Innovation in rehabilitation technology: technological opportunities and socio-economic implications

Innovation in stroke rehabilitation technology is discussed that, based on published epidemiological and economic data, represents an urgent case to deal with adopting a multidisciplinary perspective. A theoretical model is proposed for the evaluation of socioeconomic implications related to an early diagnosis and early and timely adjustments in the stroke treatment strategy. The model is applied to the case of a new rehabilitation technology: the ALLADIN diagnostic device. The model compares a traditional approach – ‘trial and error strategy’ – to the innovative one – ‘in progress evaluation’, considering the diagnostic and rehabilitative steps of the patient’s assistive route and assessing social and economic benefits of the innovative device. The new technology allows a precise initial assessment of both the severity of stroke and the level of lost functionality, as long as an evaluation of the expected return from different potential therapies. Moreover, supposing that higher severity of stroke implies higher level of disabilities and social costs, and that the negative impact increases as the level of disability increases, the use of innovative rehabilitation technologies would be more effective in the case of patients with severe and very severe stroke

Systematic review of the literature on the clinical effectiveness of the cochlear implant procedure in paediatric patients

The aim of this systematic review of the literature was to summarize the results of scientific publications on the clinical effectiveness of the cochlear implant (CI) procedure in children. The members of the Working Group first examined existing national and international literature and the principal international guidelines on the procedure. They considered as universally-accepted the usefulness/effectiveness of unilateral cochlear implantation in severely-profoundly deaf children. Accordingly, they focused attention on systematic reviews addressing clinical effectiveness and cost/efficacy of the CI procedure, with particular regard to the most controversial issues for which international consensus is lacking. The following aspects were evaluated: post-CI outcomes linked to precocity of CI; bilateral (simultaneous/ sequential) CI vs. unilateral CI and vs. bimodal stimulation; benefits derived from CI in deaf children with associated disabilities. With regard to the outcomes after implantation linked to precocity of intervention, there are few studies comparing post-CI outcomes in children implanted within the first year of life with those of children implanted in the second year. The selected studies suggest that children implanted within the first year of life present hearing and communicative outcomes that are better than those of children implanted after 12 months of age. Concerning children implanted after the first year of life, all studies confirm an advantage with respect to implant precocity, and many document an advantage in children who received cochlear implants under 18 months of age compared to those implanted at a later stage. With regard to bilateral CI, the studies demonstrate that compared to unilateral CI, bilateral CI offers advantages in terms of hearing in noise, sound localization and during hearing in a silent environment. There is, however, a wide range of variability. The studies also document the advantages after sequential bilateral CI. In these cases, a short interval between interventions, precocity of the first CI and precocity of the second CI are considered positive prognostic factors. In deaf children with associated disabilities, the studies analyzed evidence that the CI procedure is also suitable for children with disabilities associated with deafness, and that even these children may benefit from the procedure, even if these may be slower and inferior to those in children with isolated deafness, especially in terms of high communicative and perceptive skills

Fragment-based discovery of a regulatory site in thioredoxin glutathione reductase acting as "doorstop" for NADPH entry

Members of the FAD/NAD-linked reductase family are recognized as crucial targets in drug development for cancers, inflammatory disorders, and infectious diseases. However, individual FAD/NAD reductases are difficult to inhibit in a selective manner with off target inhibition reducing usefulness of identified compounds. Thioredoxin glutathione reductase (TGR), a high molecular weight thioredoxin reductase-like enzyme, has emerged as a promising drug target for the treatment of schistosomiasis, a parasitosis afflicting more than 200 million people. Taking advantage of small molecules selected from a high-throughput screen and using X-ray crystallography, functional assays, and docking studies, we identify a critical secondary site of the enzyme. Compounds binding at this site interfere with well-known and conserved conformational changes associated with NADPH reduction, acting as a doorstop for cofactor entry. They selectivity inhibit TGR from Schistosoma mansoni and are active against parasites in culture. Since many members of the FAD/NAD-linked reductase family have similar catalytic mechanisms the unique mechanism of inhibition identified in this study for TGR broadly opens new routes to selectively inhibit homologous enzymes of central importance in numerous diseases

Randomized, double-blind, parallel-group, 48-week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs. 10 cm(2)) in Alzheimer’s disease

Aim: Determine whether patients with Alzheimer’s disease demonstrating functional and cognitive decline, following 24-48 weeks of open-label treatment with 9.5 mg/24 h (10 cm(2)) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Methods: Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm(2)) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-IADL) scale and the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Results: Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAScog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. Conclusions: The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated. Copyright © 2012 S. Karger AG, Base

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

Preliminary attempt to predict risk of invasive pulmonary aspergillosis in patients with influenza. Decision trees may help?

Invasive pulmonary aspergillosis (IPA) is typically considered a disease of immunocompromised patients, but, recently, many cases have been reported in patients without typical risk factors. The aim of our study is to develop a risk predictive model for IPA through machine learning techniques (decision trees) in patients with influenza. We conducted a retrospective observational study analyzing data regarding patients diagnosed with influenza hospitalized at the University Hospital “Umberto I” of Rome during the 2018-2019 season. We collected five IPA cases out of 77 influenza patients. Although the small sample size is a limit, the most vulnerable patients among the influenza-infected population seem to be those with evidence of lymphocytopenia and those that received corticosteroid therapy

Oral anticoagulant therapy at hospital admission associates with lower mortality in older COVID-19 patients with atrial fibrillation. An insight from the Covid Registry

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: None. ONBEHALF: the GeroCovid Investigators Introduction. Atrial fibrillation (AF), the arrhythmia most frequently diagnosed in older patients, associates with serious, thrombo-embolic, complications and high mortality. COVID-19 severely affects aged subjects, determining an important prothrombotic status. Purpose. Aim of this study was to evaluate mortality-related factors in older AF patients with COVID-19.  Methods. We included 806 in-hospital COVID-19 patients aged 60 years or more hospitalized between March 1st and June 6th 2020 and enrolled in a multicenter observational study. Results. The prevalence of AF was 21.8%. In-hospital mortality was higher in the AF group (36.9 vs. 27.5%; p = 0.015). Among AF patients, those who survived were younger (81 ± 8 vs. 84 ± 7 years; p = 0.002), had a lower CHA2DS2-VASc score (3.9 ± 1.6 vs. 4.4 ± 1.3; p = 0.02) and were more frequently treated with oral anticoagulants at admission (63.1 vs. 32.3%; p < 0.001) than those who died in hospital. At multivariable logistic regression analysis, lower age (p = 0.042), a better functional profile (p = 0.007), less severe COVID-19 manifestations at admission (p = 0.001), and the use of Vitamin K antagonists (OR = 0.16, 95%CI: 0.03-0.84; p = 0.031) or DOACs (OR = 0.22, 95%CI: 0.08-0.56; p = 0.002), compared to antiplatelet therapy or no treatment at all, were associated with a lower chance of in-hospital death. Conclusions. AF is a prevalent condition and a severity factor in older COVID-19 patients. Advanced age, dependency and severe clinical manifestations of disease characterized older AF subjects with a worse prognosis. Interestingly, pre-admission anticoagulant therapy correlated positively with in-hospital survival

Tools to Detect Delirium Superimposed on Dementia:A Systematic Review

BACKGROUND: Delirium commonly occurs in patients with dementia. Though several tools for detecting delirium exist, it is unclear which are valid in patients with delirium superimposed on dementia. OBJECTIVES: Identify valid tools to diagnose delirium superimposed on dementia DESIGN: We performed a systematic review of studies of delirium tools, which explicitly included patients with dementia. SETTING: In-hospital patients PARTICIPANTS: Studies were included if delirium assessment tools were validated against standard criteria, and the presence of dementia was assessed according to standard criteria that used validated instruments. MEASUREMENTS: PubMed, Embase, and Web of Science databases were searched for articles in English published between January 1960 and January 2012. RESULTS: Nine studies fulfilled the selection criteria. Of the total of 1569 patients, 401 had dementia, and 50 had delirium superimposed on dementia. Six delirium tools were evaluated. One studyusing the Confusion Assessment Method (CAM) with 85% patients with dementia showed a high specificity (96–100%) and moderate sensitivity (77%).Two intensive care unit studies that used the CAM for the Intensive Care Unit (CAM-ICU) ICU reported 100% sensitivity and specificity for delirium among 23 dementia patients. One study using electroencephalography reported a sensitivity of 67% and a specificity of 91% among a population with 100% prevalence of dementia. No studies examined potential effects of dementia severity or subtype upon diagnostic accuracy. CONCLUSIONS: The evidence base on tools for detection of delirium superimposed on dementia is limited, although some existing tools show promise. Further studies of existing or refined tools with larger samples and more detailed characterization of dementia are now required to address the identification of delirium superimposed on dementia