Sara Ghaderi

Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012

BackgroundThe aim of the current study was to estimate sex- and age-specific incidence rates of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) using population-based registry data. CFS/ME is a debilitating condition with large impact on patients and their families. The etiology is unknown, and the distribution of the disease in the general population has not been well described.MethodsCases of CFS/ME were identified in the Norwegian Patient Register (NPR) for the years 2008 to 2012. The NPR is nationwide and contains diagnoses assigned by specialist health care services (hospitals and outpatient clinics). We estimated sex- and age-specific incidence rates by dividing the number of new cases of CFS/ME in each category by the number of person years at risk. Incidence rate ratios were estimated by Poisson regression with sex, age categories, and year of diagnosis as covariates.ResultsA total of 5,809 patients were registered with CFS/ME during 2008 to 2012. The overall incidence rate was 25.8 per 100,000 person years (95% confidence interval (CI): 25.2 to 26.5). The female to male incidence rate ratio of CFS/ME was 3.2 (95% CI: 3.0 to 3.4). The incidence rate varied strongly with age for both sexes, with a first peak in the age group 10 to 19 years and a second peak in the age group 30 to 39 years.ConclusionsEarly etiological clues can sometimes be gained from examination of disease patterns. The strong female preponderance and the two age peaks suggest that sex- and age-specific factors may modulate the risk of CFS/ME.

Reproduction and marriage among male survivors of cancer in childhood, adolescence and young adulthood: a national cohort study

Background:Increased survival after cancer in young age has made long-term follow-up studies of high external validity important. In this national cohort study, we explored the impact of cancer in young age on reproduction and marital status in male survivors.Methods:Hazard ratios (HRs) and relative risks (RRs) of reproductive and marital outcomes were studied for male survivors of cancer in young age (<25 years) and cancer-free male comparisons, born during 1965–1985, by linking compulsory national registries in Norway.Results:Male cancer survivors (n=2687) had reduced paternity (HR: 0.72, 95% confidence interval (CI): 0.68–0.76). This was most apparent in survivors of testicular cancer, brain tumours, lymphoma, leukemia and bone tumours, and when diagnosed with cancer before 15 years of age. Male cancer survivors were more likely to avail of assisted reproduction (RR: 3.32, 95% CI: 2.68–4.11). There was no increased risk of perinatal death, congenital malformations, being small for gestational age, of low birth weight or preterm birth in their first offspring. Male cancer survivors were less likely to marry (HR: 0.93, 95% CI: 0.86–1.00), in particular brain tumour survivors.Conclusions:In this national cohort study, we demonstrated reduced paternity and increased use of assisted reproduction among male cancer survivors, but no adverse outcome for their first offspring at birth.

Substance use disorders and psychotic disorders in epilepsy: A population-based registry study

BACKGROUND Epilepsy affects around 70 million people worldwide. Psychiatric comorbidity may add to the burden of the disease. We studied substance use disorders and psychotic disorders among people with epilepsy from a population-based perspective. METHODS Norwegian specialist health services (hospitals and outpatient clinics) report diagnoses for individual patients to the Norwegian Patient Register. We used information on subjects born in 1930-1994 who were registered with a diagnosis of epilepsy at least once during the five-year period of 2008-2012. We compared the proportion of people with epilepsy registered with substance use disorders (alcohol use disorders or non-alcohol drug use disorders) and psychotic disorders (schizophrenia spectrum disorders or bipolar disorder) with similar figures in the population without epilepsy. We applied chi-square tests and log-binomial regression for analysis. RESULTS Overall, 0.90% of the Norwegian adult population was registered with epilepsy in somatic hospitals during 2008-2012. The total proportion registered with alcohol use disorder was 5.74% among people with epilepsy and 1.29% in the population without epilepsy (age- and sex-adjusted relative risk [RR]: 4.42, 95% confidence interval [CI]: 4.22-4.62). The corresponding figures were 4.32% and 1.22% (RR 3.86 [95% CI: 3.67-4.06] for drug use disorder, 1.72% and 0.60% (RR 2.94 [95% CI: 2.71-3.19]) for schizophrenia spectrum disorders, and 1.50% and 0.68% (RR 2.29 [95% CI: 2.10-2.49]) for bipolar disorder. CONCLUSION People with epilepsy were more often registered with substance use disorders and psychotic disorders than people without epilepsy. Psychiatric comorbidity requires particular attention in both diagnostic work-up and management of epilepsy, and creates complex medical challenges that require close cooperation between neurologists and psychiatrists. These findings may have implications for the organization and further development of comprehensive epilepsy care.

Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: A Norwegian population-based cohort study

Background:As the number of cancer survivors increases, their health and welfare have come into focus. Thus, long-term medical consequences of cancer at a young age (<25 years), obtained from social security benefit records, were studied.Methods:Standardised incidence ratios (SIRs) of long-term medical consequences for 5-year cancer survivors, born during 1965–1985, were explored by linking population-based registries in Norway.Results:Among the 5-year cancer survivors (4031 individuals), 29.7% received social security benefits. The survivors had an overall 4.4 times (95% confidence interval (95% CI): 4.1–4.6) higher risk of social security benefit uptake than the cancer-free population. Survivors of malignancies of bone and connective tissues (SIR: 10.8; 95% CI: 9.1–12.9), CNS tumours (SIR: 7.7; 95% CI: 6.9–8.6) and malignancies of the haematopoietic system (SIR: 6.1; 95% CI: 5.3–7.0) had the highest risks of social security benefits uptake. The most notified causes of social security benefit uptake were diseases of the nervous system, and injury and poisoning.Conclusion:The uptake of social security benefits among 5-year cancer survivors increased substantially and it may represent a solid outcome measure for the burden of the most severe late effects, especially in countries with comparable social welfare systems.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine.

BACKGROUND Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination. METHODS Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression. RESULTS The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91-1.04), while it was 2.04 (95% CI: 1.78-2.33) after being diagnosed with influenza infection during the peak pandemic period. CONCLUSIONS Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.

Narcolepsy and hypersomnia in Norwegian children and young adults following the influenza A(H1N1) 2009 pandemic

BACKGROUND Associations between influenza infection and sleep disorders are poorly studied. We investigated if pandemic influenza infection or vaccination with Pandemrix in 2009/2010 was associated with narcolepsy or hypersomnia in children and young adults. METHODS We followed the Norwegian population under age 30 from January 2008 through December 2012 by linking national health registry data. Narcolepsy diagnoses were validated using hospital records. Risks of narcolepsy or hypersomnia were estimated as adjusted hazard ratios (HRs) in Cox regression models with influenza infection and vaccination as time-dependent exposures. RESULTS Among the 1,638,526 persons under age 30 in Norway in 2009, 3.6% received a physician diagnosis of influenza during the pandemic, while 41.9% were vaccinated against pandemic influenza. Between October 1st 2009 and December 31st 2012, 72 persons had onset of narcolepsy and 305 were diagnosed with hypersomnia. The risk of a sleep disorder was associated with infection during the first six months, adjusted HR 3.31 with 95% confidence interval [CI], 1.01-10.79 for narcolepsy and adjusted HR 3.13 (95% CI, 1.12-8.76) for hypersomnia. The risk of narcolepsy was strongly associated with vaccination during the first six months adjusted HR 17.21 (95% CI, 6.28-47.14), while the adjusted HR for hypersomnia was 1.54 (95% CI, 0.81-2.93). CONCLUSIONS The study confirms an increased HR of narcolepsy following pandemic vaccination. Slightly increased HRs of narcolepsy and hypersomnia are also seen after influenza infection. However, the role of infection should be viewed with caution due to underreporting of influenza.

Suicide and violent deaths in survivors of cancer in childhood, adolescence and young adulthood-A national cohort study.

Suicide risk in adult cancer patients is found to be elevated, but limited information exists regarding risks of suicide and non‐suicidal violent deaths when diagnosed with cancer in young age. We investigate suicide and violent deaths in a national cohort including individuals diagnosed with cancer before age 25. Through the linkage of different national registries (Cancer Registry of Norway, Norwegian Causes of Death Registry and the National Registry) a cohort of all live births in Norway during 1965–1985 was defined and followed up through 2008. Individuals diagnosed with cancer before age 25 and the cancer‐free references were compared using an extended Cox proportional hazard regression model. The cohort comprised 1,218,013 individuals, including 5,440 diagnosed with cancer before age 25. We identified 24 suicides and 14 non‐suicidal violent deaths in the cancer group. The hazard ratio (HR) of suicide in the cancer group was 2.5 (95% confidence interval (CI) 1.7–3.8), and was increased both when diagnosed with cancer in childhood (0–14 years of age); HR = 2.3 (95% CI: 1.2–4.6), and during adolescence/young adulthood (15–24 years); HR = 2.6 (95% CI: 1.5–4.2). Survivors of bone/soft tissue sarcomas, CNS tumors and testicular cancer were at particular risk. The risk of non‐suicidal violent death was not increased in the cancer survivors (HR = 1.0; 95% CI: 0.6–1.7). Although based on small numbers and the absolute risk of suicide being low, these are novel findings with important implications for establishing adequate follow‐up including suicide prevention strategies for young cancer survivors.

Vanishing twin syndrome among ART singletons and pregnancy outcomes

Abstract STUDY QUESTION Among babies born by ART, do singleton survivors of a vanishing twin have lower birth weight than other singletons? SUMMARY ANSWER Vanishing twin syndrome (VTS) was associated with lower birth weight among ART singletons; a sibship analysis indicated that the association was not confounded by maternal characteristics that remain stable between deliveries. WHAT IS KNOWN ALREADY Previous studies indicate that ART singletons with VTS have increased risk of adverse pregnancy outcomes, compared with other ART singletons. The potential contribution of unmeasured maternal background characteristics has been unclear. STUDY DESIGN, SIZE AND DURATION This was a Norwegian population-based registry study, including 17 368 mothers with 20 410 ART singleton deliveries between January 1984 and December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS The study population included 17 291 ART singletons without VTS, 638 ART singletons with VTS and 2418 ART singletons with uncertain vanishing twin status. We estimated differences in birth weight and gestational age comparing ART singletons with VTS first to all ART singletons without VTS, and subsequently to their ART siblings without VTS, using random- and fixed-effects linear regression, respectively. The corresponding comparisons for the associations with preterm birth and small for gestational age (SGA) were conducted using random-and fixed-effects logistic regression. The sibling analysis of preterm birth included 587 discordant siblings, while the sibling analysis of SGA included 674 discordant siblings. MAIN RESULTS AND THE ROLE OF CHANCE ART singletons with VTS had lower birth weight when compared to all ART singletons without VTS, with an adjusted mean difference (95% CI) of −116 g (−165, −67). When we compared ART singletons with VTS to their ART singletons sibling without VTS, the adjusted mean difference was −112 g (−209, −15). ART singletons with VTS also had increased risk of being born SGA, with an adjusted odds ratio (OR) (95% CI) of 1.48 (1.07, 2.03) compared to all ART singletons without VTS, and 2.79 (1.12, 6.91) in the sibship analyses. ART singletons with VTS were also more likely to be born preterm, although this difference did not reach statistical significance. LIMITATIONS REASONS FOR CAUTION We did not have information on maternal socio-economic status, but this factor is accounted for in the sibship analyses. We also had no information on whether fresh or frozen embryos were replaced. WIDER IMPLICATIONS OF THE FINDINGS The reduction in birth weight and increased risk of SGA in ART singletons with VTS may suggest the presence of harmful intrauterine factors with long-term health impact. While vanishing twins are not routinely observed in naturally conceived pregnancies, loss of a twin is potentially a risk factor for the surviving foetus in any pregnancy. This could be further explored in large samples of naturally conceived pregnancies with the necessary information. STUDY FUNDING/COMPETING INTEREST(S) The authors of this study are supported in part by the UK Medical Research Council, US National Institute of Environmental Health Sciences and the Norwegian Research Council. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

QUALITY COMPARISON BETWEEN MOLTEN METAL FROM REMELTED SHEETS; MILL FINISH AND COATED

Deterioration of metal quality caused by contamination (e.g. coatings) is an issue in remelting of aluminium scrap. Therefore molten metal quality from remelting sheet material with and without coating is compared. In the experiments the crucibles are placed inside a resistance furnace to ensure that the charges are melted under the same conditions at the same time, measuring temperature and hydrogen. The melts was subjected to (i) settling overnight (ii) blowing air through a porous plug for 2.5 min to generate oxides (iii) settle overnight and adding turnings and (iv) adding carbon. The bifilm index is used as a measure of metal quality. The results show a statistically significant difference in the quality of the samples comparing coated and non-coated for all the melt treatments (i) – (iv), even if the charge material only contained approximately 0.4 % coat.

Encephalitis after influenza and vaccination: a nationwide population-based registry study from Norway

Abstract Background Influenza is known to be associated with various neurological complications, including encephalitis. We conducted a registry-based study to assess the risk of encephalitis after influenza and A(H1N1)pdm09 vaccine. Methods Data from Norwegian national health registries during 2008–14 were linked using the unique personal identifiers given to all Norwegian residents (N = 5 210 519). Cox proportional-hazard models with time-varying variables were fitted to estimate hazard ratios (HRs) of encephalitis after influenza and A(H1N1)pdm09 vaccine, using the risk windows 0–7, 0–14, 0–30, 0–60, 0–90 and 0–180 days. Results In Norway, 684 172 individuals received an influenza diagnosis and 2793 patients were hospitalized with encephalitis during 2008–14. The risk of encephalitis increased after influenza: HR, 7-day risk window: 47.8 (95% confidence interval (CI): 35.8–63.8), and the HR decreased for longer risk windows; HR, 180-day risk window: 3.8 (95% CI: 3.1–4.7). HR of encephalitis after influenza during the 2009 main pandemic wave using a 7-day risk window was 30.0 (95% CI: 10.8–83.2). We found no differences in the risk of encephalitis after the seasonal influenza compared with influenza during the 2009 main pandemic wave; HR, 7-day risk window: 1.3 (95% CI: 0.4–4.3). A(H1N1)pdm09 vaccine was not associated with the risk of encephalitis: HR, 14-day risk window: 0.6 (95% CI: 0.2–2.1). Conclusions There was an increased risk of encephalitis following influenza but not after A(H1N1)pdm09 vaccine. The risk of encephalitis was highest in the first few weeks after influenza.