Sleep duration and mortality among breast cancer survivors in the Western New York Exposures and Breast Cancer (WEB) Study.

PURPOSE: There is increasing evidence that sleep duration may affect breast cancer survival through effects on circadian function, influencing disease progression. However, further investigation of this association is needed. METHODS: In a population-based, prospective cohort study of women from the Western New York Exposures and Breast Cancer Study, we examined mortality outcomes with invasive breast cancer identified using the National Death Index. Cox proportion hazards ratios with 95% confidence intervals were used to estimate risk of all-cause (AC) and breast cancer-specific (BC) mortality associated with self-reported usual sleep duration with adjustment for age, race/ethnicity, years of education, body mass index (BMI), menopausal status, pack-years of smoking, tumor stage, and estrogen-receptor (ER) status. We further examined associations within strata of BMI, tumor stage, menopausal status, and ER status. RESULTS: A sample of 817 patients with breast cancer were followed for a median of 18.7 years, during which 339 deaths were reported, including 132 breast cancer-specific deaths. Those who reported shorter or longer sleep tended to have a slightly higher BMI, to be less proportionately non-Hispanic White, to report a previous history of benign breast disease, and to have consumed more alcohol during their lifetime. We found no significant associations between sleep duration and AC or BC mortality, including within stratified analyses. CONCLUSION: Sleep duration was not associated with either AC or BC mortality including within strata of BMI, tumor stage, menopausal status, or ER status.

Patient-reported outcomes are the strongest predictors of disease disability in intramuscular interferon ß-1a users.

Introduction: Patient-reported outcomes (PROs) are valuable measures for routine clinical care of people with multiple sclerosis (pwMS). Materials: 646 pwMS treated with interferon-ß-1a (IFN-ß-1a) were retrospectively included from the New York State Multiple Sclerosis Consortium. Clinical and PRO data at enrollment and 3 year follow-up were collected. PwMS with stable disease and disability worsening were matched (1:1) based on age, Expanded Disability Status Scale (EDSS) scores and disease duration. Disability worsening was determined based on trial criteria. Results: PwMS with future EDSS worsening had higher baseline and follow-up timed-25-foot walk (6.6 vs 5.5 s; 9.1 vs 5.5 s; p < 0.001) when compared with stable pwMS. Worsening pwMS reported higher baseline difficulties in getting up (odds ratio [OR] = 2.4; p = 0.009), climbing stairs (OR = 1.6; p = 0.024) and standing (OR = 2.2; p < 0.001). Worsening pwMS reported greater lower limb limitations (OR = 2.3; p = 0.004) and fatigue (OR = 1.8; p = 0.002). Conclusion: Higher fatigue and lower limb functional limitations are significant predictors of future disability worsening in pwMS.

A large retrospective study was carried out on people with multiple sclerosis (PwMS) being treated with intramuscular interferon-ß medication from the New York State Multiple Sclerosis Consortium. The aim of the study was to look at whether patient-reported and clinical measures could be used early on to predict whether PwMS have worsening of their disease. The study demonstrated that patient-reported levels of limitations in multiple physical and mental symptoms can predict future worsening in objectively quantified disability in PwMS who take intramuscular interferon-ß medication. Reported limitations in lower extremities and fatigue were the most predictive of future disability worsening.

Patient-Reported Outcome Severity and Emotional Salience Network Disruption in Multiple Sclerosis.

BACKGROUND: Overall burden of white matter damage is associated with increased self-report fatigue severity in people with multiple sclerosis. However, a paradoxically opposite association was reported for white matter damage to tracts in specific subnetworks including the amygdala, temporal pole, and insula. Based on neuroanatomical principles and other data from the literature, we hypothesized that these results might be indicative of a broader relationship between damage to these subnetworks and impaired recognition of negative emotional salience central to patient-reported outcomes. OBJECTIVE: We examined whether damage in the same previously-identified subnetworks is also associated with lower self-report depressive symptoms, something which may be decreased in individuals with impaired recognition of negative emotional salience. Other patient characteristics were also explored. METHODS: In a cohort of 137 people with multiple sclerosis, we measured location-specific network white matter tract damage in the proposed negative emotional salience network, along with self-report severity of depressive symptoms and cognitive problems, personality characteristics, objective cognitive performance, and physical disability. We applied regression analyses, accounting for lesion burden, to explore the relationship between damage in the proposed negative emotional salience network and these factors. RESULTS: We found disruption within the negative emotional salience network is associated with lower self-report depressive symptoms (ß = -0.277, p = 0.036), cognitive complaints (r = -0.196, p = 0.024) and personality trait Neuroticism (r = -0.179, p = 0.042). In contrast, damage within this network was not significantly associated with objective cognitive processing speed, personality trait Openness, or physical disability. CONCLUSION: The identified network may be a generalizable network which corresponds to the recognition of negative emotional salience, but not to objective factors such as processing speed and physical disability. Damage to this network may paradoxically buffer against negative emotional perception of symptom severity, central to patient-reported outcomes.

Discontinuation of disease modifying therapies is associated with disability progression regardless of prior stable disease and age.

BACKGROUND: Multiple sclerosis (MS) patients with stable disease course might view continued treatment as unnecessary. However, guidelines regarding treatment discontinuation are currently lacking. OBJECTIVE: To assess the clinical course after treatment discontinuation in MS patients with long disease duration. METHODS: Patients who discontinued disease-modifying treatments (DMTs) and not resume treatment (n = 216) were extracted from New York State MS Consortium (NYSMSC) and followed across three time points (average 4.6 years). Stable course was defined as no change in Expanded Disability Status Scale (EDSS) scores (<1.0 increase if EDSS<6.0 or <0.5-point increase if EDSS≥6.0) from baseline (time 1) to DMT discontinuation (time 2). Both stable and worsening MS patients were later assessed again after the DMT discontinuation (time 3). Additional analyses were performed based on disease subtype, type of medication, age cut-off of 55 and EDSS of 6.0. RESULTS: From the cohort of 216 MS patients who discontinued DMT, 161 (72.5%) were classified as stable before DMT discontinuation. After DMT discontinuation, 53 previously stable MS patients (32.9%) experienced disability worsening/progression (DWP). 29.2 and 40% of previously stable RRMS and SPMS respectively had DWP after DMT discontinuation. Over two years after DMT discontinuation, the rate of DWP was similar between patients younger or older than 55 years (31.1% vs 25.9%, respectively). MS patients with EDSS≥6.0 had greater DWP when compared to less disabled patients while remaining on therapy as well as after discontinuation (40.7% vs 15.4%, p < 0.001 and 39.6% vs 15.2%, p < 0.001, respectively). CONCLUSION: MS patients with stable disease course experience DWP after treatment discontinuation, with no clear relation to age and disease subtype. Patients with EDSS≥6.0 are at higher risk for DWP.

Clinical effects associated with five-year retinal nerve fiber layer thinning in multiple sclerosis.

BACKGROUND: Neurodegenerative changes in multiple sclerosis (MS) are associated with long-term disability progression (DP). Optical coherence tomography (OCT) measures may be used to monitor DP. OBJECTIVE: To determine significant effects driving the changes in OCT-based peripapillary retinal nerve fiber layer (pRNFL) in heterogeneous group of MS patients. METHODS: Total of 144 MS patients (109 relapsing-remitting MS and 35 progressive MS (PMS) with mean age at baseline of 47.6 and 56.5 years old, respectively) underwent clinical and OCT examination over 5-year follow-up. All OCT exams were reviewed using the OSCAR-IB criteria. The 5-year DP was determined based on Expanded Disability Status Scale (EDSS) changes and MS clinical trial criteria. Data regarding previous history of MS optic neuritis (MSON) and use of disease modifying treatment (DMT) was derived by in-person interview and review of electronic medical records. Mixed model-type of repeated measure analysis determined effects driving pRNFL change for analysis which utilized all eyes separately. RESULTS: Over an average of 5.3-years follow-up, the MS population demonstrated significant pRNFL thinning (F = 16.108, p < 0.001). The pRNFL thinning was greater due to progressive MS subtype (F = 5.102, p = 0.025), greater age at baseline (F = 4.554, p = 0.034), occurrence of DP (F = 6.583, p = 0.011), and previous history of MSON (F = 7.053, p = 0.008). Use of any or highly potent DMT (natalizumab versus first-line injectable treatments versus no DMT) significantly reduced the pRNFL thinning (F = 8.367, p = 0.004) over the follow-up. Lastly, occurrence of DP in PMS patients older than 50 years old was associated with greater pRNFL thinning (F = 6.667, p = 0.013). CONCLUSION: Longitudinal pRNFL changes are modified by age, disease subtype, disabiltiy progression, history of MSON, DMT use and their interactions.

Safety and efficacy of antiplatelet use before intravenous thrombolysis for acute Ischemic stroke.

AIM: To study the effects of pretreatment with Antiplatelet (AP) before IV thrombolysis (IVT) on the rate of symptomatic intracranial hemorrhage (sICH) and functional outcome in patients with Acute Ischemic stroke (AIS). METHOD: In this retrospective study, the medical records and cerebrovascular images of all the patients who received IVT for AIS in our center in a 9.6-year period were reviewed. Patients who took at least one dose of any APs in the last 24 h prior to IVT were identified. They were categorized according to the type of AP, single versus dual AP therapy (DAPT), and dose of AP. Rate of sICH and functional outcome at discharge were compared between the AP users and non-users. RESULTS: A total of 834 patients received IVT for AIS in our center during a 9.6- year period. Multivariate models were adjusted for age, NIHSS on admission, history of atrial fibrillation, history of hypertension, INR on admission, history of stroke and diabetes mellitus. In multivariate regression analyses and after adjusting for the variables mentioned above, the use of any AP was not associated with an increased rate of sICH (OR = 1.28 [0.70-2.34], p = 0.425). Furthermore, the use of DAPT did not significantly increase the rate of sICH in multivariate regression analyses. (OR = 0.663 [0.15-2.84], p = 0.580). The patients on any AP had a lower chance of having good functional outcome in univariate analysis (OR = 0.735 [0.552-0.979], p = 0.035). However, when adjusted for age, baseline NIHSS, history of diabetes, hypertension and prior stroke, AP use was not associated with a decreased chance of having a good functional outcome at discharge. (OR = 0.967 [0.690-1.357], p = 0.848). In addition, no significant difference was noted in the rate of good functional outcome between patients on DAPT and no AP users in multivariate regression analyses. (OR = 1.174 [0.612-2.253], p = 0.629). CONCLUSION: Our study did not show any significant association between the risk of sICH and good functional outcome after IVT for AIS patients on AP therapy (dual or single) in comparison with AP naïve patients.

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR.

INTRODUCTION: Current guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. METHODS: Patients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. RESULTS: No significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. CONCLUSION: Administration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.

Does Body Mass Index Impact the Outcome of Stroke Patients Who Received Intravenous Thrombolysis?

BACKGROUND: We sought to investigate the effect of obesity and BMI on functional outcome and rate of symptomatic intracranial hemorrhage (sICH) in a large sample of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS: In a single-center retrospective, but prospectively collected data, study of patients with AIS treated with IVT in a 10-year period, patients were placed into groups based on their BMI defined as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (<30 kg/m2). The rate of sICH and discharge modified Rankin Scale (mRS) were compared between the groups using logistic regression analysis. RESULTS: In a total of 834 patients who received IVT for AIS during a 10-year period, 224 (27.0%) were obese. Obese patients did not have a higher rate of sICH after IVT for AIS on the unadjusted or adjusted analysis (adjusted OR 0.95, 95% CI 0.48-1.88). We did not find an association between obesity and poor functional outcome at discharge (adjusted OR 0.76, 95% CI 0.53-1.09). CONCLUSIONS: After adjusting for confounding factors such as age, baseline National Institute of Health Stroke Scale (NIHSS), and comorbidities, obesity was not associated with an unfavorable functional outcome at discharge nor with a higher risk of sICH in patients with AIS treated with IVT.

Statins Use and Outcome of Acute Ischemic Stroke Patients after Systemic Thrombolysis.

AIM: The aim of this was to study the effects of statins and their intensity on symptomatic intracranial hemorrhage (sICH) and outcome after IV thrombolysis (IVT) for acute ischemic stroke (AIS). METHODS: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with IVT for AIS in our center in a 10-year period. Patients were further characterized as any statin users versus non-users on admission to the emergency department. Statins were categorized in high intensity or low intensity statin based on its propensity to reduce lower low-density cholesterol by ≥45% or <45%, respectively. Safety and discharge modified Rankin Score were compared between statin users versus non-users and also between high-intensity versus low-intensity groups. RESULTS: A total of 834 patients received IVT for AIS in our center during a 10-year period. Multivariate models were adjusted for age, NIH Stroke Scale at admission, INR, and history of DM and atrial fibrillation. There was no association between odds of sICH and any statin use (OR = 0.52 [0.26-1.03], p = 0.06). In multivariate model, any statin use was not associated with odds of poor outcome (Table 4: OR = 1.01 [0.79-1.55], p = 0.57). There was no significant association between odds of sICH among patients on high-intensity statin compared to low intensity statin (multivariate model OR = 0.39 [0.11-1.40], p = 0.15). There was 47% reduced odds of poor outcome among patients on high-intensity statin as compared to low-intensity statin (OR = 0.53[0.32-0.88] p = 0.01). However, this significant association was lost in the multivariate model (OR = 0.60 [0.35-1.05], p = 0.07). CONCLUSION: Our study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy. We also did not find significant association between the risk of sICH and poor outcome after IVT and the intensity of the stain used.

Long-term drug treatment in multiple sclerosis: safety success and concerns.

INTRODUCTION: The portfolio of multiple sclerosis (MS) disease modifying treatments (DMTs) has significantly expanded over the past two decades. Given the lifelong use of MS pharmacotherapy, understanding their long-term safety profiles is essential in determining suitable and personalized treatment. AREAS COVERED: In this narrative review, we summarize the short-, mid-, and long-term safety profile of currently available MS DMTs categories. In addition to the initial trial findings, safety outcomes derived from long-term extension studies (≥5-20 years) and safety-based prescription programs have been reviewed. In order to better understand the risk-benefit ratio for each particular DMT group, a short description of the DMT-based efficacy outcomes has been included. EXPERT OPINION: Long-term extension trials, large observational studies and real-world databases allow detection of rare and potentially serious adverse events. Two-year-long trials are unable to fully capture the positive and negative effects of immune system modulation and reconstitution. DMT-based monitoring programs can provide greater insights regarding safe use of MS medications in different patient populations and clinical settings. During the process of shared DMT decision, both MS care providers and their patients should be aware of an ever-expanding number of drug-based adverse events and their influence on the risk-benefit analysis.

Tonsillectomy in multiple sclerosis patients: Retrospective, case-controlled, exploratory study.

BACKGROUND: Previous studies have shown an effect of tonsillectomy and greater risk for future autoimmune diseases. Currently there are only few outdated analyses of tonsillectomy and multiple sclerosis (MS) risk. OBJECTIVE: To investigate the prevalence of tonsillectomy in MS patients and healthy controls (HCs). METHODS: A total of 1000 subjects (779 MS patients and 221 HCs) completed a structured study questionnaire regarding MS diagnosis, age of onset, history of tonsillectomy, and age of tonsillectomy. In a subgroup of patients with available electronic medical records, Expanded Disability Status Scale (EDSS) scores at the time of recruitment and 5-years later were collected. Statistical analyses were performed with χ2 test, odds ratio (OR), Student's t-test, Mann-Whitney U test, and ordinal regression.. RESULTS: The MS population had a greater percentage of patients with history of tonsillectomy when compared to HCs [39.5% vs. 31.7%, OR 1.411 (CI 1.027-1.938), p = 0.034], driven by participants aged 50 or older [45.7% vs. 36.1%, OR 1.495 (CI 1.037-2.155) p = 0.031]. There was no difference of the age at tonsillectomy (median 8.0 vs. 6.5 years old, p = 0.26). However, the RRMS patients had their tonsillectomy procedure performed significantly later when compared to HCs (median 6.5 vs. 9.0 years old, p = 0.049). In an analysis of RRMS patients with available longitudinal data (n = 459), patients with a history of tonsillectomy were significantly older and had a longer disease duration (p < 0.001 and p = 0.025). After adjusting for the demographic differences, no history of tonsillectomy remained significant predictor of lower EDSS score categories both at the first (estimate = -0.467, Wald = 6.68, 95% CI -0.82 to -0.11, p = 0.01) and second timepoint (estimate = -0.376, Wald = 4.4, 95% CI -0.73 to -0.02 p = 0.037). CONCLUSION: When compared to HCs, a greater percentage of MS patients underwent tonsillectomy. The role of tonsils, its relationship with early infection rates and/or antibiotic use in MS should be further investigated.

Fatigue at enrollment predicts EDSS worsening in the New York State Multiple Sclerosis Consortium.

BACKGROUND: Fatigue is one of the most common and distressing symptoms among persons with multiple sclerosis (pwMS). OBJECTIVE: The aim of this study is to evaluate fatigue as a predictor for disease worsening among pwMS. METHODS: In this retrospective cohort study of New York State MS Consortium (NYSMSC) registry, MS patients reporting moderate-to-severe fatigue at study enrollment (n = 2714) were frequency matched to less-fatigued subjects (n = 2714) on age, baseline Kurtzke Expanded Disability Status Scale (EDSS), disease duration, and MS phenotype. Change from baseline patient-reported outcomes (PROs), as measured by LIFEware™, categorized participants into two groups: those with stable/improved outcomes and those who worsened. In a subgroup of patients with longitudinal data (n = 1951), sustained EDSS worsening was analyzed using Cox proportional hazards modeling to explore the effect of fatigue. RESULTS: The median survival time from study enrollment to sustained EDSS worsening was 8.7 years (CI: 7.2-10.1). Participants who reported fatigue at baseline were more likely to experience sustained EDSS worsening during follow-up (HR: 1.4, 95% CI: 1.2-1.7). Patients who were fatigued at baseline were also more likely to report worsening psychosocial limitations (all ps ⩽ 0.01). CONCLUSION: In addition to being a common symptom of MS, severe fatigue was a significant predictor for EDSS worsening in the NYSMSC.

Dimethyl Fumarate in the Treatment of Relapsing-Remitting Multiple Sclerosis: Patient Reported Outcomes and Perspectives.

Dimethyl fumarate (DMF) is a commonly prescribed oral medication for the treatment of relapsing forms of multiple sclerosis (MS) with a wide range of hypothesized downstream mechanisms of action. Randomized clinical trials have established its clinical efficacy by using standard objective clinical measures. However, MS is a chronic disease that, apart from physical ailments, can affect an individual's mood, psychosocial status, and quality of life which cannot be captured by using only objective assessment tools. Given the challenge of determining the efficacy of the treatment in a real-world clinical setting, the use of patient-reported outcomes (PROs) may help us to better address these aspects of patient care and establish a more patient-centered approach to MS care. To date, a review of PubMed identified six studies which reported on PROs in patients who are taking DMF. In total, twelve different kinds of PRO measures were utilized and 6359 patients provided at least one form of PRO in these studies. Upon review of these studies, we were able to conclude that people with MS had decreased quality of life compared to the healthy population in the US. MS patients on DMF, however, had better health-related quality of life assessment scores compared to those using a placebo. Previous studies also suggested that DMF decreased work productivity impairment scores after one year of use compared to baseline. DMF was associated with less impairment in fatigue and depression scales along with improved treatment quality assessment and adherence scores. This review will present a brief synopsis of the published literature and will provide indications for future directions with respect to PROs and DMF in people with MS.

Epidemiology and treatment of multiple sclerosis in elderly populations.

The prevalence of multiple sclerosis (MS) and the age of affected patients are increasing owing to increased longevity of the general population and the availability of effective disease-modifying therapies. However, ageing presents unique challenges in patients with MS largely as a result of their increased frequency of age-related and MS-related comorbidities as well as transition of the disease course from an inflammatory to a neurodegenerative phenotype. Immunosenescence (the weakening of the immune system associated with natural ageing) might be at least partly responsible for this transition, which further complicates disease management. Currently approved therapies for MS are effective in preventing relapse but are not as effective in preventing the accumulation of disability associated with ageing and disease progression. Thus, ageing patients with MS represent a uniquely challenging population that is currently underserved by existing therapeutic regimens. This Review focuses on the epidemiology of MS in ageing patients. Unique considerations relevant to this population are discussed, including the immunology and pathobiology of the complex relationship between ageing and MS, the safety and efficacy of disease-modifying therapies, when discontinuation of treatment might be appropriate and the important role of approaches to support wellness and cognition.

Lower self-report fatigue in multiple sclerosis is associated with localized white matter tract disruption between amygdala, temporal pole, insula, and other connected structures.

BACKGROUND: Fatigue, a frequent and disabling symptom for people with multiple sclerosis (PwMS), inconsistently correlates with white matter (WM) pathology. Network-based analysis, accounting for the manner in which lesions disrupt networks of structurally connected gray matter (GM) regions, may provide additional insight. OBJECTIVE: To identify patterns of WM tract disruption which explain self-reported fatigue severity in PwMS. METHODS: 137 PwMS and 50 age- and sex-matched healthy controls (HC) underwent fatigue assessment and brain MRI. Lesion maps were applied to determine the severity of WM tract disruption between pairs of GM regions. Then, the Network-Based-Statistics tool was applied to identify structural networks whose disruption explained fatigue severity. To determine whether these networks explain unique variance above conventional MRI measures and depression, regressions were applied controlling for age, sex, brain volume, T2-lesion volume, and depression. RESULTS: Patient-perceived fatigue in PwMS was positively associated with overall lesion burden (ß = 0.563, p-value < 0.001). In contrast, localized disruptions in WM tracts between regions including the amygdala, insula, hippocampus, putamen, temporal pole, caudal-middle-frontal gyrus, rostral-middle-frontal gyrus, inferior-parietal gyrus, and banks of the superior temporal sulcus were significantly negatively correlated with fatigue in PwMS (ß = -0.586, p-value < 0.001). Average disruption within this specific, localized network explained significant additional variance in fatigue above what was otherwise explained by depression and conventional MRI measures of neuropathology (ΔR2 = 0.078, p-value < 0.001). CONCLUSION: Although overall lesion burden correlates positively with fatigue in PwMS, localized WM damage between the amygdala, temporal pole, and other connected structures is associated with lower severity of patient-perceived fatigue.

Walking disability measures in multiple sclerosis patients: Correlations with MRI-derived global and microstructural damage.

BACKGROUND: The relationship between walking disability in multiple sclerosis (MS) patients and their macro- and microstructural MRI-derived measures still remains unclear. OBJECTIVE: To assess the correlations between walking disability and MRI-derived lesion, atrophy, and microstructural/axonal integrity outcomes. METHODS: Seventy-one (71) MS patients were clinically examined, the expanded timed get-up and go (ETGUG), and timed 25-foot walk (T25FW) tests were assessed. Additionally, the Symbol Digit Modalities Test (SDMT) was obtained. Normalized brain (NBV), gray matter (GMV), white matter (WMV), cortex (CV), and deep GM (DGM) volumes, as well as lesion volumes (LV) and diffusion tensor imaging (DTI) scalar maps of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated. Spearman correlation, partial correlation and stepwise regression analyses were performed. RESULTS: T25FW and ETGUG were associated with T2-LV (p < .001), global (NBV, p < .001), tissue-specific (GMV and CV, p < .001) and regional (DGM p < .001; and thalamus p < .001) volumes. The ETGUG remained correlated with T1-LV, GMV, CV and total DGM volume (all p < .001) after age, sex, and disease duration adjustment. The WMV was not associated with walking disability. Similarly, DTI measures did not show significant association with the walking tests. The regression analysis outlined DMG volume as best predictor of T25FW (Adj R2 = 0.231, standardized ß = -0.435, and p = .001), and CV for ETGUG (Adj R2 = 0.176, standardized ß = -0.417, and p = .004). SDMT was associated with both T25FW (p = .004) and ETGUG (p = .013). CONCLUSION: Despite the low disability levels, walking as measured by T25FW and ETGUG, is largely explained by the loss of cortical and nuclei specific GM volumes.

Sleep and Breast Cancer in the Western New York Exposures and Breast Cancer (WEB) Study.

STUDY OBJECTIVES: Night shift work is associated with increased breast cancer risk, possibly from altered sleep. Epidemiologic evidence is sparse regarding sleep disturbances and breast cancer tumor markers. We examined sleep disturbance in association with breast tumor aggressiveness and mortality following diagnosis. METHODS: We analyzed associations of measures of sleep disturbance in a sample of 1,122 incident breast cancer cases from the Western New York Exposures and Breast Cancer (WEB) Study. Sleep disturbance was assessed using self-administered questionnaires; responses about difficulty falling asleep, waking up frequently, having trouble staying asleep, and waking up feeling tired and worn out were used to create a summary sleep disturbance score. We used general linear models to examine associations of sleep disturbance with markers of tumor aggressiveness among cases: estrogen receptor (ER) status, progesterone receptor (PR) status, and human epidermal growth factor receptor-2 (HER2) status; tumor size, stage, grade, lymph node involvement, and presence of metastasis. In addition, we examined the association between sleep disturbance and survival using Cox regression. RESULTS: Among breast cancer cases, sleep disturbance was higher for women with ER- / PR- tumors compared to women with ER+ / PR+ tumors, even after adjusting for potential covariates (P for trend = .02). Results suggest that the association of sleep quality differs by menopausal status, where mild sleep disturbance is associated with higher breast cancer mortality in premenopausal women; however, we had a relatively small sample size. CONCLUSIONS: Sleep disturbance may be associated with aggressive subtypes of breast cancer; however, further studies are needed.

Fatigue and Mood States in Nursing Home and Nonambulatory Home-Based Patients with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic, progressively disabling condition of the central nervous system. We sought to evaluate and compare mood states in patients with MS with increased disability residing in nursing homes and those receiving home-based care. METHODS: We conducted a cross-sectional analysis of the New York State Multiple Sclerosis Consortium to identify patients with MS using a Kurtzke Expanded Disability Status Scale (EDSS) score of 7.0 or greater. The nursing home group was compared with home-based care patients regarding self-reported levels of loneliness, pessimism, tension, panic, irritation, morbid thoughts, feelings of guilt, and fatigue using independent-samples t tests and χ2 tests. Multivariate logistic regression analyses were used to investigate risk-adjusted differences in mood states. RESULTS: Ninety-four of 924 patients with EDSS scores of at least 7.0 lived in a nursing home (10.2%). Nursing home patients were less likely to use disease-modifying therapy and had higher mean EDSS scores compared with home-based patients. However, nursing home patients were less likely than home-based patients to report fatigue (odds ratio [OR] for no fatigue, 3.8; 95% CI, 2.1-7.2), feeling tense (OR for no tension, 1.7; 95% CI, 1.1-2.7), and having feelings of pessimism (OR for no pessimism, 1.8; 95% CI, 1.2-2.8). CONCLUSIONS: The nursing home patients with MS were less likely to report fatigue, pessimism, and tension than those receiving home-based care. Further studies should examine ways of facilitating a greater degree of autonomy and decision-making control in MS patients receiving home-based care.

Decreased risk of cancer in multiple sclerosis patients and analysis of the effect of disease modifying therapies on cancer risk.

BACKGROUND: Although dysimmunity is considered an important link between multiple sclerosis (MS), family history and cancer risk, their relationship to the use of disease modifying therapies (DMT) is not fully understood. OBJECTIVE: To assess the observed versus expected number of cancers in MS patients, and family history of cancer, among DMT users and DMT naïve patients. METHODS: Cancer, DMT use, and family history of cancer were assessed using the New York State Multiple Sclerosis Consortium (NYSMSC) registry. Self-reported cancers in MS patients were tested for associations with DMT use, family history of cancer and other factors. Expected number of cancer cases was estimated using age- and gender-specific prevalence and incidence rates from the general population. RESULTS: The prevalence of cancer in males and females in the NYSMSC cohort was lower than expected (p<0.001). Patients with cancer were older at MS diagnosis and more likely to be female (p<0.001). MS patients with a personal history of cancer were more likely to report DMT use (p<0.001) and family history of cancer (p<0.001). Multivariable analysis did not support a higher risk of cancer after DMT initiation. CONCLUSIONS: We report a lower than expected number of cancer cases in MS patients compared to the general population. MS patients with a personal history of cancer were more likely to report DMT use suggesting that DMTs may abrogate the lower incidence of cancer in MS.

Racial differences in the association of insulin-like growth factor pathway and colorectal adenoma risk.

PURPOSE: Insulin resistance is believed to play an important role in the link between energy imbalance and colon carcinogenesis. Emerging evidence suggests that there are substantial racial differences in genetic and anthropometric influences on insulin-like growth factors (IGFs); however, few studies have examined racial differences in the associations of IGFs and colorectal adenoma, precursor lesions of colon cancer. METHODS: We examined the association of circulating levels of IGF-1, IGFBP-3 and IGFBP-1, and SNPs in the IGF-1 receptor (IGF1R), IGF-2 receptor (IGF2R), and insulin receptor genes with risk of adenomas in a sample of 410 incident adenoma cases and 1,070 controls from the Case Transdisciplinary Research on Energetics and Cancer (TREC) Colon Adenomas Study. RESULTS: Caucasians have higher IGF-1 levels compared to African Americans; mean IGF-1 levels are 119.0 ng/ml (SD = 40.7) and 109.8 ng/ml (SD = 40.8), respectively, among cases (p = 0.02). Mean IGF-1 levels are also higher in Caucasian controls (122.9 ng/ml, SD = 41.2) versus African American controls (106.9, SD = 41.2), p = 0.001. We observed similar differences in IGFBP3 levels by race. Logistic regression models revealed a statistically significant association of IGF-1 with colorectal adenoma in African Americans only, with adjusted odds ratios (ORs) of 1.68 (95 % CI 1.06-2.68) and 1.68 (95 % CI 1.05-2.71), respectively, for the second and third tertiles as compared to the first tertile. One SNP (rs496601) in IGF1R was associated with adenomas in Caucasians only; the per allele adjusted OR is 0.73 (95 % CI 0.57-0.93). Similarly, one IGF2R SNP (rs3777404) was statistically significant in Caucasians; adjusted per allele OR is 1.53 (95 % CI 1.10-2.14). CONCLUSION: Our results suggest racial differences in the associations of IGF pathway biomarkers and inherited genetic variance in the IGF pathway with risk of adenomas that warrant further study.