Do we trust scientific evidence? A multicentre retrospective analysis of first IVF/ICSI cycles before and after the OPTIMIST trial.

STUDY QUESTION: Has the practice of individualizing the recombinant-FSH starting dose been superseded after the largest randomized controlled trial (RCT) in assisted reproduction technology (ART), the OPTIMIST trial? SUMMARY ANSWER: The OPTIMIST trial has influenced our ART daily practice to a limited degree, but adherence is still generally poor. WHAT IS KNOWN ALREADY: Although the 'one size fits all' approach has been discouraged for decades by most authors, the OPTIMIST study group demonstrated in a large prospective RCT that, in general, dosage individualization does not improve the prospects for live birth, although it may decrease ovarian hyperstimulation syndrome (OHSS) risk in expected high responders. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of all first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles from 1st January 2017 to 31st December 2018, before and after the OPTIMIST publication on November 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two thousand six hundred and seventy-seven patients, between 18 and 42 years old, undergoing their first IVF-ICSI cycle in seven Italian fertility centres, were included. Patients were allocated to three groups according to their ovarian reserve markers: predicted poor ovarian responders (POR), predicted normo-responders (NR) and expected hyper-responders (HRs). MAIN RESULTS AND THE ROLE OF CHANCE: Between 2017 and 2018, there was an overall increase in prescription of the standard 150 IU dose proposed by the OPTIMIST trial and a reduction in the use of a starting dose >300 IU. After subgroup analysis, the decrease in doses >300 IU remained significant in the POR and NR sub-groups. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study. Physicians need time to adapt to new scientific evidence and a comparison between 2017 and 2019 may have found a greater impact of the Optimist trial, although other changes over the longer time span might have increased confounding. We cannot be sure that the observed changes can be attributed to knowledge of the OPTIMIST trial. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians may be slow to adopt recommendations based on RCTs; more attention should be given to how these are disseminated and promoted. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. E.P. reports grants and personal fees from MSD, grants from Ferring, from IBSA, grants and personal fees from Merck, grants from TEVA, grants from Gedeon Richter, outside the submitted work. E.S. reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from Theramex, outside the submitted work. All other authors do not have conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

From building regulations and local health rules to the new local building codes: a national survey in Italy on the prescriptive and performance requirements for a new performance approach.

BACKGROUND: World Health Organization has highlighted the need to strengthen the relationship between health and built environment factors, such as inappropriate housing conditions. Building Regulations and Local Health Rules provide safety and building hygiene in construction practices. Currently the Italian Government is giving rise to a Building Regulation Type and the paper aims to verify the present contents of recent innovative Local Health Rules and Building Regulations of several Italian municipalities for supporting the performance approach of the future Building Regulations including hygienic issues. METHODS: The analysis examines both Building Regulations and Local Health Rules of a sample of about 550 cities, analysing some specific fields of interest: urban field, outdoor issues, housing features, housing restrictions, and qualitative aspects. RESULTS: The analysis focuses on some specific aspects defining the general data reported in Building Regulations and Local Health Rules, in particular around surfaces, heights, lighting and aeration ratio, basements and semi-basements, gas radon, building greenery, etc. CONCLUSION: The investigation permitted to have a wide vision on the present State of the Art in order to highlight some innovative aspects and design approaches of Building Regulations and Local Health Rules. New perspectives in the new regulations should have a performance approach, starting also from the recent SARS-CoV-2 pandemic.

A proposal of hygienic and sanitary standards for the new Building Code in Italy.

The traditional emphasis of Public Health on the type and quality of housing today merges with other wider determinants of health such as: the neighbourhood, the community and the "place" where a home is located, but also the policies that make access to a healthy home within everyone's reach. At the neighbourhood scale, context-related aspects heavily influence the internal quality and real usability of the buildings themselves, with particular reference to factors such as the quality of the site, the relationship between the building and the context, the presence and quality of the greenery and open spaces surrounding the building, as well as all measures that make it possible to reduce the building's impact on the environment, to protect it against environmental pollution, and to manage the building in an integrated manner for maintenance purposes. Creating healthy living environments means referring to the different dimensions mentioned above, and this not only requires the attention of Public Health operators, but also implies an integration of vision and objectives among various professional skills and competences that puts health at the center of all policies. This proposal, which starts from the analysis of existing local hygiene regulations and scientific literature, aims to take stock of a number of areas considered fundamental for the assessment of building hygiene aspects, with particular reference to the eco-sustainability of buildings and adaptation to climate change. The aspects identified can be considered as a starting point for the preparation of integrated building and hygiene regulations based on documented effective practices for the protection of Public Health.

Evidence Based Hospital Design. A literature review of the recent publications about the EBD impact of built environment on hospital occupants' and organizational outcomes.

INTRODUCTION: Healthcare facilities are complex infrastructures where different features from technological, social, clinical and architectural field interact. In modern healthcare systems there is a growing attention to the need of quality in terms of process and outcome, while the structural (physical) aspects are not often considered. Since the Nineties the theory of the Evidence Based Design (EBD) states that there is significant relationship between built environment and health related outcome. OBJECTIVE: Aim of this paper is to investigate, in the recent scientific literature, which are the most important occupants' and organizational outcomes influenced by EBD hospital built environment qualities. METHODOLOGY: A Literature Review based on Scopus and PubMed databases has been run in order to understand the existing situation in terms of hospital quality evaluation from the physical and architectural point of view and to highlight the current trends. The results of the different reviews, empirical studies and post Occupancy Evaluations have been analyzed according to Ulrich's EBD conceptual framework. RESULTS: 35 peer reviewed papers from the last 2 years were included. The methodologies adopted are very different and data are mainly collected through structured interviews or observations and elaborated with qualitative (33%), quantitative (26%) or mixed (41%) methodologies. The topic is mostly investigated in USA, Australia, Canada, UK and in the Scandinavian region; few contributions come also from Italy. Built environment variables that affect user's or organizational outcomes are mainly the Visual Environment (29%), the Audio Environment (20%) and the Patient Room Design (20%). DISCUSSION AND CONCLUSION: The most recurrent outcomes found to be affected by the built environmental qualities are staff job satisfaction (n=11), patients' stress reduction (n=9), patients' satisfaction (n=6) and patients' fall reduction (n=6). Organizational outcomes are mentioned only two times. Although EBD is an old theory, the topic is both contemporary and relevant. Due to the diversity of the contributions and the limitations of the research, a deep comparison is challenging. Further investigation is necessary to deepen each of the variables identified.

Strategies for Disease Prevention and Health Promotion in Urban Areas: The Erice 50 Charter.

The Erice 50 Charter titled "Strategies for Diseases Prevention and Health Promotion in Urban Areas" was unanimously approved at the conclusion of the 50th Residential Course "Urban Health. Instruments for promoting health and for assessing hygienic and sanitary conditions in urban areas", held from 29th March to 2nd April 2017 in Erice, at the "Ettore Majorana" Foundation and Centre for Scientific Culture and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group "Building Hygiene" of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). At the conclusion of the intense learning experience during the Course, with more than 20 lectures, workshops and long-lasting discussions between Professors and Students, the participants identified the major points connecting urban features and Public Health, claiming the pivotal role of urban planning strategies for the management of Diseases Prevention and Health Promotion activities. The Erice 50 Charter is configured as a Decalogue for Healthy Cities and as a Think Tank for designing effective strategic actions and best practices to develop urban regeneration interventions and improve the urban quality of contemporary cities. The Decalogue is structured into the following key strategic objectives: 1. Promoting urban planning interventions that address citizens towards healthy behaviours; 2. Improving living conditions in the urban context; 3. Building an accessible and inclusive city, with a special focus on the frail population; 4. Encouraging the foundation of resilient urban areas; 5. Supporting the development of new economies and employment through urban renewal interventions; 6. Tackling social inequalities; 7. Improving stakeholders' awareness of the factors affecting Public Health in the cities; 8. Ensuring a participated urban governance; 9. Introducing qualitative and quantitative performance tools, capable of measuring the city's attitude to promote healthy lifestyles and to monitor the population's health status; 10. Encouraging sharing of knowledge and accessibility to informations. Finally, all the participants underlined that a multidisciplinary team, composed of Physicians specialized in Hygiene, Preventive Medicine, Public Health and Technicians as Architects, Urban planners and Engineers, is needed to deepen the research topic of Urban Health.

Measuring the expected increase in cycling in the city of Milan and evaluating the positive effects on the population's health status: a Community-Based Urban Planning experience.

BACKGROUND: It's scientifically known that inactivity is one of the major risk factors for Non-Communicable Diseases. One of the elements affecting the choice of transport mode, regarding circulation in the city, is the cities' urban morphology, i.e. the infrastructural facilities for the slow mobility service. Cyclability, in fact, can help to increase daily physical activity level, therefore becoming a protective factor for individual health. METHODS: After a literature review about the state of the art regarding the correlation between built environment, active transport and quantification of the physical activity level, we have developed a specific questionnaire to collect information about current and forecast use of bicycle, in case of improvement and implementation of the cycling network. The questionnaire also investigated social and health aspects concerning the anamnesis of the interviewees (age, gender, health status, sport activity performed, etc) and users' opinions about existing infrastructure and planned interventions, designed to promote cycling mobility. Aim of the research was to quantify the increase of physical activity people would have realized in front of an improvement of the specific infrastructures, and the expected positive effects in terms of health. RESULTS: The collected data (343 interviewed in a district of Milan, named "Zona 7") demonstrate that through the implementation of the cycle network, there would be more cyclists to practice the 150 minutes weekly of physical activity recommended by WHO: time spent in cycling, indeed, would increases by 34.4% compared to the current level of cyclability, as detected by our survey. CONCLUSIONS: The investigation confirmed that urban interventions, especially those in small-scale, could play a key role in the promotion of healthy lifestyles, inducing therefore important positive effects on the population health. It was also carried out an application of the WHO "Health Economic Assessment Tool" to evaluate the benefits in terms of Non-Communicable Diseases' reduction, specifically a provisional quantification of deaths saved.

Soft qualities in healthcare. Method and tools for soft qualities design in hospitals' built environments.

BACKGROUND: The design of hospital environments is determined by functional requirements and technical regulations, as well as numerous protocols, which define the structure and system characteristics that such environments need to achieve. In order to improve people's well-being and the quality of their experience within public hospitals, design elements (soft qualities) are added to those 'necessary' features. The aim of this research has been to experiment a new design process and also to create health care spaces with high environmental quality and capable to meet users' emotional and perceptual needs. METHODS: Such needs were investigated with the help of qualitative research tools and the design criteria for one of these soft qualities - colour - were subsequently defined on the basis of the findings. The colour scheme design for the new San Paolo Hospital Emergency Department in Milan was used as case study. Focus groups were fundamental in defining the project's goals and criteria. RESULTS: The issues raised have led to believe that the proper procedure is not the mere consultation of the users in order to define the goals: users should rather be involved in the whole design process and become co-agents of the choices that determine the environment characteristics, so as to meet the quality requirements identified by the users themselves. CONCLUSIONS: The case study has shown the possibility of developing a designing methodology made by three steps (or operational tools) in which users' groups are involved in the choices, loading to plan the environments where compliance with expectations is already implied and verified by means of the process itself. Thus, the method leads to the creation of soft qualities in Healthcare.

Erythromycin- and tetracycline-resistant lactobacilli in Italian fermented dry sausages.

AIMS: To assess the frequency of erythromycin- and tetracycline-resistant lactobacilli in Italian fermented dry sausages. METHODS AND RESULTS: We isolated lactobacilli colonies from 20 salami from the north of Italy (Piacenza province) using selective medium supplemented with erythromycin or tetracycline; we determined the minimum inhibitory concentration and searched for selected erythromycin and tetracycline resistance genes. A total of 312 lactobacilli colonies were genetically ascribed to 60 different strains belonging to seven Lactobacillus species. Lactobacillus sakei, Lactobacillus curvatus and Lactobacillus plantarum were the most frequently found species. Thirty strains (50%) were phenotypically resistant to erythromycin, 45 (75%) to tetracycline and 27 (45%) were resistant to both. The most frequently detected resistance genes were tet(M) and erm(B). CONCLUSIONS: This study provides evidence of the presence of tetracycline- and, to a lesser extent, erythromycin-resistant lactobacilli in fermented dry sausages produced in northern Italy. SIGNIFICANCE AND IMPACT OF THE STUDY: Although these antibiotic-resistant lactobacilli could serve as reservoir organisms, in our study, 16 of 20 salami could be considered safe in regard to possible antibiotic resistance gene transfer to pathogens, whereas 4 of 20 could represent a borderline situation.

Changes of gut microbiota and immune markers during the complementary feeding period in healthy breast-fed infants.

INTRODUCTION: Little is known about changes in intestinal microbiota during the important period of complementary feeding (weaning). This descriptive study investigated changes of selected gut microbiota and markers of gut permeability and the immune system in breast fed infants during the complementary feeding period. METHODS: 22 healthy, exclusively breast fed infants (from birth to 4 months) with no antibiotic intake during the month prior to the study, were followed from 4 to 9 months of age. Faecal and saliva samples were collected at the start of the study (V0) and at monthly intervals (V1-V5) for measurement of selective gut microbiota (bifidobacteria, lactobacilli, vancomycin-insensitive lactobacilli, enterobacteria, enterococci, Clostridium perfringens) using semi-selective media. Immune markers (alpha-1-antitrypsin, eosinophil cationic protein (ECP), secretory IgA and TNF-alpha were measured in saliva and secretory IgA and TNF-alpha in faecal samples. RESULTS: High stool bifidobacteria counts at the start of the study (7.99 1 1.95 log10 CFU/g faeces) remained stable throughout the 5 months of complementary feeding while counts of enterobacteria and enterococci increased with age (P < 0.05 and P = 0.02 respectively). Vancomycin-insensitive lactobacilli increased significantly during weaning for V0 to V3 (P < 0.01), and then decreased slightly (V4). Faecal Clostridium perfringens remained below the detection limit during the study and parameters measured in saliva did not change. Faecal ECP decreased significantly from 1.011.4 (V0) to 0.510.9 mg/mg protein (V5) P = 0.03. CONCLUSION: Age and/or diet modifications during complementary feeding had no impact on faecal bifidobacteria counts but increased those of enterobacteria and enterococci. Transient increases in faecal lactobacilli and vancomycin-insensitive lactobacilli counts were observed. The reduction in faecal ECP may indicate a decrease in gut permeability (reinforcement of gut mucosa integrity) during the weaning period with age [corrected]

[Ultrasonography-guided percutaneous alcohol injection for hepatocellular carcinoma in the cirrhotic patient]. / Alcolizzazione percutanea ecoguidata del carcinoma epatocellulare nel paziente cirrotico.

The present study, performed in the Department of Internal Medicine and Gastroenterology of Policlinico of Modena, shows the results of the treatment with percutaneous ethanol injection of cirrhotic patients with hepatocellular carcinoma. In the period between June 1991-May 1998, 37 nodules of hepatocellular carcinoma, in 26 cirrhotic patients, were treated with ethanol injection under the ecographic guidance; the total number of sessions was 179. Ten lesions were recurrences (local or distant) in patients already treated. These patients were excluded from surgical treatment because of the high age, the high surgical risk or patient's choice. "Therapeutic success", defined as radiologic (TC or RM) demonstration of complete necrosis at the end of the first cycle of treatment, was achieved in 22/27 nodules after the first treatment (81.5%). Therapeutic success of the recurrence (second treatment) was achieved in 7/10 nodules (70%). In treated patients, survival probability (obtained with Kaplan Meier method) was 84.5%, 73.0%, 50.0%, 38.5%, 26.9%, respectively at 1st, 2nd, 3rd, 4th and 5th year. After a total number of 179 sessions, there were no relevant complications. The results obtained in our experience prove the efficacy and safety of this therapeutic technique in patients with cirrhosis and hepatocellular carcinoma.

Physiological and molecular techniques for the study of bacterial community development in sausage fermentation.

The development of the microbial community involved in the production process of Italian dry sausage was investigated using physiological analysis and molecular techniques for strain typing and taxonomical identification. A cycle of sausage production was followed collecting samples during the 2 months of ripening process. Microbiological analysis allowed the identification of the main bacterial groups responsible for the fermentation process as lactobacilli and coagulase-negative staphylococci. The use of a polymerase chain reaction-based technique of strain typing, RAPD fingerprinting, demonstrated that the environmental parameters interact to select a limited number of strains that dominate the fermentation process. The staphylococcal populations were characterized for their physiological properties and the two dominant strains were identified as Staphylococcus xylosus and Staph. sciuri. The use of 16S rDNA sequencing allowed the definition of the taxonomical position of the two dominant strains of lactic acid bacteria, as belonging to Lactobacillus sake and Lact. plantarum.

[The use of echo-guided fine-needle biopsy in the diagnosis of nodular hepatic lesions]. / Utilità della biopsia ecoguidata con ago sottile nella diagnosi delle lesioni nodulari epatiche.

211 patients were submitted to percutaneous ultrasound-guided liver biopsy: 184 patients (87.2%) had only one focal lesion, the other 27 had two or more lesions. In 9 patients (4.27%) the material drawn out from the liver was not adequate for microscopic examination (Retrieval Rate 95.7%). Histological evaluation revealed: absence of neoplasm in 67 patients (31.75%), benign lesion in 29 patients (13.74%), primitive malignant lesion in 70 patients (33.18%) and metastatic malignant lesion in 36 patients (17.06%). Combining the histological data with disease manifestation, biopsy showed a sensitivity of 95.1%, specificity of 100%, positive predictive value of 100%, negative predictive value of 89.4% and a diagnostic accuracy of 92.4%. None of the most important complications described in literature was observed. Our study confirms that ultrasound guided biopsy is a procedure of high diagnostic value in patients with nodular liver lesions, advantageous for its simplicity, low cost and safety.

Multiple ocular impairment in a patient affected by Waldenström's macroglobulinaemia.

BACKGROUND: We studied a bilateral tumefaction of the lacrimal gland in a female patient. METHOD: Ocular and general clinical examinations were carried out. RESULT: Computerized tomography (CT) of the cranial orbit showed a tumefaction of solid density in the lacrimal gland. Histological examination of material removed by needle aspiration revealed the presence of elements of a lymphoplasmacytoid nature. Fluorescein angiography showed dilatation of the veins, intraretinal flame haemorrhages and small ischaemic areas. Chest CT showed an increase in the size of the middle and upper mediastinal lymph nodes, and examination of a specimen of bone marrow from the chest revealed the presence of small lymphocytes with a plasmacytoid tendency. CONCLUSION: On the basis of the findings, we diagnosed Waldenström's disease with rare multiple ocular impairment (lacrimal gland and retina) in an early stage.

Alpha but not beta interferon is useful in chronic active hepatitis due to hepatitis C virus. A prospective, double-blind, randomized study.

Interferon-alpha has been widely used in chronic hepatitis C, but controlled studies with intramuscular interferon-beta are lacking. We therefore performed a prospective, double-blind, randomized study comparing intramuscular IFN-alpha and -beta in patients with chronic hepatitis C. Sixty patients were randomly assigned to receive 3 MU thrice weekly intramuscularly of either recombinant IFN-alpha or leukocyte IFN-alpha or fibroblast IFN-beta for six months. Nine of 20 patients (45.0%) in the recombinant IFN, 5/19 (26.3%) in the leukocyte IFN, and none in the IFN-beta group had a complete response during therapy (recombinant IFN vs IFN-beta: P < 0.01). Only in IFN-alpha-treated patients, was infection with a single HCV genotype (type 2a or 2b) associated with significantly better long-term outcome. IFN-alpha is useful in chronic hepatitis C while intramuscular IFN-beta interferon does not exert any beneficial effect. This is probably due to an insufficient bioavailability of IFN-beta when given intramuscularly.

Identification of subjects at risk for colorectal carcinoma through a test based on K-ras determination in the stool.

BACKGROUND & AIMS: The gold standard for screening for colorectal carcinoma is colonoscopy. The aim of this study was to compare endoscopic results with those obtained using the noninvasive screening test of K-ras determination in the stool in a large population of patients undergoing colonoscopy. METHODS: Two hundred thirty consecutive patients were studied by K-ras amplification on stool-derived DNA using polymerase chain reaction and oligomer-specific hybridization. RESULTS: Wild-type K-ras was amplified in 103 of 230 patients (44.8%), the rate of amplification being directly proportional to the presence of an organic disease of the intestine characterized by hyperproliferating mucosa. In 30 of these 103 patients (29.1%), a K-ras mutation was found. Four of 5 with early colorectal carcinoma, all who had K-ras mutations in the tumor, were identified. In first-degree relatives of patients with colorectal carcinoma, all subjects either carrying adenomas > 1 cm in diameter or multiple smaller adenomas were identified. In patients with inflammatory bowel disease, the test identified the only patient with neoplastic transformation. CONCLUSIONS: The sensitivity and specificity of K-ras determination on stool-derived DNA in patients with colorectal carcinoma, in first-degree relatives of patients with colorectal carcinoma, and in patients with inflammatory bowel disease support the opportunity of a large-scale trial to validate its use as a screening test.

Selection of more pathogenic hepatitis C virus genotype II during long-term follow-up of interferon-treated patients.

The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76 +/- 18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were short-term responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the short-term responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II +/- I and 1 gt II +/- III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genotype, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P < 0.01 vs. untreated patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum cholesterol levels in axenic mice colonized with Enterococcus faecium and Lactobacillus acidophilus.

Hypocholesterolemic effect was shown in axenic, mono, bicolonized and conventional mice: the effect was different depending on probiotic properties of intestinal microorganisms. Contamination by Enterococcus faecium CX determined the highest effect: haematic cholesterol level decrease was 16.9% in females and 7.8% in males. In mice contaminated by Lactobacillus acidophilus N5 the decrease of haematic cholesterol levels was less and not relevant in mice contaminated by conventional microflora. Enterococcus faecium CX and Lactobacillus acidophilus N5 strains were able to grow in presence of bile salts, to colonize intestinal tract, to survive at gastric conditions and to assimilate cholesterol (E. faecium more than L. acidophilus). The authors consider the possibility to associate probiotic strains with these characteristics for the health of consumers.