Diuretics: a contemporary pharmacological classification?
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ABSTRACT:
SUBMITTER: Kehrenberg MCA
PROVIDER: S-EPMC9072265 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsTo assess whether meeting both fasting plasma glucose (FPG) and HbA1c criteria for prediabetes in people at high risk indicates with near certainty the presence of dysglycemia on repeat testing.MethodsObservational study using data from Vitamin D and Type 2 Diabetes (D2d) study. HbA1c, FPG were measured at screening visit 1; FPG, HbA1c and 2 h plasma glucose (2hPG) measured at screening visit 2 (a median of 21 days later); participants classified as having normal glucose regulation (all 3 tests in normal range), prediabetes or diabetes (at least 1 of 3 tests in diabetes range). A predictive model was developed to estimate the probability of confirming dysglycemia and for detecting diabetes at screening visit 2 based on values of FPG and HbA1c at screening visit 1.ResultsOf 1271 participants who met both FPG and HbA1c criteria for prediabetes at screening visit 1, 98.6% exhibited dysglycemia (defined as prediabetes or diabetes) on repeat testing (84.5% were classified as having prediabetes, 14.1% were reclassified as having diabetes). Of those with diabetes, 62.6% were identified by 2hPG alone.ConclusionsCombined measurement of FPG and HbA1c is a reliable and reproducible measure to identify presence of dysglycemia among people at high risk. A prediction model is provided to help clinicians decide whether an oral glucose tolerance test will provide value in detecting diabetes based on the 2hPG criterion.
| S-EPMC7424833 | biostudies-literature
Project description:Eosinophilia is an important indicator of various neoplastic and nonneoplastic conditions. Depending on the underlying disease and mechanisms, eosinophil infiltration can lead to organ dysfunction, clinical symptoms, or both. During the past 2 decades, several different classifications of eosinophilic disorders and related syndromes have been proposed in various fields of medicine. Although criteria and definitions are, in part, overlapping, no global consensus has been presented to date. The Year 2011 Working Conference on Eosinophil Disorders and Syndromes was organized to update and refine the criteria and definitions for eosinophilic disorders and to merge prior classifications in a contemporary multidisciplinary schema. A panel of experts from the fields of immunology, allergy, hematology, and pathology contributed to this project. The expert group agreed on unifying terminologies and criteria and a classification that delineates various forms of hypereosinophilia, including primary and secondary variants based on specific hematologic and immunologic conditions, and various forms of the hypereosinophilic syndrome. For patients in whom no underlying disease or hypereosinophilic syndrome is found, the term hypereosinophilia of undetermined significance is introduced. The proposed novel criteria, definitions, and terminologies should assist in daily practice, as well as in the preparation and conduct of clinical trials.
| S-EPMC4091810 | biostudies-literature
Project description:BackgroundCurrent femoral bone loss classification systems in revision total hip arthroplasty were created at a time when the predominant reconstructive methods used cylindrical porous-coated cobalt-chrome stems. As these stems have largely been replaced by fluted-tapered titanium stems, the ability of these classification systems to help guide implant selection is limited. The purpose of this study was to describe a novel classification system based on contemporary reconstructive techniques.MethodsWe reviewed the charts of all patients who underwent femoral component revision at our institution from 2007 through 2019. Preoperative images were reviewed, and FBL was rated according to the Paprosky classification and compared to ratings using our institution's NCS. Rates of reoperation at the time of most recent follow-up were determined and compared.ResultsFour-hundred and forty-two femoral revisions in 330 patients with a mean follow-up duration of 2.7 years were identified. Femoral type according to Paprosky and NCS were Paprosky I (36, 8.1%), II (61, 13.8%), IIIA (180, 40.7%), IIIB (116, 26.2%), and IV (49 11.1%) and NCS 1 (35, 7.9%), 2 (364, 82.4%), 3 (8, 1.8%), 4 (27, 6.1%), and 5 (8, 1.8%). Of the 353 nonstaged rTHAs, there were 42 cases requiring unplanned reoperation (11.9%), including infection (18, 5.1%), instability (10, 2.8%), femoral loosening (5, 1.4%), and various other causes (9, 2.5%). The NCS was more predictive of reoperation than the Paprosky classification (Fisher's exact test, P = .008 vs P = ns, respectively).ConclusionWe present a novel femoral classification system that can help guide contemporary implant selection.
| S-EPMC8233101 | biostudies-literature
Project description:Background: The concept of Clinical Scenario (CS) classification has been widely utilized to aid in choosing appropriate management strategies for acute decompensated heart failure (ADHF). Methods and Results: The West Tokyo-Heart Failure (WET-HF) Registry is a multicenter, prospective cohort registry enrolling consecutive hospitalized ADHF patients. Based on systolic blood pressure (SBP) at admission, 4,000 patients enrolled between 2006 and 2017 were classified into 3 groups: CS1, SBP ≥140 mmHg; CS2, 100≤SBP<140 mmHg; and CS3, SBP <100 mmHg. The CS1 group had a high rate of fluid retention such as leg edema, and the largest reduction in body weight at discharge. In-hospital diuretics use was the most frequent in CS1. Although the primary endpoint of long-term all-cause death and/or ADHF re-hospitalization was more common in more advanced CS, there was no significant difference between the 3 CS groups in patients with HF with preserved ejection fraction (HFpEF; P=0.10). Although more advanced CS was associated with larger left ventricular (LV) chamber size in HF with reduced EF (HFrEF), it was associated with smaller LV size in HFpEF. Conclusions: The long-term prognostic value of CS classification was limited in HFpEF. Whereas CS was closely associated with degree of LV remodeling in HFrEF, a smaller LV chamber might be associated with a lower cardiovascular functional reserve in HFpEF.
| S-EPMC7889455 | biostudies-literature
Project description:Contemporary guidelines on thoracic aortic repair provide inconsistent reporting standards for the definition of aortic arch classification in Types I, II and III. The different reported criteria cannot be used interchangeably, due to a very low level of concordance, and this finding has relevant implications for the comparisons between studies using different classifications, and between different datasets of multicentre trials, which are not consistently analyzed with the same criteria. Also, the reported definitions, which were originally proposed for predicting difficult carotid stenting and therefore were conceived for healthy aortic arches, can be influenced by the pathological derangements of the aortic wall, including aneurysms and dissections. In this respect, the Madhwal's classification, which is based on the diameter of the left common carotid artery, appears to be the more suitable one for aortic arch classification in patients with thoracic aortic disease because it provides relevant clinical information along with an adequate reproducibility.
| S-EPMC8691520 | biostudies-literature
Project description:BackgroundTransient tachypnoea of the newborn (TTN) results from delayed clearance of lung liquid and is a common cause of admission of full-term infants to neonatal intensive care units. The condition is particularly common after elective caesarean section. Conventional treatment involves appropriate oxygen administration and continuous positive airway pressure in some cases. Most infants receive antibiotic therapy. Hastening the clearance of lung liquid may shorten the duration of the symptoms and reduce complications.ObjectivesTo determine whether diuretic administration reduces the duration of oxygen therapy and respiratory symptoms and shortens hospital stay in term infants presenting with transient tachypnoea of the newborn.Search methodsAn updated search was carried out in September 2015 of the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 9, 2015), MEDLINE via Ovid, EMBASE, PubMed, and CINAHL via OVID.Selection criteriaWe included randomised and quasi-randomised controlled trials that compared the effect of diuretics administration versus placebo or no treatment in infants of less than seven days of age, born at 37 or more weeks of gestation with the clinical picture of transient tachypnoea of the newborn.Data collection and analysisWe extracted and analysed data according to the methods outlined in the latest Cochrane Handbook for Systematic Reviews of Interventions. Two review authors assessed trial quality in each potentially eligible manuscript and two review authors extracted data.Main resultsOur previous systematic review included two trials enrolling a total of 100 infants with transient tachypnoea of the newborn (Wiswell 1985; Karabayir 2006). The updated search revealed no new trials. Wiswell 1985 randomised 50 infants to receive either oral furosemide (2 mg/kg body weight at time of diagnosis followed by a 1 mg/kg dose 12 hours later if the tachypnoea persisted) or placebo. Karabayir 2006 randomised 50 infants to receive either intravenous furosemide (2 mg/kg body weight) or an equal volume of normal saline placebo. Neither trial reported on the need for respiratory support. Neither trial demonstrated a statistically significant impact of furosemide on transient tachypnoea of the newborn regarding duration of symptoms or length of hospitalisation.Authors' conclusionsDiuretics cannot be recommended as treatment for transient tachypnoea of the newborn and it should not be used unless additional data become available. This finding suggests that either furosemide is not effective in promoting resorption of lung fluid, or factors other than delayed resorption of this fluid contribute to the pathogenesis of transient tachypnoea of the newborn. The question remains as to whether furosemide given to the infant (or even to the mother before caesarean section) might shorten the duration of the illness. As elective caesarean section continues at a high level, these two interventions might be worthy of trials.
| S-EPMC7144734 | biostudies-literature
Project description:Sleep-wake states are impaired in various neurological disorders. Impairment of sleep-wake states can be an early condition that exacerbates these disorders. Therefore, treating sleep-wake dysfunction may prevent or slow the development of these diseases. Although many gene products are likely to be involved in the sleep-wake disturbance, hypnotics and psychostimulants clinically used are limited in terms of their mode of action and are not without side effects. Therefore, there is a growing demand for developing new hypnotics and psychostimulants with high efficacy and few side effects. Toward this end, animal models are indispensable for use in genetic and chemical screens to identify sleep-wake modifiers. As a proof-of-concept study, we performed behavioral profiling of zebrafish treated with chemical and genetic sleep-wake modifiers. We were able to demonstrate that behavioral profiling of zebrafish treated with hypnotics or psychostimulants from 9 to 10 days post-fertilization was sufficient to identify drugs with specific modes of action. We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants. This behavioral profiling can serve to identify genes related to sleep-wake disturbance associated with various neuropsychiatric diseases and novel therapeutic compounds for insomnia and excessive daytime sleep with fewer adverse side effects.
| S-EPMC4630575 | biostudies-literature
Project description:Conventional diuretics such as furosemide and thiazides target salt transporters in kidney tubules, but urea transporters (UTs) have emerged as alternative targets. UTs are a family of transmembrane channels expressed in a variety of mammalian tissues, in particular the kidney. UT knockout mice and humans with UT mutations exhibit reduced maximal urinary osmolality, demonstrating that UTs are necessary for the concentration of urine. Small-molecule screening has identified potent and selective inhibitors of UT-A, the UT protein expressed in renal tubule epithelial cells, and UT-B, the UT protein expressed in vasa recta endothelial cells. Data from UT knockout mice and from rodents administered UT inhibitors support the diuretic action of UT inhibition. The kidney-specific expression of UT-A1, together with high selectivity of the small-molecule inhibitors, means that off-target effects of such small-molecule drugs should be minimal. This Review summarizes the structure, expression and function of UTs, and looks at the evidence supporting the validity of UTs as targets for the development of salt-sparing diuretics with a unique mechanism of action. UT-targeted inhibitors may be useful alone or in combination with conventional diuretics for therapy of various oedemas and hyponatraemias, potentially including those refractory to treatment with current diuretics.
| S-EPMC4743986 | biostudies-literature
Project description:Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Often the syndrome is characterized by congestion, and is associated with long hospital admissions and high risk of readmission and further healthcare expenditure. Despite a limited evidence-base, diuretics remain the first-line treatment for congestion. Loop diuretics are typically the first-line diuretic strategy with some evidence that initial treatment with continuous infusion or boluses of high-dose loop diuretic is superior to an initial lower dose strategy. In patients who have impaired responsiveness to diuretics, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. The use of intravenous low-dose dopamine is no longer supported in heart failure patients with preserved systolic blood pressure and its use to assist diuresis in patients with low systolic blood pressures requires further study. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence-base is not robust, and its place in clinical practice is yet to be established. Several novel pharmacological agents remain under investigation.
| S-EPMC4824339 | biostudies-literature
Project description:BackgroundCellular senescence, a state of stable growth arrest, is intertwined with human cancers. However, characterization of cellular senescence-associated phenotypes in hepatocellular carcinoma (HCC) remains unexplored.AimTo address this issue, we delineated cellular senescence landscape across HCC.MethodsWe enrolled two HCC datasets, TCGA-LIHC and International Cancer Genome Consortium (ICGC). Unsupervised clustering was executed to probe tumor heterogeneity based upon cellular senescence genes. Least absolute shrinkage and selection operator algorithm were utilized to define a cellular senescence-relevant scoring system. TRNP1 expression was measured in HCCs and normal tissues through immunohistochemistry, immunoblotting and quantitative real-time polymerase chain reaction. The influence of TMF-regulated nuclear protein (TRNP)1 on HCC senescence and growth was proven via a series of experiments.ResultsTCGA-LIHC patients were classified as three cellular senescence subtypes, named C1-3. The robustness and reproducibility of these subtypes were proven in the ICGC cohort. C2 had the worst overall survival, C1 the next, and C3 the best. C2 presented the highest levels of immune checkpoints, abundance of immune cells, and immunogenetic indicators. Thus, C2 might possibly respond to immunotherapy. C2 had the lowest somatic mutation rate, while C1 presented the highest copy number variations. A cellular senescence-relevant gene signature was generated, which can predict patient survival, and chemo- or immunotherapeutic response. Experimentally, it was proven that TRNP1 presented the remarkable upregulation in HCCs. TRNP1 knockdown induced apoptosis and senescence of HCC cells and attenuated tumor growth.ConclusionThese findings provide a systematic framework for assessing cellular senescence in HCC, which decode the tumor heterogeneity and tailor the pharmacological interventions to improve clinical management.
| S-EPMC10514726 | biostudies-literature