All-cause mortality following a cancer diagnosis amongst multiple sclerosis patients: A Swedish population-based cohort study

Background and purpose: A reduced cancer risk amongst patients with multiple sclerosis (MS) has been reported. Theoretically, this could represent a genuine reduction in risk or, alternatively, 'diagnostic neglect', where cancer is undiagnosed when symptoms are misattributed to MS. Objective: Assess all-cause mortality risk following a cancer diagnosis in patients with MS compared with a cohort without MS. Patients: A cohort of MS patients (n = 19 364) and a cohort of the general population (n = 192 519) were extracted from national Swedish registers from 1969 to 2005. All-cause mortality after cancer in MS was compared with the general population. Poisson regression analysis was conducted in the MS and non-MS cohorts separately. The models were adjusted for follow-up duration, year at entry, sex, region and socioeconomic index. The two cohorts were combined and differences in mortality risk were assessed using interaction testing. Results: The adjusted relative risk (and 95 confidence interval) for all-cause mortality following a cancer diagnosis in MS patients (compared with MS patients without cancer) is 3.06 (2.86-3.27; n = 1768) and amongst those without MS 5.73 (5.62-5.85; n = 24 965). This lower magnitude mortality risk in the MS patients was confirmed by multiplicative interaction testing (P < 0.001). Conclusions: A consistent pattern of lower magnitude of all-cause mortality risk following cancer in MS patients for a range of organ-specific cancer types was found. It suggests that cancer diagnoses tend not to be delayed in MS and diagnostic neglect is unlikely to account for the reduced cancer risk associated with MS. The lower magnitude cancer risk in MS may be due to disease-associated characteristics or exposures. © 2015 EAN

Capillary-Wave Model for the Solidification of Dilute Binary Alloys

Starting from a phase-field description of the isothermal solidification of a dilute binary alloy, we establish a model where capillary waves of the solidification front interact with the diffusive concentration field of the solute. The model does not rely on the sharp-interface assumption, and includes non-equilibrium effects, relevant in the rapid-growth regime. In many applications it can be evaluated analytically, culminating in the appearance of an instability which, interfering with the Mullins-Sekerka instability, is similar to that, found by Cahn in grain-boundary motion.Comment: 17 pages, 12 figure

The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly and its prevalence is set to increase rapidly in coming decades. However, there are as yet no available drugs that can halt or even stabilize disease progression. One of the main pathological features of AD is the presence in the brain of senile plaques mainly composed of aggregated β amyloid (Aβ), a derivative of the longer amyloid precursor protein (APP). The amyloid hypothesis proposes that the accumulation of Aβ within neural tissue is the initial event that triggers the disease. Here we review research efforts that have attempted to inhibit the generation of the Aβ peptide through modulation of the activity of the proteolytic secretases that act on APP and discuss whether this is a viable therapeutic strategy for treating AD.&lt;p&gt;&lt;/p&gt; Alzheimer's disease (AD) is the most common form of dementia in the elderly but as yet there are no drugs that can halt the progression of this disease. In a theory called the ‘amyloid hypothesis’, researchers have proposed that the accumulation of a small protein fragment called beta amyloid or Aβ within brain tissue is the event which triggers Alzheimer's disease. Aβ is a derivative of the longer amyloid precursor protein (APP). Here we review research efforts that have attempted to inhibit the generation of Aβ through modulation of proteins called secretases which cut APP into Aβ. Author edits made on: 20 May 2015

Hospital admission due to infections in multiple sclerosis patients

Background and purpose: Multiple sclerosis (MS) patients are at increased infection risk. Here the influences of susceptibility, severity and surveillance bias on infection-related hospital admission are assessed. Methods: Swedish registers identified 20 276 patients with MS, matched with 203 951 people from the general population without MS. Risk of first hospital admission for infection and mortality over 36 years was estimated by Poisson regression. Results: Multiple sclerosis was associated with an increased hospital admission risk for all infections, with an adjusted relative risk (and 95% confidence interval) of 4.26 (4.13-4.40). A proportion of this raised risk was probably due to surveillance and referral bias, although a raised risk remained when MS was compared with other immune-mediated diseases. The 1-month mortality rate following hospital admission for infection was higher in MS patients than in the comparison cohort, with a relative risk of 4.69 (4.21-5.22). There was no clear temporal trend in the results, and risks were higher in males and varied by MS phenotype. Conclusions: Higher hospital admission rates among MS patients for infection are likely to be due to a combination of surveillance bias, cautious medical management and greater susceptibility to severe infections. MS-related functional limitations may increase infection risk and this should be considered in MS management. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS

Mortality following a brain tumour diagnosis in patients with multiple sclerosis

Objectives: As brain tumours and their treatment may theoretically have a poorer prognosis in inflammatory central nervous system diseases such as multiple sclerosis (MS), all-cause mortality following a brain tumour diagnosis was compared between patients with and without MS. The potential role of age at tumour diagnosis was also examined. Setting: Hospital inpatients in Sweden with assessment of mortality in hospital or following discharge. Participants: Swedish national registers identified 20 543 patients with an MS diagnosis (1969-2005) and they were matched individually to produce a comparison cohort of 204 163 members of the general population without MS. Everyone with a primary brain tumour diagnosis was selected for this study: 111 with MS and 907 without MS. Primary and secondary outcome measures: 5-year mortality risk following brain tumour diagnosis and age at brain tumour diagnosis. Results: A non-statistically significant lower mortality risk among patients with MS (lower for those with tumours of high-grade and uncertain-grade malignancy and no notable difference for low-grade tumours) produced an unadjusted HR (and 95% CI) of 0.75 (0.56 to 1.02). After adjustment for age at diagnosis, grade of malignancy, sex, region of residence and socioeconomic index, the HR is 0.91 (0.67-1.24). The change in estimate was largely due to adjustment for age at brain tumour diagnosis, as patients with MS were on average 4.7 years younger at brain tumour diagnosis than those in the comparison cohort (p<0.001). Conclusions: Younger age at tumour diagnosis may contribute to mortality reduction in those with highgrade and uncertain-grade brain tumours. Survival following a brain tumour is not worse in patients with MS; even after age at brain tumour diagnosis and grade of malignancy are taken into account

Appendicectomy and multiple sclerosis risk

Background: Appendicectomy for acute appendicitis, but not for other causes, is inversely associated with immune-mediated diseases such as ulcerative colitis, suggesting appendicitis is a marker of immune characteristics influencing immune-mediated disease risk. This study investigated the association of appendectomy and its underlying diagnosis with multiple sclerosis (MS). Methods: Swedish general population registers and the Swedish MS register provided information on 20542 cases with MS diagnosed between 1964-2006 and 204157 controls matched for age, sex, period and region. Appendicectomy prior to MS diagnosis was identified in 673 cases and 6518 controls. Conditional logistic regression, with adjustment for socio-economic index, assessed the association of diagnosis underlying appendicitis with MS risk. Results: A perforated appendix, the best indicator of acute appendicitis in this material, was inversely associated with MS, although not statistically significantly, with an odds ratio (and 95% confidence interval of 0.86 (0.70-1.04). The odds ratios are 1.04 (0.94-1.16) for appendicitis without perforation and 1.14 (0.98-1.33) for appendectomy without appendicitis. Conclusion: Although inconclusive in terms of assessing the hypothesis, these results may help to explain why earlier studies of appendicitis and MS risk have been inconsistent, as there may be variation in association by diagnosis underlying appendicectomy. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS

Cancer risk among patients with multiple sclerosis and their parents

Background: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. Methods: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. Results: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. Conclusions: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicatesthat a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible). copyright © by AAN Enterprises, Inc