Long-term mortality risk by cause of death in newly diagnosed patients with epilepsy in Finland: a nationwide register-based study

To estimate long-term mortality by cause of death in a nationwide, register-based cohort of newly diagnosed patients with epilepsy (PWE). All noninstitutionalized Finnish PWE aged 10–74 years (n = 10,818) eligible for reimbursement for antiepileptic medication for the first time between 1990 and 1994 were identified in the database of Social Insurance Institution of Finland. Mortality was compared against a population-based reference cohort (n = 43,894). Hazard ratios (HR) and their 95 % confidence intervals (95 % CI) during a follow-up of 18 years were estimated using proportional hazards modeling. Potential years of life lost (PYLL) and excess fraction of causes of death attributable to epilepsy were estimated. PWE contributed 137,610 person-years of observation and there were 3,558 deaths. Mortality remained elevated up to 18 years post-diagnosis (HR 3.21, 95 % CI 3.07–3.35). Ischemic heart disease mortality in PWE was two-fold (HR 2.31, 95 % CI 2.09–2.54), and remained constantly elevated during entire follow-up in both men and women. Most premature mortality in terms of PYLL was attributable to brain cancer (17 %), other cancers (15 %), ischemic heart disease (11 %), as well as cerebrovascular diseases (10 %). The percentage of deaths in PWE statistically attributable to epilepsy was 3.9 % for accidents, 3.4 % for alcohol-related diseases, and 1.6 % for suicides. PWE had substantial excess mortality from non-communicable diseases, which did not disappear by 18 years. Diseases of the circulatory system and cancers, especially brain cancer, were the most important causes of death almost regardless of the mortality indicator.     

BMI,weight change,and incidence of disability among Korean adults: A nationwide retrospective cohort study

BackgroundLittle is known about the risk of acquired disability diagnosed by a physician in relation to baseline BMI and weight change, particularly in the Asian population.ObjectiveThis study assessed the association of baseline BMI and weight change with incidence of disability.MethodsThis study included 331,900 individuals aged ≥40 years who participated in two health-screening programs since 2002 or 2003 and who were followed up until 2013. This study measured the baseline BMI and weight change for two years and estimated the adjusted hazard ratio (aHR) of the risk of acquired disability diagnosed by a physician using a Cox proportional hazards model.ResultsThis study identified 1758 incident disability cases during an average follow-up period of 10.7 ± 1.3 years from baseline (9.1 ± 1.4 years from the follow-up health screening). Baseline underweight (BMI<18.5 kg/m²) was associated with an increased risk of acquired disability compared with those with normal BMI (aHR, 1.44; 95% confidence interval [CI], 1.14–1.83). The risk of acquired disability was higher in individuals with weight loss of 5–10% (aHR, 1.21; 95% CI, 1.04–1.40), weight loss of ≥10% (aHR, 1.61; 95% CI, 1.27–2.04), weight gain of 5–10% (aHR, 1.30; 95% CI, 1.12–1.52), or weight gain of ≥10% (aHR, 1.35; 95% CI, 1.09–1.75) compared to those with weight change of <5%.ConclusionThis study demonstrated that baseline underweight and weight changes (both loss and gain) are associated with an increased risk of acquired disability.     

A retrospective nationwide register-based study to evaluate the non-specific effects of first MMR vaccination among children in Finland

BackgroundAccording to earlier studies, live vaccines like measles-mumps-rubella (MMR) vaccine could reduce also other infections than only the infections they are targeted against. This non-specific effect has been seen especially in studies in low-income countries and results from high-income countries have not been unambiguous. In 2011 Finland changed the recommended schedule for the first MMR vaccination from 18 months to 12 months of age. This change created a natural experiment for evaluating the potential non-specific effects.MethodsThis is a retrospective nationwide register-based cohort study of Finnish children born between 2008 and 2012. Children were divided into two cohorts by age at MMR vaccination: children administered early MMR vaccination (11 through 12 months of age) and late MMR vaccination (18 through 19 months of age). Morbidity was evaluated during the main follow-up period (from 13 to 17 months of age) and before any MMR vaccination (3 to 10 months) and after all were vaccinated with MMR (20 to 35 months) as control follow-up periods. We analyzed all infections and did additional analyzes for urinary tract infections (UTI) and bronchitis. Injuries were analyzed as a control outcome.ResultsEarly MMR vaccinated children (N = 79 949) had fewer infections compared to late MMR vaccinated (N = 60 965) during the main follow-up period. The incidence rate ratio (IRR) was 0.84 (95 % confidence interval (95 % CI) 0.81–0.87). However, similar differences were also observed during the control follow-up periods. MMR vaccinated children had less UTI in the main follow-up period (IRR 0.73, 0.60–0.89) but not in the control follow-up periods. When stratified by sex, the difference was observed among girls but not in boys.ConclusionNo clear evidence was found for non-specific effects in infectious diseases morbidity. However, there could be a nonspecific effect on UTI. Confirmation is needed from other studies, especially from high-income countries.     

基线BMI水平对急性胰腺炎发病风险影响的前瞻性队列研究

目的 探讨不同BMI水平对新发急性胰腺炎（AP）发病风险的影响。方法 观察人群来自开滦研究队列,按基线BMI水平分为：正常体重组（BMI<24 kg/m²）,超重组（BMI 24~28 kg/m²）和肥胖组（BMI ≥ 28 kg/m²）,观察不同BMI组人群新发AP发病密度。经Kaplan-Meier法绘制生存曲线,计算累积发病率,以log-rank法进行检验,并采用多因素Cox比例风险回归模型分析基线BMI水平对新发AP事件的影响。结果 共纳入统计分析者123 841人,随访（11.94±2.13）年,共发生AP 395例,总人群AP发病密度为2.67例/万人年,正常体重组、超重组和肥胖组AP发病密度分别为2.20、2.72和3.58例/万人年,累积发病率分别为0.32%、0.40%和0.49%。经log-rank检验,累积发病率的组间比较差异有统计学意义（χ²=13.17,P<0.01）。校正多因素Cox比例风险回归模型分析显示,与正常体重组比较,肥胖组AP发病风险增加,HR=1.45（95%CI：1.10~1.92）。对年龄及性别进行分层,年龄<60岁时,肥胖组发生AP的HR=1.58（95%CI：1.14~2.19）;男性肥胖组发生AP的HR=1.40（95%CI：1.03~1.90）。排除随访2年内发生的AP病例,肥胖组发生AP的HR=1.60（95%CI：1.18~2.15）。结论 肥胖是新发AP的危险因素,中青年男性肥胖人群发病风险更高。     

The association of adverse events with bivalent human papilloma virus vaccination: A nationwide register-based cohort study in Finland

BackgroundA bivalent HPV vaccine (Cervarix®; HPV2, GlaxoSmithKline) was introduced into the Finnish national vaccination programme (NVP) in November 2013 for girls aged 11–13 years with a catch-up for 14–15 year-olds. We evaluated the association between HPV2 and selected autoimmune diseases and clinical syndromes by conducting a nation-wide retrospective register-based cohort study.MethodsFirst life-time occurrences of the relevant ICD-10 codes in girls aged 11–15 years between Nov-2013 and Dec-2016 were obtained from the national hospital discharge register. Population denominators were obtained from the Population Information System and vaccination records from the National Vaccination Register. Registers were linked using unique personal identity codes. Association between HPV2 and 38 selected outcomes were studied using Cox regression, with age as the main time-scale and the first vaccination dose as the time-dependent exposure. The hazard ratios (HR) with 95%CI were assessed according to the time since exposure (entire follow-up, 0-180/181-365/>365 days).ResultsOf 240 605 girls eligible for HPV2 vaccination, 134 615 (56%) were vaccinated. After adjustment for geographical area (6 hospital districts), country of origin (Finnish-born/not) and number of hospital contacts from 9 through 10 years of age, HRs ranged from 0.34 (95%CI 0.11–1.05) to 8.37 (95%CI 0.85–82.54) and HPV2 vaccination was not statistically significantly associated with a higher risk of any outcome during the entire follow-up.ConclusionsThis study found no significantly increased risk for the selected outcomes after the HPV vaccination in girls 11–15 years of age. These results provide valid evidence to counterbalance public scepticism, fears of adverse events and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere.     

Oral contraceptive use and risk of fractures

INTRODUCTION: Prior studies have suggested that oral contraceptives (OCs) may be associated with an increased fracture risk. However, the previous studies have only performed a limited adjustment for other potential risk factors. SUBJECTS AND METHODS: All women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was use of OCs between January 1, 1996, and December 31, 2000. Adjustments were made for use of other drugs, pregnancy, prior fracture, other diseases and social variables. RESULTS: In the unadjusted analysis, use of OCs in low dose was associated with a small increase in overall fracture risk. However, upon adjustment, no increase in fracture risk could be demonstrated in any age or dose group. CONCLUSION: Oral contraceptives are not associated with an increase or a decrease in fracture risk. Any change in fracture risk may be due to confounders.     

HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway

BackgroundVaccination has been suggested to be involved in the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). HPV vaccine was introduced in the Norwegian Childhood Immunisation Programme and offered 12 year old girls from 2009. We studied the association between HPV vaccination and risk of CFS/ME and also assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake.MethodsIndividual data from national registries, including the Norwegian Population Registry, the Norwegian Patient Registry and the Norwegian Immunisation Registry were linked using the unique personal identification number. Yearly incidence rates of CFS/ME for 2009–2014 were calculated among the 824,133 boys and girls, aged 10–17 living in Norway during these 6 years. A total of 176,453 girls born 1997–2002 were eligible for HPV vaccination and included in further analyses. Hazard ratios (HRs) of CFS/ME were estimated using Cox regression. Risk differences (RDs) of vaccine uptake were estimated with binomial regression.ResultsA similar yearly increase in incidence rate of CFS/ME was observed among girls and boys, IRR = 1.15 (95% confidence interval (CI) 1.10–1.19) and 1.15 (95% CI 1.09–1.22), respectively. HPV vaccination was not associated with CFS/ME, HR = 0.86 (95% CI 0.69–1.08) for the entire follow-up period and 0.96 (95% CI 0.64–1.43) for the first two years after vaccination. The risk of CFS/ME increased with increasing number of previous hospital contacts, HR = 5.23 (95% CI 3.66–7.49) for 7 or more contacts as compared to no contacts. Girls with 7 or more hospital contacts were less likely to be vaccinated than girls with no previous hospital contacts, RD = −5.5% (95% CI −6.7% to −4.2%).ConclusionsNo indication of increased risk of CFS/ME following HPV vaccination was observed among girls in the first 6 birth cohorts offered HPV vaccine through the national immunisation programme in Norway.     

Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight

BACKGROUND/OBJECTIVESThis is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction.SUBJECTS/METHODSThe experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > 23 kg/m²) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < 1 × 10^-4). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted.RESULTSWe found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; P = 8.0 × 10^-7, rs1040675; 2.3 × 10^-6) and BMI (rs10786764; P = 2.5 × 10^-5, rs10786764; 6.57 × 10^-5). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P <10 × 10^-4. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < 1 × 10^-4). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group.CONCLUSIONWe discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.     

Professional cleaning and risk of asthma – a Danish nationwide register-based study

ObjectiveThis study aimed to investigate the risk of asthma among professional cleaners in a nationwide population-based study.MethodsProfessional cleaners, aged 16–50 years, were identified according to the yearly assigned administrative job and industrial codes in a register-based, matched cohort study with other manual workers as references (1995–2016). Asthma was defined from national registers based on hospitalization and medication. Associations between recent and cumulative cleaning years and risk of asthma were estimated using Poisson regression, first in a full cohort and then in an inception cohort, among workers aged 16–20 years at the start of follow-up.ResultsThe risk of asthma was not increased for recent cleaning compared to references [adjusted incidence rate ratio (IRR_adj) 1.02 [95% confidence interval (CI) 0.99–1.04]. Similar results were seen for the inception cohort, where cumulative years of cleaning were associated with increased risk of asthma, more prominent for the group with the maximum of six years of cleaning IRR_adj 2.53 (95% CI 1.38–4.64). Cumulative years of cleaning were associated with decreased risk of asthma, more pronounced for the maximum of ten compared to one year of cleaning [IRR_adj 0.74 (95% CI 0.63–0.88)].ConclusionsAsthma risk was increased in the inception cohort for cumulative years of cleaning but decreased in the full cohort. We could not confirm that recent work within cleaning was associated with increased risk of asthma. This may be due to healthy worker bias. Thus, we cannot rule out that long-term professional cleaning may be associated with increased risk of asthma.     

A nationwide cohort study on the incidence of meningioma in women using postmenopausal hormone therapy in Finland

The authors conducted a nationwide cohort study to evaluate the association between postmenopausal hormone therapy and meningioma incidence in Finland. All women who had used hormone therapy at least for 6 months at the age of 50 years or older during 1994-2009 were included. Women who had used postmenopausal hormone therapy were identified from the medical reimbursement register of the Social Insurance Institution (131,480 estradiol users and 131,248 estradiol-progestin users), and meningioma cases were identified from the Finnish Cancer Registry. During the average 9 years of follow-up, 289 estradiol users and 196 estradiol-progestin users were diagnosed with meningioma. Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P < 0.001) than in the background population. In contrast, this risk was not increased in users of combination therapy (standardized incidence ratio = 0.93, 95% confidence interval: 0.80, 1.06). There was no difference in risk between continuous and sequential use of hormone therapy. Estradiol-only therapy was accompanied with a slightly increased risk of meningioma.     

Resource allocation of in vitro fertilization: a nationwide register-based cohort study

Background  

Infertility is common and in vitro fertilization (IVF) is a widely used treatment. In IVF the need increases and the effectiveness and appropriateness decrease by age. The purpose of this study was to describe allocation of resources for IVF by women's age, socioeconomic position, area of residence and treatment sector (public vs. private) and to discuss how fairly the IVF resources are allocated in Finland.     

BMI与中国女性三阴型乳腺癌发病风险的分析

目的 探讨不同绝经状态下,体重指数(BMI)与中国女性三阴型乳腺癌发病风险的关系及对应的敏感界值。方法 采用匹配病例对照研究设计,病例和对照按年龄和绝经状态1∶2匹配,于2010年至2014年序贯收集四川省肿瘤医院391名原发性三阴型乳腺癌新发病例,同期收集成都市妇女儿童中心医院社区来源的健康对照782名。采用结构式问卷调查收集研究对象的一般人口学特征、身高、体重、生殖生育因素、现患及既往疾病史等信息。在不同绝经状态下,采用不同BMI分类标准（WHO四分类、亚洲四分类、中国四分类）估计BMI水平与三阴型乳腺癌的关联度,统计方法采用Logistic回归分析。结果 调整了年龄、初潮年龄、初产年龄、初潮和初产年龄的时间间隔等信息后,WHO二分类划分标准提示,高BMI与绝经前、后TNBC发病呈正相关（aOR绝经前= 2.19,95%CI:1.40～3.43;aOR绝经后=2.05,95%CI:1.29～3.27）。绝经前TNBC,WHO四分类中超重（BMI:25.0～29.9 kg/m2）和肥胖（BMI≥30.0 kg/m2）的aOR分别为:1.97（95%CI:1.23～3.15）和5.45（95%CI:1.07～27.74）;绝经后TNBC,中国四分类中肥胖（BMI≥28.0 kg/m2）的aOR为2.14（95%CI:1.02～4.48）。连续性BMI的趋势分析显示,不同绝经状态下随着BMI增高乳腺癌发病风险增大（Pfor trend ＜0.05）。结论 对于中国女性,高BMI是三阴型乳腺癌发病的危险因素,且绝经前后应采用不同的BMI敏感界值（BMI绝经前 ≥25.0 kg/m2,BMI绝经后≥28kg/m2）来估计三阴型乳腺癌的发病风险。     

广东中山古镇健康中老年人体质指数与血脂水平的流行病学研究

目的 探讨体质指数(BMI)和肥胖率以及血脂变化趋势。方法 分别于1992年和1996年在广东中山古镇进行了两次心脑血管病危险因素的调查。结果 调查显示：人群BMI和肥胖率均以1996年为高，呈上升趋势且上升幅度明显；人群TC和LDL—C水平及异常率呈下降趋势；HDL—C亦有所下降，但仍高于全国水平，特别是45—54岁的男性TG异常率有所升高；多元线性逐步回归方程所示：BMI与腰围＼臀围(WHR)、TG、SBP呈正相关。结论 保持适中的体重成为当前预防心脑血管病重点之一，同时继续加强对高脂血症者的预防及控制仍十分必要。     

高校大学生体质指数变化趋势研究

目的了解大学生体质指数(BMI)变化趋势,分析其超重和肥胖发病率,为预防控制超重和肥胖,提高大学生群体的健康水平提供依据。方法采用队列研究,对北京市一所综合大学应用文理学院2004年入学的全部大学生每年进行一次身高、体重的测量,共4次,分析体质指数变化趋势,计算超重和肥胖累积人年发病率。结果男生和女生在入学时BMI分别为22.7±4.2 kg/m2、20.9±3.5 kg/m2,2005年BMI水平最低,分别为22.2±4.3 kg/m2、20.3±3.3 kg/m2(P0.05),2007年BMI水平最高,分别为24.1±4.5 kg/m2、21.2±3.5 kg/m2,且均显著高于入学时水平(P0.05)。与入学时相比,男生在第四年时低体重率显著降低(P0.05),超重和肥胖率显著升高(P0.05);而女生在第二年和第三年低体重率均显著升高(P0.05),正常体重者在第二年则显著减少(P0.05)。按照WHO判断标准和中国判断标准计算,超重和肥胖累积人年发病率分别为8.87%和11.10%。结论该校大学生超重和肥胖问题应该引起高度重视,应根据男生和女生不同特点开展针对性的健康教育,以提高大学生群体的健康水平。