Continuous diagnostic tests are often used for discriminating between healthy and diseased populations. For the clinical application of such tests, it is useful to select a cutpoint or discrimination ...value c that defines positive and negative test results. In general, individuals with a diagnostic test value of c or higher are classified as diseased. Several search strategies have been proposed for choosing optimal cutpoints in diagnostic tests, depending on the underlying reason for this choice. This paper introduces an R package, known as OptimalCutpoints, for selecting optimal cutpoints in diagnostic tests. It incorporates criteria that take the costs of the different diagnostic decisions into account, as well as the prevalence of the target disease and several methods based on measures of diagnostic test accuracy. Moreover, it enables optimal levels to be calculated according to levels of given (categorical) covariates. While the numerical output includes the optimal cutpoint values and associated accuracy measures with their confidence intervals, the graphical output includes the receiver operating characteristic (ROC) and predictive ROC curves. An illustration of the use of OptimalCutpoints is provided, using a real biomedical dataset.
Assessment of serum concentration of lipopolysaccharide (LPS)-binding protein (LBP) has been suggested as a useful biomarker to indicate activation of innate immune responses to microbial products. ...We investigated LBP concentrations and associations with demographics, lifestyle factors, and common metabolic abnormalities in adults. We also examined if LBP concentrations were associated with common polymorphisms in genes coding for LBP (rs2232618), CD14 (rs2569190), and TLR4 (rs4986790), the molecules responsible for the innate immune response to LPS, or serum levels of soluble CD14 (sCD14) and proinflammatory cytokines.
Serum LBP was measured with a commercial immunoassay in a random sample of the adult population (n = 420, 45% males, age 18-92 years) from a single municipality.
Serum LBP concentrations increased with age (P<0.001) and were higher in individuals who were overweight or obese than in normal-weight individuals (P<0.001). Similarly, LBP concentrations were higher in individuals with metabolic syndrome than in individuals without it (P<0.001). Among metabolic syndrome components, LBP concentrations were independently associated with abdominal obesity (P = 0.002) and low concentrations of HDL-cholesterol (P<0.001). Serum LBP concentrations tended to be independently associated with smoking (P = 0.05), but not with alcohol consumption. Likewise, there was not significant association between LBP concentrations and gene polymorphisms. Concentrations of LBP significantly correlated with serum levels of proinflammatory cytokines (IL-6 and IL-8), sCD14, and with liver enzymes.
Serum LBP concentrations increased with age. Overweight, obesity, and having metabolic syndrome (particularly, low HDL cholesterol levels) were associated with higher LBP concentrations. These findings are consistent with microbial exposure playing a role in these inflammatory, metabolic abnormalities.
To describe epidemiologic characteristics of asymptomatic and symptomatic meibomian gland dysfunction (MGD) in a general adult population in northwestern Spain.
A total of 1155 subjects aged 40 years ...and older were selected by an age-stratified random sample procedure in O Salnés, Spain. A standardized symptoms questionnaire was administered and a comprehensive ophthalmic evaluation, which included ocular surface tests, was carried out. Absent, viscous, or waxy white secretion upon digital expression, lid margin telangiectasia or plugging of the meibomian gland orifices was considered evidence of MGD. The prevalence and associations of asymptomatic and symptomatic MGD, and their effects on the ocular surface, were investigated.
From 937 eligible subjects, 619 (66.1%) participated (mean age SD, 63.4 14.5 years; range, 40-96; 37.0% males). The prevalence of asymptomatic MGD was 21.9% (95% confidence interval CI, 18.8-25.3). This prevalence increased with age (P = 0.000) and was higher in males than in females (P = 0.003). The prevalence of symptomatic MGD was 8.6% (95% CI, 6.7-10.9). This prevalence also increased with age (P = 0.000) but was not associated with sex. Abnormal tear breakup time and fluorescein staining prevalence estimates were higher among asymptomatic subjects. After controlling for age and sex, asymptomatic MGD was associated with diabetes (adjusted odds ratio OR(a) 2.23) and cardiovascular disease (OR(a) 1.80), and symptomatic MGD with rosacea (OR(a) 3.50) and rheumatoid arthritis (OR(a) 16.50).
Asymptomatic MGD is more common than symptomatic MGD. Symptomatology is not associated with secondary damage to the ocular surface. Some systemic diseases may lower whereas others may raise the risk of developing symptoms. Symptom-based approaches do not seem appropriate for MGD estimation.
Insulin resistance has been associated with metabolic and hemodynamic alterations and higher cardio metabolic risk. There is great variability in the threshold homeostasis model assessment of insulin ...resistance (HOMA-IR) levels to define insulin resistance. The purpose of this study was to describe the influence of age and gender in the estimation of HOMA-IR optimal cut-off values to identify subjects with higher cardio metabolic risk in a general adult population.
It included 2459 adults (range 20-92 years, 58.4% women) in a random Spanish population sample. As an accurate indicator of cardio metabolic risk, Metabolic Syndrome (MetS), both by International Diabetes Federation criteria and by Adult Treatment Panel III criteria, were used. The effect of age was analyzed in individuals with and without diabetes mellitus separately. ROC regression methodology was used to evaluate the effect of age on HOMA-IR performance in classifying cardio metabolic risk.
In Spanish population the threshold value of HOMA-IR drops from 3.46 using 90th percentile criteria to 2.05 taking into account of MetS components. In non-diabetic women, but no in men, we found a significant non-linear effect of age on the accuracy of HOMA-IR. In non-diabetic men, the cut-off values were 1.85. All values are between 70th-75th percentiles of HOMA-IR levels in adult Spanish population.
The consideration of the cardio metabolic risk to establish the cut-off points of HOMA-IR, to define insulin resistance instead of using a percentile of the population distribution, would increase its clinical utility in identifying those patients in whom the presence of multiple metabolic risk factors imparts an increased metabolic and cardiovascular risk. The threshold levels must be modified by age in non-diabetic women.
Abstract
Continuous glucose monitoring systems (CGM) are a very useful tool to understand the behaviour of glucose in different situations and populations. Despite the widespread use of CGM systems ...in both clinical practice and research, our understanding of the reproducibility of CGM data remains limited. The present work examines the reproducibility of the results provided by a CGM system in a random sample of a free-living adult population, from a functional data analysis approach. Functional intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CI) were calculated to assess the reproducibility of CGM results in 581 individuals. 62% were females 581 participants (62% women) mean age 48 years (range 18–87) were included, 12% had previously been diagnosed with diabetes. The inter-day reproducibility of the CGM results was greater for subjects with diabetes (ICC 0.46 CI 0.39–0.55) than for normoglycaemic subjects (ICC 0.30 CI 0.27–0.33); the value for prediabetic subjects was intermediate (ICC 0.37 CI 0.31–0.42). For normoglycaemic subjects, inter-day reproducibility was poorer among the younger (ICC 0.26 CI 0.21–0.30) than the older subjects (ICC 0.39 CI 0.32–0.45). Inter-day reproducibility was poorest among normoglycaemic subjects, especially younger normoglycaemic subjects, suggesting the need to monitor some patient groups more often than others.
Background
An early diagnosis and early initiation of oral anticoagulants (OAC) are main determinants for outcomes in patients with atrial fibrillation (AF). Inter‐clinician electronic consultations ...(e‐consultations) program for the general practitioner referrals to cardiologist may improve health care access by reducing the elapsed time for cardiology care.
Objective
To evaluate the effect of a reduced elapsed time to care after a inter‐clinician e‐consultations program implementation (2013–2019) in comparison with previous in‐person consultation (2010–2012) in the outpatient health care management in a Cardiology Department.
Methodology
We included 10,488 patients with AF from 1 January 2010, to 31 December 2019. Until 2012, all patients attended an in‐person consultation (2010–2012). In 2013, we instituted an e‐consult program (2013–2019) for all primary care referrals to cardiologists that preceded patient's in‐person consultation when considered. The shared electronic patient dossier (EPD) was available between GP and cardiologist, and any change in therapy advice from cardiologist was directly implemented in this EPD.
Results
During the e‐consultation period (2013–2019) were referred 6627 patients by GPs to cardiology versus 3861 during the in‐person consultation (2010–2012). The e‐consultation implementation was associated with a reduction in the elapsed time to anticoagulation prescription (177.6 ± 8.9 vs. 22.5 ± 8.1 days, p < .001), and an increase of OAC use (61% 95% IC: 19.6%–102.4%, p < .001). The e‐consult program implementation was associated with a reduction in the 1‐year CV mortality (.48 95% CI: .30–.75) and all‐cause mortality (.42 95% CI: .29–.62). The OAC reduces the stroke mortality (.15 95% CI: .06–.39) and CV mortality (.43 95% CI: .29–.62) and all‐cause mortality (.23 95% CI: .17–.31).
Conclusion
A shared EPD‐based inter‐clinician e‐consultation program significantly reduced the elapsed time for cardiology consultation and initiation of OAC. The implementation of this program was associated with a lower risk of stroke and cardiovascular/all‐cause mortality.
Corona Virus Disease 19 (COVID-19) is a new pandemic, declared a public health emergency by the World Health Organization, which could have negative consequences for pregnant and postpartum women. ...The scarce evidence published to date suggests that perinatal mental health has deteriorated since the COVID-19 outbreak. However, the few studies published so far have some limitations, such as a cross-sectional design and the omission of important factors for the understanding of perinatal mental health, including governmental restriction measures and healthcare practices implemented at the maternity hospitals. Within the Riseup-PPD COST Action, a study is underway to assess the impact of COVID-19 in perinatal mental health. The primary objectives are to (1) evaluate changes in perinatal mental health outcomes; and (2) determine the risk and protective factors for perinatal mental health during the COVID-19 pandemic. Additionally, we will compare the results between the countries participating in the study.
This is an international prospective cohort study, with a baseline and three follow-up assessments over a six-month period. It is being carried out in 11 European countries (Albania, Bulgaria, Cyprus, France, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom), Argentina, Brazil and Chile. The sample consists of adult pregnant and postpartum women (with infants up to 6 months of age). The assessment includes measures on COVID-19 epidemiology and public health measures (Oxford COVID-19 Government Response Tracker dataset), Coronavirus Perinatal Experiences (COPE questionnaires), psychological distress (BSI-18), depression (EPDS), anxiety (GAD-7) and post-traumatic stress symptoms (PTSD checklist for DSM-V).
This study will provide important information for understanding the impact of the COVID-19 pandemic on perinatal mental health and well-being, including the identification of potential risk and protective factors by implementing predictive models using machine learning techniques. The findings will help policymakers develop suitable guidelines and prevention strategies for perinatal mental health and contribute to designing tailored mental health interventions.
ClinicalTrials.gov Identifier: NCT04595123 .
The Cox proportional hazards regression model has become the traditional choice for modeling survival data in medical studies. To introduce flexibility into the Cox model, several smoothing methods ...may be applied, and approaches based on splines are the most frequently considered in this context. To better understand the effects that each continuous covariate has on the outcome, results can be expressed in terms of splines-based hazard ratio (HR) curves, taking a specific covariate value as reference. Despite the potential advantages of using spline smoothing methods in survival analysis, there is currently no analytical method in the R software to choose the optimal degrees of freedom in multivariable Cox models (with two or more nonlinear covariate effects). This paper describes an R package, called smoothHR, that allows the computation of pointwise estimates of the HRs—and their corresponding confidence limits—of continuous predictors introduced nonlinearly. In addition the package provides functions for choosing automatically the degrees of freedom in multivariable Cox models. The package is available from the R homepage. We illustrate the use of the key functions of the smoothHR package using data from a study on breast cancer and data on acute coronary syndrome, from Galicia, Spain.
Purpose: To estimate the prevalence of dry eye and to investigate its relationship with lifestyle and systemic factors in a general adult population in north-western Spain. Methods: A dry eye ...questionnaire was administered and objective tests were performed in 654 individuals mean age (Standard deviation): 63.6 (14.4) years, range: 40-96, 37.2% males. Subjects were considered symptomatic when one or more of the symptoms of the questionnaire were present often or all the time. Schirmer test ≤ 5 mm, tear film breakup time ≤ 10 s, rose bengal staining ≥ 3 and fluorescein staining ≥ 1 were considered indicative of signs. Dry eye was defined as the simultaneous presence of symptoms and at least one sign. A design based analysis was performed and all calculations were weighted to give unbiased estimates. Results: Dry eye prevalence was 11.0% (95%confidence interval CI 8.6-13.3). Dry eye was found to be more frequent in women (11.9%, 95%CI 8.8-15.1) than in men (9.0%, 95%CI 5.3-12.6), and was significantly associated with aging (p < 0.001). After controlling for age and sex, acne rosacea was the only factor associated with the disease. There were no habits or systemic factors associated with symptoms. However, autoimmune diseases, acne rosacea, and computer use were found to be independently and significantly associated with signs. Conclusions: Dry eye is a common disease in this adult European population and is more frequent in older subjects. Acne rosacea is the only factor associated with dry eye. Other factors are associated with signs but not with symptoms.
The analysis of odds ratio curves is a valuable tool in understanding the relationship between continuous predictors and binary outcomes. Traditional parametric regression approaches often assume ...specific functional forms, limiting their flexibility and applicability to complex data. To address this limitation and introduce more flexibility, several smoothing methods may be applied, and approaches based on splines are the most frequently considered in this context. To better understand the effects that each continuous covariate has on the outcome, results can be expressed in terms of splines-based odds ratio (OR) curves, taking a specific covariate value as reference. In this paper, we introduce an R package, flexOR, which provides a comprehensive framework for pointwise nonparametric estimation of odds ratio curves for continuous predictors. The package can be used to estimate odds ratio curves without imposing rigid assumptions about their underlying functional form while considering a reference value for the continuous covariate. The package offers various options for automatically choosing the degrees of freedom in multivariable models. It also includes visualization functions to aid in the interpretation and presentation of the estimated odds ratio curves. flexOR offers a user-friendly interface, making it accessible to researchers and practitioners without extensive statistical backgrounds.
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