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Background and aim: Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism. Methods: To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered. Results: Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review. Conclusions: After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.

Minor grape varieties often possess key traits to produce wines with specific territorial identity. Italy is home to a wide selection of autochthonous grapevines. In 2005, four white grape varieties from the Amalfi coast, Fenile, Ginestra, Pepella and Ripoli were registered in the National Catalogue grapevines. They are all complementary varieties with a rich biodiversity and linked to an ancient wine heritage. Studies on such varieties have not been conducted yet. Here, the metabolite content of the above four grape varieties is described. Ripoli was the richest in quercetin derivatives while very low was the content of kaempferol derivatives; Pepella possessed an equal amount of quercetins and kaempferols; Ginestra and Fenile featured a quercetins abundance twice that of kaempferols. Also, the (+)-catechin content was higher than (–)-epicatechin's; B-type procyanidins occurred in higher concentrations in Pepella and Ripoli than in Fenile and Ginestra. Hydroxycinnamic acids were also identified and quantified. Seeds from each variety were carefully analyzed and flavanols were identified up to decamers along with their galloylation percentage. The obtained data are a tool of variety differentiation and useful to develop appropriate vinification procedures to ameliorate the quality of wines.

Grape pomace, a bulky component of winery waste, is a source of healthy compounds. So far, scientific research has mainly focused on its polyphenol content, but given the impressive number of bioactivities shown by grape pomace, it is not unlikely that, besides polyphenols, additional metabolites, so far undetected, may be involved. In order to verify such hypothesis, an in-depth chemical analysis of Aglianico (Vitis vinifera) grape pomace was conducted by NMR and LC-MS/MS. In addition to a number of polyphenols, a remarkable concentration of oleanolic acid (0.45 mg/g - fresh weight) was determined in the analyzed material. Oleanolic acid is a natural triterpenoid showing many bioactivities including antitumor, anti-inflammatory, antibiotic and antiviral properties. Also, it was proven a potential antidiabetic molecule in Type1 Diabetes rats. Hence, its influence on the mitochondrial and glucose uptake activities of C2C12 myoblast was here assessed, thus supporting oleanolic acid as a promising antidiabetic metabolite.

The present work aims to characterize and investigate the anti-inflammatory activity of hop extracts (cv. Cascade) in an in vitro model of gastric inflammation. The biological activities of hydroalcoholic and aqueous extracts from cones were evaluated by comparing IL-8 inhibition induced by TNFα. The hydroalcoholic extract demonstrated a higher inhibitory effect, which was just slightly affected by an in vitro simulated gastric digestion. The identification of active compounds was performed by a bio-guided fractionation which afforded 11 fractions, one of which inhibited IL-8 release in a concentration-dependent fashion in human gastric epithelial AGS cells. Phytochemical analysis revealed xanthohumol A and xanthohumol D as the main active components. The present study provides some experimental evidences that Humulus lupulus L. may exert an anti-inflammatory activity on the gastric district by the inhibition of the IL-8 secretion, partially due to its prenylated chalcones content.

Walnut trees (Juglans regia) are a priceless source of nutrients and beneficial molecules. Besides the nuts, also the leaves have been commonly used to prepare teas and decoctions, with the purpose of curing diabetic symptoms. In vivo trials have ascertained the walnut leaf capability to ameliorate hyperglycaemia in humans. However, conclusive studies aimed at identifying the molecules responsible for the antidiabetic activity of the walnut leaves are still missing. This paper reports on a bio-guided separation of the walnut leaf extract that led to the isolation and NMR-based identification of two compounds belonging to the megastigmane class as the major antidiabetic molecules of the extract. An in-depth evaluation of their potential to affect the glucose uptake in HepG2 and Caco-2 cell lines was also conducted. The presented results are ultimately expected to allow a more rational use of walnut leaf-based beverages in the therapy of diabetes.

Objective: To examine the strategies employed by opponents of the Queensland Government's policy to restrict unhealthy food and alcohol advertising on publicly owned assets and identify which of the opposing arguments appeared to influence the policy outcomes., Methods: Retrospective qualitative policy analysis case study informed by the Policy Dystopia Model of corporate political activity. We used qualitative content analysis to examine data from stakeholder submissions to the 'Advertising content on Queensland Government advertising spaces' policies (v1 and 2), and Minister for Health's diaries., Results: Stakeholders from the food, beverage, alcohol and advertising industries and several not-for-profit health organisations opposed the policy. Industry actors used discursive strategies, coalition management (including co-option of not-for-profit health organisations), information management and direct involvement with policy makers to communicate their arguments against the policy. The second version of the policy was weaker regarding scope and key policy provisions, reflecting the arguments of industry actors., Conclusions: Influence from industries with a clear conflict of interest should be minimised throughout policy development to ensure public health is prioritised over corporate gain., Implications for Public Health: Our findings can support other jurisdictions to prepare for industry opposition when designing policies to restrict unhealthy food and alcohol marketing., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown., Objectives: To elucidate the geographical variance in the pathophysiological characteristics of CAD., Methods: Physiological indices derived from angiography-based fractional flow reserve pullbacks from patients with chronic coronary syndrome enrolled in the ASET Japan (n = 206) and ASET Brazil (n = 201) studies, which shared the same eligibility criteria, were analysed. The pathophysiological patterns of CAD were characterised using Murray law-based quantitative flow ratio (μQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the μQFR pullback pressure gradient index., Results: Significant functional stenoses pre-PCI (μQFR ≤0.80) were more frequent in ASET Japan compared to ASET Brazil (89.9% vs. 67.5%, p < 0.001), as were rates of a post-PCI μQFR <0.91 (22.1% vs. 12.9%, p = 0.013). In the multivariable analysis, pre-procedural μQFR and diffuse disease were independent factors for predicting a post-PCI μQFR <0.91, which contributed to the different rates of post-PCI μQFR ≥0.91 between the studies. Among vessels with a post-PCI μQFR <0.91, a consistent diffuse pattern of CAD pre- and post-PCI occurred in 78.3% and 76.7% of patients in ASET Japan and Brazil, respectively; only 6.3% (Japan) and 10.0% (Brazil) of vessels had a major residual gradient. Independent risk factors for diffuse disease were diabetes mellitus in ASET Japan, and age and male gender in Brazil., Conclusions: There was geographic disparity in pre-procedural angiography-based pathophysiological characteristics. The combined pre-procedural physiological assessment of vessel μQFR and diffuseness of CAD may potentially identify patients who will benefit most from PCI., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets., Methods: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed., Findings: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032)., Interpretation: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications., Funding: French Ministry of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To explore Victorian parents' and club officials' engagement with, and attitudes towards, the sponsorship of junior sports by unhealthy food and beverage companies., Methods: We conducted online surveys with 504 parents of children participating in junior sports and 16 semi-structured interviews with junior sports club officials (from clubs that accepted unhealthy food sponsorship) in Victoria, Australia., Results: Most parents were concerned about children's exposure to sponsorship by unhealthy local (58% extremely, very or moderately concerned) and large food companies (63%) in junior sports. The views of sporting club officials were grouped into four themes: (1) the existing funding challenges for junior sports, (2) how junior sports sponsorship is community dependent, (3) how the perceived risks of sponsorship by unhealthy food companies are low and (4) the need for high-level regulations and support to transition towards healthier junior sports sponsorship., Conclusions: Transitioning towards healthier junior sports sponsorship may be hindered by insufficient funding models and low concern for such actions by community leaders., Implications for Public Health: Policy actions from higher-level sporting governing bodies and governments are likely to be necessary to reduce harmful junior sports sponsorship, alongside restrictions on the marketing of unhealthy foods through other media and settings., Competing Interests: Conflicts of interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit., Methods: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345., Findings: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69)., Interpretation: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population., Funding: French Ministry of Health., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SE reports grants, lecture fees, travel support, and receipt of equipment from Aerogen and Fisher & Paykel Healthcare, and consulting fees and advisory board participation at Aerogen. M-AN reports grants, receipt of equipment, and lecture fees from Fisher & Paykel Healthcare. AWT reports grants from the French Ministry of Health, lectures fees from Sigher & Paykel and Philips, and travel support from Fisher & Paykel, GE Healthcare, and Sedana. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin-angiotensin-aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation., Objectives: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients., Methods and Results: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9-7.5] years. Data on K + levels were available in 7087 cases. Patients with K + plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K + . Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1-14.1%] and 7.3% [IQR 3.4-15%] (p = 0.678) in patients with normal and moderately high K + values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively., Conclusions: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Severity of coronavirus disease 2019 (COVID-19) is often associated with thrombotic complications and cytokine storm leading to intensive are unit (ICU) admission. Platelets are known to be responsible for abnormal hemostasis parameters (thrombocytopenia, raised D-dimers, and prolonged prothrombin time) in other viral infections through the activation of the nucleotide-binding domain leucine repeat rich containing protein 3 inflammasome induced by signaling pathways driven by Bruton tyrosine kinase (BTK) and leading to caspase-1 activation., Objectives: We hypothesized that caspase-1 activation and the phosphorylation of BTK could be associated with the severity of the disease and that ibrutinib, a BTK inhibitor, could inhibit platelet activation., Methods and Results: We studied caspase-1 activation by flow cytometry and the phosphorylation of BTK by Western blot in a cohort of 51 Afro-Carribean patients with COVID-19 disease (19 not treated in ICU and 32 treated in ICU). Patients with a platelet count of 286.7 × 10 9 /L (69-642 × 10 9 /L) were treated by steroids and heparin preventive anticoagulation. Caspase-1 and BTK activation were associated with the severity of the disease and with the procoagulant state of the patients. Furthermore, we showed in vitro that the plasma of ICU patients with COVID-19 was able to increase CD62P expression and caspase-1 activity of healthy platelets and that ibrutinib could prevent it., Conclusions: Our results show that caspase-1 and BTK activation are related to disease severity and suggest the therapeutic hope raised by ibrutinib in the treatment of COVID-19 by reducing the procoagulant state of the patients., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O 2 ; V.O 2 AT) has been reported as an absolute value (V.O 2 ATabs), as a percentage of predicted peak V.O 2 (V.O 2 AT%peak&#95;pred), or as a percentage of observed peak V.O 2 (V.O 2 AT%peak&#95;obs). A direct comparison of the prognostic power among these different ways to report AT is missing., Research Question: What is the prognostic power of these different ways to report AT?, Study Design and Methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer., Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O 2 ATabs (mean ± SD, 823 ± 305 mL/min) and V.O 2 AT%peak&#95;pred (mean ± SD, 39.6 ± 13.9%), but not V.O 2 AT%peak&#95;obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O 2 ATabs (0.680) and V.O 2 AT%peak&#95;pred (0.688) performed similarly, whereas V.O 2 AT%peak&#95;obs (0.538) was significantly weaker (P < .001). Moreover, the V.O 2 AT%peak&#95;pred AUC value was the only one performing as well as the AUC based on peak V.O 2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O 2  < 12 mL/min/kg). Finally, the combination of V.O 2 AT%peak&#95;pred with peak V.O 2 and V. per CO 2 production shows the highest prognostic power., Interpretation: In HF, V.O 2 AT%peak&#95;pred is the best way to report V.O 2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O 2 and, remarkably, in patients with severe HF., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Targeted temperature management (TTM) currently is the only treatment with demonstrated efficacy in attenuating the harmful effects on the brain of ischemia-reperfusion injury after cardiac arrest. However, whether TTM is beneficial in the subset of patients with in-hospital cardiac arrest (IHCA) remains unclear., Research Question: Is TTM at 33 °C associated with better neurological outcomes after IHCA in a nonshockable rhythm compared with targeted normothermia (TN; 37 °C)?, Study Design and Methods: We performed a post hoc analysis of data from the published Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm randomized controlled trial in 584 patients. We included the 159 patients with IHCA; 73 were randomized to 33 °C treatment and 86 were randomized to 37 °C treatment. The primary outcome was survival with a good neurologic outcome (cerebral performance category [CPC] score of 1 or 2) on day 90. Mixed multivariate adjusted logistic regression analysis was performed to determine whether survival with CPC score of 1 or 2 on day 90 was associated with type of temperature management after adjustment on baseline characteristics not balanced by randomization., Results: Compared with TN for 48 h, hypothermia at 33 °C for 24 h was associated with a higher percentage of patients who were alive with good neurologic outcomes on day 90 (16.4% vs 5.8%; P = .03). Day 90 mortality was not significantly different between the two groups (68.5% vs 76.7%; P = .24). By mixed multivariate analysis adjusted by Cardiac Arrest Hospital Prognosis score and circulatory shock status, hypothermia was associated significantly with good day 90 neurologic outcomes (OR, 2.40 [95% CI, 1.17-13.03]; P = .03)., Interpretation: Hypothermia at 33 °C was associated with better day 90 neurologic outcomes after IHCA in a nonshockable rhythm compared with TN. However, the limited sample size resulted in wide CIs. Further studies of patients after cardiac arrest resulting from any cause, including IHCA, are needed., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol and cannabis are the most widely consumed psychoactive substances worldwide. This study compared the effects of alcohol and cannabis on visual function and driving performance, as well as self-perceived effects. Also, the relationship between visual effects under the influence and driving performance was studied., Methods: Sixty-four young drivers, with a history of alcohol and/or cannabis use were included. Of these, 33 were allocated to the alcohol group and 31 to the cannabis group. All participants were evaluated in a baseline session. The alcohol group underwent two sessions: after drinking 300 ml and 450 ml of red wine (A1 and A2). The cannabis group attended one session after smoking cannabis (C). Visual function was evaluated at the contrast sensitivity, stereoacuity, and intraocular straylight level. Participants drove a driving simulator. A general score (overall visual score, OVS; overall driving performance score, ODPS) was obtained for both visual functioning and driving performance., Results: The evaluation of visual function demonstrated a significant impairment in OVS for all conditions studied (A1, p = 0.005; A2, p < 0.001; C, p < 0.001) with respect to the baseline session. General driving performance (ODPS) demonstrated a significant worsening for the A2 condition (p = 0.003). Finally, a significant relationship between driving performance and visual function was found (rho=0.163, p = 0.039 and χ 2 = 4.801, p = 0.028)., Conclusions: Cannabis and alcohol use negatively impact visual function. However, driving performance was only significantly affected by the higher alcohol dose. This impairment in visual function was significantly associated with worse driving performance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This study aimed to assess the potential financial impacts on Australian television networks of a ban on alcohol advertising during sports broadcasts., Methods: We analysed television advertising data from Nielsen, a commercial market research company. The data included details of all advertisements (ads) for the 10 highest-spending alcohol brands on free-to-air television networks in the five largest capital cities in Australia over a 12-month period (November 2018-October 2019). We estimated alcohol advertising spend during sports broadcasts. Financial value per network was estimated using ad duration and total spend per channel., Results: There were 10,660 alcohol ads (average of 75 minutes per week) shown during sports broadcasts, amounting to A$14.4 million in revenue to television networks. Forty-five per cent of these ads were at children's viewing times. Channel Seven received the largest amount of alcohol advertising revenue (A$20.8 million), of which A$10.8 million (52.0%) was during sports broadcasts (0.5% of its total advertising revenue)., Conclusions: Alcohol advertising during sports broadcasts is pervasive but contributes a relatively small proportion of revenue for television networks., Implications for Public Health: A ban on alcohol advertising during sport broadcasts is unlikely to have major financial impacts on broadcasters, whilst the health and social benefits are potentially substantial., (© 2022 The Authors.)

Introduction: The gold standard treatment for high-risk NMIBC is BCG immunotherapy. Some studies suggested an immomodulatory effects for commonly used drugs (ie, ACE-I and ARBs). We aimed to determine whether these drugs impact the prognosis of patients with high-risk NMIBC treated with BCG., Materials and Methods: Retrospective analysis on 208 patients from a single academic center with primary high-risk NMIBC treated with transurethral resection followed by 6 weekly instillations of BCG and up to 12 monthly maintenance instillations. ARBs or ACE-I use at the time of treatment initiation was recorded. Inverse probability of treatment weighting (IPTW) was used to adjust for clinical and pathological covariates. IPTW-adjusted Kaplan-Meier curves and weighted Cox proportional hazards regression were used to compare 2-yr failure-free (2-yr FFS), failure-free (FFS), overall recurrence-free (RFS) and progression-free survival (PFS)., Results: A total of 68 patients were on ACE-I, and 38 on ARBs and treatment respectively. At a median follow-up of 26 months, ACE-I treatment had no significant impact on cancer-related outcomes. Conversely, patients treated with ARBs experienced significant improvements in 2-yr FFS (HR 0.3; 0.1-0.9, P = .004), FFS (HR 0.4, 0.1-0.9, P = .005), and PFS (HR 0.001; < 0.001-0.001, P < .001). No significant impact was found for ARB use in RFS (HR 0.6; P = .09). Sensitivity analyses confirmed these results., Conclusions: our findings support a potential role of the angiotensin-renin system in bladder cancer development. We identified ARBs as potential beneficial drugs that seems to act in synergy with BCG-immunotherapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Women represent an increasing number of individuals with alcohol and substance use disorders (ASUDs), and sex-differences might affect results of interventional clinical trials (CTs). We aim at assessing the proportion of women and the reporting of sex-stratified and female-specific data in CTs for ASUDs., Methods: We extracted data from ClinicalTrials.gov on Phase 1-3 CTs of investigational drugs for ASUDs conducted from 2000 to 2021 and identified articles related to these trials. We determined the average proportions of women enrolled per trial overall, over time, and by disease area and trial phase. Next, we calculated the proportion of articles reporting sex-stratified and female-specific data., Results: In the 234 CTs identified, the overall proportion of women was 33.4% [95% CI: 32.7%-33.9%]), with an increasing temporal trend. Women's participation was higher in CTs of investigational drugs for tobacco (43.5% [95% CI: 42.4% -44.5%]) and alcohol use disorder (35.9% [95% CI: 34.54%-37.21%]), and closely mirrored their representation in the disease populations (46% and 37%). Conversely, women were underrepresented in clinical trials of drugs for cocaine and stimulant use disorders (25.8% [95% CI: 24.6%-27.1%]) and opioid use disorders (25.9% [95% CI:24.2%-27.7%]). Nine publications reported sex-stratified data in the method and/or result section, whereas none documented female-specific data., Conclusions: Enrollment of women in ASUDs CTs has increased over time but remains low in several disease areas. This, together with the low rates of reporting of sex-stratified data, calls for an adequate inclusion of sex in the design and analysis of CTs for ASUDs., (Copyright © 2022. Published by Elsevier Inc.)

To date, a very small number of serum biomarkers have been identified for clinical use in squamous carcinomas of the head and neck region. Chromatin Assembly Factor-1 (CAF-1) heterotrimeric complex subunit CAF1/p60 expression levels have been reported to be of prognostic value in Oral Squamous Cell Carcinoma (OSCC), as well as in other human solid tumors. Here our aim was to detect and quantify CAF1/p60 in the peripheral blood of Head and Neck Squamous Cell Carcinoma (HNSCC) patients, and to investigate the possible associations between serum concentration of CAF-1/p60 and HNSCC tumors. A total of 63 HNSCC patients (51 OSCC, 8 OPSCC, 3 laryngeal SCC, and 1 rhinopharynx SCC) and 30 healthy controls were enrolled. The serum levels of CAF-1/p60 were measured by ELISA assay before and after surgery. Serum CAF-1/p60 concentration resulted significantly higher in cancer patients, compared with healthy controls, in pre-surgery samples (P < 0.05). Serum levels of CAF-1/p60 significantly decreased in serum samples taken after surgery (P < 0.05). Our results demonstrated that CAF-1/p60 may be detected in serum, suggesting a role for CAF-1/p60 as potential soluble biomarkers in HNSCC tumors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study explores Australian public awareness and attitudes towards political donations from the alcohol industry and the 'revolving door' of politicians into industry or lobbyist positions., Methods: Data were collected via a nationwide online panel., Results: In total, n=1,044 participants completed the survey. More than half of the participants agreed that donations are made to influence government policy and to support the interests of the industry. More than half of the participants did not believe that it is appropriate for political parties to accept donations from the alcohol industry or for politicians to attend alcohol industry-hosted events. One-third of the participants agreed that public officials (including politicians) with a role in health policy should never be allowed to work or lobby for the alcohol industry (31.7%) and one-third endorsed a waiting time of 4-5 years., Discussion: There were demographic differences in the views that participants held of the alcohol industry and the relationship between the government and the alcohol industry. The findings suggest that the laws and controls governing industry-government relationships should be reviewed to ensure they are in line with public expectations, accompanied by education programs including a focus on corporate political activity by the alcohol industry., (© 2021 The Authors.)

An unusual prevalence of Klebsiella pneumoniae (24%) was observed in 25 adults admitted to the intensive care units of two University Hospitals in the French West Indies, for spontaneous community-acquired bacterial meningitis. All tested isolates had several prominent features of hypervirulent isolates, including rmpa and iuc genes, K1 or K2 capsular serotypes., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to evaluate the hypothesis that prasugrel monotherapy following successful everolimus-eluting stent implantation is feasible and safe in patients with stable coronary artery disease (CAD)., Background: Recent studies have suggested that short dual-antiplatelet therapy strategies may provide an adequate balance between ischemic and bleeding risks. However, the complete omission of aspirin immediately after percutaneous coronary intervention (PCI) has not been tested so far., Methods: The study was a multicenter, single-arm, open-label trial with a stopping rule based on the occurrence of definite stent thrombosis (if >3, trial enrollment would be terminated). Patients undergoing successful everolimus-eluting stent implantation for stable CAD with SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores <23 were included. All participants were on standard dual-antiplatelet therapy at the time of index PCI. Aspirin was discontinued on the day of the index procedure but given prior to the procedure; prasugrel was administered in the catheterization laboratory immediately after the successful procedure, and aspirin-free prasugrel became the therapy regimen from that moment. Patients were treated solely with prasugrel for 3 months. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 3 months., Results: From February 22, 2018, to May 7, 2019, 201 patients were enrolled. All patients underwent PCI for stable CAD. Overall, 98.5% of patients were adherent to prasugrel at 3-month follow-up. The primary ischemic and bleeding endpoints occurred in 1 patient (0.5%). No stent thrombosis events occurred., Conclusions: Aspirin-free prasugrel monotherapy following successful everolimus-eluting stent implantation demonstrated feasibility and safety without any stent thrombosis in selected low-risk patients with stable CAD. These findings may help underpin larger randomized controlled studies to evaluate the aspirin-free strategy compared with traditional dual-antiplatelet therapy following PCI. (Acetyl Salicylic Elimination Trial: The ASET Pilot Study [ASET]; NCT03469856)., (Copyright © 2020. Published by Elsevier Inc.)

Tinnitus is a clinical condition defined by hearing a sound in the absence of an objective source. Early experiments in animal models have suggested that tinnitus stems from an alteration of processing in the auditory system. However, translating these results to humans has proven challenging. One limiting factor has been the insufficient spatial resolution of non-invasive measurement techniques to investigate responses in subcortical auditory nuclei, like the inferior colliculus and the medial geniculate body (MGB). Here we employed ultra-high field functional magnetic resonance imaging (UHF-fMRI) at 7 Tesla to investigate the frequency-specific processing in sub-cortical and cortical regions in a cohort of six tinnitus patients and six hearing loss matched controls. We used task-based fMRI to perform tonotopic mapping and compared the magnitude and tuning of frequency-specific responses between the two groups. Additionally, we used resting-state fMRI to investigate the functional connectivity. Our results indicate frequency-unspecific reductions in the selectivity of frequency tuning that start at the level of the MGB and continue in the auditory cortex, as well as reduced thalamocortical and cortico-cortical connectivity with tinnitus. These findings suggest that tinnitus may be associated with reduced inhibition in the auditory pathway, potentially leading to increased neural noise and reduced functional connectivity. Moreover, these results indicate the relevance of high spatial resolution UHF-fMRI for the investigation of the role of sub-cortical auditory regions in tinnitus., Competing Interests: Declaration of Competing Interest The content of this article does not reflect the opinion of Cochlear Ltd. and Cochlear Ltd. did not affect the content of this article. The creation of this article is not financed by Cochlear Ltd., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Offspring of patients with early myocardial infarction have a higher risk to develop cardiovascular events; the underlying physiopathology is still unclear. Several lines of evidence support a role for oxidative stress in atherogenesis and NADPH oxidase-2 (NOX-2) is considered a major source of O2 - in human. Furthermore, oxidative stress regulates arachidonic acid metabolism via activation of platelet phospholipase-A2. The aim of this study was to address NOX-2 activity as well as serum thromboxane B2 (TXB2) and 8-isoPGF2-alpha in offspring of patients with premature myocardial infarction., Methods: Ninety-two consecutive subjects, including 46 offspring of patients with premature myocardial infarction and 46 healthy subjects (HS) matched for age and gender, were recruited. A cross sectional study was performed to compare serum activity of soluble NOX-2-dp (sNOX-2-dp), blood levels of isoprostanes and serum TXB2 in these two groups., Results: Compared with HS, offspring of patients with early myocardial infarction had higher values of serum TxB2, isoprostanes and sNOX-2-dp. Bivariate analysis in the overall population showed that serum sNOX-2-dp levels were significantly associated with serum isoprostanes and TXB2. A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Serum isoprostanes (SE: 0.07; standardized coefficient β: 0.579; P < 0.001) and TXB2 levels (SE: 0.06; standardized coefficient β: 0.211; P < 0.001) were significantly associated to sNOX-2-dp (R2: 0.42)., Conclusion: This study shows that Nox-2 activation is a key determinant of oxidative stress and platelet activation in offspring of patients with premature myocardial infarction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aim: Lifestyle habits including indoor and outdoor activities among community school children, adherence to the Mediterranean diet and awareness about total cholesterol blood levels represent determinant factors in cardiovascular disease (CVD) prevention. The aim of this study was to analyze the relationship between adherence to the Mediterranean diet, total cholesterol blood levels, body composition and hours per day spent in in-house or outdoor among 29,159 Italian 6-14 years-old community school children (50% boys). The KidMed questionnaire, modified to handle missing information on olive oil consumption, was used to assess the adherence to the Mediterranean diet among participants., Methods and Results: Associations between variables were tested according to 3 classes of the Mediterranean diet adherence score using analysis of variance. Participants with high adherence to Mediterranean diet were few (1%). Overall awareness of total cholesterol blood levels was low among children (4.5%), slightly higher among parents (26.2 and 24.1% in mothers and fathers, respectively). Among Mediterranean diet adherent children, BMI was significantly (p < 0.001) smaller than among the non-Mediterranean or intermediate adherent children as were the total hours spent per day watching television or playing with videogames (p < 0.001) whereas the hours/day in sport or outdoor activities were more (p < 0.001). These results were confirmed by multiple linear regression with KidMed scored 0 to 8 as dependent variable., Conclusion: Although awareness of total cholesterol blood levels and adherence to the Mediterranean diet are rare among community school children, only among these a healthier lifestyle was practiced with a tendency to lower CVD risks. These results are important as the first sized experience of this type in Italy., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

There are many ways in which women experience sleep differently from men. Women contending with distinct sleep challenges respond differently to sleep disorders, as well as sleep deprivation and deficiency, and face particular health outcomes as a result of poor sleep. Idiosyncrasies, including changes that occur with the biological life cycles of menstruation, pregnancy, and menopause, make the understanding of sleep in women an important topic to study. Each phase of a woman's life, from childhood to menopause, increases the risk of sleep disturbance in unique ways that may require distinct management. Indeed, new research is unraveling novel aspects of sleep pathology in women and the fundamental role that sex hormones play in influencing sleep regulation and arousals and possibly outcomes of sleep conditions. Moreover, studies indicate that during times of hormonal change, women are at an increased risk for sleep disturbances such as poor sleep quality and sleep deprivation, as well as sleep disorders such as OSA, restless legs syndrome, and insomnia. This article reviews sleep changes in female subjects from neonatal life to menopause., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition., Methods: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099., Findings: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04)., Interpretation: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition., Funding: La Roche-sur-Yon Departmental Hospital and French Ministry of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: Glucagon-like peptide-1 (GLP-1) agonists improve glycaemic control in type 2 diabetes mellitus (DM). Outcome trials investigating macro and microvascular effects of GLP-1 agonists reported conflicting results. The aim of this study was to assess, in a meta-analysis, the effects of GLP-1 agonists on mortality, major nonfatal cardiovascular (CV) events, renal and retinal events., Data Synthesis: MEDLINE, Cochrane, ISI Web of Science, SCOPUS and ClinicalTrial.gov databases were searched for articles published until June 2017. Randomized trials enrolling more than 200 patients, comparing GLP-1 versus placebo or active treatments in patients with DM, and assessing outcomes among all-cause death, CV death, MI, stroke, HF, diabetic retinopathy and nephropathy were included. 77 randomized trials enrolling 60,434 patients were included. Compared to control, treatment with GLP-1 significantly reduced the risk of all-cause death (RR: 0.888; CI: 0.804-0.979; p = 0.018) and the risk of CV death (RR: 0.858; CI: 0.757-0.973; p = 0.017). GLP-1 agonists did not affect the risk of MI (RR: 0.917; CI: 0.830-1.014; p = 0.092) as well as the risk of stroke (RR: 0.882; CI: 0.759-1.023; p = 0.097), HF (RR: 0.967; CI: 0.803-1.165; p = 0.725), retinopathy (RR: 1.000; CI: 0.807-1.238; p = 0.997) and nephropathy (RR: 0.866; CI: 0.625-1.199; p = 0.385)., Conclusions: Treatment with GLP-1 agonists in DM patients is associated with a significant reduction of all cause and CV mortality., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aim: The aim of this review was to summarize evidence on the role of Vitamin D deficiency in heart failure (HF), from pathophysiological mechanisms to clinical effects of Vitamin D supplementation., Data Synthesis: Chronic HF secondary to left ventricular (LV) systolic dysfunction is a growing health problem, still associated with poor clinical outcome. In recent years, experimental and epidemiological evidence focused on the role of Vitamin D in HF. Cross sectional studies demonstrated that prevalence of HF is increased in patients with Vitamin D deficiency or parathyroid hormone (PTH) plasma level increase, whereas longitudinal studies showed enhanced risk of developing new HF in patients with Vitamin D deficiency. In addition, in patients with established HF, low plasma levels of Vitamin D are associated with worsening clinical outcome. Yet, clinical studies did not definitively demonstrate a benefit of Vitamin D supplementation for preventing HF or ameliorating clinical outcome in patients with established HF., Conclusions: Despite convincing experimental and epidemiological data, treatment with Vitamin D supplementation did not show clear evidence of benefit for preventing HF or influencing its clinical course. Ongoing clinical studies will hopefully shed lights on the effects of Vitamin D supplementation on clinical endpoints along the spectrum of HF., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Increased arterial stiffness and sympathetic nervous system activity, independent markers of cardiovascular risk, are common in patients with severe obstructive sleep apnoea, who have excessive daytime sleepiness. Among patients with mild-to-moderate obstructive sleep apnoea, however, it remains unknown whether arterial stiffness and/or increased sympathetic nervous system activity correlate with excessive daytime sleepiness., Methods: We measured heart rate variability, as an index of autonomic nervous system activity, and arterial stiffness index, as a marker of vascular damage and cardiovascular risk, in 56 men aged 18 to 75years, with mild-to-moderate obstructive sleep apnoea, and matched into two groups, "sleepy" (Epworth Sleepiness Scale≥10) and "non-sleepy" (Epworth Sleepiness Scale<10)., Results: We found no association of excessive daytime sleepiness with sympathetic nervous system activation (very low frequency power 18,947±11,207ms 2 vs 15,893±8,272ms 2 , p=0.28; low frequency (LH) power 17,753±8,441ms 2 vs 15,414±5,666ms 2 , p=0.26; high frequency (HF) power 7,527±1,979ms 2 vs 8,257±3,416ms 2 , p=0.36; LF/HF ratio 3.04±1.37 vs 2.55±1.01, p=0.15) and mean arterial stiffness index (6.97±0.83 vs 7.26±0.66, p=0.18) in mild-to-moderate obstructive sleep apnoea patients., Conclusions: Symptoms of excessive daytime sleepiness are not associated with sympathetic nervous system activation and arterial stiffness in male subjects with mild-to-moderate obstructive sleep apnoea., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to assess the impact of Mediterranean diet (MD) and physical activity on metabolic syndrome (MS) prevalence in children and adolescents., Material and Methods: This cross-sectional study was carried out in 863 boys and 780 girls, 6-14years old, from primary and secondary schools in a 14-town Southern Italian community. We modified the KIDMED questionnaire to adapt it to the local reality., Results: Poor adherence to MD was seen in 18.4% of children and adolescents, while 81.6% had a medium-high compliance and the prevalence of MS was 6.6% and 3.7% respectively (OR: 1.8; 95% C.I.: 1.06-3.11; p=0.013). When participants had less physical activity, MS was more frequent as compared to those more active (5.3% versus 2.3%; OR: 2.3; 95% C.I.: 1.3-4.3; p=0.0068) which had a parallel counterpart when comparing those accustomed to seeing television for less or more than 5h per day and MS prevalence was 12.3% versus 3.8% (OR: 3.38; 95% C.I.: 1.66-6.86, p=0.0008), respectively. Finally, there was a specific abnormality in triglyceride levels, both in girls and boys, when participants were classified according to bad lifestyles, based on the combined evaluation of scarce adherence to MD and less extracurricular physical activity, accompanied by a 7-fold increased prevalence of MS as compared to those with the best lifestyle (11.0% versus 1.6%; p=0.025)., Conclusions: There is an apparent importance of healthier lifestyle habits including physical activity and adherence to the MD also among children and adolescents., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis., Methods: Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included., Results: 157 randomized trials (114 on DPP4-Is and 43 on SGLT2-Is) enrolling 140,470 patients (107,100 in DPP4-I and 33,370 in SGLT2-I studies) were included in the analysis. Compared to control, treatment with DPP4-Is did not affect all-cause (RR: 1.010; 95% CI: 0.935-1.091) and CV (RR: 0.975; CI: 0.887-1.073) mortality as well as risk of MI (RR: 0.915; CI: 0.835-1.002), stroke (RR: 0.933; CI: 0.820-1.062) and HF (RR: 1.083; CI: 0.973-1.205). Treatment with SGLT2-Is significantly reduced the risk of all-cause death by 28% (RR: 0.718; CI: 0.613-0.840), CV death by 33% (RR: 0.668; CI: 0.544-0.821), MI by 20% (RR: 0.803; CI: 0.668-0.965) and HF by 35% (RR: 0.652; CI: 0.517-0.823) without effect on stroke (RR: 1.158; CI: 0.912-1.469)., Conclusions: DPP4-Is show a safe CV profile as they do not affect mortality and CV events, including HF, in patients with type 2 DM. SGLT2-Is are associated with improved CV outcome and survival in DM patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of the current study was to assess correlates of intoxication in licensed venues in Australia., Methods: Covert observations of licensed venues and venue patron in night-time entertainment districts of five Australian cities were conducted. In total, 828 unique cross-sectional observations were completed across 62 bars, nightclubs, and large mainstream pubs. Venues were selected from the main entertainment district of smaller cities and the busiest entertainment districts of larger cities. Outcomes were the estimated percentage of patrons showing any signs of alcohol intoxication and the overall level of intoxication ('high' versus 'none to medium'). Seven predictors of patron intoxication were examined: hour of observation; estimated percentage of male patrons; estimated percentage of patrons <25 years old; venue crowding; presence of observable alcohol promotions; type of alcoholic beverage consumed by the majority of patrons; and, venue type., Results: Time of night (coefficient=11.71, p<.001; OR=9.61, p<.001), percentage of patrons aged <25 (coefficient=0.14, p<.001; OR=1.01, p=.031), and venue crowding (coefficient=4.40, p<.001; OR=1.39, p=.009) had significant positive associations with both signs of intoxication and high levels of intoxication. Nightclubs had a lower percentage of signs of intoxication compared to pubs (coefficient=-10.73, p=.021). Increased percentage of male patrons was associated with increased odds of high-level intoxication (OR=1.05, p=.020)., Conclusion: Time of night and proportion of younger patrons had a strong association with patron intoxication adding further support for the strong body of evidence that ceasing service of alcohol earlier in the evening will reduce intoxication levels., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Oxidative stress plays a crucial role in impairing endothelial function in sleep disordered breathing (SDB) but the underlying mechanism is still undefined. The objective of this study was to evaluate the interplay between oxidative stress, assessed by serum isoprostanes (8-iso-PGF2α) and soluble NOX2-dp (sNOX2-dp), and endothelial function, assessed by flow-mediated dilation (FMD), in children with SDB and healthy controls (HC)., Methods: One-hundred forty-four children including 45 with primary snoring (PS), 22 with obstructive sleep apnea (OSA) and 67 HC were recruited in this study; in 15 out of 22 OSA children FMD, serum 8-iso-PGF2α and sNOX2-dp were assessed before and after one month post adeno-tonsillectomy (AT)., Results: Compared with HC, OSA and PS children had significantly higher sNOX2-dp and serum 8-iso-PGF2α levels and lower FMD; compared with PS, FMD was significantly lower in OSA children. No significant difference for sNOX2-dp and serum 8-iso-PGF2α was observed between OSA and PS children. FMD was inversely correlated with sNOX2-dp levels (p<0.001) and with serum 8-iso-PGF2α (p<0.001). In multiple linear regression analysis, sNOX2-dp (p<0.001) and serum 8-iso-PGF2α (p<0.001) were the only independent predictive variables associated with FMD. AT significantly decreased sNOX2-dp and serum 8-iso-PGF2α levels (from 38.2±8.8 to 22.4±11.1 pg/ml, p<0.001, and from 281.4±69.7 to 226.0±66.4 pg/ml, p<0.001, respectively); conversely, FMD significantly increased after AT in OSA children (from 3.0±1.5 to 8.0±2.8%, p<0.001)., Conclusion: This study suggests that NOX2-derived oxidative stress is involved in artery dysfunction in SDB children. Such hypothesis is reinforced by FMD improvement after AT coincidentally with oxidative stress lowering., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02247167., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Characterize a NDM-1 producing K. pneumoniae isolate recovered from a patient hospitalized in Guadeloupe, French West Indies, after its transfer from Cuba, Methods: Antibiotic susceptibilities were determined by the disk diffusion method, and E-test. Carbapenemase production was assessed using the Carba NP test. Antibiotic resistance determinants and their surrounding structures were characterized by PCR mapping and DNA sequencing. Transfer of the β-lactam resistance marker was attempted by liquid mating-out assays, Results: Here we reported the first NDM-1 producing enterobacterial isolate recovered from Caribbean islands. This K. pneumoniae isolate belongs to a new sequence type (ST1649). The blaNDM-1 gene together with the aacA4 gene were carried on a self conjugative IncR plasmid of c.a. 80kb., Conclusion: This study describes the first identification of a NDM-1 producer in Caribbean islands. The uncommon incompatibility group of the blaNDM-1 carrying plasmid and the uncommon ST type of the K. pneumoniae strain suggest a possible local emergence of NDM producers., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Among 1657 children and adolescents aged 6 to 14 years (787, 47% girls and 870, 53% boys) from primary and secondary schools in a 14-town Southern Italian community, HDL cholesterol (54 ± 15 mg/dl), triglycerides (61 ± 29 mg/dl), blood glucose (78 ± 10 mg/dl), systolic (101 ± 11 mm Hg) and diastolic (62 ± 10 mm Hg) blood pressures, waist circumference (WC) (66 ± 10 cm) and WC/height (0.46 ± 0.006) and triglycerides/HDL cholesterol (1.31 ± 0.99) ratios were measured. The distributions were similar in both genders. Age did not affect triglycerides/HDL cholesterol ratio, whereas there was a slightly positive correlation (p<0.00001) between WC/height and triglycerides/HDL cholesterol ratios. We present individual gender and age specific percentile distributions (as Supplementary materials). Using percentile cut-offs (≤ 10th for HDL cholesterol and ≥ 90th for the other components), there were 183 (11%) children or adolescents with low HDL cholesterol, 162 (9.77%) with high triglycerides, 178 (10.74%) with high blood glucose, 178 (10.74%) with high WC, 244 (20.76%) with high systolic or diastolic BP and 126 (7.6%) with high systolic and diastolic BP. Abnormally high BP was seen in 470 (28.36%) children or adolescents. Using abnormal percentile values of 3 of 5 of its components, metabolic syndrome (MS) was diagnosed in 70 (4.2%) subjects, similarly in both genders. To assess out-of-limit distributions of all 5 individual MS components in children and adolescents gender- and age-distributions derived from local epidemiological data should be used: these distributions are presented and they might now be used both for comparative and applicative purposes at least in Southern Europe., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We report the case of a 11-year-old girl who developed an isolated hand-writing disorder with dysgraphia at the beginning of the school year in the sixth grade. A brain magnetic resonance angiography showed a round arteriovenous malformation sited in the left side of the midbrain extending to the ipsilateral medio-basal thalamus. Child neurologists should never neglect a thorough neurological evaluation in case of isolated worsening of handwriting, to rule out possible underlying organic causes., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Lipid standards in Italy are lacking in children and adolescents whereas those for blood pressure (BP) were derived from US surveys., Methods: In a 14-town community in Southern Italy 1657 (64%) of 2594 children aged 6-14 years were enrolled and anthropometric, BP, lipid and glucose serum levels were obtained., Results: Average systolic BP was 101 ± 11 (60-150) mm Hg and cholesterol (CholT) level was 156 ± 28 (57-264) mg/dl. There were positive (p<0.00001) age-trends for systolic BP and body mass index (BMI) in both genders whereas age-trends for CholT and heart rate were negative (p<0.00001). A negative age-trend in both genders was also seen for non-HDL cholesterol (p<0.03). Based on 95% percentile gender and age distributions, there were 177 (10.68%) hypertensive (HT) and 82 (4.94%) hypercholesterolemic (HC) children or adolescents. Univariately, HT had higher (p<0.00001) height, weight, BMI, arm circumference, hips, waist, diastolic BP and waist/height, whereas HC had higher LDL-, HDL and non-HDL-cholesterol and triglycerides (p<0.01). Systolic BP was predicted (r(2)=0.2810, p=0.00001) by age (t=2.319, p<0.0205), male gender (t=3.179, p<0.0015), glucose (t=2.357, p<0.0186), height (t=2.473, p<0.0135), arm circumference (t=3.313, p<0.0009) and heart rate (t=4.161, p<0.00001). CholT was related inversely (r(2)=0.1399, p=0.00001) to height (t=-3.928, p<0.0001), weight (t=-3.922, p<0.0001) and waist/height (t=-4.797, p<0.00001) and directly to BMI (t=3.064, p<0.0022), waist (t=5.149, p<0.0000), triglycerides (t=11.332, p<0.00001) and female gender (t=-2.041, p<0.0414)., Conclusion: In these Southern Italian children and adolescents systolic BP and CholT are related with anthropometric and other variables, not confined to height. BP is lower than previously reported., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: A low-fat, fiber-rich diet is the first step in the management for hypercholesterolemic children. Glucomannan (GM) is a natural fiber that has been demonstrated to lower total and LDL-cholesterol. The use of high-dose chromium-polynicotinate (CP) and policosanol (PC) has also shown cholesterol-lowering benefits. We aimed at investigating the effects of low-dose CP or PC and their GM combination in hypercholesterolemic children., Methods: A double-blind trial was conducted in 120 children (60 M, 60 F, 9 ± 4 years, median 9.6 years, range: 3-16 years) randomly assigned to 5 neutraceutical and 1 placebo (only resistant starch) 8-week treatment groups. Fasting blood glucose (FBG), total cholesterol (CholT), triglycerides (TG), HDL and LDL cholesterol were considered., Results: GM combination of low-dose CP or PC reduced CholT and LDL without changing HDL, TG and FBG. The highest post-treatment changes were seen after GM combination with CP (CholT 85 ± 3% and LDL 85 ± 5%, of pretreatment) which was significantly (p < 0.01) less than with low-dose CP or PC and starch. When GM was associated with starch, there was no lipid lowering effect, which was an unexpected finding as compared to previous data with GM and no starch. No adverse effects were reported., Conclusion: This is the first report to show the cholesterol-lowering efficacy of GM combined treatment with low-dose CP or PC. Further studies are needed to investigate the best combinations and doses of nutraceutics to be added to the standard GM treatment. The potential negative association of GM and nutraceutics with starch is clearly shown., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Sleepiness is one of the cardinal complaints of patients in tertiary referral centres for sleep disorders. It is commonly associated with sleep disorders, but the additional influence of obesity remains unclear. We hypothesised that obesity may be an independent predictor of sleepiness in this population., Patients and Methods: We reviewed 335 patients undergoing overnight polysomnography over a 3 month period (May-July 2011), recording selected sleep parameters in addition to subjective sleepiness as measured by the Epworth Sleepiness Scale (ESS, 0-24 points)., Results: 173 patients (120 male, age 52 (13) years, BMI 33.9 (7.4) kg/m(2)) had obstructive sleep apnoea and 59 of those were established on continuous positive airway pressure (CPAP). 55 patients (38 male, age 56 (14) years, BMI 31.7 (6.7) kg/m(2)) had PLM disorder, with 3 on medical treatment. 155 patients were obese (93 male, age 50 (14) years, BMI 37.3 (6.1) kg/m(2)) and this group was significantly sleepier than the 180 non-obese subjects (107 male, age 42 (15) years, BMI 25.3 (3.0) kg/m(2)). The mean ESS of the obese group was 12.9 (5.5) points, compared to 10.4 (5.7) points for the non-obese patients (p < 0.001). Those with a diagnosis of OSA had an ESS of 12.3 (5.8) versus 10.7 (5.7) points for those without (p = 0.007). Females had an ESS of 12.8 (5.9) compared to 10.7 (5.5) points for male patients (p < 0.001). Regression analysis revealed that obesity (p = 0.007), PLM disorder (p = 0.010) and hypertension (p = 0.032) were independently associated with subjective sleepiness (adjusted R(2) = 0.384, p = 0.02), obesity accounting for 15.7% of the variability in sleepiness., Conclusion: Independent of underlying sleep disorders, obesity contributes significantly to daytime sleepiness. Measures to promote weight loss and close links to a dietician assisted service will be helpful in the specialist setting of a sleep disorders service to improve long-term health outcomes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)