The risk of type 2-diabetes among persons with intellectual disability: a Danish population-based matched cohort study.

Background: Previous research shows that obesity, unhealthy eating, physical inactivity and a high use of psychotropic medications are prevalent among persons with intellectual disability (ID), which might increase the risk of type 2-diabetes (T2DM). This study aims to investigate: (1) whether persons with ID have an increased risk of T2DM compared with an age- and sex-matched reference group and (2) differences in T2DM risk by sex, birth year, ID inclusion diagnosis and ID severity.

Methods: This study is a nationwide cohort study, including 65 293 persons with ID and 659 723 persons in an age- and sex-matched reference group without ID.

Predicting the Long-Term Effects of Therapeutic Neutralization of Oncostatin M on Human Hematopoiesis.

Therapeutic neutralization of Oncostatin M (OSM) causes mechanism-driven anemia and thrombocytopenia, which narrows the therapeutic window complicating the selection of doses (and dosing intervals) that optimize efficacy and safety. We utilized clinical data from studies of an anti-OSM monoclonal antibody (GSK2330811) in healthy volunteers (n = 49) and systemic sclerosis patients (n = 35), to quantitatively determine the link between OSM and alterations in red blood cell (RBC) and platelet production. Longitudinal changes in hematopoietic variables (including RBCs, reticulocytes, platelets, erythropoietin, and thrombopoietin) were linked in a physiology-based model, to capture the long-term effects and variability of therapeutic OSM neutralization on human hematopoiesis.

Validation of the de Morton mobility index (DEMMI) among acute stroke patients aged ≥65 years: a register study.

Purpose: To validate the de Morton Mobility Index DEMMI) in older (≥65 years) patients with acute stroke in a hospital setting within the first week after stroke onset.

Materials And Methods: In the Danish National Database of Geriatrics, we identified 4,176 patients with acute stroke (≥65 years). Floor and ceiling effects of DEMMI were investigated.

Loneliness and the risk of type 2 diabetes.

Introduction: The incidence of type 2 diabetes is increasing globally. Recent research suggests that loneliness could be a potential risk factor for the development of type 2 diabetes. We aimed to investigate the association between loneliness and type 2 diabetes and the modifying effect of mental disorders.

The De Morton Mobility Index (DEMMI) in hospitalized geriatric patients is associated with risk of readmission, mortality, and discharge to a post-acute care facility: A nationwide register-based cohort study.

Objective: To examine the association between the de Morton Mobility Index (DEMMI) score on admission in geriatric patients and readmission and mortality within 30, 180, and 365 days after discharge, and discharge to a post-acute care facility.

Methods: A nationwide register-based cohort study including 23,941 geriatric in-patients aged ≥65 years admitted to a geriatric ward between 2014 and 2017 and included in the Danish National Database for Geriatrics. The DEMMI score was categorized into four subcategories: very low mobility (DEMMI=0-24), low mobility (DEMMI=27-39), moderately reduced mobility (DEMMI=41-57), and independent mobility (DEMMI=62-100).

Educational outcomes and the role of comorbidity among adolescents with type 1-diabetes in Denmark.

Aims: To examine educational outcomes among adolescents with type 1 diabetes and determine the role of comorbidity.

Methods: We conducted a nationwide register-based cohort study including 3370 individuals born between 1991 and 2003 and diagnosed with type 1 diabetes before the age of 16. They were all matched with up to four individuals without type 1 diabetes on age, gender, parents' educational level and immigration status.

Diabetic complications and risk of depression and anxiety among adults with type 2 diabetes.

Aims: To investigate if diabetic complications increase the risk of depression and/or anxiety among adults with type 2 diabetes.

Methods: This register-based, prospective study included 265,799 adult individuals diagnosed with type 2 diabetes between 1997 and 2017 without a recent history of depression or anxiety. Diabetic complications included cardiovascular disease, amputation of lower extremities, neuropathy, nephropathy and retinopathy.

Model-based assessment of neutrophil-mediated phagocytosis and digestion of bacteria across in vitro and in vivo studies.

Neutrophil granulocytes are key components of the host response against pathogens, and severe neutropenia, with neutrophil counts below 0.5 × 10 cells/mL, renders patients increasingly vulnerable to infections. Published in vitro (n = 7) and in vivo (n = 5) studies with time-course information on bacterial and neutrophil counts were digitized to characterize the kinetics of neutrophil-mediated bacterial killing and inform on the immune systems' contribution to the clearance of bacterial infections.

Symptoms in the acute phase of SARS-CoV-2 infection among Danish children aged 0-14 years.

Objectives: To investigate the prevalence and burden of proxy-reported acute symptoms in children in the first 4 weeks after detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, and factors associated with symptom burden.

Methods: Nationwide cross-sectional survey using parental proxy reporting of symptoms associated with SARS-CoV-2 infection. In July 2021, a survey was sent to the mothers of all Danish children aged 0-14 years with a positive SARS-CoV-2 polymerase chain reaction (PCR) test between January 2020 and July 2021.

Risk of body weight changes among Danish children and adolescents during the COVID-19 pandemic.

Background: Knowledge of COVID-19 and the pandemic's effects on Danish children's body weight is limited.

Objective: Objectives were to investigate (I) risk of weight changes among Danish children with and without SARS-CoV-2, (II) associations between weight changes, psychological symptoms, and long COVID symptoms, and (III) weight distribution pre- and post-pandemic.

Methods: A national survey was administered to all Danish children aged 0-18 years, with prior COVID-19 (cases) and matched references including questions on weight, weight changes during the pandemic and long COVID-related symptoms.

Population Pharmacokinetics of Flucloxacillin In Bone and Soft Tissue- Standard Dosing is Not Sufficient to Achieve Therapeutic Concentrations.

Purpose: Flucloxacillin is a β-lactam penicillin commonly used in the treatment of bone and soft tissue infections. In a recent porcine study, we found surprisingly low time for which the free concentration was maintained above the minimal inhibitory concentration (fT>MIC) in bone and soft tissue, following flucloxacillin oral (PO) and intravenous (IV) administration at 1g every 6h (q6h). In addition to plasma, sampling was obtained from subcutaneous tissue, knee joint, cancellous bone and cortical bone, using microdialysis.

Continuous infusion of piperacillin-tazobactam significantly improves target attainment in children with cancer and fever.

Background: Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β-lactam concentrations.

Aims: This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin-tazobactam, in order to optimize the dosing regimen.

Methods: This prospective PK study included children with cancer, aged 1-17 years, who were treated with piperacillin-tazobactam for suspected or verified infection.

The Danish National Youth Study 2019: study design and participant characteristics.

Aim: To present the study design, study population and questionnaire content of the Danish National Youth Study 2019, and to describe the differences between participants and non-participants regarding demographic and socioeconomic characteristics.

Method: The Danish National Youth Study 2019 is a nationwide web-survey among high school students in Denmark. Data was collected from January to April 2019 through a self-administered questionnaire in the classroom.

Antibiotic use in pre-school children and the correlation with adult educational levels in two Nordic counties: a replication of a 20-year-old study.

Objective: The aim of this study was to describe the change of antibiotic prescribing in pre-school children in the municipalities of the former Copenhagen County in Denmark and Skåne County in Sweden after 20 years of antibiotic stewardship effort. Furthermore, the variation in the prescribing of antibiotics between the municipalities and the correlation between municipal adult educational level and antibiotic prescribing in pre-school children was assessed.

Methods: In this ecological study, information on antibiotic prescribing in pre-school children was obtained from a central pharmacy settlement system in each Region.

Pharmacodynamics of immune response biomarkers of interest for evaluation of treatment effects in bacterial infections.

This mini-review discusses the pharmacodynamics of immune-related biomarkers in the area of bacterial infectious diseases that could be of interest from a pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) perspective in the evaluation of treatment effects. The host response to an infection is often poorly defined both in preclinical assessments and in clinical practice when it comes to characterisation of PK and PK/PD relationships. Through population modelling, the time courses and variability of immune response variables can be quantified.

Population Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target Attainment.

Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations ( = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1).

Extension of Pharmacokinetic/Pharmacodynamic Time-Kill Studies To Include Lipopolysaccharide/Endotoxin Release from Escherichia coli Exposed to Cefuroxime.

The release of inflammatory bacterial products, such as lipopolysaccharide (LPS)/endotoxin, may be increased upon the administration of antibiotics. An improved quantitative understanding of endotoxin release and its relation to antibiotic exposure and bacterial growth/killing may be gained by an integrated analysis of these processes. The aim of this work was to establish a mathematical model that relates growth/killing dynamics at various cefuroxime concentrations to endotoxin release Fifty-two time-kill experiments informed bacterial and endotoxin time courses and included both static (0×, 0.

Population pharmacokinetics of piperacillin in plasma and subcutaneous tissue in patients on continuous renal replacement therapy.

Objectives: Piperacillin is a β-lactam antimicrobial frequently used in critically ill patients with acute kidney injury treated with continuous renal replacement therapy (CRRT). However, data regarding piperacillin tissue concentrations in this patient population are limited. A prospective observational study was conducted of free piperacillin concentrations during a single 8-h dosing interval in plasma (8 samples) and subcutaneous tissue (SCT) (13 samples), in 10 patients treated with CRRT following piperacillin 4 g given every 8 h as intermittent administration over 3 min.

Antibiotic-prescribing and antibiotic-resistance patterns among elderly citizens residing in two Nordic regions.

The objective of this study was to compare antibiotic-prescribing rates in 2016 and antibiotic-resistance rates in 2017 among citizens aged ≥85 years between the Capital Region in Denmark and the Skåne Region in Sweden, with regards to overall antibiotic use and antibiotics of choice for urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inhabitants ≥85 year old on the date of prescription during 2016 and residing in the Capital Region or the Skåne Region were included for antibiotic-prescription analyses. Samples from 2017 from residents of the same regions who were ≥85 years old were included for antibiotic-resistance analyses.

Birth weight for gestational age and the risk of infertility: a Danish cohort study.

Study Question: Is birth weight for gestational age associated with infertility in adulthood among men and women?

Summary Answer: Being born small for gestational age (SGA) was associated with infertility in adulthood among men.

What Is Known Already: Fetal growth restriction may affect fertility, but results from previous studies have been inconsistent.

Study Design, Size, Duration: In this population-based cohort study, we used data from a Danish birth cohort, including 5594 men and 5342 women born between 1984 and 1987.

Population pharmacokinetics of piperacillin in febrile children receiving cancer chemotherapy: the impact of body weight and target on an optimal dosing regimen.

Background: The β-lactam antibiotic piperacillin (in combination with tazobactam) is commonly chosen for empirical treatment of suspected bacterial infections. However, pharmacokinetic variability among patient populations and across ages leads to uncertainty when selecting a dosing regimen to achieve an appropriate pharmacodynamic target.

Objectives: To guide dosing by establishing a population pharmacokinetic model for unbound piperacillin in febrile children receiving cancer chemotherapy, and to assess pharmacokinetic/pharmacodynamic target attainment (100% fT > 1×MIC and 50% fT > 4×MIC) and resultant exposure, across body weights.

A non-linear mixed effect model for innate immune response: In vivo kinetics of endotoxin and its induction of the cytokines tumor necrosis factor alpha and interleukin-6.

Endotoxin, a component of the outer membrane of Gram-negative bacteria, has been extensively studied as a stimulator of the innate immune response. However, the temporal aspects and exposure-response relationship of endotoxin and resulting cytokine induction and tolerance development is less well defined. The aim of this work was to establish an in silico model that simultaneously captures and connects the in vivo time-courses of endotoxin, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and associated tolerance development.