Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

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The primary clinical outcome measure for evaluating multiple sclerosis in clinical trials has been Kurtzke's expanded disability status scale (EDSS). New therapies appear to favourably impact the course of multiple sclerosis and render continued use of placebo control groups more difficult. Consequently, future trials are likely to compare active treatment groups which will most probably require increased sample sizes in order to detect therapeutic efficacy. Because more responsive outcome measures will be needed for active arm comparison studies, the National Multiple Sclerosis Society's Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis appointed a Task Force that was charged with developing improved clinical outcome measures. This Task Force acquired contemporary clinical trial and historical multiple sclerosis data for meta-analyses of primary and secondary outcome assessments to provide a basis for recommending a new outcome measure. A composite measure encompassing the major clinical dimensions of arm, leg and cognitive function was identified and termed the multiple sclerosis functional composite (MSFC). The MSFC consists of three objective quantitative tests of neurological function which are easy to administer. Change in this MSFC over the first year of observation predicted subsequent change in the EDSS, suggesting that the MSFC is more sensitive to change than the EDSS. This paper provides details concerning the development and testing of the MSFC.

Mammographic breast density and age are important predictors of the accuracy of screening mammography. Although HRT use is not an independent predictor of accuracy, it probably affects accuracy by increasing breast density.

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.

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2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections. OBJECTIVE To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS. DESIGN, SETTING, AND PARTICIPANTS This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. Health care professionals were asked to report patients after a minimum of 7 days from initial symptom onset and after sufficient time had passed to observe the COVID-19 disease course through resolution of acute illness or death. Data collection began April 1, 2020, and is ongoing. EXPOSURES Laboratory-positive SARS-CoV-2 infection or highly suspected COVID-19. MAIN OUTCOMES AND MEASURES Clinical outcome with 4 levels of increasing severity: not hospitalized, hospitalization only, admission to the intensive care unit and/or required ventilator support, and death. RESULTS Of 1626 patients, most had laboratory-positive SARS-CoV-2 infection (1345 [82.7%]), were female (1202 [74.0%]), and had relapsing-remitting MS (1255 [80.4%]).A total of 996 patients (61.5%) were non-Hispanic White, 337 (20.8%) were Black, and 190 (11.7%) were Hispanic/Latinx. The mean (SD) age was 47.7 (13.2) years, and 797 (49.5%) had 1 or more comorbidity. The overall mortality rate was 3.3% (95% CI, 2.5%-4.3%). Ambulatory disability and older age were each independently associated with increased odds of all clinical severity levels compared with those not hospitalized after adjusting for other risk factors

The risk of a youth pitcher sustaining a serious throwing injury within 10 years is 5%. Limiting the number of innings pitched per year may reduce the risk of injury. Young baseball pitchers are encouraged to play other positions as well but might avoid playing catcher.