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Background The IMPACT study demonstrated the benefit of interferon beta-1a (IFNβ-1a, Avonex®) two-year change in disability measured by the Multiple Sclerosis Functional Composite (MSFC) in secondary progressive multiple sclerosis (SP-MS) and health-related quality of life (HRQoL) measured by the Multiple Sclerosis Quality of Life Inventory (MSQLI). The IMPACT data permit a detailed assessment of the relation between clinical and self-reported measures. Methods IMPACT was an international randomized, double-blind, placebo-controlled trial of SP-MS patients. As the MSQLI is only in English, this report includes US and Canadian subjects. Subjects were randomized to weekly intramuscular (im) injections of INβ-1a (60 μg) or placebo for 24 months. Results At baseline and follow-up, MSQLI correlations were generally stronger with the EDSS than with the MSQLI, MSFC but comparable with MSFC components. Combining the two groups, MSQLI changes for those in the best and worst MSFC change quartiles demonstrated a statistical difference for six of the 11 MSQLI scales. Linear regression demonstrated that EDSS change from baseline to month-24 scores was correlated with change in two MSQLI components. Conclusion These data support the appropriateness of using the MSQLI with individuals who have SP-MS. [ABSTRACT FROM AUTHOR]

Cultured baby Syrian hamster kidney cells (BHK 21), synchronized with hydroxyurea (HU), were treated with varying amounts of the carcinogen diethylstilbestrol (DES) during the first mitosis. DES-induced morphologic transformation was assessed by fluorescence microscopy of acridine orange, supravitally stained cells. Traditional karyotyping techniques were used to monitor DES-induced aneuploidy in parallel cell cultures. A total of 618 photomicrographs were obtained by systematic manual scanning of three replicate experiments each using three different DES treatment levels and a no DES control. These photomicrographs were randomized and graded blind by three independent observers. Each photomicrograph was graded for cellular morphologic transformation and a judgement as to whether DES treatment had been used. A definite dose-response relationship for both morphologic transformation, as well as for aneuploidy was observed. These findings portend a significance for use of fluorescence microscopy of morphologic transformation of unfixed supravitally stained mammalian cells, for the rapid assessment (24 h or less) of compounds that promote aneuploidization and carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: The Hypertension Detection and Follow-Up Program (HDFP) carried out two pilot surveillances covering the enumerated population to test procedures to be used in assessing the ability of the program to influence life expectancy in the total population. A rigorously sequenced pilot survey of 2,611 households was conducted and carefully monitored through two mailings, telephone contacts, home visits, and communication with "contact" persons. The response rates at each stage varied among the 13 centers. Overall, there was a 42.7 per ¢ yield from the first mailing, 42.5 per ¢ of those receiving a second mailing was completed; 78.0 per ¢ for telephone 61.3 per ¢ for the home visits and 55.2 per ¢ from the "contact" persons. Overall, 97.4 per ¢ of all persons had vital status ascertained. The second phase relaxed the rigorous sequential survey requirements and reduced the reporting requirements from every ten days to monthly. Overall, 93.3 per ¢ were successfully ascertained. Reduced survey structure, slightly increased mobility (from 12 per ¢ to 13 per ¢), increased workload from 200 to 400 households per center, and a longer time interval between initial enumeration and the mortality ascertainment are among the reasons for performance decline. [ABSTRACT FROM AUTHOR]

Oral bacterial levels of 46 mother-child pairs were monitored from infant birth up to five years of age so that the acquisition of mutans streptococci (MS) by children could be studied. The initial acquisition of MS occurred in 38 children at the median age of 26 months during a discrete period we designated as the "window of infectivity". MS remained undetected in eight children (17%) until the end of the study period (median age of 56 mo). The levels of both MS and lactobacilli in saliva of mothers of children with and without MS were not significantly different. Comparisons between a caries-active cohort colonized by MS (nine of 38) and children without detectable MS revealed similar histories in terms of antibiotic usage, gestational age, and birth weight. Interestingly, half of the children between the ages of one and two years who were not colonized by MS were attended by caretakers other than the mother, while all of the caries-active children during this same time period were cared for by their mothers; the difference was statistically significant. Here we report for the first time that MS is acquired by infants during a defined period in the ontogeny of a child. Support for the notion of a discrete window of infectivity comes from other sources, including animal models. [ABSTRACT FROM AUTHOR]

Multiparametric flow cytometry (FC) of CSF allows one to easily estimate the percentage of lymphocyte subpopulations in CSF. We hypothesized that an increased ratio of B-lineage cells in CSF of MS patients, as assessed with FC, could be useful for diagnostics. We analyzed CSF of 137 patients (70 MS, 24 infectious/autoimmune neurologic disorders (INDs), and 43 non-infectious/autoimmune neurologic disorders (NINDs)), and showed that CSF plasmablasts of >0.1% had a sensitivity of 40% for MS and specificity of 92% when comparing MS and IND, while plasmablasts of >0.25% had sensitivity of 36%, and 100% specificity. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether Constraint-Induced Movement therapy (CI therapy) may benefit chronic upper extremity hemiparesis in progressive multiple sclerosis (MS). Methods Five patients with progressive MS, who had chronic upper extremity hemiparesis and evidence for learned non-use of the paretic limb in the life situation, underwent 30 hours of repetitive task training and shaping for the paretic limb over 2-10 consecutive weeks, along with physical restraint of the less-affected arm and a "transfer package" of behavioral techniques to reinforce treatment adherence. Results The patients showed significantly improved spontaneous, real-world limb use at post-treatment and 4 weeks post-treatment, along with improved fatigue ratings and maximal movement ability displayed in a laboratory motor test. Conclusions The findings suggest for the first time that slowly progressive MS may benefit from CI therapy. Further studies are needed to determine the retention of treatment responses. [ABSTRACT FROM AUTHOR]

BACKGROUND The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis. METHODS In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab. RESULTS Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches. CONCLUSIONS In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.) BACKGROUND Electronic nicotine-delivery systems -- also called e-cigarettes -- are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed. METHODS In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy. The primary outcome was biochemically validated, continuous abstinence from smoking at 6 months. Secondary outcomes included participant-reported abstinence from tobacco and from any nicotine (including smoking, e-cigarettes, and nicotine-replacement therapy) at 6 months, respiratory symptoms, and serious adverse events. RESULTS A total of 1246 participants underwent randomization; 622 participants were assigned to the intervention group, and 624 to the control group. The percentage of participants with validated continuous abstinence from tobacco smoking was 28.9% in the intervention group and 16.3% in the control group (relative risk, 1.77; 95% confidence interval, 1.43 to 2.20). The percentage of participants who abstained from smoking in the 7 days before the 6-month visit was 59.6% in the intervention group and 38.5% in the control group, but the percentage who abstained from any nicotine use was 20.1% in the intervention group and 33.7% in the control group. Serious adverse events occurred in 25 participants (4.0%) in the intervention group and in 31 (5.0%) in the control group; adverse events occurred in 272 participants (43.7%) and 229 participants (36.7%), respectively. CONCLUSIONS The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking-cessation counseling alone. (Funded by the Swiss National Science Foundation and others; ESTxENDS ClinicalTrials.gov number, NCT03589989.) [ABSTRACT FROM AUTHOR]

Background Limited data exist on the prevalence and distribution of sedentary behavior (SB) in multiple sclerosis (MS). Objective The objective of this paper is to describe sitting time as a metric of SB in a large national sample of people with MS. Methods A total of 8004 individuals from the North American Research Committee on MS (NARCOMS) Registry completed the sitting time question from the International Physical Activity Questionnaire in spring 2015. We present descriptive data on sitting time for the total sample and across sociodemographic, clinical, and behavioral characteristics. Results The final sample included 6483 individuals. Of these, 36.7% were classified with mild disability, 24.7% with moderate disability, and 38.6% with severe disability. Median sitting time for the total sample was 480 min/day (P25 = 310 min/day, P75 = 720 min/day). Sitting time was highest for individuals with MS who were male (540 min/day), not married (540 min/day), had a disease duration >30 years (540 min/day), were underweight (540.5 min/day), had an annual income of < $15,000 (585 min/day), presented with a progressive form of MS (600 min/day), were classified as insufficiently active (600 min/day), or presented with severe disability (661 min/day). Conclusion Sitting time is twice as high in individuals with MS compared to the general population (240 min/day). [ABSTRACT FROM AUTHOR]

A correction to the article "Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study" in the June 7, 2017 issue is presented. The fifth author of this article was incorrectly listed as "M. E. Lewiecki"; however, the name should be "E. M. Lewiecki."