Trajectories in early rheumatoid arthritis related fatigue over 10 years: results from the ESPOIR cohort.

OBJECTIVES: In a cohort of early rheumatoid arthritis (RA) patients, we aimed to determine and characterise fatigue trajectories over 10 years of follow-up and identify predictors of trajectory membership. METHODS: We selected patients fulfilling the 2010 ACR/EULAR criteria for RA included in the ESPOIR cohort. We used a cluster analysis to obtain fatigue (assessed by fatigue visual analogue scale) trajectories over the course of 10 years from enrolment. Chi-square tests or ANOVA were performed to evaluate differences of baseline variables between fatigue trajectories. Using a multinomial logistic regression we were able to identify predictors of trajectory membership. RESULTS: We analysed 598 patients with mean disease duration at enrolment of 26.2±40.9 days. Cluster analysis revealed 3 trajectories: high (18%), moderate (52%) and low fatigue (30%). Compared to patients with moderate or low fatigue trajectory, patients with high fatigue trajectory were predominantly women and reported significantly higher duration and intensity of morning stiffness, HAQ score, tender joints count, levels of pain, number of awakenings due to arthritis, frequency of fibromyalgic RA, levels of physician and patient global assessment, more frequent sleep problems, and increased psychological distress. Female patients with pain, psychological distress and presence of sicca symptoms had a higher risk of being in the high trajectory group. CONCLUSIONS: These findings suggest that levels of fatigue are rather stable over time in each trajectory. Baseline clinical measures and baseline patient-reported measures of functional status better distinguished the three fatigue trajectories. We did not find any differences between trajectories in baseline laboratory measures. Inflammatory activity was not a predictor of being in the high trajectory fatigue group.

Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

RATIONALE & OBJECTIVE: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. PREDICTORS: Hyperuricemia, ultrasound findings, renal histology, genetic mutations. OUTCOMES: Age at ESRD, rate of decline in estimated glomerular filtration rate. RESULTS: ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). LIMITATIONS: Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. CONCLUSIONS: The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals with ADTKD-UMOD.

Cell cycle analysis in the rat external granular layer evaluated by several bromodeoxyuridine immunoperoxidase staining protocols.

An important step in bromodeoxyuridine (BrdU) immunohistochemistry is the production of single-stranded DNA to make the incorporated BrdU accessible to the antibodies. This paper examines the effect of distinct DNA denaturation pretreatments (DNase I, sodium citrate buffer, endonuclease Eco RI and exonuclease III, and HCl hydrolysis) on detection of BrdU. We found that all the methods used in the partial denaturation of DNA combined good nuclear immunostaining with acceptable tissue integrity. We also observed that these immunohistochemical protocols revealed a spatial pattern in the distribution of DNA-synthesizing cells within the cerebellar external granular layer (EGL) of 10-day-old rats, allowing us to estimate the fraction of S-phase cells. Our results indicate that detection of BrdU-stained cells is affected by the distinct histological procedures used in such detection. Additionally, as the duration and phases of the cell cycle in EGL neuroblasts are estimated in accordance with BrdU detection, an effect on this detection can render the measurement of cell cycle inaccurate. The present work shows that DNase I and citrate buffer, at appropriate conditions, may be good alternatives for acid denaturation. However, they are less sensitive than autoradiographic techniques that use 3H-thymidine administration. Finally, current data reveal that short survival times after a single BrdU exposure do not seem to affect the cell cycle progression of the EGL neuroblasts.

Altered bivalent positioning in metaphase I human spermatocytes from Robertsonian translocation carriers.

PURPOSE: The study aims to determine whether there is an altered bivalent positioning in metaphase I human spermatocytes from Robertsonian translocation carriers. METHODS: Metaphase I human spermatocytes from three 45,XY,der(13;14)(q10;q10) individuals and a 45,XY,der(14;15)(q10;q10) individual were analyzed. Proximity relationships of bivalents were established by analyzing meiotic preparations combining Leishman staining and multiplex-FISH procedures. Poisson regression model was used to determine proximity frequencies between bivalents and to assess associations with chromosome size, gene density, acrocentric morphology, and chromosomes with heterochromatic blocks. The hierarchical cluster Ward method was used to characterize the groups of bivalents with preferred proximities in a cluster analysis. Bivalent groups obtained were individually compared with those obtained in normal karyotype individuals evaluated in a previous study. RESULTS: A total of 1288 bivalents were examined, giving a total of 2289 proximity data. Only four positive significant proximities were detected for each type of Robertsonian translocation. Significant bivalent associations were only observed by small-size chromosomes for MI,22,XY,III(13q14q). These results were clearly divergent from 46,XY individuals. Moreover, cluster analysis revealed that about 30 % of the bivalents showed changes in their proximity relationships in metaphase I. CONCLUSIONS: The territorial organization of bivalents in metaphase I human spermatocytes changes in the presence of a Robertsonian translocation.

Effects of a multidisciplinary approach on the effectiveness of antiviral treatment for chronic hepatitis C.

UNLABELLED:  Background. Despite the introduction of direct antiviral agents, pegylated interferon remains the mainstay of treatment for chronic hepatitis C. However, pegylated interferon is associated with a high rate of severe adverse events and decreased quality of life. Specific interventions can improve adherence and effectiveness. We aimed to determine whether implementing a multidisciplinary approach improved outcomes in the treatment of chronic hepatitis C. MATERIAL AND METHODS: We analyzed consecutive patients treated with pegylated interferon plus ribavirin between August 2001 and December 2011. We compared patients treated before and after the implementation of a multidisciplinary approach in 2007. We compared the baseline demographic and clinical characteristics and laboratory findings between groups, and used bivariate logistic regression models to detect factors involved in attaining a sustained virological response, calculating the odds ratios with their respective 95% confidence intervals. To evaluate the effect of the multidisciplinary team, we fitted a multivariate logistic regression model to compare the sustained virological response after adjusting for unbalanced variables and predictive factors. RESULTS: We included 514 patients [228 (44.4%) in the pre-intervention cohort]. Age, viral genotype, previous treatment, aspartate transaminase, ferritin, and triglyceride were prognostic factors of sustained virological response. After adjusting for prognostic factors, sustained virological response was higher in the multidisciplinary cohort (58 vs. 48%, p = 0.038). Despite higher psychiatric comorbidity and age in the multidisciplinary cohort, we observed a trend toward a lower rate of treatment abandonment in this group (2.2 vs. 4.9%, p = 0.107). CONCLUSION: Multidisciplinary management of chronic hepatitis C improves outcomes.

Acute effects of small changes in bicycle saddle height on gross efficiency and lower limb kinematics.

The aim of the present study was to assess the acute effects of small changes in bicycle saddle height on gross efficiency (GE) and lower-limb kinematics. Well-trained cyclists (n = 14) performed a submaximal pedaling test (~70-75% of the v[Combining Dot Above]O2max) at constant cadence (90 rpm). It consisted of 3 randomized sets of 6 minutes with the preferred saddle height, 2% higher and 2% lower. Gross efficiency was significantly lower and oxygen consumption (v[Combining Dot Above]O2) was significantly higher when raising the saddle (GE = 19.9 ± 1.5%; V[Combining Dot Above]O2max = 43.8 ml·kg·min) than when lowering it (GE = 20.4 ± 1.3%; V[Combining Dot Above]O2 = 42.8 ml·kg·min). Additionally, a change of 0.8% in GE (20.6 ± 1.6% to 19.8 ± 1.6%, p < 0.05) was observed when comparing the positions where the best and worst GE was obtained. A significant effect of the small changes in saddle height on lower limb kinematics was also observed (p < 0.05). The differences between lower and higher saddle positions, in hip, knee, and ankle joints were an increase of extension (~4, 7, and 8°, respectively), a decrease of flexion (~3, 4, and 4°, respectively) and, consequently, an increase of the range of movement (~1, 3, and 4°, respectively). The results of the present study indicate that small changes in saddle height affected GE and lower limb kinematics The observed changes in lower limb kinematics could justify, in part, the GE changes. Further research should evaluate long-term effects of these small modifications in the seat height on GE and lower limb kinematics.

Corrigendum: C-reactive protein isoforms as prognostic markers of COVID-19 severity.

[This corrects the article DOI: 10.3389/fimmu.2022.1105343.].

Restrictive diets are unnecessary for colonoscopy: Non-inferiority randomized trial.

Background and study aims In colonoscopy, preparation is often regarded as the most burdensome part of the intervention. Traditionally, specific diets have been recommended, but the evidence to support this policy is insufficient. The aim of this study was to evaluate the impact of the decision not to follow a restrictive diet on bowel preparation and colonoscopy outcomes. Patients and methods This was a multicenter, controlled, non-inferiority randomized trial with FIT-positive screening colonoscopy. The subjects were assigned to follow the current standard (1-day low residue diet [LRD]) or a liberal diet. The allocation was balanced for the risk of inadequate cleansing using the Dik et al. score. All participants received the same instructions for morning colonoscopy preparation. The primary outcome was the rate of adequate preparations as defined by the Boston Bowel Preparation Scale. Secondary outcomes included tolerability and measures of colonoscopy performance and quality. Results A total of 582 subjects were randomized. Of these, 278 who received the liberal diet and 275 who received the 1-day LRD were included in the intent-to-treat analysis. Non-inferiority was demonstrated with adequate preparation rates of 97.8% in the 1-day LRD and 96.4% in the liberal diet group. Tolerability was higher with the liberal diet (94.7% vs. 83.2%). No differences were found with respect to cecal intubation time, aspirated volume, or length of the examination. Global and right colon average adenoma detection rates per colonoscopy were similar. Conclusions The liberal diet was non-inferior to the 1-day LRD, and increased tolerability. Colonoscopy performance and quality were not affected. (NCT05032794).

C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.

Purpose: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters. Methods: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters. Results: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023). Conclusion: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.

Principal component and cluster analysis of morphological variables reveals multiple discrete sub-phenotypes in weaver mouse mutants.

The present study evaluates the usefulness of the principal component analysis-based cluster analysis in the categorization of several sub-phenotypes in the weaver mutant by using several morphological parameters from the cerebellar cortex of control, heterozygous (+/wv) and homozygous (wv/wv) weaver mice. The quantified parameters were length of the cerebellar cortex, area of the external granular layer, area of the molecular layer, number of the external granular layer cells (EGL), and number of Purkinje cells (PCs). The analysis indicated that at postnatal day 8, the genotype +/wv presented three sub-phenotypes tagged as +/wv (0), +/wv (1) and +/wv (2), whereas two sub-phenotypes designated as wv (0)/wv (1) and wv (0)/wv (2) were identified in the genotype wv/wv. The number of PCs for the genotype +/wv and the number of EGL cells for the genotype wv/wv were the variables that discriminated the best among sub-phenotypes. Each one of the sub-phenotypes showed specific abnormalities in the cytoarchitecture of the cerebellar cortex as well as in the foliar pattern. In particular, the wv (0)/wv (1) and wv (0)/wv (2) sub-phenotypes had the most altered cytoarchitectonics, followed by the +/wv (2) sub-phenotype and then by the +/wv (1) one. The sub-phenotype +/wv (0) was the less affected one. Apart from reporting for the first time the coexistence of several sub-phenotypes in the weaver mutant, our approach provides a new statistical tool that can be used to assess cerebellar morphology.

Assessment of short forms of recurrent atrial extra systoles by echocardiography with left atrial strain in ambulatory patients without organic cardiopathy.

Aim: To analyse the potential usefulness and clinical relevance of the assessment by echocardiography with left atrial strain, based on the myocardial atrial deformation curves with speckle-tracking velocity vector imaging (VVI), in the analysis of short-form recurrent atrial extra systoles in ambulatory patients not suffering from organic cardiopathy. Methods: We designed a descriptive, prospective, and observational study including 270 patients between the ages of 18 and 75 assessed during an outpatient cardiology consultation attended due to palpitations over a period of two years. Using ambulatory electrocardiographic monitoring, we selected cases with short forms of repetitive atrial extrasystole, isolated or recurrentatrial fibrillation and a control group formed by those patients without repetitive ectopia. All patients underwent a thorough echocardiographic study during their first cardiological visit. Results: The analysis of the dynamic curves segmental deformation generated after an atrial extrasystole can reveal different points of origin of the extrasystole and detect specific anatomical alterations in the interatrial conduction at the level of the Bachmann's fascicle showing different models of electro anatomical activation possibly involved in the appearance of repetitive forms. Higher values of dyssynchrony between the septal and lateral wall and elongation in the time of interatrial electromechanical conduction could also be related to the existence of repetitive ectopic beats. Conclusions: Our ambulatory study employing the left atrial longitudinal strain, particularly in its segmental analysis, provides new insights into its the usefulness and potential clinical relevance.

Objetivo: Analizar la utilidad y relevancia clínica de la evaluación mediante ecocardiografía basada en las curvas de deformación auricular miocárdica con imágenes vectoriales de velocidad (VVI) de speckle-tracking, en el análisis de las extrasístoles auriculares recurrentes de corta duración en pacientes ambulatorios sin cardiopatía orgánica. Métodos: Se diseñó un estudio descriptivo, prospectivo y observacional que incluyó a 270 pacientes de entre 18 y 75 años evaluados durante una consulta externa de cardiología a la que acudieron por palpitaciones durante un periodo de dos años. Mediante el uso de monitorización electrocardiográfica ambulatoria, se seleccionaron casos con formas cortas de extrasistolia auricular repetitiva, fibrilación auricular aislada o repetitiva y un grupo control formado por aquellos pacientes sin ectopia repetitiva. Todos los pacientes se sometieron a un estudio ecocardiográfico exhaustivo durante su primera visita cardiológica. Resultados: El análisis de las curvas dinámicas de deformación segmentaria generadas tras un extrasístole auricular diferentes modelos de activación electroanatómica posiblemente implicados en la aparición de formas repetitivas. Valores mayores de disincronía entre la pared septal y lateral y el alargamiento en el tiempo de conducción electromecánica intraauricular pudieran también relacionarse con la existencia de latidos ectópicos repetitivos. Conclusiones: Nuestro estudio ambulatorio empleando la deformación longitudinal auricular izquierda, particularmente en su análisis segmentario, proporciona nuevas perspectivas sobre su utilidad y potencial relevancia clínica.

Seroprevalence study prior and post vaccination in cancer patients in principality of Andorra (COVONCO study).

BACKGROUND: COVID-19 serologic response in patients with cancer may be lower than in the general population and may be influenced by the type of tumor or anticancer treatment. This study aims to analyze serological response prior and after vaccination of COVID-19 within the oncological population in Andorra. We set out to identify risk factors for a higher or lower serological response. PATIENTS AND METHODS: Observational, unicentric, prospective cohort study of oncologic patients in Andorra. We calculated the seroprevalence of antibodies against SARS-CoV-2 (May 2020-June 2021) and analyzed the main demographic, oncologic features and factors associated with being seropositive. RESULTS: A total of 373 patients were analyzed, mainly with solid tumours (n = 334, 89.5%). At baseline, seroprevalence was 13%, increasing during follow-up to 19%; lower seroprevalence was observed in patients with hematologic malignancies (2.6% vs 14.2%; p = 0.041) and patients receiving biological therapies (0% vs 15%, p = 0.005). In the overall seroprevalence analysis, women (23% vs 11.9%; p = 0.006) and tumour-free patients (p = 0.034) showed higher seroprevalence. The multivariable analysis showed that odds of being seropositive were higher among women (OR: 2.44, 95% CI 1.28-4.64), and patients who underwent surgery (OR: 3.35, 95% CI 1.10-10.20). About 80% of the cohort received at least one dose of COVID-19 vaccination, showing a higher seroprevalence of patients who received ChAdOx1-S than those who received BNT162b2 (24.4% vs 6.4%: p = 0.001). CONCLUSION: The seroprevalence of antibodies against SARS-COV-2 in oncologic patients in Andorra was higher among females and patients who received hormonal therapy and surgery while patients with hematologic malignancies and biologic therapies showed lower seropositivity without finding differences in the type of tumour or anticancer treatment.

Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX® as a Screening Tool.

PURPOSE: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. METHODS: This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). RESULTS: Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. CONCLUSIONS: The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.

Exploratory study on the influence of climatological parameters on Mycoplasma hyopneumoniae infection dynamics.

The objective of the present work was to elucidate the potential relationship between Mycoplasma hyopneumoniae infection and seroconversion dynamics and climatological conditions in four groups of pigs from the same farm born in different seasons of the year. Nasal swabs and blood samples were taken from 184 pigs at 1, 3, 6, 9, 12, 15, 18, 22 and 25 (slaughter age) weeks of age. Outside climatologic parameters, including temperature (°C), relative humidity (%), precipitation (l/m(2)) and wind speed (m/s) were recorded weekly from January 2003 to June 2004. Percentage of nPCR detection of M. hyopneumoniae in nasal swabs was associated significantly with the weekly precipitation rate [P = 0.0018, OR = 1.31 (IC = 1.11-1.55)]; the higher the precipitation rate, the higher the probability of being M. hyopneumoniae nPCR-positive. On the other hand, the percentage of seropositive pigs had a significant association with mean weekly temperature rate [P = 0.0012, OR = 0.89 [IC = 0.84-0.95]); the lower the temperature, the higher the probability of being M. hyopneumoniae seropositive. Animals born in autumn (when higher precipitations rates were recorded), entering finishing units in winter (when lower temperatures were recorded), and reaching slaughter in spring, had the highest probability of being infected by M. hyopneumoniae and the highest probability of being M. hyopneumoniae seropositive.

C-reactive protein isoforms as prognostic markers of COVID-19 severity.

C-reactive protein (CRP), an active regulator of the innate immune system, has been related to COVID-19 severity. CRP is a dynamic protein undergoing conformational changes upon activation in inflammatory microenvironments between pentameric and monomeric isoforms. Although pentameric CRP is the circulating isoform routinely tested for clinical purposes, monomeric CRP shows more proinflammatory properties. Therefore, we aimed to determine the potential of monomeric CRP in serum as a biomarker of disease severity in COVID-19 patients (admission to intensive care unit [ICU] and/or in-hospital mortality). We retrospectively determined clinical and biological features as well as pentameric and monomeric CRP levels in a cohort of 97 COVID-19 patients within 72h of hospital admission. Patients with severe disease had higher levels of both pentameric and monomeric CRP. However, multivariate analysis showed increased mCRP but not pCRP to be independently associated to disease severity. Notably, mCRP levels higher than 4000 ng/mL (OR: 4.551, 95% CI: 1.329-15.58), together with number of co-morbidities, low lymphocyte count, and procalcitonin levels were independent predictors of disease severity in the multivariate model. Our results show the potential of mCRP levels as a marker of clinical severity in COVID-19 disease.

COVID-19 mortality risk factors in older people in a long-term care center.

PURPOSE: Despite high rates of COVID-19 infection and increased related mortality have been reported among older adults admitted in long-term care facilities, a limited amount of information is available about the natural course of this pandemic and prognostic factors in such population. In the current study, we aimed to investigate the epidemiologic, demographics, clinical, or therapeutic factors that may predict the prognosis in a cohort of COVID-19 infected institutionalized older in a nursing home. METHODS: We conducted a retrospective analysis of all COVID-19 confirmed institutionalized older in a nursing home from March 15 to June 5, 2020. Epidemiological, demographic, and frailty status before infection, and clinical, laboratory, treatment, and outcome data during infection were collected. We used bivariate analysis and multivariate logistic regression to identify risk factors for mortality. RESULTS: The analysis comprised all 100 COVID-19 confirmed cases during the study period. The median age was 85 years; 62% were female. The case fatality rate was 20%. In the bivariate analysis, male gender, fever, respiratory symptoms, severe cognitive decline, a low Barthel index, and lymphocytopenia were significantly associated with mortality. Patients treated with hydroxychloroquine plus azithromycin were related to a higher chance of survival than those without pharmacological treatment. Multivariate logistic regression analysis identified male gender, low Barthel index, no pharmacological treatment, and lymphocytopenia as independent risk factors associated with mortality. CONCLUSIONS: Male gender, low Barthel index, and lymphocytopenia are independent risk factors for COVID-19 mortality in institutionalized older patients in long-term care nursing homes. Treatment with hydroxychloroquine and azithromycin was associated with lower mortality in these patients.

Satisfaction with Social Support Received from Social Relationships in Cases of Chronic Pain: The Influence of Personal Network Characteristics in Terms of Structure, Composition and Functional Content.

The worldwide burden of chronic illnesses, constitutes a major public health concern and a serious challenge for health systems. In addition to the strategies of self-management support developed by nursing and health organizations, an individual's personal network represents a major resource of social support in the long-term. Adopting a cross-sectional design based on personal network analysis methods, the main aim of this study is to explore the relationship between satisfaction with the social support received by individuals suffering chronic pain and the structure, composition, and functional content in social support of their personal networks. We collected personal and support network data from 30 people with chronic pain (20 person's contacts (alters) for each individual (ego), 600 relationships in total). Additionally, we examined the level of satisfaction with social support in each of the 600 relationships. Bivariate and multivariate tests were performed to analyze the satisfaction with the social support received. Using cluster analysis, we established a typology of the 600 relationships under study. Results showed that higher satisfaction was associated with a balance between degree centrality and betweenness (i.e., measures of network cohesion and network modularity, respectively). Finally, new lines of research are proposed in order to broaden our understanding of this subject.

Correction: Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C.

[This corrects the article DOI: 10.1371/journal.pone.0208112.].

Validation of the Spanish version of the questionnaire on Patient Empowerment in Long-Term Conditions.

BACKGROUND: Patient empowerment is a key factor in improving health outcomes. OBJECTIVE: To evaluate the psychometric properties of the Spanish version of the questionnaire on Patient Empowerment in Long-Term Conditions (PELC) that evaluates the degree of empowerment of patients with chronic diseases. METHODS: Three measurements were made (at baseline, 2 weeks and 12 weeks) of quality of life (QoL), self-care, self-efficacy and empowerment. Reliability was evaluated as internal consistency for the entire sample. Test-retest reproducibility was evaluated for patients who were stable from baseline to week 2 (n = 70). Validity was analysed (n = 124) as baseline correlations with QoL, self-care, self-efficacy, clinical data and psychosocial variables. Sensitivity to change was analysed in terms of effect size for patients who had improved between baseline and week 12 (n = 48). RESULTS: The study was carried out with 124 patients with a diagnosis of heart failure. Cronbach's alpha was high, at >0.9, and the interclass correlation coefficient was low, at 0.47. PELC questionnaire scores showed differences depending on New York Heart Association functional class (p<0.05) and, as posited in the a priori hypotheses, were moderately correlated with emotional dimensions of QoL (0.53) and self-efficacy (0.43). Effect size for the clinically improved subsample was moderate (0.67). CONCLUSIONS: The results suggest that the Spanish version of the PELC questionnaire has appropriate psychometric properties in terms of internal consistency and validity and is low in terms of reproducibility and sensitivity to change.

Hydroxyurea Exposure and Development of the Cerebellar External Granular Layer: Effects on Granule Cell Precursors, Bergmann Glial and Microglial Cells.

The current paper presents a histological analysis of the cell death in the cerebellar external granular layer (EGL) following the treatment with a single dose (2 mg/g) of hydroxyurea (HU). The rats were examined at postnatal days (P) 5, 10, and 15, and sacrificed at appropriate times ranging from 6 to 48 h after treatment administration. Studies were done in each cortical lobe (anterior, central, posterior, and inferior). The quantification of several parameters, such as density of 5-bromo-2'-deoxyuridine, TUNEL, vimentin, and tomato lectin-stained cells, revealed that HU compromises the viability of EGL cells. Our results indicate that P10 is a time of high vulnerability to injury. We also show here that the anterior and central lobes are the cortical regions most susceptible to the action of the HU. Additionally, our data also indicate that from 6 to 24 h after HU-exposure is a time-window of high sensibility to this agent. On the other hand, our ultrastructural analysis confirmed that HU administration produces the activation of apoptotic cellular events in the EGL, resulting in a substantial number of dying cells. Different stages of apoptosis can be observed in all cortical lobes at all investigated postnatal ages and survival times. Moreover, we observed that dying neuroblasts were covered by laminar processes of Bergmann glia, and that these unipolar astrocytes presented cytological features of phagocytes engulfing apoptotic bodies and cell debris. The electron microscopy study also revealed the participation of ameboid microglial cells in the phagocytosis of apoptotic cells in the regions of the EGL with extensive cell death.