Cancer related mortality in multiple sclerosis. A population based cohort study.

BACKGROUND: Cancer is a major cause of death, but how cancer influences mortality risk in Multiple Sclerosis (MS) is unclear. OBJECTIVES: Determine all-cause mortality and mortality following a cancer diagnosis among MS patients compared with matched population controls. METHODS: Norwegian MS patients born 1930 - 1979 (n= 6950) followed-up 1953 - 2016, were matched with 37 922 controls. We compared incident cancer diagnosis from the Cancer Registry of Norway, date of death from the Cause of Death Registry, education from the National Education Database, by multivariate Cox proportional hazard regression. RESULTS: Hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality among MS patients was 4.97 (4.64 - 5.33), and 2.61 (2.29 - 2.98) for mortality following a cancer diagnosis. Mortality in MS was highest following urinary- (2.53: 1.55 - 4.14), colorectal- (2.14: 1.47 - 3.11), hematological- (1.76: 1.08 - 2.88), ovarian - 2.30 (1.73-3.06) and breast cancer diagnosis (2.61: 1.85 - 3.68), compared to controls. High education was inversely associated with mortality among MS patients. CONCLUSIONS: All-cause mortality was five- fold and mortality following a cancer diagnosis was two- fold increased among MS patients. Mortality following specific cancers raises the possibility of diagnostic neglect.

Incidence of cancer in multiple sclerosis before and after the treatment era- a registry- based cohort study.

BACKGROUND: Whether disease-modifying therapies (DMTs) influence cancer in multiple sclerosis (MS) is uncertain. OBJECTIVES: Assess incidence of cancer diagnosis among Norwegian MS patients compared to the general population in 1953 to 1995 and 1996 to 2017-reflecting era before and after introduction of DMTs. METHODS: We performed a nationwide cohort study comprising 6949 MS patients and 37,922 controls, matched on age, sex and county. The cohort was linked to Norwegian Cancer Registry, Cause of Death Registry and National Educational database. We used Poisson regression to calculate incidence rate ratio (IRR) of cancer. RESULTS: During 1953-1995 MS patients had similar cancer frequency compared to controls (IRR: 1.11 (95% Confidence Intervals (CI): 0.90-1.37)), although MS patients had increased frequency of cancer in endocrine glands (IRR: 2.51 (1.27-4.93). During 1996-2017 we identified significant increased frequency of cancer among MS patients compared to controls (IRR: 1.38 (95% CI: 1.28-1.52): in brain (IRR: 1.97 (1.41-2.78)), meninges (IRR: 2.44 (1.54-3.77)), respiratory organs (IRR: 1.96 (1.49-2.63)). The excess cancer diagnosis was most frequent among MS patients ≥ 60 years of age (HR 1.30 (1.15-1.47)). CONCLUSION: Incidence of cancer among MS patients compared to controls was higher in 1996 to 2017, corresponding in time to the introduction of DMT for MS. This was observed more frequently among MS patients older than 60 years of age.

Risk of cancer among multiple sclerosis patients, siblings, and population controls: A prospective cohort study.

BACKGROUND: Risk of cancer in multiple sclerosis (MS) patients compared to their siblings is unknown. OBJECTIVE: The objective was to prospectively investigate the risk of cancer among MS patients compared to siblings without MS and to population controls. METHODS: We retrieved data on MS patients born between 1930 and 1979 from the Norwegian Multiple Sclerosis Registry and population studies and on cancer diagnosis from the Cancer Registry of Norway. We used adjusted Cox proportional hazard regression to estimate cancer risk among 6883 MS patients, 8918 siblings without MS, and 37,919 population controls. RESULTS: During 65 years of follow-up, cancer risk among MS patients was higher than that among population controls (hazard ratio (HR) = 1.14, 95% confidence interval (CI): 1.05-1.23) in respiratory organs (HR = 1.66, 95% CI: 1.26-2.19), urinary organs (HR = 1.51, 95% CI: 1.12-2.04), and the central nervous system (HR = 1.52, 95% CI: 1.11-2. 09). Siblings had higher risk of hematological cancers compared with MS patients (HR = 1.82, 95% CI: 1.21-2.73) and population controls (HR = 1.72, 95% CI: 1.36-2.18). CONCLUSION: MS patients were associated with increased risk of cancer compared to population controls. Siblings had increased risk of hematological cancer. This indicates that MS and hematological cancer could share a common etiology.

Chronic headache with medication overuse: Long-term prognosis after withdrawal therapy.

Background Knowledge about long-term outcomes after medication withdrawal therapy for chronic headache, including tension type and migraine headache is lacking. Methods We re-examined 56 patients an average of nine years after they participated in a medication withdrawal study with a one-year follow-up. We collected and compared data on headache, use of medication, quality of life, quality of sleep, anxiety, depression, and labor participation one and nine years after the start of withdrawal therapy. Results Headache days per month decreased from 16.7 (14.0-19.3) at one year to 13.3 (10.6-15.9) at nine years (P = 0.007). The proportion of patients meeting the criteria for chronic headache decreased from 27/56 (48%) at one year to 18/56 (32%) at nine years (P = 0.004). Medication overuse was reported in seven (13%) patients at one year and 18 (32%) at nine years (P = 0.013). The majority of patients overusing medication at nine years (10/18) belonged to a group of 14 patients who had a poor early response to withdrawal therapy and had sustained chronic headache after nine years. After excluding patients receiving retirement pensions, the proportion who received disability benefits increased from 21/55 (38%) at one year to 30/49 (61%) at nine years (P = 0.003). Conclusion Improvements after withdrawal therapy for chronic headache last at least nine years, with a parallel increase in the use of disability benefits. However, a high proportion of patients with a poor initial response to withdrawal therapy and sustained chronic headache overuse medication.

Level of education and multiple sclerosis risk over a 50-year period: Registry-based sibling study.

BACKGROUND: The conflicting results from studies on socioeconomic status (SES) and multiple sclerosis (MS) risk might be due to a change in the distribution of environmental exposures over time or to methodological limitations in previous research. OBJECTIVE: To examine the association between SES and MS risk during 50 years. METHODS: We included patients registered in Norwegian MS registries and prevalence studies born between 1930 and 1979, and identified their siblings and parents using the Norwegian Population Registry. Information on education was retrieved from the National Education Registry, categorized into four levels (primary, secondary, undergraduate and graduate) and compared in patients and siblings using conditional logistic regression. RESULTS: A total of 4494 MS patients and 9193 of their siblings were included in the analyses. Level of education was inversely associated with MS risk ( p trend < 0.001) with an odds ratio (OR) of 0.73 (95% confidence interval (CI): 0.59-0.90) when comparing the highest and lowest levels. The effect estimates did not vary markedly between participants born before or after the median year of birth (1958), but we observed a significant effect modification by parental education ( p = 0.047). CONCLUSION: Level of education was inversely associated with MS risk, and the estimates were similar in the earliest and latest birth cohorts.

Sex ratio of multiple sclerosis in persons born from 1930 to 1979 and its relation to latitude in Norway.

A remarkable increase in female to male ratio of multiple sclerosis (MS) is recognised in high incidence areas. Norway is a high-risk area for MS, spanning latitudes 58-71 °N. We studied whether the sex ratio has changed over time and whether it differs by clinical phenotype or by latitude. Population-based epidemiological data and data from the Norwegian MS Registry on patients born from 1930 to 1979 were combined in this study. Place of birth was retrieved from the Norwegian Population Registry and information on clinical subtypes was obtained from the Norwegian MS Registry. The female to male ratio ranged from 1.7 to 2.7 (median 2.0) in 5,469 patients born in Norway, and increased slightly by 5-year blocks of year of birth (p = 0.043). The sex ratio was 2.6:1 in 825 patients born 1970-1979, which is significantly higher than in those born 1930-1969 (p < 0.001). In patients with relapsing remitting onset, the sex ratio was 2.4:1, while it was 1.1:1 in those with primary progressive disease. The sex ratio did not differ between the south, the middle and the north of the country. The overall sex ratio of MS is strongly determined by cases with relapsing remitting onset. We did not observe the remarkable increase in sex ratios of MS reported from other high-risk areas. The high sex ratio in the youngest birth cohorts may change as an increasing proportion of cases in this age group is being diagnosed. Sex ratio was not associated with latitude.

Month of birth as a latitude-dependent risk factor for multiple sclerosis in Norway.

OBJECTIVE: We aimed to determine if the risk of Multiple Sclerosis (MS) is associated with month of birth in Norway and to explore a possible latitudinal gradient. METHODS: All patients with MS born between 1930 and 1979 registered in the Norwegian MS Registry or ascertained in Norwegian prevalence studies were included (n = 6649). The latitude gradient was divided in Southern, Middle and Northern Norway, according to the estimated regional yearly mean vitamin D effective UV dose. RESULTS: Risk of MS was 11% higher for those born in April (p = 0.045), and 5% higher for those born in May (p = 0.229), 5% lower for those born in November (p = 0.302) and 12% lower for those born in February (p = 0.053) compared with the corresponding population, unaffected mothers and siblings. In Southern Norway the odds ratio of MS births in April and May was 1.05 (0.98-1.24), in Middle Norway 1.11 (0.97-1.27) and in Northern Norway 1.28 (1.0-1.63) compared with the other months. CONCLUSIONS: This study confirms previous reports of increased MS births in spring and decreased MS births in the winter months. This could support the role of decreased sunlight exposure during pregnancy and vitamin D deficiency in prenatal life in MS.

Functional level during sub-acute rehabilitation after traumatic brain injury: course and predictors of outcome.

OBJECTIVES: To describe the functional level during sub-acute rehabilitation after moderate and severe traumatic brain injury (TBI) and to evaluate the impact of pre-injury and injury-related factors as predictors of early recovery. MATERIAL AND METHODS: A prospective study of 55 patients with moderate (n = 21) and severe (n = 34) TBI who received specialized, inpatient rehabilitation. Functional level was assessed by the FIM. Possible predictors were analysed in a regression model using FIM total score at discharge as outcome. RESULTS: At discharge from sub-acute rehabilitation, on average 53 (+/-24) days post-injury, 57% of moderate TBI patients and 91% of severe TBI patients were still disabled with a FIM score < 126. The disability was mild (FIM 109-126) in 95% with moderate TBI and in 62% with severe TBI. The disability was severe (FIM < 72) in 24% with severe TBI. Only one patient did not improve. Predictors of functional level at discharge from rehabilitation were Glasgow Coma Scale (GCS) score at rehabilitation admission (B = 5.991), FIM total score at rehabilitation admission (B = 0.393), length of stay (LOS) in the rehabilitation unit (B = 0.264) and length of Post-Traumatic Amnesia (PTA) (B = -0.120). Together, these predictors explained 86% of variance of FIM total scores at discharge. CONCLUSION: Less than half of moderate TBI patients reached a normal functional level at discharge from sub-acute rehabilitation. A short PTA period, a high GCS score and FIM score at admission to rehabilitation and a longer stay in the rehabilitation unit were positive predictors of functional level at discharge.