Search

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Background Evidence of the cost-effectiveness of telemedicine (TM) for the management of Multiple Sclerosis (MS) has been provided recently. However, some doubts persist about the accuracy of neurological examinations performed remotely. Objectives This study investigated the reliability of neurological evaluations performed through TM in mild MS patients as compared with standard in-person visits. Methods In total, 76 patients with relapsing–remitting MS and Expanded Disability Status Scale (EDSS) ≤ 3.5 were consecutively recruited. Of them, 40 patients (52.6%) accepted to undergo both in-person and TM evaluations with independent examiners within 48 h. We alternatively asked patients to assure or not the presence of a caregiver during TM visits. A satisfaction questionnaire was administered to all participants. Results The inter-rater agreement attributed by two independent neurologists during TM visit was high (κ > 0.80) for EDSS and Functional Systems (FS) scores. Moderate agreement between TM and in-person evaluations emerged for pyramidal (κ = 0.57; p Conclusions Despite the complexity of neurological examination, TM could be useful in monitoring MS patients with low disability.

Background: Teriflunomide (TERI) and dimethyl fumarate (DMF) are licensed as first-line disease-modifying treatments (DMTs) for relapsing remitting Multiple Sclerosis (RRMS) and are largely replacing injectable DMTs. Methods: All RRMS patients starting TERI or DMF between January 1, 2013, and December 31, 2017, were included in the analysis. Time to first relapse, time to confirmed disability progression (CDP), and time to DMT discontinuation have been investigated. Propensity score with inverse probability treatment weighting (IPTW-PS) was used to adjust comparisons for baseline confounders. The aim of the study was to compare the effectiveness, and rate of discontinuation of TERI and DMF as first therapeutic choice in the Italian MS register. Results: A total of 683 patients were considered for the analyses, 185 on TERI and 498 on DMF. Patients on TERI had higher number of relapses (2.3 ± 1.4 vs 1.9 ± 1.1, p=.033) and higher baseline disability level assessed by Expanded Disability Status Scale (EDSS) (2.0, interquartile range-IQR 1.0–3.0 vs 1.5, IQR 1.0–2.0, p=.013). IPTW adjusted Cox models did not reveal any difference between the investigated DMTs for the investigated outcomes. Conclusions: TERI and DMF have similar effectiveness and rate of discontinuation when employed as first therapeutic choice in RRMS patients.

Background: The introduction of oral disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) changed algorithms of RRMS treatment. Objectives: To compare the effectiveness of treatment with dimethyl fumarate (DMF) and teriflunomide (TRF) in a large multicentre Italian cohort of RRMS patients. Materials and Methods: Patients with RRMS who received treatment with DMF and TRF between January 1st, 2012 and December 31st, 2018 from twelve MS centers were identified. The events investigated were “time-to-first-relapse”, “time-to-Magnetic-Resonance-Imaging (MRI)-activity” and “time-to-disability-progression”. Results: 1445 patients were enrolled (1039 on DMF, 406 on TRF) and followed for a median of 34months. Patients on TRF were older (43.5 ± 8.6 vs 38.8 ± 9.2years), with a predominance of men and higher level of disability (p < 0.001 for all). Patients on DMF had a higher number of relapses and radiological activity (p 38DMF = 3.83, CI = 1.11 to 13.23, p = 0.033). Both DMTs controlled similarly MRI activity and disability progression. Conclusions: Patients on DMF had higher relapse-free survival time than TRF group after the first 38 months ontherapy.

1.AbstractBacterial quorum sensing (QS) is a cell-to-cell communication system in which specific signals are activated to coordinate, for example, pathogenic behaviors and help bacteria collectively respond to perturbations. QS in Gram-negative bacteria is typically regulated by a N-acyl-homoserine lactone (AHL) molecules-mediated system, homologous of Vibrio fischeri LuxI-R. In many cases, bacteria possess more than one QS system, based on different types of molecules, that interact through a complex regulatory network. Presumably, these configurations have emerged over time from simpler ones through the acquisition of novel players (e.g. transcription factors) that have been successfully integrated into the native regulatory systems. However, the advantages provided by these alternative/additional configurations on QS-related phenotypes is poorly predictable only based on their underlying network structure. Here, we have adopted a modelling approach to infer the possible improvements conferred by the acquisition of additional control over bacterial regulation of QS. We use the Burkholderia genus as a case study because some of these strains, besides the LuxIR-like system (named CepIR), possess an integrated regulatory module named CciIR that interferes with the CepIR system through the implementation of several positive and negative control loops. Being associated to a genomic island (cci island), this additional module is prone to being horizontally transferred, giving rise to a potentially patchy genomic distribution and, in turn, to a complete (CepIR and CciIR systems together) vs. core (CepIR only) organization of QS regulation in this group of microorganisms. By using both deterministic and stochastic modelling we show that, upon their activation, the two regulatory schemes may lead to different phenotypes and to distinct responses to the extracellular concentration of signalling molecules. In particular, our simulations show that the presence of the additional regulatory module may confer specific improvements, including a faster response time and optimized control of QS regulation. Interestingly, some of these features may be particularly advantageous during host invasion, thus highlighting once more the importance of QS in the establishment and maintenance of bacterial infections.

Introduction/Aims Individuals with refractory generalized myasthenia gravis (gMG) who have a history of rituximab use and experience persistent symptoms represent a population with unmet treatment needs. The aim of this analysis was to evaluate the efficacy and safety of eculizumab in patients with refractory anti-acetylcholine receptor antibody-positive (AChR(+)) gMG previously treated with rituximab. Methods This post hoc subgroup analysis of the phase 3 REGAIN study (NCT01997229) and its open-label extension (OLE; NCT02301624) compared baseline characteristics, safety, and response to eculizumab in participants who had previously received rituximab with those who had not. Rituximab use was not permitted within the 6 months before screening or during REGAIN/OLE. Results Of 125 REGAIN participants, 14 had received rituximab previously (7 received placebo and 7 received eculizumab). In the previous-rituximab group, 57% had used at least four other immunosuppressants compared with 16% in the no-previous-rituximab group. Myasthenia Gravis Activities of Daily Living total scores from eculizumab baseline to week 130 of eculizumab treatment improved in both the previous-rituximab and no-previous-rituximab groups (least-squares mean -4.4, standard error of the mean [SEM] 1.0 [n = 9] and least-squares mean -4.6, SEM 0.3 [n = 67], respectively; difference = 0.2, 95% confidence interval -1.88 to 2.22). In addition, in both groups, most patients who were treated with eculizumab for 130 weeks achieved a Myasthenia Gravis Foundation of America post-intervention status of minimal manifestations (66.7% and 65.0%, respectively). The eculizumab safety profile was similar between groups and consistent with its established profile. Discussion Eculizumab is an effective therapy for patients with refractory AChR(+) gMG, irrespective of whether they had received rituximab treatment previously.

Background: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood. Objective: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status. Methods: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsing–remitting MS treated with subcutaneous interferon beta-1a. Results: In total, 331 patients completed the study (168 received interferon beta-1a, 44 µg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 µg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low ( Conclusion: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found.

In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a "free-of-charge" protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period. NEDA-3 was defined as absence of relapses, disability worsening, and MRI activity. Disability improvement was defined as a sustained reduction of ≥ 1-point in Expanded Disability Status Scale (EDSS) score. At follow-up, 18 (45%) patients achieved NEDA-3, 30 (75%) were relapse-free, 33 (82.5%) were EDSS worsening-free, and 25 (62.5%) were MRI activity-free. Eleven (27.5%) patients had a sustained disability improvement. We found no predictor for the NEDA-3 status, while the interaction of higher EDSS score by higher number of pre-alemtuzumab relapses was associated with a greater chance of disability improvement (odds ratio 1.10, p = 0.049). Our study provides real-world evidence that alemtuzumab can promote clinical and MRI disease remission, as well as disability improvement, in a significant proportion of patients with RRMS despite prior multiple DMT failures. The drug safety profile was consistent with data available from clinical trials.

Marine ecosystems are characterized by an intricate set of interactions among their representatives. One of the most important occurs through the exchange of dissolved organic matter (DOM) provided by phototrophs and used by heterotrophic bacteria as their main carbon and energy source. This metabolic interaction represents the foundation of the entire ocean food-web.Here we have assembled a synthetic ecosystem to assist the systems-level investigation of this biological association. This was achieved building an integrated, genome-scale metabolic reconstruction using two model organisms (a diatom Phaeodactylum tricornutum and an heterotrophic bacterium, Pseudoalteromonas haloplanktis) to explore and predict their metabolic interdependencies. The model was initially analysed using a constraint-based approach (Flux Balance Analysis, FBA) and then turned into a dynamic (dFBA) model to simulate a diatom-bacteria co-culture and to study the effect of changes in growth parameters on such a system. Finally, we developed a simpler dynamic ODEs system that, fed with dFBA results, was able to qualitatively describe this synthetic ecosystem and allowed performing stochastic simulations to assess the effect of noise on the overall balance of this co-culture.We show that our model recapitulates known metabolic cross-talks of a phototroph-heterotroph system, including mutualism and competition for inorganic ions (i.e. phosphate and sulphate). Further, the dynamic simulation predicts realistic growth rate for both the diatom and the bacterium and a steady state balance between diatom and bacterial cell concentration that matches those determined in experimental co-cultures. This steady state, however, is reached following an oscillatory trend, a behaviour that is typically observed in the presence of metabolic co-dependencies. Finally, we show that, at high diatom/bacteria cell concentration ratio, stochastic fluctuations can lead to the extinction of bacteria from the co-culture, causing the explosion of diatom population. We anticipate that the developed synthetic ecosystem will serve in the future as a basis for the generation of testable hypotheses and as a scaffold for integrating and interpreting-omics data from experimental co-cultures.

Effective communication in clinical encounters is dependent upon the exchange of accurate information between clinician and patient and the use of interpersonal skills that foster development of the patient-provider relationship and demonstrate understanding of the patient's social and cultural background. These skills are of critical importance in the diagnosis and management of hearing loss in children of Spanish-speaking families. While the provision of family friendly, culturally sensitive services to families of children with hearing loss can be challenging for audiologists and speech-language pathologists, the quality and satisfaction of these services is widely recognized as the cornerstone of patient satisfaction and improved outcomes. The purpose of this pilot study was to explore patient, audiologist, and interpreter satisfaction of the use of remote face-to-face language interpretation technologies in the context of audiology services. Parent participants rated each session regarding satisfaction with the communication exchange, audiology services, and the interpreting experience. Audiologists rated their satisfaction with the communication exchange, relationship with the parent, and experience with the interpreter. Interpreters rated their satisfaction with the logistics regarding the appointment, information exchange, and experience in working with the audiologist. Audiologists and interpreters were asked to identify what worked well and what challenges needed to be addressed. Data from this pilot study can be used to guide future efforts in providing high quality language interpretation services to Spanish-speaking families of young children who are at risk for or have been diagnosed with hearing loss.

The Polynoidae and Sabellidae represent two polychaete families with contrasting life habits and different phylogenetic constraints. Species of both families studied in this work were collected on the shelf of the Eastern Weddell Sea (Antarctica) during the EASIZ-I (1996) and EASIZ-II (1998) expeditions. Among the Polynoidae, three different species of the genus Harmothoe were observed to brood eggs under the dorsal elytra, which is an uncommon feature in this family. The egg size of all brooding taxa ranged between 120 and 216 μm. Three Sabellidae species were studied: Myxicola cf sulcata is gonochoric with eggs among the largest (up to 1000 μm) recorded for the sabellids. Eggs, as well as larvae, are incubated within the branchial crown, a feature newly discovered for the genus Myxicola. Demonax polarsterni n. sp. (a newly discovered taxon) and Euchone pallida are gonochoric and possess relatively large eggs (350 μm and 270 μm, respectively). In comparison with cogeneric species of temperate areas, the Antarctic Sabellidae have larger egg dimensions and egg brooding that seems unconstrained by adult size.

Readability, user-friendliness, and key content are important components of newborn screening brochure design. Health information at a sixth grade or below reading level, designed for ease of navigation, with easily identifiable “action steps” can help adults with limited literacy skills find, understand, and use health information. The purpose of this study was to quantify the readability, user-friendliness, and key content components of newborn hearing screening brochures. Five readability formulae (FRE, F–K GL, FOG, FORCAST, and SMOG) were used to estimate reading levels of English language EHDI brochures (N = 48). Twenty-three participants assessed brochures for user-friendliness. Three participants assessed brochures to determine if key content elements were included and if so, the ease of locating them. Readers are provided with simple steps to follow during brochure design to maximize the message in parent education materials. This study forms the framework for quality improvement efforts and research-to-practice initiatives in the field.

Family support has evolved from a buzzword of the 1990s to a concept founded in theory, mandated by federal law, valued across disciplines, and espoused by both parents and professionals. This emphasis on family-centered practices for families of young children with disabilities, coupled with federal policy initiatives and technological advances, served as the impetus for the development of Early Hearing Detection and Intervention (EHDI) programs (Nicholson & Martin, in press). White, Forsman, Eichwald, and Muñoz (2010) provide an excellent review of the evolution of EHDI systems, which include family support as one of their 9 components. The National Center for Hearing Assessment and Management (NCHAM), the Maternal and Child Health Bureau, and the Center for Disease Control Centers cosponsored the first National EHDI Conference. This conference brought stakeholders including parents, practitioners, and researchers from diverse backgrounds together to form a learning collaborative (Forsman, 2002). Attendees represented a variety of state, national, and/or federal agencies and organizations. This forum focused effort on the development of EHDI programs infused with translating research into practices and policy. When NCHAM, recognizing the critical role of family support in the improvement of outcomes for both children and families, created a think tank to investigate the concept of a conference centered on support for families of children who are deaf or hard of hearing in 2005, the “Investing in Family Support” (IFSC) conference was born. This conference was specifically designed to facilitate and enhance EHDI efforts within the family support arena. From this venue, a model of family support was conceptualized and has served as the cornerstone of the IFSC annual conference since 2006. Designed to be a functional framework, the IFSC model delineates where and how families find support. In this article, we will promote and encourage continued efforts towards defining operational measures and program components to ultimately quantify success as it relates to improved outcomes for these children and their families. The authors view this opportunity to revisit the theoretical underpinnings of family support, the emerging research in this area, and the basics of the IFSC Model of Family Support as a call to action. We challenge professionals who work with children identified as deaf or hard of hearing to move family support from conceptualization to practices that are grounded in evidence and ever mindful of the unique and dynamic nature of individual families.

Objective The purpose of this study was (1) to determine benefit of the Baha Softband coupled to the Softband for infants and children with bilateral conductive hearing loss; and (2) to verify audibility of the speech spectrum for octave frequencies 500 through 4000 Hz. Design The research design for this retrospective chart study is pretest-posttest repeated measures. Setting The study was conducted in the Department of Audiology and Speech Pathology, Arkansas Children's Hospital. Participants Twenty-five children aged 6 months to 18 years with craniofacial disorders and bilateral conductive hearing loss participated in the study. Participants were consistent, full-time unilateral Baha users with the Baha Compact bone-conduction amplifier coupled to the head via the Softband. Interventions The intervention was the Baha device coupled to the head via the Softband as a prerequisite to surgical implantation. Main Outcome Measure(s) The primary study outcome measures used aided and unaided soundfield audiometric thresholds to calculate functional gain. Audibility of the speech spectrum was verified by comparison with target aided thresholds. Results Results revealed an improvement in soundfield thresholds with Baha amplification for the four octave frequencies. Means, standard deviations, and confidence intervals for aided and unaided thresholds are reported. Percentages of thresholds meeting target levels were significant at all frequencies, exceeding the 80% criterion. Conclusions Benefit of the Baha in providing audibility of the speech spectrum for infants and children with bilateral congenital conductive hearing loss has been demonstrated, offering important and timely data supporting third-party reimbursement.

Purpose To evaluate the effects of education level and employment status on health-related quality of life (HRQoL) in a large cohort of patients affected by relapsing-remitting multiple sclerosis (RRMS). Patients This study included 648 patients with RRMS attending 40 Italian MS centers. Inclusion criteria were an Expanded Disability Status Scale (EDSS) score between 1.0 and 5.5; stable disease on enrollment; and no previous treatment with interferons, glatiramer acetate, or immunosuppressive drugs. Quality of life (QoL) was evaluated by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Results Employed patients scored significantly higher than other patient groups in the majority of MSQoL-54 domains. Similarly, patients with academic degrees and secondary education had higher scores than those with primary education (ie, eight years of education) in several domains of HRQoL. Patients who were employed with a high educational level achieved significantly better scores than unemployed patients with a lower educational level. In multivariate analysis, occupation and educational level were found to be significant and independent predictors of HRQoL. Conclusions The results of our study suggest the importance of sustaining employment after a recent diagnosis of MS. In addition, education has a great influence on HRQoL; a higher education level may determine a stronger awareness of the disease, and a better ability to cope with the challenges of a chronic disease such as MS. Multiple Sclerosis 2007; 13: 783-791. http://msj.sagepub.com

Objective: Immunomodulatory drugs (IDs) (interferon beta (IFNβ) and glatiramer acetate (GA)) reduce relapse rate and disease progression in relapsing-remitting multiple sclerosis (RRMS) but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. The aim of this study was to evaluate the impact of IFNβ and GA in MS patients treated before 16 years of age. Methods: A research group (Immunomodulatory Treatment of Early onset MS (ITEMS)) was promoted in Italy to collect a large series of patients affected by clinically definite and RRMS and treated with IDs before 16 years of age. Fifteen centres recognized subjects suitable for inclusion: 76 patients (52 females) were collected with a mean age at onset of 12.4 (SD 2.5) years, a mean disease duration of 18.6 (SD 14.7) and a relapse rate of 3.1 (SD 2.9). Results: Results were evaluated in 65 (45 females) subjects with a pretreatment and a treatment duration >3 months: 38 were treated with IFNβ-1a once weekly (Avonex), 18 with IFNβ three times weekly (16 with Rebif, 2 with Betaferon) and nine with GA (Copaxone). The mean pretreatment period was respectively 20, 18 and 9.2 months. The treatment duration lasted respectively 23.3, 40.7 and 33.3 months. The mean annualized relapse rate decreased dramatically during the treatment: from 2.4 to 0.4 in the Avonex group, from 3.2 to 0.8 in the Rebif-Betaferon group and from 2.8 to 0.25 in the GA group. The mean final EDSS scores were respectively (in brackets the initial scores): 1.3 (1.4), 1.6 (1.8) and 0.6 (1.1). In the whole group, the final score was unchanged or reduced in all subjects except eight. Clinical side effects were recorded in 41/65 subjects (mainly in subjects treated with IFNβ), abnormal laboratory findings were observed in 13/65 subjects: they were transient in most cases. IFNβ was stopped in six cases: in four because of inefficacy and in two cases because of side effects. Conclusions: Sixty-five clinically definite MS subjects were treated during childhood or adolescence with IDs. The treatment reduced the relapse rate and the progression of the disease in most cases. Side effects were common in subjects treated with IFNβ, but were well tolerated in most cases.

Summary Objectives: Evaluate the prevalence of middle ear disease in infants failing a newborn hearing screening program. Review the outcomes of those infants diagnosed with or without middle ear disease after failed hearing screen. Design: Retrospective chart review of 76 patients referred to a tertiary care institution for evaluation of a failed newborn hearing screening test. Setting: Arkansas Children's Hospital, Little Rock, Arkansas. Results: Seventy-six patients were referred for failed OAEs and complete otolaryngology evaluation. Mean age at the time of referral was 3 months (0.25 years) old. OME was identified in 64.5% of the patients. ABR confirmed a suspected hearing loss in 15 patients (78.9%) without middle ear disease. Effusion resolved without surgical intervention in 65.3% of infants, while 17 (34.7%) of the infants required tubes. SNHL was subsequently identified in 11% of infants after resolution of the effusion. Conclusions: OME is a common cause of failed infant hearing screens, and should be looked for prior to definitive diagnostic hearing testing. OME resolves in the majority of infants, but tube insertion is necessary to allow for diagnostic testing in nearly one third of infants. The majority of infants without OME had SNHL confirmed. SNHL was also identified in 11% of infants with OME after resolution of the effusion.

Background Cognitive impairment is a common symptom of multiple sclerosis (MS), but the association between cognitive impairment and magnetic resonance imaging (MRI) disease measures in patients with relapsing–remitting (RR) MS is unclear. Objectives To study the prevalence of cognitive impairment and its relation with MRI disease measures in mildly disabled patients with RRMS. Methods Patients aged 18–50 years with RRMS (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score ≤4.0, who were enrolled in the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study, underwent baseline standardized MRI complete neurological examination and neuropsychological testing. Results A total of 550 patients were enrolled, 327 of whom underwent MRI assessments. Cognitive impairment (impaired performance in ≥3 cognitive tests) was present in approximately 20% of all patients and in the subgroup who underwent MRI. T2 hyperintense and T1 hypointense lesion volumes were significantly higher in patients with cognitive impairment (defined as impaired performance on at least three tests of the Rao’s battery) than those without. EDSS score was also significantly higher in cognitively impaired than in cognitively preserved patients. Disease duration, depression, and years in formal education did not differ significantly between cognitively impaired and cognitively preserved patients. T2 lesion volume, performance intelligence quotient, and age were significant predictors of cognitive impairment in this population. Weak correlations were found between performance on individual cognitive tests and specific MRI measures, with T1 and T2 lesion volumes correlating with performance on most cognitive tests. Conclusions Cognitive impairment occurs in approximately one-fifth of mildly disabled patients with MS and is associated with specific MRI disease measures. Assessment of cognitive function at diagnosis could facilitate the identification of patients who may benefit from therapeutic intervention with disease-modifying therapies to prevent further lesion development.

In a 12-month phase 3 study in patients with relapsing-remitting multiple sclerosis (RRMS), TRANSFORMS, fingolimod showed greater efficacy on relapse rates and MRI outcomes compared with interferon beta-1a. We had two aims in our extension: to compare year 2 with year 1 in the switched patients to assess the effect of a change from interferon beta-1a to fingolimod, and to compare over 24 months the treatment groups as originally randomised to assess the effect of delaying the start of treatment with fingolimod. METHODS: Patients randomly assigned to receive 0.5 mg or 1.25 mg daily oral fingolimod in the core study continued with the same treatment in our extension; patients who originally received 30 μg weekly intramuscular interferon beta-1a were randomly reassigned (1:1) to receive either 0.5 mg or 1.25 mg fingolimod. The initial randomisation and dose of fingolimod assigned for the extension remained masked to the patients and investigators. As in the core study, re-randomisation was done centrally in blocks of six and stratified according to site. Our efficacy endpoints were annualised relapse rate (ARR), disability progression, and MRI outcomes. Our within-group analyses were based on the intention-to-treat and safety populations that entered our extension study. Our between-group analyses were based on the intention-to-treat and safety populations from the core study. This study is registered with ClinicalTrials.gov, number NCT00340834. FINDINGS: 1027 patients entered our extension and received the study drug, and 882 completed 24 months of treatment. Patients receiving continuous fingolimod showed persistent benefits in ARR (0.5 mg fingolimod [n=356], 0.12 [95% CI 0.08-0.17] in months 0-12 vs 0.11 [0.08-0.16] in months 13-24; 1.25 mg fingolimod [n=330], 0.15 [0.10-0.21] vs 0.11 [0.08-0.16]; however, in patients who initially received interferon beta-1a, ARR was lower after switching to fingolimod compared with the previous 12 months (interferon beta-1a to 0.5 mg fingolimod [n=167], 0.31 [95% CI 0.22-0.43] in months 0-12 vs 0.22 [0.15-0.31], in months 13-24 p=0.049; interferon beta-1a to 1.25 mg fingolimod [n=174], 0.29 [0.20-0.40] vs 0.18 [0.12-0.27], p=0.024). After switching to fingolimod, numbers of new or newly enlarging T2 and gadolinium (Gd)-enhancing T1 lesions were significantly reduced compared with the previous 12 months of interferon beta-1a therapy (p

To assess the frequency of clinical features of Sjogren's syndrome (SS) in patients with multiple sclerosis (MS) receiving treatment with disease-modifying drugs (DMDs) or naïve to treatment and the possible association with clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) parameters. A multicentre cross-sectional observational study was designed, based on a structured neurologist-administered questionnaire to 440 patients. Twenty-eight of 230 (12%) patients receiving treatment with DMDs (DMDs(+)) and 14 of 210 (6.6%) treatment-naïve patients (DMDs(-) ) showed clinical features of SS. Four primary SS were diagnosed, two of which were DMDs(+) and two were DMDs(-) . Sicca symptoms were significantly associated with higher EDSS scores (P = 0.018), a low frequency of gadolinium-enhanced MRI-positive lesions (P = 0.018) and cerebral disturbances (P = 0.001).Screening for the clinical features of SS should be performed in patients with MS both receiving treatment with immunomodulatory drugs and without therapy.

PURPOSE OF REVIEW Infant hearing screening has progressed markedly over the past year. Although uncommon in the past, now almost 95% of infants in the United States are screened for hearing loss. Recent literature has expanded on several important components of hearing screening. RECENT FINDINGS A major revision of the American Academy of Pediatrics policy statement on infant hearing screening was published. This statement identifies a number of important principles and guidelines for infant hearing screening. Improvements in diagnostic techniques have been described including the need for auditory brainstem response screening in premature infants. Risk factors for congenital-hearing loss have been updated. An etiologic diagnosis for infants with hearing loss is increasingly possible with advances in genetics and molecular diagnosis. Finally, several articles provide further information on optimizing follow-up and diagnostic testing as well as early intervention. SUMMARY Despite the challenges still present in infant hearing screening, screening continues to identify infants at a very young age, and improve the early communication skills of infants with hearing loss through early diagnosis and early intervention.

The aim of this study was to compare two preference-weighted, caregiver-reported measures of health-related quality of life for children with permanent childhood hearing loss to determine whether cost-effectiveness analysis applied to deaf and hard of hearing populations will provide similar answers based on the choice of instrument.Caregivers of 103 children in Arkansas, USA, with documented hearing loss completed the Quality of Well-Being Scale (QWB) and the Health Utilities Index Mark 3 (HUI3) to describe the health status of their children. Audiology and other clinical measures were abstracted from medical records. Mean scores were compared overall and by degree of hearing loss. Linear regression was used to correlate preference scores with a four-frequency pure-tone average, cochlear implant status, and other factors.Mean preference scores for the QWB and HUI3 were similar (0.601 and 0.619, respectively) although the HUI3 demonstrated a wider range of values (-0.132 to 1.000) compared to the QWB (0.345-0.854) and was more sensitive to mild hearing loss. Both measures correlated with the pure-tone average, were negatively associated with comorbid conditions and positively associated with cochlear implant status. In the best fitting regression models, similar estimates for cochlear implant status and comorbid conditions were obtained from the two measures.Despite considerable differences in the HUI3 and the QWB scale, we found agreement between the two instruments at the mean, but clinically important differences across a number of measures. The two instruments are likely to yield different estimates of cost-effectiveness ratios, especially for interventions involving mild to moderate hearing loss.

The objective was to evaluate the safety, tolerability and effectiveness of intramuscular (IM) interferon beta-1a (IFNbeta-1a; Avonex, Biogen) 30 mg once a week in patients with onset of symptoms of multiple sclerosis (MS) in childhood or adolescence. Patients with a diagnosis of definite MS according to McDonald's criteria, relapsing course according to Lublin's criteria, onset of symptoms of MS before 16 years of age, and who had received IM IFNbeta-1a therapy before 16 years of age were eligible for the study if they had a pretreatment and treatment duration of at least 6 months. Clinical and laboratory evaluations were performed every 3 months. A total of 52 patients were identified as receiving treatment with IM IFNbeta-1a 30 mg once a week before 16 years of age. Mean age at onset of symptoms of MS was 11.7+/-2.7 years, mean disease duration was 25.9+/-30.3 months, mean annualised relapse rate was 1.9+/-1.1 and mean Expanded Disability Status Scale (EDSS) score was 1.5+/-1.1. After a mean (+/-SD) treatment duration of 42.9+/-19.9 months, annualised relapse rate decreased to 0.4+/-0.5. Final EDSS score was 1.3+/-1.1. Adverse events were recorded for 35 (67%) patients (flulike syndrome, 33%; headache, 29%; myalgia, 21%; fever, 11%; fatigue, 6%; nausea and vomiting, 6%; and skin reaction, 4%); most were transient. IM IFNbeta-1a was effective and well tolerated in these paediatric patients with MS.

We analyze the phase equilibria of systems of polydisperse hydrocarbons by means of the recently introduced moment method. Hydrocarbons are modelled with the Soave-Redlick-Kwong and Peng-Robinson equations of states. Numerical results show no particular qualitative difference between the two equations of states. Furthermore, in general the moment method proves to be an excellent method for solving phase equilibria of polydisperse systems, showing excellent agreement with previous results and allowing a great improvement in generality of the numerical scheme and speed of computation., Comment: 12 pages, 2 figures