Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada

ObjectiveTo assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood.DesignAnalysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates.SettingPopulation-based.Participants1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario).ExposureClinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy.Main outcome measuresWe extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes ‘epilepsy’ and ‘febrile seizures’.ResultsAmong 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester.ConclusionsIn this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.

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Sex specific associations between in utero exposure to persistent organic pollutants and allergy-related outcomes in childhood: The Rhea Mother–Child Cohort (Crete, Greece)

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174421000660 ◽

2021 ◽

pp. 1-9

Author(s):

Katerina Margetaki ◽

Maria Alexaki ◽

Evangelos Vittorakis ◽

Theano Roumeliotaki ◽

Vasiliki Leventakou ◽

...

Keyword(s):

Organic Pollutants ◽

Prenatal Exposure ◽

Persistent Organic Pollutants ◽

Polychlorinated Biphenyl ◽

International Study ◽

First Trimester ◽

In Utero ◽

Current Asthma ◽

Increased Risk ◽

Asthma And Allergy

Abstract Accumulating evidence suggests that in utero exposures can influence the development of the immune system. Few studies have investigated whether prenatal exposure to persistent organic pollutants (POPs) is associated with allergy-related phenotypes in childhood, nor explored sex differences. We examined the association between prenatal exposure to POPs and offspring allergic outcomes in early and mid-childhood. We included 682 mother–child pairs from the prospective birth cohort Rhea. We measured dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and 6 polychlorinated biphenyl (PCB) congeners in maternal first trimester serum. Parents completed the questionnaires adapted from the International Study on Asthma and Allergy in Childhood (ISAAC) for allergy-related phenotypes when their children were 4 and 6 years old. We used Poisson regression models to estimate Risk Ratios. Prenatal HCB was associated with increased risk for rhinoconjunctivitis at 6 years (RR (95% CI): 2.5; (1.3, 4.8) for a doubling in the exposure). Among girls, prenatal DDE was associated with increased risk for current wheeze, current asthma and current rhinoconjunctivitis at 4 years (RR (95%CI): 1.4 (0.8, 2.6), 1.6 (1.1, 2.4) and 1.8 (1.0, 3.3) and p-interaction = 0.035, 0.027 and 0.059, respectively), with increased risk for current rhinoconjunctivitis at 6 years (RR (95%CI): 1.7 (0.7, 3.8) and p-interaction = 0.028) and total PCBs were associated with increased risk for current eczema at 4 years (RR (95%CI): 2.1 (1.1, 4.2) and p-interaction = 0.028). In boys, prenatal DDE was associated with decreased risk for current wheeze and current asthma at 4 years. Our findings suggest that even low levels of exposure to POPs prenatally may affect the development of childhood allergy-related outcomes in a sex and age-specific manner.

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Sibling Alcohol Use Disorder Is Associated With Increased Risk for Suicide Attempt

Clinical Psychological Science ◽

10.1177/21677026211025041 ◽

2021 ◽

pp. 216770262110250

Author(s):

Mallory E. Stephenson ◽

Sara Larsson Lönn ◽

Jessica E. Salvatore ◽

Jan Sundquist ◽

Kenneth S. Kendler ◽

...

Keyword(s):

Alcohol Use ◽

Suicide Attempt ◽

Alcohol Use Disorder ◽

Cox Regression ◽

Population Based ◽

Swedish Population ◽

Sibling Pairs ◽

Increased Risk ◽

Using Data ◽

Shared Genetic

The association between having a sibling diagnosed with alcohol use disorder (AUD) and risk for suicide attempt may be attributable to shared genetic liability between AUD and suicidal behavior, effects of environmental exposure to a sibling’s AUD, or both. To distinguish between these alternatives, we conducted a series of Cox regression models using data derived from Swedish population-based registers with national coverage. Among full sibling pairs (656,807 males and 607,096 females), we found that, even after we accounted for the proband’s AUD status, the proband’s risk for suicide attempt was significantly elevated when the proband’s sibling was affected by AUD. Furthermore, the proband’s risk for suicide attempt was consistently higher when the sibling’s AUD registration had occurred more recently. Our findings provide evidence for exposure to sibling AUD as an environmental risk factor for suicide attempt and suggest that clinical outreach may be warranted following a sibling’s diagnosis with AUD.

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Inflammatory markers and risk of cardiovascular mortality in relation to diabetes status in the HUNT study

Scientific Reports ◽

10.1038/s41598-021-94995-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Løfblad ◽

Gunhild Garmo Hov ◽

Arne Åsberg ◽

Vibeke Videm

Keyword(s):

Cardiovascular Mortality ◽

Inflammatory Markers ◽

Cox Regression ◽

Population Based ◽

Control Group ◽

Bottom Quartile ◽

Diabetes Status ◽

Increased Risk ◽

General Populations ◽

Log Linear

AbstractInflammatory markers have been associated with increased risk of cardiovascular mortality in general populations. We assessed whether these associations differ by diabetes status. From a population-based cohort study (n = 62,237) we included all participants with diabetes (n = 1753) and a control group without diabetes (n = 1818). Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for possible associations with cardiovascular mortality of 4 different inflammatory markers; C-reactive protein (CRP), calprotectin, neopterin and lactoferrin. During a median follow-up of 13.9 years, 728 (20.4%) died from cardiovascular disease (CVD). After adjustment for age, sex and diabetes, the associations of all inflammatory markers with risk of cardiovascular mortality were log-linear (all P ≤ 0.017 for trend) and did not differ according to diabetes status (all P ≥ 0.53 for interaction). After further adjustments for established risk factors, only CRP remained independently associated with cardiovascular mortality. HRs were 1.22 (1.12–1.32) per standard deviation higher loge CRP concentration and 1.91 (1.50–2.43) when comparing individuals in the top versus bottom quartile. The associations of CRP, calprotectin, lactoferrin and neopterin with cardiovascular mortality did not differ by diabetes, suggesting that any potential prognostic value of these markers is independent of diabetes status.

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Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease

Gerontology ◽

10.1159/000512287 ◽

2021 ◽

pp. 1-9

Author(s):

Lee Butcher ◽

Jose Antonio Carnicero ◽

Karine Pérès ◽

Marco Colpo ◽

David Gomez Cabrero ◽

...

Keyword(s):

Older Adults ◽

Cox Regression ◽

Population Based ◽

Blood Levels ◽

Roc Curve Analysis ◽

Baseline Serum ◽

Frailty Status ◽

Risk Of Death ◽

Survival Difference ◽

Increased Risk

Introduction: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. Methods: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. Results: In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09–2.49, p = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18–3.29, p = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71–3.15, p = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. Conclusions: Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.

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Coeliac disease and invasive pneumococcal disease: a population-based cohort study

Epidemiology and Infection ◽

10.1017/s0950268816003204 ◽

2017 ◽

Vol 145 (6) ◽

pp. 1203-1209 ◽

Cited By ~ 9

Author(s):

A. RÖCKERT TJERNBERG ◽

J. BONNEDAHL ◽

M. INGHAMMAR ◽

A. EGESTEN ◽

G. KAHLMETER ◽

...

Keyword(s):

Cohort Study ◽

Coeliac Disease ◽

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

Cox Regression ◽

Statistical Significance ◽

Pneumococcal Vaccination ◽

Population Based ◽

Increased Risk ◽

Severe Infections

SUMMARYSevere infections are recognized complications of coeliac disease (CD). In the present study we aimed to examine whether individuals with CD are at increased risk of invasive pneumococcal disease (IPD). To do so, we performed a population-based cohort study including 29 012 individuals with biopsy-proven CD identified through biopsy reports from all pathology departments in Sweden. Each individual with CD was matched with up to five controls (n = 144 257). IPD events were identified through regional and national microbiological databases, including the National Surveillance System for Infectious Diseases. We used Cox regression analyses to estimate hazard ratios (HRs) for diagnosed IPD. A total of 207 individuals had a record of IPD whereas 45/29 012 had CD (0·15%) and 162/144 257 were controls (0·11%). This corresponded to a 46% increased risk for IPD [HR 1·46, 95% confidence interval (CI) 1·05–2·03]. The risk estimate was similar after adjustment for socioeconomic status, educational level and comorbidities, but then failed to attain statistical significance (adjusted HR 1·40, 95% CI 0·99–1·97). Nonetheless, our study shows a trend towards an increased risk for IPD in CD patients. The findings support results seen in earlier research and taking that into consideration individuals with CD may be considered for pneumococcal vaccination.

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Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001102 ◽

2017 ◽

Vol 27 (9) ◽

pp. 1804-1812 ◽

Cited By ~ 5

Author(s):

Tine H. Schnack ◽

Estrid Høgdall ◽

Lotte Nedergaard Thomsen ◽

Claus Høgdall

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Cox Regression ◽

Clear Cell ◽

Statistical Tests ◽

Gynecological Cancer ◽

Population Based ◽

Clear Cell Adenocarcinoma ◽

Ovarian Endometriosis ◽

Increased Risk

ObjectivesWomen with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status.MethodsPopulation-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ2 Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant.ResultsPatients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29–5.02], in the multivariate analysis.ConclusionsAge at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.

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Impact of pre-existing cardiovascular disease on treatment patterns and survival outcomes in patients with lung cancer

BMC Cancer ◽

10.1186/s12885-020-07487-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Atul Batra ◽

Dropen Sheka ◽

Shiying Kong ◽

Winson Y. Cheung

Keyword(s):

Lung Cancer ◽

Cardiovascular Disease ◽

Cox Regression ◽

Population Based ◽

Treatment Patterns ◽

Competing Risk ◽

Survival Outcomes ◽

Multistate Model ◽

Cancer Specific Survival ◽

Increased Risk

Abstract Background Baseline cardiovascular disease (CVD) can impact the patterns of treatment and hence the outcomes of patients with lung cancer. This study aimed to characterize treatment trends and survival outcomes of patients with pre-existing CVD prior to their diagnosis of lung cancer. Methods We conducted a retrospective, population-based cohort study of patients with lung cancer diagnosed from 2004 to 2015 in a large Canadian province. Multivariable logistic regression and Cox regression models were constructed to determine the associations between CVD and treatment patterns, and its impact on overall (OS) and cancer-specific survival (CSS), respectively. A competing risk multistate model was developed to determine the excess mortality risk of patients with pre-existing CVD. Results A total of 20,689 patients with lung cancer were eligible for the current analysis. Men comprised 55%, and the median age at diagnosis was 70 years. One-third had at least one CVD, with the most common being congestive heart failure in 15% of patients. Pre-existing CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.48–0.58; P < .0001), radiotherapy (OR, 0.76; 95% CI, 0.7–0.82; P < .0001), and surgery (OR, 0.56; 95% CI, 0.44–0.7; P < .0001). Adjusting for measured confounders, the presence of pre-existing CVD predicted for inferior OS (hazard ratio [HR], 1.1; 95% CI, 1.1–1.2; P < .0001) and CSS (HR, 1.1; 95% CI, 1.1–1.1; P < .0001). However, in the competing risk multistate model that adjusted for baseline characteristics, prior CVD was associated with increased risk of non-cancer related death (HR, 1.48; 95% CI, 1.33–1.64; P < 0.0001) but not cancer related death (HR, 0.98; 95% CI, 0.94–1.03; P = 0.460). Conclusions Patients with lung cancer and pre-existing CVD are less likely to receive any modality of cancer treatment and are at a higher risk of non-cancer related deaths. As effective therapies such as immuno-oncology drugs are introduced, early cardio-oncology consultation may optimize management of lung cancer.

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Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

Frontiers in Pediatrics ◽

10.3389/fped.2021.714406 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yen-Chu Huang ◽

Meng-Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Research Database ◽

Real World Data ◽

Childhood Disorders ◽

Cox Regression Analysis ◽

Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

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Increased risk of cancer in patients with retinal vein occlusion: a 12-year nationwide cohort study

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-316947 ◽

2020 ◽

pp. bjophthalmol-2020-316947

Author(s):

Min Seok Kim ◽

Joon Hee Cho ◽

Seong Jun Byun ◽

Chang-Mo Oh ◽

Kyu Hyung Park ◽

...

Keyword(s):

Retinal Vein Occlusion ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Control Group ◽

Time Varying ◽

Vein Occlusion ◽

Increased Risk ◽

Risk Of Cancer ◽

Subsequent Cancer

AimsTo investigate the association between incident retinal vein occlusion (RVO) and the subsequent development of cancer.MethodsIn this nationwide population-based retrospective study using 2002–2013 National Health Insurance Service database which covers the entire South Korean population, 186 701 incident RVO patients and their 1:1 propensity-score matched controls were included. We defined the fixed cohort from January 1st, 2004 to December 31st, 2013; the cohort included patients who suffered incident RVO after entering the cohort and their matched controls, and excluded patients having any cancer history before entering the cohort. The association of RVO and cancer was assessed by time-varying covariate Cox regression models; Model 1 included RVO as a time-varying covariate, Model 2 included Model 1 plus demographic information and Model 3 included Model 2 and comorbidities.ResultsRVO was associated with an increased risk of subsequent cancer (HR=1.29; 95% CI, 1.26–1.31 in Model 1), which was consistent in Models 2 and 3. The incidence rate of overall cancer during the study period was 25.55 (95% CI, 25.19–25.91) per 1000 person-years in the RVO group and 18.62 (95% CI, 18.46–18.79) per 1000 person-years in the control group. In the subgroup analysis, haematological malignancies showed the highest association with RVO (HR=1.65; 95% CI, 1.49–1.83).ConclusionPatients with RVO have an increased risk of subsequent cancer development even after adjusting for demographic factors and comorbidities. Further study is warranted to elucidate these associations to provide proper recommendations for RVO patients regarding the cancer screening.

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P0211GLOMERULAR HYPERFILTRATION AND CANCER: A NATIONWIDE POPULATION-BASED STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0211 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yaerim Kim ◽

Jeongsoo Yoon ◽

Jin Hyuk Paek ◽

Woo Yeong Park ◽

Kyubok Jin ◽

...

Keyword(s):

National Health ◽

Malignant Disease ◽

Cox Regression ◽

Asian Population ◽

Population Based ◽

Glomerular Hyperfiltration ◽

Outcome Variable ◽

Cox Regression Analysis ◽

Increased Risk ◽

The Impact

Abstract Background and Aims Glomerular hyperfiltration is associated with all-cause mortality. Herein, we evaluated the association between glomerular hyperfiltration and the development of malignant disease, the most common cause of death, in an Asian population. Method We retrospectively reviewed the National Health Insurance Service database of Korea for people who received national health screenings from 2012 to 2013. Glomerular hyperfiltration was defined as the 95th percentile and greater after adjusting for age and sex. We performed a multivariate Cox regression analysis using glomerular hyperfiltration at the first health screening as the exposure variable and cancer development as the outcome variable to evaluate the impact of glomerular hyperfiltration on the development of malignant disease. Results A total of 1,953,123 examinations who followed-up for 4.9 years were included in this study. Among the 8 different site-specific malignant disease categories, digestive organs and female genital organs showed a significant associations between glomerular hyperfiltration and malignancy. The population with glomerular hyperfiltration showed an increased risk for stomach cancer (adjusted hazard ratio [aHR], 1.27), colorectal cancer (aHR, 1.23), and liver or intrahepatic malignancy (aHR, 1.40). In addition, the risk for uterine and ovarian cancer was significantly increased in the population with glomerular hyperfiltration (aHR, 1.36). Conclusion Glomerular hyperfiltration was associated with an increased risk for the development of malignant diseases in specific organs, such as the stomach, colorectum, uterus, and ovary. Glomerular hyperfiltration needs to be considered a significant sign of the need to evaluate the possibility of hidden adverse health conditions, including malignancies.

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