Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

Maternally inherited deletion encompassing the RTL1as and MEG8 genes of the human 14q32 imprinted region in a patient with a mild Kagami-Ogata syndrome phenotype.

Kagami-Ogata syndrome and Temple syndrome are imprinting disorders caused by the abnormal expression of genes in an imprinted cluster on chromosome 14q32. Here, we report a female with mild features of the Kagami-Ogata syndrome phenotype with polyhydramnios, neonatal hypotonia, feeding difficulties, abnormal foot morphology, patent foramen ovale, distal arthrogryposis, normal facial profile, and a bell-shaped thorax without coat hanger ribs. The single nucleotide polymorphism array revealed the interstitial deletion of chromosome 14q32.2-q32.31 (117 kb in size), involving the RTL1as and MEG8 genes, and other small nucleolar RNAs and microRNAs. The differentially methylated regions (DMRs) appeared unaltered. The RTL1as gene deletion and the normal methylation pattern of the MEG3 gene loci were confirmed by methylation-specific multiplex ligation-dependent probe amplification. Deletions of the 14q32 region without involving DMRs, and encompassing only the RTL1as and MEG8 genes, are poorly described in the literature. The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient. It was not sufficient, however, to produce Temple syndrome or any other pathogenic phenotype in the patient's mother.

Duration of the patient interval in breast cancer and factors associated with longer delays in low-and middle-income countries: A systematic review with meta-analysis.

OBJECTIVE: Breast cancer survival is lower in low- and middle-income countries (LMICs) partially due to many women being diagnosed with late-stage disease. The patient interval refers to the time elapsed between the detection of symptoms and the first consultation with a healthcare provider and is considered one of the core indicators for early diagnosis and treatment. The goal of the current research was to conduct a meta-analysis of the duration of the patient interval in LMICs and investigate the socio-demographic and socio-cultural factors related to longer delays in presentation. METHODS: We conducted a systematic review with meta-analysis (pre-registered protocol CRD42020200752). We searched seven information sources (2009-2022) and included 50 articles reporting the duration of patient intervals for 18,014 breast cancer patients residing in LMICs. RESULTS: The longest patient intervals were reported in studies from the Middle East (3-4 months), followed by South-East Asia (2 months), Africa (1-2 months), Latin America (1 month), and Eastern Europe (1 month). Older age, not being married, lower socio-economic status, illiteracy, low knowledge about cancer, disregarding symptoms or not attributing them to cancer, fear, negative beliefs about cancer, and low social support were related to longer delays across most regions. Longer delays were also related to use of alternative medicine in the Middle East, South-East Asia, and Africa and distrust in the healthcare system in Eastern Europe. CONCLUSIONS: There is large variation in the duration of patient intervals across LMICs in different geographical regions. Patient intervals should be reduced and, for this purpose, it is important to explore their determinants taking into account the social, cultural, and economic context.

Use of silicone wristbands to measure firefighters' exposures to polycyclic aromatic hydrocarbons (PAHs) during live fire training.

Firefighters experience exposures to carcinogenic and mutagenic substances, including polycyclic aromatic hydrocarbons (PAHs). Silicone wristbands (SWBs) have been used as passive samplers to assess firefighters' exposures over the course of a shift but their utility in measuring short term exposures, source of exposure, and correlations with other measurements of exposure have not yet been investigated. In this study, SWBs were used to measure the concentrations of 16 priority PAHs inside and outside of firefighters' personal protective equipment (PPE) while firefighting. SWBs were placed on the wrist and jacket of 20 firefighters conducting live fire training. Correlations were made with matching data from a sister project that measured urinary concentrations of PAH metabolites and PAH concentrations from personal air samples from the same participants. Naphthalene, acenaphthylene and phenanthrene had the highest geometric mean concentrations in both jacket and wrist SWB, with 1040, 320, 180 ng/g SWB for jacket and 55.0, 4.9, and 6.0 ng/g SWB for wrist, respectively. Ratios of concentrations between the jacket and wrist SWBs were calculated as worker protection factors (WPFs) and averaged 40.1 for total PAHs and ranged from 2.8 to 214 for individual PAHs, similar to previous studies. Several significant correlations were observed between PAHs in jacket SWBs and air samples (e.g., total and low molecular weight PAHs, r = 0.55 and 0.59, p < 0.05, respectively). A few correlations were found between PAHs from SWBs worn on the wrist and jacket, and urinary concentrations of PAH metabolites and PAH concentrations in air samples. The ability of the SWBs to accurately capture exposures to various PAHs was likely influenced by short sampling time, high temperatures, and high turbulence. Future work should further examine the limitations of SWBs for PAH exposures in firefighting, and other extreme environments.

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort.

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1ß, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1ß. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.

Health-related quality of life in patients newly diagnosed with prostate cancer: CAPLIFE study.

PURPOSE: To analyse the Health-Related Quality of Life (HRQoL) at diagnosis of patients with prostate cancer (PCa) according to tumour extension and urinary symptomatology and to explore factors associated with HRQoL. METHODS: 408 Controls and 463 PCa cases were included. Eligibility criteria were a new diagnosis of PCa (cases), 40-80 years of age, and residence in the participating hospitals' coverage area for ≥ 6 months before recruitment. HRQoL was evaluated using the 12-Item Short-Form Health Survey, Mental (MCS) and Physical Component Summaries (PCS), and urinary symptoms with the International Prostate Symptom Score. HRQoL scores for all PCa cases, according to tumour extension and urinary symptoms, were compared with controls. In addition, information about lifestyles and comorbidities was collected and its association with low HRQoL (lower scores) were explored using logistic regression models. RESULTS: Overall cases had similar PCS score, but lower MCS score than controls. The lowest standardised scores for both PCS and MCS were reached by cases with severe urinary symptoms and a metastatic tumour [mean (SD); PCS: 41.9 (11.5), MCS: 42.3 (10.3)]. Having "below" PCS and MCS scores was associated with the presence of three or more comorbidities in the cases [aOR = 2.86 (1.19-6.84) for PCS and aOR = 3.58 (1.37-9.31) for MCS] and with severe urinary symptomatology [aOR = 4.71 (1.84-12.08) for PCS and aOR = 7.63 (2.70-21.58) for MCS]. CONCLUSION: The mental dimension of HRQoL at diagnosis of patients with PCa was lower than in controls, especially for cases with severe urinary symptoms and a metastatic tumour. Comorbidities and urinary symptoms were variables associated with the HRQoL of PCa cases.

Association between obesity and atopic dermatitis in children: A case-control study in a high obesity prevalence population.

BACKGROUND/OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Research suggests an association between obesity and AD, although evidence is lacking from Latin American populations. This study evaluated the association of obesity with AD in children from Chile, a country with high obesity prevalence. METHODS: A case-control study was performed in children with active AD (cases) and healthy controls (HCs) from Santiago, Chile. Body mass index was evaluated by z-score (z-BMI), with overweight defined as z-BMI ≥+1 and <+2, and obesity as z-BMI ≥+2. Abdominal obesity was defined by a waist circumference-to-height ratio (WHR) ≥0.5. AD severity was evaluated by Scoring AD (SCORAD) index. RESULTS: A total of 174 children with AD and 101 controls were included. AD patients had similar overweight (27% vs. 28%) and obesity (21% vs. 26%) rates as HCs (p = .65). Abdominal obesity rates were also comparable (64% vs. 62%, p = .81). In sex-specific analyses, girls with AD had higher abdominal obesity rates than HCs (71% vs. 53%, p < .05) while boys with AD had lower abdominal obesity rates than HCs (53% vs. 75%, p = .03). Among children with AD, higher z-BMI or WHR did not correlate with higher SCORAD, eosinophil counts or total IgE. CONCLUSION: In our study, Chilean children with AD had high but similar rates of obesity as HCs, but showed sex-specific associations of abdominal obesity and AD. Further research is needed to evaluate these associations and the roles that weight excess and weight loss could play in the pathogenesis and treatment of AD.

Implementing the WHO Labour Care Guide to reduce the use of Caesarean section in four hospitals in India: protocol and statistical analysis plan for a pragmatic, stepped-wedge, cluster-randomized pilot trial.

BACKGROUND: The World Health Organization (WHO) Labour Care Guide (LCG) is a paper-based labour monitoring tool designed to facilitate the implementation of WHO's latest guidelines for effective, respectful care during labour and childbirth. Implementing the LCG into routine intrapartum care requires a strategy that improves healthcare provider practices during labour and childbirth. Such a strategy might optimize the use of Caesarean section (CS), along with potential benefits on the use of other obstetric interventions, maternal and perinatal health outcomes, and women's experience of care. However, the effects of a strategy to implement the LCG have not been evaluated in a randomised trial. This study aims to: (1) develop and optimise a strategy for implementing the LCG (formative phase); and (2) To evaluate the implementation of the LCG strategy compared with usual care (trial phase). METHODS: In the formative phase, we will co-design the LCG strategy with key stakeholders informed by facility assessments and provider surveys, which will be field tested in one hospital. The LCG strategy includes a LCG training program, ongoing supportive supervision from senior clinical staff, and audit and feedback using the Robson Classification. We will then conduct a stepped-wedge, cluster-randomized pilot trial in four public hospitals in India, to evaluate the effect of the LCG strategy intervention compared to usual care (simplified WHO partograph). The primary outcome is the CS rate in nulliparous women with singleton, term, cephalic pregnancies in spontaneous labour (Robson Group 1). Secondary outcomes include clinical and process of care outcomes, as well as women's experience of care outcomes. We will also conduct a process evaluation during the trial, using standardized facility assessments, in-depth interviews and surveys with providers, audits of completed LCGs, labour ward observations and document reviews. An economic evaluation will consider implementation costs and cost-effectiveness. DISCUSSION: Findings of this trial will guide clinicians, administrators and policymakers on how to effectively implement the LCG, and what (if any) effects the LCG strategy has on process of care, health and experience outcomes. The trial findings will inform the rollout of LCG internationally. TRIAL REGISTRATION: CTRI/2021/01/030695 (Protocol version 1.4, 25 April 2022).

The new WHO Labour Care Guide (LCG) is an innovative partograph that emphasises women-centred, evidence-based care during labour and childbirth. Together with clinicians working at four hospitals in India, we will develop and test a strategy to implement the LCG into routine care in labour wards of these hospitals. We will use a randomised trial design where this LCG strategy is introduced sequentially in each of the four hospitals, in a random order. We will collect data on all women giving birth and their newborns during this period and analyse whether the LCG strategy has any effects on the use of Caesarean section, women's and newborn's health outcomes, and women's experiences during labour and childbirth. While the trial is being conducted, we will also collect qualitative and quantitative data from doctors, nurses and midwives working in these hospitals, to understand their perspectives and experiences of using the LCG in their day-to-day work. In addition, we will collect economic data to understand how much the LCG strategy costs, and how much money it might save if it is effective. Through this study, our international collaboration will generate critical evidence and innovative tools to support implementation of the LCG in other countries.

Patients' experiences and perceptions of dignity in end-of-life care in emergency departments: A qualitative study.

AIMS: To explore and understand the experiences of patients with advanced illness in relation to dignity during end-of-life care in emergency departments. DESIGN: Qualitative study based on Gadamer's hermeneutics. METHODS: Between September 2019 and February 2020, 16 in-depth interviews were carried out with advanced illness patients who attended emergency departments. The participants were informed priorly and signed informed consent. The data were analysed using an inductive strategy for finding emerging themes. The Consolidated Criteria for Reporting Qualitative Research was used for writing the study's report. RESULTS: In the data analysis process, two main themes emerged that glean the experiences of patients in relation to dignity during end-of-life care in emergency departments. 'Dignity as an individual's attribute' and 'Acting with dignity: Dignity as a behavioural attribute'. CONCLUSION: Patient dignity in end-of-life care is centred around the principle of control (of oneself, one's death and one's emotions). The strategies required for patients to preserve their dignity can be somewhat incompatible with the dynamics and objectives of healthcare professionals who work in emergency departments. IMPACT STATEMENT: The dignity of patients with advanced illness who attend emergency departments is a relevant issue that merits being addressed from the patients' perspective. Participants have identified that dignity is a way of being and behaving in the face of illness. Emergency departments need to respect end-of-life patients' desires by supporting and accompanying them, avoiding therapeutic obstinacy. We recommend care to be centred on patients' well-being, to respect their autonomy and decision-making processes, and to allow prompt referrals to palliative care services. PATIENT OR PUBLIC CONTRIBUTION: Managers from the Emergency Departments participated in the study design and patients' recruitment. Patients' relatives were informed about the study's aim, and they contributed to the development of the interview protocol.

Inflammatory Biomarkers in the Diagnosis and Prognosis of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case-control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. The study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR (p = 0.032) and HAQ values (p = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17-5.22]; p = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24-6.78]; p = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00-1.12]; p = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00-1.06]; p = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00-1.00]; p = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07-1.46]; p = 0.004). Our data support that the inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD.

Effectiveness of dermal cleaning interventions for reducing firefighters' exposures to PAHs and genotoxins.

Firefighters are exposed to carcinogenic and mutagenic combustion emissions, including polycyclic aromatic hydrocarbons (PAHs). Fire service and firefighter cancer advocacy groups recommend skin cleaning using wipes or washing with detergent and water after exposure to smoke, although these strategies have not been proven to reduce exposures to harmful combustion products such as PAHs. This study assessed dermal decontamination methods to reduce PAH exposures by firefighters participating in live fire training scenarios. Study participants (n = 88) were randomly assigned to an intervention group (i.e., two types of commercial skin wipes, detergent and water, or a control group who did not use any skin decontamination). PAHs were measured in personal air (during the fire) and dermal wipe samples (before and after fire suppression and after dermal decontamination). PAH metabolites and mutagenicity were measured in urine samples before and after fire suppression. Airborne PAH concentrations during the fire ranged between 200 and 3,970 µg/m3 (mean = 759 µg/m3, SD = 685 µg/m3). Firefighters had higher total PAHs and high-molecular-weight PAHs on their skin after the fire compared to before (1.3- and 2.2-fold, respectively, p < 0.01). Urinary PAH metabolites increased significantly following exposure to the training fires by 1.7 to 2.2-fold (depending on the metabolite, p < 0.001). Urinary mutagenicity did not differ significantly between pre- and post-fire for any of the decontamination methods. Detergent and water was the only intervention that removed a significant amount of total PAHs from the skin (0.72 ng/cm2 preintervention vs. 0.38 ng/cm2 postintervention, p < 0.01). However, fold changes in urinary PAH metabolites (i.e., pre- vs. post-exposure levels) did not differ among any of the dermal decontamination methods or the control group. These data suggest that despite on-site attempts to remove PAHs from firefighters' skin, the examined interventions did not reduce the internal dose of PAHs. Future work should investigate preventing initial exposure using other interventions, such as improved personal protective equipment.

Prevalence of frailty and its association with oral hypofunction in older adults: a gender perspective.

BACKGROUND: Previous studies have indicated an association between oral hypofunction and frailty in community-dwelling older adults. However, this issue has not been evaluated in institutionalized older patients. We aimed to determine the prevalence of physical frailty in this particularly vulnerable group and evaluate its association with oral hypofunction, analyzing possible differences by gender. METHODS: This cross-sectional study was conducted in private and public care homes in Guayaquil (Ecuador) from January 2018 until December 2019. Participants were classified as robust, pre-frail, and frail according to the Fried's frailty phenotype. Oral hypofunction was defined as the presence of at least three positive items in the following list: poor oral hygiene, oral dryness, reduced occlusal force, decreased masticatory function, and deterioration of swallowing function. The relationships between frailty and oral hypofunction were analyzed using logistic regression models for the whole sample and stratified by gender. Statistical analyses were performed using STATA 15.0 software (Stata Corp. LP, College Station, TX, USA). RESULTS: Among the 589 participants analyzed (65% women), the median age was 72 years (interquartile range: 66-82). Pre-frailty and frailty were presented in 66.7% and 28.9% of them respectively. Weakness was the most frequent item (84.6%). There was a significant relationship between frailty and oral hypofunction in women. In the overall sample, the frequency of frailty was 2.06 times higher (95% CI 1.30-3.29) in patients with oral hypofunction, and this association was maintained in women (ORa: 2.18; 95% CI 1.21-3.94). Reduced occlusal force and decreased swallowing function were items significantly associated with the presence of frailty (ORa: 1.95; 95% CI 1.18-3.22 and ORa: 2.11; 95% CI 1.39-3.19, respectively). CONCLUSION: The prevalence of frailty and pre-frailty was high among institutionalized older people and was associated with the presence of hypofunction, especially in women. Decreased swallowing function was the most strongly item associated with frailty.

Braille literacy as a human right: A challenge to the "inefficiency" argument against braille instruction.

The United Nations Convention on the Rights of Persons with Disabilities (CRPD) affirms a right to education for disabled persons and aims to ensure braille instruction for blind individuals. However, there is evidence that braille instruction is often circumvented or abandoned early in CRPD nations because it is perceived as an inefficient learning medium for blind students. This perception persists despite insufficient empirical evidence and a lack of understanding of the efficiency of reading versus listening for learning in sighted individuals. We therefore investigated the efficiency of learning written versus spoken words in blind and sighted samples. Participants (23 blind, 20 sighted) studied the written definitions of 70 rare English words in successive rounds, presented in conjunction with written or spoken wordforms. Blind participants learned with equal efficiency across modalities, whereas sighted participants learned spoken words more efficiently. The findings indicate the inefficiency argument against teaching braille is groundless, both because braille word learning is not less efficient than auditory word learning for blind individuals, and because reading is valued in the education of sighted individuals despite its apparent inefficiency in that population.

Understanding university teachers' digital competencies: a systematic mapping study.

Being digitally competent is an imperative requirement for the 21st century university teacher, a fact recognized by both the literature and policymakers. Although this topic has been addressed in different reviews and critical studies recently, none of them have systematically and explicitly addressed the factors that explain, or are explained by, the digital competencies of university teachers. Examples of these factors include, among others, demographic, professional and psychological aspects of university teachers, as well as very specific digital competencies. The present study seeks to close this gap through a systematic mapping of the literature published until 2021 in journals indexed by Scopus and Web of Science (WOS). Based on the selection of 53 primary studies, we characterized the literature and summarized the main results reported so far. The analysis allowed us to conclude the following: 1) there is a growing number of contributions aimed at understanding the acquisition of digital competencies, especially from external factors; 2) European, and more specifically Spanish, university teachers from multiple disciplines are the most studied population; 3) most studies adopted quantitative approaches to explain but not prove causality; 4) there is a great heterogeneity of relationships and results that explain the digital competencies of university professors. The implications of these results are discussed with a view to identifying the gaps that provide scope for future research.

Identification of novel prostate cancer genes in patients stratified by Gleason classification: Role of antitumoral genes.

Prostate cancer (PCa) is a tumor with a great heterogeneity, both at a molecular and clinical level. Despite its global good prognosis, cases can vary from indolent to lethal metastatic and scientific efforts are aimed to discern those with worse outcomes. Current prognostic markers, as Gleason score, fall short when it comes to distinguishing these cases. Identification of new early biomarkers to enable a better PCa distinction and classification remains a challenge. In order to identify new genes implicated in PCa progression we conducted several differential gene expression analyses over paired samples comparing primary PCa tissue against healthy prostatic tissue of PCa patients. The results obtained show that this approach is a serious alternative to overcome patient heterogeneity. We were able to identify 250 genes whose expression varies along with tissue differentiation-healthy to tumor tissue, 161 of these genes are described here for the first time to be related to PCa. The further manual curation of these genes allowed to annotate 39 genes with antitumoral activity, 22 of them described for the first time to be related to PCa proliferation and metastasis. These findings could be replicated in different cohorts for most genes. Results obtained considering paired differential expression, functional annotation and replication results point to: CGREF1, UNC5A, C16orf74, LGR6, IGSF1, QPRT and CA14 as possible new early markers in PCa. These genes may prevent the progression of the disease and their expression should be studied in patients with different outcomes.

The Development of a New International Generic Measure (EQ-HWB): Face Validity and Psychometric Stages in Argentina.

OBJECTIVES: This study aimed to present the face validity and psychometric stages performed in Spanish in Argentina, the only Spanish-speaking country of an international collaboration that undertook the construction of a new measure that can be used in economic evaluation across health, social care, and public health, the EQ EQ-HWB (EQ Health and Wellbeing). We also explored the relationship among 3-level version EQ-5D (EQ-5D-3L), 5-level version EQ-5D (EQ-5D-5L), and EQ-HWB. METHODS: Face validity was based on semistructured face to face interviews of a purposive sample to explore translatability of language and concepts of 97 candidate items, translated into Argentina Spanish. The psychometric evaluation using an online panel assessed the psychometric properties of 64 items that were carried forward (floor and ceiling effects, item correlations, known-group differences in relevant prespecified subgroups by the international and local teams, exploratory and confirmatory factor analysis, and item response theory). EQ-5D-3L, EQ-5D-5L, and EQ-HWB correlations were explored. RESULTS: In the face validity stage, 24 interviews with carers, general public, patients, and users of social services were included. Most items showed adequate face validity. In the psychometric assessment, 497 participants were recruited (64% reporting a long-term health condition). Most of the items showed adequate psychometrics in an Argentinian context. EQ-5D-3L and EQ-5D-5L had strong correlations, and EQ-HWB was moderately correlated to EQ visual analog scale. The Argentina team recommended 23 of the final 25 items. CONCLUSIONS: The assessment of Spanish items contributed to the overall development of EQ-HWB and helped inform the design of an internationally relevant 25-item and a short 9-item measure intended to be used in economic evaluations.

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis.

BACKGROUND: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats. OBJECTIVE: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain. METHODS: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis. RESULTS: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (ß: 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (ß: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semi-rural residents, where ß-HCH was also marginally-significantly associated to APC (ß: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (ß: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by ß-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (ß: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses. CONCLUSION: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies.

Factors associated with the development of second primary tumours in head and neck cancer patients.

INTRODUCTION: The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to review the evidence about factors associated with developing SPTs in patients with HNC. METHODS: An updated systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and the search was performed in Pubmed and Scopus. Only original articles with a cohort or case-control design were included. Article quality was assessed with the Newcastle-Ottawa scale. RESULTS: Thirty-six and two case-control studies were included, with quality medium (n = 5) to high (n = 33). Tobacco showed a significant association with SPT development, with risks ranging from 1.41 (95%CI: 1.04-1.91) to 5.52 (95%CI: 2.91-10.49). Regarding alcohol, risks ranged from 1.46 (95%CI: 1.12-1.91) to 21.3 (95%CI: 2.9-156). Location of the index tumour in the hypopharynx/oropharynx, absence of human papillomavirus and presence of a premalignant lesion also increased the risk of SPTs. More controversy was found for sex, age and other clinical factors of the tumour. CONCLUSION: Toxic lifestyle habits and clinical factors were associated with the risk of SPTs in HNC patients. These findings may improve individualised prevention strategies in its follow-up.

Determinants of masticatory performance assessed by mixing ability tests.

STATEMENT OF PROBLEM: Studies determining the main predictors of masticatory performance by using mixing ability tests are sparse. PURPOSE: The purpose of this clinical study was to identify potential determinants of masticatory performance assessed by analyzing a patient's masticatory ability using bicolored chewing gum and visual, quantitative, and interactive methods. MATERIAL AND METHODS: Nondental participants attending healthcare centers were consecutively recruited in Granada, Spain. The inclusion criteria were older than18 years and resident in the coverage area of the reference healthcare centers for at least the previous 6 months. The participants were excluded if they had received dental treatment in the previous 6 months or they were unable to communicate. The masticatory performance was determined by using 2-colored chewing gum (Kiss 3 white and blue; Smint) that was masticated for a total of 20 strokes. The masticated gum was crushed between 2 transparent glass slides, creating a 1-mm-thick specimen that was subsequently scanned. The mixed-color area was calculated as a percentage by using Photoshop as described by Schimmel et al and designated as the standard method. In addition, all images made were analyzed by using the Web application the Chewing Performance Calculator. In addition, the masticated bolus was inspected visually, and mastication performance was classified as being poor, moderate, or good. Sociodemographic data, as well as data on behaviors, medical and nutritional status, health-related quality of life, saliva, and general oral health, were collected for all participants to identify the main determinants of masticatory performance. RESULTS: One hundred thirty-seven participants were enrolled. The masticatory performance values obtained using both methods (standard method and Chewing Performance Calculator) were significantly greater for well masticated gum (P<.001), which had been visually classified as being poorly masticated (69.1% for standard method and 43.5% for Chewing Performance Calculator), moderately masticated (89.7% for standard method and 67.3% for Chewing Performance Calculator), and well masticated (97.3% for standard method and 80.3% for Chewing Performance Calculator). The bivariate analyses revealed that masticatory performance was significantly higher in younger people (<65 years) (P=.008), who also had a higher basal salivary flow rate (P<.001), were nondenture users (P=.002), and had more standing teeth and occlusal units (P<.001). However, the multiple regression analyses showed that the number of occlusal units was the only significant predictor of masticatory performance. In addition, the mean masticatory performance (95% confidence interval: 47.7% to 56.8%) was found to be greatly improved (by 1.2% to 2.2%), with each occlusal unit, in accordance with the Chewing Performance Calculator and between 0.8% and 1.8% according to the standard method; the basal masticatory performance was calculated as 72.1% to 81.2% (95% confidence interval). CONCLUSIONS: The number of occlusal units is one of the main predictors of masticatory performance when a 2-color bolus is used to test mixing ability.

Frequency of Polyautoimmunity in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus.

OBJECTIVE: To describe the frequency of polyautoimmunity and multiple autoimmune syndrome in patients with rheumatoid arthritis (RA) and patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: This was a cross-sectional observational study of patients with RA, SLE, and controls without autoimmune rheumatic disease. Cases were those with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and SLE according to the 2019 American College of Rheumatology/European League Against Rheumatism criteria, consecutively recruited in a rheumatology clinic. Controls were subjects with no rheumatic autoimmune disease (AIDs) recruited in the same area. Patients filled out a questionnaire on polyautoimmunity. Variables of interest were polyautoimmunity (RA or SLE with other AIDs), whereas secondary variables were rheumatic, skin, endocrine, digestive, and neurological AIDs. Multiple autoimmune syndrome is defined as the presence of 3 or more AIDs and a family history of AIDs. Statistical analyses performed were descriptive, bivariate, and multivariate (dependent variable: polyautoimmunity). RESULTS: The study population comprised 109 patients with RA, 105 patients with SLE, and 88 controls. Polyautoimmunity was recorded in 15 patients with RA (13.8%), 43 with SLE (41%), and 2 controls (2.2%). The most frequent AID in RA was Sjögren syndrome (53.3%), followed by Hashimoto thyroiditis and psoriasis; the most frequent AIDs in SLE were Sjögren syndrome (55.8%) and antiphospholipid syndrome (30.2%), followed by Hashimoto thyroiditis. Obesity was associated with polyautoimmunity in RA (odds ratio [OR], 3.362; p = 0.034). In SLE, joint damage (OR, 2.282; p = 0.038) and anti-RNP antibodies (OR, 5.095; p = 0.028) were risk factors for polyautoimmunity, and hydroxychloroquine was a protective factor (OR, 0.190; p = 0.004). CONCLUSIONS: Polyautoimmunity is frequent in RA and even more frequent in SLE. It was associated with obesity in RA and with joint damage and anti-RNP in SLE. Hydroxychloroquine was a protector.