The search for optimal blood pressure control in type 2 diabetes mellitus: have we found the holy grail?
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ABSTRACT:
SUBMITTER: Verbraecken J
PROVIDER: S-EPMC8041107 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC6543727 | biostudies-literature
Project description:Inadequate pain management but also inappropriate use of analgesics in early infancy has negative effects on neurodevelopmental outcome. As a consequence, neonatal pain management is still in search for the Holy Grail. At best, effective pain management is based on prevention, assessment, and treatment followed by a re-assessment of the pain to determine if additional treatment is still necessary. Unfortunately, epidemiological observations suggest that neonates are undergoing painful procedures very frequently, unveiling the need for effective preventive, non-pharmacological strategies. In addition, assessment is still based on validated, multimodal, but subjective pain assessment tools. Finally, in neonatal intensive care units, there is a shift in clinical practices (e.g., shorter intubation and ventilation), and this necessitates the development and validation of new pharmacological treatment modalities. To illustrate this, a shift in the use of opioids to paracetamol has occurred and short-acting agents (remifentanil, propofol) are more commonly administered to neonates. In addition to these new modalities and as part of a more advanced approach of the developmental pharmacology of analgesics, pharmacogenetics also emerged as a tool for precision medicine in neonates. To assure further improvement of neonatal pain management the integration of pharmacogenetics with the usual covariates like weight, age and/or disease characteristics is needed.
| S-EPMC5012190 | biostudies-other
Project description:The terms microparticles (MPs) and microvesicles (MVs) refer to large extracellular vesicles (EVs) generated from a broad spectrum of cells upon its activation or death by apoptosis. The unique surface antigens of MPs/MVs allow for the identification of their cellular origin as well as its functional characterization. Two basic aspects of MP/MV functions in physiology and pathological conditions are widely considered. Firstly, it has become evident that large EVs have strong procoagulant properties. Secondly, experimental and clinical studies have shown that MPs/MVs play a crucial role in the pathophysiology of inflammation-associated disorders. A cardinal feature of these disorders is an enhanced generation of platelets-, endothelial-, and leukocyte-derived EVs. Nevertheless, anti-inflammatory effects of miscellaneous EV types have also been described, which provided important new insights into the large EV-inflammation axis. Advances in understanding the biology of MPs/MVs have led to the preparation of this review article aimed at discussing the association between large EVs and inflammation, depending on their cellular origin.
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Project description: Not available
| S-EPMC7656358 | biostudies-literature
Project description:BackgroundThere is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.MethodsA total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.ResultsAfter 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P=0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P=0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001).ConclusionsIn patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.)
| S-EPMC4123215 | biostudies-literature
Project description:BackgroundThe search for an accurate, gene-based test to identify heritable risk factors for Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published studies about the role of dopamine in addictive behaviors, including risk for drug dependence and compulsive/impulsive behavior disorders. The term RDS was first coined by Blum's group in 1995 to identify a group of behaviors with a common neurobiological mechanism associated with a polymorphic allelic propensity for hypodopaminergia.ObjectivesTo outline the process used to select risk alleles of reward genes for the Genetic Addiction Risk Score (GARS) test. Consequently, to address the limitations caused by inconsistent results that occur in many case-control behavioral association studies. These limitations are perhaps due to the failure of investigators to adequately screen controls for drug and alcohol use disorder, and any of the many RDS behaviors, including nicotine dependence, obesity, pathological gambling, and internet gaming addiction.MethodsReview of the literature related to the function of risk alleles of reward genes associated with hypodopaminergia relevant case-control association studies for the selection of alleles to be measured by the Genetic Addiction Risk Score (GARS) test.ResultsThe prevalence of the DRD2 A1 allele in unscreened controls (33.3%), compared to "Super-Controls" [highly screened RDS controls (3.3%) in proband and family] is used to exemplify a possible solution.ConclusionUnlike one gene-one disease (OGOD), RDS is polygenetic, and very complex. In addition, any RDS-related behaviors must be eliminated from the control group in order to obtain the best possible statistical analysis instead of comparing the phenotype with disease-ridden controls.
| S-EPMC7236426 | biostudies-literature
Project description:A 3-dimensional, robust, and sustained myocardial restoration by means of tissue engineering remains an experimental approach. Prolific protocols have been developed and tested in small and large animals, but, as clinical cardiac surgeons, we have not arrived at the privilege of utilizing any of them in our clinical practice. The question arises as to why this is. The heart is a unique organ, anatomically and functionally. It is not an easy target to replicate with current techniques, or even to support in its viability and function. Currently, available therapies fail to reverse the loss of functional cardiac tissue, the fundamental pathology remains unaddressed, and heart transplantation is an ultima ratio treatment option. Owing to the equivocal results of cell-based therapies, several strategies have been pursued to overcome the limitations of the current treatment options. Preclinical data, as well as first-in-human studies, conducted to-date have provided important insights into the understanding of injection-based approaches for myocardial restoration. In light of the available data, injectable biomaterials suitable for transcatheter delivery appear to have the highest translational potential. This article presents a current state-of-the-literature review in the field of hydrogel-based myocardial restoration therapy.
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Project description:RAS GTPases (H-, K-, and N-RAS) are the most frequently mutated oncoprotein family in human cancer. However, the relatively smooth surface architecture of RAS and its picomolar affinity for nucleotide have given rise to the assumption that RAS is an "undruggable" target. Recent advancements in drug screening, molecular modeling, and a greater understanding of RAS function have led to a resurgence in efforts to pharmacologically target this challenging foe. This review focuses on the state of the art of RAS inhibition, the approaches taken to achieve this goal, and the challenges of translating these discoveries into viable therapeutics.
| S-EPMC6258355 | biostudies-literature
Project description:At present, there is no cure for asthma, and treatment typically involves therapies that prevent or reduce asthma symptoms, without modifying the underlying disease. A "disease-modifying" treatment can be classed as able to address the pathogenesis of a disease, preventing progression or leading to a long-term reduction in symptoms. Such therapies have been investigated and approved in other indications, e.g. rheumatoid arthritis and immunoglobulin E-mediated allergic disease. Asthma's heterogeneous nature has made the discovery of similar therapies in asthma more difficult, although novel therapies (e.g. biologics) may have the potential to exhibit disease-modifying properties. To investigate the disease-modifying potential of a treatment, study design considerations can be made, including: appropriate end-point selection, length of trial, age of study population (key differences between adults/children in physiology, pathology and drug metabolism) and comorbidities in the patient population. Potential future focus areas for disease-modifying treatments in asthma include early assessments (e.g. to detect patterns of remodelling) and interventions for patients genetically susceptible to asthma, interventions to prevent virally induced asthma and therapies to promote a healthy microbiome. This review explores the pathophysiology of asthma, the disease-modifying potential of current asthma therapies and the direction future research may take to achieve full disease remission or prevention.
| S-EPMC9488532 | biostudies-literature
Project description:Background The association between blood pressure (BP) control and incident diabetes mellitus remains unknown. We aim to investigate the association between degree of time-averaged on-treatment systolic blood pressure (SBP) control and incident diabetes mellitus in hypertensive adults. Methods and Results A total of 14 978 adults with hypertension without diabetes mellitus at baseline were included from the CSPPT (China Stroke Primary Prevention Trial). Participants were randomized double-masked to daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. BP measurements were taken every 3 months after randomization. The primary outcome was incident diabetes mellitus, defined as physician-diagnosed diabetes mellitus, or use of glucose-lowering drugs during follow-up, or fasting glucose ≥126 mg/dL at the exit visit. Over a median of 4.5 years, a significantly higher risk of incident diabetes mellitus was found in participants with time-averaged on-treatment SBP 130 to <140 mm Hg (10.3% versus 7.4%; odds ratio [OR], 1.37; 95% CI, 1.15‒1.64), compared with those with SBP 120 to <130 mm Hg. Moreover, the risk of incident diabetes mellitus increased by 24% (OR, 1.24; 95% CI, 1.00‒1.53) and the incidence of regression to normal fasting glucose (<100 mg/dL) decreased by 29% (OR, 0.71; 95% CI, 0.57‒0.89) in participants with intermediate BP control (SBP/diastolic blood pressure, 130 to <140 and/or 80 to <90 mm Hg), compared with those with a tight BP control of <130/<80 mm Hg. Similar results were found when the time-averaged BP were calculated using the BP measurements during the first 6- or 24-month treatment period, or in the analysis using propensity scores. Conclusions In this non-diabetic, hypertensive population, SBP control in the range of 120 to <130 mm Hg, compared with the 130 to <140 mm Hg, was associated with a lower risk of incident diabetes mellitus.
| S-EPMC7660809 | biostudies-literature