Wilson's Disease in Finland: A Nationwide Population‐Based Study

Background Data on the epidemiology and prognosis of Wilson's disease are scarce, and no clinical data are available from Finland. Methods All persons diagnosed and treated for Wilson's disease in Finnish hospitals in 1998 to 2017 were identified. Data were collected from national registries and patient charts. Results The point prevalence was 0.45/100,000 (95% confidence interval, 0.29-0.67) on December 31, 2017, but no more than 0.35/100,000 (95% confidence interval, 0.21-0.55) among native Finns. Annual incidence was 0.016/100,000 (95% confidence interval, 0.0093-0.026). Median age at diagnosis was 15.8 years (interquartile range, 8.3-32.2; range, 3.8-48.1 years). Upon presentation, liver damage was observed in 58%, neurological signs and symptoms (most often tremor and dysarthria) in 40%, and 32% of patients were asymptomatic. Patients had poorer long-term survival (hazard ratio, 2.92 for death;P= 0.005) compared with matched controls. Conclusions Wilson's disease is very rare in Finland. Patients have an increased risk of death indicating an unmet treatment need. </div

Unverricht-Lundborg disease (EPM1) in Finland: A nationwide population-based study

To investigate the epidemiology and prognosis of Unverricht-Lundborg disease (EPM1) in a nationwide, population-based setting.Data from multiple registries were combined and analyzed. Clinical data were obtained from medical records. All patients treated for EPM1 in Finland between January 1, 1998, and December 31, 2016 were included.A total of 135 persons with EPM1 (54% women) were identified and 105 were alive on December 31, 2016 (point prevalence 1.91/100,000 persons). The age-standardized (European Standard Population 2013) prevalence was 1.53/100,000 persons. Annual incidence during the study period was 0.022/100,000 person-years, with a mean age at onset of 9.4 ± 2.3 years (range 7.0-14.6 years, no sex difference). The median age at death (n = 34) was 53.9 years (interquartile range 46.4, 60.3; range 23.2-63.8), with no sex differences. The immediate cause of death was a lower respiratory tract infection in 56% of deaths. The survival rates of the patients were comparable to matched controls up to 40 years of age, but poorer during long-term follow-up (cumulative survival 26.4% vs 78.0%), with a hazard ratio (HR) for death of 4.61. The risk of death decreased with increasing age at onset (HR 0.76 per year, 95% confidence interval 0.65-0.89). In approximately 10% of all cases, the disease progression appeared very mild; some patients retained functional independence for decades.Unverricht-Lundborg disease is rare in Finland but still more common than anywhere else in the world. The disease course appears somewhat more severe than elsewhere, disability mounts early, and death occurs prematurely.</div

HTT haplogroups in Finnish patients with Huntington disease

Objective To study genetic causes of the low frequency of Huntington disease (HD) in the Finnish population, we determined HTT haplogroups in the population and patients with HD and analyzed intergenerational Cytosine-Adenosine-Guanosine (CAG) stability. Methods A national cohort of patients with HD was used to identify families with mutant HTT (mHTT). HTT haplogroups were determined in 225 archival samples from patients and from 292 population samples. CAG repeats were phased with HTT haplotypes using data from parent-offspring pairs and other mHTT carriers in the family. Results The allele frequencies of HTT haplotypes in the Finnish population differed from those in 411 non-Finnish European subjects (p Conclusions The low frequency of HD in Finland is partly explained by the low frequency of the HD-associated haplogroup A in the Finnish population. There were remarkable differences in intergenerational CAG repeat dynamics that depended on HTT haplotype and parent gender.</div

Changes in ischemic stroke occurrence following daylight saving time transitions

Background: Circadian rhythm disruption has been associated with increased risk of ischemic stroke ( IS). Daylight saving time (DST) transitions disrupt circadian rhythms and shifts the pattern of diurnal variation in stroke onset, but effects on the incidence of IS are unknown.Methods: Effects of 2004-2013 DST transitions on IS hospitalizations and in-hospital mortality were studied nationwide in Finland. Hospitalizations during the week following DST transition (study group, n = 3033) were compared to expected hospitalizations (control group, n = 11,801), calculated as the mean occurrence during two weeks prior to and two weeks after the index week.Results: Hospitalizations for IS increased during the first two days (Relative Risk 1.08; CI 1.01-1.15, P = 0.020) after transition, but difference was diluted when observing the whole week (RR 1.03; 0.99 -1.06; P = 0.069). Weekday-specific increase was observed on the second day (Monday; RR 1.09; CI 1.00 -1.90; P = 0.023) and fifth day (Thursday; RR 1.11; CI 1.01-1.21; P = 0.016) after transition. Women were more susceptible than men to temporal changes during the week after DST transitions. Advanced age (> 65 years) (RR 1.20; CI 1.04-1.38; P = 0.020) was associated with increased risk during the first two days, and malignancy (RR 1.25; CI 1.00-1.56; P = 0.047) during the week after DST transition.Conclusions: DST transitions appear to be associated with an increase in IS hospitalizations during the first two days after transitions but not during the entire following week. Susceptibility to effects of DST transitions on occurrence of ischemic stroke may be modulated by gender, age and malignant comorbidities. (C) 2016 Elsevier B.V. All rights reserved

Changing epidemiology of traumatic brain injury among the working-aged in Finland : Admissions and neurosurgical operations

Background: Recent studies from Finland have highlighted an increase in the incidence of traumatic brain injuries (TBI) in older age groups and high overall mortality. We performed a comprehensive study on the changing epidemiology of TBI focusing on the acute events in the Finnish working-age population. Methods: Nationwide databases were searched for all emergency ward admissions with a TBI diagnosis for persons of 16–69 years of age during 2004–2018. Results: In the Finnish working-age population, there were 52,487,099 person-years, 38,810 TBI-related hospital admissions, 4664 acute neurosurgical operations (ANO), and 2247 cases of in-hospital mortality (IHM). The TBI-related hospital admission incidence was 94/100,000 person-years in men, 44/100,000 in women, and 69/100,000 overall. The incidence rate of admissions increased in women, while in men and overall, the rate decreased. The incidence rate increased in the group of 60–69 years in both genders. Lowest incidence rates were observed in the age group of 30–39 years. Occurrence risk for TBI admission was higher in men in all age groups. Trends of ANOs decreased overall, while decompressive craniectomy was the only operation type in which a rise in incidence was found. Evacuation of acute subdural hematoma was the most common ANO. Mean length of stay and IHM rate halved during the study years. Conclusions: In Finland, the epidemiology of acute working-aged TBI has significantly changed. The rates of admission incidences, ANOs, and IHM nowadays represent the lower end of the range of these acute events reported in the western world.acceptedVersionPeer reviewe

Adult Migraine Hospital Admission Trends in Finland: A Nationwide Registry Study

Population-level data on migraine hospital admission trends are unavailable. Changes in stroke care may have influenced these, since migraine is one of the most common stroke mimics. In this study, all hospital admissions on neurological, internal medicine, and pediatric wards in Finland with migraine as the primary diagnosis for persons at least 16 years of age in 2004-2014 were studied, resulting in an analysis of 6195 individuals with 7764 migraine discharges. The number of discharges increased by 4.2% annually (p = 0.000084), with no change in age of the admitted patients. Comorbidity burden was low but increased during the study period (p < 0.0001). The frequency of common vascular risk factors as comorbidities increased by 11-19% annually. Admission duration shortened by 2% annually (p < 0.0001). An intravenous thrombolysis was given in four admissions. It seems that migraine hospital admissions have become more frequent and the patients more often have cardiovascular risk factors, suggesting increased awareness and more aggressive acute evaluation of suspected stroke as the cause

High-Risk Periods for Adult Traumatic Brain Injuries : A Nationwide Population-Based Study

Introduction: There is minimal existing available information on nationwide seasonal peaks in traumatic brain injuries (TBIs). This lack of information is an impediment to the effective development of prevention programs, societal policies, and hinders the resourcing of medical emergency services. Our current aim is to study nationwide population-based high-risk periods TBI over a 15-year study period in Finland. Methods: Nationwide databases were searched for all admissions with a TBI diagnosis and later for deaths of persons ≥16 years of age during 2004-2018. The search included all hospitals that provide acute TBI care in Finland. Results: The study period included 69,231 TBI-related hospital admissions (men = 62%). We found that for men, the highest rate of TBIs occurred on Saturdays, whereas women experience the highest rate of TBIs on Mondays. The highest rate of TBIs in men occurred in July, while women experienced the highest rate of TBIs in January. TBI-related hospital admissions (incidence risk ratio [IRR] 1.090, 95% CI 1.07-1.11, p < 0.0001) and mortality within 30 days after TBI (hazard ratio [HR] 1.057, 95% CI 1.001-1.116, p = 0.0455) were more common on public holidays and weekends than on weekdays. There was an increasing trend in the proportion of TBI-related hospital admissions occurring on public holidays and weekends from 2004 (31.5%) to 2018 (33.4%) (p = 0.0007). In summer months, TBI-related hospital admissions (IRR 1.10, 95% CI 1.08-1.12, p < 0.0001) and 30-day mortality (HR 1.069, 95% CI 1.010-1.131, p = 0.0211) were more common than in other months. TBIs occurred more often in younger and healthier individuals on these index days and times. In terms of specific public holidays, the TBI risk was overall higher on New Year's Eves and Days (IRR 1.40, 95% CI 1.25-1.58, p < 0.0001) and Midsummer's Eves and Days (IRR 1.36, 95% CI 1.20-1.54, p < 0.0001), compared to nonworking days. This finding was significant in both genders. Conclusions: TBI-related hospital admissions and mortality were more common on public holidays, weekends, and in summer months in Finland. People who sustained TBIs on these days were on average younger and healthier. The occurrence of TBIs on public holidays and weekends is increasing at an alarming rate.acceptedVersionPeer reviewe

Prognosis of patients with operated chronic subdural hematoma

Chronic subdural hematoma (cSDH), previously considered fairly benign and easy to treat, is now viewed a possible sign of incipient clinical decline. We investigated case-fatality, excess fatality and need for reoperations following operated cSDH in a nationwide setting focusing on patient-related characteristics. Finnish nationwide databases were searched for all admissions with operated cSDH as well as later deaths in adults (≥ 16 years) during 2004–2017. There were 8539 patients with an evacuated cSDH (68% men) with a mean age of 73.0 (± 12.8) years. During the follow-up, 3805 (45%) patients died. In-hospital case-fatality was 0.7% (n = 60) and 30-day case-fatality 4.2% (n = 358). The 1-year case-fatality was 14.3% (95% CI = 13.4–15.2%) among men and 15.3% (95% CI = 14.0–16.7%) among women. Comorbidity burden, older age, and alcoholism were significantly associated with fatality. One-year excess fatality rate compared to general Finnish population was 9.1% (95% CI = 8.4–9.9) among men and 10.3% (95% CI = 9.1–11.4) among women. Highest excess fatality was observed in the oldest age group in both genders. Reoperation was needed in 19.4% (n = 1588) of patients. Older age but not comorbidity burden or other patient-related characteristics were associated with increased risk for reoperation. The overall case-fatality and need for reoperations declined during the study era. Comorbidities should be considered when care and follow-up are planned in patients with cSDH. Our findings underpin the perception that the disease is more dangerous than previously thought and causes mortality in all exposed age groups: even a minor burden of comorbidities can be fatal in the post-operative period.publishedVersionPeer reviewe

Trends and characteristics of infection-related hospital admissions in multiple sclerosis patients in Southwest Finland in 2009–2018

BackgroundMultiple sclerosis (MS) patients are at increased risk for infections. The aim of this study was to investigate the trends in hospital admissions of patients with MS and to identify the factors predisposing to infection-related admissions.MethodsHospital admissions with MS as a primary or an auxiliary diagnosis in the hospital district of Southwest Finland in 2009–2018 were searched and MS patients with infection admissions compared with other MS patients in the hospital district. Data were derived from hospital registries, patient charts and the Finnish MS register. Group comparisons were performed using Pearson´s chi-squared test, Fisher´s exact test or Wilcoxon rank sum test. Overdispersion-adjusted Poisson regression was used to analyze the annual admission numbers and multivariable logistic regression to examine the predictors of infection-related admissions.Results1380 hospital admissions for 532 patients were identified. The annual number of admissions decreased by 8.9% annually (pConclusionHospital admissions, with or without an infection, have become more infrequent in MS patients of Southwest Finland over the decade from 2009 to 2018. Infection-related admissions were associated with lesser use of DMTs, older age, male gender and disability.</div

Impact of Oral Anticoagulation and Adenosine Diphosphate Inhibitor Therapies on Short-term Outcome of Traumatic Brain Injury

BACKGROUND AND OBJECTIVES: Usage of oral anticoagulants (OACs) or adenosine diphosphate inhibitors (ADPi) is known to increase the risk of bleeding. We aimed to investigate the impact of OAC and ADPi therapies on short-term outcomes after traumatic brain injury (TBI). METHODS: All adult patients hospitalized for TBI in Finland during 2005-2018 were retrospectively studied using a combination of national registries. Usage of pharmacy-purchased OACs and ADPi at the time of TBI was analyzed with the pill-counting method (Social Insurance Institution of Finland). The primary outcome was 30-day case-fatality (Finnish Cause of Death Registry). The secondary outcomes were acute neurosurgical operation (ANO) and admission duration (Finnish Care Register for Health Care). Baseline characteristics were adjusted with multivariable regression, including age, sex, comorbidities, skull or facial fracture, OAC/ADPi treatment, initial admission location, and the year of TBI admission. RESULTS: The study population included 57,056 persons (mean age 66 years) of whom 0.9% used direct OACs (DOACs), 7.1% vitamin K antagonists (VKA), and 2.3% ADPi. Patients with VKAs had higher case-fatality than patients without OAC (15.4% vs 7.1%; adjusted hazard ratio [aHR] 1.35, CI 1.23-1.48; p < 0.0001). Case-fatality was lower with DOACs (8.4%) than with VKAs (aHR 0.62, CI 0.44-0.87; p = 0.005) and was not different from patients without OACs (aHR 0.93, CI 0.69-1.26; p = 0.634). VKA usage was associated with a higher neurosurgical operation rate compared with non-OAC patients (9.1% vs 8.3%; adjusted odds ratio 1.33, CI 1.17-1.52; p < 0.0001). There was no difference in operation rate between DOAC and VKA. ADPi was not associated with case-fatality or operation rate in the adjusted analyses. VKAs and DOACs were not associated with longer admission length compared with the non-OAC group, whereas the admissions were longer in the ADPi group compared with the non-ADPi group. DISCUSSION: Preinjury use of VKA is associated with increases in short-term mortality and in need for ANOs after TBI. DOACs are associated with lower fatality than VKAs after TBI. ADPi were not independently associated with the outcomes studied. These results point to relative safety of DOACs or ADPi in patients at risk of head trauma and encourage to choose DOACs when oral anticoagulation is required. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among adults with TBI, mortality was significantly increased in those using VKAs but not in those using DOACs or ADPi.Peer reviewe