Mortality in biopsy-proven alcohol-related liver disease: a population-based nationwide cohort study of 3453 patients

ObjectivePatients with alcohol-related liver disease (ALD) are at increased risk of death, but studies have rarely investigated the significance of histological severity or estimated relative risks compared with a general population. We examined mortality in a nationwide cohort of biopsy-proven ALD.DesignPopulation-based cohort study in Sweden comparing 3453 individuals with an International Classification of Disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 16 535 matched general population individuals. Swedish national registers were used to ascertain overall and disease-specific mortality, starting follow-up at the latest of first ICD diagnosis or liver biopsy plus 3 months. Cox regression adjusted for relevant confounders was used to estimate HRs in ALD and histopathological subgroups.ResultsMedian age at diagnosis was 58 years, 65% were men and 52% had cirrhosis at baseline. Five-year cumulative mortality was 40.9% in patients with ALD compared with 5.8% in reference individuals. The risk for overall mortality was significantly increased (adjusted HR (aHR)=4.70, 95% CI 4.35 to 5.08). The risk of liver-related death was particularly high (43% of all deaths, aHR=167.6, 95% CI 101.7 to 276.3). Mortality was significantly increased also in patients with ALD without cirrhosis and was highest in the first year after baseline but persisted after ≥10 years of follow-up (aHR=2.74, 95% CI 2.37 to 3.16).ConclusionIndividuals with biopsy-proven ALD have a near fivefold increased risk of death compared with the general population. Individuals with ALD without cirrhosis were also at increased risk of death, reaffirming the need to increase vigilance in the management of these individuals.

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OP14 Risk of colorectal cancer diagnosis and colorectal cancer mortality in Crohn’s disease: A Scandinavian population-based cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.013 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S013-S014

Author(s):

O Olen ◽

R Erichsen ◽

M C Sachs ◽

L Pedersen ◽

J Halfvarson ◽

...

Keyword(s):

Colorectal Cancer ◽

Cohort Study ◽

Crohn’S Disease ◽

Crohn's Disease ◽

General Population ◽

Cox Regression ◽

Population Based ◽

Tumour Stage ◽

Increased Risk

Abstract Background Crohn’s disease (CD) is a risk factor for colorectal cancer (CRC). Earlier studies reflect older treatment and surveillance strategies, and most have studied incident CRC without addressing potential lead-time and surveillance biases. Such bias can be reduced by examining tumour stage-adjusted CRC incidence and CRC mortality. We aimed to assess risks of CRC mortality and incident CRC among patients with CD compared with the general population. Methods Nationwide register-based cohort study during 1969–2017 of 47,035 patients with CD in Denmark (n = 13,056) and Sweden (n = 33,979), compared with 463,187 general population reference individuals, matched for sex, age, calendar year, and place of residence. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality. In a multistate model, assessing competing events during follow-up (CRC diagnosis, CRC death, other death), we also took a tumour stage into account. Results During 1969–2017, 499 patients with CD developed CRC, corresponding to an adjusted HR of 1.40 [95% confidence interval (CI) 1.27–1.53]. We observed 296 (0.47/1000 person-years) deaths from CRC in patients with CD compared with 1968 (0.31/1000) in reference individuals [HR 1.74 (95% CI 1.54–1.96)]. CD patients diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC [HR = 1.30 (95% CI 1.06–1.59)] and tumour stage at CRC diagnosis did not differ between groups (p = 0.27). CD patients who had 8 or more years of follow-up or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death [HR 1.41 (95% CI 1.18–1.69)] or CRC diagnosis [HR = 1.12 (95% CI = 0.98–1.28)]. However, in patients potentially eligible for CRC surveillance, we only found significantly increased risks in patients with CD onset <40 years, disease activity in the colon only, or with PSC (Figure 1). Conclusion CD patients are at increased risk of a CRC diagnosis and CRC death. Despite repeated colonoscopies during follow-up, CD patients are not diagnosed earlier (less severe tumour stage) with CRC than reference individuals. Nevertheless, CD patients with CRC have higher mortality than non-CD patients also diagnosed with CRC. CRC surveillance could likely be improved and should be focussed on CD patients <40 years at CD onset, patients with colon inflammation, and patients who have PSC.

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Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽

10.1177/0333102413513181 ◽

2013 ◽

Vol 34 (5) ◽

pp. 327-335 ◽

Cited By ~ 22

Author(s):

Knut Hagen ◽

Eystein Stordal ◽

Mattias Linde ◽

Timothy J Steiner ◽

John-Anker Zwart ◽

...

Keyword(s):

Risk Factor ◽

Cohort Study ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Health Study ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

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Endometrial Cancer Risk in Women with Germline BRCA1 or BRCA2 Mutations: Multicenter Cohort Study

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djab036 ◽

2021 ◽

Author(s):

Marthe M de Jonge ◽

Cornelis D de Kroon ◽

Denise J Jenner ◽

Jan Oosting ◽

Joanne A de Hullu ◽

...

Keyword(s):

Endometrial Cancer ◽

Cohort Study ◽

General Population ◽

Cox Regression ◽

Statistical Tests ◽

Brca1 Mutation ◽

Brca2 Mutation ◽

Mutation Carriers ◽

Increased Risk

Abstract Background Endometrial cancer (EC) risk in BReast CAncer gene 1/2 (BRCA1/2) mutation carriers is uncertain, therefore we assessed this in a large Dutch nationwide cohort study. Methods 5,980 BRCA1/2 (3,788 BRCA1, 2,151 gBRCA2, 41 both BRCA1/BRCA2) and 8,451 non-BRCA1/2 mutation carriers were selected from the HEBON-cohort. Follow-up started at date of nationwide PALGA coverage (January 1, 1989) or at the age of 25 years (whichever came last), and ended at date of EC diagnosis, last follow-up or death (whichever came first). EC risk in BRCA1/2 mutation carriers was compared to: 1) general population, estimating standardized incidence ratios (SIRs) based on Dutch population-based incidence rates; and 2) non-BRCA1/2 mutation carriers, using Cox-regression analyses, expressed as hazard ratio (HR). Statistical tests were two-sided. Results Fifty-eight BRCA1/2 and 33 non-BRCA1/2 mutation carriers developed EC over 119,296 and 160,841 person-years, respectively (SIR = 2.83, 95% confidence interval (CI) = 2.18–3.65; and HR = 2.37, 95% CI = 1.53–3.69, respectively). gBRCA1 mutation carriers showed increased risks for EC overall (SIR = 3.51, 95% CI = 2.61–4.72; HR = 2.91, 95% CI = 1.83–4.66), serous-like EC (SIR: 12.64, 95% CI = 7.62–20.96; HR = 10.48, 95% CI = 2.95–37.20), endometrioid EC (SIR = 2.63, 95% CI = 1.80–3.83; HR = 2.01, 95% CI = 1.18–3.45) and TP53-mutated EC (HR = 15.71, 95% CI = 4.62–53.40). For BRCA2 mutation carriers, overall (SIR = 1.70, 95% CI = 1.01–2.87), and serous-like EC risks (SIR = 5.11, 95% CI = 1.92–13.63) were increased when compared to the general population. Absolute risks by 75 years remained low (overall EC = 3.0%; serous-like EC = 1.1%). Conclusions BRCA1/2 mutation carriers have a 2- to 3-fold increased risk for EC, with highest risk observed for the rare subgroups of serous-like and p53-abnormal EC in BRCA1 mutation carriers.

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Cancer Risk in Patients with Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study with Histopathology

American Journal of Epidemiology ◽

10.1093/aje/kwab119 ◽

2021 ◽

Author(s):

Rajani Sharma ◽

Elizabeth C Verna ◽

Tracey G Simon ◽

Jonas Söderling ◽

Hannes Hagström ◽

...

Keyword(s):

Cohort Study ◽

General Population ◽

Cancer Risk ◽

Autoimmune Hepatitis ◽

Cox Regression ◽

Population Based ◽

Swedish Population ◽

Non Melanoma Skin Cancer ◽

Incident Cancer ◽

Increased Risk

Abstract We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared to the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and a liver biopsy in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed 1969-2016 and 22,996 matched general population reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios (HRs) were determined for any incident cancer and sub-types determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2/1000 person-years) and 4,450 reference individuals (12.0/1000 person-years). This corresponded to an HR of 1.53 (95%CI: 1.42,1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95%CI, 17.52,48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to non-melanoma skin cancer (HR=2.69) and lymphoma (HR=1.89). Sibling analyses yielded similar risk estimates for any cancer (HR=1.84) and HCC (HR=23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extra-hepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.

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Hypothyroidism and hyperthyroidism and breast cancer risk: a nationwide cohort study

Acta Endocrinologica ◽

10.1530/eje-15-0989 ◽

2016 ◽

Vol 174 (4) ◽

pp. 409-414 ◽

Cited By ~ 59

Author(s):

Mette Søgaard ◽

Dóra Körmendiné Farkas ◽

Vera Ehrenstein ◽

Jens Otto Lunde Jørgensen ◽

Olaf M Dekkers ◽

...

Keyword(s):

Breast Cancer ◽

Cohort Study ◽

Breast Cancer Risk ◽

General Population ◽

Cancer Risk ◽

Thyroid Disease ◽

Estrogen Receptor Status ◽

Population Based ◽

Increased Risk

ObjectiveThe association between thyroid disease and breast cancer risk remains unclear. We, therefore examined the association between hypothyroidism, hyperthyroidism and breast cancer risk.DesignThis was a population-based cohort study.MethodsUsing nationwide registries, we identified all women in Denmark with a first-time hospital diagnosis of hypothyroidism or hyperthyroidism, 1978–2013. We estimated the excess risk of breast cancer among patients with hypothyroidism or hyperthyroidism compared with the expected risk in the general population, using standardized incidence ratios (SIRs) as a measure of risk ratio. Breast cancer diagnoses in the first 12 months following diagnosis of thyroid disease were excluded from the calculations to avoid diagnostic work-up bias.ResultsWe included 61 873 women diagnosed with hypothyroidism and 80 343 women diagnosed with hyperthyroidism. Median follow-up time was 4.9 years (interquartile range (IQR): 1.8–9.5 years) for hypothyroidism and 7.4 years (IQR: 3.1–13.5 years) for hyperthyroidism. Hyperthyroidism was associated with a slightly increased breast cancer risk compared with the general population (SIR: 1.11, 95% CI: 1.07–1.16), which persisted beyond 5 years of follow-up (SIR: 1.13, 95% CI: 1.08–1.19). In comparison, hypothyroidism was associated with a slightly lower risk of breast cancer (SIR: 0.94, 95% CI: 0.88–1.00). Stratification by cancer stage at diagnosis, estrogen receptor status, age, comorbidity, history of alcohol-related disease and clinical diagnoses of obesity produced little change in cancer risk.ConclusionsWe found an increased risk of breast cancer in women with hyperthyroidism and a slightly decreased risk in women with hypothyroidism indicating an association between thyroid function level and breast cancer risk.

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Multimorbidity, ageing and mortality: normative data and cohort study in an American population

BMJ Open ◽

10.1136/bmjopen-2020-042633 ◽

2021 ◽

Vol 11 (3) ◽

pp. e042633

Author(s):

Walter A Rocca ◽

Brandon R Grossardt ◽

Cynthia M Boyd ◽

Alanna M Chamberlain ◽

William V Bobo ◽

...

Keyword(s):

Cohort Study ◽

Race And Ethnicity ◽

Age Groups ◽

Population Based ◽

Olmsted County ◽

Risk Of Death ◽

Rochester Epidemiology Project ◽

Risk Of Mortality ◽

Increased Risk

ObjectivesTo describe the percentile distribution of multimorbidity across age by sex, race and ethnicity, and to demonstrate the utility of multimorbidity percentiles to predict mortality.DesignPopulation-based descriptive study and cohort study.SettingOlmsted County, Minnesota (USA).ParticipantsWe used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years).MethodsFor each person, we obtained the count of chronic conditions (out of 20 conditions) present on each birthday by extracting all of the diagnostic codes received in the 5 years before the index birthday from the electronic indexes of the REP. To compare each person’s count to peers of same age, the counts were transformed into percentiles of the total population and displayed graphically across age by sex, race and ethnicity. In addition, quintiles 1, 2, 4 and 5 were compared with quintile 3 (reference) to predict the risk of death at 1 year, 5 years and through end of follow-up using time-to-event analyses. Follow-up was passive using the REP.ResultsWe identified 238 010 persons who experienced a total of 1 458 094 birthdays during the study period (median of 6 birthdays per person; IQR 3–10). The percentiles of multimorbidity across age did not vary noticeably by sex, race or ethnicity. In general, there was an increased risk of mortality at 1 and 5 years for quintiles 4 and 5 of multimorbidity. The risk of mortality for quintile 5 was greater for younger age groups and for women.ConclusionsThe assignment of multimorbidity percentiles to persons in a population may be a simple and intuitive tool to assess relative health status, and to predict short-term mortality, especially in younger persons and in women.

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Mortality in Eosinophilic Esophagitis – a nationwide, population-based matched cohort study from 2005 to 2017

Upsala Journal of Medical Sciences ◽

10.48101/ujms.v126.7688 ◽

2021 ◽

Vol 126 (1) ◽

Author(s):

Lovisa Röjler ◽

John J. Garber ◽

Bjorn Roelstraete ◽

Marjorie M. Walker ◽

Jonas F. Ludvigsson

Keyword(s):

Cohort Study ◽

General Population ◽

Eosinophilic Esophagitis ◽

Population Based ◽

Sensitivity Analyses ◽

Matched Cohort ◽

Matched Cohort Study ◽

Risk Of Death ◽

Gastrointestinal Pathology ◽

Increased Risk

Background: There is a lack of knowledge about mortality in eosinophilic esophagitis (EoE). Therefore, this study aimed to examine the mortality in EoE. Methods: A nationwide, population-based matched cohort study was conducted of all EoE patients in Sweden diagnosed between July 2005 and December 2017. Individuals with EoE (n = 1,625) were identified through prospectively recorded histopathology codes from all gastrointestinal pathology reports in Sweden, representing 28 pathology departments (the ESPRESSO study). Each individual with EoE was then matched with up to five reference individuals from the general population (n = 8,003) for age, sex, year of birth, and place of residence. We used the Cox proportional hazard modeling to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) while adjusting for other potential confounders. In sensitivity analyses, mortality in EoE patients was compared with mortality in their siblings. Results: Through December 2017, 34 deaths were confirmed in EoE patients (4.60 per 1,000 person-years) compared with 165 in reference individuals (4.57 per 1,000 person-years). This rate corresponds to an aHR of 0.97 (95% CI = 0.67–1.40). HRs were similar in males (aHR = 1.00 [0.66–1.51]) and females (aHR = 0.92 [0.38–2.18]). We observed no increased risk in mortality due to esophageal or other gastrointestinal cancers in patients with EoE (aHR = 1.02 [0.51–2.02]). Mortality was similar in EoE patients and their siblings (aHR = 0.91 [0.44–1.85]). Conclusion: In this nationwide, population-based matched cohort study in Sweden, there was no increased risk of death in patients with EoE compared with their siblings and the general population.

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High BMI in late adolescence predicts future severe liver disease and hepatocellular carcinoma: a national, population-based cohort study in 1.2 million men

Gut ◽

10.1136/gutjnl-2016-313622 ◽

2017 ◽

Vol 67 (8) ◽

pp. 1536-1542 ◽

Cited By ~ 29

Author(s):

Hannes Hagström ◽

Per Tynelius ◽

Finn Rasmussen

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Cox Regression ◽

Population Based ◽

Late Adolescent ◽

Severe Liver ◽

Increased Risk ◽

Severe Liver Disease ◽

High Bmi

ObjectiveA high body mass index (BMI) is associated with an increased risk for severe liver disease. It is unclear if this risk differs across BMI categories, and if the association is partially attributed to development of type 2 diabetes mellitus (T2DM).DesignWe used register data from more than 1.2 million Swedish men enlisted for conscription between 1969 and 1996. Data regarding new events of severe liver disease and T2DM during follow-up were obtained by record-linkage of population-based registers. We used Cox regression to estimate adjusted HRs for future inpatient care and mortality in severe liver disease and incidence of hepatocellular carcinoma (HCC) across BMI categories, using BMI of 18.5–22.5 kg/m2 as reference.ResultsDuring a follow-up of more than 34 million person-years, 5281 cases of severe liver disease including 251 cases of HCC were identified. An association with severe liver disease was found for overweight (HR 1.49, 95% CI 1.35 to 1.64) and for obese men (HR 2.17, 95% CI 1.82 to 2.59). Development of T2DM further increased the risk for severe liver disease across all BMI categories, for instance, men with obesity and T2DM had a higher risk of severe liver disease (HR 3.28, 95% CI 2.27 to 4.74) than men with obesity free of T2DM (HR 1.72, 95% CI 1.72 to 2.54).ConclusionsA high BMI in late adolescent men was associated with an increased risk of future severe liver disease, including HCC. Development of T2DM during follow-up was associated with a further increased risk of severe liver disease, independent of baseline BMI.

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Increased risk of bisphosphonate-related osteonecrosis of the jaw in patients with Sjögren’s syndrome: nationwide population-based cohort study

BMJ Open ◽

10.1136/bmjopen-2018-024655 ◽

2019 ◽

Vol 9 (2) ◽

pp. e024655 ◽

Cited By ~ 2

Author(s):

Min-Tser Liao ◽

Wu-Chien Chien ◽

Jen-Chun Wang ◽

Chi-Hsiang Chung ◽

Shi-Jye Chu ◽

...

Keyword(s):

Cohort Study ◽

Tooth Extraction ◽

Cox Regression ◽

Sjogren’S Syndrome ◽

Population Based ◽

Osteonecrosis Of The Jaw ◽

Sjogren's Syndrome ◽

Control Group ◽

Increased Risk

ObjectiveThe aim of this study was to explore whether patients with Sjögren’s syndrome (SS) were susceptible to bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) after tooth extraction in the entire population of Taiwan.DesignA nationwide population-based retrospective cohort study.SettingData were extracted from Taiwan’s National Health Insurance Research Database (NHIRD).MethodologyMedical conditions for both the study and control group were categorised using the International Classification of Diseases, 9th Revision. ORs and 95% CIs for associations between SS and osteonecrosis of the jaw (ONJ) were estimated using Cox regression.ResultsOverall, 13 398 patients diagnosed with SS were identified from the NHIRD. An additional 53 592 matched patients formed the control group. At the 3-year follow-up, patients with SS started to exhibit a significantly increased cumulative risk of developing BRONJ compared with that of patients without SS (log rank test <0.001). At the end of the follow-up period, patients with SS exhibited a significantly increased incidence of ONJ compared with that of the controls (0.08%vs0.03%, p=0.017). The Cox regression model showed that patients with SS also exhibited a significantly increased risk of developing BRONJ compared with that of the patients without SS (adjusted HR=7.869, 95% CI 3.235 to 19.141, p<0.001).ConclusionPatients with SS exhibit an increased risk of developing BRONJ after tooth extraction. BPs should be used with caution in patients with SS.

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Risk of Seizures in Patients with Organophosphate Poisoning: A Nationwide Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16173147 ◽

2019 ◽

Vol 16 (17) ◽

pp. 3147 ◽

Cited By ~ 5

Author(s):

Chieh-Sen Chuang ◽

Kai-Wei Yang ◽

Chia-Ming Yen ◽

Cheng-Li Lin ◽

Chia-Hung Kao

Keyword(s):

General Population ◽

Cox Regression ◽

Population Based ◽

Organophosphate Poisoning ◽

Research Database ◽

Population Based Study ◽

Increased Risk ◽

Taiwan National Health Insurance ◽

History Of

Objective: Previous research has demonstrated that patients with a history of organophosphate poisoning tend to have a higher risk of neurological disorder. However, research on the rate of seizure development in patients after organophosphate poisoning is lacking. This study examined whether individuals with organophosphate poisoning have an increased risk of seizures through several years of follow-up. Patients and Methods: We conducted a retrospective study on a cohort of 45,060 individuals (9012 patients with a history of organophosphate poisoning and 36,048 controls) selected from the Taiwan National Health Insurance Research Database. The individuals were observed for a maximum of 12 years to determine the rate of new-onset seizure disorder. We selected a comparison cohort from the general population that was randomly frequency-matched by age, sex, and index year and further analyzed the risk of seizures using a Cox regression model adjusted for sex, age, and comorbidities. Results: During the study period, the risk of seizure development was 3.57 times greater in patients with organophosphate poisoning compared with individuals without, after adjustments for age, sex, and comorbidities. The absolute incidence of seizures was highest in individuals aged 20 to 34 years in both cohorts (adjusted hazard ratio = 13.0, 95% confidence interval = 5.40−31.4). A significantly higher seizure risk was also observed in patients with organophosphate poisoning and comorbidities other than cirrhosis. Conclusions: This nationwide retrospective cohort study demonstrates that seizure risk is significantly increased in patients with organophosphate poisoning compared with the general population.

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