 (64.3 %) had some form of disability. The results showed significantly shorter median time intervals in minutes, including collapse to cardiopulmonary resuscitation (CPR) (3 vs. 6, P = 0.001), CPR duration (12 vs. 35, P = 0.001), CPR to extracorporeal cardiopulmonary resuscitation (ECPR) (20 vs. 40, P = 0.001), and collapse-to-ECPR (23 vs. 45, P = 0.001), in the good outcome group compared to the poor outcome group. ConclusionThis study emphasizes the importance of minimizing the time between collapse and CPR/ECMO initiation to improve neurological outcomes and reduce disability in cardiac arrest patients. However, no significant associations were found between outcomes and other demographic or clinical variables in this study. Further research with a larger sample size is needed to validate these findings. Implications for clinical practiceThe study underscores the significance of reducing the time between collapse and the initiation of CPR and ECMO. Shorter time intervals were associated with improved neurological outcomes and reduced disability in cardiac arrest patients.

Impact of fremanezumab treatment on disability outcomes in patients with migraine and major depressive disorder: Results of the UNITE study

Impact of fremanezumab treatment on disability outcomes in patients with migraine and major depressive disorder: Results of the UNITE study

Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries.

In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset. The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries. Adult RRMS patients who initiated their first-ever DMT between 2013 and 2016 and were included in the Swedish MS register were compared with a similar cohort from the MS register of the Czech Republic using propensity score overlap weighting as a balancing method. The main outcomes of interest were time to confirmed disability worsening (CDW), time to achieve an expanded disability status scale (EDSS) value of 4, time to relapse, and time to confirmed disability improvement (CDI). To support the results, a sensitivity analysis focusing solely on patients from Sweden starting with HE-DMT and patients from the Czech Republic starting with LE-DMT was performed. In the Swedish cohort, 42% of patients received HE-DMT as initial therapy compared to 3.8% of patients in the Czech cohort. The time to CDW was not significantly different between the Swedish and Czech cohorts (p-value 0.2764), with hazard ratio (HR) of 0.89 and a 95% confidence interval (CI) of 0.77-1.03. Patients from the Swedish cohort exhibited better outcomes for all remaining variables. The risk of reaching EDSS 4 was reduced by 26% (HR 0.74, 95%CI 0.6-0.91, p-value 0.0327), the risk of relapse was reduced by 66% (HR 0.34, 95%CI 0.3-0.39, p-value <0.001), and the probability of CDI was three times higher (HR 3.04, 95%CI 2.37-3.9, p-value <0.001). The analysis of the Czech and the Swedish RRMS cohorts confirmed a better prognosis for patients in Sweden, where a significant proportion of patients received HE-DMT as initial treatment.

A Deep Learning System to Predict Recurrence and Disability Outcomes in Patients with Transient Ischemic Attack or Ischemic Stroke

Ischemic strokes (IS) and transient ischemic attacks (TIA) account for approximately 80% of all strokes and are leading causes of death worldwide. Assessing the risk of recurrence or functional impairment in IS and TIA patients is essential to both acute phase treatment and secondary prevention. Current risk prediction systems that rely on clinical parameters alone without leveraging imaging data have only modest performance. Herein, a deep learning‐based risk prediction system (RPS) is developed to predict the probability of stroke recurrence or disability (i.e., deep‐learning stroke recurrence risk score, SRR score). Then, Kaplan–Meier analysis to evaluate the ability of SRR score to stratify patients at stroke recurrence risk is discussed. Using 15 166 Third China National Stroke Registry (CNSR‐III) cases, the RPS's receiver operating characteristic curve (AUC) values of 0.850 for 14 day TIA recurrence prediction and 0.837 for 3 month IS disability prediction are used. Among patients deemed high risk by SRR score, 22.9% and 24.4% of individuals with TIA and IS respectively have stroke recurrence within 1 year, which are significantly higher than the rates in low‐risk individuals. Deep learning‐based RPS can outperform conventional risk scores and has the potential to assist accurate prognostication in stroke patients to optimize management.

Coma Recovery Scale-Revised Predicts Disability Rating Scale in Acute Rehabilitation of Severe Traumatic Brain Injury

ObjectiveTo explore the prognostic value of the Coma Recovery Scale-Revised (CRS-R) in predicting disability outcomes in patients with severe traumatic brain injury using the Disability Rating Scale (DRS). DesignSecondary analysis including linear and logistic regressions were performed. SettingData were collected in a previous clinical trial. ParticipantsOne hundred eighty-four participants across 3 countries (N=184). Main Outcome MeasuresDisability Rating Scales. ResultsAnalyses showed an inverse relation between CRS-R scores obtained at baseline and change in DRS scores at 6 weeks. Similarly, changes in CRS-R scores between baseline and 4 weeks were also found to have an inverse relation to change in DRS scores at 6 weeks. ConclusionsThis study generates a tool that can be used to predict the probability that a patient with severe traumatic brain injury lands in 1 of 3 disability categories. The CRS-R may be useful in prognostication of disability in patients with severe traumatic brain injury.

Effectiveness of lyophilized growth factors injection for subacromial impingement syndrome: a prospective randomized double-blind placebo-controlled study

BackgroundPlatelet-derived lyophilized growth factors (L-GFs) use a standardized number of allogenic pathogen-free platelets instead of autologous platelets used in PRP as a source of growth factors. This study aimed to evaluate the efficacy of L-GF injection versus placebo in subacromial impingement (SIS) treatment.MethodsThe current randomized double-blind placebo-controlled study included sixty patients (40 females and 20 males, aged between 24 and 75 years) diagnosed with SIS (both clinically and sonographically). Patients were randomly assigned to two equal groups. Under ultrasound guidance, group 1 received subacromial saline injection, and group 2 received L-GF injection. Clinical examination, pain visual analogue scale (VAS), shoulder pain and disability index (SPADI) and shoulder ultrasound were performed before and at the 8th week after injection.ResultsFollow-up assessment showed statistically significant improvement in the L-GF group regarding active flexion, active and passive internal rotation and extension, SPADI-disability scale, VAS and thickness of the supraspinatus tendon by US. Regression analysis showed that group 1 was approximately 30 times more likely than the L-GF group to experience painful arc at follow-up. Both groups showed statistically significant improvement in SPADI-pain scale and SPADI-total, flexion and abduction (still the mean value of abduction was significantly higher in the L-GF group).ConclusionsL-GF injection resulted in clinically significant reductions in pain and functional disability outcomes in patients with SIS. An objective significant reduction in the thickness of the supraspinatus tendon, measured by ultrasound, in the L-GF group hopefully encourages proper healing and functioning in SIS.Trial registration: The identification number is NCT04330027, date of first registration (01/04/2020). Unique on 21/11/2019, Protocol ID: 0106178.

Impact of fremanezumab on disability outcomes in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies

BackgroundMigraine is the second leading cause of disability worldwide. Although many preventive treatments reduce migraine frequency and severity, it is unclear whether these treatments reduce migraine-related disability in a clinically meaningful way. This pooled analysis evaluated the ability of fremanezumab to reduce migraine-related disability, based on responses and shifts in severity in patient-reported disability outcomes.MethodsThis pooled analysis included 3 double-blind phase 3 trials (HALO EM, HALO CM, FOCUS) in which patients with episodic or chronic migraine were randomly assigned 1:1:1 to quarterly or monthly fremanezumab or matched placebo for 12 weeks. Migraine-related disability was assessed using the 6-item Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questionnaires. A clinically meaningful improvement in disability was defined per American Headache Society guidelines: for HIT-6, a ≥ 5-point reduction; for MIDAS, a ≥ 5-point reduction when baseline score was 11 to 20 or ≥ 30% reduction when baseline score was > 20. Proportions of patients who demonstrated shifts in severity for each outcome were also evaluated.ResultsFor patients with baseline MIDAS scores of 11 to 20 (n = 234), significantly higher proportions achieved 5-point reductions from baseline in MIDAS scores with fremanezumab (quarterly, 71%; monthly, 70%) compared with placebo (49%; both P ≤ 0.01). For patients with baseline MIDAS scores of > 20 (n = 1266), proportions achieving ≥30% reduction from baseline in MIDAS scores were also significantly higher with fremanezumab (quarterly, 69%; monthly, 79%) compared with placebo (58%; both P < 0.001). For HIT-6 scores, proportions of patients achieving 5-point reductions from baseline were significantly higher with fremanezumab (quarterly, 53%; monthly, 55%) compared with placebo (39%; both P < 0.0001). Proportions of patients with shifts of 1 to 3 grades down in MIDAS or HIT-6 disability severity were significantly greater with quarterly and monthly fremanezumab compared with placebo (all P < 0.0001).ConclusionFremanezumab demonstrated clinically meaningful improvements in disability severity in this pooled analysis.Trial registrationsHALO CM, NCT02621931; HALO EM, NCT02629861; FOCUS, NCT03308968.

A multicentre observational study of the use of antiseizure medication in patients with aneurysmal subarachnoid haemorrhage in the PROMOTE-SAH study

Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5–12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration.

Long-Term Disability Outcomes for Patients With Ischemic Stroke Presenting With Visual Deficits.

Ischemic strokes in both the anterior and posterior circulation can lead to visual deficits, which can affect functional ability. Thrombolytic therapies are often withheld to patients with visual deficits because of either being missed on initial evaluation or because of the misconception that their deficits are not as severe or as disabling. Alternatively, delays in patient arrival for emergent evaluation lead to missed opportunities for acute stroke treatment. This retrospective study aims to explore the differences in perceived long-term disability for patients with stroke who present with visual deficits vs those who do not as a manifestation of their acute stroke syndrome. In addition, we explore the differences in treatment effect with thrombolytics and further analyze if the region of ischemia causing the deficit leads to differences in disability outcomes. We conducted a retrospective analysis of patients with visual deficits as evidenced by an abnormal score on NIHSS categories related to vision (gaze palsy, visual fields, or extinction/inattention). Patients with Acute Ischemic Stroke were reviewed from the Houston Methodist Hospital Outcomes-based Prospective Endpoints in Stroke (HOPES) Registry from 2016-2021 for visual deficits. In total, 155 patient charts with visual deficits and 155 patient charts without a documented visual deficit were reviewed for ischemic stroke location (anterior vs posterior circulation), NIHSS scores, and thrombolytic therapies. The outcome variable was categorized using mRS, as mRS between 0 and 3 while mRS 4 to 6 was considered as poor functional outcome at 90 days. The independent variable was the vision group. A multivariable logistic regression model was constructed adjusting for demographics and comorbidities on the binary outcome. Multivariable logistic model after adjusting for demographics and comorbidities showed that patients with acute ischemic stroke with vision defects were 4 times more likely to have poor functional outcomes at 90 days, with most of these patients (14% vs 6%; P < 0.05) suffering from severe disability compared with patients in the control group (i.e., patients with acute ischemic stroke without vision defects) (OR = 4.05; 95% CI [2.28-7.19]; P < 0.001). The application of thrombolytics and the location of ischemia (ACS vs PCS) did not result in a significant change in disability outcomes in patients with visual defects in this limited sample size. The results of this study indicated that a large population of patients with ischemic stroke experience visual deficits and are, therefore, at an increased likelihood of worse functional outcome. This reveals the necessity for rehabilitation techniques that specifically target visual deficits to speed up the recovery process of these patients. Further studies with larger sample size are needed to assess whether the location of ischemic event and the application of thrombolytic treatments plays a role in the disability outcomes of these patients.

The Mediating Role of Pain Catastrophizing: Understanding the Relationship Between Psychological Distress and Functional Disability in Mild Traumatic Brain Injury

Background. Recovery following brain injury can be significantly impeded by the way in which an individual appraises pain, which in turn, can affect ability to cope with pain, and result in psychological distress. Pain catastrophizing, implicated in the appraisal of pain, can exacerbate the intensity of pain-related distress and impact psychological well-being. However, the concurrent evaluation of these phenomena via functional outcomes has not been examined in mild traumatic brain injury. Material and methods. The present study evaluated de-identified archival data of 190 patients with mild traumatic brain injury following injury in motor vehicle accidents. Of primary interest was whether pain catastrophizing mediated the relationship among psychological distress (i.e., anxiety, depression) and functional disability outcomes in patients with mild traumatic brain injury. Results. Pain catastrophizing was found to have a significant mediating effect on the relationship between anxiety and functional disability, as well as for depression and functional disability. Age, gender, time since injury, and/or pain intensity, were not significant predictors of outcome. Although, pain severity was linked to pain catastrophizing. Moreover, the current work also evaluated feigning amongst a subset of patients with mild traumatic brain injury. Interestingly, it appears that the presence of psychological distress, irrespective of the nature of that reporting, is itself predictive of functional well-being. This is an important clinical finding and supports the role of psychological factors on real-life functional compromise in patients with mild traumatic brain injury. Conclusion. The present study found that psychological distress and functional disability are mediated by pain catastrophizing in patients with mild traumatic brain injury. It also appears that the presence of psychological distress, irrespective of the level of reported complaints (i.e., the over-reporting of symptomatology) itself, is predictive of functional well-being.

Factor Structure, Validity, and Reliability of the STarT Back Screening Tool in Italian Obese and Non-obese Patients With Low Back Pain.

Background: The STarT Back Screening Tool (SBST) is a self-report questionnaire developed for prognostic purposes which evaluates risk factors for disability outcomes in patients with chronic low back pain. Previous studies found that its use enables to provide a cost-effective stratified care. However, its dimensionality has been assessed only using exploratory approaches, and reports on its psychometric properties are conflicting.Objective: The objective of this study was to assess the factorial structure and the psychometric properties of the Italian version of the STarT Back Screening Tool (SBST).Materials and Methods: Patients with medical diagnosis of low back pain were enrolled from a rehabilitation unit of a tertiary care hospital specialized in obesity care (Sample 1) and from a clinical internship center of an osteopathic training institute (Sample 2). At baseline and after 7 days patients were asked to fill a battery of self-report questionnaires. The factorial structure, internal consistency, test-retest reliability, and construct validity of the SBST were assessed.Results: One hundred forty-six patients were enrolled (62 from Sample 1 and 84 from Sample 2). The confirmatory factor analysis showed that the fit of the original two-correlated factors model was adequate (CFI = 0.98, TLI = 0.99, RMSEA = 0.03). Cronbach's α of the total scale (α = 0.64) and of the subscales (physical subscale α = 0.55; psychological subscale α = 0.61) was below the cutoffs, partly because of the low correlation of item 2 with the other items. Test-retest reliability was adequate (ICC = 0.84). The SBST had moderate correlations with comparisons questionnaires, except for the Roland-Morris Disability Questionnaire, which had a high correlation (r = 0.65).Discussion: The SBST has adequate psychometric properties and can be used to assess prognostic factors for disability in low back pain patients.

Error-Manipulation Gait Training for Veterans With Nontraumatic Lower Limb Amputation: A Randomized Controlled Trial Protocol.

he purpose of this study will be to determine the efficacy of error-manipulation gait training (error-augmentation or error-correction) to improve step length symmetry and secondary health outcomes in veterans with unilateral nontraumatic transtibial amputation (TTA). This will be a 3-arm, parallel, assessor-blinded, randomized controlled trial, with baseline, postintervention, and 3-month follow-up assessments in a VA Geriatric Research Education and Clinical Center. Participants are 54 US military veterans ranging in age from 50 to 85years with a unilateral transtibial nontraumatic amputation. Participants will be randomized into 1 of 3 groups: error-augmentation training (EAT), error-correction training (ECT), or supervised walking (CTL). Each group will complete 8 split-belt treadmill walking training sessions of 25minutes each over 4weeks. The EAT group will walk with belts moving at asymmetrical speeds. The ECT group will walk to the cadence of a metronome and the split belts moving at symmetrical speeds. The CTL group will walk with symmetrical belt speeds and without feedback. Step length symmetry is the primary outcome and will be assessed using an asymmetry index during overground walking. Secondary outcomes include lower extremity joint work during treadmill walking, 6-Minute Walk Test performance, daily step count, participant-perceived disability, and residual-limb integumentary health. Outcomes will be assessed at preintervention, 1-week postintervention (primary endpoint), and 13weeks postintervention. This study protocol focuses on an understudied area of rehabilitation for patients with nontraumatic unilateral TTA who have high levels of spatiotemporal gait asymmetry and mobility impairment. The results of this study will inform future implementation of clinical gait training interventions to improve spatiotemporal gait symmetry and long-term health and disability outcomes in patients with nontraumatic unilateral TTA.

Does Patient Body Mass Index Affect the Outcome of Multimodal Rehabilitation in Chronic Mechanical Low Back Pain?

Retrospective. The aim of this study was to investigate the effect of body mass index (BMI) on pain and disability in patients with chronic mechanical low back pain (LBP) treated with multimodal rehabilitation. Despite being a well-known risk factor for developing LBP, there is minimal data on the effect of BMI on pain and disability in patients with chronic mechanical low back pain (LBP) treated with multimodal rehabilitation. Data from patients with chronic mechanical LBP who underwent multimodal rehabilitation treatment at a chain of spine rehabilitation outpatient clinics in one of the three BMI groups-1564 patients in normal body weight (BMI ≥18.5-24.9), 1990 patients in overweight (BMI ≥25-29.9), and 891 patients in obese (BMI ≥ 30) groups-were retrospectively analyzed. Pre- and post-treatment Numerical Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI) scores, and final treatment outcomes were compared between the three groups. Multivariate analysis was used to determine the association between pre-treatment covariates and post-treatment clinical outcomes. Post-treatment, the mean NPRS (P = 0.005) and mean ODI (P < 0.001) scores were significantly higher with a significantly lower percentage of full success outcome (P = 0.009) in the obese group when compared to normal and overweight groups. However, multivariate analysis showed a significant correlation between age, the number of treatment sessions, pre-treatment NPRS and ODI scores, and post-treatment NPRS and ODI scores and treatment failure, and no correlation with patient BMI. Patient BMI may not affect pain and disability outcomes in patients undergoing a multimodal rehabilitation treatment for chronic LBP. In contrast to BMI, other covariates such as age, treatment sessions, and pre-treatment NPRS and ODI scores may be associated with increased risk for poor treatment outcome. Obese individuals can expect clinical outcomes similar to normal or overweight individuals with multimodal physical rehabilitation for chronic LBP.Level of Evidence: 3.

Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register

The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p < 0.05) and a lower mean age (36.1 ± 10.9 vs 38.9 ± 11.8, p < 0.001). The event time to first relapse demonstrated a lower risk in the OG (HR = 0.58; CI 95% 0.48–0.72, p < 0.001). However, no differences were found between the two groups with respect to the risk of CDP (HR = 0.94; CI 95% 0.76–1.29, p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58–0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs.

Association of Sustained Immunotherapy With Disability Outcomes in Patients With Active Secondary Progressive Multiple Sclerosis

It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation. In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53 680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020. The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated. Two outcomes were analyzed as measures of disability accumulation during SPMS: the rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models). Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P = .009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent. In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study's results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.

Long-term outcome in multiple sclerosis patients treated with fingolimod

Background and PurposeOngoing disease activity during treatment has been associated to worse disability outcomes in patients with Multiple Sclerosis (MS). The aim of this study was to assess the 5-year response to fingolimod (FTY) treatment in patients with relapsing-remitting (RRMS) in a real-life setting. MethodsWe included RRMS patients who received FTY for at least 6 months and had a follow-up ≥ 60 months. Treatment response was assessed through the No Evidence of Disease Activity (NEDA)-3 status. ResultsEighty-eight patients were included, of which 51 (58.0%) were NTZ-naïve and 37 (42.0%) NTZ-switchers. The mean age was 38.9 (9.5) years and 58 (65.9%) were females. The proportion of patients on FTY treatment who maintained the NEDA-3 status at 5 years was 55.9% among NTZ-naïve patients and 35.0% among NTZ-switchers (p=0.138). Predictors of NEDA-3 status were lower Expanded Disability Status Scale score at baseline (adjOR=0.28, 95% CI 0.10-0.77; p=0.013) in NTZ-naïve patients and fewer relapses in the 12 months before starting FTY in NTZ-switchers (adjOR=0.05, 95% CI 0.003-0.79; p=0.034). ConclusionsThis study supports the potential of FTY as a disease-modifying treatment for the long-term management of RRMS patients. Patients with milder disability and fewer clinical relapses before treatment may achieve a better disease control.

Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.

Clinical Features, Gender Differences, Disease Course, and Outcome in Neuromyelitis Optica Spectrum Disorder.

Introduction:Neuromyelitis optica spectrum disorder (NMOSD) is an astrocytopathy with a predilection for the optic nerve, spinal cord, and brainstem. In this ambispective study, we evaluate clinical characteristics, responses to therapy, and disability outcomes in patients with NMOSD.Methods:Patients diagnosed as NMOSD and following up for at least 1 year at a tertiary care center in India were recruited. Patient data were collected ambispectively from January 2012 until December 2018.Results:A total of 106 patients (29M/77F) with NMOSD were evaluated. The mean age of onset was 29 (±11.6) years. About 77 patients (72.64%) were positive for the AQP4 antibody. Age of onset was higher for those presenting with an opticospinal syndrome (34.2 years) as compared to either isolated longitudinally extensive transverse myelitis (LETM) (30 years) or optic neuritis (ON) (25.3 years). The most common syndrome at onset was LETM in 57 patients (53.77%) followed by ON in 31 patients (29.24%). Azathioprine was the most common immunotherapy (83.96%) prescribed followed by rituximab (7.54%) and mycophenolate mofetil (1.88%). There was a significant decrease in the number of relapses post-azathioprine (P < 0.001). Out of 67 patients with ON, 21 (31.34%) had complete recovery while 17 (25.37%) patients had a severe deficit at a 3-month follow-up. Out of 92 patients with a motor deficit, 49 (53.26%) patients had a partial motor deficit at a 6-month follow-up. The severe visual deficit at baseline and female gender predicted poor visual and motor recovery, respectively.Conclusion:This is the largest descriptive study on patients with NMOSD from India. Relapse rates were similar irrespective of the clinical presentation, age, gender, and disease course. Treatment with immunosuppressive treatment significantly affected the disease course.

Why does the adverse effect of inappropriate MRI for LBP vary by geographic location? An exploratory analysis

BackgroundEarly magnetic resonance imaging (eMRI) for nonspecific low back pain (LBP) not adherent to clinical guidelines is linked with prolonged work disability. Although the prevalence of eMRI for occupational LBP varies substantially among states, it is unknown whether the risk of prolonged disability associated with eMRI varies according to individual and area-level characteristics. The aim was to explore whether the known risk of increased length of disability (LOD) associated with eMRI scanning not adherent to guidelines for occupational LBP varies according to patient and area-level characteristics, and the potential reasons for any observed variations.MethodsA retrospective cohort of 59,360 LBP cases from 49 states, filed between 2002 and 2008, and examined LOD as the outcome. LBP cases with at least 1 day of work disability were identified by reviewing indemnity service records and medical bills using a comprehensive list of codes from the International Classification of Diseases, Ninth Edition (ICD-9) indicating LBP or nonspecific back pain, excluding medically complicated cases.ResultsWe found significant between-state variations in the negative impact of eMRI on LOD ranging from 3.4 days in Tennessee to 14.8 days in New Hampshire. Higher negative impact of eMRI on LOD was mainly associated with female gender, state workers’ compensation (WC) policy not limiting initial treating provider choice, higher state orthopedic surgeon density, and lower state MRI facility density.ConclusionState WC policies regulating selection of healthcare provider and structural factors affecting quality of medical care modify the impact of eMRI not adherent to guidelines. Targeted healthcare and work disability prevention interventions may improve work disability outcomes in patients with occupational LBP.

Retrospectively acquired cohort study to evaluate the long-term impact of two different treatment strategies on disability outcomes in patients with relapsing multiple sclerosis (RE.LO.DI.MS): data from the Italian MS Register.

The increase in disease-modifying drugs (DMDs) allows individualization of treatment in relapsing multiple sclerosis (RMS); however, the long-term impact of different treatment sequences is not well established. This is particularly relevant for MS patients who may need to postpone more aggressive DMD strategies. To evaluate different therapeutic strategies and their long-term outcomes, measured as relapses and confirmed disability progression (CDP), in MS 'real-world' settings. Multicentre, observational, retrospectively acquired cohort study evaluating the long-term impact of different treatment strategies on disability outcomes in patients with RMS in the Italian MS Register. We evaluated 1152 RMS-naïve patients after propensity-score adjustment. Patients included were receiving: interferon beta-1a (IFN-β1a) 44µg switching to fingolimod (FTY; IFN-switchers; n = 97); FTY only (FTY-stayers; n = 157); IFN-β1a only (IFN-stayers; n = 849). CDP and relapses did not differ between FTY-stayers and IFN-switchers [HR (95% CI) 0.99 (0.48-2.04), p = 0.98 and 0.81 (0.42-1.58), p = 0.55, respectively]. However, IFN-stayers showed increased risk of relapses compared with FTY-stayers [HR (95% CI) 1.46 (1.00-2.12), p = 0.05]. The ideal treatment option for MS is becoming increasingly complex, with the need to balance benefit and risks. Our results suggest that starting with FTY affects the long-term disease outcome similarly to escalating from IFN-β1a to FTY.