Towards development of core domain sets for short term and long term studies of calcium pyrophosphate crystal deposition (CPPD) disease: A framework paper by the OMERACT CPPD working group.

Introduction: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets.

Methods: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study.

Improved Survival Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Treated With Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study.

Background: There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone.

Methods: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied.

Direct small molecule ADaM-site AMPK activators reveal an AMPKγ3-independent mechanism for blood glucose lowering.

Objective: Skeletal muscle is an attractive target for blood glucose-lowering pharmacological interventions. Oral dosing of small molecule direct pan-activators of AMPK that bind to the allosteric drug and metabolite (ADaM) site, lowers blood glucose through effects in skeletal muscle. The molecular mechanisms responsible for this effect are not described in detail.

Drug-related challenges following primary total hip and knee arthroplasty.

We aimed to characterize the in-hospital analgesic use among total hip or knee arthroplasty (THA or TKA) patients, and to identify possible drug-related challenges. We identified 15 263 patients operated with a THA or TKA between 1 January 2012 and 30 April 2016. The prevalence of analgesic users and patients with potential clinically relevant drug-drug interactions (DDIs), along with the prevalence of readmission among patients with vs.

Postprandial amino acid availability after intake of intact or hydrolyzed meat protein in a mixed meal in healthy elderly subjects: a randomized, single blind crossover trial.

The absorption of dietary proteins affects the anabolic response, among others protein synthesis. For elderly, optimal amino acid absorption is warranted to preserve the amino acid pool of the body, especially skeletal muscle proteins. Therefore, the aim of this study was to characterize if hydrolyzing meat protein (HMP) would improve the amino acid absorption after ingestion of meat compared to equal amounts of the same meat proteins but present in a different structure; steak or minced meat.

Experience and impact of crystal pyrophosphate deposition (CPPD) from a patient and caregiver perspective: A qualitative exploration from the OMERACT CPPD working group.

Objective: To explore the lived experience of people with calcium pyrophosphate deposition (CPPD) disease and the impact of this condition on their daily lives.

Methods: Patients with CPPD and their caregivers were invited to take part in a one-to-one (patient only) or paired (patient and caregiver) semi-structured interview. Interviews covered patients' diagnosis and treatment experiences, and the impact of CPPD on their daily lives.

Outcome domains reported by patients, caregivers, healthcare professionals and stakeholders for calcium pyrophosphate deposition (CPPD): A content analysis based on semi-structured qualitative interviews from the OMERACT CPPD working group.

Introduction: Although calcium pyrophosphate deposition (CPPD) disease is common, there are no validated outcome measures for clinical research in this condition. The aim of this study was to generate a list of outcome domains as reported by patients, their caregivers, healthcare professionals (HCPs) and stakeholders to inform the development of an Outcome Measures in Rheumatology (OMERACT) Core Domain Set for CPPD.

Methods: Patients with CPPD and their caregivers, HCPs and stakeholders took part in semi-structured qualitative interviews to explore potential outcome domains for CPPD clinical research relevant to their lived experience and knowledge of CPPD.

Increased oral sodium chloride intake in humans amplifies selectively postprandial GLP-1 but not GIP, CCK, and gastrin in plasma.

Human studies have demonstrated that physiologically relevant changes in circulating glucagon-like peptide-1 (GLP-1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g.

Association Between Fexofenadine Use During Pregnancy and Fetal Outcomes.

Importance: Fexofenadine hydrochloride is a frequently used drug for treatment of allergic conditions during pregnancy, but the fetal safety of fexofenadine use has not been well studied.

Objective: To investigate the risk of adverse fetal outcomes associated with fexofenadine use during pregnancy.

Design, Setting, And Participants: A nationwide registry-based cohort study was conducted on pregnancies in Denmark from January 1, 2001, to December 31, 2016.

Outcome of concomitant treatment with thiopurines and allopurinol in patients with inflammatory bowel disease: A nationwide Danish cohort study.

Background: Thiopurine and allopurinol in combination are associated with clinical remission in inflammatory bowel diseases but their influence on subsequent outcomes is unclear. We compared outcomes during exposure to both thiopurines and allopurinol versus thiopurines alone.

Methods: We established a nationwide cohort of patients with inflammatory bowel diseases exposed to thiopurines ± allopurinol during 1999-2014, using registry data.

Desloratadine Use During Pregnancy and Risk of Adverse Fetal Outcomes: A Nationwide Cohort Study.

Background: Desloratadine is a frequently used drug for the treatment of allergic disorders, which often also require treatment during pregnancy. However, information on the fetal safety of desloratadine use during pregnancy is limited.

Objective: To investigate the association between desloratadine use during pregnancy and adverse fetal outcomes.

Imaging markers of small vessel disease and brain frailty, and outcomes in acute stroke.

Objective: To assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.

Methods: ENOS randomized 4,011 patients with acute stroke (<48 hours of onset) to transdermal glyceryl trinitrate (GTN) or no GTN for 7 days. The primary outcome was functional outcome (modified Rankin Scale [mRS] score) at day 90.

Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome, and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage.

Background and Purpose- Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage. Methods- The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage.

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.

Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants.

Diurnal Variation of Markers for Cholesterol Synthesis, Cholesterol Absorption, and Bile Acid Synthesis: A Systematic Review and the Bispebjerg Study of Diurnal Variations.

Human studies have shown diurnal rhythms of cholesterol and bile acid synthesis, but a better understanding of the role of the circadian system in cholesterol homeostasis is needed for the development of targeted interventions to improve metabolic health. Therefore, we performed a systematic literature search on the diurnal rhythms of cholesterol synthesis and absorption markers and of bile acid synthesis markers. We also examined the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and of the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg study.

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility.

The impact of human CES1 genetic variation on enzyme activity assessed by ritalinic acid/methylphenidate ratios.

The present clinical trial investigated the impact of selected SNPs in CES1 on the metabolic activity of the enzyme. For this purpose, we used methylphenidate (MPH) as a pharmacological probe and the d-RA/d-MPH (metabolite/parent drug) ratios as a measure of enzymatic activity. This metabolic ratio (MR) was validated against the AUC ratios (AUC /AUC ).

The effect of structured personal care on RNA oxidation: A 19-year follow-up of the randomized trial Diabetes Care in General Practice (DCGP).

Aims: The urinary marker of RNA oxidation, 8‑oxo‑7,8‑dihydroguanosine (8-oxoGuo), but not the corresponding marker of DNA oxidation, 8‑oxo‑7,8‑dihydro‑2'‑deoxyguanosine (8-oxodG), is a prognostic biomarker in patients with type 2 diabetes (T2D). The aim of the present study was to investigate the effect of structured personal care (individualized multifactorial treatment) versus standard care on RNA oxidation level in patients with T2D and to assess if the effect of structured personal care on all-cause and diabetes-related mortality was modified by RNA oxidation level.

Methods: Urine samples were analyzed for 8-oxoGuo/8-oxodG from 1381 newly diagnosed T2D patients from the cluster randomized trial Diabetes Care in General Practice cohort, and 970 patients were reexamined after six years of intervention.

RNA oxidation and iron levels in patients with diabetes.

Aim: The urinary biomarker for oxidative stress to RNA, 8-oxo-7,8-dihydro-guanosine (8-oxoGuo) is associated with mortality in patients with type 2 diabetes. Iron has also been linked to diabetes. In individuals with untreated hereditary iron overload it has been observed that 8-oxoGuo was higher compared to controls.

Indicator of RNA oxidation in urine for the prediction of mortality in patients with type 2 diabetes and microalbuminuria: A post-hoc analysis of the Steno-2 trial.

Objective: The RNA oxidation product, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), has been associated with mortality in patients with type 2 diabetes (T2D). However, the identification and the potential effect of approved treatments decreasing urine 8-oxoGuo level remain unraveled. In the Steno-2 study intensified multifactorial treatment compared with conventional multifactorial treatment reduced mortality in T2D patients with microalbuminuria by 45%.

Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness - An autopsy-based study.

Elevated systemic oxidative stress levels of 8-oxoGuo and 8-oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8-oxoGuo and 8-oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy-based material to elucidate this aspect. Additionally, we investigated the impact of 8-oxoGuo and 8-oxodG levels on the prevalence of somatic co-morbidities.

BMI at school age and incident asthma admissions in early adulthood: a prospective study of 310,211 children.

Background: Excess body weight in adulthood is associated with risk for asthma admission (AA). Our aim was to investigate if this association also applies to the relation between body mass index (BMI) in childhood and AAs in early adulthood (age 20-45 years).

Methods: This was a prospective study of 310,211 schoolchildren (born 1930-1989) from the Copenhagen School Health Records Register.