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https://www.readbyqxmd.com/read/29920776/nickel-toxicity-in-wood-frog-tadpoles-bioaccumulation-and-sublethal-effects-on-body-condition-food-consumption-activity-and-chemosensory-function
#1
Jaimie L Klemish, Sarah J Bogart, Andreas Luek, Michael J Lannoo, Greg G Pyle
Nickel (Ni) concentrations in aquatic ecosystems can be amplified by anthropogenic activities including resource extraction. Compared to fish and invertebrates, knowledge of Ni toxicity in amphibians is limited, especially for northern species. We examined the effect of Ni on Wood Frog tadpoles (Lithobates sylvaticus), the species with the widest and most northern distribution of any anuran in North America. Wood Frog tadpoles were exposed to a Ni concentration gradient (0.02 to 5.5 mg/L of Ni at 164 mg/L as CaCO3 water hardness) for 8 d and examined for lethality, Ni bioaccumulation, and several sublethal endpoints, including body condition, food consumption, swimming activity, and chemosensory function...
June 19, 2018: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29909004/sglt2-inhibitors-and-the-kidney-effects-and-mechanisms
#2
REVIEW
V Tsimihodimos, T D Filippatos, M S Elisaf
AIMS: Numerous clinical trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors exert a favorable effect on the indices of renal function (albuminuria, glomerular filtration rate decline over time) and the incidence of hard renal endpoints such as renal death or time to initiation of renal replacement therapy. MATERIALS AND METHODS: In this review, we describe in detail the evidence regarding the nephroprotective mechanisms of SGLT2 inhibitors and describe the risk factors that may predispose to the development of acute kidney injury in patients receiving these drugs...
June 6, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29900589/mineral-and-bone-disorders-in-conventional-hemodialysis-challenges-and-solutions
#3
Takayuki Hamano
Despite the advent of cinacalcet and noncalcium-containing phosphate binders, controlling the progression of vascular calcification (VC) is still challenging. Recent reports demonstrate that carbamylation driven by high urea concentration aggravates VC, suggesting the importance of adequate dialysis in retarding its progression. Theoretically, other promising measures include the use of iron-based phosphate binders, vitamin K, and magnesium supplements, which should be investigated in future randomized controlled trials (RCTs), ideally with hard outcomes...
June 13, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29898668/meta-analysis-and-systematic-review-of-intravascular-ultrasound-versus-angiography-guided-drug-eluting-stent-implantation-in-left-main-coronary-disease-in-4592-patients
#4
Yue Wang, Gary S Mintz, Zhichun Gu, Yue Qi, Yue Wang, Mengru Liu, Xiaofan Wu
BACKGROUND: Although several meta-analyses have demonstrated the utility of intravascular ultrasound (IVUS) in guiding drug-eluting stent (DES) implantation compared to angiography-guidance, there has been a dearth of evidence in the left main coronary artery (LMCA) lesion subset. METHODS: We performed a meta-analysis to compare clinical outcomes of IVUS versus conventional angiography guidance during implantation of DES for patients with LMCA disease. Pubmed, Cochrane Library, Embase were searched...
June 14, 2018: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29895722/deleting-death-and-dialysis-conservative-care-of-cardio-vascular-risk-and-kidney-function-loss-in-chronic-kidney-disease-ckd
#5
REVIEW
Raymond Vanholder, Steven Van Laecke, Griet Glorieux, Francis Verbeke, Esmeralda Castillo-Rodriguez, Alberto Ortiz
The uremic syndrome, which is the clinical expression of chronic kidney disease (CKD), is a complex amalgam of accelerated aging and organ dysfunctions, whereby cardio-vascular disease plays a capital role. In this narrative review, we offer a summary of the current conservative (medical) treatment options for cardio-vascular and overall morbidity and mortality risk in CKD. Since the progression of CKD is also associated with a higher cardio-vascular risk, we summarize the interventions that may prevent the progression of CKD as well...
June 12, 2018: Toxins
https://www.readbyqxmd.com/read/29887150/clinical-trials
#6
Simon Mead, Fabrizio Tagliavini
Arguably the most important goal of prion research is the discovery of a safe and effective treatment for the human diseases. The final stages of the pathway to develop a treatment require clinical trials. Choices about how a trial is designed and conducted have a large impact on the chances of success. The gold-standard large randomized double-blind placebo-controlled study, which minimizes sources of bias and has been incredibly successful in other diseases, has been hard to achieve in Creutzfeldt-Jakob disease principally because of the rarity and rapidity of the clinical syndrome...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29865997/combination-of-sglt-2-inhibitors-and-glp-1-receptor-agonists-potential-benefits-in-surrogate-and-hard-endpoints
#7
Michael Doumas, Κonstantinos Imprialos, Konstantinos Stavropoulos, Andromachi Reklou, Alexandros Sachinidis, Vasilios G Athyros
BACKGROUND: The treatment of type 2 diabetes mellitus (T2DM) is complex; only few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. METHODS: The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA)...
June 3, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29747913/complete-revascularization-during-primary-percutaneous-coronary-intervention-reduces-death-and-myocardial-infarction-in-patients-with-multivessel-disease-meta-analysis-and-meta-regression-of-randomized-trials
#8
Vincenzo Pasceri, Giuseppe Patti, Francesco Pelliccia, Carlo Gaudio, Giulio Speciale, Roxana Mehran, George D Dangas
OBJECTIVES: The aim of this study was to compare complete revascularization with a culprit-only strategy in patients presenting with ST-segment elevation myocardial infarction (MI) and multivessel disease by a meta-analysis of randomized trials. BACKGROUND: Although several trials have compared complete with culprit-only revascularization in ST-segment elevation MI, it remains unclear whether complete revascularization may lead to improvement in hard endpoints (death and MI)...
May 14, 2018: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29740199/is-it-possible-to-stop-nucleos-t-ide-analogue-treatment-in-chronic-hepatitis-b-patients
#9
REVIEW
Elia Moreno-Cubero, Robert T Sánchez Del Arco, Julia Peña-Asensio, Eduardo Sanz de Villalobos, Joaquín Míquel, Juan Ramón Larrubia
Chronic hepatitis B (CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue (NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus (HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen (HBsAg), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBsAg loss...
May 7, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29719915/the-average-hazard-ratio-a-good-effect-measure-for-time-to-event-endpoints-when-the-proportional-hazard-assumption-is-violated
#10
Geraldine Rauch, Werner Brannath, Matthias Brückner, Meinhard Kieser
BACKGROUND: In many clinical trial applications, the endpoint of interest corresponds to a time-to-event endpoint. In this case, group differences are usually expressed by the hazard ratio. Group differences are commonly assessed by the logrank test, which is optimal under the proportional hazard assumption. However, there are many situations in which this assumption is violated. Especially in applications were a full population and several subgroups or a composite time-to-first-event endpoint and several components are considered, the proportional hazard assumption usually does not simultaneously hold true for all test problems under investigation...
May 2018: Methods of Information in Medicine
https://www.readbyqxmd.com/read/29707348/cerebral-protection-devices-in-transcatheter-aortic-valve-replacement-a-clinical-meta-analysis-of-randomized-controlled-trials
#11
Nelson Wang, Kevin Phan
Background: Neurological complications after undergoing transcatheter aortic valve replacement (TAVR) may be reduced with cerebral protection (CP) devices. However, randomized controlled trials (RCTs) have failed to demonstrate convincing evidence of improvements in hard clinical endpoints in patients with CP. The aim of this study was to compare clinical outcomes of TAVR patients with and without CP devices. Methods: Electronic searches were performed using four electronic databases from their dates of inception to May 2017...
March 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29704026/the-relation-of-low-levels-of-bone-mineral-density-with-coronary-artery-calcium-and-mortality
#12
N Ahmadi, S S Mao, F Hajsadeghi, B Arnold, S Kiramijyan, Y Gao, F Flores, S Azen, M Budoff
Osteoporosis and atherosclerosis are two prevalent major healthcare concerns that frequently coexist. The clinical outcome of 5590 consecutive subjects who underwent coronary artery calcium (CAC) scanning and thoracic bone mineral density (BMD) measurement was assessed. A significant link between low BMD levels and CAC with increased risk of mortality in both genders across ethnicities noted. INTRODUCTION: While a relation of CAC with lower levels of BMD reported previously; it is unclear whether low levels of BMD would be an independent risk factor for CAC and mortality...
April 27, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29700817/medicine-based-evidence-and-personalized-care-of-patients
#13
Ralph I Horwitz, Mary E Charlson, Burton H Singer
BACKGROUND: For the past 70- years patient care has been dominated by Evidence Based Medicine (EBM) with its emphasis on Randomized Controlled Trials (RCTs) and clinical guidelines to standardize medical decision-making. METHODS: Critical assessment of the literature and analyses of the arguments that favor patient care based primarily on individual variability in disease risk or treatment response versus emphasis on group standardization. RESULTS: Medicine Based Evidence (MBE) is used to guide decision making for an individual patient at hand by profiling the clinical features (biology) and life experience (biography) of the patient and then finding approximate matches to the patient in a clinical library of patients assembled from diverse sources (RCTs, cohorts, registries, electronic health records and more)...
April 27, 2018: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29695512/individual-participant-data-analysis-of-two-trials-on-aldosterone-blockade-in-myocardial-infarction
#14
Farzin Beygui, Eric Van Belle, Patrick Ecollan, Jacques Machecourt, Christian W Hamm, Estaeban Lopez De Sa, Marcus Flather, Freek W A Verheugt, Eric Vicaut, Faiez Zannad, Bertram Pitt, Gilles Montalescot
BACKGROUND: Two recent randomised trials studied the benefit of mineralocorticoid receptor antagonists (MRAs) in ST-segment elevation myocardial infarction (STEMI) irrespective or in absence of heart failure. The studies were both undersized to assess hard clinical endpoints. A pooled analysis was preplanned by the steering committees. METHODS: We conducted a prespecified meta-analysis of patient-level data of patients with STEMI recruited in two multicentre superiority trials, randomised within 72 hours after symptom onset...
April 25, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29659672/adi-peg-20-plus-best-supportive-care-versus-placebo-plus-best-supportive-care-in-patients-with-advanced-hepatocellular-carcinoma
#15
G Abou-Alfa, S Qin, B-Y Ryoo, S-N Lu, C-J Yen, Y-H Feng, H Y Lim, F Izzo, M Colombo, D Sarker, L Bolondi, G Vaccaro, W P Harris, Z Chen, R A Hubner, T Meyer, W Sun, J J Harding, E M Hollywood, J Ma, P J Wan, M Ly, J Bomalaski, A Johnston, C-C Lin, Y Chao, L-T Chen
Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme - arginine deiminase - conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and Patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2:1 to ADI-PEG 20 18 mg/m2 vs...
April 5, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29628378/pegvaliase-for-the-treatment-of-phenylketonuria-a-pivotal-double-blind-randomized-discontinuation-phase-3-clinical-trial
#16
Cary O Harding, R Stephen Amato, Mary Stuy, Nicola Longo, Barbara K Burton, John Posner, Haoling H Weng, Markus Merilainen, Zhonghua Gu, Joy Jiang, Jerry Vockley
INTRODUCTION: Pegvaliase is a recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL) enzyme under investigation for treatment of adult phenylketonuria (PKU). This manuscript describes results of a randomized discontinuation trial (RDT) designed to evaluate the effects of pegvaliase treatment on blood phenylalanine (Phe) and neuropsychiatric outcomes in adults with PKU. METHODS: PRISM-2 is a 4-part, Phase 3 study that enrolled adults with PKU receiving pegvaliase treatment (initiated in a prior Phase 2 or Phase 3 study)...
May 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29627120/attending-diabetes-clinics-is-associated-with-a-lower-all-cause-mortality-a-meta-analysis-of-observational-studies-performed-in-italy
#17
E Bonora, M Monami, G Bruno, G Zoppini, E Mannucci
OBJECTIVE: The epidemiological explosion of diabetes is a challenge for Health Systems and the identification of the most appropriate models of care are warranted. The inclusion of primary care physicians in the models is unquestioned whereas the role played by secondary and tertiary care (Diabetes Clinic) is often debated. However, studies focusing on hard endpoints and comparing Diabetes Clinic attendance vs. no attendance are scant. RESEARCH DESIGN AND METHODS: A meta-analysis was performed including all observational cohort studies performed in Italy, reporting crude and/or adjusted estimates of all-cause mortality in patients with diabetes attending or not attending Diabetes Clinics...
May 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29533391/a-dataset-on-human-navigation-strategies-in-foreign-networked-systems
#18
Attila Kőrösi, Attila Csoma, Gábor Rétvári, Zalán Heszberger, József Bíró, János Tapolcai, István Pelle, Dávid Klajbár, Márton Novák, Valentina Halasi, András Gulyás
Humans are involved in various real-life networked systems. The most obvious examples are social and collaboration networks but the language and the related mental lexicon they use, or the physical map of their territory can also be interpreted as networks. How do they find paths between endpoints in these networks? How do they obtain information about a foreign networked world they find themselves in, how they build mental model for it and how well they succeed in using it? Large, open datasets allowing the exploration of such questions are hard to find...
March 13, 2018: Scientific Data
https://www.readbyqxmd.com/read/29520449/cardiac-ct-in-the-emergency-department-contrasting-evidence-from-registries-and-randomized-controlled-trials
#19
REVIEW
Nam Ju Lee, Harold Litt
PURPOSE OF REVIEW: To compare outcomes between registries and randomized controlled trials of coronary computed tomographic angiography (CCTA)-based versus standard of care approaches to the initial evaluation of patients with acute chest pain. RECENT FINDINGS: Randomized trials have demonstrated CCTA to be a safe and efficient tool for triage of low- to intermediate-risk patients presenting to the emergency department with chest pain. Recent studies demonstrate heterogeneous result using different standard of care approaches for evaluation of hard endpoints in comparison with standard evaluation...
March 8, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29516192/randomized-controlled-trial-of-remote-ischaemic-conditioning-in-st-elevation-myocardial-infarction-as-adjuvant-to-primary-angioplasty-ric-stemi
#20
António Gaspar, André P Lourenço, Miguel Álvares Pereira, Pedro Azevedo, Roberto Roncon-Albuquerque, Jorge Marques, Adelino F Leite-Moreira
To test whether remote ischaemic conditioning (RIC) as adjuvant to standard of care (SOC) would prevent progression towards heart failure (HF) after ST-elevation myocardial infarction (STEMI). Single-centre parallel 1:1 randomized trial (computerized block-randomization, concealed allocation) to assess superiority of RIC (3 cycles of intermittent 5 min lower limb ischaemia) over SOC in consecutive STEMI patients (NCT02313961, clinical trials.gov). From 258 patients randomized to RIC or SOC, 9 and 4% were excluded because of unconfirmed diagnosis and previously unrecognized exclusion criteria, respectively...
March 7, 2018: Basic Research in Cardiology
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