scholarly journals Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study

BMJ ◽  
2018 ◽  
pp. k3851 ◽  
Author(s):  
Anton Pottegård ◽  
Kasper Bruun Kristensen ◽  
Martin Thomsen Ernst ◽  
Nanna Borup Johansen ◽  
Pierre Quartarolo ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cancer Risk ◽  
Confidence Interval ◽  
Cox Regression ◽  
Uterine Cancer ◽  
Hazard Ratio ◽  
Cancer Outcomes ◽  
Single Cancer ◽  
One Year ◽  
Risk Of Cancer

AbstractObjectiveTo perform an expedited assessment of cancer risk associated with exposure to N-nitrosodimethylamine (NDMA) through contaminated valsartan products.DesignNationwide cohort study.SettingDanish health registries on individual level prescription drug use, cancer occurrence, and hospital diagnoses.Participants5150 Danish patients with no history of cancer, aged 40 years or older, and using valsartan at 1 January 2012 or initiating use between 1 January 2012 and 30 June 2017. Participants were followed from one year after cohort entry (lag time period) until experiencing a cancer outcome, death, migration, or end of study period (30 June 2018). Each participant’s exposure to NDMA (ever exposure and predefined categories of cumulative valsartan exposure) was mapped out as a time varying variable while also applying a one year lag.Main outcome measuresAssociation between NDMA exposure and a primary composite endpoint comprising all cancers except non-melanoma skin cancer, estimated using Cox regression. In supplementary analyses, the risk of individual cancers was determined.ResultsThe final cohort comprised 5150 people followed for a median of 4.6 years. In total, 3625 cohort participants contributed 7344 person years classified as unexposed to NDMA, and 3450 participants contributed 11 920 person years classified as ever exposed to NDMA. With 104 cancer outcomes among NDMA unexposed participants and 198 among exposed participants, the adjusted hazard ratio for overall cancer was 1.09 (95% confidence interval 0.85 to 1.41), with no evidence of a dose-response relation (P=0.70). For single cancer outcomes, increases in risk were observed for colorectal cancer (hazard ratio 1.46, 95% confidence interval 0.79 to 2.73) and for uterine cancer (1.81, 0.55 to 5.90), although with wide confidence intervals that included the null.ConclusionsThe results do not imply a markedly increased short term overall risk of cancer in users of valsartan contaminated with NDMA. However, uncertainty persists about single cancer outcomes, and studies with longer follow-up are needed to assess long term cancer risk.

scholarly journals Risk of Cancer Following the Use of N-Nitrosodimethylamine (NDMA) Contaminated Ranitidine Products: A Nationwide Cohort Study in South Korea

2021 ◽  
Vol 10 (1) ◽  
pp. 153
Author(s):  
Hong Jin Yoon ◽  
Jie-Hyun Kim ◽  
Gi Hyeon Seo ◽  
Hyojin Park
Keyword(s):  
Cohort Study ◽  
Cancer Risk ◽  
South Korea ◽  
Primary Study ◽  
Study Cohort ◽  
Matched Cohort ◽  
Cancer Outcomes ◽  
H2 Receptor Antagonist ◽  
Carcinogenic Agent ◽  
Risk Of Cancer

N-nitrosodimethylamine (NDMA), a known carcinogenic agent, was recently detected in some products of ranitidine. Several studies have investigated the detectability of NDMA, in drugs and their risks. However, only a few epidemiological studies have evaluated cancer risk from the use of such individual drugs. This study investigates the risk of cancer in ranitidine users. We conducted an observational population-based cohort study using the Health Insurance Review and Assessment databases, which contain information about the use of medicines in South Korea. The primary study cohort consisted of ranitidine users (n = 88,416). For controls, we enrolled users of famotidine, another H2-receptor antagonist in which no NDMA has been detected. A 4:1 matched cohort was constructed to compare cancer outcomes of the two groups. Our matched cohort comprised of 40,488 ranitidine users and 10,122 famotidine users. There was no statistical difference in the overall cancer risk between the ranitidine and famotidine groups (7.45% vs. 7.56%, HR 0.99, 95% CI 0.91–1.07, p = 0.716). Additionally, no significant differences were observed in the analysis of 11 single cancer outcomes. We found no evidence that exposure to NDMA through ranitidine increases the risk of cancer.

scholarly journals Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study

2016 ◽  
Vol 209 (5) ◽  
pp. 393-399 ◽  
Author(s):  
Ru-Yu Huang ◽  
Kun-Pin Hsieh ◽  
Wan-Wen Huang ◽  
Yi-Hsin Yang
Keyword(s):  
Bipolar Disorder ◽  
Cohort Study ◽  
Cancer Risk ◽  
Cox Regression ◽  
Glycogen Synthase ◽  
Control Group ◽  
Defined Daily Dose ◽  
Research Database ◽  
Hazard Ratios ◽  
Risk Of Cancer

BackgroundLithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer.AimsTo investigate the association between lithium and cancer risk in patients with bipolar disorder.MethodA retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer.ResultsCompared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554–0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516–1.125), 0.919 (95% CI 0.640–1.318) and 0.552 (95% CI 0.367–0.831), respectively.ConclusionsLithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose–response relationship for cancer risk reduction was observed.

scholarly journals Estimated Glomerular Filtration Rate and the Risk of Cancer

2019 ◽  
Vol 14 (4) ◽  
pp. 530-539 ◽  
Author(s):  
Hong Xu ◽  
Kunihiro Matsushita ◽  
Guobin Su ◽  
Marco Trevisan ◽  
Johan Ärnlöv ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Confidence Interval ◽  
Cancer Incidence ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Reverse Causation ◽  
Detection Bias ◽  
Lower Egfr ◽  
Risk Of Cancer

Background and objectivesCommunity-based reports regarding eGFR and the risk of cancer are conflicting. We here explore plausible links between kidney function and cancer incidence in a large Scandinavian population–based cohort.Design, setting, participants, & measurementsIn the Stockholm Creatinine Measurements project, we quantified the associations of baseline eGFR with the incidence of cancer among 719,033 Swedes ages ≥40 years old with no prior history of cancer. Study outcomes were any type and site-specific cancer incidence rates on the basis of International Classification of Diseases-10 codes over a median follow-up of 5 years. To explore the possibility of detection bias and reverse causation, we divided the follow-up time into different time periods (≤12 and >12 months) and estimated risks for each of these intervals.ResultsIn total, 64,319 cases of cancer (affecting 9% of participants) were detected throughout 3,338,226 person-years. The relationship between eGFR and cancer incidence was U shaped. Compared with eGFR of 90–104 ml/min, lower eGFR strata associated with higher cancer risk (adjusted hazard ratio, 1.08; 95% confidence interval, 1.05 to 1.11 for eGFR=30–59 ml/min and adjusted hazard ratio, 1.24; 95% confidence interval, 1.15 to 1.35 for eGFR<30 ml/min). Lower eGFR strata were significantly associated with higher risk of skin, urogenital, prostate, and hematologic cancers. Any cancer risk as well as skin (nonmelanoma) and urogenital cancer risks were significantly elevated throughout follow-up time, but they were higher in the first 12 months postregistration. Associations with hematologic and prostate cancers abrogated after the first 12 months of observation, suggesting the presence of detection bias and/or reverse causation.ConclusionsThere is a modestly higher cancer risk in individuals with mild to severe CKD driven primarily by skin and urogenital cancers, and this is only partially explained by bias.

scholarly journals The Influence of Constipation on Asthma: A Real-world, Population-based Cohort Study

2021 ◽  
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 ◽  
World Population ◽  
Research Database ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
One Year

Background Among respiratory diseases, asthma is one of the most burdensome disorder worldwide. Growing evidence disclose gut dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microflora. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess the risk of asthma in constipated patients by a nationwide population-based cohort study. Methods We analyzed 82421 constipated patients and 82421 individuals without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Analysis of propensity score was utilized to match age, gender, comorbidities, and medications at a ratio of 1:1. Besides, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were conducted. Results The incidence of asthma was 10.8 per 1,000 person-years in the constipation group, which was higher than the rate of 5.6 per 1,000 person-years observed in the non-constipation group. After adjustment for age, gender, comorbidities, and medications, constipated patients had a 1.91-fold greater risk of asthma compared to those without constipation (adjusted hazard ratio [aHR]: 1.91 (95% C.I. 1.84-1.99). In subgroup analyses, patients aged 20-39 years had a 2.04-fold highest risk of asthma in the constipation cohort (aHR:2.04, 95% CI, 1.84-2.26). Besides, the severity of constipation is associated with an increased risk of asthma; the aHR was 1.76 (1.69-1.85), 2.15(2.03-2.27), and 2.29(2.10-2.49) for < 3 times, 3-12 times, and ≥12 times of laxatives prescription within one year, respectively. (p<0.001) Moreover, constipated patients had a higher likelihood of asthma, regardless of gender, comorbidities, and medications. Conclusion Constipation relates to a significantly increased risk of asthma. Physicians should be aware of the possibility of asthma in constipated people. Further research is warranted to investigate the possible pathological mechanisms of this association.

scholarly journals Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children: A Nationwide Case-Cohort Study

2020 ◽  
Vol 189 (8) ◽  
pp. 779-787 ◽  
Author(s):  
Johanna Metsälä ◽  
Annamari Lundqvist ◽  
Lauri J Virta ◽  
Minna Kaila ◽  
Mika Gissler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cohort Study ◽  
Confidence Interval ◽  
Cox Regression ◽  
Inhaled Corticosteroids ◽  
Anatomical Therapeutic Chemical ◽  
Hazard Ratio ◽  
Increased Risk ◽  
Reference Cohort

Abstract Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995–2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled β-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled β-agonists might be at increased risk of type 1 diabetes.

scholarly journals Adherence to the Mediterranean diet and risk of lung cancer in the Netherlands Cohort Study

2018 ◽  
Vol 119 (6) ◽  
pp. 674-684 ◽  
Author(s):  
Maya Schulpen ◽  
Piet A. van den Brandt
Keyword(s):  
Lung Cancer ◽  
Cancer Research ◽  
Cohort Study ◽  
Cancer Risk ◽  
The Netherlands ◽  
Mediterranean Diet ◽  
Dietary Habits ◽  
Lung Cancer Risk ◽  
Cox Regression ◽  
The Mediterranean

AbstractThe evidence on a cancer-protective effect of the Mediterranean diet (MD) is still limited. Therefore, we investigated the association between MD adherence and lung cancer risk. Data were used from 120 852 participants of the Netherlands Cohort Study (NLCS), aged 55–69 years. Dietary habits were assessed at baseline (1986) using a validated FFQ and alternate and modified Mediterranean diet scores (aMED and mMED, respectively), including and excluding alcohol, were calculated. After 20·3 years of follow-up, 2861 lung cancer cases and 3720 subcohort members (case-cohort design) could be included in multivariable Cox regression analyses. High (6–8) v. low (0–3) aMED excluding alcohol was associated with non-significantly reduced lung cancer risks in men and women with hazard ratios of 0·91 (95 % CI 0·72, 1·15) and 0·73 (95 % CI 0·49, 1·09), respectively. aMED-containing models generally fitted better than mMED-containing models. In never smokers, a borderline significant decreasing trend in lung cancer risk was observed with increasing aMED excluding alcohol. Analyses stratified by the histological lung cancer subtypes did not identify subtypes with a particularly strong inverse relation with MD adherence. Generally, the performance of aMED and World Cancer Research Fund/American Institute for Cancer Research dietary score variants without alcohol was comparable. In conclusion, MD adherence was non-significantly inversely associated with lung cancer risk in the NLCS. Future studies should focus on differences in associations across the sexes and histological subtypes. Furthermore, exclusion of alcohol from MD scores should be investigated more extensively, primarily with respect to a potential role of the MD in cancer prevention.

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

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 &lt; 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 &lt; 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p &lt; 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.

scholarly journals Maternal and child gluten intake and risk of type 1 diabetes: The Norwegian Mother and Child Cohort Study

2019 ◽  
Author(s):  
Nicolai A Lund-Blix ◽  
German Tapia ◽  
Karl Mårild ◽  
Anne Lise Brantsaeter ◽  
Pål R Njølstad ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cohort Study ◽  
Confidence Interval ◽  
Population Based ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Pregnancy Cohort ◽  
Increased Risk ◽  
Mother And Child

ABSTRACTOBJECTIVETo examine the association between maternal and child gluten intake and risk of type 1 diabetes in children.DESIGNPregnancy cohortSETTINGPopulation-based, nation-wide study in NorwayPARTICIPANTS86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018.MAIN OUTCOME MEASURESClinical type 1 diabetes, ascertained in a nation-wide childhood diabetes registry. Hazard ratios were estimated using Cox regression for the exposures maternal gluten intake up to week 22 of pregnancy and child’s gluten intake when the child was 18 months old.RESULTSDuring a mean follow-up of 12.3 years (range 0.7-16.0), 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child (adjusted hazard ratio 1.02 (95% confidence interval 0.73 to 1.43) per 10 grams/day increase in gluten intake). However, the child’s gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake).CONCLUSIONSThis study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child.WHAT IS ALREADY KNOWN ON THIS TOPICA national prospective cohort study from Denmark found that a high maternal gluten intake during pregnancy could increase the risk of type 1 diabetes in the offspring (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 grams/day increase in gluten intake). No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood.WHAT THIS STUDY ADDSIn this prospective population-based pregnancy cohort with 86,306 children of whom 346 developed type 1 diabetes we found that the child’s gluten intake at 18 months of age was associated with the risk of type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake). This study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the child’s risk of type 1 diabetes.

scholarly journals The Risk of Newly Diagnosed Cancer in Patients with Rheumatoid Arthritis by TNF Inhibitor Use: A Nationwide Cohort Study

2021 ◽  
Author(s):  
Boyoon Choi ◽  
Hyun Jin Park ◽  
Yun-Kyoung Song ◽  
Yoon-Jeong Oh ◽  
In-Wha Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Risk ◽  
Cox Regression ◽  
Tnf Inhibitors ◽  
Tnf Inhibitor ◽  
Matched Cohort ◽  
Korean Patients ◽  
Study Results ◽  
The One ◽  
Risk Of Cancer

Abstract Background Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. Methods Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1,000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. Results Of the 22,851 patients in the before matching cohort, 4,592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1,000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820). Conclusions The use of TNF inhibitors was associated with a lower cancer incidence in Korean patients with RA. A further study linking claims and clinical data is needed to confirm our results.

scholarly journals Impact of paliperidone palmitate one-month formulation on relapse prevention in patients with schizophrenia: A post-hoc analysis of a one-year, open-label study stratified by medication adherence

2018 ◽  
Vol 32 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tianmei Si ◽  
Nan Li ◽  
Huafei Lu ◽  
Shangli Cai ◽  
Jianmin Zhuo ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Hazard Ratio ◽  
Paliperidone Palmitate ◽  
Open Label ◽  
First Relapse ◽  
Continued Use ◽  
One Year ◽  
Long Acting ◽  
Post Hoc

Background: Limited data are available to help identify patients with schizophrenia who are most likely to benefit from long-acting injectable antipsychotics. Aim: To investigate the efficacy of long-acting injectable antipsychotic paliperidone palmitate one-month formulation for preventing relapses, factors influencing time to first relapse, and the effect of different antipsychotic adherence levels on time to first relapse in Chinese patients with schizophrenia. Methods: This was a post-hoc analysis from an open-label, single-arm study of stable patients (Positive and Negative Syndrome Scale total score <70; n=367) receiving paliperidone palmitate one-month formulation at the end of an acute 13-week treatment phase, who entered a naturalistic one-year follow-up period, either continuing with flexibly dosed paliperidone palmitate one-month formulation (75–150 mg eq.) or switching to another antipsychotic(s). Results: There were 362/367 patients (age=31.4±10.75 years) included in the analysis of time to first relapse (primary outcome) and 327/362 patients (39/327, poor antipsychotic adherence (<80%)) willing to receive antipsychotics were included in the exposure/adherence analysis. Overall, 84.6% (95% confidence interval=79.2–88.7) patients remained relapse-free. Poor adherence during follow-up (hazard ratio=2.97, 95% confidence interval=1.48–5.98, p=0.002) and frequent hospitalizations in the previous year (hazard ratio=1.29, 95% confidence interval=1.02–1.62, p=0.03) were associated with a significant risk of shorter time to first relapse in the univariate analysis. In patients with poor adherence, ‘no use’ (hazard ratio=13.13, 95% confidence interval=1.33–129.96, p=0.03) and ‘interrupted use’ (hazard ratio=11.04, 95% confidence interval=1.03–118.60, p=0.047) of paliperidone palmitate one-month formulation (vs continued use) showed a significantly higher risk of relapse; this was not observed in patients with good (≥80%) antipsychotic adherence. No new safety concerns were identified. Conclusion: Continued use of paliperidone palmitate one-month formulation/long-acting injectable antipsychotic was effective in preventing schizophrenia relapses, especially in patients with suboptimal antipsychotic adherence.

Sign in / Sign up

Export Citation Format

Share Document