Risk factors for immune-related adverse events associated with anti-PD-1 pembrolizumab

Abstract We investigated risk factors for immune-related adverse events (irAEs) in patients treated with anti-programmed cell death protein1 antibody pembrolizumab. A retrospective medical record review was performed to identify all patients who received at least one dose of pembrolizumab at Samsung Medical Center, Seoul, Korea between June 2015 and December 2017. Three hundred and ninety-one patients were included in the study. Data were collected on baseline characteristics, treatment details, and adverse events. Univariate and multivariate logistic regression models were used to identify risk factors for irAEs. Sixty-seven (17.1%) patients experienced clinically significant irAEs; most commonly dermatologic disorders, followed by pneumonitis, musculoskeletal disorders, and endocrine disorders. Fourteen patients (3.6%) experienced serious irAEs (grade ≥ 3). Most common serious irAEs were pneumonitis (2.3%). Four deaths were associated with irAEs, all of which were due to pneumonitis. In multivariate regression analysis, a higher body mass index (BMI) and multiple cycles of pembrolizumab were associated with higher risk of irAEs (BMI: odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01–1.16; pembrolizumab cycle: OR 1.15, 95% CI 1.08–1.22). A derived neutrophil-lymphocyte ratio (dNLR) greater than 3 at baseline was correlated with low risk of irAEs (OR 0.37, 95% CI 0.17–0.81). Our study demonstrated that an elevated BMI and higher number of cycles of pembrolizumab were associated with an increased risk of irAEs in patients treated with pembrolizumab. Additionally, increased dNLR at baseline was negatively correlated with the risk of developing irAEs.

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Relationship of lymphocyte and eosinophil counts and immune-related adverse events in recipients of programmed death-1 (PD-1) inhibitor therapy: A single-center retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e14586 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e14586-e14586 ◽

Cited By ~ 1

Author(s):

Adam Diehl ◽

Mark Yarchoan ◽

Ting Yang ◽

Blake Scott ◽

Burles Avner Johnson ◽

...

Keyword(s):

Adverse Events ◽

Univariate Analysis ◽

Retrospective Chart Review ◽

Absolute Lymphocyte Count ◽

Multivariate Regression Analysis ◽

Tumor Type ◽

Increased Risk ◽

Investigational Therapies ◽

Clinically Significant ◽

Eosinophil Counts

e14586 Background: Inhibition of the PD-1 checkpoint can cause immune activation in non-target tissues, resulting in immune-related adverse events (irAE) in up to 50% of patients. Biomarkers that are associated with irAEs in patients treated with PD-1 inhibitors may have implications for patient selection and clinical management. Methods: We performed an IRB-approved retrospective chart review of adult solid tumor patients treated with nivolumab or pembrolizumab at a single institution from January 2015 until November 2016. Patients were excluded if concurrently receiving investigational therapies, or on unreported clinical trials. Data were collected on treatment history, leukocyte counts, and irAE, defined as adverse events with a potential immunologic basis with grading performed using CTCAE v.4.0. Results: 172 patients were included (lung n = 54; melanoma n = 61; kidney n = 25; esophageal n = 12; bladder n = 8; other tumors n = 12) with median age 67. 18% were treated with concurrent ipilimumab. 31% experienced an adverse event of any grade with a mean time to develop an irAE of 3.5 months. Of those with an irAE, 85% required treatment, 68% were grade ≥ 2, 32% were grade 3 or 4 and 35% required therapy discontinuation due to the irAE. In univariate analysis, a higher ALC at both the start of therapy and at 1 month was associated with increased risk of an irAE of grade ≥ 2 (p < 0.05). A higher absolute lymphocyte count (ALC) or higher absolute eosinophil count (AEC) at 1 month into therapy was associated with increased risk of all irAE (p < 0.05) as well as irAE requiring treatment (p < 0.05). In addition, in a multivariate regression analysis including age, race, tumor type, prior chemotherapy, prior radiation, and concurrent ipilimumab therapy, an ALC > 2000 at the start of therapy was a significant predictor of irAE of grade ≥ 2 (p < 0.05 and OR 2.0), as was an ALC > 2000 at 1 month into therapy (p < 0.05 and OR 1.86). Conclusions: These results suggest that high lymphocyte and eosinophil counts early in the course of anti-PD1 therapy may be associated with a higher risk for clinically significant irAE.

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THU0417 READMISSION RISK AND QUALITY OF CARE IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH GOUT FLARES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3302 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 446.2-446

Author(s):

L. Brunetti ◽

J. Vekaria ◽

P. Lipsky ◽

N. Schlesinger

Keyword(s):

Risk Factors ◽

Emergency Department ◽

Economic Burden ◽

Hospital Admissions ◽

Medical Center ◽

Research Support ◽

Increased Risk ◽

Comorbidity Index ◽

Anti Inflammatory ◽

Gout Flares

Background:Gout is the most common form of inflammatory arthritis and its economic burden is substantial, with estimates for the overall cost exceeding $20 billion (US) annually. Contributing to the economic burden are hospital admissions and iatrogenic events associated with pharmacotherapy. Identification of modifiable risk factors would be an important contribution to clinical practice.Objectives:The aim of this study was to identify opportunities for enhancing gout care in patients presenting to the Emergency Department (ED) with gout flares.Methods:This retrospective cohort study used data from electronic medical records (EMR) at a large community hospital. All consecutive patients visiting the medical center ED with a primary diagnosis of gout from 1/1/2016 to 7/1/2019 were included. Patients were then followed for 90 days to determine whether they were readmitted to the ED for any reason. A chart review identified whether they were on appropriate medications in terms of gout flare management. All data were summarized using descriptive statistics. A multiple logistic regression was constructed to identify risk factors for ED utilization within 90 days of the index visit.Results:A total of 214 patients were included in the analysis. Most patients were male (79%), mean age was 59.4 ± 15.6 years, and mean Charlson comorbidity index was 0.5 ± 1.14. The most common medications prescribed during the ED visit included NSAIDs (41.6%), opioids (28%), corticosteroids (26.6%), and colchicine (21%). Allopurinol and febuxostat were initiated in the ED in 4.7% and 0.9%, respectively. Discharge medications for the management of gout included NSAIDs (37%), corticosteroids (34.6%), opioids (23.8%), colchicine (14%), febuxostat (7%), and allopurinol (6.5%). Of the patients sent home with an opioid, 40% were newly prescribed. An anti-inflammatory medication was not prescribed in 29.6% of patients discharged from the ED. Readmission within 90 days was recorded in 16.8% of patients. Of these readmissions, 33.3% were gout-related and 11.1% were cardiac related.After adjusting for age and comorbidity index, patients receiving colchicine were 2.8 times more likely (OR, 2.81; 95% CI, 1.12 to 7.02; p=0.027) to return to the ED within 90 days. The most common cause of readmission in this subset was gout-related (54.5%).Conclusion:Nearly 30% of patients were discharged from the ED without an anti-inflammatory medication, whereas initiation of urate lowering therapy was rare. Opiates were used frequently, but the indication was uncertain. Only 5.6% of subjects revisited the ED for gout-related diagnoses in the subsequent 3 months. Colchicine prescription was associated with an increased risk of gout-related ED utilization within 90 days. Treatment of gout in the ED is sub-optimal and often does not follow established guidelines.Disclosure of Interests: :Luigi Brunetti Grant/research support from: Astellas Pharma, CSL Behring, Consultant of: Horizon Foundation of New Jersey, Janaki Vekaria: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon

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Risk factors for macular pucker after rhegmatogenous retinal detachment surgery

Scientific Reports ◽

10.1038/s41598-021-97738-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Toshiaki Hirakata ◽

Yoshimune Hiratsuka ◽

Shutaro Yamamoto ◽

Koki Kanbayashi ◽

Hiroaki Kobayashi ◽

...

Keyword(s):

Risk Factors ◽

Retinal Detachment ◽

Surgical Technique ◽

Regression Models ◽

Rhegmatogenous Retinal Detachment ◽

Surgical Repair ◽

Macular Pucker ◽

Logistic Regression Models ◽

Retinal Breaks ◽

Increased Risk

AbstractMacular pucker, also known as an epiretinal membrane, sometimes forms after surgical repair of a rhegmatogenous retinal detachment (RRD) and can decrease visual acuity and cause aniseikonia. However, few reports are evaluating the risk factors of macular pucker using multivariate analysis. To evaluate the risk factors for macular pucker after RRD surgery, 226 patients who underwent RRD surgery and were monitored for greater than 12 months (23.2 ± 6.4 months) after surgery were analyzed retrospectively. Of these cases, macular pucker developed in 26 cases. Multiple logistic regression models of 22 clinical characteristics were performed. An increased risk of macular pucker after RRD surgery was significantly associated with preoperative vitreous haemorrhage (Odds ratio (OR), 4.71; 95% CI 1.19–18.62), multiple retinal breaks (OR, 8.07; 95% CI 2.35–27.71), re-detachment (OR, 19.66; 95% CI 4.87–79.38), and retinal detachment area (OR, 12.91; 95% CI 2.34–71.19). Macular pucker was not associated with the surgical technique. Regardless of the surgical technique used, careful observation for postoperative macular pucker is needed after RRD surgery in high-risk cases. These findings can be used to improve the surgical management of patients with RRD. (183 words).

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History of Depression and Increased Risk of Sternal Wound Infection After Cardiothoracic Surgery: A Novel and Potentially Modifiable Risk Factor

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz083 ◽

2019 ◽

Vol 6 (3) ◽

Author(s):

Deborah A Theodore ◽

Renee D Goodwin ◽

Yuan (Vivian) Zhang ◽

Nancy Schneider ◽

Rachel J Gordon

Keyword(s):

Risk Factors ◽

Wound Infection ◽

Medical Center ◽

Academic Medical Center ◽

Cardiothoracic Surgery ◽

Sternal Wound Infection ◽

Composite Variable ◽

Increased Risk ◽

History Of ◽

History Of Depression

Abstract Background Sternal wound infection (SWI) is a leading cause of postoperative disease and death; the risk factors for SWI remain incompletely understood. The goal of the current study was to investigate the relationship between a preoperative history of depression and the risk of SWI after cardiothoracic surgery. Methods Among patients undergoing cardiothoracic surgery in a major academic medical center between 2007 and 2012, those in whom SWI developed (n = 129) were matched, by date of surgery, with those in whom it did not (n = 258). Multivariable logistic regression was used to examine the strength of relationships between risk factors and development of infection. History of depression was defined as a composite variable to increase the sensitivity of detection. Results History of depression as defined by our composite variable was associated with increased risk of SWI (adjusted odds ratio, 2.4; 95% confidence interval, 1.2–4.7; P = .01). Staphylococcus aureus was the most common organism isolated. Conclusions History of depression was associated with increased risk of SWI. Future prospective studies are warranted to further investigate this relationship. Depression is highly treatable, and increased efforts to identify and treat depression preoperatively may be a critical step toward preventing infection-related disease and death.

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Factors associated with mechanical and systemic adverse events after colonoscopy (France, 2010-2015)

European Journal of Public Health ◽

10.1093/eurpub/ckz186.606 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

M Laanani ◽

A Weill ◽

P O Blotière ◽

J Pouchot ◽

F Carbonnel ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Adverse Events ◽

Older Patients ◽

Public Hospitals ◽

Serious Adverse Events ◽

Logistic Regression Models ◽

Factors Associated ◽

Increased Risk ◽

Experienced Endoscopists

Abstract Background More than one million colonoscopies are performed every year in France. They are associated with risks of mechanical and systemic serious adverse events (SAEs) which can be associated with patient, procedure, endoscopist, and facility characteristics. We tried to identify the factors associated with colonic perforation, gastrointestinal bleeding, splenic injury, shock, myocardial infarction, stroke, pulmonary embolism, acute renal failure, and urolithiasis after colonoscopy. Methods We analysed data from the French national claims databases (SNDS). A total of 4,088,799 patients, 30 years or older, undergoing a first screening or diagnostic colonoscopy between 2010 and 2015 were identified. SAE rates were estimated, and risk factors associated with SAEs were identified using multilevel logistic regression models, adjusted for patient, colonoscopy, endoscopist, and facility characteristics. Results Increasing age was associated with an increasing incidence of mechanical and systemic SAEs. Cancer and cardiovascular comorbidities were associated with mechanical SAEs, and a higher number of pre-existing conditions was associated with shock and acute renal failure. Polypectomy, especially of polyps larger than 1 cm, was associated with an increased risk of perforation (OR = 4.1; 95% CI, 3.4-5.0) and bleeding (OR = 13.3; 95% CI, 11.7-15.1). Mechanical SAEs were associated with the endoscopist’s experience, while systemic SAEs were more frequent in public hospitals than in private clinics. Conclusions SAEs related to colonoscopy were more frequent in older patients and in those with comorbidities. Mechanical SAEs were more frequent when colonoscopy was performed by less experienced endoscopists. Systemic SAEs were more frequent in public hospitals, reflecting patient selection processes. The risk of both mechanical and systemic SAEs should be taken into account when deciding to perform colonoscopy, particularly in older patients with multiple pre-existing conditions. Key messages Systemic SAEs are not uncommon after colonoscopy and, together with intestinal SAEs, should be considered when considering the need for colonoscopy. Patients at risk of SAEs should be identified and colonoscopy should be performed by experienced endoscopists in these patients. Less invasive alternatives should also be considered in these patients.

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Prevalence of and Risk Factors for Cerebral Microbleeds in Moyamoya Disease and Syndrome in the American Population

Cerebrovascular Diseases Extra ◽

10.1159/000504530 ◽

2019 ◽

Vol 9 (3) ◽

pp. 139-147

Author(s):

Nadeem I. Khan ◽

Ali A. Saherwala ◽

Mo Chen ◽

Sepand Salehian ◽

Hisham Salahuddin ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Moyamoya Disease ◽

Hemorrhagic Stroke ◽

Medical Center ◽

Cerebral Microbleeds ◽

Age At Diagnosis ◽

University Hospital ◽

Vascular Events ◽

Increased Risk

Background and Purpose: Cerebral microbleeds (CMB) are reported to be frequent in moyamoya disease (MMD) and moyamoya syndrome (MMS) in the Asian population. It is associated with an increased risk of intracerebral hemorrhage. The significance of CMB in MMD/MMS in non-Asian populations has not been well established. Our study aimed to investigate the prevalence of CMB in MMD/MMS in a moymoya cohort with a majority of non-Asians and to identify risk factors for developing a CMB and its predictive value for subsequent vascular events. Methods: The moyamoya database was compiled by screening for MMD/MMS among patients admitted to the Zale-Lipshy University Hospital at the University of Texas Southwestern Medical Center. We identified and analyzed data of 67 patients with MMD or MMS. Patients were characterized as CMB+ or CMB– based on MRI findings. In CMB+ patients, the total number and location of CMB were identified. Univariate and multivariate logistic regression were used to identify risk factors for developing CMB and whether CMB are associated with the development of subsequent vascular events. Results: Out of a total of 67 patients, 11 (16%) had CMB. Males had significantly higher odds of having CMB as compared to females (OR 1.76; 95% CI 1.40–24.3, p = 0.021). The incidence of CMB was also associated with age at diagnosis (mean age of CMB+ patients vs. CMB– patients: 44 vs. 34 years, respectively, p = 0.024), smoking (p = 0.006), and hemorrhagic stroke at presentation (p = 0.034). Logistic regression with multivariate analysis found that gender and age at diagnosis remained statistically significant. New ischemic events occurred in 2 (20%) out of 10 CMB+ patients and 13 (23%) out of 55 CMB– patients, respectively (p = 0.79). While 2 (3%) CMB– patients had a new cerebral hemorrhage during follow-up, none of the CMB+ patients did. Conclusions: CMB are less prevalent in MMD/MMS in the USA than in Asia. An older age at diagnosis and male gender were associated with CMB. The presence of CMB was not associated with an increased risk of a subsequent ischemic or hemorrhagic stroke.

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Increase in Candida parapsilosis candidemia in cancer patients

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2019.012 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 5

Author(s):

Mingyue Sun ◽

Chunguang Chen ◽

Weiqiang Xiao ◽

Yanmin Chang ◽

Cailin Liu ◽

...

Keyword(s):

Risk Factors ◽

Parenteral Nutrition ◽

Cancer Patients ◽

Candida Parapsilosis ◽

Cancer Center ◽

Candida Spp ◽

Logistic Regression Models ◽

Need To Evaluate ◽

Clinically Significant ◽

Antifungal Use

Background: This study aimed to identify the risk factors of candidemia and asses possible clinically significant differences between Candida parapsilosis and other candida species among cancer patients.Methods: A retrospective study was conducted in a Chinese tertiary cancer center over a 6-year period. A total of 323 cancer patients were enrolled and analyzed from 2012 to 2018. Data about demographic characteristics, underlying diseases, and risk factors of candidemia were collected. Univariate and multivariate logistic regression models were used to identify the risk factors associated with the development of candidemia.Results: Among the isolates, the species most frequently isolated was C. parapsilosis (37.15%, 120/323), and C. albicans only accounted for 34.37%. Based on statistical analysis, when candidemia patients who had C. parapsilosis were compared with other Candida spp., the following factors were found to be significantly associated with C. parapsilosis fungemia: parenteral nutrition (p < 0.001), neutropenia (p < 0.001), receipt of chemotherapy (p = 0.002), and previous antifungal use (p < 0.001). Parenteral nutrition was a factor that independently predicted C. parapsilosis candidemia (OR, 0.183; 95% CI, 0.098–0.340; p < 0.001).Conclusions: In short, C. parapsilosis as the leading non-albicans Candida spp. isolates in candidemia is posing a major threat for cancer patients. The study highlights the urgent need to evaluate the possibility of development of C. parapsilosis candidemia in cancer patients exposed to these risk factors effective and prevention strategies against this causative agent transmitted through nosocomial route should be implemented.

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Relation of Perceived Stigma to Adverse Events of Medications in Patients with Epilepsy

Epilepsy Research and Treatment ◽

10.1155/2016/5362806 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Ekaterina Viteva

Keyword(s):

Adverse Events ◽

Multivariate Regression ◽

Multivariate Regression Analysis ◽

Medical Documentation ◽

Clinical Factors ◽

Perceived Stigma ◽

Increased Risk ◽

Study Results ◽

Study Participants ◽

Patients With Epilepsy

Purpose. We aimed to assess the influence of adverse events (AEs) of antiepileptic drugs (AEDs) on perceived stigma of Bulgarian patients with epilepsy. Methods. Our study was based on questionnaires (Liverpool Adverse Events Profile (LAEP) and stigma scale), information from medical documentation, and an interview on clinical factors of 153 consecutive patients with epilepsy. Results. Perceived stigma was observed in 64.71% of the study participants. There was a significant association between perceived stigma and the total LAEP score (p<0.05, F=13.71). Patients who reported AEs had an increased risk of perceiving stigma compared to those who did not experience AEs. A significant correlation between perceived stigma and the presence of neurological and psychiatric AEs (p<0.001, r=+0.60) and a mild correlation between perceived stigma and the presence of nonneurological AEs (p<0.01, r=+0.20) were verified. In a multivariate regression analysis the only predictors of perceived stigma were AED polytherapy and the presence of neurological and psychiatric AEs. Conclusions. AEs of AEDs in patients with epilepsy significantly correlate with perceived stigma. Our study results will be useful in the campaign to overcome stigma predictors.

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Incidence and prediction of checkpoint inhibitor immune-related nephrotoxicity.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.5_suppl.91 ◽

2020 ◽

Vol 38 (5_suppl) ◽

pp. 91-91

Author(s):

Jonathan D Sorah ◽

Tracy L. Rose ◽

Roshni Radhakrishna ◽

Vimal Derebail ◽

Matthew I. Milowsky

Keyword(s):

Autoimmune Disease ◽

Adverse Events ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Retrospective Chart Review ◽

Tumor Type ◽

True Incidence ◽

Platinum Based Chemotherapy ◽

Increased Risk ◽

Clinically Significant

91 Background: Immune checkpoint inhibitors (ICIs), through inhibition of self-tolerance, have the potential to cause immune-related adverse events that can affect any organ, including the kidneys. Our study aimed to better characterize the incidence of and predictive characteristics for immune-related nephrotoxicity. Methods: All patients at the University of North Carolina (UNC) who received ICIs between April 2014 and December 2018 for any malignancy were identified. Patients on dialysis or those who received concurrent platinum-based chemotherapy were excluded. Any patient who subsequently had a clinically significant acute kidney injury (AKI), defined as a doubling or more of baseline creatinine, was included for analysis. A retrospective chart review was performed to determine the cause of AKI. Any uncertain cases were reviewed by two nephrologists for expert consensus (R.R. and V.D.). Results: 1766 patients received an ICI during the study period. 123 (7%) patients had AKI within one year of the first ICI dose. 14 were due to immune-related nephrotoxicity (11% of patients with AKI and 0.8% of all ICI patients). Pre-existing autoimmune disease was more likely in patients with immune-related nephrotoxicity than in those with non-immune AKI (14% vs 3%, p = 0.04). Similarly, concurrent or prior other immune-related adverse events were more common in patients with immune-related AKI (57% vs 6%, p = 0.01). Patients with immune-related AKI were more likely to see a nephrologist (57% vs 23%, p = 0.007) and had a more profound increase in creatinine from baseline (median 2.6 vs 1.6, p = 0.02). Age, sex, urinalysis findings, and primary tumor type were not associated with increased risk. Conclusions: The true incidence of ICI related nephrotoxicity is difficult to ascertain due to the many confounders that contribute to AKI in this population. Severe immune-related nephrotoxicity is rare, but patients with preexisting autoimmune disease or history of immune-related adverse events are at increased risk.

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Irregularity of energy intake at meals: prospective associations with the metabolic syndrome in adults of the 1946 British birth cohort

British Journal Of Nutrition ◽

10.1017/s0007114515004407 ◽

2015 ◽

Vol 115 (2) ◽

pp. 315-323 ◽

Cited By ~ 8

Author(s):

Gerda K. Pot ◽

Rebecca Hardy ◽

Alison M. Stephen

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Waist Circumference ◽

Energy Intake ◽

Cardiometabolic Risk ◽

Cardiometabolic Risk Factors ◽

Logistic Regression Models ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Health And Development

AbstractIrregularity in eating patterns could be a potential cardiometabolic risk factor. We aimed to study the associations of irregular intake of energy at meals in relation to cardiometabolic risk factors 10 and 17 years later. Variability of energy intake data – derived from 5-d estimated diet diaries of cohort members of the National Survey for Health and Development collected at ages 36 (n1416), 43 (n1505) and 53 years (n1381) – was used as a measure for irregularity. Associations between meal irregularity scores with cardiometabolic risk factors measured 10 and 17 years later were investigated using linear mixed models and logistic regression models. The results showed that irregularity scores changed significantly over the years (P<0·05). At age 36 years, subjects with a more irregular intake of energy at lunch (OR 1·42; 95 % CI 1·05, 1·91) and between meals (OR 1·35; 95 % CI 1·01, 1·82) had an increased risk for the metabolic syndrome 17 years later; at lunch was also associated with an increased waist circumference (OR 1·58; 95 % 1·27, 1·96) and TAG levels (OR 1·33; 95 % CI 1·02, 1·72). At age 43 years, subjects with a more irregular intake at breakfast had an increased risk of the metabolic syndrome 10 years later (OR 1·53; 95 % CI 1·15, 2·04), as well as an increased BMI (OR 1·66; 95 % CI 1·31, 2·10), waist circumference (OR 1·53; 95 % CI 1·23, 1·90) and diastolic blood pressure (OR 1·42; 95 % CI 1·13, 1·78). In conclusion, subjects with a more irregular intake of energy, mostly at breakfast and lunch, appeared to have an increased cardiometabolic risk 10 and 17 years later.

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