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Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

ObjectiveTo explore the behavioural drivers of fear of litigation among healthcare providers influencing caesarean section (CS) rates.DesignScoping review.Data sourcesWe searched MEDLINE, Scopus and WHO Global Index (1 January 2001 to 9 March 2022).Data extraction and synthesisData were extracted using a form specifically designed for this review and we conducted content analysis using textual coding for relevant themes. We used the WHO principles for the adoption of a behavioural science perspective in public health developed by the WHO Technical Advisory Group for Behavioural Sciences and Insights to organise and analyse the findings. We used a narrative approach to summarise the findings.ResultsWe screened 2968 citations and 56 were included. Reviewed articles did not use a standard measure of influence of fear of litigation on provider’s behaviour. None of the studies used a clear theoretical framework to discuss the behavioural drivers of fear of litigation. We identified 12 drivers under the three domains of the WHO principles: (1) cognitive drivers: availability bias, ambiguity aversion, relative risk bias, commission bias and loss aversion bias; (2) social and cultural drivers: patient pressure, social norms and blame culture and (3) environmental drivers: legal, insurance, medical and professional, and media. Cognitive biases were the most discussed drivers of fear of litigation, followed by legal environment and patient pressure.ConclusionsDespite the lack of consensus on a definition or measurement, we found that fear of litigation as a driver for rising CS rates results from a complex interaction between cognitive, social and environmental drivers. Many of our findings were transferable across geographical and practice settings. Behavioural interventions that consider these drivers are crucial to address the fear of litigation as part of strategies to reduce CS.

ObjectiveTo synthesise the evidence from studies that implemented interventions to increase/reintroduce the use of assisted vaginal births (AVB).DesignSystematic review.Eligibility criteriaWe included experimental, semi-experimental and observational studies that reported any intervention to reintroduce/increase AVB use.Data sourcesWe searched PubMed, EMBASE, CINAHL, LILACS, Scopus, Cochrane, WHO Library, Web of Science, ClinicalTrials.gov and WHO.int/ictrp through September 2021.Risk of biasFor trials, we used the Cochrane Effective Practice and Organisation of Care tool; for other designs we used Risk of Bias for Non-Randomised Studies of Interventions.Data extraction and synthesisDue to heterogeneity in interventions, we did not conduct meta-analyses. We present data descriptively, grouping studies according to settings: high-income countries (HICs) or low/middle-income countries (LMICs). We classified direction of intervention effects as (a) statistically significant increase or decrease, (b) no statistically significant change or (c) statistical significance not reported in primary study. We provide qualitative syntheses of the main barriers and enablers for success of the intervention.ResultsWe included 16 studies (10 from LMICs), mostly of low or moderate methodological quality, which described interventions with various components (eg, didactic sessions, simulation, hands-on training, guidelines, audit/feedback). All HICs studies described isolated initiatives to increase AVB use; 9/10 LMIC studies tested initiatives to increase AVB use as part of larger multicomponent interventions to improve maternal/perinatal healthcare. No study assessed women’s views or designed interventions using behavioural theories. Overall, interventions were less successful in LMICs than in HICs. Increase in AVB use was not associated with significant increase in adverse maternal or perinatal outcomes. The main barriers to the successful implementation of the initiatives were related to staff and hospital environment.ConclusionsThere is insufficient evidence to indicate which intervention, or combination of interventions, is more effective to safely increase AVB use. More research is needed, especially in LMICs, including studies that design interventions taking into account theories of behaviour change.PROSPERO registration numberCRD42020215224.

The COVID-19 pandemic highlighted the vital importance and impact of human behaviour on viral transmission. During 2020, large amounts of global survey data were collected and made freely available to help the response. Many teams responding to the pandemic lack capacity to interpret and apply behavioural data. A collaboration of the World Health Organization’s Behavioural Insights team and UCL’s Centre for Behaviour Change designed and piloted two templates to enable survey data use during the first months of the pandemic. The first template documents key behaviours, thoughts and emotions related to the pandemic, with social interactions and population adherence to behavioural guidelines. The second template enables countries to formulate questions or issues that they would like behavioural data to address. This collaborative process applying behavioural science theory produced structured templates to enable the organisation, interpretation, sharing and application of survey data to inform policy and practice in different country contexts.

Background: Safety and efficacy of benralizumab (BEN) for severe eosinophilic asthma (SEA) have been demonstrated in Phase III clinical trials. Obesity is a risk factor for SEA and might affect the beneficial effect of asthma medication. ANANKE is part of AstraZeneca’s global XALOC real-world evidence program for benralizumab. Aims: To explore whether benralizumab efficacy is affected by body mass index (BMI) in SEA patients. Methods: Post-hoc analysis of an observational, multicenter, retrospective Italian study of SEA patients with at least 12 weeks of BEN treatment. Patients were stratified according to BMI: normal/underweight (Nr) (BMI Results: 182 patients were included, Nr=70 (68.6% female, mean age 55±12.8, median BEN duration 9.2 months), OW=79 (48.1% female, mean age 56.6±12.9, median BEN duration 9.4 months), Ob=33 (75.8% female, mean age 56.5±14.7, median BEN duration 10.2 months). Any AER passed from 4.49 to 0.18 (-96%) in Nr (N=66), from 3.99 to 0.32 (-92%) in OW (N=76) and from 3.72 to 0.34 (-90.9%) in Ob (N=30). Severe AER changed from 1.32 to 0.04 (-97%) in Nr, from 1.12 to 0.10 (-91.1%) in OW and from 1.13 to 0.08 (-92.9%) in Ob. ACT increased from a median of 15 in Nr (N=57), 14 in OW (N=61) and 13 in Ob (N=25) to 22 in Nr (N=29) and Ob (N=11) and 23 in Ow (N=35) at week 48. Conclusions: In an Italian real-world setting, the efficacy of BEN in SEA patients seems not to be affected by obesity, leading to asthma control al >90% reduction of AER and severe AER regardless of BMI.

Background An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. Objective The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. Methods As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. Results The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. Conclusions Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.

BACKGROUND An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. OBJECTIVE The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. METHODS As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. RESULTS The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. CONCLUSIONS Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.

The COVID-19 pandemic has highlighted the vital importance and impact of human behaviour on viral transmission. During 2020, large amounts of global survey data were collected and made freely available to help the response. Many teams responding to the pandemic lack capacity to identify and interpret behavioural data. A collaboration of the World Health Organization’s Behavioural Insights team and UCL’s Centre for Behaviour Change designed and piloted two templates to enable survey data use during the first months of the pandemic. The first template documents key behaviours, thoughts and emotions related to the pandemic, along with social interactions and population adherence to behavioural guidelines. The second template enables countries to formulate questions or issues that they would like behavioural data to address. This collaborative process applying behavioural science theory produced structured templates to enable organisation and interpretation of survey data to inform policy and practice in different country contexts.

BackgroundMedia coverage of road traffic collisions (RTCs) may influence preventative action. India experiences some of the highest RTC mortality and morbidity rates globally, but advocacy and effective action to mitigate this has been limited. We conducted an analysis of Indian media in English to assess whether coverage met the WHO’sReporting on Road Safetyguidelines for evidence-based reporting of RTCs.MethodsEnglish-language articles published online between March 2018 and February 2019 were assessed against the seven recommended story angles and seven recommended key elements in the WHO guidelines.Results458 articles were included in the analysis. The most common story angle was descriptions of single collisions, which was not a WHO-recommended story angle. These included limited key elements such as use of human story or linking to road safety risks or evidence-based solutions. However, some articles did follow the WHO-recommended story angles, with 22.1% discussing specific road safety solutions and a further 6.3% discussing vulnerable groups. Almost all articles avoided the use of technical language, but only 2.0% explicitly stated that RTCs were preventable. More than half identified at least one evidence-based solution. Very few articles discussed economic or health impacts of RTCs, including the burden they present to the public health system.ConclusionIndian media in English can improve reporting by focusing on human stories and documenting experiences of those injured in RTCs. Coverage should also focus more on evidence-based solutions, emphasising the systems approach which encourages government action rather than changes to individual behaviour.

Introductions: Safety and efficacy of benralizumab for severe eosinophilic asthma (SEA) have been demonstrated in Phase III clinical trials. However real-word evidence in Italy is limited. ANANKE is part of AstraZeneca’s global XALOC RWE program for benralizumab. Objects: To describe the clinical impact of benralizumab on adult patients with SEA in a real-life setting. Methods: This is an ongoing observational, multicentre, retrospective study of the clinical characteristics and asthma exacerbations for SEA patients in Italy with at least 12 weeks of benralizumab treatment. Clinical (including comorbidities and atopic status) and laboratory (blood eosinophil count and total IgE) data have been collected. Annualized exacerbation rates (AER) before and after the first benralizumab injection (index date) were analysed. Results: 61 patients were included in this interim analysis [70.5% female, mean age 52.8 ± 13.9, median duration of disease 9.5 years (IQR 3.7-23.1), median eosinophil count (N=41) 410/mm3 (IQR 300-680/mm3), median total IgE (N=39) 215 IU/L (IQR 83-477 IU/L), atopic status 55.7%]. Comorbidities were frequent (44/61 patients, 72.1%), and 34.4% reported chronic rhinosinusitis with nasal polyps (CRSwNP) in the past year. Patients were treated with benralizumab for a median of 9.3 months (IQR 6.1-11.7).During the year prior to index date, AER was 4.98 for any exacerbation and 1.25 for severe exacerbations (N=52). After index date, AER was reduced to 0.38 for any exacerbation(92.4% reduction) and 0.08 for severe exacerbations (93.6% reduction). Conclusion: benralizumab has been prescribe to adult-onset SEA patients, with high prevalence of CRSwNP, indipendent of atopy. Benralizumab led to 93.6% reduction in severe AER

Ceftolozane-tazobactam is a novel fifth-generation cephalosporin/β-lactamase inhibitor combination recently approved for treatment of both complicated intra-abdominal and urinary tract infections in adults. Considering its potent bactericidal activity against Pseudomonas aeruginosa, it might represent an important option also for treating children with exacerbations of cystic fibrosis due to Pseudomonas aeruginosa when other alternative treatments have been exhausted. We hereby review available data on the use of ceftolozane-tazobactam in children, focusing on cystic fibrosis.

Sepsis is still related to high mortality and hospitalization rates in the paediatric population despite medical progress. Prompt recognition of sepsis and consequent initiation of an appropriate treatment are essential elements in securing a positive outcome in adults and children. In such scenario, various biomarkers have been studied to support the clinician in the diagnosis of severe infections, in the identification of patients at risk of progression towards sepsis as well as in the evaluation of the response to treatment. In children, the performance of C-reactive protein and procalcitonin has been largely investigated, whereas data on newer biomarkers of sepsis are scant. The aim of the present review is to summarise the available data on the use of pro-adrenomedullin in the paediatric age.

In a lung cancer survey in 2000 we showed significantly less favourable stage distribution and lower resection rate in Teesside (UK) than in the comparable industrialised area of Varese (Italy). Lung cancer services in Teesside were subsequently reorganised according to National Cancer Plan recommendations.For all new lung cancer cases diagnosed in Teesside (n=324) and Varese (n=260) during the 12 months October 2010 to September 2011 (hereafter 'the 2010 cohort'), demographic, clinico-pathological and disease management data were prospectively recorded using the same database and protocol as the 2000 survey. Findings were analysed focusing on resection rate.In the 2010 cohort compared with 2000, both in Teesside and Varese emergency referral decreased (p0.001), performance status improved (p0.001), but cancer stage shift was not seen; resection rate improved in Teesside, from 7% to 11% (p=0.054), and was unchanged in Varese (24%). Moreover, in Teesside compared with Varese the stage distribution remained less favourable, stage I-II non-small cell lung cancer (NSCLC) proportion being respectively 12% and 19% (p=0.040), and resection rate in all lung cancers remained lower (11% and 24%; p0.001). On multivariate analysis, resection predictors in Teesside were as follows: stage I-II NSCLC (OR 86.14; 95% CI 31.80 to 233.37), performance status 0-1 (OR 5.02; 95% CI 1.48 to 17.07), belonging to 2010 cohort (OR 2.85; 95% CI 1.06 to 7.64).In Teesside the main independent predictor of resection was disease stage; in 2010-2011 compared with 2000, lung cancer service improved but stage shift did not occur, and resection rate increased but remained significantly lower than in Varese.

The clomiphene citrate challenge test is a tool to predict ovarian reserve and fertility. It has mainly been used as a predictor of success of IVF/intracytoplasmic sperm injection (ICSI) cycles. Infertile young women with diminished ovarian reserve have a worse prognosis than women with adequate ovarian reserve attempting IVF/ICSI cycles. Nothing is known regarding the outcome of young women with diminished ovarian reserve undergoing low-complexity assisted reproductive treatment such as ovulation induction plus intrauterine insemination (IUI). This study included all women under 37 years who consulted in the authors’ centre between May 2004 and August 2005 who underwent ovulation induction and IUI. Ninety-six women younger than 37 years with adequate ovarian reserve, and 50 women with diminished ovarian reserve were found. The pregnancy rate and pregnancy rate per cycle in the adequate ovarian reserve group were significantly higher than those of the diminished ovarian reserve group (46.7% versus 25%, P < 0.02; 15.9% versus 7.6%, P < 0.02 respectively). It is concluded that the clomiphene citrate challenge test is a good predictor of low-complexity infertility intervention outcome, and represents an effective tool to establish a prognosis. Therefore, it is very useful in planning therapy, and advising the infertile couple.

The precise mechanisms by which corpus luteum (CL) function is modulated during early pregnancy are not known. Evidence in failed pregnancies (ectopic, abortions), shows that factors other than human chorionic gonadotrophin (HCG) could be involved in its regulation. The objective of this study was to investigate the dynamics of beta-HCG, progesterone and oestradiol production in early pregnancy and its relation to embryonic quality and topographic localization. Plasma concentrations of progesterone, oestradiol and beta-HCG were studied between days +12 and +21 after an in-vitro fertilization (IVF) embryo transfer in 11 intrauterine pregnancies, 10 intrauterine abortions and seven tubal pregnancies. Tubal pregnancies and abortions were grouped according to doubling time (DT) of HCG. Results showed that oestradiol concentrations were apparently reduced in both ectopic pregnancies and abortions compared with normal pregnancies. The fall in oestradiol concentrations was seen in ectopic pregnancies with an abnormal DT for HCG and in all abortions. When the ectopic pregnancy had a normal DT, oestradiol and progesterone concentrations were normal. In abortions, the fall in oestradiol and progesterone concentrations was less influenced by the DT of HCG. These findings suggest that corpus luteum function depends on an adequate DT of HCG more than an absolute value, and with normal trophoblastic tissue the site of implantation does not affect CL function.

The expression of the glucocorticoid receptor (GR) in untreated or in steroid-dependent asthmatic patients is poorly understood. We therefore studied GR mRNA and protein levels in bronchial biopsies obtained from seven untreated asthmatic patients, seven control volunteers, and seven patients with chronic bronchitis. We also studied in bronchial epithelial cells obtained by brushing from 13 untreated asthmatics, 18 steroid-dependent asthmatics, 11 control volunteers, and 12 patients with chronic bronchitis, GR and heat shock protein 90 kD (hsp90) mRNA as well as the immunoreactivity of GR, intercellular adhesion molecule (ICAM-1), and granulocyte macrophage-colony-stimulating factor (GM-CSF). GR mRNA and protein level was similar in all subject groups in both biopsies and bronchial epithelial cells. Hsp90 mRNA level was also similar in all subject groups. ICAM-1 expression was significantly increased in bronchial epithelial cells from untreated asthmatics, but ICAM-1 was not expressed in those from steroid-dependent asthmatic patients. GM-CSF expression was significantly increased in bronchial epithelial cells from untreated and steroid-dependent asthmatic patients. GR expression within the airways is unaltered by oral long-term steroid treatment in asthma, but the expression of some but not all specific markers for asthma is modified by oral steroid.

59 Background: The Pain Control Center Hospice of Solofra (Italy) is managed with a mixed public / private, the first experience in the Campania region.We have evaluated the treatment procedures and the clinical outcome to make a comparison by between 123 evaluable patients in palliative care in 2015 and 232 evaluable patients in the biennium 2012-2014. Methods: The following characteristics: patient gender, mean hospitalization time, differentiation between cancer and non cancer patients, medical weapon use, venous access type, enteral and parenteral feeding, pain killer use,Karnofsky scale. Results: the average age is nearly overlapping being 70.5 yr vs 70.69 yr; average length of stay in hospice 24.33 days vs. 27.52 days; 79.67% had cancer vs 73.70%, while the non-cancer 20.32% vs 26.30%; 55.26% died in hospice vs 71.98%, while 44.7% were discharged home vs 24.56%; the performance status according to Karnofsky scale before admission to hospice 23.1% had index rating (%)- 50, 10.56 -40, 52.03%-30, 35.7%-20, 23.1%-10. 8.9% had ostomy vs 13.79%; 4.4% were carriers of PEG vs 6.3%; the central venous access already implanted at admission in 32.52% vs 26.72%; enteral feeding was administered in 23.7% vs 13.79% and parenteral feeding in 52.84% vs 46.98%; analgesic therapy with more opiates was already present on admission in 48.78% vs 40.94% with prevalence of trans TD formulations. Analgesic therapy was administered during the hospitalization in 66.66% vs 81.89%. 14.28% of cancer patients in 2015 have received morphine treatment vs 15.3%, 22.11% oxycodone / naloxone vs 19%, 58.16% trans-dermal fentanyl vs. 34%, 14.7% have supplements onset fentanyl, 2.4% with tapentadol vs na, 15.30% tramadol vs 9%, 4.2% codeine vs 15.3%. Conclusions: This report is a feasibility model of end of life-care in the Avellino province submitted to the public administrative control with the private organization supporting House Hospital Onlus. The present study shows gradual improvement of the knowledge of palliative care by the family doctors and the population of a territory with peculiar topography and induces public health authority to improve the care offered.

This article presents examples of grassroots aid projects and programs that delivers results, within the framework of the Development Marketplace. It discusses the extent to which such community-based efforts can be replicated.

Premature infants (PI) are neonates born

The venoms of Latrodectus sp. have been reported to induce contraction probably mediated by adrenergic and cholinergic transmitters. We have demonstrated that the venom of Chilean Latrodectus mactans contains neurotoxins that induce a contraction partially independent of transmitters release. Transmembrane mobility of Na+ and Ca2+ ions and more specifically, the increase of cytoplasmic calcium concentration are responsible for tonic contraction in smooth muscle. Calcium may enter the cell by several ways, such as the voltage-dependent Ca2+ L-type channels and the Na+/Ca2+ exchanger. This study aimed to examine the participation of this exchanger in the tonic contraction of smooth muscle in vas deferent of rat induced by the venom of the Chilean spider L. mactans. Blockers of Na+ channels (amiloride) and Ca2+ L-type channels (nifedipine), and a stimulator of the exchanger (modified Tyrode, Na+ 80 mM) were used. Simultaneously, variations of the cytoplasmic concentration of Ca2+ were registered by microfluorimetry (Fura-2 indicator) in the presence of nifedipine. In presence of amiloride, dose-dependent inhibition of venom-induced contraction was observed, suggesting the participation of voltage-dependent Ca2+ L-type channels. The contraction was only partially inhibited by nifedipine and the Ca2+ cytoplasmic concentration increased, as assessed by the microfluorimetric registration. Finally, the venom-induced contraction increased in the presence of modified Tyrode, probably due to the action of the Na+/Ca2+ exchanger. Taken together, our results support the idea that the Na+/Ca2+ exchanger is active and may be, at least in part, responsible for the contraction induced by the venom of Chilean L. mactans.

To study the follicular growth profile of normal women, 25 multiparous volunteers were assessed daily by ultrasound to measure the growing follicle and underwent venipuncture daily for detection of the luteinizing hormone (LH) peak. Eleven subjects conceived during the first cycle, 1 during the second cycle, and 1 during the third cycle. The 15 cycles where conception was not achieved showed unequivocal signs of ovulation (i.e., an LH peak and progesterone concentrations in the luteal phase greater than 20 nM/l). The mean prerupture follicular diameter was not significantly different in either group, 19.65 mm and 19.1 mm, respectively; however, the growth profile showed marked differences with a stabilization of follicular growth 24 hours prior to rupture in all patients in the conception group. On the other hand, the LH peak occurred within the 24 hours immediately preceding follicular rupture in the conception cycles; whereas in the nonconception group, this time interval extended up to 48 hours prior to rupture.

Ketoconazole, an imidazole derivative known to inhibit cytochrome P450-dependent adrenal enzymes was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 weeks of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the first day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg/24 h to near normal levels within a week of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17 beta-estradiol fell likewise from 1096 to 150 pg/ml. In contrast, cortisol levels in serum and urine increased in the first 2 weeks of the trial and subsequently fell to values below the basal levels. Similarly, serum 17 alpha-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. Nine months after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. We conclude that ketoconazole was effective in blocking tumoral steroidogenesis which resulted in clinical benefit.