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Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.
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CONTEXT: Experimental and observational studies suggest that circulating micronutrients, including vitamin D (VD), may increase COVID-19 risk and its associated outcomes. Mendelian randomization (MR) studies provide valuable insight into the causal relationship between an exposure and disease outcomes. OBJECTIVES: The aim was to conduct a systematic review and meta-analysis of causal inference studies that apply MR approaches to assess the role of these micronutrients, particularly VD, in COVID-19 risk, infection severity, and related inflammatory markers. DATA SOURCES: Searches (up to July 2023) were conducted in 4 databases. DATA EXTRACTION AND ANALYSIS: The quality of the studies was evaluated based on the MR-STROBE guidelines. Random-effects meta-analyses were conducted where possible. RESULTS: There were 28 studies (2 overlapped) including 12 on micronutrients (8 on VD) and COVID-19, 4 on micronutrients (all on VD) and inflammation, and 12 on inflammatory markers and COVID-19. Some of these studies reported significant causal associations between VD or other micronutrients (vitamin C, vitamin B6, iron, zinc, copper, selenium, and magnesium) and COVID-19 outcomes. Associations in terms of causality were also nonsignificant with regard to inflammation-related markers, except for VD levels below 25 nmol/L and C-reactive protein (CRP). Some studies reported causal associations between cytokines, angiotensin-converting enzyme 2 (ACE2), and other inflammatory markers and COVID-19. Pooled MR estimates showed that VD was not significantly associated with COVID-19 outcomes, whereas ACE2 increased COVID-19 risk (MR odds ratio = 1.10; 95% CI: 1.01-1.19) but did not affect hospitalization or severity of the disease. The methodological quality of the studies was high in 13 studies, despite the majority (n = 24) utilizing 2-sample MR and evaluated pleiotropy. CONCLUSION: MR studies exhibited diversity in their approaches but do not support a causal link between VD/micronutrients and COVID-19 outcomes. Whether inflammation mediates the VD-COVID-19 relationship remains uncertain, and highlights the need to address this aspect in future MR studies exploring micronutrient associations with COVID-19 outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022328224.
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Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk, although some studies also reported no association. Furthermore, the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited. Thus, we investigated the associations between dietary intake by degree of food processing and breast cancer risk, overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intake of EPIC participants was assessed via questionnaires at baseline. More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system: unprocessed/minimally processed (NOVA 1), culinary ingredients (NOVA 2), processed (NOVA 3) and ultra-processed (NOVA 4). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer per standard deviation increase in daily consumption (grams) of foods from each NOVA group. The current analysis included 14,933 breast cancer cases, diagnosed among the 318,686 EPIC female participants, (median follow-up of 14.9 years). No associations were found between breast cancer risk and the level of dietary intake from NOVA 1 [HR per 1 SD=0.99 (95% CI 0.97 - 1.01)], NOVA 2 [HR per 1 SD =1.01 (95% CI 0.98 - 1.03)] and NOVA 4 [HR per 1 SD =1.01 (95% CI 0.99 - 1.03)] foods. However, a positive association was found between NOVA 3 and breast cancer risk [HR per 1 SD =1.05 (95% CI 1.03 - 1.07)] which became non-significant after adjustment for alcohol intake [HR per 1 SD =1.01 (95% CI 0.98 - 1.05)] or when beer and wine were excluded from this group [HR per 1 SD =0.99 (95% CI 0.97 - 1.01)]. The associations did not differ by breast cancer subtype, menopausal status or body mass index. Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption. Supplementary Information: The online version contains supplementary material available at 10.1186/s43014-024-00264-2.
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BACKGROUND: Inflammation influences tumour progression and cancer prognosis, but its role preceding breast cancer (BC) and its prognostic implications remain inconclusive. METHODS: We studied pre-diagnostic plasma inflammatory biomarkers in 1538 women with BC from the EPIC study. Cox proportional hazards models assessed their relationship with all-cause and BC-specific mortality, adjusting for tumour characteristics and lifestyle factors. RESULTS: Over a 7-year follow-up after diagnosis, 229 women died, 163 from BC. Elevated IL-6 levels were associated with increased all-cause mortality risk (HR1-SD 1.25, 95% CI 1.07-1.47). Among postmenopausal, IL-6 was associated with higher all-cause (HR1-SD 1.41, 95% CI 1.18-1.69) and BC-specific mortality (HR1-SD 1.31, 95% CI 1.03-1.66), (PHeterogeneity (pre/postmenopausal) < 0.05 for both), while IL-10 and TNFα were associated with all-cause mortality only (HR1-SD 1.19, 95% CI 1.02-1.40 and HR1-SD 1.28, 95% CI 1.06-1.56). Among ER+PR+, IL-10 was associated with all-cause and BC-specific mortality (HR1-SD 1.35, 95% CI 1.10-1.65 and HR1-SD 1.42 95% CI 1.08-1.86), while TNF-α was associated with all-cause mortality in HER2- (HR1-SD 1.31, 95% CI 1.07-1.61). An inflammatory score predicted higher all-cause mortality, especially in postmenopausal women (HR1-SD 1.30, 95% CI 1.07-1.58). CONCLUSIONS: Higher pre-diagnosis IL-6 levels suggest poorer long-term survival among BC survivors. In postmenopausal survivors, elevated IL-6, IL-10, and TNFα and inflammatory scores seem to predict all-cause mortality.
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BACKGROUND: Sensitive skin is a highly prevalent problem. The objective of the study was to assess whether the tested products are effective and safe in terms of improving the symptoms of sensitive skin. METHODS: A clinical randomized split-face study was carried out on 24 healthy female subjects. Three cosmetic combinations were tested versus vehicle: product A (Solía Thermal Spring Water-TSW-from Cantabria, Spain + diatom algae-P. tricornutum-extract), product B (Solía TSW + diatom algae extract + Annona cherimola Fruit Extract) and product C (Solía TSW + diatom algae extract + Annona cherimola Fruit Extract + niacinamide). Prior to each application of the study Product (A, B, or C)/vehicle, 10% of aqueous solution of capsaicin to induce skin irritation was applied, mimicking the symptoms of sensitive skin. Stinging and burning sensations were evaluated at different time points. RESULTS: All three tested products A, B, and C showed to act better in calming the symptoms induced by capsaicin when compared to the vehicle. CONCLUSIONS: The tested products would be an interesting option for treating stinging and burning sensations in sensitive skin patients.
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This study aimed to elucidate the genetic causes underlying the juvenile parkinsonism (JP) diagnosed in a girl with several family members diagnosed with spinocerebellar ataxia type 2 (SCA2). To achieve this, whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification were performed. As a result, a homozygous missense mutation SNP T>C (rs2254562) in synaptojamin 1 (SYNJ1), which has been implicated in the regulation of membrane trafficking in the synaptic vesicles, was identified. Additionally, we observed overexpression of L1 cell adhesion molecule (L1CAM), Cdc37, GPX1, and GPX4 and lower expression of ceruloplasmin in the patient compared to the control. We also found changes in sphingolipid, inositol, and inositol phosphate metabolism. These findings help to clarify the mechanisms of JP and suggest that the etiology of JP in the patient may be multifactorial. This is the first report of the rs2254562 mutation in the SYNJ gene identified in a JP patient with seizures and cognitive impairment.
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Transtornos Parkinsonianos , Humanos , Feminino , Transtornos Parkinsonianos/genética , Mutação de Sentido Incorreto , Sequenciamento do Exoma , Linhagem , Polimorfismo de Nucleotídeo Único , Proteínas do Tecido Nervoso/genética , Criança , MultiômicaRESUMO
PURPOSE: We developed a proxy questionnaire for parents of children with Developmental Delay (DD) to provide comprehensive information for instructors about the child's functioning before participating in aquatic activities. This dedicated information will enable a high-quality treatment plan to promote the child's functioning in everyday life. METHODS: Based on the International Classification of Functioning, Disability, and Health (ICF) Coreset development and linking rules method, a set of questions was constructed in a preliminary process. A draft version was sent to instructors and parents in Israel. Seventy-five questionnaires from instructors and 25 from parents returned to the statistical analysis procedure. Reliability and face validity were analyzed by experts. RESULTS AND CONCLUSIONS: The questionnaire showed high validity and reliability for its purposes and allowed self-completion by the parents.
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Desenvolvimento Infantil , Deficiências do Desenvolvimento , Pais , Humanos , Inquéritos e Questionários/normas , Deficiências do Desenvolvimento/diagnóstico , Reprodutibilidade dos Testes , Masculino , Feminino , Criança , Pré-Escolar , Desenvolvimento Infantil/fisiologia , Israel , Psicometria/normas , Psicometria/instrumentação , Psicometria/métodosRESUMO
BACKGROUND AND OBJECTIVE: Reducing patient decision delay - the time elapsed between symptom onset and the moment the patient decides to seek medical attention - can help improve acute coronary syndrome survival. Patient decision delay is typically investigated in retrospective studies of acute coronary syndrome survivors that are prone to several biases. To offer an alternative approach, the goal of this research was to investigate anticipated patient decision delay in the general population in response to different symptom clusters. METHODS: We developed scenarios representing four commonly experienced symptom clusters: classic (chest symptoms only), heavy (a large number of very intense symptoms including chest pain), diffuse (mild symptoms including chest pain), and weary (mild symptoms without clear chest involvement). The scenarios were administered in random order in a representative survey of 1002 adults ≥55 years old from the non-institutionalized general population in Spain. We measured help-seeking intentions, anticipated patient decision delay (waiting >30 min to seek help), and symptom attribution. RESULTS: Patient decision delay was most common in the diffuse scenario (55%), followed by the weary (34%), classic (22%), and heavy (11%) scenarios. Attributing the symptoms to a cardiovascular cause and intentions to call emergency services were least frequent in the weary and diffuse scenarios. Women were less likely to intend to seek help than men in the classic (OR = 0.48, [0.27, 0.85], diffuse (OR = 0.67, [0.48, 0.92]), and weary (OR = 0.66, [0.44, 0.98]) scenarios, despite being more likely to attribute symptoms to cardiovascular causes. Participants with traditional cardiovascular risk factors (e.g., diabetes, hypercholesterolemia, hypertension) reported faster help-seeking, whereas participants with obesity and history of depression were more likely to delay. DISCUSSION: The diverse manifestations of acute coronary syndrome generate fundamentally different appraisals. Anticipated patient decision delay varies as a function of socio-demographic characteristics and medical history, supporting findings from studies with patients who experienced ACS. Measuring anticipated patient decision delay in the general population can help reveal potential barriers to help-seeking and capture effects of population interventions.
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Síndrome Coronariana Aguda , Tomada de Decisões , Humanos , Síndrome Coronariana Aguda/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Espanha/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Fatores de Tempo , Dor no Peito/psicologia , Dor no Peito/etiologia , Inquéritos e Questionários , Serviços Médicos de Emergência/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear. METHODS: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls). FINDINGS: In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03-1.57)], HGF [1.48 (1.06-2.07)], PIK3AP1 [1.22 (1.00-1.50)] and CLEC4G [1.52 (1.00-2.32)] were positively associated; HSD11B1 [0.67 (0.49-0.91)], SCF [0.68 (0.49-0.94)], and CCL25 [0.80 (0.65-0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. In complementary MR analysis, IL-6 [OR per inverse-rank normalized NPX = 1.19 (95% CI 1.04-1.36)] and HSD11B1 [0.91 (0.84-0.99)] were associated with endometrial cancer risk. INTERPRETATION: Altered IL-6 signalling and reduced glucocorticoid activity via HSD11B1 might play important roles in endometrial carcinogenesis. FUNDING: Funding for IIG_FULL_2021_008 was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme; Funding for INCA_15849 was obtained from Institut National du Cancer (INCa).
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Neoplasias do Endométrio , Análise da Randomização Mendeliana , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/etiologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Idoso , Razão de Chances , Inflamação/sangue , Inflamação/genética , Fatores de Risco , AdultoRESUMO
Pseudomonas aeruginosa infections are difficult to treat due to rapid development of antibiotic drug resistance. The synergistic combination of already-in-use drugs is an alternative to developing new antibiotics to combat antibiotic-resistant bacteria. Here we demonstrate that bismuth-based drugs (bismuth subsalicylate, colloidal bismuth subcitrate) in combination with different classes of antibiotics (tetracyclines, macrolides, quinolones, rifamycins and so on) can eliminate multidrug-resistant P. aeruginosa and do not induce development of antibiotic resistance. Bismuth disrupts iron homeostasis by binding to P. aeruginosa siderophores. Inside cells, bismuth inhibits the electron transport chain, dissipates the proton motive force and impairs efflux pump activity by disrupting iron-sulfur cluster-containing enzymes, including respiration complexes. As a result, bismuth facilitates antibiotic accumulation inside bacteria, enhancing their efficacy. The combination therapy shows potent antibacterial efficacy and low toxicity in an ex vivo bacteraemia model and increases the survival rate of mice in in vivo mouse lung-infection models. Our findings highlight the potential of bismuth-based drugs to be repurposed to combat P. aeruginosa infections in combination with clinically used antibiotics.
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Antibacterianos , Bismuto , Sinergismo Farmacológico , Homeostase , Ferro , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Antibacterianos/farmacologia , Ferro/metabolismo , Animais , Bismuto/farmacologia , Homeostase/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Camundongos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Modelos Animais de Doenças , FemininoRESUMO
Carcinogenesis is closely related to the expression, maintenance, and stability of DNA. These processes are regulated by one-carbon metabolism (1CM), which involves several vitamins of the complex B (folate, B2, B6, and B12), whereas alcohol disrupts the cycle due to the inhibition of folate activity. The relationship between nutrients related to 1CM (all aforementioned vitamins and alcohol) in breast cancer has been reviewed. The interplay of genes related to 1CM was also analyzed. Single nucleotide polymorphisms located in those genes were selected by considering the minor allele frequency in the Caucasian population and the linkage disequilibrium. These genes were used to perform several in silico functional analyses (considering corrected p-values < 0.05 as statistically significant) using various tools (FUMA, ShinyGO, and REVIGO) and databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO). The results of this study showed that intake of 1CM-related B-complex vitamins is key to preventing breast cancer development and survival. Also, the genes involved in 1CM are overexpressed in mammary breast tissue and participate in a wide variety of biological phenomena related to cancer. Moreover, these genes are involved in alterations that give rise to several types of neoplasms, including breast cancer. Thus, this study supports the role of one-carbon metabolism B-complex vitamins and genes in breast cancer; the interaction between both should be addressed in future studies.
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Neoplasias da Mama , Carbono , Polimorfismo de Nucleotídeo Único , Complexo Vitamínico B , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Complexo Vitamínico B/metabolismo , Carbono/metabolismo , Ácido Fólico/metabolismo , Bases de Dados Genéticas , Simulação por Computador , Regulação Neoplásica da Expressão Gênica , Vitamina B 6/metabolismo , Desequilíbrio de LigaçãoRESUMO
Background: Previous studies have shown that meal timing, poor sleep quality, and chronotype may play a relevant role in the development of type 2 diabetes mellitus (T2DM). However, its relationship with macronutrients by eating occasions has not been explored deeply. Objective: Our aim was to estimate the association between chrono-nutrition, sleep quality, chronotype, and the prevalence of T2DM. Methods: This cross-sectional study included a subset of 3465 middle-aged Caucasian adults (2068 women) from the European Prospective Investigation into Cancer and Nutrition (EPIC) Spain cohort study. In the 2017-18 follow-up, we assessed chronotype, sleep quality, diet, and sociodemographic data using validated questionnaires. Further, we used blood samples to determine serum levels of glucose. We defined a case of T2DM when serum glucose concentration was ≥126 mg/dL or when participants self-reported diabetes. Results: A higher prevalence of T2DM was associated with poor sleep quality (ORpoorvsgood = 2.90, 95% CI = 1.30, 6.28). Carbohydrate intake at breakfast was inversely associated with the prevalence of T2DM (OR = 0.75, 95% CI = 0.66, 0.85). Finally, lipid intake at breakfast was associated with a 13% higher prevalence of T2DM (OR = 1.13, 95% CI = 1.01, 1.26) for each 1 standard deviation (1-SD) increase. Conclusions: This study concludes that a higher content of carbohydrates at breakfast is correlated with a reduced prevalence of T2DM, while higher lipids intake at breakfast is associated with a higher prevalence of T2DM. Furthermore, poor sleep quality is a potential factor associated with an elevated prevalence of T2DM. Our results emphasize the need for prospective studies to validate and strengthen these observed associations.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Feminino , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prevalência , Qualidade do Sono , Espanha/epidemiologia , Adulto , Dieta , Comportamento Alimentar , Estado Nutricional , Ritmo Circadiano/fisiologia , Glicemia/análise , Glicemia/metabolismo , Refeições , Europa (Continente)/epidemiologiaRESUMO
All over the world, many companies are including oocyte cryopreservation for nonmedical reasons, also popularly known as nonmedical egg freezing (NMEF), within their employee benefits packages. However, it is important to ask whether companies are ethically justified in offering NMEF as a benefit for their employees. The inclusion of NMEF within companies' employee benefits packages could be ethically justified in two ways. On the one hand, company-sponsored NMEF can serve as a strategy to mitigate or eliminate gender inequalities in the workplace, such as female underrepresentation in positions of authority and leadership and the so-called work/motherhood conflict. On the other hand, company-sponsored NMEF can be a means to expand women's reproductive autonomy by making egg freezing accessible to those women who are not able to afford it otherwise. This article calls into question these ethical justifications. We argue that by offering NMEF as an employee benefit, companies maintain current workplace inequalities and impose an option for women with multiple risks and externalities. Therefore, companies' offering of NMEF benefits cannot be ethically justified. Furthermore, we argue that companies that offer NMEF benefits incur fiduciary responsibilities related to the physiological, emotional, psychological, and financial costs of the use of company-sponsored NMEF.
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Las infecciones por el VSR en constituyen una causa importante de morbilidad, hospitalización, ausentismo escolar y laboral, así como de mortalidad, en el mundo, así como en el Paraguay.En la actualidad, existen herramientas para la prevención del VSR. En el año 2012, el Paraguay, ha incorporado el palivizumab (MedImmune, EE. UU.), anticuerpo monoclonal, producido por tecnología de DNA recombinante. Este anticuerpo se administra en 5 dosis, cada 30 días y está indicado en lactantes nacidos prematuros y aquellos con trastornos cardiopulmonares. Por otro lado, actualmente se cuenta con una nueva herramienta para la prevención del VSR. El anticuerpo monoclonal de vida media prolongada Nirsevimab, específico para la conformación de prefusión de la proteína F, aprobado por EMA y FDA. Este monoclonal, está indicado para la prevención de las Infecciones respiratorias agudas bajas, causada por VSR en recién nacidos y lactantes nacidos durante o al ingresar a su primera temporada de VSR, en prematuros y lactantes hasta los 24 meses de edad que siguen siendo vulnerables a la enfermedad grave por VSR durante su segunda temporada de VSR. Luego de analizar la situación epidemiológica del VSR en el país así como la evidencia de eficacia, eficiencia y efectividad de este monoclonal; instituciones académicas, sociedades científicas, organizaciones no gubernamentales y gubernamentales se reunieron y elaboraron un consenso interinstitucional para la prevención de las infecciones por VSR, sugiriendo la incorporación del Nirsevimab, en menores de 12 meses de edad antes de su primera temporada de VSR y en reemplazo del Palivizumab, debido a que el nuevo monoclonal tiene el potencial de cambiar el panorama de las infecciones por VSR en el lactante y producir un impacto en la reducción la mortalidad y morbilidad infantil; reduciendo la carga al sistema de salud, en lo que se refiere a la disminución de la ocupación de camas hospitalarias tanto en sala como en unidades de cuidados intensivos, así como la disminución de la carga para los cuidadores, médicos y proveedores de atención médica y la mortalidad infantil.
Respiratory syncytial virus (RSV) infections constitute a significant cause of morbidity, hospitalization, school and work absenteeism, as well as mortality worldwide, including in Paraguay. Currently, tools for RSV prevention are available. In 2012, Paraguay approved the use of palivizumab (MedImmune, USA), a monoclonal antibody produced through recombinant DNA technology. This antibody is administered in 5 doses, every 30 days and is indicated in infants born prematurely and those with cardiopulmonary disorders. Furthermore, a novel tool for RSV prevention has recently become available. Nirsevimab, a long-acting monoclonal antibody specific to the prefusion conformation of the F protein, has been approved by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). This monoclonal antibody is indicated for the prevention of acute lower respiratory tract infections caused by RSV in newborns and infants born during or entering their first RSV season, as well as in premature infants and infants up to 24 months of age who remain vulnerable to severe RSV disease during their second RSV season. After analyzing the epidemiological situation of RSV in our country and evaluating the evidence of efficacy, efficiency, and effectiveness of this monoclonal antibody, academic institutions, scientific societies, and non-governmental and governmental organizations developed consensus guidelines on a new prevention alternative for the prevention of RSV infections, suggesting the incorporation of Nirsevimab in children under 12 months of age before their first RSV season and replacing Palivizumab. The new monoclonal has the potential to change the panorama of RSV infections in infants and produce an impact on the reduction of infant mortality and morbidity reducing the burden on the health system by decreasing hospital bed occupancy both in wards and in intensive care units, as well as the decrease in the burden on caregivers, physicians and health care providers.
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Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, Nε-[carboxy-methyl]lysine (CML), Nε-[carboxy-ethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (Pinteraction = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HRQ5vs.Q1 = 1.67, 95% CI: 1.21-2.30, Ptrend = .02) or any cause (HRQ5vs.Q1 = 1.38, 95% CI: 1.05-1.83, Ptrend = .09). These associations tended to be stronger among cases with diabetes (Pinteraction = .03) and pre-diabetes (Pinteraction <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.
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Neoplasias Colorretais , Produtos Finais de Glicação Avançada , Receptor para Produtos Finais de Glicação Avançada , Humanos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/diagnóstico , Masculino , Feminino , Produtos Finais de Glicação Avançada/sangue , Pessoa de Meia-Idade , Receptor para Produtos Finais de Glicação Avançada/sangue , Idoso , Estudos Prospectivos , Lisina/sangue , Lisina/análogos & derivados , Ornitina/sangue , Ornitina/análogos & derivados , Modelos de Riscos Proporcionais , Biomarcadores Tumorais/sangue , ImidazóisRESUMO
BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.
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Fator de Crescimento Insulin-Like I , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análise , Pessoa de Meia-Idade , Estudos de Casos e Controles , Estudos Prospectivos , Europa (Continente)/epidemiologia , Idoso , Fatores de Risco , Biomarcadores Tumorais/sangue , Peptídeos Semelhantes à InsulinaRESUMO
BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.
Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Humanos , Asma/tratamento farmacológico , Asma/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Produtos Biológicos/uso terapêutico , Antiasmáticos/uso terapêutico , Estudos Longitudinais , Resultado do Tratamento , Índice de Gravidade de Doença , Corticosteroides/uso terapêutico , Sistema de Registros , Idoso , Estudos de CoortesRESUMO
BACKGROUND: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. METHODS: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). FINDINGS: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. INTERPRETATION: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. FUNDING: Italian Ministry of Health, European Commission, Estonian Research Council.
Assuntos
Gastos em Saúde , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Adulto , Gastos em Saúde/estatística & dados numéricos , Idoso , Europa (Continente)/epidemiologia , Adulto Jovem , Adolescente , Linfoma/mortalidade , Linfoma/epidemiologia , Linfoma/economia , Sistema de Registros , Idoso de 80 Anos ou mais , Prognóstico , Fatores de TempoRESUMO
BACKGROUND: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). RESULTS: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. CONCLUSIONS: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.
Assuntos
Estilo de Vida Saudável , Neoplasias , Humanos , Pessoa de Meia-Idade , Neoplasias/mortalidade , Feminino , Masculino , Adulto , Estudos Prospectivos , Idoso , Europa (Continente)/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Eyelashes play a crucial role in self-image and ocular protection. Enhancements to their structure are of both cosmetic and clinical interest. AIMS: To assess the efficacy of a peptide and glycosaminoglycan-based eyelash enhancer serum in improving eyelash structure. PATIENTS/METHODS: This open-label clinical trial involved 30 females aged 25-65. Eyelashes were assessed at baseline (D0), 4 weeks (D28), and 12 weeks (D84) using specialized software and high-resolution imagery. Measurements included lash number, width, length, volume, arc, and angle. RESULTS: At 12 weeks, significant increases were observed in lash length (+8.3%), number (+5%), width (+10.1%), volume (+14.1%), arc (+13.4%), and angle (+28.3%) compared to baseline. Global Eyelash Assessment (GEA) scores significantly improved, and patient treatment satisfaction increased from 73.34% at D28 to 84.33% at D84. No adverse effects were reported. CONCLUSIONS: The eyelash growth enhancer serum demonstrated significant efficacy in improving eyelash structure by Week 12, with early signs of improvement evident by Week 4. The high patient satisfaction levels underscore the perceived effectiveness of the product.