Corticosteroid treatment for acute hydrocephalus in neurosarcoidosis: a case report.

BACKGROUND: Neurosarcoidosis occurs symptomatically in 5-10% of patients with sarcoidosis, and hydrocephalus is a rare complication of neurosarcoidosis, with either acute or subacute onset and presenting symptoms related to increased intracranial pressure. It represents a potentially fatal manifestation with a mortality rate of 22% (increased to 75% in case of coexistence of seizures) that requires a prompt initiation of treatment. High-dose intravenous corticosteroid treatment and neurosurgical treatment must be considered in all cases of neurosarcoidosis hydrocephalus. CASE PRESENTATION: Here we present a case of hydrocephalus in neurosarcoidosis, complicated by generalized seizures, in a 29-year-old Caucasian male patient treated with medical treatment only, with optimal response. CONCLUSION: Since neurosurgery treatment can lead to severe complications, this case report underlines the possibility to undergo only medical treatment in selected cases. Further studies are needed to stratify patients and better identify those eligible for only medical approach.

Neuropathological hints from CSF and serum biomarkers in corticobasal syndrome (CBS): a systematic review.

Corticobasal syndrome (CBS) is a clinical syndrome determined by various underlying neurodegenerative disorders requiring a pathological assessment for a definitive diagnosis. A literature review was performed following the methodology described in the Cochrane Handbook for Systematic Reviews to investigate the additional value of traditional and cutting-edge cerebrospinal fluid (CSF) and serum/plasma biomarkers in profiling CBS. Four databases were screened applying predefined inclusion criteria: (1) recruiting patients with CBS; (2) analyzing CSF/plasma biomarkers in CBS. The review highlights the potential role of the association of fluid biomarkers in diagnostic workup of CBS, since they may contribute to a more accurate diagnosis and patient selection for future disease-modifying agent; for example, future trial designs should consider baseline CSF Neurofilament Light Chains (NfL) or progranulin dosage to stratify treatment arms according to neuropathological substrates, and serum NfL dosage might be used to monitor the evolution of CBS. In this scenario, prospective cohort studies, starting with neurological examination and neuropsychological tests, should be considered to assess the correlations of clinical profiles and various biomarkers.

Brain Health and Cognition in Older Adults: Roadmap and Milestones towards the Implementation of Preventive Strategies.

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that might benefit the most from risk-based approaches-namely, people with subjective cognitive decline. Additionally, we consider universal prevention in cognitively unimpaired middle-aged and older adults. Delving into multidomain personalized preventive strategies, we report on empirical evidence surrounding modifiable risk factors and interventions crucial in mitigating cognitive decline. Next, we highlight the emergence of brain health services (BHS). We explain their proposed role in risk assessment, risk communication, and tailored interventions to reduce the risk of dementia. Commenting on ongoing BHS pilot experiences, we present the inception and framework of our own BHS in Monza, Italy, outlining its operational structure and care pathways. We emphasize the need for global collaboration and intensified research efforts to address the intricate determinants of brain health and their potential impact on healthcare systems worldwide.

A new national survey of centers for cognitive disorders and dementias in Italy.

INTRODUCTION: A new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a comprehensive description of the characteristics, organizational aspects of the CCDDs, and experiences during the COVID-19 pandemic. METHODS: A list of all national CCDDs was requested from the delegates of each Italian region. The online questionnaire is divided in two main sections: a profile section, containing information on location and accessibility, and a data collection form covering organization, services, treatments, activities, and any service interruptions caused by the COVID-19 outbreak. RESULTS: In total, 511 out of 534 (96%) facilities completed the profile section, while 450 out of 534 (84%) CCDDs also completed the data collection form. Almost half of the CCDDs (55.1%) operated for 3 or fewer days a week. About one-third of the facilities had at least two professional figures among neurologists, geriatricians and psychiatrists. In 2020, only a third of facilities were open all the time, but in 2021, two-thirds of the facilities were open. CONCLUSION: This paper provides an update on the current status of CCDDs in Italy, which still shows considerable heterogeneity. The survey revealed a modest improvement in the functioning of CCDDs, although substantial efforts are still required to ensure the diagnosis and care of patients with dementia.

Current use of fluid biomarkers as outcome measures in Multiple Sclerosis (MS): a review of ongoing pharmacological clinical trials.

The present study aims to describe the state of the art of fluid biomarkers use in ongoing multiple sclerosis (MS) clinical trials.A review of 608 ongoing protocols in the clinicaltrials.gov and EudraCT databases was performed. The trials enrolled patients with a diagnosis of relapsing remitting MS, secondary progressive MS, and/or primary progressive MS according to Revised McDonald criteria or relapsing MS according to Lublin et al. (2014). The presence of fluid biomarkers among the primary and/or secondary study outcomes was assessed.Overall, 5% of ongoing interventional studies on MS adopted fluid biomarkers. They were mostly used as secondary outcomes in phase 3-4 clinical trials to support the potential disease-modifying properties of the intervention. Most studies evaluated neurofilament light chains (NfLs). A small number considered other novel fluid biomarkers of neuroinflammation and neurodegeneration such as glial fibrillary acid protein (GFAP).Considering the numerous ongoing clinical trials in MS, still a small number adopted fluid biomarkers as outcome measures, thus testifying the distance from clinical practice. In most protocols, fluid biomarkers were used to evaluate the effectiveness of approved second-line therapies, but also, new drugs (particularly Bruton kinase inhibitors). NfLs were also adopted to monitor disease progression after natalizumab suspension in stable patients, cladribine efficacy after anti-CD20 discontinuation, and the efficacy of autologous hematopoietic stem cell transplant (AHSCT) compared to medical treatment. Nevertheless, further validation studies are needed for all considered fluid biomarkers to access clinical practice, and cost-effectiveness in the "real word" remains to be clarified.

Sensory neuropathy in amyotrophic lateral sclerosis: a systematic review.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and non-motor symptoms. Recent evidence suggests that ALS is indeed a multisystem disorder, associated with cognitive impairment, dysautonomia, pain and fatigue, excess of secretions, and sensory symptoms. To evaluate whether sensory neuropathy could broaden its spectrum, we systematically reviewed its presence and characteristics in ALS, extracting data on epidemiological, clinical, neurophysiological, neuropathological, and genetic features. Sensory neuropathy can be found in up to 20% of ALS patients, affecting both large and small fibers, although there is a great heterogeneity related to different techniques used for its detection (electromyography vs skin biopsy vs nerve biopsy). Moreover, the association between CIDP-like neuropathy and ALS needs to be better explored, although it could be interpreted as part of the neuroinflammatory process in the latter disease. Sensory neuropathy in ALS may be associated with a spinal onset and might be more frequent in SOD1 patients. Moreover, it seems mutually exclusive with cognitive impairment. No associations with sex and other genetic mutation were observed. All these data in the literature reveal the importance of actively looking for sensory neuropathy in ALS patients, and suggest including sensory neuropathy among ALS non-motor features, as it may explain sensory symptoms frequently reported throughout the course of the disease. Its early identification could help avoid diagnostic delays and improve patients' treatment and quality of life.

An updated overview of recent and ongoing deep brain stimulation (DBS) trials in patients with dementia: a systematic review.

BACKGROUND: Dementia affects more than 55 million people worldwide. Several technologies have been developed to slow cognitive decline: deep brain stimulation (DBS) of network targets in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have been recently investigated. OBJECTIVE: This study aimed to review the characteristics of the populations, protocols, and outcomes of patients with dementia enrolled in clinical trials investigating the feasibility and efficacy of DBS. MATERIALS AND METHODS: A systematic search of all registered RCTs was performed on Clinicaltrials.gov and EudraCT, while a systematic literature review was conducted on PubMed, Scopus, Cochrane, and APA PsycInfo to identify published trials. RESULTS: The literature search yielded 2122 records, and the clinical trial search 15 records. Overall, 17 studies were included. Two of 17 studies were open-label studies reporting no NCT/EUCT code and were analysed separately. Of 12 studies investigating the role of DBS in AD, we included 5 published RCTs, 2 unregistered open-label (OL) studies, 3 recruiting studies, and 2 unpublished trials with no evidence of completion. The overall risk of bias was assessed as moderate-high. Our review showed significant heterogeneity in the recruited populations regarding age, disease severity, informed consent availability, inclusion, and exclusion criteria. Notably, the standard mean of overall severe adverse events was moderately high (SAEs: 9.10 ± 7.10%). CONCLUSION: The population investigated is small and heterogeneous, published results from clinical trials are under-represented, severe adverse events not negligible, and cognitive outcomes uncertain. Overall, the validity of these studies requires confirmation based on forthcoming higher-quality clinical trials.

A supervised machine-learning algorithm predicts intraoperative CSF leak in endoscopic transsphenoidal surgery for pituitary adenomas.

BACKGROUND: Despite advances in endoscopic transnasal transsphenoidal surgery (E-TNS) for pituitary adenomas (PAs), cerebrospinal fluid (CSF) leakage remains a life-threatening complication predisposing to major morbidity and mortality. In the current study we developed a supervised ML model able to predict the risk of intraoperative CSF leakage by comparing different machine learning (ML) methods and explaining the functioning and the rationale of the best performing algorithm. METHODS: A retrospective cohort of 238 patients treated via E-TNS for PAs was selected. A customized pipeline of several ML models was programmed and trained; the best five models were tested on a hold-out test and the best classifier was then prospectively validated on a cohort of 35 recently treated patients. RESULTS: Intraoperative CSF leak occurred in 54 (22,6%) of 238 patients. The most important risk's predictors were: non secreting status, older age, x-, y- and z-axes diameters, ostedural invasiveness, volume, ICD and R-ratio. The random forest (RF) classifier outperformed other models, with an AUC of 0.84, high sensitivity (86%) and specificity (88%). Positive predictive value and negative predictive value were 88% and 80% respectively. F1 score was 0.84. Prospective validation confirmed outstanding performance metrics: AUC (0.81), sensitivity (83%), specificity (79%), negative predictive value (95%) and F1 score (0.75). CONCLUSIONS: The RF classifier showed the best performance across all models selected. RF models might predict surgical outcomes in heterogeneous multimorbid and fragile populations outperforming classical statistical analyses and other ML models (SVM, ANN etc.), improving patient management and reducing preventable morbidity and additional costs.

Computer-Based Cognitive Training in Children with Primary Brain Tumours: A Systematic Review.

Background: Late neurocognitive sequelae are common among long-term brain tumour survivors, resulting in significantly worse quality of life. Cognitive rehabilitation through specific APP/software for PC/tablets represents an innovative intervention spreading in recent years. In this study, we aim to review the current evidence and trends regarding these innovative approaches. Methods: A systematic literature review was performed. Inclusion criteria were: (i) Studies recruiting patients diagnosed with any brain tumour before 21 years of age; (ii) studies assessing the role of digital interventions on cognitive outcomes. Case reports, case series, reviews, letters, conference proceedings, abstracts, and editorials were excluded. Results: Overall, nine studies were included; 152 patients (67.8% males) with brain tumours underwent a digital intervention. The mean age at diagnosis and the intervention enrolment ranged from 4.9 to 9.4 years and 11.1 to 13.3 years, respectively. The computer-based software interventions employed were: Cogmed, Captain's Log, Fast ForWord, and Nintendo Wii. Most of these studies assessed the effects of cognitive training on working memory, attention, and performance in daily living activities. Conclusions: The studies suggest that this type of intervention improves cognitive functions, such as working memory, attention, and processing speed. However, some studies revealed only transient positive effects with a significant number of dropouts during follow-up. Trials with greater sample sizes are warranted. Motivating families and children to complete cognitive interventions could significantly improve cognitive outcomes and quality of life.

Safety and Efficacy of Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials.

BACKGROUND: Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD). OBJECTIVE: Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes. METHODS: A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library. RESULTS: Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD -0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD -0.15). CONCLUSION: Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset.

A Deep Learning Model for Preoperative Differentiation of Glioblastoma, Brain Metastasis and Primary Central Nervous System Lymphoma: A Pilot Study.

Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) remains challenging in specific cases showing similar appearances or atypical features. Overall, advanced MRI protocols have high diagnostic reliability, but their limited worldwide availability, coupled with the overlapping of specific neuroimaging features among tumor subgroups, represent significant drawbacks and entail disparities in the planning and management of these oncological patients. Objective: To evaluate the classification performance metrics of a deep learning algorithm trained on T1-weighted gadolinium-enhanced (T1Gd) MRI scans of glioblastomas, atypical PCNSLs and BMs. Materials and Methods: We enrolled 121 patients (glioblastoma: n=47; PCNSL: n=37; BM: n=37) who had undergone preoperative T1Gd-MRI and histopathological confirmation. Each lesion was segmented, and all ROIs were exported in a DICOM dataset. The patient cohort was then split in a training and hold-out test sets following a 70/30 ratio. A Resnet101 model, a deep neural network (DNN), was trained on the training set and validated on the hold-out test set to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. Results: The DNN achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.98; 95%CI: 0.95 - 1.00) and glioblastomas (AUC: 0.90; 95%CI: 0.81 - 0.97) and moderate ability in differentiating BMs (AUC: 0.81; 95%CI: 0.70 - 0.95). This performance may allow clinicians to correctly identify patients eligible for lesion biopsy or surgical resection. Conclusion: We trained and internally validated a deep learning model able to reliably differentiate ambiguous cases of PCNSLs, glioblastoma and BMs by means of T1Gd-MRI. The proposed predictive model may provide a low-cost, easily-accessible and high-speed decision-making support for eligibility to diagnostic brain biopsy or maximal tumor resection in atypical cases.

A nationwide survey of Italian Centers for Cognitive Disorders and Dementia on the provision of care for international migrants.

BACKGROUND: More than 500,000 dementia cases can be estimated among migrants living in Europe. There is the need to collect "real world" data on the preparedness of healthcare services to support the inclusion of migrants in the public health response to dementia. The present study aimed (i) to estimate the number of migrants referred to Italian memory clinics (Centers for Cognitive Disorders and Dementia [CCDDs]) and (ii) to identify possible barriers and resources for the provision of diversity-sensitive care. METHODS: A survey of all Italian CCDDs was conducted between December 2020 and April 2021. An online questionnaire was developed to obtain information on the number of migrants referred to Italian CCDDs in 2019, the challenges encountered in the diagnostic approach, and possible facilitators in the provision of care. RESULTS: Overall, 343 of the 570 contacted CCDDs completed the survey questionnaire (response rate: 60.2%). Nearly 4527 migrants were referred to these services in 2019. Migrants accounted for a median 1.1% (IQR: 0.9%-2.8%) of overall CCDD referrals. More than one-third of respondents reported that the number of migrants referred to their facilities had increased in the last 5 years. The overall quality of the migrants' cognitive assessment was deemed to be very poor or insufficient in most cases. A minority of CCDDs had translated information material on dementia and reported the possibility to contact cultural mediators and interpreters. CONCLUSIONS: A relevant number of migrants are being referred to Italian CCDDs that are still not adequately prepared to deliver diversity-sensitive care and support.

Artificial intelligence-enhanced intraoperative neurosurgical workflow: current knowledge and future perspectives.

INTRODUCTION: Artificial intelligence (AI) and machine learning (ML) augment decision-making processes and productivity by supporting surgeons over a range of clinical activities: from diagnosis and preoperative planning to intraoperative surgical assistance. We reviewed the literature to identify current AI platforms applied to neurosurgical perioperative and intraoperative settings and describe their role in multiple subspecialties. EVIDENCE ACQUISITION: A systematic review of the literature was conducted following the PRISMA guidelines. PubMed, EMBASE, and Scopus databases were searched from inception to December 31st, 2020. Original articles were included if they: presented AI platforms implemented in perioperative, intraoperative settings and reported ML models' performance metrics. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed appropriate. The risk of bias and applicability of predicted outcomes were assessed using the PROBAST tool. EVIDENCE SYNTHESIS: Forty-one articles were included. All studies evaluated a supervised learning algorithm. A total of 10 ML models were described; the most frequent were neural networks (N.=15) and tree-based models (N.=13). Overall, the risk of bias was medium-high, but applicability was considered positive for all studies. Articles were grouped into four categories according to the subspecialty of interest: neuro-oncology, spine, functional and other. For each category, different prediction tasks were identified. CONCLUSIONS: In this review, we summarize the state-of-art applications of AI for the intraoperative augmentation of neurosurgical workflows across multiple subspecialties. ML models may boost surgical team performances by reducing human errors and providing patient-tailored surgical plans, but further and higher-quality studies need to be conducted.

Supporting and Protecting People with Dementia in the COVID-19 Pandemic.

We aimed to explore the awareness and preparedness of dementia caregivers and people with mild cognitive deficits on how to prevent COVID-19 infection and cope with the indirect consequences of the pandemic. A total of 139 patient-caregiver dyads received a telephone survey and 109 completed the survey. The majority of respondents reported having a moderate-to-good knowledge of the typical manifestations of COVID-19. Conversely, only few of them were informed of the atypical presentations and on how to recognize emergency warning signs. Filling the knowledge gaps on COVID-19 in the most vulnerable people may represent a significant resource to tackle the pandemic.

Anticancer drugs repurposed for Alzheimer's disease: a systematic review.

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.

Exploring the association of early life physical activity and risk of dementia: a systematic review.

INTRODUCTION: Physical activity has been included in the list of twelve modifiable risk factors for dementia, despite conflicting results from observational and controlled studies. In particular it is not clear whether physical inactivity near the time of dementia diagnosis is a consequence or cause of dementia. We review all available studies reporting the possible association between having engaged in PA before 60 years of age and the risk of dementia. EVIDENCE ACQUISITION: We performed a systematic review based on the methodology reported in the Cochrane handbook for systematic reviews and following the PRISMA statement. Bibliographic searches were carried out on the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. Further references were retrieved from published systematic reviews on the same topic. Included studies were assessed using the Newcastle Ottawa scale. EVIDENCE SYNTHESIS: The bibliographic search yielded 1381 records. A total of 11 studies were included. Three of the included studies were case control studies, while the remaining 8 were cohort studies The overall quality of included studies was high. However, clinical criteria for the diagnosis of dementia, criteria to define and measure and PA and time-reference of exposure were heterogeneous, with some studies considering specific age range of exposure, and other reports dealing with more generic "adult age." CONCLUSIONS: This review suggests that there is insufficient evidence to conclude whether PA in early life may affect the incidence of dementia in later life. Studies in this field are very complicated and recognizing the impact of PA in early life given all the confounding factors is very difficult. Further studies are warranted. In these studies, it will be crucial to define the type, quantity and intensity of PA as well as to stratify analysis by sex, cultures and social classes.

Decreasing trend in the incidence and prevalence of dementia: a systematic review.

INTRODUCTION: The progressive ageing of the population is one of the main socio-demographic phenomena, taking place at a global level. Several recent population-based studies conducted worldwide suggest that the age-specific risk of dementia may be changing in some countries and areas. EVIDENCE ACQUISITION: This systematic review was performed using the methodology proposed by the Cochrane handbook for systematic reviews and reported following the PRISMA statement. A structured bibliographic search was performed on the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. All included studies were qualitatively assessed using the Methodological Evaluation of Observational REsearch (MORE). EVIDENCE SYNTHESIS: The bibliographic search yielded 2394 records. Three more articles were retrieved from other sources. A total of ten studies were included, five reported data on a possible reduction in the prevalence of dementia, and five reported data on a possible reduction in its incidence. CONCLUSIONS: The present systematic review focused on the recent observations of a possible decrease in the frequency of dementia and cognitive impairment in some Western countries (USA, UK, Sweden, the Netherlands, France, Iceland) between 1977 and 2014. The included studies have a high heterogeneity in terms of the clinical criteria used to diagnose dementia, and of the criteria used to define the clinical condition preceding dementia, such as isolated cognitive impairment. Moreover, the methodological quality with which they were conducted was also heterogeneous, with scores ranging from 1 to 7 using the MORE tool.

The Italian national survey on Coronavirus disease 2019 epidemic spread in nursing homes.

INTRODUCTION: Residents in facilities such as nursing homes (NHs) are particularly vulnerable to Coronavirus disease 2019 (COVID-19). A national survey was carried out to collect information on the spreading and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in nursing homes, and on how suspected and/or confirmed cases were managed. We carried out a survey between 25 March 2020 and 5 May 2020. MATERIALS AND METHODS: All Italian nursing homes either public or providing services both privately and within the NHS were included in the study. An on-line questionnaire was sent to 3292 nursing homes across all Italian regions. Nursing homes were also contacted by telephone to provide assistance in completing the questionnaire. RESULTS: A total of 1356 nursing homes voluntarily participated to the survey, hosting a total of 100,806 residents. Overall, 9154 residents died due to any cause from February 1 to the time when the questionnaire was completed (from March 25 to May 5). Of these, 7.4% had COVID-19 and 33.8% had flu-like symptoms, corresponding to a cumulative incidence of 0.7 and 3.1, respectively. Lack of personnel, difficulty in transferring patients to hospital or other facility, isolating residents with COVID-19, number of beds and geographical area were the main factor positively associated to the presence of COVID-19 in nursing homes. DISCUSSION: This survey showed the dissemination and impact of SARS-CoV-2 infection in Italian nursing homes and on how older and potentially chronically ill people residing in these long-term care facilities were managed.

Adverse Events in Italian Nursing Homes During the COVID-19 Epidemic: A National Survey.

Older people living in nursing homes (NHs) are particularly vulnerable in the ongoing COVID-19 pandemic, due to the high prevalence of chronic diseases and disabilities (e.g., dementia). The phenomenon of adverse events (AEs), intended as any harm or injury resulting from medical care or to the failure to provide care, has not yet been investigated in NHs during the pandemic. We performed a national survey on 3,292 NHs, either public or providing services both privately and within the national health system, out of the 3,417 NHs covering the whole Italian territory. An online questionnaire was addressed to the directors of each facility between March 24 and April 27, 2020. The list of NHs was provided by the Dementia Observatory, an online map of Italian services for people with dementia, which was one of the objectives of the implementation of the Italian National Dementia Plan. About 26% of residents in the Italian NHs for older people listed within the Dementia Observatory site had dementia. The objective of our study was to report the frequency of AEs that occurred during the months when SARS-CoV-2 spreading rate was at its highest in the Italian NHs and to identify which conditions and attributes were most associated with the occurrence of AEs by means of multivariate regression logistic analysis. Data are referred to 1,356 NHs that participated in the survey. The overall response rate was 41.2% over a time-period of six weeks (from March 24 to May 5). About one third of the facilities (444 out of 1,334) (33.3%) reported at least 1 adverse event, with a total of 2,000 events. Among the included NHs, having a bed capacity higher than the median of 60 beds (OR=1.57, CI95% 1.17-2.09; p=0.002), an observed increased in the use of psychiatric drugs (OR=1.80, CI95% 1.05-3.07; p=0.032), adopting physical restraint measures (OR=1.97, CI95% 1.47-2.64; p<0.001), residents hospitalized due to flu-like symptoms (OR =1.73, CI95% 1.28-2.32; p<0.001), and being located in specific geographic areas (OR=3.59, CI95% 1.81-7.08; OR = 2.90, CI95% 1.45-5.81 and OR = 4.02, CI05% 2.01-8.04 for, respectively, North-West, North-East and Centre vs South, p<0.001) were all factors positively associated to the occurrence of adverse events in the facility. Future recommendations for the management and care of residents in NHs during the COVID-19 pandemic should include specific statements for the most vulnerable populations, such as people with dementia.

The Pipeline of Therapeutics Testing During the Emergency Phase of the COVID-19 Outbreak.

The coronavirus disease 19 (COVID-19) pandemic poses a serious threat to the sustainability of healthcare systems and is currently having a significant effect on living conditions worldwide. No therapeutic agent has yet proven to be effective for the treatment of COVID-19. The management of this disease currently relies on supportive care and the off-label and compassionate use of antivirals and immunomodulators. Nevertheless, there has been a great worldwide effort to progress research and test the efficacy and safety/tolerability profiles of numerous candidate agents that may positively affect the various clinical syndromes associated with COVID-19. In parallel, vaccination and chemoprophylaxis strategies are being investigated. This article provides a summary of interventional studies targeting COVID-19 during the emergency phase of the outbreak to broadly inform clinicians and researchers on what happened and what they can expect in upcoming months. The clinicaltrials.gov database and the European Union (EU) Clinical Trials Register were investigated on March 31, 2020, to identify all ongoing phase 1-4 research protocols testing pharmacological interventions targeting SARS-CoV-2 infection and/or clinical syndromes associated with COVID-19. Overall, six phase 1, four phase 1-2, 14 phase 2, ten phase 2-3, 19 phase 3, and nine phase 4 studies were identified, and the features of these studies are described in the present review. We also provide an updated overview of the change overtime in the pipeline following this emergency phase and based on the current epidemiology of the COVID-19 pandemic.