Measuring coping in multiple sclerosis: The Coping Index-MS.

BACKGROUND: Coping in multiple sclerosis (MS) refers to cognitive and behavioural efforts to manage stresses imposed by the illness. Existing generic and disease-specific coping scales do not meet modern guidelines for scale development and cannot produce interval-level metrics to allow for change scores. OBJECTIVE: The main aim of this study was to develop a brief patient-reported outcome measure for coping in MS, capable of interval-level measurement. METHODS: Qualitative work in 43 people with MS leads to a draft scale which was administered to 5747 participants, with longitudinal collection in 2290. A calibration sample of 1000 subjects split into development and validation sets was used to generate three scales consistent with Rasch model expectations. RESULTS: The total Coping Index-MS (CI-MS-T), CI-MS-Internal (CI-MS-I) and CI-MS-External (CI-MS-E) cover total, internal and externally focused coping. All three scales are capable of interval-level measurement. Trajectory analysis of 9000 questionnaires showed two trajectories in CI-MS-T: Group 1 showed a low level of coping with slight decline over 40 months, while Group 2 had a better and stable level of coping due to improving CI-MS-I which compensated for the deteriorating CI-MS-E over time. CI-MS-T < 30 identified group membership at baseline. CONCLUSION: The CI-MS-T, CI-MS-I and CI-MS-E, comprising 20 items, provide interval-level measurement and are free-for-use in not-for-profit settings.

The four self-efficacy trajectories among people with multiple sclerosis: Clinical associations and implications.

BACKGROUND: Longitudinal studies among people with Multiple Sclerosis (pwMS) have shown that self-efficacy is linked to physical, cognitive and psychological functioning. OBJECTIVES: To determine the distribution of self-efficacy in a large sample of pwMS, examining whether there are distinct groups which show different self-efficacy trajectories over time, and the health status characteristics of any groups identified. METHODS: Participants completed serial questionnaire packs, including Unidimensional Self-efficacy-MS (USE-MS) scale, for the Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study over an average 46-month period. The resulting longitudinal data were analysed by a group-based trajectory model. RESULTS: 5887 pwMS were studied: mean age 50.2 years (SD 12.0); 73.6% female; Relapsing Remitting MS (61.8%), Secondary Progressive (22.9%), Primary Progressive (11.1%), Rapidly Evolving Relapsing Remitting MS (4.2%). Four distinct self-efficacy trajectories emerged, with declining, slightly declining, stable or improving self-efficacy, each showing different patterns of health status indicators such as EQ-5D-5L, disability and depression. USE-MS ≤ 18 at baseline detected all participants in the two declining groups. CONCLUSION: Future trials on interventions for self-efficacy should assume a priori that those with low levels of self-efficacy (USE-MS ≤ 18 at baseline) are likely to be on a declining trajectory and may need different interventions from those with stable self-efficacy.

Heads Up Football Training Decreases Concussion Rates in High School Football Players.

OBJECTIVE: The objective of this study was to determine whether football players receiving heads up (HU) training would display a lower rate of sport-related concussion (SRC) compared to those without HU training. DESIGN: Prospective cohort. SETTING: Scholastic football fields. PATIENTS: Two thousand five hundred fourteen scholastic football players during the 2015 to 2016 football season were monitored throughout the football season. INTERVENTIONS: Before the preseason, 1 coach from 14 schools received HU training from US football. These schools were matched with 10 control schools performing standard football training [non-heads up (NHU)]. Random monitoring for proper coaching instruction was performed during the season. School athletic trainers monitored injuries and return to sport over the season for all schools. MAIN OUTCOME MEASURES: The outcome measures of concussions and associated time loss were determined before data collection began. Injury incidence and rate ratios were calculated to determine program effectiveness. RESULTS: During the season, football players sustained 117 concussions (HU = 75; NHU = 42). The HU players displayed a significantly lower concussion rate (4.1 vs 6.0/100 players) compared with NHU teams [rate ratio = 1.5; 95% confidence interval (CI), 1.1-5.4]. The HU group returned to full participation 27% faster than athletes in the NHU group [time loss: 18.2 days (95% CI, 15.8-20.6) vs 24.8 days (95% CI, 19.9-29.7)], respectively. CONCLUSIONS: This is the first study to evaluate the impact of the HU program on the incidence of SRC in high school football players. Our data demonstrated that the HU program reduced SRC rates by 33% supporting the use of US HU football training as an effective method to decrease the rate of SRCs in scholastic football. CLINICAL RELEVANCE: This study is the first to prospectively explore the effect of HU training on the incidence and recovery from SRC in high school football players.

Transcript specific regulation of expression influences susceptibility to multiple sclerosis.

Genome-wide association studies (GWAS) have identified over 100 loci containing single nucleotide variants (SNVs) that influence the risk of developing multiple sclerosis (MS). Most of these loci lie in non-coding regulatory regions of the genome that are active in immune cells and are therefore thought to modify risk by altering the expression of key immune genes. To explore this hypothesis we screened genes flanking MS-associated variants for evidence of allele specific expression (ASE) by quantifying the transcription of coding variants in linkage disequilibrium with MS-associated SNVs. In total, we were able to identify and successfully analyse 200 such coding variants (from 112 genes) in both CD4+ and CD8+ T cells from 106 MS patients and 105 controls. Fifty-six of these coding variants (from 43 genes) showed statistically significant evidence of ASE in one or both cell types. In the Lck interacting transmembrane adaptor 1 gene (LIME1), for example, we were able to show that in both cell types, the MS-associated variant rs2256814 increased the expression of some transcripts while simultaneously reducing the expression of other transcripts. In CD4+ cells from an additional independent set of 96 cases and 93 controls we were able to replicate the effect of this SNV on the balance of alternate LIME1 transcripts using qPCR (p = 5 × 10-24). Our data thus indicate that some of the MS-associated SNVs identified by GWAS likely exert their effects on risk by distorting the balance of alternate transcripts rather than by changing the overall level of gene expression.

Athletic Trainers' Effect on Population Health: Improving Access to and Quality of Care.

CONTEXT: The scope of athletic training practice combined with the magnitude of scholastic athletic injuries means that the scholastic athletic trainer (AT) is uniquely positioned to positively affect the overall health care of this population. The AT is equipped to serve in the prevention and primary management of injuries and return to activity of scholastic athletes. However, to optimize the musculoskeletal health of all athletes within a given setting, the gaps in clinical care must be continuously evaluated. Quality improvement (QI) approaches are often used to establish a framework for delivering care that promotes the best health status of the targeted population. OBJECTIVE: To describe the creation, implementation, and early results of a QI initiative aimed at advancing the health of the scholastic athletes served in the Greenville County, South Carolina, school district. DESIGN: Cohort study. PATIENTS OR OTHER PARTICIPANTS: A total of 49 793 athletes. MAIN OUTCOME MEASURE(S): The QI framework consisted of a process that documented the magnitude of athletic injuries, established risk factors for injury, defined intervention steps for at-risk athletes, and evaluated the QI process before and after implementation. The results were regularly reported to participating stakeholders, including ATs, athletic directors, coaches, parents, and athletes. RESULTS: After the QI process, injury rates decreased (absolute risk difference between the 2011-2012 and 2016-2017 academic years = 22%) and resources were more strategically allocated, which resulted in a decrease in health care costs of more than 50%. CONCLUSIONS: Collectively, the QI framework as described provides a systematic process for empowering the AT as the foundation of the scholastic sports medicine team.

Some recent advances in multiple sclerosis.

In this article, we review some of the key advances in multiple sclerosis (MS) over the last 3 years. Significant progress has been made in understanding the genetics and pathogenesis of MS. The classification of MS phenotypes has been revised and the landscape of therapeutics is rapidly evolving. We provide a practical summary of the main developments for the practising neurologist.

Long-term remission with rituximab in refractory leucine-rich glioma inactivated 1 antibody encephalitis.

Autoimmune encephalitis associated with antibodies to leucine-rich glioma inactivated 1 (LGI1) is recently described and there is a lack of detailed reports on the treatment of relapsing or refractory cases and long-term outcomes. Two case reports are presented. Both cases had faciobrachial dystonic seizures (FBDS) and received rituximab after relapsing or refractory disease. Both cases achieved sustained clinical remission of up to 15 and 56 months respectively. Rituximab use allowed withdrawal of corticosteroids and was well tolerated. Randomized clinical trials are needed in LGI1 encephalitis and other autoimmune encephalitides.

Post-infective transverse myelitis following Streptococcus pneumoniae meningitis with radiological features of acute disseminated encephalomyelitis: a case report.

INTRODUCTION: Post-infectious autoimmune demyelination of the central nervous system is a rare neurological disorder typically associated with exanthematous viral infections. We report an unusual presentation of the condition and a previously undocumented association with Streptococcus pneumonia meningitis. CASE PRESENTATION: A 50-year-old Caucasian woman presented to our facility with an acute myelopathy three days after discharge following acute Streptococcus pneumoniae meningitis. Imaging studies of the spine ruled out an infective focus and no other lesions were seen within the cord. Diffuse, bilateral white matter lesions were seen within the cerebral hemispheres, and our patient was diagnosed as having a post-infective demyelination syndrome that met the diagnostic criteria for an acute transverse myelitis. Our patient clinically and radiologically improved following treatment with steroids. CONCLUSIONS: The novel association of a Streptococcus pneumoniae infection with post-infectious autoimmune central nervous system demyelination should alert the reader to the potentially causative role of this common organism, and gives insights into the pathogenesis. The unusual dissociation between the clinical presentation and the location of the radiological lesions should also highlight the potential for the condition to mimic the presentation of others, and stimulates debate on the definitions of acute transverse myelitis and acute disseminated encephalomyelitis, and their potential overlap.

Intimate partner violence: a predictor of worse HIV outcomes and engagement in care.

For HIV-infected patients, experiencing multiple traumas is associated with AIDS-related and all-cause mortality, increased opportunistic infections, progression to AIDS, and decreased adherence to therapy. The impact of intimate partner violence (IPV) on adherence and HIV outcomes is unknown. HIV-infected patients recruited from a public HIV clinic participated in this observational cohort study (n=251). Participants completed interviews evaluating IPV and covariates. CD4 count <200 (CD4<200), detectable HIV viral load (VL), and engagement in care ("no show rate" [NSR]) were the outcomes of interest. Medication adherence was not measured. Univariate and multivariate regression analyses were performed with covariates included if p<0.3 in the univariate phase. Seventy-four percent of the participants were male, 55% Caucasian, and 52.2% self-identified as "men who have sex with men." IPV prevalence was 33.1% with no difference by gender or sexual orientation. In univariate analysis, IPV exposure predicted having a CD4<200 (p=0.005) and a detectable VL (p=0.04) but trended toward significance with a high NSR (p=0.077). Being threatened by a partner was associated with a CD4<200 (p=0.005), a detectable VL (p=0.011), and high NSR (p=0.019) in univariate analysis. In multivariate analysis, IPV predicted having a CD4<200 (p=0.005) and detectable VL (p=0.035). Being threatened by a partner predicted having a CD4<200 (p=0.020), a detectable VL (p=0.007), and a high NSR (p=0.020). Our results suggest IPV impacts biologic outcomes and engagement in care for HIV-infected patients. IPV alone predicts worse biologic outcomes, whereas the specific experience of being threatened by a partner was associated with all three outcomes in univariate and multivariate analyses.

Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE Study.

BACKGROUND: The EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study demonstrated that patients with multiple sclerosis (MS) who initiate interferon beta-1a therapy with 44 microg 3 times weekly (TIW) were less likely to have a relapse or activity on magnetic resonance imaging (MRI) compared with those who initiate therapy at a dosage of 30 microg 1 time weekly (QW). OBJECTIVE: To determine the effect of changing the dosage from 30 microg QW to 44 microg TIW in this extension of the EVIDENCE Study. DESIGN/PATIENTS: Patients with relapsing MS originally randomized to interferon beta-1a, 30 microg QW, during the comparative phase of the study changed to 44 microg TIW, whereas patients originally randomized to 44 microg TIW continued that regimen. Patients were followed up, on average, for an additional 32 weeks. MAIN OUTCOME MEASURE: The within-patient pretransition to post-transition change in relapse rate. RESULTS: At the transition visit, 223 (73%) of 306 patients receiving 30 microg QW converted to 44 microg TIW, and 272 (91%) of 299 receiving 44-microg TIW continued the same therapy. The post-transition annualized relapse rate decreased from 0.64 to 0.32 for patients increasing the dose (P<.001) and from 0.46 to 0.34 for patients continuing 44-microg TIW (P = .03). The change was greater in those increasing dose and frequency (P = .047). Patients converting to the 44-mug TIW regimen had fewer active lesions on T2-weighted MRI compared with before the transition (P = .02), whereas those continuing the 44-microg TIW regimen had no significant change in T2 active lesions. Patients who converted to high-dose/high-frequency interferon beta-1a therapy had increased rates of adverse events and treatment terminations consistent with the initiation of high-dose subcutaneous interferon therapy. CONCLUSIONS: Patients receiving interferon beta-1a improved on clinical and MRI disease measures when they changed from 30 microg QW to 44 microg TIW.

DOES COSMOPOLITANISM RESULT FROM OVERCONSERVATIVE SYSTEMATICS? A CASE STUDY USING THE MARINE SPONGE CHONDRILLA NUCULA.

The sponge species Chondrilla nucula has a simple morphology and a very wide geographical distribution. To verify whether the latter might be an artifact of the former, samples of this species were collected across 10,000 km of its range, in the Mediterranean, the Caribbean, and the southwestern atlantic. The classical (spicule morphology) and molecular (allozymes) systematic approaches were compared, to try to define the geographic limits between populations and detect possible cryptic species. We found five distinct genetic forms within C. nucula that sometimes showed morphological homogeneity and other times plasticity. The difference in size of spicules could not be related to the clear-cut genetic differences, suggesting that the use of spicule sizes for sponge systematics should be reappraised. The population of one of the genetic forms along 3000 km of the Brazilian coast was highly structured (FST = 0.21; Ne m = 0.96). Our results reject the null hypothesis of cosmopolitanism of C. nucula and indicate that the putative worldwide distribution of some marine sponges, and possibly many other benthic invertebrates, may be the result of overly conservative systematics. Cryptic species appear to be particularly prevalent when genera are well defined but species are characterized by only a few morphological characters.