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In immunoglobulin A nephropathy (IgAN), the abnormal expression of intercellular adhesion molecule-1 (ICAM-1) on proximal tubule epithelium is associated with the glomerular and interstitial infiltration of leucocytes, but its clinical significance remains uncertain. We analysed the relationship between the ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes, macrophages (CD14) and T lymphocytes (CD3) with the histologic features, proteinuria and serum creatinine at the time of renal biopsy and after 2.42 years in 45 patients with IgAN and after 1.8+/-1.5 years in 29 patients with non-glomerulonephritis (non-GN). In IgAN, ICAM-1+ tubule epithelium was 0.1+/-0.18 (x+/-SD), and this was associated with extracapillary proliferation (up to 20% of Bowman's space), glomerular sclerosis involving less than 50% of glomerular area, interstitial cellular infiltration, tubular atrophy and proteinuria level. ICAM-1+ interstitial leucocytes were correlated with glomerular sclerosis involving less than 50% of glomerular area, glomerular sclerosis involving more than 50% of glomerular area, tubular atrophy, interstitial fibrosis and serum creatinine level. In patients with an increase of 50% in serum creatinine, ICAM-1+, CD14+ and CD3+, interstitial leucocytes were significantly outnumbered than in patients with stable serum creatinine. In non-GN, ICAM-1+ tubule epithelium was 0.02+/-0.04 (U=344, P<0.05, vs IgAN), and this was inversely correlated with the percentage of the normal glomeruli and associated with glomerular sclerosis covering more than 50% of glomerular area, tubular atrophy and serum creatinine level. The association between tubular ICAM-1 and proteinuria and the association between interstitial ICAM-1+, CD14+ and CD3+, leucocytes and renal failure at presentation and the deterioration in IgAN in contrast with non-GN suggest that tubular and interstitial expression of ICAM-1 may be a marker of tubulointerstitial disturbance in IgAN. [ABSTRACT FROM AUTHOR]

Abstract Background The objective was to study the seasonal effect on the spatial distribution of the incidence of malaria in children under 10 years old living in the Manhiça district, Mozambique. Methods The data of the clinical malaria incidence were obtained from a study of two cohorts of children followed from December 1996 to July 1999. The cases were obtained by the active detection method. Hierarchical Bayesian models were used to model the incidence of malaria, including spatial correlation nested to climatic season. The models were compared with the deviance information criterion. The age and gender of the children were also taken into account. Results The incidence of malaria is associated with age, period and climate season. The incidence presents a clear spatial pattern, with a higher incidence in the neighbourhoods situated in the north and northeast of the Manhiça area. The transmission of malaria is highest during the wet season but the spatial pattern of malaria does not differ from that during the dry season. Conclusion The incidence of malaria in Manhiça presents a spatial pattern which is independent of the seasonal climatic conditions. The climate modifies the incidence of malaria in the entire region but does not change the spatial pattern of the incidence of this disease. These findings may be useful for the planning of malaria control activities. These activities can be performed taking account that the neighbourhoods with more incidence of malaria do not change over the annual climate seasons.

Background: This study evaluated the clinical outcomes of applying a 68 Gy EQD2 (α/β=3) dose constraint to the most exposed 2 cm 3 area of the vagina in post-operative endometrial cancer patients treated with vaginal-cuff brachytherapy after external beam irradiation and the impact of vaginal dilator use on late vaginal complications., Material and Methods: We analyzed 131 patients treated with vaginal-cuff brachytherapy after external beam irradiation. Group-1 (65 patients) received one fraction of 7 Gy, and Group-2 (66 patients) received one fraction of between 5.5 and 7.0 Gy after applying a 68 Gy EQD2 (α/β=3) dose constraint. Vaginal-cuff relapse, late toxicity, clinical target volume, vaginal dilator use, D90, and EQD2 (α/β=3) at 2 cm 3 of the most exposed part of the clinical target volume were evaluated. Descriptive analysis, the chi-squared test, Student's t -test, and the Cox proportional and Kaplan-Meier models were used for the statistical analysis., Results: With a median follow-up of 60 months, the vaginal-cuff relapse rate was 1/131 (0.8%). Late vaginal complications appeared in 36/65 (55.4%) Group-1 patients and 17/66 (25.8%) Group-2 patients ( p = 0.003). Multivariate analysis showed that belonging to Group-1 and vaginal dilator use of <9 months were independent prognostic factors of late vaginal complications with hazard ratios of 1.99 ( p = 0.021) and 3.07 ( p = 0.010), respectively., Conclusions: A 68 Gy EQD2 (α/β=3) constraint at 2 cm 3 of clinical target volume and vaginal dilator use of ≥9 months were independent prognostic factors, having protective effects on late vaginal complications.

Background: Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR., Methods: We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8-12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus., Results: Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8-28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3-9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9-20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1-13.3)., Conclusions: The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions., (© International Society of Travel Medicine 2024. Published by Oxford University Press.)

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in β-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption., (© 2024. The Author(s).)

(1) Background: High dose gradients and manual steps in brachytherapy treatment procedures can lead to dose errors which make the use of in vivo dosimetry (IVD) highly recommended for verifying brachytherapy treatments. A new procedure was presented to obtain a calibration factor which allows fast and robust calibration of plastic scintillation detector (PSD) probes for the geometry of a compact phantom using Monte Carlo simulations. Additionally, characterization of PSD energy, angular, and temperature dependences was performed. (2) Methods: PENELOPE/PenEasy code was used to obtain the calibration factor. To characterize the energy dependence of the PSD, the signal was measured at different radial and transversal distances. The sensitivity to the angular position was characterized in axial and azimuthal planes. (3) Results: The calibration factor obtained allows for an absorbed dose to water determination in full scatter conditions from ionization measured in a mini polymethylmethacrylate (PMMA) phantom. The energy dependence of the PSD along the radial distances obtained was (2.3 ± 2.1)% ( k = 1). The azimuthal angular dependence measured was (2.6 ± 3.4)% ( k = 1). The PSD response decreased by (0.19 ± 0.02)%/°C with increasing detector probe temperature. (4) Conclusions: The energy, angular, and temperature dependence of a PSD is compatible with IVD.

Objective: To explore the perceptions and experiences of health professionals who participated in a multicomponent program for fibromyalgia (FM) patients based on health education, physical exercise and cognitive-behavioral therapy., Methods: In this qualitative, descriptive study that was based on a pragmatic and utilitarian approach, we conducted two focus groups (FGs) with 12 professionals (nurses and general practitioners) from the primary healthcare system of Spain who had been trained as FM experts. A thematic content analysis was carried out., Results: The findings were organized into four key domains, each with explanatory emerging themes. Overall, the professionals positively valued the program for the knowledge gain it offered, its integrated approach, the group effect and other benefits to patients. Work overload and peers' lack of acknowledgement of the program's value were identified as barriers. A reduction in the amount of content in each session, the creation of quality-of-care indicators and the promotion of the new professional role (FM expert) were proposed., Conclusions: The FM experts supported the program and recognized its usefulness. To implement the program within the primary healthcare system, the program needs to be adjusted to accommodate professionals' and patients' reality, and institutional health policies must be improved by providing training on FM to the healthcare community.

Purpose: To compare two vaginal brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) patients considering vaginal-cuff relapses (VCR), late toxicities, dosimetry analysis and vaginal dilator use., Material and Methods: 110 PEC patients were treated with exclusive high-dose-rate VBT using two schedules. Group-1:44-patients received 6 Gy×3fractions (September-2011-April-2014); Group-2:66-patients were treated with 7.5 Gy×2fractions with a dose limit of equivalent total doses in 2-Gy fr (EQD2 (α/β=3) ) of 68 Gy in the most exposed 2 cm 3 of clinical target volume (CTV) (July-2015-November-2021). The dose was prescribed at 5 mm from the applicator surface. Were evaluated the overall radiation dose delivered to 90% of the CTV (D90), the CTV receiving 100% of the prescription dose (V100) and the EQD2 (α/β=3) received in the most exposed 2 cm 3 to dose in CTV. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum and objective LENT-SOMA criteria for late vaginal toxicity (LVT)., Statistics: Descriptive analysis, Chi-square, Student's t-tests and Kaplan and Meier method., Results: The median follow-up was 60 months (15.9-60). There were no VCR or late toxicities in bladder or rectum. LVT ≥ G1 appeared in 26/44 (59.1%) in Group-1 and 25/66 (37.9%) in Group-2. The mean EQD2 (α/β=3) received by the most exposed 2 cm 3 of CTV was 63.7 Gy ± 10.0 in Group-1 and 60.5 Gy ± 3.8 in Group-2 (p = 0.063). There were no differences in adherence to vaginal dilator use ≥9 months, overall D90 and V100., Conclusion: Considering the lack of vaginal relapses and similar LVT over time, 7.5 Gy×2fractions seem more efficient in terms of patient comfort, workload, and cost. This is the first study using dosimetry parameters to compare effectivity of schedules. Larger series are needed to confirm the present results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Analyse the impact of different prognostic factors on G2-late vaginal complications after vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) in postoperative endometrial cancer (PEC)., Methods: One hundred and twenty-six PEC patients treated with VBT ± EBRT were retrospectively analysed considering age, body mass index, applicator diameter, clinical target volume (CTV), use of dilators, chemotherapy and EQD2 (α/β=3) at the most exposed 2 cm 3 of the CTV as prognostic factors for vaginal complications. Late vaginal complications were evaluated using objective LENT-SOMA criteria., Statistics: descriptive analysis, Chi-square, Fisher and Student tests were applied. Univariate and multivariate analyses were performed with the Baptista-Pike exact method and multiple logistic regression., Results: Mean age was 65 years (SD ± 10), and median follow-up was 66 months (8-104). 19/126 patients (15%) showed G2-late vaginal complications, and 107/126 (85%) G0-G1. Univariate analysis showed: CTV ≤ 9 cm 3 (p = 0.036), use of dilators < 9 months (p = 0.015), and total ≥ 68 Gy EQD2 received by 2 cm 3 of CTV (p = 0.039) were associated with G2-late vaginal toxicity. Multivariate analysis showed the use of dilators < 9 months as an independent prognostic factor for G2-late vaginal toxicity (p = 0.043, OR 8.59, CI 1.59-159.9)., Conclusion: The use of dilators < 9 months in VBT ± EBRT for PEC was an independent prognostic factor for G2-late vaginal toxicity. The use of vaginal dilators ≥ 9 months requires further analysis in studies evaluating late vaginal toxicity., (© 2023. The Author(s).)

(1) Background: In brachytherapy, there are still many manual procedures that can cause adverse events which can be detected with in vivo dosimetry systems. Plastic scintillator dosimeters (PSD) have interesting properties to achieve this objective such as real-time reading, linearity, repeatability, and small size to fit inside brachytherapy catheters. The purpose of this study was to evaluate the performance of a PSD in postoperative endometrial brachytherapy in terms of source dwell time accuracy. (2) Methods: Measurements were carried out in a PMMA phantom to characterise the PSD. Patient measurements in 121 dwell positions were analysed to obtain the differences between planned and measured dwell times. (3) Results: The repeatability test showed a relative standard deviation below 1% for the measured dwell times. The relative standard deviation of the PSD sensitivity with accumulated absorbed dose was lower than 1.2%. The equipment operated linearly in total counts with respect to absorbed dose and also in count rate versus absorbed dose rate. The mean (standard deviation) of the absolute differences between planned and measured dwell times in patient treatments was 0.0 (0.2) seconds. (4) Conclusions: The PSD system is useful as a quality assurance tool for brachytherapy treatments.

Objective: To create an electronic frailty index (eFRAGICAP) using electronic health records (EHR) in Catalunya (Spain) and assess its predictive validity with a two-year follow-up of the outcomes: homecare need, institutionalization and mortality in the elderly. Additionally, to assess its concurrent validity compared to other standardized measures: the Clinical Frailty Scale (CFS) and the Risk Instrument for Screening in the Community (RISC)., Methods: The eFRAGICAP was based on the electronic frailty index (eFI) developed in United Kingdom, and includes 36 deficits identified through clinical diagnoses, prescriptions, physical examinations, and questionnaires registered in the EHR of primary health care centres (PHC). All subjects > 65 assigned to a PHC in Barcelona on 1st January, 2016 were included. Subjects were classified according to their eFRAGICAP index as: fit, mild, moderate or severe frailty. Predictive validity was assessed comparing results with the following outcomes: institutionalization, homecare need, and mortality at 24 months. Concurrent validation of the eFRAGICAP was performed with a sample of subjects (n = 333) drawn from the global cohort and the CFS and RISC. Discrimination and calibration measures for the outcomes of institutionalization, homecare need, and mortality and frailty scales were calculated., Results: 253,684 subjects had their eFRAGICAP index calculated. Mean age was 76.3 years (59.5% women). Of these, 41.1% were classified as fit, and 32.2% as presenting mild, 18.7% moderate, and 7.9% severe frailty. The mean age of the subjects included in the validation subsample (n = 333) was 79.9 years (57.7% women). Of these, 12.6% were classified as fit, and 31.5% presented mild, 39.6% moderate, and 16.2% severe frailty. Regarding the outcome analyses, the eFRAGICAP was good in the detection of subjects who were institutionalized, required homecare assistance, or died at 24 months (c-statistic of 0.841, 0.853, and 0.803, respectively). eFRAGICAP was also good in the detection of frail subjects compared to the CFS (AUC 0.821) and the RISC (AUC 0.848)., Conclusion: The eFRAGICAP has a good discriminative capacity to identify frail subjects compared to other frailty scales and predictive outcomes., (© 2022. The Author(s).)

Background: Information regarding short-term vital prognosis in patients with heart failure at advanced stages of the disease is scarce. Objective: To develop a three-month mortality predictive model for patients with advanced heart failure. Methods: Prospective observational study carried out in primary care and a convalescence community facility. Heart failure patients either New York Heart Association (NYHA) III with at least two HF hospitalizations during the previous six months or NYHA IV with/without previous recent hospitalization were included in the study. Multivariable predictive models using Cox regression were performed. Results: Of 271 patients included, 55 (20.3%) died during the first three months of follow-up. Mean age was 84.2 years (SD 8.3) and 59.8% were women. Predictive model including NT-proBNP had a C-index of 0.78 (95% CI 0.71; 0.85) and identified male gender, low body mass index, high potassium and NT-proBNP levels, and moderate-to-severe dependence for daily living activities (Barthel index < 40) as risk factors of mortality. In the model without NT-proBNP, C index was 0.72 (95% CI 0.64; 0.79) and, in addition to gender, body mass index, low Barthel index, and severe reductions in glomerular filtration rate showed the highest predictive hazard ratios for short-term mortality. Conclusions: In addition to age, male gender, potassium levels, low body mass index, and low glomerular filtration, dependence for activities of daily living add strong power to predict mortality at three months in patients with advanced heart failure.

Aims: Because evidence regarding risk stratification predicting prognosis of patients with heart failure (HF) decompensation attended in primary care is lacking, we developed and externally validated a model to forecast death/hospitalization during the first 30 days after an episode of decompensation. The predictive model is based on variables easily obtained in primary care settings., Methods and Results: HEFESTOS is a multinational study consisting of a derivation cohort of HF patients recruited in 14 primary healthcare centres in Barcelona and a validation cohort from primary healthcare in 9 other European countries. The derivation and validation cohorts included 561 and 250 patients, respectively. Percentages of women in the derivation and validation cohorts were 56.3% and 47.6% (P = 0.026), respectively. Mean age was 82.2 years (SD 8.03) in the derivation cohort, and 79.3 years (SD 10.3) in the validation one (P = 0.001). HF with preserved ejection fraction represented 72.1% in the derivation cohort and 58.8% in the validation one (P = 0.004). Mortality/hospitalization during the first 30 days after a decompensation episode was 30.5% and 26% (P = 0.225) for the derivation and validation cohorts, respectively. Multivariable logistic regression models were performed to develop a score of risk. The identified predictors were worsening of dyspnoea [odds ratio (OR): 2.5; P = 0.001], orthopnoea (OR: 2.16; P = 0.01), paroxysmal nocturnal dyspnoea (OR: 2.25; P = 0.01), crackles (OR: 2.35; P = 0.01), New York Heart Association functional class III/IV (OR: 2.11; P = 0.001), oxygen saturation ≤ 90% (OR: 4.98; P < 0.001), heart rate > 100 b.p.m. (OR: 2.72; P = 0.002), and previous hospitalization due to HF (OR: 2.45; P < 0.001). The model showed an area under the curve (AUC) of 0.807, 95% confidence interval (CI): [0.770; 0.845] in the derivation cohort and AUC 0.73, 95% CI: [0.660; 0.808] in the validation one. No significant differences between both cohorts were observed (P = 0.08). Regarding probability of hospitalization/death, three risk groups were defined: low <5%, medium 5-20%, and high >20%. Outcome incidence was 2.7% for the low-risk group, 12.8% for medium risk, and 46.2% for high risk in the derivation cohort, and 9.1%, 12.9%, and 39.6% in the validation one., Conclusions: The HEFESTOS score, based on variables easily accessible in a community setting and validated in an external European cohort, properly predicted the risk of death/hospitalization during the first 30 days after an HF decompensation episode., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Several scores to identify patients at high risk of suffering atrial fibrillation have been developed. Their applicability in hypertensive diabetic patients, however, remains uncertain. Our aim is to develop and validate a diagnostic predictive model to calculate the risk of developing atrial fibrillation at five years in a hypertensive diabetic population., Methods: The derivation cohort consisted of patients with both hypertension and diabetes attended in any of the 52 primary healthcare centres of Barcelona; the validation cohort came from the 11 primary healthcare centres of Terres de l'Ebre (Catalonia South) from January 2013 to December 2017. Multivariable Cox regression identified clinical risk factors associated with the development of atrial fibrillation. The overall performance, discrimination and calibration of the model were carried out., Results: The derivation data set comprised 54 575 patients. The atrial fibrillation rate incidence was 15.3 per 1000 person/year. A 5-year predictive model included age, male gender, overweight, heart failure, valvular heart disease, peripheral vascular disease, chronic kidney disease, number of antihypertensive drugs, systolic and diastolic blood pressure, heart rate, thromboembolism, stroke and previous history of myocardial infarction. The discrimination of the model was good (c-index = 0.692; 95% confidence interval, 0.684-0.700), and calibration was adequate. In the validation cohort, the discrimination was lower (c-index = 0.670)., Conclusions: The model accurately predicts future atrial fibrillation in a population with both diabetes and hypertension. Early detection allows the prevention of possible complications arising from this disease., (© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.

Objective: To evaluate the precipitating factors for heart failure decompensation in primary care and associations with short-term prognosis. Design Prospective cohort study with a 30-d follow-up from an index consultation. Regression models to determine independent factors associated with hospitalisation or death., Setting: Primary care in ten European countries. Patients Patients with diagnosis of heart failure attended in primary care for a heart failure decompensation (increase of dyspnoea, unexplained weight gain or peripheral oedema)., Main Outcome Measures: Potential precipitating factors for decompensation of heart failure and their association with the event of hospitalisation or mortality 30 d after a decompensation., Results: Of 692 patients 54% were women, mean age 81 (standard deviation [SD] 8.9) years; mean left ventricular ejection fraction (LVEF) 55% (SD 12%). Most frequently identified heart failure precipitation factors were respiratory infections in 194 patients (28%), non-compliance of dietary recommendations in 184 (27%) and non-compliance with pharmacological treatment in 157 (23%). The two strongest precipitating factors to predict 30 d hospitalisation or death were respiratory infections (odds ratio [OR] 2.8, 95% confidence interval [CI] (2.4-3.4)) and atrial fibrillation (AF) > 110 beats/min (OR 2.2, CI 1.5-3.2). Multivariate analysis confirmed the association between the following variables and hospitalisation/death: In relation to precipitating factors: respiratory infection (OR 1.19, 95% CI 1.14-1.25) and AF with heart rate > 110 beats/min (OR 1.22, 95% CI 1.10-1.35); and regarding patient characteristics: New York Heart Association (NYHA) III or IV (OR 1.22, 95% CI 1.15-1.29); previous hospitalisation (OR 1.15, 95% CI 1.11-1.19); and LVEF < 40% (OR 1.14, 95% CI 1.09-1.19)., Conclusions: In primary care, respiratory infections and rapid AF are the most important precipitating factors for hospitalisation and death within 30 d following an episode of heart failure decompensation. Key points Hospitalisation due to heart failure decompensation represents the highest share of healthcare costs for this disease. So far, no primary care studies have analysed the relationship between precipitating factors and short term prognosis of heart failure decompensation episodes. We found that in 692 patients with heart failure decompensation in primary care, the respiratory infection and rapid atrial fibrillation (AF) increased the risk of short-term hospital admission or death. Patients with a hospital admission the previous year and a decompensation episode caused by respiratory infection were even more likely to be hospitalized or die within 30 d.

Objectives: This study is aimed at analyzing the impact of the main factors contributing to short and long-term mortality in patients at final stages of heart failure (HF)., Setting: Patients attended at any of the 279 primary health care centers belonging to the Institut Català de la Salut, in Catalonia (Spain)., Participants: Patients with Advanced HF., Design: Multicenter cohort study including 1148 HF patients followed for one-year after reaching New York Heart Association (NYHA) IV., Main Measurements: The primary outcome was all-cause mortality. Multivariate logistic regression models were performed to assess the outcomes at 1, 3, 6, and 12 months., Results: Mean age of patients was 82 (SD 9) years and women represented 61.7%. A total of 135 (11.8%) and 397 (34.6%) patients died three months and one year after inclusion, respectively. Male gender, age, and decreased body mass index were associated with higher mortality at three, six and twelve months. In addition, low systolic blood pressure levels, severe reduction in glomerular filtration, malignancy, and higher doses of loop diuretics were related to higher mortality from 6 to 12 months. The most important risk factor over the whole period was presenting a body mass index lower than 20kg/m 2 (three months OR 3.06, 95% CI: 1.58-5.92; six months OR 4.42, 95% CI: 2.08-9.38; and 12 months OR 3.68, 95% CI: 1.76-7.69)., Conclusions: We may conclude that male, age, and decreased body mass index determined higher short-term mortality in NYHA IV. In addition, low systolic blood pressure, reduced glomerular filtration, malignancy, and higher doses of loop diuretics contribute to increasing the risk of mortality at medium and long-term. Such variables are easily measurable and can help to decide the best way to face the most advances stages of the disease., (Copyright © 2019 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction and Objective: The optimal iron supplementation route of administration (intravenous vs oral) in patients with chronic kidney disease (CKD) not on dialysis is a hot topic of debate. An oral preparation (liposomal iron, FeSu) has recently been developed with high bioavailability and low incidence of side effects. The objective was to evaluate the efficacy of FeSu in patients with stage 3 CKD and gastrointestinal intolerance to conventional oral iron therapy., Material and Methods: Prospective observational study of patients with stable stage 3 CKD and gastrointestinal intolerance to conventional oral iron therapy. An oral 30mg/day dose of FeSu was administered for 12 months. The primary outcome measure was haemoglobin increase at 6 and 12 months. Treatment adherence and adverse effects were also evaluated., Results: 37 patients aged 72.6±14.7 years and with an estimated glomerular filtration rate (eGFR) of 42±10ml/min/1.73m 2 were included. 32 patients had received previous treatment with conventional oral formulations, 73% of which exhibited gastrointestinal intolerance with treatment adherence of 9.4%. After 6 months with FeSu, an increase in haemoglobin was observed versus baseline, which was sustained at 12 months (0.49±0.19 and 0.36±0.19g/dl, respectively, P<.05), despite a significant eGFR decrease of 3.16±1.16 and 4.20±1.28ml/min/1.73 m 2 at 6 and 12 months, respectively. None of the patients experienced adverse reactions that required the treatment to be suspended. Adherence was 100% at both 6 and 12 months., Conclusions: FeSu is effective in a cohort of patients with stage 3 CKD with similar characteristics to the general population of moderate CKD patients, with a low rate of adverse reactions and excellent tolerability., (Copyright © 2019. Published by Elsevier España, S.L.U.)

Dientamoeba fragilis is a trichomonad parasite of the human intestine that is found worldwide. However, the biological cycle and transmission of this parasite have yet to be elucidated. Although its pathogenic capacity has been questioned, there is increasing evidence that clinical manifestations vary greatly. Different therapeutic options with antiparasitic drugs are currently available; however, very few studies have compared the effectiveness of these drugs. In the present longitudinal study, we evaluate 13,983 copro-parasitological studies using light microscopy of stools, during 2013-2015, in Terrassa, Barcelona (Spain). A total of 1150 (8.2%) presented D. fragilis. Of these, 739 episodes were finally analyzed: those that involved a follow-up parasitology test up to 3 months later, corresponding to 586 patients with gastrointestinal symptoms (53% under 15 years of age). Coinfection by Blastocystis hominis was present in 33.6% of the subjects. Our aim was to compare therapeutic responses to different antiparasitic drugs and the factors associated with the persistence of D. fragilis post-treatment. Gender, age, and other intestinal parasitic coinfections were not associated with parasite persistence following treatment. Metronidazole was the therapeutic option in most cases, followed by paromomycin: 65.4% and 17.5% respectively. Paromomycin was found to be more effective at eradicating parasitic infection than metronidazole (81.8% vs. 65.4%; p = 0.007), except in children under six years of age (p = 0.538). Although Dientamoeba fragilis mainly produces mild clinical manifestations, the high burden of infection means we require better understanding of its epidemiological cycle and pathogenicity, as well as adequate therapeutic guidelines in order to adapt medical care and policies to respond to this health problem., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Fibromyalgia (FM) is a chronic condition characterized by chronic pain, fatigue and loss of function which significantly impairs quality of life. Although treatment of FM remains disputed, some studies point at the efficacy of interdisciplinary therapy. This study aims to analyze the effectiveness, cost-utility and benefits of a multicomponent therapy on quality of life (main variable), functional impact, mood and pain in people suffering from FM that attend primary care centers (PCCs) of the Catalan Institute of Health (ICS)., Methods and Analysis: A 2-phase, mixed methods study has been designed following Medical Research Council guidance. Phase 1: Pragmatic randomized clinical trial with patients diagnosed with FM that attend one of the 11 PCCs of the ICS Gerència Territorial Terres de l'Ebre. We estimate a total sample of 336 patients. The control group will receive usual clinical care, while the multicomponent therapy group (MT group) will receive usual clinical care plus group therapy (consisting of health education, exercise and cognitive-behavioural therapy) during 12 weeks in 2-hourly weekly sessions., Analysis: the standardized mean response and the standardized effect size will be assessed at 3, 9, and 15 months after the beginning of the study using multiple linear regression models. Utility measurements will be used for the economic analysis. Phase 2: Qualitative socio constructivist study to evaluate the intervention according to the results obtained and the opinions and experiences of participants (patients and professionals). We will use theoretical sampling, with 2 discussion groups of participants in the multicomponent therapy and 2 discussion groups of professionals of different PCCs. A thematic content analysis will be carried out., Ethics and Dissemination: This study protocol has been approved by the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P18/068). Articles will be published in international, peer-reviewed scientific journals., Trial Registration: Clinical-Trials.gov: NCT04049006.

In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Toxocara canis Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91-1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children.

A logistic regression with random effects model is commonly applied to analyze clustered binary data, and every cluster is assumed to have a different proportion of success. However, it could be of interest to obtain the proportion of success over clusters (i.e. the marginal proportion of success). Furthermore, the degree of correlation among data of the same cluster (intraclass correlation) is also a relevant concept to assess, but when using logistic regression with random effects it is not possible to get an analytical expression of the estimators for marginal proportion and intraclass correlation. In our paper, we assess and compare approaches using different kinds of approximations: based on the logistic-normal mixed effects model (LN), linear mixed model (LMM), and generalized estimating equations (GEE). The comparisons are completed by using two real data examples and a simulation study. The results show the performance of the approaches strongly depends on the magnitude of the marginal proportion, the intraclass correlation, and the sample size. In general, the reliability of the approaches get worsen with low marginal proportion and large intraclass correlation. LMM and GEE approaches arises as reliable approaches when the sample size is large., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Heart failure (HF) is a chronic condition that usually leads to death a few years after diagnosis. Although several clinical factors have been found to be related to increased mortality, less is known about the impact of social context, especially at the end stage of the disease. Knowing about social context is important to properly classify risk and provide holistic management for patients with advanced HF., Objective: The aim of this study was to determine the impact of social context on mortality in patients with advanced HF., Methods: A retrospective cohort study was conducted using data from clinical records on community-dwelling patients with HF and with New York Heart Association IV functional class living in Catalonia in northeastern Spain. Clinical data, patient dependency for basic activities of daily living, and social assessments were collected between 2010 and 2013. The primary outcome was all-cause mortality., Results: Data from 1148 New York Heart Association class IV patients were analyzed. Mean (SD) age was 82 (9.0) years, and 61.7% were women. The mean (SD) follow-up was 18.2 (11.9) months. Mortality occurred in 592 patients. Social risk was identified in 63.6% of the patients, and 9.3% acknowledged having social problems. In the adjusted multivariate model, being male (hazard ratio (HR), 1.82; 95% confidence interval [CI], 1.16-2.83), having high dependency on others for basic activities of daily living (HR, 2.16; 95% CI, 1.21-3.85), and presenting with a social problem (HR, 2.46; 95% CI, 1.22-4.97) were related to an increased risk of mortality., Conclusions: An unfavorable social profile is an independent risk factor for mortality in patients with advanced HF.

Background: The impact of atrial fibrillation (AF) on mortality of patients with heart failure (HF) has been established. Nevertheless, the effect of some factors in mortality, such as digoxin or diuretic use, remains controversial. This study aims at assessing mortality in community-dwelling patients with stable HF related to AF and determines the relation of these drugs with prognosis., Materials and Methods: Community-based cohort study of HF patients diagnosed between January 2010 and December 2014 attended at any one of the 279 primary healthcare centres of the Catalan Institute of Health (Spain). Follow-up ended on December 31, 2015, and the main outcome was mortality for all causes. The effect of clinical and demographic characteristics on survival was assessed by Cox proportional hazards model., Results: A total of 13 334 HF patients were included. Mean age was 78.7 years (SD 10.1), and 36.8% had AF. Mean follow-up was 26.9 months (SD 14.0). At the end of the study, 25.8% patients had died, and mortality was higher when AF was present (28.8% vs 24.1%, P < 0.001, respectively). Multivariate model confirmed the higher risk of death for AF patients (HR 1.10 95%, CI 1.02-1.19). Digoxin and diuretics were not associated with higher mortality in AF patients (HR 1.04 95% CI 0.92-1.18 and HR 1.04 95% CI 0.85-1.26, respectively)., Conclusions: An excess of mortality in HF patients with AF was found in a large retrospective community-based cohort. Digoxin and diuretics did not affect mortality in HF patients with AF., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Information regarding the effect of social determinants of health on heart failure (HF) community-dwelling patients is scarce. We aimed to analyse the presence of socioeconomic inequalities, and their impact on hospitalisations and mortality, in patients with HF attended in a universal healthcare coverage system., Methods: A retrospective cohort study carried out in patients with HF aged >40 and attended at the 53 primary healthcare centres of the Institut Català de la Salut in Barcelona (Spain). Socioeconomic status (SES) was determined by an aggregated deprivation index (MEDEA). Cox proportional hazard models and competing-risks regression based on Fine and Gray's proportional subhazards were performed to analyse hospitalisations due to of HF and total mortality that occurred between 1 January 2009 and 31 December 2012., Results: Mean age was 78.1 years (SD 10.2) and 56% were women. Among the 8235 patients included, 19.4% died during the 4 years of follow-up and 27.1% were hospitalised due to HF. A gradient in the risk of hospitalisation was observed according to SES with the highest risk in the lowest socioeconomic group (sHR 1.46, 95% CI 1.27 to 1.68). Nevertheless, overall mortality did not differ among the socioeconomic groups., Conclusions: In spite of finding a gradient that linked socioeconomic deprivation to an increased risk of hospitalisation, there were no differences in mortality regarding SES in a universal healthcare coverage system., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Two key aims of diagnostic research are to accurately and precisely estimate disease prevalence and test sensitivity and specificity. Latent class models have been proposed that consider the correlation between subject measures determined by different tests in order to diagnose diseases for which gold standard tests are not available. In some clinical studies, several measures of the same subject are made with the same test under the same conditions (replicated measurements), and thus, replicated measurements for each subject are not independent. In the present study, we propose an extension of the Bayesian latent class Gaussian random effects model to fit the data with binary outcomes for tests with replicated subject measures. We describe an application using data collected on hookworm infection carried out in the municipality of Presidente Figueiredo, Amazonas State, Brazil. In addition, the performance of the proposed model was compared with that of current models (the subject random effects model and the conditional (in)dependent model) through a simulation study. As expected, the proposed model presented better accuracy and precision in the estimations of prevalence, sensitivity and specificity. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Introduction: For adequate disease control the World Health Organization has proposed the diagnosis and treatment of latent tuberculous infection (LTBI) in groups of risk of developing the disease such as children. There is no gold standard (GS) test for the diagnosis of LTBI. The objective of this study was to estimate the prevalence of LTBI in young children in contact with a household case of tuberculosis (TB-HCC) and determine the accuracy and precision of the Tuberculin Skin Test (TST) and QuantiFERON-TB Gold in-tube (QFT) used in the absence of a GS., Methods: We conducted a cross-sectional study in children up to 6 years of age in Manaus/Brazil during the years 2009-2010. All the children had been vaccinated with the BCG and were classified into two groups according to the presence of a TB-HCC or no known contact with tuberculosis (TB). The variables studied were: the TST and QFT results and the intensity and length of exposure to the index tuberculosis case. We used the latent class model to determine the prevalence of LTBI and the accuracy of the tests., Results: Fifty percent of the children with TB-HCC had LTBI, with the prevalence depending on the intensity and length of exposure to the index case. The sensitivity and specificity of TST were 73% [95% confidence interval (CI): 53-91] and 97% (95%CI: 89-100), respectively, versus 53% (95%CI: 41-66) and 81% (95%CI:71-90) for QFT. The positive predictive value of TST in children with TB-HCC was 91% (95%CI: 61-99), being 74% for QFT (95%CI: 47-95)., Conclusions: This is one of the first studies to estimate the prevalence of LTBI in children and the parameters of the main diagnostic tests using a latent class model. Our results suggest that children in contact with an index case have a high risk of infection. The accuracy and the predictive value of the two tests did not significantly differ. Combined use of the two tests showed scarce improvement in the diagnosis of LTBI., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Few studies have described the risk factors of intestinal parasitic infections in the Amazon., Methods: A cross-sectional survey was performed in a City of the State of Amazonas (Brazil) to estimate the prevalence of intestinal parasites and determine the risk factors for helminth infections., Results: Ascaris lumbricoides was the most prevalent parasite. The main risk factors determined were: not having a latrine for A. lumbricoides infection; being male and having earth or wood floors for hookworm infection; and being male for multiple helminth infections., Conclusions: We reported a high prevalence of intestinal parasites and determined some poverty-related risk factors.

Background: We aimed to identify challenges and to propose solutions for the implementation of tuberculosis (TB) programmes in rural Sub-Saharan Africa (SSA) by evaluating the outcomes of the TB programme in the Ancuabe district in rural Northern Mozambique., Methods: Retrospective descriptive study of the patients included in the TB programme in 2012-2013. Follow-up was continued till June 2014., Results: Three hundred nineteen patients were registered, 62.1% male, mean age 36.3 (SD 14.4), estimated case detection rate (eCDR) of 24.24%. Two hundred seventy-two were new cases, 21 transferred-in, 11 back after lost to follow-up (LTFU), 10 relapsing TB, 5 previous treatment failures. 94.4% were tested for Human immunodeficiency virus (HIV), 41.9% HIV-positive. 87.5% of the new cases were pulmonary TB (PTB), 43.4% were HIV co-infected. Initial sputum results were available in 207 cases, with 145 smear-positive (SP) cases. Outcomes of new cases: 122 (44.9%) LTFU, 55 (20.2%) cured, 43 (15.8%) treatment completed (98-36%-treatment success), 31 (11.4%) died, 19 (7%) transferred out and 2 (0.7%) failures., Conclusions: A low eCDR and high proportion of LTFU demonstrate that few patients were identified and had a low probability of complete treatment, suggesting a fragile health system. This raises the hypothesis that, probably, to improve TB health care in rural SSA, interventions should aim at improving health systems. Special attention should be given to social protection and compensation of the financial burden associated with TB.

Background: The feminization of medicine has risen dramatically over the past decades. The aim of this article was to compare the advance of women with that of men and determine the differences between hierarchical status and professional recognition achieved by women in medicine., Methods: A retrospective study was carried out in the Hospital Clinic Barcelona, Spain, of the period from 1996 to 2008. Data relating to temporary and permanent positions, hierarchy and career promotion achieved, specialty, age and the sex of the participants were analysed with the ANOVA test and logistic regression using the generalized estimated equation., Results: After completion of specialist training, fewer women than men doctors obtained permanent positions. The ratios between the proportions of women and men remained 1.2 for permanent non-hierarchal medical positions and below 0.2 for higher hierarchal levels. Fewer women than men with hierarchy and fewer women than men achieved the rank of consultant. Promotion to consultant and senior consultant was lower than that to senior specialist, being higher in specialties with gender parity and in masculinised specialties. On comparing the two genders using a statistical model, the probability of continuous promotion decreased with the year of the application and the age of the applicant, except in women., Conclusions: Despite the number of women training as specialists having increased to 50%, women remained in temporary positions twofold longer than men. Compared to women, men showed significant representation in hierarchal medical positions, and women showed a lower adjusted probability of internal professional promotion throughout the study period.