Economic impact of reducing treatment gaps in depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent across Europe. While evidence-based treatments exist, many people with MDD have their condition undetected and/or untreated. This study aimed to assess the cost-effectiveness of reducing treatment gaps using a modeling approach. METHODS: A decision-tree model covering a 27-month time horizon was used. This followed a care pathway where MDD could be detected or not, and where different forms of treatment could be provided. Expected costs pertaining to Germany, Hungary, Italy, Portugal, Sweden, and the UK were calculated and quality-adjusted life years (QALYs) were estimated. The incremental costs per QALY of reducing detection and treatment gaps were estimated. RESULTS: The expected costs with a detection gap of 69% and treatment gap of 50% were €1236 in Germany, €476 in Hungary, €1413 in Italy, €938 in Portugal, €2093 in Sweden, and €1496 in the UK. The incremental costs per QALY of reducing the detection gap to 50% ranged from €2429 in Hungary to €10,686 in Sweden. The figures for reducing the treatment gap to 25% ranged from €3146 in Hungary to €13,843 in Sweden. CONCLUSIONS: Reducing detection and treatment gaps, and maintaining current patterns of care, is likely to increase healthcare costs in the short term. However, outcomes are improved, and reducing these gaps to 50 and 25%, respectively, appears to be a cost-effective use of resources.

Algorithms for Vision-Based Quality Control of Circularly Symmetric Components.

Quality inspection in the industrial production field is experiencing a strong technological development that benefits from the combination of vision-based techniques with artificial intelligence algorithms. This paper initially addresses the problem of defect identification for circularly symmetric mechanical components, characterized by the presence of periodic elements. In the specific case of knurled washers, we compare the performances of a standard algorithm for the analysis of grey-scale image with a Deep Learning (DL) approach. The standard algorithm is based on the extraction of pseudo-signals derived from the conversion of the grey scale image of concentric annuli. In the DL approach, the component inspection is shifted from the entire sample to specific areas repeated along the object profile where the defect may occur. The standard algorithm provides better results in terms of accuracy and computational time with respect to the DL approach. Nevertheless, DL reaches accuracy higher than 99% when performance is evaluated targeting the identification of damaged teeth. The possibility of extending the methods and the results to other circularly symmetrical components is analyzed and discussed.

Cognitive Assessment in SARS-CoV-2 Patients: A Systematic Review.

Background: Patients with post-infective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often show both short- and long-term cognitive deficits within the dysexecutive/inattentive spectrum. However, little is known about which cognitive alterations are commonly found in patients recovered from SARS-CoV-2, and which psychometric tools clinicians should consider when assessing cognition in this population. The present work reviewed published studies to provide a critical narrative of neuropsychological (NPs) deficits commonly observed after SARS-CoV-2 infection and the tests most suited for detecting such cognitive sequelae depending on illness severity. Methods: This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and was pre-registered on Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253079). Observational studies quantitatively assessing cognition in patients with post-infective SARS-CoV-2 were considered. From 711 retrieved articles, 19 studies conducted on patients with SARS-CoV-2 without medical comorbidities were included and stratified by disease severity. Results: The majority of studies (N = 13) adopted first-level tests. The most frequently administered screeners were the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE)-with the former more likely to detect mild, and the latter moderate/severe deficits. Among second-level tests, those assessing attention and executive functions (EFs) were highly represented. Remotely-delivered tests yielded lower percentages of cognitive impairment. Overall, cognitive domains often found to be impaired were EFs, attention, and memory. Conclusion: Cognitive sequelae in patients with post-infective SARS-CoV-2 can be detected with NPs testing. Depending on the psychometric test features, the likelihood of observing cognitive deficits can vary. Further studies on larger sample sizes are needed to investigate the clinical usefulness of second-level tools. The primary goal of preventative health services should be the early detection and intervention of emerging cognitive deficits.

The Italian version of the Brief Assessment of Cognition in Affective Disorders: performance of patients with bipolar disorder and healthy controls.

OBJECTIVES: Cognitive deficits in Bipolar Disorder (BD) are significant enough to have an impact on daily functioning. Therefore, appropriate tools must be used to improve our understanding of the nature and severity of cognitive deficits in BD. In this study, we aimed to compare the cognitive profiles of patients with BD and healthy controls (HC) applying the Italian version of the Brief Assessment of Cognition in Affective Disorders (BAC-A). METHODS: This cross-sectional study included 127 patients with BD and 134 HC. The participants' cognitive profiles were evaluated using the Italian version of the BAC-A, which assesses verbal memory, working memory, motor speed, verbal fluency, attention & processing speed, executive functions, and two new measures of affective processing. The BAC-A raw scores were corrected using the normative data for the Italian population. In addition, we explored whether intelligence quotient (IQ) and specific clinical variables would predict the BAC-A affective, non-affective, and total composite scores of patients with BD and HC. RESULTS: HC performed better than patients with BD in all BAC-A subtests (all p < .001), except for subtests of the Affective Interference Test. (p ≥ .05). The effect sizes varied in magnitude and ranged between d = 0.02 and d = 1.27. In patients with BD, lower BAC-A composite scores were predicted by a higher number of hospitalizations. There was a significant association between IQ and BAC-A composite scores in both bipolar patients and HC. CONCLUSIONS: The Italian BAC-A is sensitive to the cognitive impairments of patients with BD in both affective and non-affective cognitive domains.

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium.

BACKGROUND: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. METHODS: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). RESULTS: Kaplan-Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02-1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03-1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02-1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01-1.25, p = 0.04) and HR 1.10; 95% CI 1.01-1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. CONCLUSIONS: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.

Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative.

BACKGROUND: Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. STRUCTURE: The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/ ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. CONCLUSIONS: The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

The brief assessment of cognition in affective disorders: Normative data for the Italian population.

BACKGROUND: To date there are no validated tests in Italian to assess cognitive functions in Bipolar Disorder. Therefore, this study aimed to provide normative data for the Italian version of the Brief Assessment of Cognition in Affective Disorders (BAC-A), a battery targeting neuro- and affective-cognition in affective disorders. METHODS: Data were collected from 228 healthy participants (age range: 18-67; mean age: 34.68 ± 12.15 years) across eight recruiting sites. The influence of age, sex and education was measured and adjusted for using multivariate stepwise regression models. Normative values were established by means of the Equivalent Score approach. RESULTS: Most of the BAC-A subtests showed patterns of association with age (inversely associated with overall cognitive performance), education (positively associated with Verbal Memory and Fluency, Digit Sequencing and Affective Processing subtests) and sex (females performed better than males in the Affective Interference Test but worse in the Emotion Inhibition Task, Digit Sequencing and Tower of London). LIMITATIONS: The sample size was not sufficiently large for developing stratified norms, using 10-years ranges. Moreover, the participants included in the study were, on average, highly educated. CONCLUSIONS: The normative data of the BAC-A provided in this study can serve as a cognitive functioning reference for Italian-speaking participants within the age range of the study sample. This can increase the applicability of this test in both clinical and research settings. The reliability and validity of the Italian BAC-A need to be further investigated.

Sleep habits and pattern in 1-14 years old children and relationship with video devices use and evening and night child activities.

BACKGROUND: Sleep in childhood and adolescence is crucial for mental and physical health; however several researches reported an increasing trend towards a sleep deprivation in this age. Due to the lack of recent epidemiological studies in Italy, the aim of our study was to depict sleep habits and patterns in Italian children aged 1-14 years and to evaluate their relationships with video devices use (TV, tablet, smartphone, PC) and evening/night child activities. METHODS: A structured interview was conducted during 2015 by 72 Family Pediatricians in 2030 healthy children aged 1-14 years by a cross-sectional survey named "Ci piace sognare". Total sleep duration was calculated, 2015 National Sleep Foundation Recommendations were used as reference. Optimal sleepers were defined children sleeping in own bed all night without awakenings. Multivariable median regression was performed to identify predictors of sleep duration and multivariable logistic regression for predictors of optimal sleep. RESULTS: Total sleep duration and numbers of awakenings decreased with age. Only 66.9% of children had sleep duration in agreement with Recommendations (50% in 10-14 years group). Before sleeping 63.5% of children used video devices (39.6% at 1-3 years), 39.1% read, 27.5% drank and 19.5% ate. Bottle users at bedtime were 30.8% at 1-3 years, 16.6% at 3-5 years and 4.9% at 5-7 years. Overall, 23.4% of children changed sleeping place during the night, 22.4% referred sleeping problems in the first year of life. Video devices use was negative predictor of sleep duration (-0.25 h [95%CI:-0.35,-0.14], p < 0.001). Optimal sleep was inversely related with bedroom TV (OR 0.63 [0.50,0.79], p < 0.001), with sleeping disorders in the first year (OR 0.62 [0.48,0.80], p < 0.001)), with bottle use (OR 0.64 [0.44,0.94], p < 0.05) and posivively related with high mother's education level (OR 1.44 [1.11,1.88], p < 0.01). CONCLUSIONS: About one third of 1 to 14 year Italian children sleep less than recommended, one half in teenage. Modifiable risk factors for sleep abnormalities such as video devices use, bedroom TV and bottle use should be target of preventive strategies for a correct sleep. Pediatricians should give priority to the identification of sleep disorders early in life.

An educational web-based external quality assessment outcome and evaluation: first experiences with urinary sediment and hemostaseology.

External quality assessment is a standard procedure for many medical laboratories, especially those accredited according to ISO 15189. INSTAND has developed web-based quality control surveys (WQ) with integrated case-based learning in collaboration with the Institute for Teaching and Educational Research in Health Sciences (IDBG), University of Witten/Herdecke. The WQs were presented via a weblink using the learning management system CASUS. Laboratories registered with INSTAND for conventional EQAs covering the same topic were invited to participate in the WQs. Statistics were calculated with the INSTAND EQA-evaluation program and with the "Statistical Program for Social Sciences" (SPSS Version 20). While the two pilot surveys (hemostaseology) were designed for laboratory technicians, WQ III (urine sediment) addressed the whole laboratory team. From the invited laboratories more than 80% participated successfully and the evaluations showed that, in general, more than half the participants solved the tasks as a team. The web-based EQAs were well accepted by the users, with some technical problems in WQ III and moderate criticism on the images and relevance for daily practice in the evaluation sheets. Well above 80% would like to participate in further WQs and would recommend them to other laboratories. Thus web-based quality control surveys can emerge as an important supplement to conventional EQAs.

Cardiovascular risk assessment in children: role of physical activity, family history and parental smoking on BMI and blood pressure.

OBJECTIVE: Aim of the study was to assess the role of family history, physical activity and parental smoking in the prediction of BMI, SBP and hypertension risk in children. PARTICIPANTS AND METHODS: In a paediatric primary care setting, a sample of 1310 children aged 5-14 years was systematically selected by 48 family paediatricians in northern Italy. BMI, waist circumference-to-height ratio (WtHr), SBP and DBP were measured and the information on the presence of small birth weight for gestational age (SGA) and early adiposity rebound (EAR) was collected. Data concerning exercise, video time, family history for cardiovascular diseases and parental smoking were derived from parental interview. Data were collected using an 'ad hoc designed' electronic sheet available online. RESULTS: Multiple linear regression showed that the presence of EAR, low exercise (<2 h/week), high video time (>2  h/day TV/videogames/computer) and parental smoking were associated to higher BMI (z-score; P < 0.005). Age, BMI (z-score), WtHr, presence of SGA, low exercise, high video time and family history of cardiovascular diseases were associated to SBP values (P < 0.03). Logistic regression analysis showed that factors related to risk of hypertension and prehypertension were BMI (z-score; odds ratio, OR 2.63; 95% confidence interval, CI 2.12-3.28), WtHr (OR 1.13; 95% CI 1.10-3.28) and low exercise (OR 1.58; 95% CI 1.12-2.24; P <0.01). CONCLUSION: Our study demonstrates that a simple tool like a cardiovascular multi-item sheet can provide useful information to paediatricians for child health. Physical exercise plays a pivotal role in obesity prevention and protection from hypertension risk.

Is neuregulin 1 involved in determining cerebral volumes in schizophrenia? Preliminary results showing a decrease in superior temporal gyrus volume.

BACKGROUND/AIMS: Reduced left superior temporal gyrus (STG) volume is one of the most replicated imaging findings in schizophrenia. However, it remains unclear whether genes play any role in our understanding of such structural alteration. It has been proposed that Neuregulin 1 (NRG1) might be a promising gene involved in schizophrenia, because of its role in neurodevelopment and neuroplasticity. In this study, the association between NRG1 and STG anatomy in patients with schizophrenia was explored for the first time. METHODS: We investigated a 1-year treated prevalence cohort of patients with schizophrenia in contact with the South Verona Community-Based Mental Health Service. A blood sample was collected for DNA extraction and brain structure was assessed with an MRI scan. A total of 27 subjects with schizophrenia underwent both assessments and were included in the study. RESULTS: We investigated the association between the polymorphism SNP8NRG222662 (rs4623364) of NRG1 and volume of the STG. We found that patients homozygous for the C allele had reduced left STG gray and white matter volumes in comparison to those homozygous for the G allele (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: This exploratory study suggests that NRG1 may be involved in determining STG size in schizophrenia, and may play a role in the neurogenetic basis of the language disturbances seen in this disorder. However, due to our small sample size, the results should be regarded as preliminary and replicated in a larger sample.

Assessment of cerebral blood volume in schizophrenia: A magnetic resonance imaging study.

Brain atrophy has consistently been observed in schizophrenia, representing a 'gross' evidence of anatomical abnormalities. Reduced cerebral blood volume (CBV) may accompany brain size decrement in schizophrenia, as suggested by prior small SPECT studies. In this study, we non-invasively investigated the hemisphere CBV in a large sample of patients suffering from schizophrenia with perfusion-weighted imaging (PWI). PWI images were obtained, following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), for 54 DSM-IV patients with schizophrenia (mean age+/-SD=39.19+/-12.20 years; 34 males, 20 females) and 24 normal controls (mean age+/-SD=44.63+/-10.43 years; 9 males, 15 females) with a 1.5T Siemens magnet using an echo-planar sequence (TR=2160 ms, TE=47 ms, slice thickness=5mm). The contrast of enhancement (CE), a semi-quantitative parameter inversely estimating the CBV, were calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/Sox100) for right and left hemisphere on two axial images. Specifically, higher CE values correspond to lower CBV and viceversa Compared to normal controls, patients with schizophrenia had significantly higher bilateral hemisphere CE values (p=0.02) and inverse CE laterality index (p=0.02). This study showed abnormally reduced and inverse hemisphere CBV in a large population of patients with schizophrenia. Hypothetically, chronic low CBV may sustain neural hypoactivation and concomitant increase of free radicals, ultimately resulting in neuronal loss and cognitive impairments. Thus, altered intracranial hemodynamics may accompany brain atrophy and cognitive deficits, being a crucial factor in the pathophysiology of schizophrenia.