77 research outputs found

    Trends in the conduct and reporting of clinical prediction model development and validation: a systematic review

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    OBJECTIVES: This systematic review aims to provide further insights into the conduct and reporting of clinical prediction model development and validation over time. We focus on assessing the reporting of information necessary to enable external validation by other investigators.MATERIALS AND METHODS: We searched Embase, Medline, Web-of-Science, Cochrane Library, and Google Scholar to identify studies that developed 1 or more multivariable prognostic prediction models using electronic health record (EHR) data published in the period 2009-2019.RESULTS: We identified 422 studies that developed a total of 579 clinical prediction models using EHR data. We observed a steep increase over the years in the number of developed models. The percentage of models externally validated in the same paper remained at around 10%. Throughout 2009-2019, for both the target population and the outcome definitions, code lists were provided for less than 20% of the models. For about half of the models that were developed using regression analysis, the final model was not completely presented.DISCUSSION: Overall, we observed limited improvement over time in the conduct and reporting of clinical prediction model development and validation. In particular, the prediction problem definition was often not clearly reported, and the final model was often not completely presented.CONCLUSION: Improvement in the reporting of information necessary to enable external validation by other investigators is still urgently needed to increase clinical adoption of developed models.</p

    Prognostic Value of a 6-Minute Walk Test in Patients With Transthyretin Cardiac Amyloidosis

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    Background The 6-minute walk test (6MWT) represents a comprehensive functional assessment that is commonly used in patients with heart failure; however, data are lacking in patients with transthyretin cardiac amyloidosis (ATTR-CA). Objectives This study aimed to assess the prognostic importance of the 6MWT in patients with ATTR-CA.Methods A retrospective analysis of patients diagnosed with ATTR-CA at the National Amyloidosis Centre who underwent a baseline 6MWT between 2011 and 2023 identified 2,141 patients, of whom 1,118 had follow-up at 1 year.Results The median baseline 6MWT distance was 347 m (Q1-Q3: 250-428 m) and analysis by quartiles demonstrated an increased death rate with each distance reduction (deaths per 100 person-years: 6.3 vs 9.2 vs 13.6 vs 19.0; log-rank P &lt; 0.001). A 6MWT distance of 35 m) and relative worsening (reduction of &gt;5%) of 6MWT at 1 year was associated with an increased risk of mortality (HR: 1.80; 95% CI: 1.51-2.15; P &lt; 0.001 and HR: 1.89; 95% CI: 1.59-2.24; P &lt; 0.001, respectively), which was similar across the aforementioned subgroups. When combined with established measures of disease progression (N-terminal pro–B-type natriuretic peptide progression and outpatient diuretic intensification), each incremental increase in progression markers was associated with an increased death rate (deaths per 100 person-years: 7.6 vs 13.9 vs 22.4 vs 32.9; log-rank P &lt; 0.001). Conclusions The baseline 6MWT distance can refine risk stratification beyond traditional prognosticators. A worsening 6MWT distance can stratify disease progression and, when combined with established markers, identifies patients at the highest risk of mortality

    Albuminuria in transthyretin cardiac amyloidosis: Prevalence, progression and prognostic importance

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    Aims: Transthyretin cardiac amyloidosis (ATTR-CA) is an infiltrative cardiomyopathy that commonly presents with concomitant chronic kidney disease. Albuminuria is common in heart failure and associated with worse outcomes, but its prevalence and relationship to outcome in ATTR-CA remains unclear.Methods and results: A total of 1181 patients with ATTR-CA were studied (mean age 78.1 +/- 7.9 years; 1022 [86.5%] male; median estimated glomerular filtration rate 59 ml/min/1.73m(2) [interquartile range: 47-74]). Albuminuria was present in 563 (47.7%) patients (499 [88.6%] with microalbuminuria and 64 [11.4%] with macroalbuminuria). Patients with albuminuria had a more severe cardiac phenotype evidenced by higher serum cardiac biomarkers (median N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 4027 ng/L [2173-6889] vs. 1851 ng/L [997-3209], p < 0.001; median troponin T: 69 ng/L [46-101] vs. 48 ng/L [34-68], p < 0.001) and worse echocardiographic indices of systolic (longitudinal strain: -10.0 +/- 3.6% vs. -11.6 +/- 3.8%, p < 0.001) and diastolic function (E/e': 17.5 +/- 6.4 vs. 16.4 +/- 6.7, p < 0.001) than those with a normal urinary albumin to creatinine ratio (UACR). Microalbuminuria and macroalbuminuria were independently associated with mortality in the overall population (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.13-1.92, p = 0.005 and HR 1.87, 95% CI 1.15-3.05, p = 0.012, respectively). In a subgroup of patients (n = 349) without concomitant hypertension, diabetes mellitus or chronic kidney disease, albuminuria was also associated with mortality (HR 2.98, 95% CI 1.72-5.17, p < 0.001). At 12 months, 330 patients had a repeat UACR measurement; those in whom UACR increased by 30% or more (n = 148, 44.8%) had an increased risk of mortality (HR 1.84, 95% CI 1.06-3.19, p = 0.030).Conclusions: Albuminuria is common in patients with ATTR-CA, and more prevalent in those with a more severe cardiac phenotype. Albuminuria at diagnosis and a significant increase in UACR during follow-up are associated with mortality

    Application of the urban exposome framework using drinking water and quality of life indicators: a proof-of-concept study in Limassol, Cyprus

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    Background Cities face rapid changes leading to increasing inequalities and emerging public health issues that require cost-effective interventions. The urban exposome concept refers to the continuous monitoring of urban environmental and health indicators using the city and smaller intra-city areas as measurement units in an interdisciplinary approach that combines qualitative and quantitative methods from social sciences, to epidemiology and exposure assessment. Methods In this proof of concept study, drinking water and quality of life indicators were described as part of the development of the urban exposome of Limassol (Cyprus) and were combined with agnostic environment-wide association analysis. This study was conducted as a two-part project with a qualitative part assessing the perceptions of city stakeholders, and quantitative part using a cross-sectional study design (an urban population study). We mapped the water quality parameters and participants’ opinions on city life (i.e., neighborhood life, health care, and green space access) using quarters (small administrative areas) as the reference unit of the city. In an exploratory, agnostic, environment-wide association study analysis, we used all variables (questionnaire responses and water quality metrics) to describe correlations between them. Results Overall, urban drinking-water quality using conventional indicators of chemical (disinfection byproducts-trihalomethanes (THM)) and microbial (coliforms, E. coli, and Enterococci) quality did not raise particular concerns. The general health and chronic health status of the urban participants were significantly (false discovery rate corrected p-value < 0.1) associated with different health conditions such as hypertension and asthma, as well as having financial issues in access to dental care. Additionally, correlations between THM exposures and participant behavioral characteristics (e.g., household cleaning, drinking water habits) were documented. Conclusion This proof-of-concept study showed the potential of using integrative approaches to develop urban exposomic profiles and identifying within-city differences in environmental and health indicators. The characterization of the urban exposome of Limassol will be expanded via the inclusion of biomonitoring tools and untargeted metabolomics

    Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis

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    Background: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression. Objectives: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA. Methods: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n&nbsp;=&nbsp;1,598) and validated in the external cohort from the remaining centers (n&nbsp;=&nbsp;677). Results: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase &gt;700&nbsp;ng/L and &gt;30%), which was associated with mortality (NAC cohort: HR: 1.82; 95%&nbsp;CI: 1.57-2.10; P&nbsp;&lt; 0.001; validation cohort: HR: 1.75; 95%&nbsp;CI: 1.32-2.33; P&nbsp;&lt; 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95%&nbsp;CI: 1.62-2.18; P&nbsp;&lt; 0.001; validation cohort: HR: 2.05; 95%&nbsp;CI: 1.53-2.74; P&nbsp;&lt; 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95%&nbsp;CI: 1.65-2.27; P&nbsp;&lt; 0.001; validation cohort: HR: 1.94; 95%&nbsp;CI: 1.36-2.77; P&nbsp;&lt; 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95%&nbsp;CI: 2.42-3.67; P&nbsp;&lt; 0.001; validation cohort: HR: 3.23; 95%&nbsp;CI: 2.17-4.79; P&nbsp;&lt; 0.001). Conclusions: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of&nbsp;mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA

    Impact of point-of-care pre-procedure creatinine and eGFR testing in patients with ST segment elevation myocardial infarction undergoing primary PCI: The pilot STATCREAT study

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    Background: Contrast-induced acute kidney injury (CI-AKI) is a recognised complication during primary PCI that affects short and long term prognosis. The aim of this study was to assess the impact of point-of-care (POC) pre-PPCI creatinine and eGFR testing in STEMI patients. Methods 160 STEMI patients (STATCREAT group) with pre-procedure POC testing of Cr and eGFR were compared with 294 consecutive retrospective STEMI patients (control group). Patients were further divided into subjects with or without pre-existing CKD. Results: The incidence of CI-AKI in the whole population was 14.5% and not different between the two overall groups. For patients with pre-procedure CKD, contrast dose was significantly reduced in the STATCREAT group (124.6 ml vs. 152.3 ml, p = 0.015). The incidence of CI-AKI was 5.9% (n = 2) in the STATCREAT group compared with 17.9% (n = 10) in the control group (p = 0.12). There was no difference in the number of lesions treated (1.118 vs. 1.196, p = 0.643) or stents used (1.176 vs. 1.250, p = 0.78). For non-CKD patients, there was no significant difference in contrast dose (172.4 ml vs. 158.4 ml, p = 0.067), CI-AKI incidence (16.7% vs. 13.4%, p = 0.4), treated lesions (1.167 vs. 1.164, p = 1.0) or stents used (1.214 vs. 1.168, p = 0.611) between the two groups. Conclusions: Pre-PPCI point-of-care renal function testing did not reduce the incidence of CI-AKI in the overall group of STEMI patients. In patients with CKD, contrast dose was significantly reduced, but a numerical reduction in CI-AKI was not found to be statistically significant. No significant differences were found in the non-CKD group

    Niemann-Pick disease type C

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    Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include other lipidoses; idiopathic neonatal hepatitis and other causes of cholestatic icterus should be considered in neonates, and conditions with cerebellar ataxia, dystonia, cataplexy and supranuclear gaze palsy in older children and adults. Symptomatic management of patients is crucial. A first product, miglustat, has been granted marketing authorization in Europe and several other countries for specific treatment of the neurological manifestations. The prognosis largely correlates with the age at onset of the neurological manifestations

    Biomarkers of end of shift exposure to disinfection byproducts in nurses

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    Increased disinfectant use commonly takes place in hospitals and other health care settings. A cross-sectional study among active nurses in two Cypriot public hospitals (n = 179) was conducted to examine the prevalence of exposure to disinfection byproducts (DBPs), such as trihalomethanes (THMs) using both self-reported information and biomarker measurements. The objectives of this study were to: i) quantify the magnitude and variability of occupational exposure to disinfectants/DBPs in nurses, ii) generate job exposure matrices (JEM) and job task exposure matrices (JTEM) for disinfectants, and iii) assess the major determinants of urinary THMs in nurses. End of shift urinary total THM values showed high variability among the nurses, but did not differ between hospitals. The disinfectant group of alcohols/phenols was used by > 98% of nurses, followed by octenidine (82%), iodine and chlorine (39%, each), chlorhexidine (25%), formaldehyde (12%), hydrogen peroxide (11%), and peracetic acid/ammonia/quaternary ammonium compounds (QACs), all being < 8% each. Chlorine use during the past 24 hr was associated with significantly (p < 0.05) lower brominated THMs (BrTHMs) after adjusting for age, gender and BMI, while a positive association was shown for TCM and the sum of all THMs (TTHMs), albeit not significant. Nurses were exposed to nearly double the levels of TTHMs and BrTHMs (median and IQR, 1027 [560, 2475] ng/g and 323 [212, 497] ng/g, respectively) when compared to those of the general population (552 [309,989] ng/g and 152 [87,261] ng/g, respectively). This was the first occupational health dataset reporting measurements of biomarkers of end of shift exposures to disinfectants/DBPs
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