Comparing sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors on new-onset depression: a propensity score-matched study in Hong Kong.

The risk of new onset depression associated with sodium-glucose co-transporter 2 inhibitor (SGLT2I) use in patients with type 2 diabetes mellitus (T2DM) remains unclear. This study investigated the risk of new onset depression between SGLT2I and dipeptidyl peptidase 4 inhibitor (DPP4I) users. This was a population-based cohort study of T2DM patients in Hong Kong between January 1st, 2015, and December 31st, 2019. T2DM patients over 18 with either SGLT2I or DPP4I use were included. 1:1 propensity-score matching using the nearest-neighbour method was conducted based on demographics, past comorbidities and non-DPP4I/SGLT2I medication use. Cox regression analysis models were used to identify significant predictors for new onset depression. The study cohort included a total of 18,309 SGLT2I users and 37,269 DPP4I users (55.57% male, mean age: 63.5 ± 12.9 years) with a median follow-up duration of 5.56 (IQR: 5.23-5.8) years. After propensity score matching, SGLT2I use was associated with a lower risk of new onset depression compared to DPP4I use (HR: 0.52, 95% CI: [0.35, 0.77], P = 0.0011). These findings were confirmed by Cox multivariable analysis and sensitive analyses. SGLT2I use is associated with significantly lower risk of depression compared to DPP4 use in T2DM patients using propensity score matching and Cox regression analyses. [Abstract copyright: © 2023. The Author(s).

Combinations of bleeding and ischemic risk and their association with clinical outcomes in acute coronary syndrome.

Background: Clinical predictors of future ischemic events in patients with acute coronary syndrome (ACS) are also risk factors for bleeding, with patients often at high-risk of both outcomes. We aimed to define the clinical outcomes and provision of guideline-recommended care in ACS management for different combinations of ischemic and bleeding risk defined using a combined GRACE and CRUSADE score.Methods: A retrospective observational analysis of a national ACS database was performed for patients with ACS admitted to three tertiary centres from January 2010 to March 2016. Patients were stratified into 9 groups based on possible CRUSADE-GRACE risk combinations. Multiple logistic regression was used to estimate adjusted odds ratios (ORs [95% CI]) for outcomes (in-hospital net adverse cardiac events (NACE), in-hospital all-cause mortality, 30-day mortality and treatment strategy).Results: A total of 17,701 patients were included in the analysis. We observed a graded risk of mortality and adverse events in the high-risk GRACE strata (Groups 3, 6 and 9). Almost a third of patients with ACS were at a ‘dual high-risk’ (Group 9, 32%) and were independently associated with higher in-hospital NACE (composite of cardiac mortality, all-cause bleeding and re-infarction): aOR 6.33 [3.55, 11.29], all-cause mortality: aOR 14.17 [5.27, 38.1], all-cause bleeding: aOR 4.82 [1.96, 11.86], and 30-day mortality: aOR 10.79 [5.33, 21.81]. This group was also the least likely to be offered coronary angiography (aOR 0.24 [0.20, 0.29]) and dual anti-platelet therapy (aOR 0.26 [0.20, 0.34]). Conclusions: One in five patients presenting with an ACS are high ischemic and high bleeding risk, and these patients are more likely to experience poor clinical outcomes and reduced odds of receiving guideline-recommended therapy. <br/

Pharmacological Undertreatment of Coronary Risk Factors in Patients with Psoriasis: Observational Study of the Danish Nationwide Registries

BACKGROUND: Patients with psoriasis have increased prevalence of coronary risk factors and limited recent results have suggested that these risk factors are undertreated in patients with psoriasis. This may contribute to the increased risk of cardiovascular diseases observed in patients with psoriasis. OBJECTIVE: To examine the pharmacological treatment of coronary risk factors in patients with severe psoriasis treated with biologic agents in a real-world setting. METHODS AND FINDINGS: Medical history of patients with severe psoriasis treated with biologic agents in the time period 2007-09 was retrieved from a Danish nationwide registry (DERMBIO). Individual-level linkage of nationwide administrative registries of hospitalizations, concomitant medications, and socioeconomic status was performed to gain insights into the use of pharmacological treatment. A total of 693 patients (mean age 46.1 ± 12.7 years, 65.7% male) with severe psoriasis treated with biologic agents were identified. Hypertension, hypercholesterolemia, and diabetes mellitus were identified in 16.6%, 9.2%, and 6.7% of cases, respectively. Patients with severe psoriasis were significantly less likely to receive cardiovascular pharmacotherapy compared to age, sex, and coronary risk factor matched controls. In psoriatic patients with hypertension 27.7% received no antihypertensive pharmacotherapy. Patients with dyslipidemia received cholesterol-lowering medications in 55.8% of cases and patients with diabetes mellitus received angiotensin converting enzyme inhibitors/angiotensin II receptor blockers and cholesterol-lowering medications in 42.1% and 23.7% of cases, respectively. Similar results were found for the subset of patients with >1 coronary risk factor and for high risk patients with established atherosclerotic disease. CONCLUSION: This nationwide study of patients with severe psoriasis demonstrated substantial undertreatment of coronary risk factors. Increased focus on identifying cardiovascular risk factors and initiation of preventive cardiovascular pharmacotherapy in patients with psoriasis is warranted

Corruption Kills: Estimating the Global Impact of Corruption on Children Deaths

BACKGROUND: Information on the global risk factors of children mortality is crucial to guide global efforts to improve survival. Corruption has been previously shown to significantly impact on child mortality. However no recent quantification of its current impact is available. METHODS: The impact of corruption was assessed through crude Pearson's correlation, univariate and multivariate linear models coupling national under-five mortality rates in 2008 to the national "perceived level of corruption" (CPI) and a large set of adjustment variables measured during the same period. FINDINGS: The final multivariable model (adjusted R(2)= 0.89) included the following significant variables: percentage of people with improved sanitation (p.value<0.001), logarithm of total health expenditure (p.value = 0.006), Corruption Perception Index (p.value<0.001), presence of an arid climate on the national territory (p = 0.006), and the dependency ratio (p.value<0.001). A decrease in CPI of one point (i.e. a more important perceived corruption) was associated with an increase in the log of national under-five mortality rate of 0.0644. According to this result, it could be roughly hypothesized that more than 140000 annual children deaths could be indirectly attributed to corruption. INTERPRETATIONS: Global response to children mortality must involve a necessary increase in funds available to develop water and sanitation access and purchase new methods for prevention, management, and treatment of major diseases drawing the global pattern of children deaths. However without paying regard to the anti-corruption mechanisms needed to ensure their proper use, it will also provide further opportunity for corruption. Policies and interventions supported by governments and donors must integrate initiatives that recognise how they are inter-related

Prospects for beyond the Standard Model physics searches at the Deep Underground Neutrino Experiment: DUNE Collaboration

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach

Volume III. DUNE far detector technical coordination

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay-these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- A nd dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay-these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- A nd dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Supernova neutrino burst detection with the deep underground neutrino experiment: DUNE Collaboration

The deep underground neutrino experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE’s ability to constrain the νe spectral parameters of the neutrino burst will be considered

Long-baseline neutrino oscillation physics potential of the DUNE experiment: DUNE Collaboration

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all δCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all δCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin 22 θ13 to current reactor experiments