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      Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study

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          Summary

          Background

          Prurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN. However, small cohort sizes, partially discrepant outcomes, missing data, and incomplete risk assessment limit these findings.

          Methods

          Electronic health records (EHR)s of 64,801 patients (59.44% females) with PN and an equal sized propensity-matched control group were retrieved. In these cohorts, the risks to develop cardiac and vascular diseases and mortality following the diagnosis of PN were determined. Sub-analyses included stratification for sex, ethnicity, and treatments.

          Findings

          PN was associated with a higher risk for a broad range of acute cardiac events including heart failure and myocardial infarction. For example, the hazard ratio of myocardial infarction was 1.11 (95%-CI: 1.041–1.184, p = 0.0015) following PN diagnosis. Also, all-cause mortality was higher in patients with PN. Further, chronic vascular as well as structural heart diseases, e.g., peripheral arterial disease, chronic ischaemic heart disease and valval disorders were found more frequently following a PN diagnosis. Risks were more pronounced in white and female patients. Having established an increased risk for death and cardiovascular disease, we next addressed if dupilumab that has been recently licenced for use in this indication can modulate these risks. The risk of death but not of any cardiovascular disease was slightly reduced in patients with PN treated with dupilumab as opposed to those treated with systemic therapies other than dupilumab. The study is limited by retrospective data collection and reliance on ICD10-disease classification.

          Interpretation

          PN is associated with higher mortality and an increased risk for the development of a wide range of cardiac and vascular diseases. Health care professionals should take this into account when managing patients with PN.

          Funding

          This work was supported by the doi 10.13039/501100004168, University of Lübeck; , the doi 10.13039/501100001659, Deutsche Forschungsgemeinschaft; and the State of Schleswig-Holstein.

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          Most cited references43

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          General cardiovascular risk profile for use in primary care: the Framingham Heart Study.

          Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions ("general CVD" algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P<0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non-laboratory-based predictors. A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care.
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            Scikit-learn: machine learning in python

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              Comparison of Propensity Score Methods and Covariate Adjustment: Evaluation in 4 Cardiovascular Studies.

              Propensity scores (PS) are an increasingly popular method to adjust for confounding in observational studies. Propensity score methods have theoretical advantages over conventional covariate adjustment, but their relative performance in real-word scenarios is poorly characterized. We used datasets from 4 large-scale cardiovascular observational studies (PROMETHEUS, ADAPT-DES [the Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents], THIN [The Health Improvement Network], and CHARM [Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity]) to compare the performance of conventional covariate adjustment with 4 common PS methods: matching, stratification, inverse probability weighting, and use of PS as a covariate. We found that stratification performed poorly with few outcome events, and inverse probability weighting gave imprecise estimates of treatment effect and undue influence to a small number of observations when substantial confounding was present. Covariate adjustment and matching performed well in all of our examples, although matching tended to give less precise estimates in some cases. PS methods are not necessarily superior to conventional covariate adjustment, and care should be taken to select the most suitable method.
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                Author and article information

                Contributors
                Journal
                eBioMedicine
                EBioMedicine
                eBioMedicine
                Elsevier
                2352-3964
                16 April 2024
                May 2024
                16 April 2024
                : 103
                : 105123
                Affiliations
                [a ]Department of Dermatology, University of Lübeck, Lübeck, Germany
                [b ]Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel
                [c ]Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
                [d ]TriNetX, LLC, Cambridge, MA, USA
                [e ]Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany
                [f ]Department of Dermatology, University of Kiel, Kiel, Germany
                Author notes
                []Corresponding author. Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. henning.olbrich@ 123456uksh.de
                [g]

                Equal contribution.

                Article
                S2352-3964(24)00158-0 105123
                10.1016/j.ebiom.2024.105123
                11035034
                38631094
                9f7af505-8700-409a-a2da-8dc5fada6f19
                © 2024 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 November 2023
                : 2 April 2024
                : 3 April 2024
                Categories
                Articles

                prurigo nodularis,cardiovascular disease,mortality,myocardial infarction,stroke,trinetx

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