With the purpose of reducing the well-known negative impact of late presentation (LP) on people living with HIV (PLWH), guidelines on early HIV diagnosis were published in 2014 in Spain, but since ...then no data on LP prevalence have been published. To estimate prevalence and risk factors of LP and to evaluate their impact on the development of clinical outcomes in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) during 2004-2018.
CoRIS is an open prospective multicenter cohort of PLWH, adults, naive to ART at entry. LP was defined as HIV diagnosis with CD4 count ≤350 cells/μL or an AIDS defining event (ADE). Multivariable Poisson regression models were used to estimate both prevalence ratios (PR) for the association of potential risk factors with LP and Incidence rate ratios (IRRs) for its impact on the development of the composite endpoint (first ADE, first serious non-AIDS event SNAE or overall mortality).
14,876 individuals were included. Overall, LP prevalence in 2004-2018 was 44.6%. Risk factors for LP included older age, having been infected through injection drug use or heterosexual intercourse, low educational level and originating from non-European countries. LP was associated with an increased risk of the composite endpoint (IRR: 1.34; 95%CI 1.20, 1.50), ADE (1.39; 1.18, 1.64), SNAE (1.22; 1.01, 1.47) and mortality (1.71; 1.41, 2.08).
LP remains a health problem in Spain, mainly among certain populations, and is associated with greater morbidity and mortality. Public policies should be implemented to expand screening and early diagnosis of HIV infection, for a focus on those at greatest risk of LP.
In environmental surveys, risk perception may be a source of bias when information on health outcomes is reported using questionnaires. Using the data from a survey carried out in the largest ...chipboard industrial district in Italy (Viadana, Mantova), we devised a score of health risk perception and described its determinants in an adult population.
In 2006, 3697 parents of children were administered a questionnaire that included ratings on 7 environmental issues. Items dimensionality was studied by factor analysis. After testing equidistance across response options by homogeneity analysis, a risk perception score was devised by summing up item ratings.
Factor analysis identified one latent factor, which we interpreted as health risk perception, that explained 65.4% of the variance of five items retained after scaling. The scale (range 0–10, mean±SD 9.3±1.9) had a good internal consistency (Cronbach's alpha 0.87). Most subjects (80.6%) expressed maximum risk perception (score=10). Italian mothers showed significantly higher risk perception than foreign fathers. Risk perception was higher for parents of young children, and for older parents with a higher education, than for their counterparts. Actual distance to major roads was not associated with the score, while self-reported intense traffic and frequent air refreshing at home predicted higher risk perception.
When investigating health effects of environmental hazards using questionnaires, care should be taken to reduce the possibility of awareness bias at the stage of study planning and data analysis. Including appropriate items in study questionnaires can be useful to derive a measure of health risk perception, which can help to identify confounding of association estimates by risk perception.
•Concern towards environmental hazards may bias questionnaire surveys•There is no published formal evaluation of a score of health risk perception•We devised a score of health risk perception in an adult population in Italy•This score can be used to rate risk perception and assess its effects empirically
Vitamin D (VD) is a fat-soluble vitamin, and pivotal for maintaining health. Several genetic markers have been related to a deficient VD status; these markers could confer an increased risk to ...develop osteoporosis and other chronic diseases. A VD deficiency could also be a determinant of a severe COVID-19 disease. This study aimed to interrogate genetic/biological databases on the biological implications of a VD deficiency and its association with diseases, to further explore its link with COVID-19. The genetic variants of both a VD deficiency and COVID-19 were identified in the genome-wide association studies (GWAS) catalog and other sources. We conducted enrichment analyses (considering corrected p-values < 0.05 as statistically significant) of the pathways, and gene-disease associations using tools, such as FUMA, REVIGO, DAVID and DisGeNET, and databases, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). There were 26 and 46 genes associated with a VD deficiency and COVID-19, respectively. However, there were no genes shared between the two. Genes related to a VD deficiency were involved in the metabolism of carbohydrates, retinol, drugs and xenobiotics, and were associated with the metabolic syndrome and related factors (obesity, hypertension and diabetes mellitus), as well as with neoplasms. There were few enriched pathways and disease connections for the COVID-19-related genes, among which some of the aforementioned comorbidities were also present. In conclusion, genetic factors that influence the VD levels in the body are most prominently associated with nutritional and metabolic diseases. A VD deficiency in high-risk populations could be therefore relevant in a severe COVID-19, underlining the need to examine whether a VD supplementation could reduce the severity of this disease.
To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or ...advanced presenters (CD4 count < 200/µL or AIDS event at enrolment).
We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time.
Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status.
A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities.
Background: Platinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). In retrospective studies, patients with ...basal/squamous (BASQ)-like tumors present with more advanced disease and have worse prognosis. Transcriptomics-defined tumor subtypes are associated with response to NAC. Aim: To investigate whether immunohistochemical (IHC) subtyping predicts NAC response. Methods: Patients with muscle-invasive UBC having received platinum-based NAC were identified. Tissue microarrays were used to type tumors for KRT5/6, KRT14, GATA3, and FOXA1. Outcomes: progression-free survival and disease-specific survival; univariable and multivariate Cox regression models were applied. Results: We found a very high concordance between mRNA and protein expression. Using IHC-based hierarchical clustering, we classified 126 tumors in three subgroups: BASQ-like (FOXA1/GATA3 low; KRT5/6/14 high), Luminal-like (FOXA1/GATA3 high; KRT5/6/14 low), and mixed-cluster (FOXA1/GATA3 high; KRT5/6 high; KRT14 low). Applying multivariable analyses, patients with BASQ-like tumors were more likely to achieve a pathological response to NAC (OR 3.96; p = 0.017). The clinical benefit appeared reflected in the lack of significant survival differences between patients with BASQ-like and luminal tumors. Conclusions: Patients with BASQ-like tumors—identified through simple and robust IHC—have a higher likelihood of undergoing a pathological complete response to NAC. Prospective validation is required.
Asthma is a complex disease characterized by an intricate interplay of both heritable and environmental factors. Understanding the mechanisms through which genes and environment interact represents ...one of the major challenges for pulmonary researchers. This review provides an overview of the recently published literature on gene-environment (G × E) interactions in asthma, with a special focus on the new methodological developments in the postgenomewide association studies (GWAS) era.
Most recent studies on G × E interaction in asthma used a candidate-gene approach. Candidate-gene studies considering exposure to outdoor air pollutants showed significant interactions mainly with variants in the GSTP1 gene on asthma in children. G × E studies on passive and active smoking, including one genomewide interaction study, identified novel genes of susceptibility to asthma and a time-dependent effect of maternal smoking. Other recent studies on asthma found interactions between candidate genes and occupational allergen exposure and several domestic exposures such as endotoxin and gas cooking. New methods were developed to efficiently estimate G × E interaction in GWAS, and a pathway-based strategy to select an enriched gene-set for G × E studies has recently been proposed.
The G × E studies presented in this review offer a good example on how candidate-gene approaches can complement and help in validating GWAS findings.
Background
8-Hydroxydeoxyguanosine (8-OHdG) is a commonly used marker of DNA oxidative stress in epidemiological studies. The aim of this study was to establish whether the urinary concentration of ...8-OHdG varies during the first part of the day, when clinical tests are usually performed, and whether it can therefore be measured without bias in spot urine samples.
Material and methods
Spot urine samples were collected using a convenience sample. A linear mixed-effects model for repeated measurements was used to analyze 8-OHdG levels.
Results
A significant increasing trend in time in the 8-OHdG concentration was found among smokers, but not in the case of nonsmokers.
Conclusions
In epidemiological studies on oxidative stress, all participants should collect their early morning urine specimens – before their first cigarette if they are smokers – to gather information on individual background oxidation levels.
...chronic exposures, such as smoking, occupational exposure to silica, and firefighting, are associated with decreased serum CC-16 levels.2,3 Clinical studies have shown decreased serum levels of ...CC-16 in asthmatic subjects4,5 and in patients with chronic obstructive pulmonary disease (COPD).6 A positive association between serum CC-16 levels and FEV1 was recently observed in a large clinical study on patients with COPD.7 However, there is a lack of epidemiological studies addressing the relation of serum CC-16 levels with asthma and lung function in the general population. A positive association between serum CC-16 levels and lung function has been reported in clinical studies7 and in occupationally exposed subjects.\n38-1.30) <.001 Table I Unadjusted and adjusted estimates (95% CI and P) for the association between a 1-SD increase in serum CC-16 level (g/L) and asthma, spirometric patterns, and lung function BMI, Body mass index; GOLD, Global Initiative for Obstructive Lung Disease; LLN, lower limit of normal; OR, odds ratio; RRR, relative risk ratio.
Background:
The link between coagulation system disorders and COVID-19 has not yet been fully elucidated.
Aim:
Evaluating the association of non-previously reported coagulation proteins with COVID-19 ...severity and mortality.
Design:
Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals.
Methods:
Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis.
Results:
We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death.
Conclusion:
COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might “paradoxically” imply a higher risk of progression to severe disease and COVID-19-related mortality.
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