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Abstract The inflow of CSF into perivascular spaces (PVS) in the brain is crucial for clearing waste molecules. Inefficiency in PVS flow leads to neurodegeneration. Failure of PVS flushing is associated with CSF flow impairment in the intracranial hydrodynamic condition of CSF hypo-pulsatility. However, enlarged PVS (ePVS), a finding indicative of PVS flow dysfunction, is also present in patients with derangement of CSF dynamics characterized by CSF hyper-pulsatility, which increases CSF flow. Intriguingly, two opposite intracranial hydrodynamic conditions would lead to the same result of impairing the PVS flushing. To investigate this issue, we assessed the subsistence of a dysfunctional interplay between CSF and PVS flows and, if the case, the mechanisms preventing a hyper-pulsatile brain from providing an effective PVS flushing. We analyzed the association between phase contrast MRI aqueductal CSF stroke volume (aqSV), a proxy of CSF pulsatility, and the burden of ePVS in chronic adult hydrocephalus, a disease involving a broad spectrum of intracranial hydrodynamics disturbances. In the 147 (85 males, 62 females) patients, the age at diagnosis ranged between 28 and 88 years (median 73 years). Ninety-seven patients had tri-ventriculomegaly and 50 tetra-ventriculomegaly. According to the extent of ePVS, 113 patients had a high ePVS burden, while 34 had a low ePVS burden. aqSV, which ranged between 0 and 562 μL (median 86 μL), was increased with respect to healthy subjects. Patients presenting with less ePVS burden had higher aqSV (p

Objectives Our study aimed to investigate how physical activity (PA) changes over an 11-year follow-up among adults from different socioeconomic positions (SEP) near retirement age. Moreover, an analysis of different PA types is considered.Methods We used data from the EPIC-Italy cohort. We evaluated PA using the Cambridge Physical Activity Index (CPAI) and the metabolic equivalent of tasks (MET) per hour of activity for recreational PA and household PA. Educational level was assessed using the Relative Index of Inequality (RII). Occupational classes were classified according to LIFEPATH Consortium knowledge. Logistic regression was used to analyse PA among SEP and changes during follow-up. Analyses were also conducted separately for sex.Results The higher educated were more prevalent in the higher quartile of recreational PA than the lower educated both at baseline and follow-up (37% vs 28% and 37% vs 27%, respectively). At the baseline, the lower educated had a higher risk of being physically inactive than the higher educated based on recreational PA (overall OR: 1.50, 95% CI 1.40 to 1.60). Manual workers did not show a higher risk of less PA than professionals/managers (overall OR: 1.03, 95% CI 0.91 to 1.16).At follow-up, the lower educated and manual workers showed a higher risk of being physically inactive (lower educated OR: 1.46, 95% CI 1.37 to 1.56; manual worker OR: 1.33, 95% CI 1.18 to 1.50). The analyses of changes in PA showed that those who were less educated or manual workers had a higher risk of worsening their PA during the follow-up period, particularly women in recreational PA and men in CPAI measurement.Conclusion Individuals who had a disadvantaged SEP showed a higher risk of performing less PA over time.

Objectives, setting and participants: We aimed to examine changes in dietary habits, lifestyles (e.g., smoking, physical activity levels, and alcohol intake), anthropometry, other individual health-relevant characteristics, and overall adherence to 2018 WCRF/AICR cancer prevention recommendations, among women enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Florence cohort. Design and measurements: We fitted age- and energy intake-adjusted generalized linear models to describe (a) changes occurring over a person’s lifetime in the transition from adulthood to older age, and (b) differences between women aged 56−60 years belonging to two birth cohorts spaced apart by around 25 years (born in 1933−1941 vs. 1958−1964). Results: Dietary habits and overall adherence to cancer prevention recommendations improved among women (n = 3,309) followed from adulthood to older age (mean age 47.4 and 71.8 years, respectively), despite increases in the prevalence of adiposity and sedentary lifestyle. Women in the younger birth cohort (n = 163) showed significantly greater overall adherence to cancer prevention recommendations than in the older birth cohort (n = 355), but had more often a positive smoking history and an average larger waist circumference. Conclusion: A trend toward better adherence to cancer prevention recommendations emerged when analyzing adult-to-older-age trajectories and differences across birth cohort, yet some critical issues were also identified. Continuous monitoring is essential to detect changing prevention needs and adapt public health policies and practices.

Objectives: The COVID-19 pandemic significantly changed respiratory viruses’ epidemiology due to non-pharmaceutical interventions and possible viral interactions. This study investigates whether the circulation patterns of respiratory viruses have returned to pre-pandemic norms by comparing their peak timing and duration during the first three SARS-CoV-2 seasons to pre-pandemic times. Methods: Global Influenza Surveillance and Response System data from 194 countries (2014-2023) was analyzed for epidemic peak timing and duration, focusing on pre-pandemic and pandemic periods across both hemispheres and the intertropical belt. The analysis was restricted to countries meeting specific data thresholds to ensure robustness. Results: In 2022/2023, the northern hemisphere experienced earlier influenza and respiratory syncytial virus (RSV) peaks by 1.9 months (P

IntroductionOver the past years, there has been a growing interest in the role of immunotherapy in locally advanced (LA) and recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). High-quality data from prospective trials are lacking for the elderly subpopulation. This systematic review and meta-analysis aims to review the efficacy and safety of immunotherapy in older patients.MethodsA systematic literature search was conducted. Randomized clinical trials providing outcome data on a subgroup of elderly (>65 years old) were available for meta-analysis. Primary outcomes of interest were OS and PFS for efficacy analysis.ResultsSeven studies were included in the systematic review and four in the efficacy analysis. The pooled analysis of OS and PFS showed a consistent benefit (HR 0.78 and 0.91, respectively).ConclusionsImmunotherapy may be an effective and well-tolerated treatment option in the elderly population, but more prospective and randomized data are needed.Systematic Review RegistrationPROSPERO (CRD42022333891).

IntroductionCigarette smoking has been recognized as a risk factor for breast cancer (BC) also if the biological mechanism remains poorly understood. High mammographic breast density (MBD) is associated with BC risk and many BC risk factors, such as genetic, anthropometric, reproductive and lifestyle factors and age, are also able to modulate MBD. The aim of the present study was to prospectively explore, in post-menopausal women, the association between smoking habits and MBD, assessed using an automated software, considering duration and intensity of smoking.MethodsThe analysis was carried out in 3,774 women enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) Florence cohort in 1993-98, participating in the 2004-06 follow up (FU) and with at least one full-field digital mammography (FFDM) performed after FU. For each woman, detailed information on smoking habits, anthropometry, lifestyle and reproductive history was collected at enrollment and at FU. Smoking information at baseline and at FU was integrated. The fully automated Volpara™ software was used to obtain total breast volume (cm3), absolute breast dense volume (DV, cm3) and volumetric percent density (VPD, %) from the first available FFDM (average 5.3 years from FU). Multivariable linear regression models were applied to evaluate the associations between smoking habits and VPD or DV.ResultsAn inverse association between smoking exposure and VPD emerged (Diff% -7.96%, p

Abstract Background Vaccination can prevent bacterial and viral infections that could otherwise increase the chances of receiving (unnecessary) antibiotic treatment(s). As a result, vaccination may provide an important public health intervention to control antimicrobial resistance (AMR). Objectives Perform a systematic literature review to better understand the impact of influenza, pneumococcal and COVID-19 vaccination on antibiotic use, and to identify differences in effect between world regions and study designs. Methods We performed a systematic literature review and meta-analysis which updated previous literature reviews with new data from 1 October 2018 to 1 December 2021. The study focuses on randomised controlled trials (RCTs) and observational studies. Results from the meta-analysis of RCTs were stratified by WHO region and age group. Vote counting based on the direction of effect was applied to synthesize the results of the observational studies. Results Most studies are performed in the WHO European Region and the Region of the Americas in high-income countries. RCTs show that the effect of influenza vaccination on the number of antibiotic prescriptions or days of antibiotic use (Ratio of Means (RoM) 0.71, 95% CI 0.62–0.83) is stronger compared to the effect of pneumococcal vaccination (RoM 0.92, 95% CI 0.85–1.00). These studies also confirm a reduction in the proportion of people receiving antibiotics after influenza vaccination (Risk Ratio (RR) 0.63, 95% CI 0.51–0.79). The effect of influenza vaccination in the European and American regions ranged from RoM 0.63 and 0.87 to RR 0.70 and 0.66, respectively. The evidence from observational studies supports these findings but presents a less consistent picture. No COVID-19 studies were identified. Conclusion We find that both RCTs and observational studies show that influenza vaccination significantly reduces antibiotic use, while the effect of pneumococcal vaccination is less pronounced. We were unable to study the effect of COVID-19 vaccination and no clear regional patterns were found due to the high heterogeneity between studies. Overall, our data supports the use of influenza vaccination as an important public health intervention to reduce antibiotic use and possibly control AMR.

Abstract Background High mammographic breast density (MBD) is an established risk factor for breast cancer (BC). Body fatness conveys an increased BC risk in postmenopause but is associated with less dense breasts. Here, we studied the relationship between body fatness and breast composition within the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) longitudinal study. Methods Repeated anthropometric data and MBD parameters (obtained through an automated software on BC screening digital mammograms) were available for all participants, as well as information on other BC risk factors. Multivariate linear regression and functional data analysis were used to longitudinally evaluate the association of body fatness, and changes thereof over time, with dense (DV) and non-dense (NDV) breast volumes and volumetric percent density (VPD). Results A total of 5,262 women were included, with anthropometric data available at 20 and 40 years of age, at EPIC baseline (mean 49.0 years), and an average of 9.4 years thereafter. The mean number of mammograms per woman was 3.3 (SD 1.6). Body fatness (and increases thereof) at any age was positively associated with DV and NDV (the association being consistently stronger for the latter), and inversely associated with VPD. For instance, an increase by 1 kg/year between the age of 40 years and EPIC baseline was significantly associated with 1.97% higher DV, 8.85% higher NDV, and 5.82% lower VPD. Conclusion Body fatness and its increase from young adulthood until midlife are inversely associated with volumetric percent density, but positively associated with dense and non-dense breast volumes in postmenopausal women.

Abstract Background Vaccination can reduce antibiotic use by decreasing bacterial and viral infections and vaccines are highlighted in the WHO Global Action Plan on Antimicrobial Resistance (AMR) as an infection prevention measure to reduce AMR. Our study aimed to analyze whether WHO Member States have developed AMR national action plans that are aligned with the Global Action Plan regarding objectives on vaccination. Methods We reviewed 77 out of 90 AMR national action plans available in the WHO library that were written after publication of the Global Action Plan in 2015. Each plan was analyzed using content analysis, with a focus on vaccination and key components as defined by WHO (I. Strategic plan (e.g. goals and objectives), II. Operational plan, III. Monitoring and Evaluation plan). Results Vaccination was included in 67 of 77 AMR plans (87%) across all WHO Regions (Africa: n = 13/13, the Eastern Mediterranean: n = 15/16, Europe: n = 10/14, the Americas: n = 8/8, South-East Asia: n = 8/11, and the Western Pacific: n = 13/15). Pneumococcal and influenza vaccination were most frequently highlighted (n = 12 and n = 11). We found indications that vaccination objectives are more often included in AMR plans from lower income countries, while higher income countries more often include specific vaccines. The key WHO components of national action plans were frequently not covered (I. 47% included, II. 57%, III. 40%). In total, 33 countries (43%) included indicators (e.g. strategic objectives) to capture the role of vaccines against AMR. Conclusions While vaccination to reduce AMR is seen as an important global public health issue by WHO, there appears to be a gap in its adoption in national AMR plans. Country income levels seem to influence the progress, implementation and focus of national action plans, guided by a lack of funding and prioritization in developing countries. To better align the global response to AMR, our review suggests there is a need to update national action plans to include objectives on vaccination with more focus on specific vaccines that impact antibiotic use.

PurposeBiochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Methods/patientsPatients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes.ResultsData from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS).ConclusionCholine PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life.

Abstract Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We designed a matched case–case study in the EPIC Florence cohort, to evaluate possible associations between the pre-diagnostic metabolomic profile and the risk of BC in high- versus low-MBD women who developed BC during the follow-up. A case–case design with 100 low-MBD (MBD ≤ 25%) and 100 high-MDB BC cases (MBD > 50%) was performed. Matching variables included age, year and type of mammographic examination. 1H NMR metabolomic spectra were available for 87 complete case–case sets. The conditional logistic analyses showed an inverse association between serum levels of alanine, leucine, tyrosine, valine, lactic acid, pyruvic acid, triglycerides lipid main fraction and 11 VLDL lipid subfractions and high-MBD cases. Acetic acid was directly associated with high-MBD cases. In models adjusted for confounding variables, tyrosine remained inversely associated with high-MBD cases while 3 VLDL subfractions of free cholesterol emerged as directly associated with high-MBD cases. A pathway analysis showed that the “phenylalanine, tyrosine and tryptophan pathway” emerged and persisted after applying the FDR procedure. The supervised OPLS-DA analysis revealed a slight but significant separation between high- and low-MBD cases. This case–case study suggested a possible role for pre-diagnostic levels of tyrosine in modulating the risk of BC in high- versus low-MBD women. Moreover, some differences emerged in the pre-diagnostic concentration of other metabolites as well in the metabolomic fingerprints among the two groups of patients.

Abstract Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged

Abstract CSF shunting with adjustable valve is the treatment of idiopathic normal pressure hydrocephalus. The opening pressure valve setting is left to the neurosurgeon’s experience. Aqueductal CSF stroke volume by phase-contrast magnetic resonance measures the CSF passing through the Sylvian aqueduct and it changes with intracranial hydrodynamics. We sought to identify a window of stroke volume differences associated with the best clinical outcome and lowest rate of complications. The records of 69 patients were reviewed. At every clinical check, stroke volume, opening pressure valve, clinical outcome, and CSF overdrainage were analyzed. The correlation between stroke volume differences and negative outcome was also analyzed. The median follow-up was 2.3 years (range 0.3–10.4 years). The odds of negative outcome between two consecutive checks significantly increased by 16% (95%CI 4–28%, p = 0.006). Taking the lowest risk group as reference, the odds ratio of negative outcome was 1.16 (95%CI 0.51–2.63, p = 0.726) for SV differences less than − 37.6 µL, while it was 1.96 (95%CI 0.97–3.98, p = 0.062) for stroke volume changes above + 23.1 µL. Maintaining stroke volume values within a definite range might help maximize clinical benefit and avoid the risk of CSF overdrainage.

Breast cancer (BC) is a multifactorial disease caused by an interaction between genetic predisposition and environmental exposures. MicroRNAs are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and seem to be related to cancer risk factors. We conducted a systematic review and meta-analysis to identify circulating microRNAs related to BC diagnosis, paying special attention to methodological problems in this research field. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seventy-five studies were included in the systematic review. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seven studies were included in the MIR21 and MIR155 meta-analysis, while four studies were included in the MIR10b metanalysis. The pooled sensitivity and specificity of MIR21 for BC diagnosis were 0.86 (95%CI 0.76–0.93) and 0.84 (95%CI 0.71–0.92), 0.83 (95%CI 0.72–0.91) and 0.90 (95%CI 0.69–0.97) for MIR155, and 0.56 (95%CI 0.32–0.71) and 0.95 (95%CI 0.88–0.98) for MIR10b, respectively. Several other microRNAs were found to be dysregulated, distinguishing BC patients from healthy controls. However, there was little consistency between included studies, making it difficult to identify specific microRNAs useful for diagnosis.

We conducted a systematic review and meta-analysis to investigate the role of alcohol consumption with the prognosis of prostate cancer (PCa). Published reports were gathered on 15 October 2022, from PUBMED/MEDLINE and EMBASE. We found 19 independent eligible studies on the association between consumption of alcoholic beverages and the risk of fatal PCa (n = 5), PCa mortality (n = 5) in healthy subjects, and PCa patients’ survival (n = 7) or surrogates thereof (n = 2). We used random effects meta-analysis to obtain a summary risk estimate (SRE) and 95% confidence intervals (95%CI) for incidence of fatal PCa and PCa mortality. The meta-analysis revealed no association between alcohol consumption and fatal prostate cancer incidence risk in healthy subjects with an indication for publication bias, but omitting the study that mainly increased the between-study heterogeneity, the SRE becomes significant (SRE 1.33, 95%CI 1.12–1.58), and the heterogeneity disappeared (I2 = 0%) with no indication of publication bias. No association of alcohol consumption was found with mortality risk in PCa patients (SRE 0.97, 95%CI 0.92–1.03) and PCa mortality risk in healthy subjects (SRE 1.03, 95%CI 0.82–1.30). In conclusion, this study suggests that there is some evidence of an association between high alcohol consumption and an increased risk of incidence of fatal prostate cancer in healthy subjects. Given the inconsistencies this result warrants further confirmation.

Background: Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and it is of interest, for prevention purposes, to consider lifestyle factors that may modulate both MBD and BC risk. Here, we conducted a systematic review of the most up-to-date evidence on the association between diet as a whole and MBD. Methods: We considered as eligible for inclusion in our review (PROSPERO registration code CRD42022335289) the studies published until 31 December 2021, that reported on the association between a priori or a posteriori dietary patterns (in observational studies) or dietary interventions (in randomized controlled trials) and MBD. Results: In total, twelve studies were included. MBD tended to be inversely associated with adherence to dietary patterns characterized by high consumption of plant-based foods and low in meat, animal fats, and alcohol, defined both a priori (e.g., Mediterranean diet and WCRF/AICR guidelines) or a posteriori (e.g., “fruit-vegetable-cereal” and “salad-sauce-pasta/grains” patterns). Findings from intervention studies were in fair agreement with those from observational studies. Conclusions: While further studies are needed, we found suggestive evidence that the adoption of a healthy diet is associated with lower MBD.

Objectives: Understanding the proportion of pandemic deaths captured as ‘laboratory-confirmed’ deaths is crucial. We assessed the ability of laboratory-confirmed deaths to capture mortality in the EU during the 2009 pandemic, and examined the likelihood that these findings are applicable to the SARS-CoV-2 pandemic. Methods: We present unpublished results from the Global Pandemic Mortality (GLaMOR) project, in which country-specific mortality estimates were made for the 2009 influenza H1N1p pandemic. These estimates were compared with laboratory-confirmed deaths during the 2009 pandemic to estimate the ability of surveillance systems to capture pandemic mortality. Results: For the 2009 influenza H1N1p pandemic, we estimated that the proportion of true pandemic deaths captured by laboratory-confirmed deaths was approximately 67%. Several differences between the two pandemics (e.g. age groups affected) make it unlikely that this capture rate will be equally high for SARS-CoV-2. Conclusion: The surveillance of laboratory-confirmed deaths in the EU during the 2009 pandemic was more accurate than previously assumed. We hypothesize that this method is less reliable for SARS-CoV-2. Near-real-time excess all-cause mortality estimates, routinely compiled by EuroMOMO, probably offer a better indicator of pandemic mortality. We urge more countries to join this project and that national-level absolute mortality numbers are presented.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Primary and secondary preventions are key to reducing the global burden. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and to be related to cancer risk factors, such as obesity and inflammation. We conducted a systematic review and meta-analysis to identify circulating miRNAs related to CRC diagnosis that could be selected as biomarkers in a meet-in-the-middle analysis. Forty-four studies were included in the systematic review and nine studies in the meta-analysis. The pooled sensitivity and specificity of miR-21 for CRC diagnosis were 77% (95% CI: 69–84) and 82% (95% CI: 70–90), respectively, with an AUC of 0.86 (95% CI: 0.82–0.88). Several miRNAs were found to be dysregulated, distinguishing patients with CRC from healthy controls. However, little consistency was present across the included studies, making it challenging to identify specific miRNAs, which were consistently validated. Understanding the mechanisms by which miRNAs become biologically embedded in cancer initiation and promotion may help better understand cancer pathways to develop more effective prevention strategies and therapy approaches.

Background: Respiratory viral infections (RVI) are a leading cause of mortality worldwide. We compared the epidemiology and severity of RVI in Ecuador during 2009–2016. Methods: Respiratory specimens collected within the national surveillance system were tested for influenza viruses, respiratory syncytial virus (RSV), adenovirus, parainfluenza virus, and human metapneumovirus. Overall and virus-specific positive detection rate (PDR) were calculated and compared the timing of epidemics caused by the different viruses. Logistic regression models were used to compare the age distribution and risk of death across respiratory viruses. Results: A total of 41,172 specimens were analyzed: influenza (PDR = 14.3%) and respiratory syncytial virus (RSV) (PDR = 9.5%) were the most frequently detected viruses. Influenza epidemics typically peaked in December–January and RSV epidemics in March; seasonality was less evident for the other viruses. Compared to adults, children were more frequently infected with RSV, adenovirus, parainfluenza, and influenza B, while the elderly were less frequently infected with influenza A(H1N1)p. The age-adjusted risk of death was highest for A(H1N1)p (odds ratio [OR] 1.73, 95% confidence intervals [CI] 1.38–2.17), and lowest for RSV (OR 0.75, 95%CI 0.57–0.98). Conclusions: Whilst influenza and RSV were the most frequently detected pathogens, the risk of death differed by RVI, being highest for pandemic influenza and lowest for RSV. Keywords: Respiratory viral infections, Epidemiology, Age distribution, Case-fatality ratio, Ecuador

Abstract Background Description of the epidemiology of influenza is needed to inform influenza vaccination policy. Here we examined influenza virus circulation in countries in the Asia-Pacific region and compared the timing of seasonal epidemics with the timing of influenza vaccination. Methods Data were obtained from the World Health Organization (WHO) FluNet database for 2010–2017 for countries in the WHO Asia-Pacific region. Data from countries covering ≥5 consecutive seasons and ≥ 100 influenza positive cases per year were included. Median proportions of cases for each influenza virus type were calculated by country and season. The timing and amplitude of the epidemic peaks were determined by Fourier decomposition. Vaccination timing was considered appropriate for each country if it was recommended ≤4 months before the primary peak of influenza circulation. Results Seven hundred eleven thousand seven hundred thirty-four influenza cases were included from 19 countries. Peak circulation coincided with the winter seasons in most countries, although patterns were less clear in some countries in the inter-tropical area due to substantial secondary peaks. Influenza A/H3N2 dominated overall, but proportions of A and B strains varied by year and by country. Influenza B represented 31.4% of all cases. The WHO-recommended timing for influenza vaccination was appropriate in 12 countries. Vaccination timing recommendations were considered inappropriate in Laos, Cambodia, and Thailand, and were inconclusive for India, Sri Lanka, Singapore, and Vietnam due to unclear seasonality of influenza virus circulation. Conclusions Influenza virus circulation varied considerably across the Asia-Pacific region with an unusually high burden of influenza B. The recommended timing for vaccination was appropriate in most countries, except for several countries with unclear seasonality, mainly located in the inter-tropical area.

Temporal variation of respiratory syncytial virus (RSV) epidemics was recently reported to be determined by the dominant RSV subtype. However, when we repeated the analysis for 4 countries in the Northern and Southern Hemispheres, the dominant subtype did not seem to affect temporal variation of RSV epidemics.

IntroductionWe aimed to develop an innovative population-based method to estimate the health effect of influenza vaccination based on electronic medical records collected within a general practitioner (GP)-based influenza surveillance system in the Netherlands.MethodsIn each season between 2006/07 and 2015/16, we fitted multilevel Poisson regression models to compare GP consultation rates for clinically diagnosed influenza, acute respiratory infections (ARI), pneumonia, and lower back pain (as a control) between vaccinated vs. unvaccinated individuals. Season-specific relative risks and 95% confidence intervals (CI) were pooled into summary risk ratio (SRR) through random-effects meta-analysis models. Analyses were stratified by patient age (ResultsOverall, 12.6% and 21.4% of study subjects were vaccinated because of their age only or because of an underlying medical condition. Vaccine uptake declined over time, especially among subjects aged ≤74 years with medical indications for vaccination. Vaccinated individuals had significantly higher GP consultation rates for clinically diagnosed influenza (SRR 1.24, 95% CI 1.12-1.38, p-value DiscussionContrary to expectations, influenza vaccinees have GP consultation rates for clinically diagnosed influenza, ARI and pneumonia that are 24-33% higher compared to unvaccinated individuals. The lower back pain finding suggests that the increase in consultation rates is partially caused by confounding. Importantly, considering the data are not laboratory-confirmed, our results cannot be linked directly to influenza, but only to respiratory illnesses in general.

Abstract Background Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases). Methods For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity. Results The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries’ geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play. Conclusions These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

Several studies have investigated the beneficial effects of vitamin D on survival of cancer patients. Overall evidence has been accumulating with contrasting results. This paper aims at narratively reviewing the existing articles examining the link between vitamin D supplementation and cancer mortality. We performed two distinct searches to identify observational (ObS) studies and randomized clinical trials (RCTs) of vitamin D supplementation (VDS) in cancer patients and cohorts of general population, which included cancer mortality as an outcome. Published reports were gathered until March 2021. We identified 25 papers published between 2003 and 2020, including n. 8 RCTs on cancer patients, n. 8 population RCTs and n. 9 ObS studies. There was some evidence that the use of VDS in cancer patients could improve cancer survival, but no significant effect was found in population RCTs. Some ObS studies reported evidence that VDS was associated with a longer survival among cancer patients, and only one study found an opposite effect. The findings do not allow conclusive answers. VDS may have the potential as treatment to improve survival in cancer patients, but further investigations are warranted. We strongly support investment in well-designed and sufficiently powered RCTs to fully evaluate this association.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.

BackgroundHealth literacy(HL) has recently been proposed as a potential mediator in the pathway through which socio-economic status(SES) affects health. However, empirical research investigating the contribution of HL in this relationship remains scarce. This study investigated whether functional HL mediates the association between SES and self-reported health(SRH) in an adult population-based sample.MethodsThe study adopted a cross-sectional design. Education level and financial status were used as measures of SES, while functional HL was assessed with the Newest Vital Sign. Moderated mediation analyses were conducted using SES variables as independent variables, SRH as dependent variable and functional HL as mediator variable. Furthermore, age, sex and chronic diseases were tested as moderators of the effect mediated by functional HL.Results452 subjects completed the study (58,8% female; mean age 53,25±11,7). Results showed that functional HL mediates on average 18.5% of the association between education and SRH (p = 0.02) and 12.9% (p = 0.01) of the association between financial status and SRH. Furthermore, the proportion of effect mediated by functional HL was found to be higher in lower socio-economic classes for both SES variables considered. No significant moderation effects of age, sex or chronic diseases were observed for both SES variables.ConclusionFindings suggest that functional HL may serve as a pathway by which SES affects health status, especially in lower SES groups. HL may be a valuable and actionable intermediate target for addressing health inequalities. However, further studies are needed to better define the mediating role of HL across socio-economic classes.

There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). We meta-analyzed studies reporting on obesity and colorectal cancer (CRC) risk in LS patients to test whether obese subjects were at increased risk of cancer compared to those of normal weight. We explored also a possible sex-specific relationship between adiposity and CRC risk among patients with LS. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We investigated the causes of between-study heterogeneity and assessed the presence of publication bias. We were able to retrieve suitable data from four independent studies. We found a twofold risk of CRC in obese men compared to nonobese men (SRR = 2.09; 95%CI: 1.23–3.55, I2 = 33%), and no indication of publication bias (p = 0.13). No significantly increased risk due to obesity was found for women. A 49% increased CRC risk for obesity was found for subjects with an MLH1 mutation (SRR = 1.49; 95%CI: 1.11–1.99, I2 = 0%). These results confirm the different effects of sex on obesity and CRC risk and also support the public measures to reduce overweight in people with LS, particularly for men.

IntroductionAbout 1.25 million people worldwide die every year because of road accidents. Risk is higher when drivers use mobile phones, whereas seat belts help to prevent crash-related injury. We aimed to evaluate the prevalence, associated factors, and temporal trend of the use of seat belts and mobile phones among drivers and passengers in Florence, Italy (2005-2015).MethodsUse of seat belts and mobile phones use was monitored via direct observation in four areas in the province of Florence. We fitted Poisson regression models with robust variance to investigate the factors associated with the use of seat belts and mobile phones use by the drivers and to explore long-term trends and seasonal patterns in the two time-series.ResultsWe observed a total of an overall 134,775 vehicles: seat belts were worn by 71.8% of drivers and front-seat passengers and 27.6% of back-seat passengers, while mobile phones were being used by 4.8% of drivers. Drivers were more likely to wear seat belt when transporting passengers (≥2 vs none: prevalence ratio [PR] 1.21, 95% confidence intervals [CI] 1.14-1.29) and while driving in the afternoon (PR 1.04, 95% CI 1.03-1.05), and less likely when the front-seat passenger was not wearing seat belts (PR 0.33, 95% CI 0.32-0.34). After an initial increase, seat belts use by the driver decreased over time (-0.5% each year during 2010-2015), with significant peaks and troughs in July and January, respectively. Mobile phone use by the driver was inversely associated with wearing seat belts (PR 0.67, 95% CI 0.64-0.70) and carrying passengers (≥2 vs. none PR 0.20, 95% CI 0.07-0.52). The proportion of drivers using mobile phones did not vary over time nor showed any clear seasonality.ConclusionsDrivers' risky behaviours (not wearing a seat belt and using a mobile phone) are associated, showing a global misperception of risk among a subset of drivers. The number of passengers and their behaviour is also associated with the driver's attitude. The effectiveness of primary enforcement laws has declined in Italy in recent years; therefore, other strategies should be devised and implemented.

INTRODUCTION:The increased availability of influenza surveillance data in recent years justifies an actual and more complete overview of influenza epidemiology in Latin America. We compared the influenza surveillance systems and assessed the epidemiology of influenza A and B, including the spatio-temporal patterns of influenza epidemics, in ten countries and sub-national regions in Latin America. METHODS:We aggregated the data by year and country and characteristics of eighty-two years were analysed. We calculated the median proportion of laboratory-confirmed influenza cases caused by each virus strain, and compared the timing and amplitude of the primary and secondary peaks between countries. RESULTS:37,087 influenza cases were reported during 2004-2012. Influenza A and B accounted for a median of 79% and, respectively, 21% of cases in a year. The percentage of influenza A cases that were subtyped was 82.5%; for influenza B, 15.6% of cases were characterized. Influenza A and B were dominant in seventy-five (91%) and seven (9%) years, respectively. In half (51%) of the influenza A years, influenza A(H3N2) was dominant, followed by influenza A(H1N1)pdm2009 (41%) and pre-pandemic A(H1N1) (8%). The primary peak of influenza activity was in June-September in temperate climate countries, with little or no secondary peak. Tropical climate countries had smaller primary peaks taking place in different months and frequently detectable secondary peaks. CONCLUSIONS:We found that good influenza surveillance data exists in Latin America, although improvements can still be made (e.g. a better characterization of influenza B specimens); that influenza B plays a considerable role in the seasonal influenza burden; and that there is substantial heterogeneity of spatio-temporal patterns of influenza epidemics. To improve the effectiveness of influenza control measures in Latin America, tropical climate countries may need to develop innovative prevention strategies specifically tailored to the spatio-temporal patterns of influenza in this region.

INTRODUCTION:Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. METHODS:This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. RESULTS:212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. DISCUSSION:Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.

Studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system.The IBVD (Influenza B in Vircases Database) study collected information on signs and symptoms at disease onset from laboratory-confirmed influenza patients of any age who consulted a sentinel practitioner in France. We compared the clinical presentation of influenza patients across age groups (0-4, 5-14, 15-64 and 65+ years), virus types (A, B) and subtypes/lineages (A(H3N2), pandemic A(H1N1), B Victoria, B Yamagata).Overall, 14,423 influenza cases (23.9% of which were influenza B) were included between 2003-2004 and 2012-2013. Influenza A and B accounted for over 50% of total influenza cases during eight and two seasons, respectively. There were minor differences in the distribution of signs and symptoms across influenza virus types and subtypes/lineages. Compared to patients aged 0-4 years, those aged 5-14 years were more likely to have been infected with type B viruses (OR 2.15, 95% CI 1.87-2.47) while those aged 15-64 years were less likely (OR 0.83, 95% CI 0.73-0.96). Males and influenza patients diagnosed during the epidemic period were less likely to be infected with type B viruses.Despite differences in age distribution, the clinical illness produced by the different influenza virus types and subtypes is indistinguishable among patients that consult a general practitioner for acute respiratory infections.

Influenza B represents a high proportion of influenza cases in some seasons (even over 50%). The Influenza B study in General Practice (IBGP) is a multicenter study providing information about the clinical, demographic and socio-economic characteristics of patients affected by lab-confirmed influenza A or B. Influenza B patients and age-matched influenza A patients were recruited within the sentinel surveillance networks of France and Turkey in 2010-11 and 2011-12 seasons. Data were collected for each patient at the swab test day, after 9±2 days and, if not recovered, after 28±5 days. It was related to patient's characteristics, symptoms at presentation, vaccination status, prescriptions of antibiotics and antivirals, duration of illness, follow-up consultations in general practice or emergency room. We performed descriptive analyses and developed a multiple regression model to investigate the effect of patients and disease characteristics on the duration of illness. Overall, 774 influenza cases were included in the study: 419 influenza B cases (209 in France and 210 in Turkey) and 355 influenza A cases (205 in France and 150 in Turkey). There were no differences between influenza A and B patients in terms of clinical presentation and number of consultations with a practitioner; however, the use of antivirals was higher among influenza B patients in both countries. The average (median) reported duration of illness in the age groups 0-14 years, 15-64 years and 65+ years was 7.4 (6), 8.7 (8) and 10.5 (9) days in France, and 6.3 (6), 8.2 (7) and 9.2 (6) days in Turkey; it increased with age but did not differ by virus type; increased duration of illness was associated with antibiotics prescription. In conclusion, our findings show that influenza B infection appears not to be milder disease than influenza A infection.