Temporal Stability of Management Zone Patterns: Case Study with Contact and Non-Contact Soil Electrical Conductivity Sensors in Dryland Pastures.

Precision agriculture (PA) intends to validate technological tools that capture soil and crop spatial variability, which constitute the basis for the establishment of differentiated management zones (MZs). Soil apparent electrical conductivity (ECa) sensors are commonly used to survey soil spatial variability. It is essential for surveys to have temporal stability to ensure correct medium- and long-term decisions. The aim of this study was to assess the temporal stability of MZ patterns using different types of ECa sensors, namely an ECa contact-type sensor (Veris 2000 XA, Veris Technologies, Salina, KS, USA) and an electromagnetic induction sensor (EM-38, Geonics Ltd., Mississauga, ON, Canada). These sensors were used in four fields of dryland pastures in the Alentejo region of Portugal. The first survey was carried out in October 2018, and the second was carried out in September 2020. Data processing involved synchronizing the geographic coordinates obtained using the two types of sensors in each location and establishing MZs based on a geostatistical analysis of elevation and ECa data. Although the basic technologies have different principles (contact versus non-contact sensors), the surveys were carried out at different soil moisture conditions and were temporarily separated (about 2 years); the ECa measurements showed statistically significant correlations in all experimental fields (correlation coefficients between 0.449 and 0.618), which were reflected in the spatially stable patterns of the MZ maps (averaging 52% of the total area across the four experimental fields). These results provide perspectives for future developments, which will need to occur in the creation of algorithms that allow the spatial variability and temporal stability of ECa to be validated through smart soil sampling and analysis to generate recommendations for sustained soil amendment or fertilization.

Using a Non-Contact Sensor to Delineate Management Zones in Vineyards and Validation with the Rasch Model.

The production of high-quality wines is one of the primary goals of modern oenology. In this regard, it is known that the potential quality of a wine begins to be determined in the vineyard, where the quality of the grape, initially, and later that of the wine, will be influenced by the soil properties. Given the spatial variability of the fundamental soil properties related to the potential grape production, such as texture, soil organic matter content, or cation exchange capacity, it seems that a uniform management of a vineyard is not the most optimal way to achieve higher grape quality. In this sense, the delineation of zones with similar soil characteristics to implement site-specific management is essential, reinforcing the interest in incorporating technologies and methods to determine these homogeneous zones. A case study was conducted in a 3.3 ha vineyard located near Évora, south of Portugal. A non-contact sensor (DUALEM 1S) was used to measure soil apparent electrical conductivity (ECa) in the vineyard, and later, a kriged ECa map was generated. ECa and elevation maps were utilised to delineate homogeneous zones (management zones, MZs) in the field through a clustering process. MZs were validated using some soil properties (texture; pH; organic matter-OM; phosphorous-P2O5; potassium-K2O; the sum of the exchange bases-SEB; and cation exchange capacity-CEC), which were determined from 20 soil samples taken in the different MZs. Validation was also performed using Rasch measures, which were defined based on the formulation of the objective and probabilistic Rasch model, integrating the information from the aforementioned soil properties at each sampling location. The comparison of the MZs was more evident with the use of the Rasch model, as only one value was to be employed in each MZ. Finally, an additional validation was conducted using a vegetation index to consider the plant response, which was different in each MZ. The use of a non-contact sensor to measure ECa constitutes an efficient technological tool for implementing site-specific management in viticulture, which allows for the improvement of decision-making processes by considering the inherent spatial variability of the soil.

Management of particular clinical situations in psoriatic arthritis: an expert's recommendation document based on systematic literature review and extended Delphi process.

To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA.

Role of edge inclination in an optical microdisk resonator for label-free sensing.

In this paper, we report on the measurement and modeling of enhanced optical refractometric sensors based on whispering gallery modes. The devices under test are optical microresonators made of silicon nitride on silicon oxide, which differ in their sidewall inclination angle. In our approach, these microresonators are vertically coupled to a buried waveguide with the aim of creating integrated and cost-effective devices. Device modeling shows that the optimization of the device is a delicate balance of the resonance quality factor and evanescent field overlap with the surrounding environment to analyze. By numerical simulations, we show that the microdisk thickness is critical to yield a high figure of merit for the sensor and that edge inclination should be kept as high as possible. We also show that bulk-sensing figures of merit as high as 1600 RIU(-1) (refractive index unit) are feasible.

External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

OBJECTIVES: To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD). DESIGN: Prospective population-based cohort study. SETTING: 10 primary healthcare centres in the north of the city of Madrid (Spain). PARTICIPANTS: A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose <200 mg/dL (<11.1 mmol/L) were followed up for 7.3 years (median) using their electronic health records (EHRs) and telephone contact. PRIMARY AND SECONDARY OUTCOME MEASURES: Diabetes risk scores (FINDRISC, DESIR, ADA), PHQ-9 questionnaire and 2-hour-OGTT were measured at baseline. Incident diabetes was defined as treatment for diabetes, fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L), new EHR diagnosis or self-reported diagnosis. External validation was performed according to optimal cut-off, sensitivity, specificity and Youden Index. Comparison between diabetes risk scores, including FINDRISC-MOOD (original FINDRISC score plus five points if PHQ-9 ≥10), was measured by area under the receiver operating characteristic curve (AUROC). RESULTS: During follow-up, 104 (8.4%; 95% CI, 6.8 to 9.9) participants developed diabetes and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67 to 0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65 to 0.71) for the original FINDRISC. The AUROCs for DESIR and ADA were 0.66 (95% CI, 0.63 to 0.68) and 0.66 (95% CI, 0.63 to 0.69), respectively. There were no significant differences in AUROC between FINDRISC-MOOD and the other scores. CONCLUSIONS: The results of FINDRISC-MOOD were like those of the other risk scores and do not allow it to be recommended for clinical use.

Prevalence of Gabapentinoids and Central Nervous System Depressant Drugs, and Their Association with Risk Factors for Respiratory Depression in Primary Care Patients.

BACKGROUND AND OBJECTIVES: Warnings have been published regarding an increased risk of severe respiratory depression in patients receiving gabapentinoids either alone or in combination with opioids and/or anxiolytics/hypnotics, especially in individuals with a respiratory risk factor. The aim is to report the prevalence of the use of gabapentinoids alone and associated with central nervous system depressant drugs, and possible associated risk factors for respiratory depression, in order to identify the most fragile population and establish intervention strategies. METHODS: We performed a cross-sectional study using computerized prescription records from the northern area of Barcelona at Catalan Institute of Health for 363,007 inhabitants registered during 2021. Patients aged ≥ 18 years with one or more gabapentinoid prescription were included. Age, gender, polypharmacy, adjusted morbidity groups, quantity of chronic diseases, and the number of consultations per year were independent variables. Four age categories were defined (18-64 years, then 64-74, 75-84, and those aged 85 years or older). Descriptive and inferential statistics were employed. Level of statistical significance was 5% (p ≤ 0.05). For the analysis, the SPSS program (version 22) was employed. RESULTS: Of the study sample, 9218 were prescribed gabapentidoids. Overall prevalence of use was 3.0% (women 3.6%, men 2.4%). On the whole, women used more drugs than men. In contrast to their younger counterparts, consumption increased 2.6 times, 3.8 times, and 4.0 times in the 65-74 age group, 75-84 age group, and those aged ≥ 85 years, respectively. Mean age was 65.59 (±15.80) years. Polypharmacy (5-9 drugs) was present in 41.7% of the patients and extreme polypharmacy (≥ 10 drugs) was present in 39.3% of the patients. Regarding renal function, 2396 patients (25.9%) had glomerular filtration that required dose adjustment (76.1% with gabapentin and 23.8% with pregabalin). In 141 patients (5.9%), a total daily dose higher than that authorized (109 with gabapentin, 29 with pregabalin) had been prescribed. The prescription of gabapentinoids combined with opioids and/or anxiolytics/hypnotics was significantly associated with (i) polypharmacy (5-9 drugs, OR: 3.42 [95% CI 3.00-3.88]; ≥ 10 drugs, OR 8.72 [95% CI 7.42-10.25]); (ii) quantity of chronic diseases, OR: 1.14 (95% CI 1.11-1.17); (iii) augmented number of consultations/year, OR: 1.01 (95% CI 1.00-1.01); (iv) female gender, OR: <  1 for men, OR: 0.66 (95% CI 0.60-0.73); (v) being elderly: 65-74 years, OR: 0.71 (95% CI 0.62-0.81); 75-84 years, OR: 0.62 (95% CI 0.54-0.71); ≥85 years, OR: 0.68 (95% CI 0.58-0.81); and (vi) adjusted morbidity groups, OR: 0.90 (95% CI 0.88-0.92), (p <  0.0001). CONCLUSION: Exposure to gabapentinoids occurs in a non-negligible percentage of the population. Greater numbers of combinations of gabapentinoids and opioids and/or anxiolytics/hypnotics were associated with polypharmacy, quantity of chronic diseases, and augmented number of consultations, but not with male gender, older age, and adjusted morbidity groups.

Patient Journey in Atopic Dermatitis: The Real-World Scenario.

INTRODUCTION: The diagnosis and management of atopic dermatitis (AD) is extensively addressed in detailed clinical guidelines. However, the high heterogeneity regarding presentation and progression and the increasingly broad therapeutic landscape suggest a complex real-world scenario, leading to multiple trajectories of AD patients. METHODS: Using a Delphi methodology for assessing the degree of consensus, we explored the views of a panel of dermatologists regarding the patients' trajectory through the diagnosis (block 1), treatment (block 2), and long-term management (block 3) of AD. Based on a systematic search of the literature, a scientific committee prepared a questionnaire of relevant items that were rated on a 10-point scale (from "totally agree" to "totally disagree") by a panel of dermatologists attending patients with AD in the hospital setting. Consensus was established based on predefined rules. RESULTS: The final questionnaire included 58 items and was answered by 17 dermatologists. Overall, consensus was reached on 22 items (37.9%), each of which was a consensus for agreement. The consensus rates in blocks 1, 2, and 3 were 22.7%, 19.0%, and 86%, respectively. CONCLUSIONS: Our analysis revealed a remarkable lack of consensus on various aspects of the routine diagnosis and treatment of AD. These findings suggest the presence of unmet needs or limited implementation of guidelines for the management of AD and encourage further research to explore the causes of this low consensus on the management of AD in the real-world setting.

[Development and validation of the first Spanish questionnaire of quality of life in patients with prostate cancer, based on the patient's perception]. / Desarrollo y validación del primer cuestionario español de calidad de vida en pacientes con cáncer de próstata, basado en la percepción del paciente.

BACKGROUND: To ensure health related quality of life (HRQOL) during the survival of patients with prostate cancer (PCa) is a priority. The development of specific HRQOL questionnaires aids to assess the disease impact, its treatment and the patient's perception (concerns, expectations and interests) that might go unnoticed. OBJECTIVES: To develop and validate the first Spanish HRQL questionnaire specific for patients with PCa. MATERIALS AND METHODS: The questionnaire CAVIPRES had 3 phases of development: 1.-generation of items (literature research, expert meeting and 2 focus groups with patients), 2.- reduction of items (self-administered survey with a preliminary version and clinimetric and psychometric analyses), 3: validation of the questionnaire (observational study with 2 visits where patients completed the CAVIPRES, SF-36 and UCLA-PCI tests and analysis of psychometric properties in terms of validity, reliability and sensitivity to change). RESULTS: A preliminary list of 75 potential items was obtained in phase 1.412 patients were recruited and answered this preliminary version in phase 2. 35 items were deleted. 436 patients responded to the definitive-30-items obtained version (CAVIPRES-30) in Phase 3. CAVIPRES-30 showed feasibility (items lost <4%, ceiling effect: 0% floor effect: 0% in the overall score), high reliability in terms of internal consistency (alpha = 0.77) and re-test reliability (ICC = 0.92). There was a good correlation between tests CAVIPRES and SGF-36 and UCLA-PCI for similar domains CONCLUSION: The questionnaire CAVIPRES-30 is a feasible, reliable and sensitive to change, useful in clinical research for prostate cancer.

Effects of etanercept on the patient-perceived results (PROs) in patients with moderate-to-severe plaque psoriasis: systematic review of the literature and meta-analysis.

PURPOSE: To evaluate the efficacy of etanercept (ETN) compared with placebo for moderate-to-severe psoriasis regarding patient-reported outcomes (PROs). METHODS: Systematic review of studies retrieved by a sensitive search strategy in Medline, Embase, Cochrane Library. SELECTION CRITERIA: (population) studies had to include patients with for moderate-to-severe psoriasis; (intervention and control) studies had to test ETN vs. placebo; and (outcomes), studies had to report PROs including quality of life, pain, pruritus, or sleep. Only randomized controlled trials (RCT) were included. Two reviewers independently selected the articles and collected data. Studies quality was assessed using the Jadad score. For the meta-analysis, a random effects model was followed and statistical heterogeneity was tested with statistic I2. RESULTS: We finally included 12 RCT. Compared with placebo, ETN significantly improved quality of life, patient global assessment, pruritus and pain in the short and medium term, fatigue in the short term (although the effect size and differences with placebo are unclear). ETN also produces a high patient's satisfaction, which increases over time and is higher compared with placebo and might improve depressive symptoms in the long term. CONCLUSIONS: ETN is an effective option for improving PROs in patients with moderate-to-severe psoriasis.

[Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice]. / Diez años de experiencia con el primer biosimilar autorizado de hormona del crecimiento recombinante humana en la práctica clínica habitual.

INTRODUCTION: Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. MATERIALS AND METHODS: This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. RESULTS: The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. CONCLUSION: The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug.

Influenza vaccination in people with type 2 diabetes, coverage, predictors of uptake, and perceptions. Result of the MADIABETES cohort a 7years follow up study.

OBJECTIVES: We aim to determine influenza vaccination uptake among people with diabetes included in the MADIABETES cohort study in order to identify predictors of uptake and to analyze reasons for adherence and non-adherence with vaccination. METHODS: Using data from the MADIABETES Study we conducted a retrospective case record form based study without controls. We included outpatients with type 2 diabetes mellitus. Information was obtained from computerized clinical records and by telephone survey. The main dependent variables were influenza vaccination uptake in the year 2013 and the reason for receiving or refusing vaccination. RESULTS: Overall, 65.7% had received the influenza vaccine in 2013. The mean number of influenza vaccines received from 2007 to 2013 was 3.24 (SD1.15), although 19.23% had not received any influenza vaccine and 23.3% had been vaccinated against pneumococcus. The variables that increased the probability of being vaccinated were inclusion in the age-based recommendation (⩾60years), having a chronic respiratory disease, previous pneumococcal vaccination, higher number of visits to the general practitioner, higher number of influenza vaccines, and longer time since diabetes diagnosis. A higher mean glycated haemoglobin value in 2013 was associated with a reduced probability of vaccination. Most patients (90%) agreed to be vaccinated following their physician's advice because of their age or their chronic conditions. The most common reason for refusal among men was the belief that they were not at risk (41.6% vs. 29.79% in women); the most common reason for refusal among women was fear of adverse reactions (32.53% vs. 20.23% in men). CONCLUSIONS: The uptake of influenza vaccination among diabetic patients in the present study was below desirable levels. The main barrier to vaccination was lack of knowledge regarding the need for and risks and advantages of influenza vaccination. Healthcare professionals should educate and encourage influenza vaccination among people with diabetes.

Cardiovascular and all-cause mortality in patients with type 2 diabetes mellitus in the MADIABETES Cohort Study: Association with chronic kidney disease.

AIMS: To assess the prevalence of stage 3-5 chronic kidney disease (CKD) at baseline and to identify associated risk factors. To determine the effect of CKD and CKD stage according to estimated glomerular filtration rate (eGFR) and albuminuria categories on all-cause and cardiovascular mortality after a 5-year follow-up. METHODS: Prospective cohort study of 3443 outpatients with type 2 diabetes mellitus. RESULTS: The prevalence of CKD was 28.32% (95% CI, 26.84-29.86); and variables most strongly associated were: age >74 years (OR, 19.88; 95% CI, 12.89-30.68) and albuminuria (OR, 2.27; 95% CI, 1.72-3.00). During follow-up, 221 CKD patients (22.90%) died compared with 203 non-CKD patients (8.31%) (p<0.01). The adjusted HR of CKD for cardiovascular and all-cause mortality was 1.82 (95% CI, 1.36-2.44) and 2.11 (95% CI, 1.61-2.76) for those with LDL cholesterol =135 mg/dl, respectively. The adjusted HR of very-high-risk CKD for all-cause mortality was 4.44 (95% CI, 2.31-8.53) in aged <75 years and 1.80 (95% CI, 1.19-2.72) in aged ≥75 years. CONCLUSIONS: CKD at baseline is an independent risk factor for all-cause and cardiovascular mortality in the overall cohort, men and women, or in primary and secondary prevention of coronary heart disease. Albuminuria is an independent risk factor for all-cause and cardiovascular mortality only in primary prevention.

A follow-up study to monitor adult height among Spanish children with growth hormone deficiency who received biosimilar human recombinant growth hormone (Omnitrope®) during a phase III clinical trial.

INTRODUCTION: An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope(®), Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on treatment (as in usual clinical practice), and continued to be monitored. The aim of this study was to determine the adult height achieved by the Spanish children who participated in the initial Phase III clinical trial, and to evaluate the long-term safety of rhGH treatment. METHODS: This study was a multicenter, observational, retrospective follow-up study of patients who participated in the Phase III clinical trial (70 patients recruited). Auxological parameters [including height, height velocity, and their associated height standard deviation scores (HSDS)] were obtained from 39 patients. Safety was assessed by recording any adverse events (AEs). RESULTS: In total, 27 men and 12 women provided auxological data. At the start of the follow-up study, the mean age of the patients was 12.5 ± 2.7 years, mean height was 144.8 ± 13.9 cm and mean HSDS was -1.16 ± 0.63. By the end of the follow-up period, mean height had increased to 163.1 ± 7.6 cm (n = 36; men 165.5 ± 7.8 cm, women 157.6 ± 3.2 cm) and mean HSDS also increased to -1.01 ± 0.59 (n = 36; men -1.07 ± 0.52, women -0.86 ± 0.72). In terms of safety, no treatment-related AEs were reported during the study. CONCLUSION: This cohort of Spanish patients with GHD showed a positive response to rhGH treatment, achieving adult height within the local normal ranges. In addition, rhGH treatment was well tolerated, with no new or additional safety concerns.

Five-year incidence of chronic kidney disease (stage 3-5) and associated risk factors in a Spanish cohort: the MADIABETES Study.

OBJECTIVE: To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m2) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use. DESIGN: The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain). RESULTS: The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12-11.44) and the incidence density was 2.07 (95% CI = 1.83-2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19-2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥ 300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13-4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42-2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25-2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30-2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02-2.24). CONCLUSIONS: After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.

Leptin as a marker of nutrition and cardiovascular risk in peritoneal dialysis patients.

Anorexia and protein malnutrition, occasionally associated with obesity, are frequently observed in peritoneal dialysis (PD) patients. Both are recognized risk factors for cardiovascular (CV) morbidity and mortality. Leptin is produced by adipocytes and regulates body-fat mass through a satiety central effect. Leptin accumulates in the uremic state. We analyzed the relationship between plasma leptin levels, nutritional status, obesity, CV risk factors, and atherosclerosis in PD patients. Leptin was determined using a polyclonal antibody [radioimmunoassay: Linco Research, St. Louis, MO, U.S.A.]. The normal range was 1-7.8 ng/mL. We studied 38 PD patients. Mean leptin levels were 59.1 +/- 57.5 ng/mL (elevated in 32 patients). Women (n = 21) showed higher leptin levels than did men (80.4 +/- 60 ng/mL vs. 32.3 +/- 43.3 ng/mL, p < 0.01), in spite of both groups having a similar body mass index (BMI). A statistically significant direct correlation was found between leptin and BMI (r = 0.7, p < 0.01) and triceps skin-fold measurement (r = 0.77, p < 0.01). Leptin levels and renal creatinine clearance (CCr) showed no significant correlation. Independent of BMI, higher leptin levels were associated with parameters considered to be CV risk factors (Framingham study), such as serum triglycerides < 150 mg/dL (n = 29) as compared with > 150 mg/dL (44.2 +/- 53.2 ng/mL vs. 80 +/- 58.4 ng/mL, p < 0.05), cholesterol < 250 mg/dL (n = 28) as compared with > 250 mg/dL, (50 +/- 55.6 mg/dL vs. 84.7 +/- 57.7 mg/dL, p < 0.05), uric acid < 7 mg/dL (n = 28) as compared with > 7 mg/dL (47 +/- 53.7 mg/dL vs. 93.1 +/- 56.6 mg/dL, p < 0.05), and the presence or lack of presence of left ventricular hypertrophy [68.8 +/- 60 (n = 30) vs. 29.5 +/- 23.7 (n = 5), p < 0.05]. The patients were classified into two groups according to a clinical atherosclerosis score (CAS). Nineteen patients had low CAS scores, and they showed higher plasma leptin values than did the other patients (82.4 +/- 65.7 ng/mL vs 35.8 +/- 36.6 ng/mL, p < 0.05). Twelve patients with anorexia had lower leptin values than did patients with normal appetite (19.2 +/- 15.8 ng/mL vs. 91.3 +/- 58.8 ng/mL, p < 0.001). In non obese patients (BMI < 25 and CCr < 3 mL/min, n = 14), leptin had a statistically significant direct linear correlation with markers of nutrition, including albumin (r = 0.63, p < 0.05), transferrin (r = 0.4, p < 0.05), cholesterol (r = 0.65, p < 0.05), and triglycerides (r = 0.6, p < 0.05). Finally, plasma leptin levels were notably increased in the PD population, indicating increased production (possibly by chronic hyperinsulinism), or uremic retention, or both. By multivariate analysis, we confirmed the association between leptin levels and sex, leptin and BMI, and leptin levels > 40 ng/mL and sex and LVH. All of those features suggest that plasma leptin levels could be considered a marker of CV risk and food intake in non obese PD patients without inflammation.

True deficiency of antioxidant vitamins E and A in dialysis patients. Relationship with clinical patterns of atherosclerosis.

Atherosclerosis is an important cause of morbidity and mortality in peritoneal dialysis (PD) patients. Oxidative stress plays a role in the pathogenesis of uremic atherosclerosis. Although antioxidant substances (vitamins A and E) are elevated in the plasma of dialysis patients, intracellular and clinical signs of hypovitaminosis are frequently found. Recently, the importance of vitamin/carrier complexes as a marker of vitamin bioavailability has been demonstrated. In the present study, we analyzed vitamin A and E bioavailability, measured as vitamin/carrier complexes, and the relationship of those measurements with clinical atherosclerosis status in PD patients. We studied 45 patients (15 men, 30 women), who were divided into four groups according to clinical atherosclerotic score (CAS). Five cases were scored as CAS grade 1 (low CAS); 9 as CAS-2; 18 as CAS-3; and 13 as CAS-4. Vitamins A and E and their carriers [prealbumin and retinol binding protein (vitamin A), and cholesterol and triglycerides (vitamin E)] were determined. Plasma levels of vitamin A were low in 5 patients, normal in 7 patients, and high in 33 patients. By correcting the values for the carrier levels, we created three groups: 24 patients showed low vitamin A/carrier complex (5 from the low plasma vitamin A group, 6 from the normal-value group, and 13 from the high-value group); 11 patients were in the group with normal vitamin A/carrier (1 from the normal plasma vitamin A group, and 10 from the high-value group); and 10 patients were in the group with high vitamin A/carrier. The vitamin A/carrier complex showed a statistically significant, negative linear correlation with CAS and with serum iron. Low vitamin E plasma levels were found in 1 patient, normal levels in 28 patients, and high levels in 16 patients. When those values were corrected using the carrier values, three groups were also created. The group with low vitamin E/carrier complex contained 24 patients (1 from the low-value group, 22 from the normal-value group, and 1 from the high-value group). The group with normal vitamin E/carrier complex contained 21 patients (15 from the group with high vitamin E values, and 6 from the normal-value group). By univariate logistic regression analysis, significant associations between CAS and vitamin E plasma levels, vitamin E/carrier, age, and serum albumin were found. In the multiple logistic regression analysis, we confirmed that vitamin E/carrier complex, age, and serum albumin showed independent associations with CAS, but not with vitamin-only plasma levels. Our results in PD patients show a vitamin/carrier complex disorder that results in elevated vitamin mobilization from pool and target cells. Our results and the findings of other researchers about intracellular vitamin A and E deficiencies may change the traditional concept of hypervitaminosis A and E in uremic patients.

Four-year incidence of diabetic retinopathy in a Spanish cohort: the MADIABETES study.

OBJECTIVE: To evaluate the incidence of diabetic retinopathy in patients with Type 2 Diabetes Mellitus, to identify the risk factors associated with the incidence of retinopathy and to develop a risk table to predict four-year retinopathy risk stratification for clinical use, from a four-year cohort study. DESIGN: The MADIABETES Study is a prospective cohort study of 3,443 outpatients with Type 2 Diabetes Mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain). RESULTS: The cumulative incidence of retinopathy at four-year follow-up was 8.07% (95% CI = 7.04-9.22) and the incidence density was 2.03 (95% CI = 1.75-2.33) cases per 1000 patient-months or 2.43 (95% CI = 2.10-2.80) cases per 100 patient-years. The highest adjusted hazard ratios of associated risk factors for incidence of diabetic retinopathy were LDL-C >190 mg/dl (HR = 7.91; 95% CI = 3.39-18.47), duration of diabetes longer than 22 years (HR = 2.00; 95% CI = 1.18-3.39), HbA1c>8% (HR = 1.90; 95% CI = 1.30-2.77), and aspirin use (HR = 1.65; 95% CI = 1.22-2.24). Microalbuminuria (HR = 1.17; 95% CI = 0.75-1.82) and being female (HR = 1.12; 95% CI = 0.84-1.49) showed a non-significant increase of diabetic retinopathy. The greatest risk is observed in females who had diabetes for more than 22 years, with microalbuminuria, HbA1c>8%, hypertension, LDL-Cholesterol >190 mg/dl and aspirin use. CONCLUSIONS: After a four-year follow-up, the cumulative incidence of retinopathy was relatively low in comparison with other studies. Higher baseline HbA1c, aspirin use, higher LDL-Cholesterol levels, and longer duration of diabetes were the only statistically significant risk factors found for diabetic retinopathy incidence. This is the first study to demonstrate an association between aspirin use and diabetic retinopathy risk in a well-defined cohort of patients with Type 2 Diabetes Mellitus at low risk of cardiovascular events. However, further studies with patients at high cardiovascular and metabolic risk are needed to clarify this issue.