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Mobility restrictions are successfully used to contain the diffusion of epidemics. In this work we explore their effect on the epidemic growth by investigating an extension of the Susceptible-Infected-Removed (SIR) model in which individual mobility is taken into account. In the model individual agents move on a chessboard with a Lévy walk and, within each square, epidemic spreading follows the standard SIR model. These simple rules allow to reproduce the sub-exponential growth of the epidemic evolution observed during the Covid-19 epidemic waves in several countries and which cannot be captured by the standard SIR model. We show that we can tune the slowing-down of the epidemic spreading by changing the dynamics of the agents from Lévy to Brownian and we investigate how the interplay among different containment strategies mitigate the epidemic spreading. Finally we demonstrate that we can reproduce the epidemic evolution of the first and second COVID-19 waves in Italy using only 3 parameters, i.e , the infection rate, the removing rate, and the mobility in the country. We provide an estimate of the peak reduction due to imposed mobility restrictions, i. e., the so-called flattening the curve effect. Although based on few ingredients, the model captures the kinetic of the epidemic waves, returning mobility values that are consistent with a lock-down intervention during the first wave and milder limitations, associated to a weaker peak reduction, during the second wave.

Mild cognitive impairment (MCI) refers to a transitional zone between normal ageing and dementia. Despite the uncertainty regarding the definition of MCI as a clinical entity, clinical trials have been conducted in the attempt to study the role of cholinesterase inhibitors (ChEIs) currently approved for symptomatic treatment of mild to moderate Alzheimer disease (AD), in preventing progression from MCI to AD. The objective of this review is to assess the effects of ChEIs (donepezil, rivastigmine, and galantamine) in delaying the conversion from MCI to Alzheimer disease or dementia. The terms \"donepezil\", \"rivastigmine\", \"galantamine\", and \"mild cognitive impairment\" and their variants, synonyms, and acronyms were used as search terms in four electronic databases (MEDLINE, EMBASE, Cochrane, PsycINFO) and three registers: the Cochrane Collaboration Trial Register, Current Controlled Trials, and ClinicalTrials.gov. Published and unpublished studies were included if they were randomized clinical trials published (or described) in English and conducted among persons who had received a diagnosis of MCI and/or abnormal memory function documented by a neuropsychological assessment. A standardized data extraction form was used. The reporting quality was assessed using the Jadad scale. Three published and five unpublished trials met the inclusion criteria (three on donepezil, two on rivastigmine, and three on galantamine). Enrolment criteria differed among the trials, so the study populations were not homogeneous. The duration of the trials ranged from 24 wk to 3 y. No significant differences emerged in the probability of conversion from MCI to AD or dementia between the treated groups and the placebo groups. The rate of conversion ranged from 13% (over 2 y) to 25% (over 3 y) among treated patients, and from 18% (over 2 y) to 28% (over 3 y) among those in the placebo groups. Only for two studies was it possible to derive point estimates of the relative risk of conversion: 0.85 (95% confidence interval 0.64-1.12), and 0.84 (0.57-1.25). Statistically significant differences emerged for three secondary end points. However, when adjusting for multiple comparisons, only one difference remained significant (i.e., the rate of atrophy in the whole brain). The use of ChEIs in MCI was not associated with any delay in the onset of AD or dementia. Moreover, the safety profile showed that the risks associated with ChEIs are not negligible. The uncertainty regarding MCI as a clinical entity raises the question as to the scientific validity of these trials.

Objective In this prospective, controlled, monocentric study, we described the clinical and neuroimaging 12-month follow-up of two parallel cohorts of subjects with idiopathic normal pressure hydrocephalus (iNPH), who did or did not undergo lumboperitoneal shunt (LPS). Methods We recruited 78 iNPH patients. At baseline, subjects underwent clinical and neuropsychological assessments, 3 T magnetic resonance imaging (MRI), and tap test. After baseline, 44 patients (LPS group) opted for LPS implantation, whereas 34 subjects (control group) declined surgery. Both cohorts were then followed up for 12 months through scheduled clinical and neuropsychological evaluations every 6 months. 3 T MRI was repeated at 12-month follow-up. Results Gait, balance, and urinary continence improved in the LPS group, without significant influence on cognitive functions. Conversely, gait and urinary continence worsened in the control group. No preoperative MRI parameter was significant outcome predictor after LPS. Of relevance, in responders to LPS, we found postoperative reduction of periventricular white matter (PWM) hyperintensities, which were instead increased in the control group. Conclusions LPS is safe and effective in iNPH. An early surgical treatment is desirable to prevent clinical worsening. Post-surgery decrease of PWM hyperintensities may be a useful MRI marker surrogate for clinical effectiveness of LPS.

Our previous study in patients with cerebellar ataxias of different causes showed significant benefit of riluzole after 8 weeks. We aimed to confirm these results in patients with spinocerebellar ataxia or Friedreich's ataxia in a 1-year trial. Patients with spinocerebellar ataxia or Friedreich's ataxia (2:1 ratio) from three Italian neurogenetic units were enrolled in this multicentre, double-blind, placebo-controlled trial, and randomly assigned to riluzole (50 mg orally, twice daily) or placebo for 12 months. The randomisation list was computer-generated and a centralised randomisation system was implemented. Participants and assessing neurologists were masked to treatment allocation. The primary endpoint was the proportion of patients with improved Scale for the Assessment and Rating of Ataxia (SARA) score (a drop of at least one point) at 12 months. An intention-to-treat analysis was done. This trial is registered at ClinicalTrials.gov, number NCT01104649. Between May 22, 2010, and Feb 25, 2013, 60 patients were enrolled. Two patients in the riluzole group and three in the placebo group withdrew their consent before receiving treatment, so the intention-to-treat analysis was done on 55 patients (19 with spinocerebellar ataxia and nine with Friedreich's ataxia in the riluzole group, and 19 with spinocerebellar ataxia and eight with Friedreich's ataxia in the placebo group). The proportion with decreased SARA score was 14 (50%) of 28 patients in the riluzole group versus three (11%) of 27 in the placebo group (OR 8·00, 95% CI 1·95–32·83; p=0·002). No severe adverse events were recorded. In the riluzole group, two patients had an increase in liver enzymes (less than two times above normal limits). In two participants in the riluzole group and two participants in the placebo group, sporadic mild adverse events were reported. Our findings lend support to the idea that riluzole could be a treatment for cerebellar ataxia. Longer studies and disease-specific trials are needed to confirm whether these findings can be applied in clinical practice. Agenzia Italiana del Farmaco.

There are no currently available disease-modifying pharmacological treatments for most of the chronic hereditary ataxias; thus, effective rehabilitative strategies are crucial to help improve symptoms and therefore the quality of life. We propose to gather all available evidence on the use of video games, exergames, and apps for tablet and smartphone for the rehabilitation, diagnosis, and assessment of people with ataxias. Relevant literature published up to June 8, 2020, was retrieved searching the databases PubMed, ISI Web of Science, and the Cochrane Database. Data were extracted using a standardized form, and their methodological quality was assessed using RoB and QUADAS-2. Six studies of 434 retrieved articles met the predefined inclusion/exclusion criteria. Two of them were diagnostic, while 4 were experimental studies. Studies included participants ranging from 9 to 28 in trials and 70 to 248 in diagnostic studies. Although we found a small number of trials and of low methodological quality, all of them reported an improvement of motor outcomes and quality of life as measured by specific scales, including the SARA, BBS, DHI, and SF-36 scores. The main reason for such low quality in trials was that most of them were small and uncontrolled, thus non-randomized and unblinded. As video games, exergames, serious games, and apps were proven to be safe, feasible, and at least as effective as traditional rehabilitation, further and more high-quality studies should be carried out on the use of these promising technologies in people with different types of ataxia.

Background and objectives There is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery. Methods EVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma. Results The proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS). Conclusion Our results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS.

BackgroundCognitive and physical deficits independently raise the risk for negative events in older adults. Less is known about whether their co-occurrence constitutes a distinct risk profile. This study quantifies the association between cognitive impairment, no dementia (CIND), slow walking speed (WS) and their combination and disability and mortality.MethodsWe examined 2546 dementia-free people aged ≥ 60 years, part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) up to 12 years. The following four profiles were created: (1) healthy profile; (2) isolated CIND (scoring 1.5 SD below age-specific means on at least one cognitive domain); (3) isolated slow WS (< 0.8 m/s); (4) CIND+ slow WS. Disability was defined as the sum of impaired activities of daily living and trajectories of disability were derived from mixed-effect linear regression models. Piecewise proportional hazard models were used to estimate mortality rate [hazard ratios (HRs)]. Population attributable risks of death were calculated.ResultsParticipants with both CIND and slow WS had the worst prognosis, especially in the short-term period. They experienced the steepest increase in disability and five times the mortality rate (HR 5.1; 95% CI 3.5–7.4) of participants free from these conditions. Similar but attenuated results were observed for longer follow-ups. Co-occurring CIND and slow WS accounted for 30% of short-term deaths.ConclusionsCo-occurring cognitive and physical limitations constitute a distinct risk profile in older people, and account for a large proportion of short-term deaths. Assessing cognitive and physical function could enable early identification of people at high risk for adverse events.

Background/Objectives: The etiology of dementia is complex and multifactorial, with both genetic and environmental factors contributing to its onset. The Lancet Commission has identified several risk factors for this condition, but it is increasingly urgent to confirm their etiological role while accounting for both measured and unmeasured confounding effects. Our study, conducted on a population-based sample of Italian twins, examines the link between known risk factors and cognitive impairment, and the contribution of genetic and environmental influences to this link. Methods: Study participants were adult twins from the Italian Twin Registry who completed self-administered questionnaires. Cognitive impairment was evaluated by the SAGE questionnaire, while risk factors were assessed using the checklist proposed by the Lancet Commission. Individual-level and matched-pair analyses were performed for each risk factor, and their results were compared to detect potential genetic or environmental confounding, and to infer “quasi-causality” in the examined associations. Results: A total of 483 twins participated in the study (mean age 69.14 years, 63% women, 47% monozygotic twins). In matched-pair analyses, the association between hearing loss and cognitive impairment decreased in magnitude and became non-significant, suggesting confounding by genetics or early-life environment; in contrast, the association with sleep disturbances resulted strong and significant in both individual-level and matched-pair analyses, indicating a genuine effect of sleep on cognition. Conclusions: Our findings suggest a potential “quasi-causal” role of sleep disorders in cognitive decline. This relationship should be clarified through well-powered longitudinal studies incorporating precise clinical definitions and biomarker data.

Background The relationship between cancer and dementia is triggering growing research interest. Several preclinical studies have provided the biological rationale for the repurposing of specific anticancer agents in Alzheimer’s disease (AD), and a growing number of research protocols are testing their efficacy and safety/tolerability in patients with AD. Methods The aim of the present systematic review was to provide an overview on the repurposing of approved anticancer drugs in clinical trials for AD by considering both ongoing and completed research protocols in all phases. In parallel, a systematic literature review was conducted on PubMed, ISI Web, and the Cochrane Library to identify published clinical studies on repurposed anticancer agents in AD. Results Based on a structured search on the ClinicalTrials.gov and the EudraCT databases, we identified 13 clinical trials testing 11 different approved anticancer agents (five tyrosine kinase inhibitors, two retinoid X receptor agonists, two immunomodulatory agents, one histone deacetylase inhibitor, and one monoclonal antibody) in the AD continuum. The systematic literature search led to the identification of five published studies (one phase I, three phase II, and one phase IIb/III) reporting the effects of antitumoral treatments in patients with mild cognitive impairment or AD dementia. The clinical findings and the methodological characteristics of these studies are described and discussed. Conclusion Anticancer agents are triggering growing interest in the context of repurposed therapies in AD. Several clinical trials are underway, and data are expected to be available in the near future. To date, data emerging from published clinical studies are controversial. The promising results emerging from preclinical studies and identified research protocols should be confirmed and extended by larger, adequately designed, and high-quality clinical trials.

The scope of practice of the osteopathic profession in Italy is underreported. The first part of the present study investigated the Italian osteopaths' profile, focusing on the socio-demographic information and geographical distribution together with the main characteristics of their education. The OPERA-IT study highlighted that the majority of respondents declared to work as sole practitioners (58.4%), while the remaining declared to work as part of a team. Since teamwork and networking are recognized as fundamental aspects of healthcare, the present study aims to compare the osteopathic practice, diagnostic and treatment modalities of osteopaths who work as a sole practitioner and osteopaths who work as part of a team to highlight possible differences. Moreover, patients' characteristics will be presented. The OPERA-IT study population was chosen to provide a representative sample. A web campaign was set up to inform the Italian osteopaths before the beginning of the study. The OPERA IT study used a previously tested questionnaire. The questionnaire was translated into Italian following the World Health Organization recommendation. The questionnaire was composed of 57 items grouped in five sections, namely: socio-demographics, osteopathic education and training, working profile, organization, and management of the clinical practice and patient profile. The survey was delivered online through a dedicated platform. The survey was completed by 4,816 individuals. Osteopaths who work as sole practitioners represented the majority of the sample (n = 2814; 58.4%). Osteopaths who work as part of a team declared to collaborate mostly with physiotherapists (n = 1121; 23.3%), physicians with speciality (n = 1040; 21.6%), and other osteopaths (n = 943; 19.6%). The two groups showed heterogeneous characteristics. Significative differences were observed in all the factors, namely: geographical distribution, age, gender, training, working contract and working place, daily consultations and time for each consultation, fees, and the average waiting period to book an appointment. The principal component analysis supported a ten-component model and explained 80.5% of the total variance. The analysis showed that osteopaths working as sole practitioners have an increased probability (OR = 0.91; CI 95%: 0.88-0.94; p<0.01) of using systemic diagnostic and treatment techniques and have distinct clinical features with higher probability (OR = 0.92; 0.88-0.96; p<0.01) of spending less time with patients, being paid less but treating a higher number of patients per week. The most represented patients' age groups were 41-64 years old (n = 4452; 92.4%) and 21-40 years old (n = 4291; 89.1%). Similarly, the most reported new patients' age groups were 41-64 years old (n = 4221; 87.7%) and 21-40 years old (n = 3364; 69.9%). The most common presenting complaints were back pain, neck pain, cervical radiculopathy, sciatica, shoulder pain, and headaches. Osteopathic practice in Italy seems to be characterised by interprofessional collaboration, mostly with physiotherapists. Our results highlighted two different profiles in terms of sociodemographic characteristics and work modalities between osteopaths who work as sole practitioners and those who work as part of a team. Although according to the respondents, people of all ages consult Italian osteopaths, the majority of patients are adults. Most of them have been referred to osteopathy by other patients or acquaintances. Patients seek osteopathic care mostly for musculoskeletal related complaints.