Patients with a first episode of psychosis (FEP) display a broad range of metabolic risk factors related to the development of diverse medical comorbidities. Initial stages of these disorders are ...essential in understanding the increased vulnerability of developing cardiometabolic disturbances, associated with a reduced life expectancy. This study aimed to evaluate the metabolic profile of a cohort of patients with a FEP and its evolution during a two year follow-up, as well as the factors that influence the changes in their metabolic status.
16 participating centers from the PEPs Project recruited 335 subjects with a FEP and 253 matched healthy controls, aged 9–35years. We investigated a set of anthropometric measures, vital signs and laboratory data obtained from each participant over two years in a prospective, naturalistic study.
From the beginning of the study the FEP group showed differences in the metabolic profile compared to the control group, together with a progressive worsening in the major part of the analyzed variables during the follow-up period, with higher rates of obesity and metabolic syndrome. Certain risk factors were related to determinate clinical variables such as male gender, the presence of affective symptoms or an early onset or to treatment variables such as the use of antipsychotic polypharmacy, antidepressants or mood stabilizers.
Our results highlight the extremely high risk of patients at early phases of schizophrenia and other psychotic disorders of developing cardiovascular comorbidity and the fast worsening of the metabolic profile during the first two years.
Covadonga Ruiz de Miguel ; directora, Mercedes García García.
Tesis de la Universidad Complutense de Madrid, Facultad de Educación, Departamento de Métodos de Investigación y Diagnóstico en ...Educación, leída el 24-09-2002.
La tesis profundiza en el campo del conocimiento de la calidad de la educación infantil, identificando factores del proceso educativo que logran explicar el logro de los objetivos de la etapa. Apoyándose en una extensa y actual literatura científica, propone e identifica un modelo viable de calidad basado en la investigación sobre eficacia escolar, seleccionando los constructos más relevantes y pertinentes para esta primera etapa del sistema educativo español. En la primera parte, se delimita conceptualmente el campo de estudio en torno a los temas de educación infantil, calidad y evaluación. En la segunda parte del trabajo se presenta el estudio empírico realizado con la pretensión de elaborar y validar un modelo de evaluación de la calidad de la educación infantil. El modelo elaborado se ha validado empíricamente a través de la metodología causal, y en él se identifican, como factores de calidad relevantes del proceso educativo en el aula, las relaciones entre pares, las relaciones profesor alumnos y la implicación de la familia, mediados por el tamaño del grupo, puesto que todos ellos contribuyen, de forma directa o indirecta, pero significativa, a la explicación del desarrollo infantil en las áreas personal, cognitiva, social, motora y lectoescritora.
Covadonga Ruiz de Miguel ; directora, Mercedes García García.
Tesis de la Universidad Complutense de Madrid, Facultad de Educación, Departamento de Métodos de Investigación y Diagnóstico en Educación, leída el 24-09-2002.
La tesis profundiza en el campo del conocimiento de la calidad de la educación infantil, identificando factores del proceso educativo que logran explicar el logro de los objetivos de la etapa. Apoyándose en una extensa y actual literatura científica, propone e identifica un modelo viable de calidad basado en la investigación sobre eficacia escolar, seleccionando los constructos más relevantes y pertinentes para esta primera etapa del sistema educativo español. En la primera parte, se delimita conceptualmente el campo de estudio en torno a los temas de educación infantil, calidad y evaluación. En la segunda parte del trabajo se presenta el estudio empírico realizado con la pretensión de elaborar y validar un modelo de evaluación de la calidad de la educación infantil. El modelo elaborado se ha validado empíricamente a través de la metodología causal, y en él se identifican, como factores de calidad relevantes del proceso educativo en el aula, las relaciones entre pares, las relaciones profesor alumnos y la implicación de la familia, mediados por el tamaño del grupo, puesto que todos ellos contribuyen, de forma directa o indirecta, pero significativa, a la explicación del desarrollo infantil en las áreas personal, cognitiva, social, motora y lectoescritora.
Audience: Specialized
Aims:
Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with ...second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up.
Methods:
These patients were recruited in the multicentre PEPs study (Phenotype−genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis.
Results:
After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin.
Conclusions:
Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.
Abstract Background and Aims In 2020, European Kidney Function Consortium (EKFC) proposed a new equation that estimates glomerular filtration rate (GFR) in European population. Using creatinine and ...age, as well as CKDEPI, EKFC gives an estimation which has been demonstrated to correlate better to measured GFR, particularly at extreme ages. CKDEPI equation is the most common equation used in our clinical practice. Few studies have compared EKFC with CKDEPI, particularly in kidney transplant (KT) recipients. Our objective is to compare estimation of GFR with EKFC and CKDEPI in KT patients. Method We conduct a retrospective observational study including all consecutive KT performed at our centre from 1993 to 2022 with survival greater than one year, and laboratory tests at third month and one-year post-transplant. Using Creatinine and Age we calculate estimated GFR (eGFR) by CKDEPI and EKFC equations. We compare both results in terms of correlation and agreement in the global sample and classifying by subgroups according to a) Sex, b) Age by 10-year sections, c) Body Mass Index (BMI) as WHO classification and d) presence or absence of Diabetes Mellitus (DM). We use SPSS as statistics program. Results We include 968 KT, depicted in Table 1. CKDEPI and EKFC at 3rd month and EKFC at one-year have a non-normal distribution (Kolmogorov-Smirnov test with p = 0.003, p = 0.035 and p = 0.002, respectively), contrary to normality in CKDEPI at one year (p = 0.058). Levene test for homogeneity of variances shows no differences (3rd month p = 0.102, one year p = 0.165), as well as in subgroups. We perform, besides Mann-Whitney, Student's T-test despite limitations over means without significant differences in any subgroup. Mean global difference at 3rd month is 0.23 ml/min greater by CKDEPI. There are no relevant differences between subgroups related to DM and BMI. We can describe a difference between women (0.85 ml/min) and men (0.05 ml/min), and it is larger in 20-30 years group (3.4 ml/min) and in 70-80 years (2.74 ml/min). As measure of agreement, Intraclass Correlation Coefficient (ICC) shows excellent correlation in all subdivisions (Cronbach's Alpha statistic (CA) > 0.99), without significant decrease in any subgroup; minimum ICC = 0.987 is in 20-30 years group, and maximum ICC = 0.999 in 40-60 years. Bland-Altman plot is shown in Fig. 1, where we appreciate a negative bias in low eGFR against a positive in higher values. Mean global difference at one-year eGFR is 0.25 ml/min greater by CKDEPI. We observe a difference between women (0.75 ml/min) and men (0.04 ml/min), larger in 20-30 years group (2.94 ml/min) and 70-80 years (2.27 ml/min) without significance. ICC shows excellent correlation without significant decrease in any subgroup; minimum ICC = 0.992 is in 20-30 years group, and maximum ICC = 0.999 in 50-60 years. Conclusion We find no significant differences between means in eGFR by CKDEPI and EKFC. We observe a tendency to a greater estimation in women than in men. Both CKDEPI and EKFC equations for eGFR show an excellent concordance in our cohort of KT but differences in scatter analysis in Bland-Altman plot, greater in higher values of eGFR. ICC and CA are both slightly minor in the extreme age groups of our cohort. It matches what described in major studies; these differences may be not clinically relevant in this age range group but are probably greater in patients beyond this range.
Abstract Background and Aims In 2020, European Kidney Function Consortium (EKFC) proposed a new equation that estimates glomerular filtration rate (GFR) in European population. Few studies have ...compared EKFC with CKDEPI, particularly in kidney transplant (KT) recipients. Chronic Kidney Disease (CKD) classification by KDIGO is used not only by nephrologists who evaluate more parameters of kidney function, but also by every other specialist who are going to be guided mainly by this stage. Our objective is to compare EKFC equation and CKDEPI in classifying CKD in KT patients and its relationship with associated comorbidities. Method We conduct a retrospective observational study including all KT performed at our centre from 1993 to 2022 with survival greater than one year. We collect creatinine, haemoglobin (Hb), phosphorus (P−), potassium (K+), and bicarbonate (Bic) values at three months and one-year post-transplant. We define anaemia as Hb < 11 g/dl, hyperphosphataemia as serum P− > 4.5 mg/dl, hyperkalaemia as serum K+ > 5 mEq/ml, and acidosis as Bic < 22 mEq/L. We calculate estimated GFR (eGFR) using CKDEPI and EKFC equations, classify CKD stage according to KDIGO, and compare both results in terms of correlation and differences. We use Kappa Coefficient and Chi-Square by contingency tables, and ROC curves with homogeneity test for prediction of these comorbidities. We use SPSS and MedCalc as statistics programs. Results We include 968 KT, with median age at the time of transplant 52.75 year 41.25-61.27. 294 KT (30.4%) are in women. Comorbidity frequencies are depicted in Table 1. ROC analysis shows no significant differences in predicting acidosis at one year, hyperphosphataemia at any time, hyperkalaemia at 3rd month, anaemia at any time, and composite event at any time. We find significant differences in favour to CKDEPI for acidosis at 3rd month (ΔAUC 0.00575 95% CI 0.00182-0.00969; p = 0.0042) and for hyperkalaemia at one year (ΔAUC = 0.00853 0.00161-0.0154; p = 0.0157). Through contingency tables we compare classification into stages, finding very good agreement based on the Kappa coefficient (κ) but significant differences by Chi-Square. With κ = 0.905, EKFC reclassifies 70 patients, 7.23% overall, but not significantly down nor upstaging (31 vs 39). It reclassifies more men than women: 8.46% vs 4.42%. In 10-year age groups, the largest reclassification occurs in the 70-80 years group, a 17.07% with κ = 0.774, all cases upstaged. At one-year eGFR, contingency tables also show a very good agreement based on κ but significant differences by Chi-Square. EKFC reclassifies 83 KT (κ = 0.887), 8.57% overall. It reclassifies 7.48% women and 9.05% men. In 10-year age groups, the largest reclassification occurs in 20-30 years group with 17.24% (κ = 0.767) and 14.81% in 70-80 years (κ = 0.796). All patients in these groups were upstaged. We resume graphically the reclassification of the groups in Fig. 1, observing how EKFC upstages CKD (worsen CKD stage) in high eGFR stages, and downstages CKD in low eGFR stages. Conclusion Estimation of GFR in KT recipients using the new EKFC equation yields similar results to CKDEPI, showing very good agreement for CKD classification although there is a non-negligible percentage of reclassification, which may be clinically relevant in terms of treatment indications and diagnostic tests. It is to a worse CKD stage in high eGFR and to a better stage in low eGFR, and when EKFC reclassification percentage is greater—in the extreme ages of our cohort—it is always by upstaging. Except for minimal differences which we consider clinically inconsequential, we find no significant differences between both equations in discriminating presence of hyperphosphatemia, hyperkalaemia, anaemia or acidosis.
To assess the role of age (early onset psychosis-EOP < 18 years vs. adult onset psychosis-AOP) and diagnosis (schizophrenia spectrum disorders-SSD vs. bipolar disorders-BD) on the duration of ...untreated psychosis (DUP) and prodromal symptoms in a sample of patients with a first episode of psychosis. 331 patients with a first episode of psychosis (7–35 years old) were recruited and 174 (52.6%) diagnosed with SSD or BD at one-year follow-up through a multicenter longitudinal study. The Symptom Onset in Schizophrenia (SOS) inventory, the Positive and Negative Syndrome Scale and the structured clinical interviews for DSM-IV diagnoses were administered. Generalized linear models compared the main effects and group interaction. 273 AOP (25.2 ± 5.1 years; 66.5% male) and 58 EOP patients (15.5 ± 1.8 years; 70.7% male) were included. EOP patients had significantly more prodromal symptoms with a higher frequency of trouble with thinking, avolition and hallucinations than AOP patients, and significantly different median DUP (91 33–177 vs. 58 21–140 days; Z = − 2.006, p = 0.045). This was also significantly longer in SSD vs. BD patients (90 31–155 vs. 30 7–66 days; Z = − 2.916, p = 0.004) who, moreover had different profiles of prodromal symptoms. When assessing the interaction between age at onset (EOP/AOP) and type of diagnosis (SSD/BD), avolition was significantly higher (Wald statistic = 3.945; p = 0.047), in AOP patients with SSD compared to AOP BD patients (p = 0.004). Awareness of differences in length of DUP and prodromal symptoms in EOP vs. AOP and SSD vs. BD patients could help improve the early detection of psychosis among minors.
Background:
Hyperprolactinemia is a common side-effect of antipsychotics (APs), which may trigger serious secondary problems and compromise the adherence to treatment which is crucial for prognosis, ...especially in patients presenting with a first-episode of psychosis (FEP).
Aims:
We evaluated, in some cases for the first time, the effect of polymorphisms in multiple candidate genes on serum prolactin (PRL) levels in an AP-treated FEP cohort recruited in the multicenter PEPs study (Phenotype − genotype and environmental interaction; Application of a predictive model in first psychotic episodes).
Methods:
PRL concentration was measured in serum from 222 patients. A total of 167 polymorphisms were selected in 23 genes. Genetic association analysis was performed in the whole sample and also in homogenous subgroups of patients treated with APs with a high (N = 101) or low risk (N = 95) of increasing PRL release, which showed significant differences in their PRL levels.
Results:
After Bonferroni correction, polymorphisms in NTRK2, DRD2 and ACE genes were associated with PRL concentration.
Conclusion:
Our results give more support to the impact of DRD2, but also of other genes related to dopamine availability such as ACE. Moreover, this study provides the first evidence for the involvement of NTRK2, which suggests that pathways other than the ones related to dopamine or serotonin may participate in the AP-related PRL levels.
The ankle-brachial index (ABI) is widely used to diagnose subclinical peripheral artery disease (PAD) in the general population, but data assessing its prevalence and related factors in different ...chronic kidney disease (CKD) stages are scarce. The aim of this study is to evaluate the prevalence and associated factors of pathological ABI values in CKD patients.
NEFRONA is a multicentre prospective project that included 2445 CKD patients from 81 centres and 559 non-CKD subjects from 9 primary care centres across Spain. A trained team collected clinical and laboratory data, performed vascular ultrasounds and measured the ABI.
PAD prevalence was higher in CKD than in controls (28.0 versus 12.3%, P < 0.001). Prevalence increased in more advanced CKD stages, due to more patients with an ABI ≥1.4, rather than ≤0.9. Diabetes was the only factor predicting both pathological values in all CKD stages. Age, female sex, carotid plaques, higher carotid intima-media thickness, higher high-sensitivity C-reactive protein (hsCRP) and triglycerides, and lower 25-hydroxi-vitamin D were independently associated with an ABI ≤0.9. Higher phosphate and hsCRP, lower low-density lipoprotein (LDL)-cholesterol and dialysis were associated with an ABI ≥1.4. A stratified analysis showed different associated factors in each CKD stage, with phosphate being especially important in earlier CKD, and LDL-cholesterol being an independent predictor only in Sage 5D CKD.
Asymptomatic PAD is very prevalent in all CKD stages, but factors related to a low or high pathological ABI differ, revealing different pathogenic pathways. Diabetes, dyslipidaemia, inflammation and mineral-bone disorders play a role in the appearance of PAD in CKD.
ABSTRACT
Background
Chronic kidney disease (CKD) is associated with increased atherosclerotic burden and higher risk for cardiovascular events (CVE). Atherosclerosis has a significant genetic ...component and, in CKD, it is influenced by mineral metabolism alterations. Therefore, genetic modifications of mineral metabolism–related proteins could affect atherosclerosis in CKD patients. In the present study we investigated the role of single nucleotide polymorphisms (SNPs) of the matrix gamma-carboxy glutamic acid protein (MGP) on atherosclerosis progression and CVE in a CKD cohort.
Methods
A total of 2187 CKD patients from the Observatorio Nacional de Aterosclerosis en Nefrologia (NEFRONA) study were genotyped for SNPs present in the matrix gamma-carboxy glutamic acid (Gla) protein (MGP) gene. Atheromatosis was detected by vascular ultrasound. Progression of atheromatosis, defined as an increase in territories with plaque, was assessed after 24 months. Patients were followed for 48 months for CVE. Association of SNPs with plaque progression was assessed by logistic regression and their capacity to predict CVE by Cox regression.
Results
Three SNPs of the MGP gene were analyzed. No association of the rs4236 or the rs1800801 SNPs was detected with any of the outcomes. However, patients homozygotes for the minor allele of the rs1800802 SNP showed higher adjusted risk for plaque progression odds ratio 2.3 (95% confidence interval 1.06–4.9) and higher risk of suffering a CVE hazard ratio 2.16 (95% confidence interval 1.13–4.12) compared with the rest of genotypes. No association of the SNP with total or dp-ucMGP levels was found in a subsample.
Conclusions
The rs1800802 polymorphism of MGP is associated with plaque progression and CVE in CKD patients.
Graphical Abstract
Graphical Abstract
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