CSF sTREM2 in deliriumrelation to Alzheimer's disease CSF biomarkers A42, t-tau and p-tau

Background: Delirium and dementia share symptoms of cognitive dysfunctions, and mechanisms of neuroinflammation appear involved in both conditions. Triggering receptor expressed on myeloid cells 2 (TREM2) is linked to dementia and neurodegenerative disease. It encodes expression of an innate immune receptor in the brain expressed by microglia. The level of the soluble fragment of TREM2 (sTREM2) is reported to increase in the cerebrospinal fluid (CSF) already in prodromal and asymptomatic Alzheimer’s disease. Methods: We analyzed the level of CSF sTREM2 in relation to delirium and dementia. The study included patients with or without pre-existing dementia who underwent acute hip fracture surgery (n = 120), and some of the patients developed delirium (n = 65). A medical delirium cohort (n = 26) was also examined. ELISA was used to determine the level of sTREM2 in CSF. Results: Delirium was associated with a higher level of CSF sTREM2 only among those without pre-existing dementia (p = 0.046, n = 15, n = 44), particularly among patients developing delirium after CSF sampling (p = 0.02, n = 7, n = 44). Between patients with dementia, there was no group difference, but the CSF sTREM2 level increased with waiting time for surgery (rS = 0.39, p = 0.002, n = 60) and correlated well with the CSF Alzheimer’s disease biomarkers, Aβ42, and t-tau/p-tau (rS = 0.40, p = 0.002, rS = 0.46, p < 0.001/ rS = 0.49, p < 0.001, n = 60). Among patients with dementia, the level of Aβ38 and Aβ40 also correlated positively with sTREM2 in CSF (Aβ38MSDrS = 0.44, p = 0.001; Aβ40MSDrS = 0.48, p < 0.001; Aβ42MSDrS = 0.43, p < 0.001, n = 60). Conclusion: The findings reinforce the involvement of neuroinflammation in delirium, yet with separate responses in patients with or without pre-existing dementia. Our findings support the concept of primed microglia in neurodegenerative disease and central immune activation after a peripheral trauma in such patients. A CSF biomarker panel of neuroinflammation might be valuable to prevent delirium by identifying patients at risk

Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia : Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age

PURPOSE Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored. PATIENTS AND METHODS We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. RESULTS Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse. CONCLUSION Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse. (C) 2019 by American Society of Clinical OncologyPeer reviewe

The PreCardio-study protocol – a randomized clinical trial of a multidisciplinary electronic cardiovascular prevention programme

<p>Abstract</p> <p>Background</p> <p>Cardiovascular diseases (CVD) are the leading cause of death and the third cause of disability in Europe. Prevention programmes should include interventions aimed at a reduction of medical risk factors (hypertension, hypercholesterol, hyperglycemia, overweight and obesity) as well as behavioural risk factors (sedentary lifestyle, high fat intake and low fruit and vegetable intake, smoking). The aim of this study is to investigate the effects of a multifaceted, multidisciplinary electronic prevention programme on cardiovascular risk factors.</p> <p>Methods/Design</p> <p>In a randomized controlled trial, one group will receive a maximal intervention (= intervention group). The intervention group will be compared to the control group receiving a minimal intervention. An inclusion of 350 patients in total, with a follow-up of 3 years is foreseen. The inclusion criteria are age between 25–65 and insured by the Onderlinge Ziekenkas, insuring for guaranteed income in case of illness for self-employed. The maximal intervention group receives several prevention consultations by their general practitioner (GP) using a new type of cardiovascular risk calculator with personalised feedback on behavioural risk factors. These patients receive a follow-up with intensive support of health behaviour change via different methods, i.e. a tailored website and personal advice of a multidisciplinary team (psychologist, physiotherapist and dietician). The aim of this strategy is to reduce cardiovascular risk factors according to the guidelines. The primary outcome measures will be cardiovascular risk factors. The secondary outcome measures are cardiovascular events, quality of life, costs and incremental cost effectiveness ratios. The control group receives prevention consultations using a new type of cardiovascular risk calculator and general feedback.</p> <p>Discussion</p> <p>This trial incorporates interventions by GPs and other health professionals aiming at a reduction of medical and behavioural cardiovascular risk factors. An assessment of clinical, psychological and economical outcome measures will be performed.</p> <p>Trial registration</p> <p>ISRCTN23940498</p

Low HDL Cholesterol, Smoking and IL-13 R130Q Polymorphism are Associated with Myocardial Infarction in Greek Cypriot Males. A Pilot Study

This study was carried out in Greek Cypriot males to identify risk factors that predispose to myocardial infarction (MI). Genetic and lipid risk factors were investigated for the first time in a Greek Cypriot male case-control study.Contrary to other studies, mean low density lipoprotein cholesterol did not differ between cases and controls. High density lipoprotein cholesterol on the other hand, although within normal range in cases and controls, was significantly higher in the control population. In agreement with many other studies, smoking was significantly more prevalent in cases compared with controls. In pooled cases and controls, smokers had a significantly lower HDL-C level compared with non-smokers. The frequency of the IL-13 R130Q homozygotes for the mutation (QQ), as well as the mutant allele were significantly higher in cases compared with controls. The IL-13 R130Q variant, or another locus, linked to it, may increase the risk of MI

Small Cash Rewards for Big Losers Experimental Insights into the Fight Against the Obesity Epidemic

We complement the empirical evidence on the sustainability of weight loss achieved through cash rewards and, for the first time, rigorously examine the potential of cash rewards to prevent weight cycling. In a three period randomized controlled trial, about 700 obese persons were first assigned to two treatment groups, which were promised cash contingent on the achievement of an individually assigned target weight, and to a control group. Successful participants were subsequently allocated to two treatment groups offered cash rewards for confirming the previously achieved target weight and to a control group. This is the first experiment of this kind that finds effects of weight loss rewards up to 18 months after they were removed. Additional rewards only significantly improve the sustainability of weight loss while they are in place.Die empirische Analyse untersucht zum einen die Nachhaltigkeit einer Gewichtsreduktion, die mittels Geldanreizen erzielt wurde, und zum anderen die Wirksamkeit von Geldanreizen zur Verhinderung des Jo-Jo-Effekts nach einer erfolgreichen Gewichtsreduktion. In einem drei-phasigen Feldexperiment wurden ca. 700 fettleibige Teilnehmer zunächst zufällig auf zwei Anreizgruppen und einer Kontrollgruppe verteilt. Unabhängig von der Gruppenzugehörigkeit sollten ein individuelles Gewichtsreduktionziel erreicht werden, wobei nur Mitglieder der Anreizgruppen eine Geldprämie für das Erreichen des Zieles erhalten konnten. Erfolgreiche Teilnehmer wurden danach erneut zufällig einer Kontrollgruppe und zwei Anreizgruppen zugewiesen, wobei das Halten des Zielgewichts nur für letztere durch eine Geldprämie inzentiviert wurde. Anders als in früheren Experimenten, können Effekt der Abnehmprämie selbst 18 Monate nach ihrem Auslaufen nachgewiesen werden. Monetäre Anreize zur Verhinderung des Jo-Jo-Effekt wirken hingegen nicht über ihr Auslaufen hinaus

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P &lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Effectiveness of two intensive treatment methods for smoking cessation and relapse prevention in patients with coronary heart disease: study protocol and baseline description

Contains fulltext : 111068.pdf (publisher's version ) (Open Access)BACKGROUND: There is no more effective intervention for secondary prevention of coronary heart disease than smoking cessation. Yet, evidence about the (cost-)effectiveness of smoking cessation treatment methods for cardiac inpatients that also suit nursing practice is scarce. This protocol describes the design of a study on the (cost-)effectiveness of two intensive smoking cessation interventions for hospitalised cardiac patients as well as first results on the inclusion rates and the characteristics of the study population. METHODS/DESIGN: An experimental study design is used in eight cardiac wards of hospitals throughout the Netherlands to assess the (cost-)effectiveness of two intensive smoking cessation counselling methods both combined with nicotine replacement therapy. Randomization is conducted at the ward level (cross-over). Baseline and follow-up measurements after six and 12 months are obtained. Upon admission to the cardiac ward, nurses assess patients' smoking behaviour, ensure a quit advice and subsequently refer patients for either telephone counselling or face-to-face counselling. The counselling interventions have a comparable structure and content but differ in provider and delivery method, and in duration. Both counselling interventions are compared with a control group receiving no additional treatment beyond the usual care. Between December 2009 and June 2011, 245 cardiac patients who smoked prior to hospitalisation were included in the usual care group, 223 in the telephone counselling group and 157 in the face-to-face counselling group. Patients are predominantly male and have a mean age of 57 years. Acute coronary syndrome is the most frequently reported admission diagnosis. The ultimate goal of the study is to assess the effects of the interventions on smoking abstinence and their cost-effectiveness. Telephone counselling is expected to be more (cost-)effective in highly motivated patients and patients with high SES, whereas face-to-face counselling is expected to be more (cost-)effective in less motivated patients and patients with low SES. DISCUSSION: This study examines two intensive smoking cessation interventions for cardiac patients using a multi-centre trial with eight cardiac wards. Although not all eligible patients could be included and the distribution of patients is skewed in the different groups, the results will be able to provide valuable insight into effects and costs of counselling interventions varying in delivery mode and intensity, also concerning subgroups. TRIAL REGISTRATION: Dutch Trial Register NTR2144