Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: A systematic review and meta-analysis.

Abstract Background In the elderly, traditional influenza inactivated vaccines are often only modestly immunogenic, owing to immunosenescence. Given that adjuvantation is a means of enhancing the immune response, the trivalent inactivated vaccine adjuvanted with MF59 (MF59-TIV) was specifically designed to overcome this problem. Considering that, for ethical reasons, the absolute effectiveness of an influenza vaccine in the elderly cannot be demonstrated in placebo-controlled studies, the present study aimed to assess the effectiveness of MF59-TIV in preventing influenza-related outcomes in the elderly. Methods We conducted a systematic review of observational studies aimed at evaluating the effectiveness of MF59-TIV against influenza-related outcomes. Results of single studies were pooled whenever possible. Results Of the 1993 papers screened, 11 (6 case-control, 3 cohort and 2 prospective case-control) studies were identified. Hospitalization due to pneumonia/influenza and laboratory-confirmed influenza were reported in more than one study, while other outcomes (influenza-like illness, cardio- and cerebrovascular accidents) were investigated only by one study each. Pooled analysis of four case-control studies showed an adjusted MF59-TIV effectiveness of 51% (95% CI: 39–61%) against hospitalizations for pneumonia/influenza among community-dwelling seniors. Pooled results of the adjusted vaccine effectiveness against laboratory-confirmed influenza were also high (60.1%), although the 95% CI passed through zero (−1.3 to 84.3%). Other single community-based studies showed very high effectiveness of MF59-TIV in preventing hospitalizations for acute coronary [87% (95% CI: 35–97%)] and cerebrovascular [93% (95% CI: 52–99%)] events. MF59-TIV proved highly effective [94% (95% CI: 47–100%] in reducing influenza-like illness among institutionalized elderly. Furthermore, MF59-TIV displayed greater efficacy than non-adjuvanted vaccines in preventing hospitalizations due to pneumonia/influenza [adjusted risk ratio 0.75 (95% CI: 0.57–0.98)] and laboratory-confirmed influenza [adjusted odds ratio 0.37 (0.14–0.96)]. Conclusions Our results suggest that MF59-TIV is effective in reducing several influenza-related outcomes among the elderly, especially hospitalizations due to influenza-related complications

Production of vegetables and artichokes is associated with lower cardiovascular mortality: An ecological study

Mortality due to cardiovascular disease (CVD), including cerebrovascular disease (CED) and ischaemic heart disease (IHD), was considerably different in eight municipalities of the province of Castellón, Community of Valencia (Spain) during the period of 1991–2011. In addition, these villages showed differences in agricultural practices and production. Since high vegetable consumption has been linked to decreased all-cause, CVD, and CED mortalities, we hypothesized that the diversity in vegetable and artichoke production, used as proxies for their consumption, could be associated with the diversity of mortality rates. In order to test our hypothesis, we estimated the smoothed standardized mortality ratios (SMRs) of CVD, CED, and IHD mortalities and a directed, age-adjusted mortality rate (AMR). We used a multilevel linear regression analysis to account for the ecological nature of our study. After adjustment, the CVD and CED SMRs were inversely associated with vegetable and artichoke production, with a reduction in SMRs for CVD: −0.19 (95% Confidence Interval [CI] −0.31 to −0.07) and −0.42 (95% CI −0.70 to −0.15) per hectare/103 inhabitants, respectively. The SMRs for CED also decreased: −0.68 (95% CI −1.61 to −0.19) and −1.47 (95% CI −2.57 to −0.36) per hectare/103 inhabitants, respectively. The SMRs for IHD were not associated with vegetal and artichoke production. When the directed AMR was used, CED mortality was consistent with the previous results, whereas the CVD mortality association was lost. Our results indicate that vegetable and artichoke production may act as protective factors of CED and CVD mortalities

Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011–2012 influenza season: A comparative effectiveness study using the Valencia health care information system

AbstractBackgroundThe use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking.MethodsWe conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011–2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR).ResultsOverall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50–0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52–0.85).ConclusionsDuring the 2011–2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV

Cigarette smoke challenges bone marrow mesenchymal stem cell capacities in guinea pig

BACKGROUND: Cigarette smoke (CS) is associated with lower numbers of circulating stem cells and might severely affect their mobilization, trafficking and homing. Our study was designed to demonstrate in an animal model of CS exposure whether CS affects the homing and functional capabilities of bone marrow-derived mesenchymal stem cells (BM-MSCs). METHODS: Guinea pigs (GP), exposed or sham-exposed to CS, were administered via tracheal instillation or by vascular administration with 2.5 × 106 BM-MSCs obtained from CS-exposed or sham-exposed animal donors. Twenty-four hours after cell administration, animals were sacrificed and cells were visualised into lung structures by optical microscopy. BM-MSCs from 8 healthy GP and from 8 GP exposed to CS for 1 month were isolated from the femur, cultured in vitro and assessed for their proliferation, migration, senescence, differentiation potential and chemokine gene expression profile. RESULTS: CS-exposed animals showed greater BM-MSCs lung infiltration than sham-exposed animals regardless of route of administration. The majority of BM-MSCs localized in the alveolar septa. BM-MSCs obtained from CS-exposed animals showed lower ability to engraft and lower proliferation and migration. In vitro, BM-MSCs exposed to CS extract showed a significant reduction of proliferative, cellular differentiation and migratory potential and an increase in cellular senescence in a dose dependent manner. CONCLUSION: Short-term CS exposure induces BM-MSCs dysfunction. Such dysfunction was observed in vivo, affecting the cell homing and proliferation capabilities of BM-MSCs in lungs exposed to CS and in vitro altering the rate of proliferation, senescence, differentiation and migration capacity. Additionally, CS induced a reduction in CXCL9 gene expression in the BM from CS-exposed animals underpinning a potential mechanistic action of bone marrow dysfunction

Snail1 transcriptional repressor binds to its own promoter and controls its expression

The product of Snail1 gene is a transcriptional repressor of E-cadherin expression and an inductor of the epithelial–mesenchymal transition in several epithelial tumour cell lines. Transcription of Snail1 is induced when epithelial cells are forced to acquire a mesenchymal phenotype. In this work we demonstrate that Snail1 protein limits its own expression: Snail1 binds to an E-box present in its promoter (at −146 with respect to the transcription start) and represses its activity. Therefore, mutation of the E-box increases Snail1 transcription in epithelial and mesenchymal cells. Evidence of binding of ectopic or endogenous Snail1 to its own promoter was obtained by chromatin immunoprecipitation (ChIP) experiments. Studies performed expressing different forms of Snail1 under the control of its own promoter demonstrate that disruption of the regulatory loop increases the cellular levels of Snail protein. These results indicate that expression of Snail1 gene can be regulated by its product and evidence the existence of a fine-tuning feed-back mechanism of regulation of Snail1 transcription

Long COVID Prevalence and the Impact of the Third SARS-CoV-2 Vaccine Dose: A Cross-Sectional Analysis from the Third Follow-Up of the Borriana Cohort, Valencia, Spain (2020–2022)

Background: In March 2020, a COVID-19 outbreak linked to mass gathering dinners at the Falles Festival in Borriana, Spain, resulted in an estimated attack rate of 42.6% among attendees. Methods: In June 2022, we conducted a cross-sectional follow-up study of 473 adults aged 18 to 64 who attended the dinners at the Falles Festival in 2020, examining the cumulative experience after SARS-CoV-2 infection and vaccination responses. Data included demographic details, lifestyle habits, medical history, infection records, and vaccinations from a population-based vaccine registry. Blood samples were analyzed for SARS-CoV-2 antibodies and cellular immunity. We employed a doubly robust inverse-probability weighting analysis to estimate the booster vaccine dose’s impact on long COVID prevalence and symptom count. Results: A total of 28.1% of participants met the WHO criteria for long COVID, with older individuals showing higher rates. Long COVID diagnosis was less likely with factors including O blood group, higher occupational status, physical activity, three vaccine doses, strong SARS-CoV-2-S-reactive IFNγ-producing-CD8+ response, and infection during the Omicron period. Increased age, high or low social activity, underlying health conditions, a severe initial COVID episode, and reinfection were associated with higher long COVID likelihood. A booster dose, compared to one or two doses, reduced long COVID risk by 74% (95% CI: 56% to 92%) and symptom count by 55% (95% CI: 32% to 79%). Conclusion: Long COVID was prevalent in a significant portion of those who contracted COVID-19, underscoring the need for sustained followup and therapeutic strategies. Vaccinations, notably the booster dose, had a substantial beneficial effect on long-term infection outcomes, affirming the vaccination’s role in mitigating SARS-CoV-2 infection consequencesProject funded by Conselleria de Sanitat Universal i Salut Pública (Generalitat Valenciana, Spain) and the EU Operational Program of the European Regional Development Fund (ERDF) for the Valencian Community 2014–2020, within the framework of the REACT-EU programme, as the Union’s response to the COVID-19 pandemic.Medicin

Assessment of the Variability in Influenza A(H1N1) Vaccine Effectiveness Estimates Dependent on Outcome and Methodological Approach

Estimation of Influenza vaccine effectiveness (VE) varies with study design, clinical outcome 10 considered and statistical methodology used. By estimating VE using differing outcomes and 11 statistical methods on the same cohort of individuals the variability in the estimates produced can 12 be better understood. The Pandemic Influenza Primary Care Reporting (PIPeR) cohort of approximately 193,000 individuals 14 was used to estimate pandemic VE in Scotland during season 2009-10. VE results for three 15 outcomes; influenza related consultations, virological confirmed influenza and death were 16 considered. Use of individualised records allowed all models to be adjusted for age, sex, 17 deprivation, risk status relating to chronic illnesses, seasonal vaccination status and a marker of the 18 individual’s propensity to consult. For the consultation and death outcomes, VE was calculated by 19 comparing consultation rates in the unvaccinated and vaccinated groups, adjusted for the listed 20 factors, using both Cox and Poisson regression models. For the consultation outcome, the 21 unvaccinated group was split into individuals before vaccination and those never vaccinated to allow 22 for potential differences in the health seeking behaviour of these groups. For the virology outcome 23 estimates were calculated using a generalised additive logistic regression model. All models were 24 adjusted for time. Vaccine effect was demonstrated for the influenza-like illness consultation outcome using the Cox 26 model (VE=49% 95% CI (19%, 67%)) with lower estimates from the model splitting the before and 27 never vaccinated groups (VE=34.2% with 95% CI (-0.5%, 58.9%)). Vaccine effect was also illustrated 28 for overall mortality (VE=40% (95% CI 18%, 56%)) and a virological confirmed subset of symptomatic 29 individuals (VE=60% (95% CI -38%, 89%))

Atopic dermatitis incidence and risk factors in young adults in Castellon (Spain): A prospective cohort study

Introduction: There are few atopic dermatitis (AD) incidence cohort studies in young adults, the etiology of this disease remains obscure, and AD risk factors in adults are not well understood. The objective of this study was to estimate AD ten-year incidence and prevalence in a cohort of adolescent aged 14–16 at inception in Castellon province in Valencia Region, Spain and describe related risk factors. Material and methods: From 2002 to 2012, a population-based prospective cohort study was carried out. Questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC) were used with an additional questionnaire for related factors completed by participants and their parents, respectively, in 2002. In 2012 the same questionnaires were completed by the participants’ through a telephone interview, and incidence and prevalence of AD were estimated. Directed acyclic graphs, Poisson regression and inverse probability weighted regression adjustment were used. Results: The participation rate was 79.5% (1435/1805) with AD lifetime prevalence of 34.9% and AD incidence of 13.5 per 1000 person years. Females presented higher prevalence and incidence than males. After adjustment significant risk factors were being female, history of asthma or allergic rhinitis, family history of AD, history of respiratory infections, history of bronchitis, history of pneumonia, history of sinusitis, and birthplace outside Castellon province. The highest AD population attributable risks were female, 30.3%, and history of respiratory infections 15.3%. Differences with AD childhood risk factors were found. Conclusions: AD incidence in our cohort was high and several risks factors were related to AD