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The treatment of coronary artery disease (CAD), which is defined by stable anatomical atherosclerotic and functional alterations of epicardial vessels or microcirculation, focuses on managing intermittent angina symptoms and preventing major adverse cardiovascular events with optimal medical therapy. When patients with known CAD present with angina and no acute coronary syndrome, they have historically been evaluated with a variety of noninvasive stress tests that utilize electrocardiography, radionuclide scintigraphy, echocardiography, or magnetic resonance imaging for determining the presence and extent of inducible myocardial ischemia. Patient event-free survival, however, is largely driven by the coronary atherosclerotic disease burden, which is not directly assessed by functional testing. Direct evaluation of coronary atherosclerotic disease by coronary computed tomography angiography (coronary CTA) has emerged as the first line noninvasive imaging modality as it improves diagnostic accuracy and positively influences clinical management. Compared to functional assessment of CAD, coronary CTA-guided management results in improved patient outcomes by facilitating prevention of myocardial infarction. Other strengths of coronary CTA include detailed atherosclerotic plaque characterization and the ability to assess functional significance of specific lesions, which may further improve risk assessment and prognosis and lead to more appropriate referrals for additional testing, such as invasive coronary angiography.

Oxygen free radical burst is a prominent early event in the pathogenesis of Alzheimer’s disease (AD). Posttranslational modifications of Tau protein, primarily hyper-phosphorylation and truncation, are indicated as critical mediators of AD pathology. This finding is confirmed by the high levels of oxidative stress markers and by the increased susceptibility to oxygen radicals found in cultured neurons and in brains from transgenic animal models expressing toxic Tau forms, in concomitance with a dramatic reduction in their viability/survival. Here, we collect the latest progress in research focused on the reciprocal and dynamic interplay between oxygen radicals and pathological Tau, discussing how these harmful species cooperate and/or synergize in the progression of AD. In this context, a better understanding of the role of oxidative stress in determining Tau pathology, and vice versa, primarily could be able to define novel biomarkers of early stages of human tauopathies, including AD, and then to develop therapeutic strategies aimed at attenuating, halting, or reversing disease progression.

Background: Acute adrenal insufficiency is a rare but potentially lethal condition, that is important to identify promptly and treat with replacement therapy. It can be consequent to adrenal hemorrhage that can occur after major orthopedic surgery. Few data are available about potential recovery of adrenal function, as well as both timing and modality of cortisone acetate withdrawal, probably due to the assumption that adrenal failure should be definitive. The extension of adrenal damage can be different, so justifying a partial, or potentially complete, recovery of adrenal function. The aim of our article is to highlight the opportunity of a periodical revaluation of adrenal reserve in order to identify those patients which are able to interrupt replacement therapy. Case Presentation: We had recently described one case of acute adrenal insufficiency, which developed short time after hip replacement; the patient was able to discontinue cortisone acetate treatment 46 months after the diagnosis and remained untreated up to five years later. We collected other two cases of acute adrenal insufficiency, developed about one week after major orthopedic surgery. We followed such patients for about three years, repeatedly reassessing adrenal imaging and cortisol response to 250 μg ACTH test, in order to ascertain the real need of lifetime substitutive treatment with cortisone acetate. Acute adrenal insufficiency partially reverted during the follow up for both patients. We observed a reduction in adrenal glands’ volume and a progressive improvement of cortisol basal levels, without response (or with a poor one) to ACTH stimulation, as well as with ACTH basal levels persistently above the normal range after 36 and 28 months respectively spent from the acute event. Conclusions: The present finding suggests the opportunity that patients developing acute adrenal insufficiency after major orthopedic surgery undergo long-term surveillance, in order to establish if steroid replacement has to be continued, or it can be safely withdrawn.

Background: Hemodynamic monitoring, implemented by the placement of peripheral arterial catheters (PACs), is a characterizing aspect of the intensive care units. Peripheral arterial catheters can continually detect blood pressure and quickly conduct blood sampling. The use of PACs is generally considered safe, without serious complications. Currently, only 25% of the implanted catheters are actually subject to complications, including accidental removal, dislocation, occlusion, and infection. All of these complications arise from inadequate catheter stabilization at the level of the skin. This study aimed to summarize and describe the effectiveness and characteristics of dressings and securement devices for catheter stabilization. Methods: A systematic review of literature from the following databases was conducted: MEDLINE, CINAHL, Cochrane, EMBASE, and OvidSP. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to guide article selection and reporting. Results: Herein 626 articles were referred, with 5 directly related to the topic under discussion. We found 3 studies that describe PAC failure and 4 about dislodgement. We described 6 types of dressings or securement devices and classified them into 3 categories for classifying PAC dressings or securement devices. These were detected and grouped as adhesive tissues, sutureless devices, and transparent polyurethane dressings. Conclusions: Current research indicates that transparent polyurethane dressings offer the most effective catheter stabilization, but adhesive tissues may constitute a valid alternative. However, there are limited high-quality studies about effective dressings and securement devices for PACs.

Background: Work functioning impairment is a key diagnostic and transnosographic criterion for psychiatric disorders in both DSM-5 and ICD-11. Occupational inclusion is a fundamental aspect of the care path for patients attending the territorial services provided by the Italian Mental Health and Addiction Departments (DSMDs). Since 2009, the Regional Innovative Programme (PIR) TR106, promoted by the Fatebenefratelli-Sacco hospital of Milan, Italy, in collaboration with six other metropolitan DSMDs, was created to promote integration for people suffering from mental health problems in the city of Milan. Method: Here we present the results of a retrospective epidemiologic analysis on 2,142 interventions on 1,066 patients, conducted between 2012 and 2019. Results: Most of the interventions were conducted with people with psychotic disorders (39%), followed by personality disorders (25.2%) and affective disorders (22.2%). The age range of 25 to 54 years represented 91.5% of the whole sample, mainly in the 35 to 44 years range (36.4%). Significant age group-related changes in interventions were observed in the observation period, with a reduction in the interventions provided to subjects of the 35 to 44 age group, and an increase in the 25 to 34 age group. Conclusions: PIR TR106 provided the most accurate assessment and data collection so far for the city of Milan. Our data characterised psychiatric groups in order to develop specific treatment plans and work inclusion interventions.

Background We conducted a systematic review to evaluate and compare the accuracy of pre-hospital triage tools for major trauma in the context of the development of the Italian National Institute of Health guidelines on major trauma integrated management. Methods PubMed, Embase, and CENTRAL were searched up to November 2019 for studies investigating pre-hospital triage tools. The ROC (receiver operating characteristics) curve and net clinical benefit for all selected triage tools were performed. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies–2. Certainty of the evidence was judged with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We found 15 observational studies of 13 triage tools for adults and 11 for children. In adults, according to the ROC curve and the net clinical benefit, the most reliable tool was the Northern French Alps Trauma System (TRENAU), adopting injury severity score (ISS) > 15 as reference (sensitivity (Sn), 0.92; specificity (Sp), 0.41; 1 study; sample size, 2572; high certainty of the evidence). When mortality as reference was considered, the pre-hospital triage tool with the best net clinical benefit trajectory was the New Trauma Score (NTS) < 18 (Sn, 0.82; Sp, 0.86; 1 study; sample size, 1001; moderate certainty of the evidence). In children, high variability among all triage tools for sensitivity and specificity was found. Conclusion Sensitivity and specificity varied across all available pre-hospital trauma triage tools. TRENAU and NTS are the best accurate triage tools for adults, whereas in the pediatric area a large variability prevents any firm conclusion.

At the 2018 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), Stephano Gandolfi presented a retrospective study of his patients at the University of Parma, Italy, in which a regimen of low-energy selective laser trabeculoplasty (SLT) repeated annually irrespective of intraocular pressure (IOP) produced significantly longer medication-free survival than standard SLT repeated as needed, in patients with primary open-angle glaucoma (POAG) or high-risk ocular hypertension (OHTN).(1) Specifically, newly-diagnosed POAG eyes were treated primarily either with ALT 360° performed once, standard SLT 360° repeated as needed at standard energy, and low-energy 360° SLT (0.4 mJ/spot x 50–60 spots) repeated annually at low energy regardless of IOP. After 10 years of follow-up, medication-free rates were 22.6% in the ALT group, 25.0% in the standard SLT group, and 58.3% in the low-energy SLT group (p

The aim: To determine physiological and hygienic correlates of teachers’ occupational burnout syndrome development in general secondary education institutions. Materials and methods: The study involved 427 teachers of general secondary education institutions of Sumy region aged 21 to 71 years old, representing four pedagogical categories. During the study physiological, hygienic, psychological, mathematical and statistical research methods were used. Results: A high level of occupational burnout was found in teachers of general secondary education institutions of the regional center (12,43 %), which was mainly accompanied by the formed resistance symptom-complex (39,45 %, р

Trauma is one of the leading causes of uncontrolled haemorrhage, death, and disability. Use of a tourniquet can be considered an optimal anti-haemorrhagic resource, in pre-hospital and emergency settings, and its lifesaving effect is clinically contradictory. This review aims to assess the clinical efficacy of the tourniquet in the emergency pre-hospital care setting for the management of haemorrhage. We conducted the systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the PRISMA statement. We searched the following electronic databases: EMBASE, MEDLINE, and Cochrane-CENTRAL. All studies included were appraised for risk of bias. Prevalent primary outcomes were mortality and use of blood products. Secondary outcomes were related to adverse effects. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Four studies were involved (1762 trauma patients). The adjusted odds ratio (aOR) of 0.47 (95% confidence Interval (CI) 0.19–1.16; three studies; 377 patients) for overall mortality estimates did not give a clear indication of the benefits of emergency pre-hospital tourniquets (PH-TQ) versus no pre-hospital tourniquet (NO PH-TQ) placement. The adjusted mean difference for blood product use was −3.28 (95% CI −11.22, 4.66) for packed red blood cells (pRBC) and −4.80 (95% CI −5.61, −3.99) for plasma, respectively. The certainty of evidence was downgraded to very low for all outcomes. Our results suggest an unclear effect of emergency pre-hospital tourniquet placement on overall mortality and blood product use. However, this systematic review highlights the availability of only observational studies and the absence of high quality RCTs assessing the efficacy of PH-TQs. Randomized controlled trials are needed.

Alterations of adult neurogenesis have been reported in several Alzheimer's disease (AD) animal models and human brains, while defects in this process at presymptomatic/early stages of AD have not been explored yet. To address this, we investigated potential neurogenesis defects in Tg2576 transgenic mice at 1.5 months of age, a prodromal asymptomatic age in terms of Aβ accumulation and neurodegeneration. We observe that Tg2576 resident and SVZ-derived adult neural stem cells (aNSCs) proliferate significantly less. Further, they fail to terminally differentiate into mature neurons due to pathological, tau-mediated, and microtubule hyperstabilization. Olfactory bulb neurogenesis is also strongly reduced, confirming the neurogenic defect in vivo. We find that this phenotype depends on the formation and accumulation of intracellular A-beta oligomers (AβOs) in aNSCs. Indeed, impaired neurogenesis of Tg2576 progenitors is remarkably rescued both in vitro and in vivo by the expression of a conformation-specific anti-AβOs intrabody (scFvA13-KDEL), which selectively interferes with the intracellular generation of AβOs in the endoplasmic reticulum (ER). Altogether, our results demonstrate that SVZ neurogenesis is impaired already at a presymptomatic stage of AD and is caused by endogenously generated intracellular AβOs in the ER of aNSCs. From a translational point of view, impaired SVZ neurogenesis may represent a novel biomarker for AD early diagnosis, in association to other biomarkers. Further, this study validates intracellular Aβ oligomers as a promising therapeutic target and prospects anti-AβOs scFvA13-KDEL intrabody as an effective tool for AD treatment.

Coronary heart disease is a chronic, systemic disease with a wide range of associated symptoms, clinical outcomes, and health care expenditure. Adverse events from coronary heart disease can be mitigated or avoided with lifestyle and risk factor modifications, and medical therapy. These measures are effective in slowing the progression of atherosclerotic disease and in reducing the risk of thrombosis in the setting of plaque disruptions. With increasing effectiveness of prevention and medical therapy, the role of coronary artery revascularization has decreased and is largely confined to subgroups of patients with unacceptable angina, severe left ventricular systolic dysfunction, or high-risk coronary anatomy. There is a compelling need to allocate resources appropriately to improve prevention. Herein, we review the scientific evidence in support of medical therapy and revascularization for the management of patients with stable coronary heart disease and discuss implications for the evaluation of patients with stable angina and public policy.

Purpose The impact of patient’s characteristics on glucocorticoid (GC) replacement therapy in adrenal insufficiency (AI) is poorly evaluated. Aims of this study were to assess the influence of sex and body weight on GC dosing and to describe the choice of GC in AI of different etiologies. Methods We retrospectively evaluated hydrocortisone (HC) equivalent total daily dose (HC-TDD) and per-kg-daily dose (HC-KDD) in 203 patients (104 primary AI [pAI], 99 secondary AI [sAI]) followed up for ≥ 12 months. They were treated with HC, modified-release HC (MRHC) or cortisone acetate (CA) and fludrocortisone acetate (FCA) in pAI. Results At baseline, CA was preferred both in pAI and sAI; at last visit, MRHC was most used in pAI (49%) and CA in sAI (73.7%). Comparing the last visit with baseline, in pAI, HC-TDD and HC-KDD were significantly lower (p = 0.04 and p = 0.006, respectively), while FCA doses increased during follow-up (p = 0.02). The reduction of HC-TDD and HC-KDD was particularly relevant for pAI women (p = 0.04 and p = 0.002, respectively). In sAI patients, no change of HC-KDD and HC-TDD was observed, and we found a correlation between weight and HC-TDD in males (r 0.35, p = 0.02). Conclusions Our real-life study demonstrated the influence of etiology of AI on the type of GC used, a weight-based tailoring in sAI, a likely overdosage of GC treatment in pAI women at the start of treatment and the possibility to successfully increase FCA avoiding GC over-treatment. These observations could inform the usual clinical practice.

Objective: To evaluate calcitonin (CT) levels in sporadic primary hyperparathyroidism (PHPT), which has to date rarely been considered. Methods: We evaluated serum CT levels in 290 consecutive patients with sporadic PHPT at diagnosis. Results: Mild elevations in CT levels (hyperCT) were found in 25 patients (8.6%), with no correlation among the demographic, clinical, and biochemical findings. In addition, no differences were found between patients with and without hyperCT. Follow-up data were available for 19/25 patients, but CT values were only available for 10. CT normalized in all surgically cured patients regardless of the extent of the surgery (parathyroidectomy [PTX] only in 8 and associated with partial or total thyroidectomy for benign nodular goiters in 7). Conclusion: hyperCT is an uncommon feature of sporadic PHPT and not related to biochemical or clinical features of the disease. In addition, hyperCT is reversible after PTX, regardless of whether concomitant thyroidectomies have been conducted. Abbreviations: CT = calcitonin; eGFR = estimated glomerular filtration rate; hyperCT = hypercalcitoninemia; MEN = multiple endocrine neoplasm; MTC = medullary thyroid carcinoma; PHPT = primary hyperparathyroidism; PPI = proton pump inhibitor; PTH = parathyroid hormone; PTX = parathyroidectomy

Violence against women is a pervasive phenomenon affecting one in three women aged ≥15 in the world that are more likely to visit an emergency department (ED) for the serious physical and psychological consequences of the abuse. The aim of this observational single-centre study is to describe the socio-demographic and clinical variables associated with violence against women. We enrolled 425 female patients who attended an Italian ED for trauma on 2019 and the patients' information was collected and analyzed with descriptive statistics. The average age of the patients was 41.5 (standard deviation = 14.2) years. 74.6% of the women were Italians, and 86.6% were of metropolitan origin. The reasons for the ED visit included aggression (67.5%), accidental trauma (29.0%) and unknown reasons (3.5%). Multivariate analysis confirmed that three factors were independently associated with violence: nationality (odds ratio [OR] = 0.27; 95% confidence interval [CI], 0.09–0.77), head/face/neck injuries (OR = 7.32; 95% CI, 3.76–14.27) and multiple injuries (OR = 8.52; 95% CI, 1.03–70.47). Age over 25 was a protective factor. The study confirmed that being a foreigner and having head/face/neck injuries or multiple injuries are associated with violence against women.

Introduction Pain is multidimensional, and as such it is the chief reason patients require urgent health care services. If inadequately assessed and untreated, pain may negatively impact on the quality of life of the patient. Pain management is an essential part of Nursing. The aim to this study is to examine the level of knowledge and attitudes with regard to pain among Italian nurses who work in clinical settings. Methods The Ferrell and McCaffery's Knowledge and Attitudes Survey Regarding Pain was distributed to 266 nurses employed in one specialized hospital in Rome, Italy. The staff in the survey work in three different settings: the intensive care unit, the sub-intensive care unit, and an ordinary ward. Descriptive statistics were employed and a logistic regression model was performed to evaluate the factors that may influence the attitude and knowledge of care providers. Results 49.6% of the sample correctly answered items about attitudes, 47.4% about knowledge, and 36.5% about assessment. The results show that the odds ratio of developing positive attitudes towards pain was 1.76 times higher in nurses employed in the sub-intensive care unit than in other settings. There are no statistically significant associations of knowledge between setting, sex or education. Conclusions Our survey revealed a limited overall level of knowledge and attitudes with regards to pain management among nurses. Implementing specific training for health professionals, starting with academic education, is therefore a priority. Further research is needed on a larger sample of Italian nurses.

Osteoarthritis is a degenerative disease considered a leading cause of functional disability. Its treatment is based on a combination of pharmacological and non-pharmacological interventions, but the role of these latter is still debated. This overview of systematic reviews aimed at evaluating the short-term efficacy of different thermal modalities in patients with osteoarthritis. We searched PubMed, Scopus, CINHAL, Web of Science, ProQuest and the Cochrane Database of Systematic Reviews from inception until October 2020, with no language restrictions. We selected the following outcomes a priori: pain, stiffness and quality of life. Seventeen systematic reviews containing 27 unique relevant studies were included. The quality of the reviews ranged from low to critically low. Substantial variations in terms of interventions studied, comparison groups, population, outcomes and follow-up between the included SRs were found. From a re-analysis of primary data, emerged that balneotherapy was effective in reducing pain and improving stiffness and quality of life, mud therapy significantly reduced pain and stiffness, and spa therapy showed pain relief. However, the evidence supporting the efficacy of different thermal modalities could be seriously flawed due to methodological quality and sample size, to the presence of important treatment variations, and to the high level of heterogeneity and the absence of a double-blind design. There is some encouraging evidence that deserves clinicians' consideration, suggesting that thermal modalities are effective on a short-term basis for treating patients with AO.

Tau cleavage plays a crucial role in the onset and progression of Alzheimer’s Disease (AD), a widespread neurodegenerative disease whose incidence is expected to increase in the next years. While genetic and familial forms of AD (fAD) occurring early in life represent less than 1%, the sporadic and late-onset ones (sAD) are the most common, with ageing being an important risk factor. Intracerebroventricular (ICV) infusion of streptozotocin (STZ)—a compound used in the systemic induction of diabetes due to its ability to damage the pancreatic β cells and to induce insulin resistance—mimics in rodents several behavioral, molecular and histopathological hallmarks of sAD, including memory/learning disturbance, amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress and brain glucose hypometabolism. We have demonstrated that pathological truncation of tau at its N-terminal domain occurs into hippocampi from two well-established transgenic lines of fAD animal models, such as Tg2576 and 3xTg mice, and that it’s in vivo neutralization via intravenous (i.v.) administration of the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) is strongly neuroprotective. Here, we report the therapeutic efficacy of 12A12mAb in STZ-infused mice after 14 days (short-term immunization, STIR) and 21 days (long-term immunization regimen, LTIR) of i.v. delivery. A virtually complete recovery was detected after three weeks of 12A12mAb immunization in both novel object recognition test (NORT) and object place recognition task (OPRT). Consistently, three weeks of this immunization regimen relieved in hippocampi from ICV-STZ mice the AD-like up-regulation of amyloid precursor protein (APP), the tau hyperphosphorylation and neuroinflammation, likely due to modulation of the PI3K/AKT/GSK3-β axis and the AMP-activated protein kinase (AMPK) activities. Cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations occurring in STZ-infused mice were also strongly attenuated by 12A12mAb delivery. These results further strengthen the causal role of N-terminal tau cleavage in AD pathogenesis and indicate that its specific neutralization by non-invasive administration of 12A12mAb can be a therapeutic option for both fAD and sAD patients, as well as for those showing type 2 diabetes as a comorbidity.

BackgroundEvidence is needed on the effectiveness of wearing face masks in the community to prevent SARS-CoV-2 transmission.MethodsSystematic review and meta-analysis to investigate the efficacy and effectiveness of face mask use in a community setting and to predict the effectiveness of wearing a mask. We searched MEDLINE, EMBASE, SCISEARCH, The Cochrane Library and pre-prints from inception to 22 April 2020 without restriction by language. We rated the certainty of evidence according to Cochrane and GRADE approach.FindingsOur search identified 35 studies, including 3 randomised controlled trials (RCTs) (4017 patients), 10 comparative studies (18984 patients), 13 predictive models, 9 laboratory experimental studies. For reducing infection rates, the estimates of cluster-RCTs were in favour of wearing face masks versus no mask, but not at statistically significant levels (adjusted OR 0.90, 95%CI 0.78-1.05). Similar findings were reported in observational studies. Mathematical models indicated an important decrease in mortality when the population mask coverage is near-universal, regardless of mask efficacy. In the best-case scenario, when the mask efficacy is at 95%, the R0 can fall to 0.99 from an initial value of 16.90. Levels of mask filtration efficiency were heterogeneous, depending on the materials used (surgical mask: 45-97%). One laboratory study suggested a viral load reduction of 0.25 (95%CI 0.09-0.67) in favour of mask versus no mask.InterpretationThe findings of this systematic review and meta-analysis support the use of face masks in a community setting. Robust randomised trials on face mask effectiveness are needed to inform evidence-based policies.Fundingnone.PROSPERO registrationCRD42020184963.Contribution to the fieldGuidelines by various organizations provide conflicting evidence about the effectiveness of face mask use in the community. We performed a systematic review of the available evidence, including 35 studies, across 41 countries and six continents. Previous systematic reviews on the effectiveness of face mask use mainly focused on healthcare and household setting including only randomized controlled trials and observational studies with most of them of low quality. In our review, we included randomized controlled trials, observational studies, laboratory experimental studies as well as mathematical modelling studies in order to answer different questions and provide quantitative estimates for planning pandemic response efforts.Our review supports the use of surgical masks in the community for providing protection during the COVID-19 pandemic. However, the infection rate, mortality, spread of transmission (R0), filtering capacity of masks and viral load reduction are highly dependent on the type of face mask worn and on the adherence of the population wearing masks. Policy makers should promote face mask use in the community.

Background: Several risk factors, such as age, alcohol abuse, dementia, and severe illness, can contribute to the development of delirium. However, limited information is available in the literature regarding the risk of delirium among surgical, trauma, neurological, and medical intensive care patients. Aims and objectives: To describe the prevalence of risk factors associated with delirium in intensive care units. Design: This study used an observational design. Methods: We enrolled 165 patients hospitalized in two intensive care units in Italy. Patients were first evaluated using the Prediction of Delirium model and were subsequently evaluated using the Intensive Care Delirium Screening Checklist; evaluation lasted a maximum of 5 days for each admitted patient after sedation. A logistic regression model was used to identify the prevalence and risk factors of delirium. Results: The average age of the patients was 57.6 (SD = 18.3) years, and the patients were predominantly male (65.0%). The majority of patients had been subjected to trauma (38.8%); 37.6% had undergone general surgical interventions, and 23.6% had undergone medical interventions. Delirium occurred in 55.8% of the 165 patients. The risk of delirium was independently associated with coma (odds ratio = 10.6; 95% confidence interval, 3.08-39.9) and the Acute Physiology and Chronic Health Evaluation II score (odds ratio = 4.27; 95% confidence interval, 1.58-11.53). Conclusions: This study confirmed that coma and the Acute Physiology and Chronic Health Evaluation II score were non-modifiable risk factors for delirium. Further studies could categorize the different types of coma. Proper delirium management could limit the impact on the recovery of these patients, their autonomy, and their reintegration into the social and professional world. Relevance to clinical practice: Delirium increases intensive care unit and hospital length of stay. Early identification and risk factor assessment by critical care nurses are considered the key factors in the treatment of delirium.

Background: Advanced cancer patients often die in hospital after receiving needless, aggressive treatment. Although palliative care improves symptom management, barriers to accessing palliative care services affect its utilisation, and such disparities challenge the equitable provision of palliative care. This study aimed to identify which factors are associated with inequitable palliative care service utilisation among advanced cancer patients by applying the Andersen Behavioural Model of Health Services Use.Material and methods: This was a retrospective cohort study using administrative healthcare data. A total of 13,656 patients residing in the Lazio region of Italy, who died of an advanced cancer-related cause-either in hospital or in a specialised palliative care facility-during the period of 2012-2016 were included in the study. Potential predictors of specialised palliative service utilisation were explored by grouping the following factors: predisposing factors (i.e., individuals' characteristics), enabling factors (i.e., systemic/structural factors) and need factors (i.e., type/severity of illness).Results: The logistic hierarchical regression showed that older patients (odds ratio [OR] = 1.45

Chronic non-cancer pain is a complex health condition that affects more than a quarter of the Italian population who mainly refers to general practitioners and primary care for their treatment. There are little information on the epidemiological and clinical characteristics and types of treatments for these patients who suffer from chronic pain. The aim of the study was to provide epidemiological and clinical information about patients with chronic non-cancer pain who refers to GPs for their treatment. An observational, multicentre, cross-sectional study was carried out using retrospectively reviewed clinical records from 29 GPs. Some pharmacoeconomic aspects were also investigated. A total of 1,007 patients who had chronic pain were selected for the study. Chronic pain was more common in women than in men (ratio 2.7 : 1) (P = 0.002). With regard to incomes, the women earned less than the men (P = 0.017). The chronic pain was musculoskeletal (73.4%), mixed (21.4%), neuropathic (4.9%) and visceral (0.3%). More women than men had pain in two or more sites, and 33.5% of the patients reported more than one diagnosis that related to chronic pain. The general practitioners had prescribed nonsteroidal anti-inflammatory drugs for 71.8% of the cases, opioids for 16.9%, adjuvants for 9.0% and acetaminophen for 2.4%, and about pharmacoeconomic aspects, the total cost for the sample was € 111,331.42. Primary care is the essential frontline for patients who suffer from non-cancer pain. An interdisciplinary assessment and approach should start in primary care delivery to maximize the clinical outcomes.

Introduction: Adolescents’ pain experiences are complex and multidimensional, and evaluating pain only from a sensory and affective point of view may be in many instances limiting and inadequate; this is the reason why it is of paramount importance to identify the tools which can better assess the pain experienced by young patients. A person-oriented approach is highly encouraged, as it may better investigate the cognitive and behavioral development typical of this age group. The aim of this review paper is to describe the available tools which are able to adequately assess pain intensity in adolescents, in particular those validated in Italian. Methods: We conducted a systematic review using four databases: CINAHL, PsycINFO, PubMed and Cochrane, and selected all the articles published between January 1970 and November 2017. We selected all the papers reporting the validation process of pain assessment tools specifically tailored for adolescent patients (age range 10–18 years) and based on psychometric and linguistic parameters, and focused especially on the tools available in Italian and able to measure acute and chronic pain. Results: The results of our investigation have revealed the existence of 40 eligible tools, 17 of which are monodimensional and the remaining 23 multidimensional, more specifically tailored to assess both acute and chronic pain. Some of the instruments (26) were self-reports while others were classified as behavioral (13) and/or mixed. Only one tool turned out to be suitable for fragile adolescents, while six adopted a person-oriented approach that better emphasized the cognitive and behavioral process typical of the adolescent population. None of them has ever been validated in Italian. Conclusion: Valid and reliable psychometric tools specifically organized to provide a cultural and linguistic evaluation of the patient are indeed the most recommended instruments to assess the intensity of the pain experienced by the patient, as they may provide useful information to implement a health policy aimed at identifying the best assistance programs.

Alzheimer’s disease (AD) is an age-associated neurodegenerative disease which is the most common cause of dementia among the elderly. Imbalance in nerve growth factor (NGF) signaling, metabolism, and/or defect in NGF transport to the basal forebrain cholinergic neurons occurs in patients affected with AD. According to the cholinergic hypothesis, an early and progressive synaptic and neuronal loss in a vulnerable population of basal forebrain involved in memory and learning processes leads to degeneration of cortical and hippocampal projections followed by cognitive impairment with accumulation of misfolded/aggregated Aβ and tau protein. The neuroprotective and regenerative effects of NGF on cholinergic neurons have been largely demonstrated, both in animal models of AD and in living patients. However, the development of this neurotrophin as a disease-modifying therapy in humans is challenged by both delivery limitations (inability to cross the blood–brain barrier (BBB), poor pharmacokinetic profile) and unwanted side effects (pain and weight loss). Age-related macular degeneration (AMD) is a retinal disease which represents the major cause of blindness in developed countries and shares several clinical and pathological features with AD, including alterations in NGF transduction pathways. Interestingly, nerve fiber layer thinning, degeneration of retinal ganglion cells and changes of vascular parameters, aggregation of Aβ and tau protein, and apoptosis also occur in the retina of both AD and AMD. A protective effect of ocular administration of NGF on both photoreceptor and retinal ganglion cell degeneration has been recently described. Besides, the current knowledge about the detection of essential trace metals associated with AD and AMD and their changes depending on the severity of diseases, either systemic or locally detected, further pave the way for a promising diagnostic approach. This review is aimed at describing the employment of NGF as a common therapeutic approach to AMD and AD and the diagnostic power of detection of essential trace metals associated with both diseases. The multiple approaches employed to allow a sustained release/targeting of NGF to the brain and its neurosensorial ocular extensions will be also discussed, highlighting innovative technologies and future translational prospects.

Efforts to better control risk factors for cardiovascular disease and prevent the development of subsequent cardiovascular events are crucial to maintaining healthy populations. In today's busy practice environment and with the overwhelming pace of new research findings, ensuring appropriate emphasis and implementation of evidence-based preventive cardiovascular care can be challenging. The ABCDEF approach to cardiovascular disease prevention is intended to improve dissemination of contemporary best practices and ease the implementation of comprehensive preventive strategies for clinicians. This review serves as a succinct yet authoritative overview for interested internists as well as for cardiologists not otherwise focused on cardiovascular disease prevention. The goal of this 2-part series is to compile a state-of-the-art list of elements central to primary and secondary prevention of cardiovascular disease, using an ABCDEF checklist. In Part 2, we review new recommendations about lipid-modifying strategies, contemporary best practice for tobacco cessation, new evidence related to cardiovascular risk reduction in diabetes using novel therapies, ways to implement a heart-healthy diet, modern interventions to improve physical exercise, and how best to prevent the onset of heart failure.

Background Preschool-based interventions offer promise to instill healthy behaviors in children, which can be a strategy to reduce the burden of cardiovascular disease later. However, their efficacy in underserved communities is not well established. Objectives The purpose of this study was to assess the impact of a preschool-based health promotion educational intervention in an underserved community. Methods This cluster-randomized controlled study involved 15 Head Start preschools in Harlem, New York. Schools and their children were randomized 3:2 to receive either a 4-month (50 h) educational intervention to instill healthy behaviors in relation to diet, physical activity, body/heart awareness, and emotion management; or their standard curriculum (control). The primary outcome was the change from baseline in the overall knowledge, attitudes, and habits (KAH) score of the children at 5 months. As secondary outcomes, we evaluated the changes in KAH subcomponents and emotion comprehension. Linear mixed-effects models were used to test for intervention effects. Results The authors enrolled 562 preschool children age 3 to 5 years, 51% female, 54% Hispanic/Latino, and 37% African-American. Compared with the control group, the mean relative change from baseline in the overall KAH score was ∼2.2 fold higher in the intervention group (average absolute difference of 2.86 points; 95% confidence interval: 0.58 to 5.14; p = 0.014). The maximal effect was observed in children who received >75% of the curriculum. Physical activity and body/heart awareness components, and knowledge and attitudes domains, were the main drivers of the effect (p values Conclusions This multidimensional school-based educational intervention may be an effective strategy for establishing healthy behaviors among preschoolers from a diverse and socioeconomically disadvantaged community. Early primordial prevention strategies may contribute to reducing the global burden of cardiovascular disease. (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health [FAMILIA]; NCT02343341)

Lenvatinib (LEN) is a multikinase inhibitor with antiangiogenic properties recently approved in radioactive iodine-refractory differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma in combination with everolimus. LEN-treated patients frequently have adverse events (AEs) that generally require such dose modifications, including drug discontinuation. Hypertension, diarrhea, weight loss, proteinuria, fatigue, and palmar-plantar erythrodysesthesia are reported among the most frequent AEs, often leading to discontinuations or dose modifications. This paper reports a case series focusing on the role of the immediate multidisciplinary approach to manage AEs.

Strokes, being a heterogeneous syndrome, are the result of multifactorial accumulative disorders of the body. The urgency of the problem of cerebral stroke is due to the high level of occurrence and prevalence on a global scale, as well as the consequences. Thus, vascular diseases of the brain vessels occupy the second place in the structure of mortality from diseases of the circulatory system and total mortality of the population. The expected aging of the population, coupled with a decrease in mortality from stroke, creates a predisposition to an increase in the burden of strokes in the form of an increase in the number of victims. In Kazakhstan, as in most countries of the world, ischemic strokes prevail, which are the main cause of disability of the working-age population. Despite certain advances in the treatment of brain catastrophes caused by the introduction of protocols for early diagnosis and the development of algorithms for urgent actions, as well as the development of innovative pharmaceutical approaches, prevention of stroke development remains the most effective approach in all respects - medical, economic, social. Risk factors for stroke can be classified as changeable (modifiable) and not subject to change (non-modifiable, or risk markers). Age, gender and race, ethnicity, genetic predisposition are unchangeable risk factors for both ischemic and hemorrhagic stroke, while hypertension, smoking, diet and physical inactivity are among the most common modifiable risk factors. Stroke prevention mainly focuses on managing variable risk factors. Lifestyles and behavior modification, such as changes in diet or smoking cessation, not only reduce stroke risk, but also reduce the risk of other cardiovascular diseases. Other preventive areas include the identification and treatment of diseases that increase the risk of stroke, such as hypertension, diabetes and atrial fibrillation.

Background The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA). Methods All patients with FIB-4 Results Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups (P < .0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8–13.64). Conclusions HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients.

In Italy, chronic pain affects more than a quarter of the population, whereas the average European prevalence is 21%. This high prevalence might be due to the high percentage of Italian people who do not receive treatment, even after the passing of law 38/2010 (the right to access pain management in Italy), which created a regional network for the diagnosis and treatment of noncancer chronic pain. Italian epidemiologic studies on chronic pain are scanty, and this observational, multicenter, cross-sectional study is the first to investigate the clinical characteristics of patients who attended the pain management clinics in the Latium Region, Italy, for the management of their noncancer chronic pain. A total of 1,606 patients (mean age 56.8 years, standard deviation ± 11.4), 67% women, were analyzed. Severe pain was present in 54% of the sample. Women experienced pain and had it in two or more sites more often than men (57% vs. 50%, p = .02; and 55.2% vs. 45.9%, p .001, respectively). Chronic pain was musculoskeletal (45%), mixed (34%), and neuropathic (21%). In more than 60% of the cases, chronic pain was continuous, and in 20% it had lasted for more than 48 months; long-lasting pain was often neuropathic. Low back (33.4%) and lower limbs (28.2%) were the main locations. Severe intensity of pain was statistically significantly associated with female gender (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.06-1.84); with International Classification of Diseases, Ninth Revision, codes for chronic pain syndrome (OR 2.14; 95% CI 1.55-2.95); and with continuous pain (OR 2.02; 95% CI 1.54-2.66). Neuropathic pain and mixed pain were significantly associated with number of sites, and a trend seemed to be present (OR 2.11 and 3.02 for 2 and 3 + sites; 95% CI 1.59-2.79 and 2.00-4.55, respectively).

Background Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI.

Introduction: Conventional resolution coronary CTA (CRCT) is frequently avoided in patients with heavy calcification and prior stents given the diminished diagnostic accuracy. Ultra-high-resolution CT (UHRCT) with detector width of 0.25 mm may overcome partial volume effect limitations. Hypothesis: We hypothesize that UHRCT yields high accuracy for detecting obstructive coronary arterial stenoses in patients with severe coronary artery disease using cardiac catheterization as reference standard. Methods: Nine patients ≥45 years with severe coronary artery disease referred for invasive coronary angiography were prospectively enrolled at a single center. Patients underwent UHRCT within 30 days prior to catheterization and results for significant coronary artery stenoses (≥70%) by visual assessment by blinded expert readers for the two tests were compared. Diagnostic accuracy assessment was performed at a patient-level (N=9) and vessel-level (N=36). Results: Median patient age was 67 (range 53-77). Six patients were obese and 6 had prior stent placement. Estimated radiation dose was 9.3 mSv. Mean Agatston calcium score of patients without stents was 1,688. UHRCT correctly classified all patients as having obstructive or non-obstructive coronary heart disease, respectively, yielding 100% accuracy (95% confidence interval [CI] 64-100%). On a vessel level UHRCT had an accuracy of 93% (95% CI 78-98%). Conclusions: Our initial experience with UHRCT in patients with severe coronary calcification or prior stenting suggests high accuracy for detecting and excluding obstructive stenoses. These results warrant further studies to confirm a role of UHRCT in this challenging population.

Introduction: Elevated Lipoprotein(a) [Lp(a)] is associated with an increased risk of coronary heart disease (CHD). Although Lp(a) is mostly heritable, and controlled by the apo(a) gene, acute increases are described in small studies following acute coronary syndrome (ACS). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition modestly reduces Lp(a) in people with stable CHD but its effects during the early phase of an ACS are unknown. Hypothesis: Early administration of a PCSK9 inhibitor prevents a rise in Lp(a) following an ACS/NSTEMI. Methods: Participants from the EVACS trial (Evolocumab in Acute Coronary Syndrome; NCT03515304), all with a NSTEMI and a troponin-I of > 5 ng/ml were randomized to placebo or to evolocumab. Serum Lp(a) was obtained at study entry prior to study drug and at 30 days. Normally distributed data were summarized using means and standard deviations and non-normally distributed data using medians and interquartile ranges. Results: Fifty-six participants were randomized to placebo (27) or to evolocumab (29). Mean age was 55±13 years, 41% were women and 27% were African American. The Scatterplots (Fig.1) demonstrate for those with a baseline Lp(a) of ≤75 nmol/L (the previously described optimal level) there was no increase in Lp(a) over the 30-day study period in either group. However, for those with a baseline Lp(a) of >75 nmol/L there was a significant increase in the placebo group (Panel A), from a baseline of 176.5 nmol/L [131.5, 245.0] to 266 nmol/L [195.8, 302.5] at 30 days, p=0.02, but no increase in the evolocumab group (Panel B; baseline of 142 nmol/L [93, 177] to 137 nmol/L [96.8, 178.3], p=NS). The baseline values of those with Lp(a) of >75 nmol/L did not differ between the groups; at 30 days, however, Lp(a) was higher in the placebo than in the evolocumab group (p=0.02; Panel C). Conclusions: Early administration of evolocumab prevents the acute increase in Lp(a) in those with a baseline Lp(a) of over 75 nmol/L following an ACS/NSTEMI.

We propose a theoretical model of insomnia symptoms and non‐suicidal self‐injury (NSSI) that posits bidirectional linkages. We hypothesised that heightened depressive symptoms and impulsivity that result from insomnia increase NSSI. We also posit that the shame associated with NSSI triggers repetitive negative thinking, in turn increasing insomnia. Using three longitudinal waves of questionnaire data collected annually from a sample of Swedish adolescents (n = 1,457; M age = 13.2, SD = 0.43; 52.7% boys), we assessed the mediating role of depressive symptoms, impulsivity, rumination, and worry on the link between insomnia and NSSI. After controlling for depressive symptoms, we found that insomnia was related to increases in NSSI from the second to the third time point (ß 23 = 0.09, p = .01). NSSI was consistently related to increased insomnia (ß 12 = 0.09, p = .01; ß 23 = 0.11, p

Background Up to 30% of women with vaginal symptoms are not assigned a diagnosis after standard diagnostic assessment. Methods We compared premenopausal women with idiopathic vaginitis (IV) or vulvodynia (VVD) to healthy controls. Microbiota were characterized using rRNA sequencing. Cytokines/chemokines (IL-10, IL-1α, IL-1β, IL-6, IL-8, IL-2, IL-18, IL-4, IL-9, and IL-13) were measured in vaginal lavage fluid using the Meso Scale Discovery platform or ELISA (IL-1ra). Immunoglobulins were measured in vaginal lavage fluid using a bead-based immunoassay (Millipore). Cases and controls were compared using Kruskal-Wallis, analysis of variance, and linear regression or (for microbiome composition) the Bray-Curtis dissimilarity statistic. Results We compared 20 women with IV, 30 with VVD, and 52 controls. Most (80%) had greater than 90% 16S rRNA gene sequences from Lactobacillus crispatus, L. jensenii, L. gasseri, or L. iners. In analyses adjusted for age and hormonal contraception (HC), Gardnerella vaginalis was less prevalent and abundant in women with VVD (2/30, 7%) versus controls (16/52, 31%) or IV (5/20, 25%) (P = 0.030). Bray-Curtis dissimilarity was not significantly different between IV and controls or VVD. Fungal sequences were only detected in 5 participants: 2 control, 1 IV, 2 VVD. In univariate analysis, cytokines were not associated with diagnosis. Median vaginal concentration of IgE (but not other immunoglobulins) was lower in women with VVD (P = 0.006). Conclusions Minimal differences in vaginal microbiota and inflammatory markers between women with IV, VVD or controls suggest no striking association between vaginal bacteria, fungi or inflammation and diagnosis in these women.

Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making tau an attractive target for the cure of Alzheimer’s disease. We have explored whether passive immunization with the 12A12 monoclonal antibody (26–36aa of tau protein) could improve the Alzheimer’s disease phenotype of two well-established mouse models, Tg2576 and 3xTg mice. 12A12 is a cleavage-specific monoclonal antibody which selectively binds the pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) of tau protein without cross-reacting with its full-length physiological form(s). We found out that intravenous administration of 12A12 monoclonal antibody into symptomatic (6 months old) animals: (i) reaches the hippocampus in its biologically active (antigen-binding competent) form and successfully neutralizes its target; (ii) reduces both pathological tau and amyloid precursor protein/amyloidβ metabolisms involved in early disease-associated synaptic deterioration; (iii) improves episodic-like type of learning/memory skills in hippocampal-based novel object recognition and object place recognition behavioural tasks; (iv) restores the specific up-regulation of the activity-regulated cytoskeleton-associated protein involved in consolidation of experience-dependent synaptic plasticity; (v) relieves the loss of dendritic spine connectivity in pyramidal hippocampal CA1 neurons; (vi) rescues the Alzheimer’s disease-related electrophysiological deficits in hippocampal long-term potentiation at the CA3-CA1 synapses; and (vii) mitigates the neuroinflammatory response (reactive gliosis). These findings indicate that the 20–22 kDa NH2-terminal tau fragment is crucial target for Alzheimer’s disease therapy and prospect immunotherapy with 12A12 monoclonal antibody as safe (normal tau-preserving), beneficial approach in contrasting the early Amyloidβ-dependent and independent neuropathological and cognitive alterations in affected subjects., Intercepting the pathologically relevant species without interfering with the physiological form(s) of protein is one of the challenges of tau-directed immunotherapy. The present study shows that antibody-mediated selective neutralization of the toxic N-truncated tau fragment in hippocampi from two transgenic Alzheimer’s disease mice significantly improves the synaptic functions., Graphical Abstract Graphical Abstract

Tau truncation occurs at early stages during the development of human Alzheimer's disease (AD) and other tauopathy dementias. Tau cleavage, particularly in its N-terminal projection domain, is able to drive per se neurodegeneration, regardless of its pro-aggregative pathway(s) and in fragment(s)-dependent way. In this short review, we highlight the pathological relevance of the 20-22 kDa NH2-truncated tau fragment which is endowed with potent neurotoxic “gain-of-function” action(s), both in vitro and in vivo. An extensive comment on its clinical value as novel progression/diagnostic biomarker and potential therapeutic target in the context of tau-mediated neurodegeneration is also provided.

Adrenal insufficiency is a potentially life-threatening condition when it occurs acutely, as in adrenal hemorrhage. Generally it is not reversible and requires chronic replacement therapy. Acute intermittent porphyria (AIP) is a rare genetic disease characterized by alterations in heme biosynthesis that result in accumulation of precursors in tissues. A crisis can be triggered by many conditions such as surgery and infections. Symptoms are similar to those of acute hypoadrenalism. Moreover, both conditions are characterized by hyponatremia. We describe the case of a postmenopausal woman known to be affected by AIP who developed after surgery a primary adrenal insufficiency associated with adrenal enlargement; the latter completely reverted in six months.

Leiomyosarcomas, neoplasms of smooth muscle, are rarely found within the orbit. Orbital leiomyosarcoma may be primary, metastatic, or secondary to radiation. When they are metastatic, patients almost exclusively have a history of a primary leiomyosarcoma, often occurring in the spermatic cord, skin, gastrointestinal tract, or the uterus. We present the case of 48-year-old woman who presented with a metastatic orbital leiomyosarcoma, which was identified before the primary tumor.

We proposed that having mutually hostile interactions with others is a strong environmental stress factor that, together with diverse psychosocial problems, characterizes adolescents who self-harm. Using cluster analysis, this study examined the naturally occurring patterns of hostility conditions and psychosocial difficulties in a normative sample of 2,029 adolescents (50% boys; M

In the literature, bully-victims report a wider range of adjustment problems than “pure” bullies or victims. This may not be confined to the school context, but might be found in other settings as well. Involvement in mutually hostile interactions across everyday settings may more reflect adolescents' characteristic way of handling conflicts with others. We used data from a longitudinal study of a community sample of adolescents (N = 992). Cluster analyses for specific everyday settings and across settings yielded clusters high on both exposing others and being exposed to hostility. Adolescents in these clusters, and particularly across settings, reported a wider range of externalizing, internalizing, and academic problems, than adolescents in other cluster groups. Longitudinal analyses showed support for bidirectional relationships between mutually hostile conditions and problematic adjustment. We conclude that adolescents' mutual hostility experiences are associated with profoundly problematic adjustment.

What do we already know about this subject? • Chronic pain can have negative effects on quality of life. It is associated with a reduced ability to work, quality of life and disability, conditions that should be treated in specialized pain management clinics. In Italy very little information on clinical outcomes after chronic pain treatments is provided. What does our study add to the already existing information • This study is the first to provide clinical data about the impact of chronic pain in terms of quality of life and disability on patients who attended pain management clinics in Italy. • Chronic pain has a negative impact on quality of life and disability and causes presenteeism. • Statistical significant results in pain management do not often correspond to best results in clinical settings

PURPOSE: Conventional CT technology yields only modest accuracy of coronary artery stenosis assessment in severely calcified lesions. Reported herein are this study's initial observations on the potential of ultra-high-resolution CT (UHR-CT) for evaluating severely calcified coronary arterial lesions. MATERIALS AND METHODS: Fifteen patients 45 years of age or older, with history of coronary artery disease, referred for invasive coronary angiography, were prospectively enrolled. Patients underwent UHR-CT within 30 days prior to cardiac catheterization. Image noise levels and diagnostic confidence (level 1–5) using UHR-CT were compared with reconstructed images simulating conventional CT technology. Stenosis assessment for the major coronary arteries and the left main coronary artery with UHR-CT and invasive angiography were compared. Results from clinically driven coronary CT using conventional technology were considered for comparison when available. RESULTS: Mean patient age was 67 years (range, 53–79 years). Thirteen patients were men, nine had obesity. Radiation dose was 9.3 mSv owing to expanded x-ray exposure to accommodate research software application (70%–99% of R-R cycle). Overall image noise was considerably greater for UHR-CT (50.9 ± 7.8 [standard deviation]) versus conventional CT image reconstruction (19.5 ± 8.3, P < .01), yet diagnostic confidence scores for UHR-CT were high (4.3 ± 0.9). Average calcium score in patients without stents (n = 6) was 1205, and of 86 vessels evaluated, 22 had 70% or greater stenosis depicted with invasive angiography (26%). Stenosis comparison with invasive angiography yielded 86% (19 of 22) sensitivity and 88% (56 of 64) specificity (95% CI: 65%, 97%; and 77%, 95%, respectively). CONCLUSION: Initial observations suggest UHR-CT may be effective in overcoming the limitation of conventional CT for accurately evaluating coronary artery stenoses in severely calcified vessels. Keywords: CT-Angiography, Coronary Arteries, Arteriosclerosis Clinical trial registration no. NCT04272060 See also commentary by Shanbhag and Chen in this issue. © RSNA, 2021

Background The 2020 American Heart Association Impact Goal aims to improve cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular disease and stroke by 20%. A large step toward this goal would be to better understand and take advantage of the significant intersection between behavior and biology across the entire life-span. In the proposed FAMILIA studies, we aim to directly address this major knowledge and clinical health gap by implementing an integrated family-centric health promotion intervention and focusing on the intersection of environment and behavior, while understanding the genetic and biologic basis of cardiovascular disease. Methods We plan to recruit 600 preschool children and their 600 parents or caregivers from 12-15 Head Start schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster randomization of the schools. The preschool children will receive our intensive 37-hour educational program as the intervention for 4 months. For the adults, those in the "intervention" group will be randomly assigned to 1 of 2 intervention programs: an "individual-focused" or "peer-to-peer based." The primary outcome in children will be a composite score of knowledge (K), attitudes (A), habits (H), related to body mass index Z score (B), exercise (E), and alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements. For adults, the primary outcome will be a composite score for behaviors/outcomes related to blood pressure, exercise, weight, alimentation (diet) and tobacco (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP genotyping, and blood will be collected from adults for RNA sequencing to identify network models and predictors of primary prevention outcomes. Conclusion The FAMILIA studies seek to demonstrate that targeting a younger age group (3-5 years) and using a family-based approach may be a critical strategy in promoting cardiovascular health across the life-span.

To characterize primary hyperparathyroidism (PHPT) patients with renal stones and to compare silent with symptomatic stone formers.We reviewed clinical data from 234 patients with PHPT, comparing those with and without renal stones (n = 109 and 125, respectively), and among stone formers those symptomatic versus silent (n = 93 and 16, respectively).Stone formers were younger, had higher urinary calcium levels and higher estimated glomerular filtration rates (eGFRs) compared to patients without stones. Patients with silent stones had higher parathyroid hormone (PTH) and lower 25OH-vitamin D (25OHD) levels and more frequently experienced microlithiasis than patients with symptomatic renal stones.Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones have microlithiasis, associated to some features of more severe disease. Lower 25OHD levels in silent stone formers raise the hypothesis that vitamin D status can influence the clinical expression of nephrolithiasis in PHPT patients.BMI = body mass index Ca = serum total calcium DM = diabetes mellitus eGFR = estimated glomerular filtration rate HOMA-IR = Homeostasis Model Assessment-Insulin Resistance 25OHD = 25OH-vitamin D PHPT = primary hyperparathyroidism PTH = parathyroid hormone UCa = 24-h urine for calcium US = ultrasound.