Asthma and asthma symptom control in relation to incidence of lung cancer in the HUNT study

AbstractLarge prospective studies on asthma, especially asthma symptom control, as a potential risk factor for lung cancer are limited. We followed up 62,791 cancer-free Norwegian adults from 1995–1997 to 2017. Self-reported doctor-diagnosed asthma was categorized into active and non-active asthma. Levels of asthma symptom control were classified into controlled and partially controlled (including partly controlled and uncontrolled) according to the Global Initiative for Asthma guidelines. Incident lung cancer cases were ascertained from the Cancer Registry of Norway. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for possible associations. Totally, 984 participants developed lung cancer during a median follow-up of 21.1 years. After adjustment for smoking and other potential confounders, an increased incidence of lung cancer was found for adults with partially controlled asthma (HR 1.39, 95% CI 1.00–1.92) compared with those without asthma at baseline. Adults with active asthma had a tendency of increased lung cancer incidence (HR 1.29, 95% CI 0.95–1.75). Sensitivity analyses indicated that the observed associations were less likely resulted from reverse causation or residual confounding by smoking. Our findings suggested that proper control of asthma symptoms might contribute to a reduced incidence of lung cancer.

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P4795Comparative safety of factor-xa inhibitors vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease - insights from the RELOADED study

European Heart Journal ◽

10.1093/eurheartj/ehz745.1171 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H Bonnemeier ◽

R Kreutz ◽

D Enders ◽

N Schmedt ◽

T Vaitsiakhovich ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Disease ◽

Hospital Discharge ◽

Cox Regression ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Sensitivity Analyses ◽

Hazard Ratios ◽

Fatal Bleeding ◽

Number Of Patients

Abstract Background Data on safety of Factor-Xa inhibitors and phenprocoumon in patients with non-valvular atrial fibrillation (NVAF) and renal disease is scarce. Among others, our study aimed to investigate the safety risks of fatal bleeding and intracranial haemorrhage (ICH) in new users of Factor-Xa inhibitors vs. phenprocoumon, the vitamin-K antagonist (VKA) of choice in Germany. Methods We conducted a new user cohort study (one year washout period) in patients with NVAF and renal disease. German claims data between January 1st, 2013 and June 30th, 2017 were utilized and a multiple Cox-regression was performed to calculate confounder-adjusted hazard ratios (HRs) for the risk of fatal bleeding and ICH in Factor-Xa inhibitors and phenprocoumon initiators. Additionally, a propensity score matching and an inverse probability of treatment weight analysis were performed as sensitivity analyses. Cases of fatal bleeding were defined as hospitalization with a primary hospital discharge diagnoses for bleeding with documented death as reason for hospital discharge or within 30 days after hospital discharge. Results The overall population comprised 23,552 phenprocoumon initiators, 22,338 rivaroxaban initiators and 16,201 apixaban initiators, where the number of patients with renal disease initiating these agents were 7,289 for phenprocoumon, 5,121 patients for rivaroxaban 15mg or 20mg and 4,750 patients for apixaban 2.5mg or 5mg, respectively. In the confounder-adjusted analysis, a beneficial effect for rivaroxaban and apixaban over phenprocoumon was observed for the risk of ICH and fatal bleeding (figure 1) for both the overall and renal disease population. Hazard ratios for rivaroxaban and the risk of ICH were calculated as 0.57 (0.43; 0.75) for the overall population and 0.62 (0.37; 1.01) for the renal disease population where hazard ratios for apixaban were calculated as 0.43 (0.31; 0.60) for the overall population and 0.41 (0.23; 0.74) for the renal disease population, respectively. There was not sufficient data to conduct the analyses for edoxaban. Figure 1 Conclusion This large retrospective database study conducted in Germany confirms the safety profile of rivaroxaban and apixaban over VKA in patients overall and specifically in patients with renal disease when assessing the risk of ICH and fatal bleeding. Our study adds evidence in a relevant subgroup of patients where anticoagulation is often challenging. Acknowledgement/Funding This study was funded by Bayer AG

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Infections in childhood and subsequent diagnosis of autism spectrum disorders and intellectual disability: a register-based cohort study

10.1101/2021.03.10.21252968 ◽

2021 ◽

Author(s):

Håkan Karlsson ◽

Hugo Sjöqvist ◽

Martin Brynge ◽

Renee Gardner ◽

Christina Dalman

Keyword(s):

Intellectual Disability ◽

Regression Models ◽

Cox Regression ◽

Autism Spectrum ◽

Sensitivity Analyses ◽

Childhood Infections ◽

Specialized Care ◽

Icd Codes ◽

Spectrum Disorders ◽

Residual Confounding

AbstractObjectiveTo explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID) and their co-occurrence.MethodsThe association between specialized care for any infection, defined by ICD-codes and later ASD or ID was investigated in a register-based cohort of 556,732 individuals born 1987-2010, resident in Stockholm County, followed from birth to their 18th birthday or December 31, 2016. We considered as potential confounders children’s characteristics, family socioeconomic factors, obstetric complications, and parental histories of both treatment for infection and psychiatric disorders in survival analyses with extended Cox regression models. Residual confounding by shared familial factors was addressed in sibling analyses using within-strata estimation in Cox regression models. Sensitivity analyses with exclusion of congenital causes of ASD/ID and documented risk for infections were also performed.ResultsCrude estimates indicated that infections during childhood were associated with later ASD and ID with largest risks observed for diagnoses involving ID. Inclusion of covariates, exclusion of congenital causes of ASD/ID from the population and sibling comparisons highlighted the potential for confounding by both heritable and non-heritable factors, though risks remained in all adjusted models. In adjusted sibling comparisons, excluding congenital causes, infections were associated with later ‘ASD without ID’ (HR 1.24, 95%CI 1.15-1.33), ‘ASD with ID’ (1.57, 1.35-1.82) and ‘ID without ASD’ (2.01, 1.76-2.28). Risks associated with infections varied by age at exposure and by age at diagnosis of ASD/ID.ConclusionsInfections during childhood cannot be excluded in the etiology of ASD, particularly ASD with co-occurring ID.

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Self-reported visual impairment, physical activity and all-cause mortality: The HUNT Study

Scandinavian Journal of Public Health ◽

10.1177/1403494816680795 ◽

2016 ◽

Vol 45 (1) ◽

pp. 33-41 ◽

Cited By ~ 4

Author(s):

Audun Brunes ◽

W. Dana Flanders ◽

Liv Berit Augestad

Keyword(s):

Physical Activity ◽

Visual Impairment ◽

Mortality Risk ◽

Cox Regression ◽

Age Groups ◽

Health Study ◽

Cox Models ◽

Hazard Ratios ◽

All Cause Mortality ◽

Hunt Study

Aims: To examine the associations of self-reported visual impairment and physical activity (PA) with all-cause mortality. Methods: This prospective cohort study included 65,236 Norwegians aged ⩾20 years who had participated in the Nord-Trøndelag Health Study (HUNT2, 1995−1997). Of these participants, 11,074 (17.0%) had self-reported visual impairment (SRVI). The participants’ data were linked to Norway’s Cause of Death Registry and followed throughout 2012. Hazard ratios and 95% confidence intervals (CI) were assessed using Cox regression analyses with age as the time-scale. The Cox models were fitted for restricted age groups (<60, 60−84, ⩾85 years). Results: After a mean follow-up of 14.5 years, 13,549 deaths were identified. Compared with adults with self-reported no visual impairment, the multivariable hazard ratios among adults with SRVI were 2.47 (95% CI 1.94–3.13) in those aged <60 years, 1.22 (95% CI 1.13–1.33) in those aged 60–84 years and 1.05 (95% CI 0.96–1.15) in those aged ⩾85 years. The strength of the associations remained similar or stronger after additionally controlling for PA. When examining the joint associations, the all-cause mortality risk of SRVI was higher for those who reported no PA than for those who reported weekly hours of PA. We found a large, positive departure from additivity in adults aged <60 years, whereas the departure from additivity was small for the other age groups. Conclusions: Adults with SRVI reporting no PA were associated with an increased all-cause mortality risk. The associations attenuated with age.

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Peak flow as a predictor of cause-specific mortality in China: results from a 15-year prospective study of ∼170 000 men

International Journal of Epidemiology ◽

10.1093/ije/dyt079 ◽

2013 ◽

Vol 42 (3) ◽

pp. 803-815 ◽

Cited By ~ 11

Author(s):

Margaret Smith ◽

Maigeng Zhou ◽

Lijun Wang ◽

Richard Peto ◽

Gonghuan Yang ◽

...

Keyword(s):

Lung Cancer ◽

Cardiovascular Disease ◽

Cox Regression ◽

Forced Expiratory Volume ◽

Respiratory Mortality ◽

Hazard Ratios ◽

Specific Mortality ◽

Study Population ◽

Log Linear

Abstract Background Forced expiratory volume in one second (FEV1) is inversely associated with mortality in Western populations, but few studies have assessed the associations of peak expiratory flow (PEF) with subsequent cause-specific mortality, or have used populations in developing countries, including China, for such assessments. Methods A prospective cohort study followed ∼170 000 Chinese men ranging in age from 40–69 years at baseline (1990–1991) for 15 years. In the study, height-adjusted PEF (h-PEF), which was uncorrelated with height, was calculated by dividing PEF by height. Hazard ratios (HR) for cause-specific mortality and h-PEF, adjusted for age, area of residence, smoking, and education, were calculated through Cox regression analyses. Results Of the original study population, 7068 men died from respiratory causes (non-neoplastic) and 22 490 died from other causes (including 1591 from lung cancer, 5469 from other cancers, and 10 460 from cardiovascular disease) before reaching the age of 85 years. Respiratory mortality was strongly and inversely associated with h-PEF. For h-PEF ≥ 250 L/min, the association was log-linear, with a hazard ratio (HR) of 1.29 (95% CI: 1.25–1.34) per 100 L/min reduction in h-PEF. The association was stronger but not log-linear for lower values of h-PEF. Mortality from combined other causes was also inversely associated with h-PEF, and the association was log-linear for all values of h-PEF, declining with follow-up, with HRs per 100 L/min reduction in h-PEF of 1.13 (1.10–1.15), 1.08 (1.06–1.11), and 1.06 (1.03–1.08) in three consecutive 5-year follow-up periods. Specifically, lower values of h-PEF were associated with higher mortality from cardiovascular disease and lung cancer, but not from other cancers. Conclusions A lower value of h-PEF was associated with increased mortality from respiratory and other causes, including lung cancer and cardiovascular disease, but its associations with the other causes of death declined across the follow-up period.

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Pre-eclampsia and risk of dementia later in life: nationwide cohort study

BMJ ◽

10.1136/bmj.k4109 ◽

2018 ◽

pp. k4109 ◽

Cited By ~ 27

Author(s):

Saima Basit ◽

Jan Wohlfahrt ◽

Heather A Boyd

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Vascular Dementia ◽

Cox Regression ◽

Late Onset ◽

Hazard Ratio ◽

Sensitivity Analyses ◽

Hazard Ratios ◽

Increased Risk ◽

History Of

AbstractObjectiveTo explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one live birth or stillbirth between 1978 and 2015.Main outcome measureHazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression.ResultsThe cohort consisted of 1 178 005 women with 20 352 695 person years of follow-up. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia (hazard ratio 3.46, 95% confidence interval 1.97 to 6.10) later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late onset disease (hazard ratio 6.53, 2.82 to 15.1) than for early onset disease (2.32, 1.06 to 5.06) (P=0.08). Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios only moderately; sensitivity analyses suggested that body mass index was unlikely to explain the association with vascular dementia. In contrast, only modest associations were observed for Alzheimer’s disease (hazard ratio 1.45, 1.05 to 1.99) and other/unspecified dementia (1.40, 1.08 to 1.83).ConclusionsPre-eclampsia was associated with an increased risk of dementia, particularly vascular dementia. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that pre-eclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways. Asking about a history of pre-eclampsia could help physicians to identify women who might benefit from screening for early signs of disease, allowing for early clinical intervention.

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Metformin reduces risk of benign nodular goiter in patients with type 2 diabetes mellitus

Acta Endocrinologica ◽

10.1530/eje-19-0133 ◽

2019 ◽

Vol 180 (6) ◽

pp. 365-372 ◽

Cited By ~ 2

Author(s):

Chin-Hsiao Tseng

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Propensity Score ◽

Lower Risk ◽

Cox Regression ◽

Nodular Goiter ◽

Sensitivity Analyses ◽

Hazard Ratios

BackgroundWhether metformin might affect the risk of benign nodular goiter in patients with type 2 diabetes mellitus has not been investigated.MethodsPatients with new-onset type 2 diabetes mellitus during 1999–2005 were enrolled from Taiwan’s National Health Insurance database. Analyses were conducted in a propensity score matched-pairs of 20,048 ever users and 20,048 never users of metformin. The patients were followed until December 31, 2011, for the incidence of benign nodular goiter. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the propensity score.ResultsAmong the never users and ever users of metformin, 392 and 221 cases were diagnosed of benign nodular goiter during follow-up, with incidence of 457.88 and 242.45 per 100,000 person-years, respectively. The overall hazard ratio for ever versus never users was 0.527 (95% confidence interval: 0.447–0.621). When cumulative duration of metformin therapy was divided into tertiles, the hazard ratios for the first (<25.3 months), second (25.3–57.3 months) and third (>57.3 months) tertiles were 0.815 (0.643–1.034), 0.648 (0.517–0.812) and 0.255 (0.187–0.348), respectively. Sensitivity analyses estimating the overall hazard ratios for patients enrolled in each specific year from 1999 to 2005 consistently showed a lower risk of benign nodular goiter among users of metformin.ConclusionMetformin use is associated with a lower risk of benign nodular goiter in patients with type 2 diabetes mellitus.

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Advanced cancer survival in a rural community: The impact of hospice services.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e20628 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e20628-e20628

Author(s):

David Eric Cowall ◽

Veera Holdai

Keyword(s):

Lung Cancer ◽

Rural Community ◽

Cancer Survival ◽

Cox Regression ◽

P Value ◽

Cox Regression Analysis ◽

Rank Analysis ◽

Lung Cancer Patients ◽

Hazard Ratios ◽

The Impact

e20628 Background: The intensity of end-of-life (EOL) cancer care in a rural community has been previously reported (Cowall et al: J Oncol Pract 8: 40e-44e, 2012) using a random sample of all cancer deaths from Wicomico County, Maryland for calendar years 2004-2008. We now examine the impact of hospice services on survival in this same population. Methods: Significance (P-value) of diagnosis to death median survivals (MS) between different groups was calculated by log-rank analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were obtained using Cox regression analysis. Results: 179 patients from our sample did not receive hospice services, and 211 were enrolled in hospice at some point during their illness. MS were 6.0 and 9.0 months respectively (P= 0.050, HR 1.222, CI 1.000-1.492). In the lung cancer subset, 54 patients did not receive hospice services and 78 were enrolled in hospice. MS were 5.0 and 7.0 months respectively (P=0.034, HR 1.468, CI 1.030-2.093). Other subsets were too small for analysis. Conclusions: Prolongedsurvival was significantly associated with hospice services in our sample, and that effect was more pronounced with lung cancer patients. The hospice effect on survival may reflect some combination of the following: hospice services result in better symptom management as well as counseling against toxic therapies at EOL and/or the bias of some patients against toxic treatments even before hospice enrollment.

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Heart Rate Fluctuation and Mortality in Critically Ill Myocardial Infarction Patients: A Retrospective Cohort Study

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.577742 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qi Guo ◽

Hongwei Li ◽

Huijun Ouyang ◽

Runlu Sun ◽

Junjie Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Rate ◽

Cohort Study ◽

Intensive Care ◽

Critically Ill ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Cox Regression ◽

Sensitivity Analyses ◽

Hazard Ratios

Background: Whether heart rate (HR) fluctuation after admission has an impact on the outcomes of critically ill myocardial infarction (MI) patients in intensive care unit remains unknown.Methods: A total of 2,031 MI patients were enrolled from the Medical Information Mart for Intensive Care (MIMIC-III) database. HR fluctuation was calculated as the maximum HR minus the minimum HR in the initial 24 h after admission. Participants were divided into 3 groups, namely, low HR fluctuation [<30 beats per minute (bpm)], medium HR fluctuation (30–49 bpm), and high HR fluctuation (≥ 50 bpm). The main outcomes were 30–day and 1-year mortality. Cox regression and restricted cubic spline model were used.Results: Each 10-bpm increase in HR fluctuation was associated with a higher risk of 30-day mortality and 1-year mortality, with adjusted hazard ratios of 1.122 (95% CI, 1.083–1.162) and 1.107 (95% CI, 1.074–1.140), respectively. Compared with the low HR fluctuation group, the high HR fluctuation group suffered a significantly higher risk of mortality after adjustment, with hazard ratios of 2.156 (95% CI, 1.483–3.134) for 30-day mortality and 1.796 (95% CI, 1.354–2.381) for 1-year mortality. A typical J-type curve was observed in restricted cubic splines for the association between HR fluctuation and 30-day or 1-year mortality of MI patients, with the lowest risk on the HR fluctuation of 30 bpm. Sensitivity analyses emphasized the robustness of our results.Conclusions: This retrospective cohort study revealed an independent positive association between HR fluctuation and 30-day and 1-year mortality in critically ill MI patients, which warrants further investigation.

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Analysis of survival and objective response (OR) in patients with hepatocellular carcinoma in a phase III study of lenvatinib (REFLECT).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.186 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 186-186 ◽

Cited By ~ 12

Author(s):

Masatoshi Kudo ◽

Richard S. Finn ◽

Shukui Qin ◽

Kwang-Hyub Han ◽

Kenji Ikeda ◽

...

Keyword(s):

Cox Regression ◽

Objective Response ◽

Fixed Time ◽

Phase Iii ◽

Sensitivity Analyses ◽

Hazard Ratios ◽

Independent Review ◽

Phase Iii Study ◽

Landmark Analyses ◽

The Relationship

186 Background: In REFLECT, Lenvatinib (LEN) demonstrated treatment effect on overall survival (OS) by statistical confirmation of noninferiority to sorafenib (SOR). OR rates for LEN versus SOR were: 24% versus 9% by investigator review and 41% versus 12% by independent review (Kudo et al 2018). Since the relationship between OR and OS in phase III HCC studies is unclear, we explored the relationship between OR and OS in REFLECT. Methods: OR assessed by investigators per mRECIST were used to analyze the association between OR and OS of pts treated with LEN or SOR. The median OS of responders (CR or PR) was compared to that of nonresponders (SD, PD, or UNK/NE) irrespective of treatment. Landmark analyses were performed by OR status at several fixed time points as sensitivity analyses, and the effect on OS was evaluated by Cox regression with OR as a time-dependent covariate, with other prognostic factors. Results: Median OS was 22.4 months for responders and 11.4 months for nonresponders. Hazard ratios (HR) of landmark analyses at 2, 4, and 6 months were 0.75 (95% CI, 0.57–0.98), 0.72 (95% CI, 0.56–0.92), and 0.73 (95% CI, 0.57–0.93). Independent predictors of OS based on unstratified Cox regression are in the table. Conclusions: In REFLECT, OR was an independent predictor of OS in pts with HCC regardless of treatment. The results indicate this correlation is worth further investigation. Clinical trial information: NCT01761266. [Table: see text]

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The risk of venous thromboembolism attributed to established prothrombotic genotypes

Thrombosis and Haemostasis ◽

10.1055/a-1698-6717 ◽

2021 ◽

Author(s):

Line Holted Evensen ◽

Carl Arne Lochen Arnesen ◽

Frits R. Rosendaal ◽

Maiken Elvestad Gabrielsen ◽

Ben Michael Brumpton ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cox Regression ◽

Population Attributable Fraction ◽

The Elderly ◽

Population Based ◽

Single Nucleotide ◽

Hazard Ratios ◽

Hunt Study ◽

Fv Leiden ◽

The Individual

Background: The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to estimate the proportion of VTEs in the population that could be attributed to established prothrombotic genotypes using a population-based case-cohort. Methods: Cases with incident VTE (n=1,493) and a randomly sampled sub-cohort (n=13,069) were derived from the Tromsø Study (1994-2012) and the Nord-Trøndelag Health (HUNT) Study (1995-2008). DNA-samples were genotyped for 17 single nucleotide polymorphism (SNPs) associated with VTE. Hazard ratios with 95% confidence intervals (CIs) were estimated in Cox regression models. Population attributable fraction (PAF) with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated using a cumulative model where SNPs significantly associated with VTE were added one-by-one in ranked order of the individual PAFs. Results: Six SNPs were significantly associated with VTE (rs1799963 [Prothrombin], rs2066865 [FGG], rs6025 [FV Leiden], rs2289252 [F11], rs2036914 [F11] and rs8176719 [ABO]. The cumulative PAF for the six-SNP model was 45.3% (95% CI 19.7-71.6) for total VTE and 61.7% (95% CI 19.6-89.3) for unprovoked VTE. The PAF for prothrombotic genotypes was higher for DVT (52.9%) than for PE (33.8%), and higher for those aged <70 years (66.1%) than for those aged ≥70 years (24.9%). Conclusions: Our findings suggest that 45-62% of all VTE events in the population can be attributed to known prothrombotic genotypes. The PAF of established prothrombotic genotypes was higher in DVT than in PE, and higher in the young than in the elderly.

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