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Background As the time available to spend with patients decreases, a rapid test for bedside diagnosis of carpal tunnel syndrome (CTS) could be useful. Design and Methods We describe the forearm elevation–compression test (FECT) in this context. The FECT was assessed in 40 patients with clinically suspected CTS and compared to Tinel's and Phalen's signs. Routine electromyography and nerve conduction tests (EMG/NCT) were performed in all cases. In addition, 85 healthy controls were examined by FECT and compared to the patient group. Results All three provocative tests, particularly FECT, were frequently positive in suspected CTS. Neurophysiological tests were normal in 5 of 40 cases of clinically suspected CTS, and the FECT was positive in all of these suggesting a positive predictive value of 87.5% if one accepts EMG/NCT as the reference. Amongst the healthy controls, 18 of 85 (21.2%) were positive on the FECT suggestive of a high false-positive rate or subclinical disease. Conclusion It is proposed that the FECT is a useful addition to the clinical examination of suspected CTS. Although the positive rate may be falsely elevated, this is offset by restricting the latency for tingling onset to 10 s or less (FECT2). [ABSTRACT FROM AUTHOR]

Hydrogen sulfide is produced by heterotrophic bacteria in anoxic waters and via carbonyl sulfide hydrolysis and phytoplankton emissions under oxic conditions. Apparent losses of dissolved cadmium (dCd) and zinc (dZn) in oxygen minimum zones (OMZs) of the Atlantic and Pacific Oceans have been attributed to metal‐sulfide precipitation formed via dissimilatory sulfate reduction. It has also been argued that such a removal process could be a globally important sink for dCd and dZn. However, our studies from the North Pacific OMZ show that dissolved and particulate sulfide concentrations are insufficient to support the removal of dCd via precipitation. In contrast, apparent dCd and dZn deficits in the eastern tropical South Pacific OMZ do reside in the oxycline with particulate sulfide maxima, but they also coincide with the secondary fluorescence maxima, suggesting that removal via sulfide precipitation may be due to a combination of dissimilatory and assimilatory sulfate reduction. Notably, dCd loss via precipitation with sulfide from assimilatory reduction was found in upper oxic waters of the North Pacific. While dissimilatory sulfate reduction may explain local dCd and dZn losses in some OMZs, our evaluation of North Pacific OMZs demonstrates that dCd and dZn losses are unlikely to be a globally relevant sink. Nevertheless, metal sulfide losses due to assimilatory sulfate reduction in surface waters should be considered in future biogeochemical models of oceanic Cd (and perhaps Zn) cycling. Plain Language Summary: The Pacific Ocean hosts multiple oxygen minimum zones (OMZs), chiefly in the Northeast Pacific and the Eastern Tropical Pacific. Despite studies identifying apparent deficits of dissolved cadmium (dCd) and zinc (dZn) relative to established relationships with macronutrients within OMZ waters and hypothesizing that precipitation of insoluble metal sulfides is the cause, our measurements of particulate metal sulfides are too small to support this removal hypothesis. However, we demonstrate that a possible loss of dCd related to metal‐sulfide precipitation is actually more likely in the surface oxygenated ocean rather than in OMZ waters. Key Points: Sulfide concentrations are too low to support the 0.1 nM deficit observed in dissolved Cd in the low oxygen North PacificAssimilatory and dissimilatory sulfate reduction can explain the dissolved metal deficits in the shallow Eastern Tropical South Pacific OMZParticulate sulfide maxima coincide with the largest apparent dissolved Cd deficits observed in the subsurface waters of the Pacific Ocean [ABSTRACT FROM AUTHOR]

Background: Performing cognitive–motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown. Objective: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level. Methods: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5–5.5, ≥ 6). Spearman correlations were conducted between the DTCmotor with clinical measures. Adjusted significance level was 0.01. Results: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTCmotor of 15.8% and DTCcognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTCmotor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTCcognitive did not differ from zero for any of the groups (p ≥ 0.039). Conclusion: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups. [ABSTRACT FROM AUTHOR]

Diel vertical migration (DVM) is common in zooplankton populations worldwide. Every day, zooplankton leave the productive surface ocean and migrate to deepwater to avoid visual predators and return to the surface at night to feed. This behavior may also help retain migrating zooplankton in biological hotspots. Compared to fast and variable surface currents, deep ocean currents are sluggish, and can be more consistent. The time spent in the subsurface layer is driven by day length and the depth of the surface mixed layer. A subsurface, recirculating eddy has recently been described in Palmer Deep Canyon (PDC), a submarine canyon in a biological hotspot located adjacent to the West Antarctic Peninsula. Circulation model simulations have shown that residence times of neutrally buoyant particles increase with depth within this feature. We hypothesize that DVM into the subsurface eddy increases local retention of migrating zooplankton in this feature and that shallow mixed layers and longer days increase residence times. We demonstrate that simulated vertically migrating zooplankton can have residence times on the order of 30 days over the canyon, which is five times greater than residence times of near‐surface, nonmigrating zooplankton within PDC and other adjacent coastal regions. The potential interaction of zooplankton with this subsurface feature may be important to the establishment of the biological hotspot around PDC by retaining food resources in the region. Acoustic field observations confirm the presence of vertical migrators in this region, suggesting that zooplankton retention due to the subsurface eddy is feasible. Plain Language Summary: Diel vertical migration (DVM) is considered the world's largest migration by biomass. Zooplankton migrate into the sea's surface waters to feed at night when risk of predation by visual predators is low. During the day, zooplankton migrate to deeper waters when risk of predation by predators like seabirds and fish is highest. This behavior may also retain zooplankton in areas of high biological activity, or hotspots. Migration between a rapidly moving surface layer and a sluggish subsurface layer may reduce the net horizontal movement of organisms. Since this behavior is modulated by light intensity, more daylight hours may increase the time spent in the slower subsurface layer and help retain zooplankton in these hotspots. We used simulated zooplankton in a numerical model over Palmer Deep Canyon to test how DVM behavior, and the factors that control the time spent in the subsurface layer, affects zooplankton retention within biological hotspots. Retention was highest for zooplankton when migrations were deepest, days were long, and surface mixed layer was shallow. Performing migrations also increased retention relative to near‐surface nonmigrating zooplankton. Acoustic observations within our study site suggest that the magnitudes of DVM simulated are feasible in this system. Key Points: Simulated diel vertical migrating zooplankton have increased residence time compared to nonmigrators near a biological hotspotShallow surface layers and long days lead to longer residence times of simulated diel vertical migrating zooplanktonField acoustic measurements show the presence of zooplankton diel vertical migration consistent with simulated migration [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low-dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis. We demonstrate both models instigate renal dysfunction, inflammatory cytokine responses, and fibrosis. However, the models exhibit differences in urinary excretory function, inflammatory cell infiltration, and degree of fibrotic response. UIRI without CLN demonstrated worsening perfusion and function, measured with 99mTc-mercaptoacetyltriglycine-3 imaging, and physiologic compensation in the contralateral kidney. Furthermore, UIRI without CLN elicited a robust inflammatory response that was characterized by a prolonged polymorphonuclear cell and natural killer cell infiltrate and an early expansion of kidney resident macrophages, followed by T-cell infiltration. Symmetrical diminished function occurred in RLDC kidneys and progressively worsened until day 17 of the study. Surprisingly, RLDC mice demonstrated a decrease in inflammatory cell numbers relative to controls. However, RLDC kidneys expressed increased levels of kidney injury molecule-1 (KIM-1), high mobility group box-1 (HMGB1), and colony stimulating factor-1 (CSF-1), which likely recruits inflammatory cells in response to injury. These data emphasize how the divergent etiologies of AKI to CKD models affect the kidney microenvironment and outcomes. This study provides support for subtyping AKI by etiology in human studies, aiding in the elucidation of injuryspecific pathophysiologic mechanisms of the AKI to CKD transition. [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]

Summary: The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide 'drug holiday' clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. Introduction: The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. Methods: We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. Results: Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. Conclusions: Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a comprehensive recruitment approach will be needed to effectively achieve the scientific goals of the EDGE study. [ABSTRACT FROM AUTHOR]

Health promotion programs that develop and implement strategies to promote sun safety practices to children have the potential to reduce skin cancer occurrence later in life. Go Sun Smart (GSS), a sun safety program for employees and guests of ski areas, was distributed to determine if an enhanced dissemination strategy was more effective than a basic dissemination strategy at reaching parents at ski and snowboard schools. On-site observations of GSS use and surveys of 909 parents/caregivers with children enrolled in ski and snowboard schools at 63 ski areas were conducted and analyzed using techniques for clustered designs. No differences were identified by dissemination strategy. Greater implementation of GSS (>5 messages posted) was associated with greater parental recall, 36.6% versus 16.7%, of materials, but not greater sun protection practices. Greater recall of messages, regardless of level of implementation, resulted in greater sun protection practices including applying sunscreen (p < .05), providing sunglasses and goggles (p < .01), and more use of all sun protection practices (p < .01). Ski areas with more program materials appeared to reach parents with sun safety advice and thus convinced them to take more precautions for their children. Sun safety need not be at odds with children’s outdoor recreation activities. [ABSTRACT FROM AUTHOR]

There is a compelling need for early, accurate diagnosis of Parkinson's disease (PD). Various magnetic resonance imaging modalities are being explored as an adjunct to diagnosis. A significant challenge in using MR imaging for diagnosis is developing appropriate algorithms for extracting diagnostically relevant information from brain images. In previous work, we have demonstrated that individual subject variability can have a substantial effect on identifying and determining the borders of regions of analysis, and that this variability may impact on prediction accuracy. In this paper we evaluate a new statistical algorithm to determine if we can improve accuracy of prediction using a subjects left-out validation of a DTI analysis. Twenty subjects with PD and 22 healthy controls were imaged to evaluate if a full brain diffusion tensor imaging-fractional anisotropy (DTI-FA) map might be capable of segregating PD from controls. In this paper, we present a new statistical algorithm based on bootstrapping. We compare the capacity of this algorithm to classify the identity of subjects left out of the analysis with the accuracy of other statistical techniques, including standard cluster-thresholding. The bootstrapped analysis approach was able to correctly discriminate the 20 subjects with PD from the 22 healthy controls (area under the receiver operator curve or AUROC 0.90); however the sensitivity and specificity of standard cluster-thresholding techniques at various voxel-specific thresholds were less effective (AUROC 0.72-0.75). Based on these results sufficient information to generate diagnostically relevant statistical maps may already be collected by current MRI scanners. We present one statistical technique that might be used to extract diagnostically relevant information from a full brain analysis. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the reliability of composite disability end points as alternatives to Expanded Disability Status Scale (EDSS) in assessing delay of disability progression. The study used 96-week data from the Olympus trial or rituximab in patients with progressive MS to determine SDP rates which are then analyzed using composite disability end points. The study concluded that composite end points could be superior to EDSS alone in analyzing disability progression.

Background. Potential exposure to carbon monoxide (CO) in private homes is largely unquantified. Aim. To estimate prevalence of potential exposure to CO in residential dwellings and describe associated interventions in an inner-city community. Methods. A housing association in London, Hackney Homes, began fitting CO alarms in the 22,831 local authority homes it is responsible for in January 2010. A gas engineer investigated each alarm activation and recorded the information on a standard form. We undertook a cross-sectional study of all 22,831 homes, using data from these forms. Descriptive analysis was performed, including incidence, monthly variation, cause of alarmactivation, and actions taken. Results. Between November 2011 and April 2012, 106 incidents were reported. Of these, 34.6% identified an issue with a gas appliance, and 10.6% identified misuse of cooking methods as the cause of activation. Relevant interventions were put in place, including disconnection of the gas appliance and education around cooking methods. Discussion. Little is known about the burden of CO poisoning in residential dwellings. This study provides important information on the path to quantifying population exposure to CO as well as establishing a possible approach to access this key information and realistic interventions to reduce potential exposure. [ABSTRACT FROM AUTHOR]

Background and purpose Multiple sclerosis (MS) patients discontinuing natalizumab are at risk of rebound of disease activity. Methods In the present multi-center, open-label, non-randomized, prospective, pilot study, we tested whether treatment with glatiramer acetate (GA) is safe and effective after natalizumab in MS patients. The study was performed at academic tertiary medical centers. Forty active relapsing-remitting MS patients who never failed GA therapy and who discontinued natalizumab after 12-18 months of therapy were enrolled. GA was initiated 4 weeks after the last dose of natalizumab. Results 62.5% of patients were relapse-free 12 months after GA initiation. Annualized relapse rate and time to relapse were significantly lower than before natalizumab. Notably, the frequency of relapses was significantly lower amongst those patients who had experienced ≤2 relapses the year before initiation of natalizumab therapy, compared with patients who had had three or more relapses. No evidence of rebound was observed in magnetic resonance imaging scans. Furthermore, Expanded Disability Status Scale and Multiple Sclerosis Functional Composite were stable in our patients, again suggesting that 12 months of post-natalizumab-GA therapy is not associated with clinical deterioration. Conclusions: Following discontinuation of natalizumab, 12 months of therapy with GA is safe and well tolerated in MS patients. GA can reduce the risk of early reactivation/rebound of disease activity in this setting. [ABSTRACT FROM AUTHOR]

Marrie RA, Horwitz R, Cutter G, Tyry T. Cumulative Impact of Comorbidity on Quality of Life in MS. Acta Neurol Scand: 2012: 125: 180-186. © 2011 John Wiley & Sons A/S. Background - Little is known about the impact of comorbidity on health-related quality of life (HRQOL) in multiple sclerosis (MS). We investigated the association of comorbidity and health-related HRQOL among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS). Materials and Methods - In 2006, we queried NARCOMS participants regarding physical and mental comorbidities and HRQOL, using the Short-Form 12. We summarized physical HRQOL using the aggregate Physical Component Scale (PCS-12) score and mental HRQOL using the aggregate Mental Component Scale (MCS-12) score. We assessed multivariable associations between comorbidity and HRQOL using a general linear model, adjusting for potential confounders. Results - Among 8983 respondents, the mean (SD) PCS-12 was 36.9 (11.8) and MCS-12 was 45.6 (11.6). After adjustment for sociodemographic and clinical factors, participants with any physical comorbidity had a lower PCS-12 (37.2; 95% CI: 36.4-38.1) than those without any physical comorbidity (40.1; 95% CI: 39.0-41.1). As the number of physical comorbidities increased, PCS-12 scores decreased ( r = −0.25; 95% CI: −0.23 to −0.27) indicating lower reported HRQOL. Participants with any mental comorbidity had a lower MCS-12 (40.7; 95% CI: 39.8-41.6) than those without any mental comorbidity (48.5; 95% CI: 47.7-49.4). Conclusions - Comorbidity is associated with reduced HRQOL in MS. Further research should evaluate whether more aggressive treatment of comorbidities improves the HRQOL of MS patients. [ABSTRACT FROM AUTHOR]

Background: Quantitative measures derived from magnetic resonance imaging (MRI) have been widely investigated as non-invasive biomarkers in multiple sclerosis (MS). However, the correlation of single measures with Expanded Disability Status Scale (EDSS) is poor, especially for studies with large population samples.Objective: To explore the correlation of MRI-derived measures with EDSS through composite MRI scores.Methods: Magnetic resonance images of 126 patients with relapsing—remitting MS were segmented into white and gray matter, cerebrospinal fluid, T2-hyperintense lesions, gadolinium contrast-enhancing lesions, T1-hypointense lesions (‘black holes’: BH). The volumes and average T2 values for each of these tissues and lesions were calculated and converted to a z-score (in units of standard deviation from the mean). These z-scores were combined to construct composite z-scores, and evaluated against individual z-scores for correlation with EDSS.Results: Composite scores including relaxation times of different tissues and/or volumetric measures generally correlated more strongly with EDSS than individual measures. The maximum observed correlation of a composite with EDSS was r = 0.344 (p < 0.0001), which is an improvement over the highest-performing single MRI measure (BH; r = 0.298, p < 0.001).Conclusion: Z-transformation permits construction of composite scores including volumetric and T2-relaxation measures. Inclusion of multiple MRI measures in the composite can provide a broader characterization of the disease process, resulting in more robust correlations with EDSS. [ABSTRACT FROM PUBLISHER]

The number of new gadolinium-enhancing lesions discovered via magnetic resonance imaging is a well-established outcome for multiple sclerosis studies, especially Phase II Studies. Due to the high cost of magnetic resonance imaging scans, many investigators select participants for the presence of lesions. While this selection procedure is thought to improve the power of inferences, the effect of screening for baseline activity on parameter estimation and interval coverage has not yet been examined. The objective of this study was to investigate the performance of the negative binomial distribution for modeling lesion count data in multiple sclerosis when patients have been selected for activity on a baseline scan. We performed computer simulations to investigate the influence of the screening process on inferences made using a negative binomial model about treatment effects in two independent samples. We also demonstrate how the statistical properties of screening can be incorporated into trial design. We demonstrate that when the negative binomial distribution is used to model lesion counts, while screening for baseline activity improves point estimation, this practice also has the potential to decrease interval coverage and inflate the Type I error rate. For data that is to be modeled using a negative binomial distribution, screening for baseline activity can create a trade-off between cost effectiveness and a higher than desired false positive rate that must be carefully considered in planning Phase II trials. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the reproducibility of individual versus pooled plaque sampling of permanent first molars (PFM) to quantitate Streptococcus mutans (SM)/total streptococci (TS). Ten individual and pooled plaque samples were collected from 35 subjects, randomly assigned to individual-first or pooled-first group. Plaque samples were processed and quantified for SM and TS. SM/TS ratio was used to determine the reproducibility within two group samples. Mean percentage of SM/TS in both methods were not significantly different. However, within subject detection of SM was found to be significantly more sensitive for individual sampling method. Despite the lack of a difference between both methods for SM/TS quantitation, the difference in SM detection suggests that individual sampling is more sensitive. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background There is considerable interest in tissue-protective treatments for multiple sclerosis (MS). Methods and Objectives We convened a group of MS clinical trialists and related researchers to discuss designs for proof of concept studies utilizing currently available data and assessment methods. Results Our favored design was a randomized, double-blind, parallel-group study of active treatment versus placebo focusing on changes in brain volume from a post-baseline scan (3-6 months after starting treatment) to the final visit 1 year later. Study designs aimed at reducing residual deficits following acute exacerbations are less straightforward, depending greatly on the anticipated rapidity of treatment effect onset. Conclusions The next step would be to perform one or more studies of potential tissue-protective agents with these designs in mind, creating the longitudinal data necessary to refine endpoint selection, eligibility criteria, and sample size estimates for future trials. [ABSTRACT FROM AUTHOR]

Objective To study the relation of retinal nerve fiber layer thinning to clinical and physiologic measures of visual function in patients with MS or neuromyelitis optica and unilateral optic neuropathy. Methods We studied a cohort of control subjects (n = 64) and patients (n = 24) with evidence of unilateral thinning of their average retinal nerve fiber layer as measured by optical coherence tomography in order to characterize the relationship between ganglion cell axonal degeneration and its impact upon vision and pupillary light reflex metrics using infrared pupillometry. Results When compared to the normal fellow eye, and with respect to normal subjects' eyes, we confirmed significant abnormalities in retinal nerve fiber layer thickness, total macular volume, low-contrast letter acuity, and pupillary reflex metrics in the eye with the thinner retinal nerve fiber layer. For each -5% change in pupil diameter, there was a corresponding 7.1 μm reduction in the average retinal nerve fiber layer thickness. There was a significant difference between the pupillary metric of percent change in diameter and a decrease in low-contrast letter acuity (P < 0.001). Each -5% change in pupil diameter was associated with a substantial 3.4 line loss of low-contrast letter acuity (P < 0.001). Each -5% change in pupil diameter was associated with a 0.2 mm² decrease in total macular volume (P < 0.001). Conclusion These findings further corroborate the hypothesis that the retina can be utilized as a model to advance our understanding of the mechanisms of axonal and neurodegeneration, and the corresponding impact of these processes upon the pathophysiology of MS and related disorders. [ABSTRACT FROM AUTHOR]

Background Mental comorbidity is common in multiple sclerosis (MS), but some studies suggest that mental comorbidity may be underrecognized and undertreated. Objective Using the North American Research Committee on MS Registry, we assessed the frequency of mental comorbidities in MS and sociodemographic characteristics associated with diagnosis and treatment of depression. Methods We queried participants regarding depression, anxiety, bipolar disorder, and schizophrenia. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CESD); a score ≥21 indicated probable major depression. Results Mental comorbidity affected 4264 (48%) responders; depression most frequently (4012, 46%). Among participants not reporting mental comorbidity, 751 (16.2%) had CESD scores ≥21 suggesting undiagnosed depression. Lower socioeconomic status was associated with increased odds of depression (Income $15,000-30,000 vs >$100,000 OR 1.34; 1.11-1.62), undiagnosed depression (Income $15,000-30,000 vs >$100,000 OR 1.52; 1.08-2.13), and untreated depression (

Background Health behaviors influence chronic disease risks in the general population, and may influence health outcomes independently of comorbid diseases. Health behaviors receive less attention in multiple sclerosis (MS) than in the general population. We assessed health behaviors among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and the demographic characteristics associated with particular health behaviors. Methods In October 2006, we surveyed NARCOMS participants regarding smoking using questions from the Behavioral Risk Factor Surveillance Survey; physical activity using questions from the PEPI study, alcohol use using the AUDIT-C; and height and weight. To determine the independent demographic predictors of health behaviors, we used multivariable logistic regression, either binary or polytomous as appropriate. Results Of 8983 responders, 4867 (54.2%) ever smoked; 1542 (17.3%) currently smoked. On the basis of the AUDIT-C, 1632 (18.2%) were at risk for alcohol abuse or dependence. A quarter of participants were obese (n = 2269), and 2780 (31.3%) were overweight. Fewer than 25% of participants reported moderate or heavy leisure-time physical activity. Generally, lower socioeconomic status was associated with a higher frequency of adverse health behaviors accounting for other demographic factors. With increasing levels of disability, the reported intensity of physical activity was lower, and the frequency of overweight or obesity was higher. Conclusions Patients with MS exhibit frequent adverse health behaviors, increasing the risk of other chronic diseases. Further research is needed to determine how these behaviors influence disability progression, quality of life, and other MS-related outcomes. [ABSTRACT FROM AUTHOR]

Objective Multiple sclerosis (MS) is associated with substantial morbidity. The impact of comorbidity on MS is unknown, but comorbidity may explain some of the unpredictable progression. Comorbidity is common in the general population, and is associated with adverse health outcomes. To begin understanding the impact of comorbidity on MS, we need to know the breadth, type, and frequencies of comorbidities among MS patients. Using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry, we aimed to describe comorbidities and their demographic predictors in MS. Methods In October 2006, we queried NARCOMS participants regarding physical comorbidities. Of 16,141 participants meeting the inclusion criteria, 8983 (55.7%) responded. Results Comorbidity was relatively common; if we considered conditions which are very likely to be accurately self-reported, then 3280 (36.7%) reported at least one physical comorbidity. The most frequently reported comorbidities were hypercholesterolemia (37%), hypertension (30%), and arthritis (16%). Associated with the risk of comorbidity were being male [females vs. males, odds ratio (OR) 0.77; 0.69-0.87]; age (age >60 years vs. age ≤44 years, OR 5.91; 4.95-7.06); race (African Americans vs. Whites, OR 1.46; 1.06-2.03); and socioeconomic status (Income <$15,000 vs. Income >$100,000, OR 1.37; 1.10-1.70). Conclusions Comorbidity is common in MS and similarly associated with socioeconomic status. [ABSTRACT FROM AUTHOR]

Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy. [ABSTRACT FROM AUTHOR]

The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a patient registry, wherein the diagnoses of multiple sclerosis (MS) are unverified. We compared self-reported diagnoses of registry participants to physician-reported diagnoses, and with diagnoses based on medical records review. Registry participants with more than one of the following: age of onset /50 years, no bladder symptoms or fatigue, or zero or more than four relapses in the last year, were considered atypical. All others were considered typical. We sent letters to participants describing the study, surveyed treating physicians regarding the participants' diagnosis, and reviewed medical records. Diagnosis was classified by the McDonald and Poser criteria. Of the 240 participants sampled, 109 were in active registry status with accurate contact information. Of these, 52 consented, 29 refused and 28 did not respond (weighted response rate 76.3±/4.5%). Some 37 of 38 physician surveys confirmed the diagnosis of MS (98.8±/1.2%). After reviewing 41 medical records, we classified 53.2±/8.9% of participants as definite MS, 16.9±/6.8% as possible MS, while the remainder had insufficient data for diagnostic confirmation. We confirmed a diagnosis of MS in 98.7±/1.3% of participants based on records review, physician survey or telephone interview, supporting the validity of the diagnoses reported by NARCOMS participants. [ABSTRACT FROM AUTHOR]

A letter to the editor about the predictive value of the retinoblastoma protein inactivation in canine non-Hodgkin's lymphoma is presented

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]

Obesity is a major health problem facing the developed and developing world. Efforts by individuals, health professionals, educators, and policy makers to combat the escalating trend of growing obesity prevalence have been multifaceted and mixed in outcome. Various dietary supplements have been marketed to reduce obesity. These products have been suggested to accomplish this by decreasing energy intake and energy absorption, and/or increasing metabolic rate. Ephedra, one such supplement, was banned from sale in the US market because of concerns about adverse events. Another substance, Citrus aurantium, which contains several compounds including synephrine alkaloids, has been suggested as a safe alternative. This review examines the evidence for safety and efficacy of C. aurantium and synephrine alkaloids as examined in animal studies, clinical weight loss trials, acute physiologic studies and case reports. Although at least three reviews of C. aurantium have been published, our review expands upon these by: (i) distinguishing and evaluating the efficacy of C. aurantium and related compounds; (ii) including results from previously unreviewed research; (iii) incorporating recent case reports that serve to highlight, in an anecdotal way, potential adverse events related to the use of C. aurantium and related compounds; and (iv) offering recommendations to guide the design of future trials to evaluate the safety and efficacy of C. aurantium. While some evidence is promising, we conclude that larger and more rigorous clinical trials are necessary to draw adequate conclusions regarding the safety and efficacy of C. aurantium and synephrine alkaloids for promoting weight loss. [ABSTRACT FROM AUTHOR]

Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNβ-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of ≤3.5 at entry, disability progression at follow-up was defined as EDSS ≥6.0. Two methods were used to estimate the expected proportions that reached EDSS ≥6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing–remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNβ-1a patients reached an EDSS ≥6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNβ-1a patients should have reached an EDSS ≥6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNβ-1a group. Treatment effect sizes of 75–90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to vigorously followed cohorts of patients. [ABSTRACT FROM AUTHOR]

Following the withdrawal of ephedrine from the dietary supplement marketplace sales of products containing Citrus aurantium (CA) (bitter orange) for weight loss are believed to have increased dramatically. CA contains a number of constituents speculated to lead to weight loss, of which the most frequently cited constituent is synephrine. Concerns have been raised about the safety of products containing synephrine. To develop an adequate basis for clinical and public health recommendations, it is necessary to understand the nature of the synephrine alkaloids in CA. There are six possible isomers of synephrine (para, meta, ortho; and for each a d or l form). Some authors have stated that CA contains only p-synephrine, whereas other authors have stated that CA contains m-synephrine. This is an important distinction because the two molecules have different pharmacologic properties, which may differentially affect safety and efficacy. We are unable to identify published data that explicitly show whether CA contains p-synephrine, m-synephrine, or both. In this brief report, we show that at least one product purportedly containing synephrine alkaloids from CA contains both p-synephrine and m-synephrine. We believe this justifies further investigation into which synephrine alkaloids are present in CA and products purportedly containing synephrine alkaloids from CA and the relative quantities of each of the different isomers.International Journal of Obesity (2005) 29, 443-446. doi:10.1038/sj.ijo.0802879 Published online 8 February 2005 [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to examine diffusion of and predictors of helmet use among skiers and snowboarders in the Western United States and Canada. DESIGN: 6400 skiers and snowboarders at 29 ski resorts in the Western United States and Canada were interviewed on chair lifts and observed for helmet use during two consecutive ski seasons (winters 2001 and 2002). SETTING: Skiers and snowboarders were observed and interviewed at 29 ski resorts in Alaska, California, Colorado, Idaho, Montana, New Mexico, Nevada, Oregon, Utah, and British Columbia as part of a sun protection project. SUBJECTS: Participants completing the survey consisted of 3525 adult skiers and snowboarders in the 2002 season and 2978 adult skiers and snowboarders in the 2001 season. MAIN OUTCOME MEASURE: The outcome measure for all analyses was prevalence of helmet use by skiers and snowboarders. RESULTS: Helmet use by skiers and snowboarders is increasing and is most prevalent among snowboarders, experts, and more frequent skiers/snowboarders. No evidence was found for the hypothesis that helmet use is diffusing more rapidly among earlier adopters of helmets than later adopters. CONCLUSIONS: Although controversy remains, helmets are rapidly diffusing as a safety device at western North American ski resorts. Expert and more frequent skiers and snowboarders are more likely to wear helmets, which may indicate that helmets are recognized as a safety device. [ABSTRACT FROM AUTHOR]

Objective: Patients with progressive relapsing (PR) multiple sclerosis (MS) may accrue disability by incomplete recovery from acute exacerbations and by ongoing deterioration. In primary progressive (PP) MS, disability accumulates solely by continuous decline. Because it is the least common form of MS, there is scant information regarding the clinical characteristics of PRMS, but relapses are reportedly uncommon. The purpose of this study is to describe the clinical features of a cohort of patients with PRMS. Methods: A retrospective chart review of 16 patients diagnosed with PRMS at two academic MS centres over a four-year period. Results: Nine men and seven women had PRMS. The mean age at onset was 35.1±11.2 years. The most common presenting symptom was a progressive myelopathy. The mean disease duration was 10.1±8.5 years and the average time to first exacerbation was 4.1±3.7 years. Patients had an average of 2.8±2.3 relapses with an annualized relapse rate of 0.6±0.8. Time to Expanded Disability Status Scale (EDSS) 6.0 was strongly associated with time to first exacerbation. Although there was no correlation between the number of relapses and time to EDSS 6.0, there was a modest inverse relation between time to EDSS 6.0 and annualized relapse rate. Conclusions: Relapses in PRMS may occur more often than previously described and disability may accumulate more rapidly in PRMS than in PPMS. We suggest differentiating between these two forms of MS. [ABSTRACT FROM AUTHOR]