Psychotropic drug use following venous thromboembolism versus diabetes mellitus in adolescence or young adulthood: A Danish nationwide cohort study

© Author(s) (or their employer(s)) 2018. Objectives Critical and chronic illness in youth such as diabetes can lead to impaired mental health. Despite the potentially traumatic and life-Threatening nature of venous thromboembolism (VTE), the long-Term mental health of adolescents and young adults with VTE is unclear. We compared the long-Term mental health of adolescents and young adults with VTE versus adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) using psychotropic drug purchase as proxy for mental health. Design Nationwide registry-based cohort study. Setting Denmark 1997-2015. Participants All patients aged 13-33 years with an incident diagnosis of VTE (n=5065) or IDDM (n=6609). Exposure First time primary hospital diagnosis of VTE or IDDM. Primary and secondary outcome measures Adjusted absolute risk and risk difference at 1 and 5 years follow-up for first psychotropic drug purchase comparing patients with VTE and patients with IDDM. Results The absolute 1 year risk of psychotropic drug use was 6.2% among VTE patients versus 3.6% among patients with IDDM, at 5 years this was 19.3%-14.7%, respectively. After adjusting for the effect of sex, age and risk factors for VTE this corresponded to a 1 year risk differences of 1.9% (95 % CI 0.1% to 3.3%). At 5 years follow-up the risk difference was 1.9% (95% CI 0.5% to 3.3%). Conclusion One-fifth of adolescents and young adults with incident VTE had claimed a prescription for a psychotropic drug within 5 years, a risk comparable to that of young patients with IDDM

Speaking Up for Fundamental Care: the ILC Aalborg Statement.

OBJECTIVE: The International Learning Collaborative (ILC) is an organisation dedicated to understanding why fundamental care, the care required by all patients regardless of clinical condition, fails to be provided in healthcare systems globally. At its 11th annual meeting in 2019, nursing leaders from 11 countries, together with patient representatives, confirmed that patients' fundamental care needs are still being ignored and nurses are still afraid to 'speak up' when these care failures occur. While the ILC's efforts over the past decade have led to increased recognition of the importance of fundamental care, it is not enough. To generate practical, sustainable solutions, we need to substantially rethink fundamental care and its contribution to patient outcomes and experiences, staff well-being, safety and quality, and the economic viability of healthcare systems. KEY ARGUMENTS: We present five propositions for radically transforming fundamental care delivery:Value: fundamental care must be foundational to all caring activities, systems and institutionsTalk: fundamental care must be explicitly articulated in all caring activities, systems and institutions.Do: fundamental care must be explicitly actioned and evaluated in all caring activities, systems and institutions.Own: fundamental care must be owned by each individual who delivers care, works in a system that is responsible for care or works in an institution whose mission is to deliver care. RESEARCH: fundamental care must undergo systematic and high-quality investigations to generate the evidence needed to inform care practices and shape health systems and education curricula. CONCLUSION: For radical transformation within health systems globally, we must move beyond nursing and ensure all members of the healthcare team-educators, students, consumers, clinicians, leaders, researchers, policy-makers and politicians-value, talk, do, own and research fundamental care. It is only through coordinated, collaborative effort that we will, and must, achieve real change

Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids

Khat (Catha edulis Forsk.) is a flowering perennial shrub cultivated for its neurostimulant properties resulting mainly from the occurrence of (S)-cathinone in young leaves. The biosynthesis of (S)-cathinone and the related phenylpropylamino alkaloids (1S,2S)-cathine and (1R,2S)-norephedrine is not well characterized in plants. We prepared a cDNA library from young khat leaves and sequenced 4,896 random clones, generating an expressed sequence tag (EST) library of 3,293 unigenes. Putative functions were assigned to > 98% of the ESTs, providing a key resource for gene discovery. Candidates potentially involved at various stages of phenylpropylamino alkaloid biosynthesis from L-phenylalanine to (1S,2S)-cathine were identified

Incidence Rates and Risk Factors of Clostridioides difficile Infection in Solid Organ and Hematopoietic Stem Cell Transplant Recipients

BACKGROUND: Transplant recipients are an immunologically vulnerable patient group and are at elevated risk of Clostridioides difficile infection (CDI) compared with other hospitalized populations. However, risk factors for CDI post-transplant are not fully understood. // METHODS: Adults undergoing solid organ (SOT) and hematopoietic stem cell transplant (HSCT) from January 2010 to February 2017 at Rigshospitalet, University of Copenhagen, Denmark, were retrospectively included. Using nationwide data capture of all CDI cases, the incidence and risk factors of CDI were assessed. // RESULTS: A total of 1687 patients underwent SOT or HSCT (1114 and 573, respectively), with a median follow-up time (interquartile range) of 1.95 (0.52–4.11) years. CDI was diagnosed in 15% (164) and 20% (114) of the SOT and HSCT recipients, respectively. CDI rates were highest in the 30 days post-transplant for both SOT and HSCT (adjusted incidence rate ratio [aIRR], 6.64; 95% confidence interval [CI], 4.37–10.10; and aIRR, 2.85; 95% CI, 1.83–4.43, respectively, compared with 31–180 days). For SOT recipients, pretransplant CDI and liver and lung transplant were associated with a higher risk of CDI in the first 30 days post-transplant, whereas age and liver transplant were risk factors in the later period. Among HSCT recipients, myeloablative conditioning and a higher Charlson Comorbidity Index were associated with a higher risk of CDI in the early period but not in the late period. // CONCLUSIONS: Using nationwide data, we show a high incidence of CDI among transplant recipients. Importantly, we also find that risk factors can vary relative to time post-transplant

Speaking up for Fundamental Care: The ILC Aalborg Statement

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjective The International Learning Collaborative (ILC) is an organisation dedicated to understanding why fundamental care, the care required by all patients regardless of clinical condition, fails to be provided in healthcare systems globally. At its 11th annual meeting in 2019, nursing leaders from 11 countries, together with patient representatives, confirmed that patients' fundamental care needs are still being ignored and nurses are still afraid to 'speak up' when these care failures occur. While the ILC's efforts over the past decade have led to increased recognition of the importance of fundamental care, it is not enough. To generate practical, sustainable solutions, we need to substantially rethink fundamental care and its contribution to patient outcomes and experiences, staff well-being, safety and quality, and the economic viability of healthcare systems. Key arguments We present five propositions for radically transforming fundamental care delivery: Value: fundamental care must be foundational to all caring activities, systems and institutions Talk: fundamental care must be explicitly articulated in all caring activities, systems and institutions. Do: fundamental care must be explicitly actioned and evaluated in all caring activities, systems and institutions. Own: fundamental care must be owned by each individual who delivers care, works in a system that is responsible for care or works in an institution whose mission is to deliver care. Research: fundamental care must undergo systematic and high-quality investigations to generate the evidence needed to inform care practices and shape health systems and education curricula. Conclusion For radical transformation within health systems globally, we must move beyond nursing and ensure all members of the healthcare team - educators, students, consumers, clinicians, leaders, researchers, policy-makers and politicians - value, talk, do, own and research fundamental care. It is only through coordinated, collaborative effort that we will, and must, achieve real change

Single Nucleotide Polymorphisms in IL1B and the Risk of Acute Coronary Syndrome: A Danish Case-Cohort Study

BACKGROUND: Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary syndrome (ACS) have not been thoroughly investigated. The aims of this study were to examine the associations between individual SNPs in and SNP haplotypes of the promoter region of IL1B and incident ACS in a prospective study. Furthermore, we wanted to explore potential interactions with other risk factors for ACS on an additive scale. METHODOLOGY/PRINCIPAL FINDINGS: The present study was based on the Danish prospective study Diet, Cancer and Health comprising more than 57 000 participants aged 50-64 at baseline. During a median follow-up of 7.2 years we identified 989 cases of incident ACS (755 men and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire cohort. Weighted Cox proportional hazard models with age as time axis were used in the statistical analyses. Individual IL1B SNPs, SNP haplotypes, or haplotype combinations were not significantly associated with incident ACS, and, likewise, we found no evidence of interaction on an additive scale between IL1B haplotypes and risk factors, respectively. CONCLUSIONS/SIGNIFICANCE: Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth

We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20ppm in feed) or Reporcin (recombinant growth hormone; GH; 10mg/48hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p=0.002) and muscle weights (Vastus Lateralis: p<0.001; Semitendinosus: p=0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p<0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p<0.05) and 7 (p<0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p<0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth

Adult Subependymal Neural Precursors, but Not Differentiated Cells, Undergo Rapid Cathodal Migration in the Presence of Direct Current Electric Fields

BACKGROUND: The existence of neural stem and progenitor cells (together termed neural precursor cells) in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. METHODS AND FINDINGS: With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR) signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. CONCLUSIONS: These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma