Early prediction of unfavorable evolution after a first clinical episode suggestive of multiple sclerosis: the EUMUS score.

BACKGROUND: Predicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA). METHODS: Retrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort. RESULTS: After 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93-0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27-3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47-5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41-5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort. CONCLUSIONS: The EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making.

Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long-term follow-up of seven patients from four families and appraisal of the literature.

OBJECTIVE: Adenylosuccinate lyase (ADSL) deficiency is a rare inherited metabolic disorder with a wide phenotypic presentation, classically grouped into three types (neonatal, type I, and type II). We aim to better delineate the pathological spectrum, focusing on the electroclinical characteristics and phenotypic differences of patients with ADSL deficiency. PATIENTS AND METHODS: Seven patients, from four different families, underwent serial electroencephalogram (EEG), clinical assessment, and neuroimaging. We also performed a systematic review of the cases published in the literature, summarizing the available clinical, neurophysiological, and genetic data. RESULTS: We report seven previously unreported ADSL deficiency patients with long-term follow-up (10-34 years). From the literature review, we collected 81 previously reported cases. Of the included patient population, 58 % (51/88) were classified as having ADSL deficiency type I, 28% (25/88) as having type II, and 14% (12/88) as having neonatal. The most frequently reported pathogenic variants are p.R426H homozygous (19 patients), p.Y114H in compound heterozygosity (13 patients), and p.D430N homozygous (6 patients). In the majority (89.2%), disease onset was within the first year of life. Epilepsy is present in 81.8% of the patients, with polymorphic and often intractable seizures. EEG features seem to display common patterns and developmental trajectories: (i) poor general background organization with theta-delta activity; (ii) hypsarrhythmia with spasms, usually adrenocorticotropic hormone-responsive; (iii) generalized epileptic discharges with frontal or frontal temporal predominance; and (iv) epileptic discharge activation in sleep with an altered sleep structure. Imaging features present consistent findings of cerebral atrophy with frontal predominance, cerebellar atrophy, and white matter abnormalities among the three types. SIGNIFICANCE: ADSL deficiency presents variable phenotypic expression, whose severity could be partially attributed to residual activity of the mutant protein. Although a precise phenotype-genotype correlation was not yet feasible, we delineated a common pattern of clinical, neuroradiological, and neurophysiological features.

Asthma, COPD, Respiratory, and Allergic Health Effects in an Adult Population Living near an Italian Refinery: A Cross-Sectional Study.

BACKGROUND AND AIM: Asthma and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality worldwide. Globally, 545 million people suffer from chronic respiratory diseases with a wide geographical variability. Risk factors for asthma are both genetic and related to several environmental factors (internal and external pollutants); these also have an important role in the occurrence of COPD. The aim of this study was to describe the prevalence of asthma, COPD, and asthma/COPD overlap (ACO) in an adult population living in two municipalities located in the Po Valley. METHODS: A standardized questionnaire on respiratory symptoms and sociodemographic characteristics was self-administered to a random sample of the adult population aged 20-64 years, living near a refinery in Northern Italy during the period between 2016 and 2019. Logistic and multinomial regression were implemented to explore factors associated with asthma, COPD, and ACO. RESULTS: In total, 1108 subjects filled out the questionnaire, the mean age was 48.02 ± 12.34 years (range 21-68), and 53% of the respondents/participants were female. Half of the responders were non-smokers, but the frequency of current and former smokers was significantly greater in men than in women (p < 0.001). The likelihood of being a probable case of asthma decreased with increasing age and increased for smokers. Tobacco smoke was associated with the presence of COPD and ACO. CONCLUSION: Respiratory diseases such as asthma and COPD are common in the general population, with differences among countries worldwide. Our findings show, on the basis of the main confirmed risk factor, namely smoking, that it is useful to plan target programs and actions in order to reduce smoking, thus improving the quality of life in public health.

Health status of petrochemical workers: a narrative review.

SUMMARY: Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial.

Dementia and Risk Factors: Results from a Prospective, Population-Based Cohort Study.

The incidence rate of dementia varies between studies. The influence of some sociodemographic factors is reasonably established, but less is known about the role of comorbidities, which are common in the elderly. The objectives of this study was to estimate the incidence of dementia in a population of Italian elders and evaluate the role of walking speed, comorbidity and ApoE-ɛ4 as well as various sociodemographic factors on the new onset of dementia. The InveCe.Ab study is a population-based longitudinal study in people born between 1935 and 1939 and resident in Abbiategrasso, Milan, Italy. After excluding subjects with a diagnosis of dementia and those without a definite diagnosis, 1103 individuals with a median follow-up time of 4.1 years were included in the analyses. The cumulative four-year incidence of dementia was 5.3%. Demographic factors such as old age, male, less educated, ApoE-ɛ4 carrier status and slower gait were risk factors for dementia onset in a cognitively healthy sub-cohort. Comorbidity did not influence the onset of dementia; instead, slow walking speed appears to be a strong predictor of dementia onset.

Lifestyle-Related Risk Factors of Orthorexia Can Differ among the Students of Distinct University Courses.

Orthorexia nervosa (ON) is defined as the excessive attention on healthy eating, and studies especially focused on food quality ON prevalence in university students can be extremely variable. The objective of this study is to investigate whether there was a difference in ON risk between health-scientific, economic-humanistic, sport sciences and dietetics and nutrition students, and to evaluate if lifestyle-related ON risk factors (dieting, physical activity, drugs and supplements use) could have an impact in different ways in determining ON risk among students attending these four programs. Participants were recruited at the University of Pavia and received a two-section questionnaire including demographic and lifestyle information and the ORTO-15 questionnaire. A total of 671 students (54% F e 46% M) completed the questionnaire (median age 21.00 (IQR 20.00−23.00), median BMI 21.77 kg/m2 (IQR 20.06−23.66 kg/m2)). The 31.2% had ORTO-15 test scores < 35, and were considered at risk of having ON. No differences were found in ON risk among the students attending the four university courses. Dieting was confirmed as the major ON risk factor for health-scientific, economic-humanistic and sport sciences students. The type of sport practiced was an important determinant of ON risk only for the economic-humanistic course, while supplements use was statistically different between sport sciences students with or without ON. Our findings may suggest that lifestyle-related risk factors of orthorexia can differ among the students of distinct university courses, but these results need to be supported by further longitudinal and prospective studies.

Physical activity and quality of cardiopulmonary resuscitation: A secondary analysis of the MANI-CPR trial.

INTRODUCTION: The association between the level of physical activity and quality of cardio-pulmonary resuscitation (CPR) performed by laypeople is unclear. The aim of this study was to evaluate the associations between physical activity level and laypeople performance during an eight-minute scenario of CPR. MATERIALS AND METHODS: This study was a secondary analysis of the MANI-CPR Trial. The entire cohort of participants was grouped based on the level of physical activity assessed using the International Physical Activity Questionnaire (IPAQ) into a "low-moderate" level group and a "high" level group. Descriptive statistics were used for unadjusted analysis and multivariate logistic and linear regression models were also performed. RESULTS: A total of 492 participants who reached the score of "Advanced CPR performer" at the 1-min final test monitored by Laerdal Resusci Anne QCPR were included in this analysis; 224 with a low-moderate level and 268 with a high level of physical activity. A statistically significant difference was found for the outcome of percentage of compressions with adequate depth (low-moderate group: 87.8% [41·4%-99·3%], high group: 97% [63·2%-100%]; P = 0·003). No associations remained significant after controlling for biometric characteristics of the participants, compression protocols and sex. CONCLUSION: Adequate quality CPR may not need high baseline level of physical activity to be performed by a lay rescuer.

Cognitive, physical and disability trajectories in community-dwelling elderly people.

BACKGROUNDS AND AIMS: Health trajectories in aging, rather than single time-point assessments, could be early indicators of the onset of conditions such as dementia. The aim of this study was to identify different aging trajectories and to investigate their influence on the cumulative incidence of dementia. METHODS: We evaluated data referring to 993 elders from the InveCe.Ab study cohort. All subjects were free from dementia at baseline and re-assessed on at least one other occasion thereafter. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), physical function using the Walking Speed Test (WST), and disability on the basis of the Activities of Daily Living (ADL) score. To describe the different courses of the three outcomes combined, the Group-Based Trajectory Model (GBTM) method was applied. We looked for differences in age, gender, education, ApoE-e4 carrier status and obesity, and then investigated the influence of the observed trajectories on the incidence of dementia. RESULTS: Three trajectories were identified: a "good" scenario was observed in 703 (70.2%) individuals, who showed substantially stable cognitive and physical function and no disability; an "intermediate" scenario in 248 subjects (25.5%), who recorded a longer walking time, lower MMSE score, and a one-point higher ADL score; and a "severe" scenario in 42 elders (4.3%), who recorded declines in all the outcomes. Female gender, obesity and low education were most represented in the "severe" group. ApoE-e4 carrier status showed no difference between groups. The estimated cumulative incidence of dementia was higher in the "severe" (37%) than in the "intermediate" (7%) and "good" (< 1%) scenarios. CONCLUSIONS: Using simple measurements, we built different aging trajectories, and observed that the worst performers had the highest incidence of dementia. Better knowledge of trajectories of aging would be useful for preventive interventions aimed at promoting healthier aging.

A Multicenter International Randomized Controlled Manikin Study on Different Protocols of Cardiopulmonary Resuscitation for Laypeople: The MANI-CPR Trial.

BACKGROUND: Compression-only cardiopulmonary resuscitation (CPR) is a suggested technique for laypeople facing out-of-hospital cardiac arrest (OHCA). However, it is difficult performing high-quality CPR until emergency medical services arrival with this technique. We aimed to verify whether incorporating intentional interruptions of different frequency and duration increases laypeople's CPR quality during an 8-minute scenario compared with compression-only CPR. METHODS: We performed a multicenter randomized manikin study selecting participants from 2154 consecutive laypeople who followed a basic life support/automatic external defibrillation course. People who achieved high-quality CPR in 1-minute test on a computerized manikin were asked to participate. Five hundred seventy-six were enrolled, and 59 were later excluded for technical reasons or incorrect test recording. Participants were randomized in an 8-minute OHCA scenario using 3 CPR protocols (30 compressions and 2-second pause, 30c2s; 50 compressions and 5-second pause, 50c5s; 100 compressions and 10-second pause, 100c10s) or compression-only technique. The main outcome was the percentage of chest compressions with adequate depth. RESULTS: Five hundred seventeen participants were evaluated. There was a statistically significant difference regarding the percentage of compressions with correct depth among the groups (30c2s, 96%; 50c5s, 96%; 100c10s, 92%; compression only, 79%; P = 0.006). Post hoc comparison showed a significant difference for 30c2s (P = 0.023) and for 50c5s (P = 0.003) versus compression only. Regarding secondary outcome, there were a higher chest compression fraction in the compression-only group and a higher rate of pauses longer than 10 seconds in the 100c10s. CONCLUSIONS: In a simulated OHCA, 30c2s and 50c5s protocols were characterized by a higher rate of chest compressions with correct depth than compression only. This could have practical consequences in laypeople CPR training and recommendations.Clinical Trial Registration: NCT02632500.

Risk Perception and Worries among Health Care Workers in the COVID-19 Pandemic: Findings from an Italian Survey.

The ongoing pandemic scenario, due to the coronavirus disease 2019 (COVID-19), has had a considerable impact on public health all over the world. Italy was one of the most affected countries, as the first European full-blown outbreak occurred there. The exposure of the Italian health care workers to COVID-19 may be an important risk factor for psychological distress. The aim of this cross-sectional study was to describe worries and risk perception of being infected among Italian Health Care Workers (HCWs) during the first wave of the pandemic. In total, 2078 HCWs participated in a web survey (78.8% were females). The highest percentage of respondents were physicians (40.75%) and nurses (32.15%), followed by medical (18.00%), health care support (4.50%) and administrative (4.60%) staff. In a score range between 0 (not worried) and 4 (very worried), our results showed that participants declared that they were worried about the Coronavirus infection with a median score of 3 (IQR 2-3) and for 59.19% the risk perception of being infected was very high. In addition, HCWs reported they suffered from sleep disturbances (63.43%). From the analysis of the psychological aspect, a possible divergence emerged between the perceived need for psychological support (83.85%) and the relative lack of this service among health care providers emerged (9.38%). Our findings highlight the importance of psychological and psychiatric support services not only during the COVID-19 pandemic, but also in other emerging infectious diseases (EIDs) scenarios. These services may be useful for health authorities and policymakers to ensure the psychological well-being of health care professionals and to promote precautionary behaviors among them.

Use of Remote Monitoring by E-mail for Long-Term Management of the Classic Ketogenic Diet.

The classic ketogenic diet (cKD) requires constant nutritional monitoring over time both to ensure its effectiveness and to reduce the likelihood of short- and long-term adverse effects. We retrospectively described the use of remote monitoring by e-mail during the first year of follow-up on cKD in 34 children (47% males; age range: 2-17 years) diagnosed with drug-resistant epilepsy (DRE; n = 14) or glucose transporter type 1 deficiency syndrome (GLUT1-DS; n = 20). All the e-mails were evaluated analyzing their frequency and content at 3, 6 and 12 months. Three families never sent e-mails. A median of 36.0 (IQR 23.0-64.0) e-mails per family were sent during the 12 follow-up months by the 31 patients. GLUT1-DS patients sent a greater number of e-mails than the DRE group (median 39.0 (IQR 25.5-56.5) vs. median 26.0 (IQR 19.0-65.0)). At the end of the follow-up period, a greater number of e-mails had been exchanged between the nutritional team and the families belonging to the group that increased its linear growth (median 83.5; IQR 48.0-102.0), compared to the other ones. Constant remote monitoring by e-mail could be a feasible and effective way for a better cKD management.

COVID-19 Trend Estimation in the Elderly Italian Region of Sardinia.

December 2019 saw a novel coronavirus (COVID-19) from China quickly spread globally. Currently, COVID-19, defined as the new pandemic by the World Health Organization (WHO), has reached over 750,000 confirmed cases worldwide. The virus began to spread in Italy from the 22nd February, and the number of related cases is still increasing. Furthermore, given that a relevant proportion of infected people need hospitalization in Intensive Care Units, this may be a crucial issue for National Healthcare System's capacity. WHO underlines the importance of specific disease regional estimates. Because of this, Italy aimed to put in place proportioned and controlled measures, and to guarantee adequate funding to both increase the number of ICU beds and increase production of personal protective equipment. Our aim is to investigate the current COVID-19 epidemiological context in Sardinia region (Italy) and to estimate the transmission parameters using a stochastic model to establish the number of infected, recovered, and deceased people expected. Based on available data from official Italian and regional sources, we describe the distribution of infected cases during the period between 2nd and 15th March 2020. To better reflect the actual spread of COVID-19 in Sardinia based on data from 15th March (first Sardinian declared outbreak), two Susceptible-Infectious-Recovered-Dead (SIRD) models have been developed, describing the best and worst scenarios. We believe that our findings represent a valid contribution to better understand the epidemiological context of COVID-19 in Sardinia. Our analysis can help health authorities and policymakers to address the right interventions to deal with the rapidly expanding health emergency.

Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study.

The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016. Urine samples were collected at admission for [TIMP-2]∙[IGFBP7] measurement. Baseline patient characteristics were recorded including patients' demographics, prior health history, and the main reason for admission to build a logistic regression model to predict AKI. AKI occurrence differed between patients with [TIMP-2]∙[IGFBP7] ≤0.3 and >0.3 (ng/ml)2/1000 (31.9% and 68.10% respectively; p < 0.001). Patients with AKI had higher biomarker values compared to those without AKI (0.66 (0.21-2.84) vs 0.22 (0.08-0.63) (ng/ml)2/1000; p < 0.001). [TIMP-2]∙[IGFBP7] at ICU admission had a lower performance in predicting AKI at any stage within 48 hours and 7 days after measurement (area under the receiver operating characteristic curve (AUC) equal to 0.70 (95%CI 0.65-0.76), AUC 0.68 (95%CI 0.63-0.73)). In the logistic regression model, 0.1 (ng/ml)2/1000-unit increment was likely to increase the risk of AKI by 2% (p = 0.002).

[Epidemiological analysis on the hospitalization from neurological diseases in the Province of Pavia (Lombardy Region, Northern Italy)]. / Analisi epidemiologica dei ricoveri per patologie neurologiche in Provincia di Pavia.

OBJECTIVES: to evaluate time and spatial distribution of hospitalization due to neurological diseases in the province of Pavia (Lombardy Region, Northern Italy). DESIGN: ecological study. SETTING AND PARTICIPANTS: the study was performed on aggregate data of people residing in the province of Pavia in the period 2005-2014. MAIN OUTCOME MEASURES: hospital discharge records of neurological diseases and raw and standardized hospitalization rates. RESULTS: hospitalization due to neurological diseases in the Province of Pavia showed a slight decreasing trend in time. For the year 2014, the spatial analysis of hospitalizations highlights excesses of risk in the Lomellina district, both in males and in females. CONCLUSION: spatial analysis confirms previous results on specific neurological diseases and suggests more detailed analysis on hospitalization excesses in Lomellina area.

Impact of the Ketogenic Diet on Linear Growth in Children: A Single-Center Retrospective Analysis of 34 Cases.

Data on the impact of the ketogenic diet (KD) on children's growth remain controversial. Here, we retrospectively investigated the occurrence of linear growth retardation in 34 children (47% males; age range: 2-17 years) diagnosed with drug-resistant epilepsy (DRE; n = 14) or glucose transporter type 1 deficiency syndrome (GLUT1-DS; n = 20) who had been treated with the KD for 12 months. The general characteristics of children with and without growth retardation were also compared. All participants received a full-calorie, traditional KD supplemented with vitamins, minerals, and citrate. Most children (80%; 11/14 in the DRE subgroup and 16/20 in the GLUT1-DS subgroup) treated with the KD did not show growth retardation at 12 months. Although participants with and without delay of growth did not differ in terms of baseline clinical characteristics, dietary prescriptions, or supplementation patterns, marked ketosis at 12 months tended to occur more frequently in the latter group. Altogether, our results indicate that growth retardation may occur in a minority of children treated with the KD. However, further research is required to identify children at risk and to clarify how increased ketones levels may affect endocrine pathways regulating growth during KD administration.

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit.

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78-4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48-3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19-2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08-2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0-2; 3-4; 5-6; 7-8 and 9-10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels.

A pilot study assessing T1-weighted muscle MRI in amyotrophic lateral sclerosis (ALS).

The authors set out to study the role of T1-weighted muscle MRI in the diagnostic phase of ALS, comparing images from ten patients and nine age-matched healthy controls (HCs). All subjects underwent MRI of 68 muscles in the hands, paraspinal regions and lower limbs; the images were semi-quantitatively scored. Atrophy was more frequent in muscles of ALS patients than HCs (p < 0.0001); fatty infiltration was particularly marked in iliopsoas (p = 0.046), anterior (p = 0.020) and posterior (p = 0.047) calf muscles in patients. A trend towards agreement was found between MRI and clinic-EMG data for the first dorsal interosseous, paraspinal, and tibial anterior muscles. Muscle T1-weighted MRI can distinguish ALS patients from HCs for specific regions (i.e., legs). MRI abnormalities could be found in pauci-symptomatic spinal muscles in bulbar-onset patients. Muscle MRI may be a useful diagnostic tool in ALS, in particular for muscles difficult to investigate using clinical-EMG methods.

Mortality for neurological diseases and pesticides: etiological hypotheses by a spatial analysis in the province of Pavia.

BACKGROUND: Neurological and neurodegenerative diseases are multifactorial and their causes are not well understood yet. Among the relevant risk factors, pesticides and the productive activities in which they are used are included. OBJECTIVES: To evaluate the association of mortality from neurological diseases within the Province of Pavia (Italy) with the agricultural activities, as a proxy of pesticides exposure. METHODS: Population data for 2012 were provided by the local health unit (ATS) and by the registry office of the Regional Health Service. Spatial analyses were carried out by both a classical and Bayesian approach, to obtain a mortality map of the relative risk for neurological diseases in the Province of Pavia. Spatial distribution of main agricultural activities within the same territory, used as proxy of pesticides use, was made possible by data from the Geoportale Territoriale of the Lombardy region. Finally, a comparison between spatial distribution of mortality from neurological diseases and spatial distribution of main agricultural activities has been conducted. RESULTS: Mortality for neurological diseases in the Province of Pavia in 2012 was 4.41 for men and 6.53 for women per 10,000 subjects living in this area. Female mortality for neurological diseases showed a cluster in the Oltrepò district, where viticulture and fruit/horticulture are more common than elsewhere. More precisely, Bayesian relative risk (RR) had higher values in comparison with the median RR of the Province (100.8), with a posterior probability (PP) between 0.75 and 0.95 (not significant). Similarly, mortality for Parkinson's disease in women showed RR greater than the median value of the Province (100.6), with PP between 0.25 and 0.75 (not significant). CONCLUSIONS: Notwithstanding the ecological nature of the study, our results suggest the need to further investigate the possible link between pesticides exposure or related activities and neurological and neurodegenerative diseases, particularly Parkinson's disease. An ad hoc study on a random sample of the population living in the Province of Pavia, with the collection of individual data by means of standardized questionnaire, would allow to control for biases usually present when an ecological study design is applied.

Protocol of a Multicenter International Randomized Controlled Manikin Study on Different Protocols of Cardiopulmonary Resuscitation for laypeople (MANI-CPR).

INTRODUCTION: Out-of-hospital cardiac arrest is one of the leading causes of death in industrialised countries. Survival depends on prompt identification of cardiac arrest and on the quality and timing of cardiopulmonary resuscitation (CPR) and defibrillation. For laypeople, there has been a growing interest on hands-only CPR, meaning continuous chest compression without interruption to perform ventilations. It has been demonstrated that intentional interruptions in hands-only CPR can increase its quality. The aim of this randomised trial is to compare three CPR protocols performed with different intentional interruptions with hands-only CPR. METHODS AND ANALYSIS: This is a prospective randomised trial performed in eight training centres. Laypeople who passed a basic life support course will be randomised to one of the four CPR protocols in an 8 min simulated cardiac arrest scenario on a manikin: (1) 30 compressions and 2 s pause; (2) 50 compressions and 5 s pause; (3) 100 compressions and 10 s pause; (4) hands-only. The calculated sample size is 552 people. The primary outcome is the percentage of chest compression performed with correct depth evaluated by a computerised feedback system (Laerdal QCPR). ETHICS AND DISSEMINATION: . Due to the nature of the study, we obtained a waiver from the Ethics Committee (IRCCS Policlinico San Matteo, Pavia, Italy). All participants will sign an informed consent form before randomisation. The results of this study will be published in peer-reviewed journal. The data collected will also be made available in a public data repository. TRIAL REGISTRATION NUMBER: NCT02632500.