Encyclopedia of Caves is a self-contained, beautifully illustrated work dedicated to caves and their unique environments. It includes more than 100 comprehensive articles from leading scholars and ...explorers in 15 different countries. Each entry is detailed and scientifically sound, yet accessible for students and non-scientists. This large-format reference is enchanced with hundreds of full-color photographs, maps, and drawings from the authors' own work, which provide unique images of the underground environment.
Global in reach--authors are an international team of experts covering caves from around the worldIncludes 24 new articles commissioned especially for this 2nd edition Articles contain extensive bibliographies cross-referencing related essaysHundreds of color photographs, maps, charts and illustrations of cave features and biotaA-Z sequence and a comprehensive index allow for easy location of topics Glossary presents definitions of all key vocabulary items
The accurate measurement of blood pressure (BP) is essential for the diagnosis and management of hypertension. This article provides an updated American Heart Association scientific statement on BP ...measurement in humans. In the office setting, many oscillometric devices have been validated that allow accurate BP measurement while reducing human errors associated with the auscultatory approach. Fully automated oscillometric devices capable of taking multiple readings even without an observer being present may provide a more accurate measurement of BP than auscultation. Studies have shown substantial differences in BP when measured outside versus in the office setting. Ambulatory BP monitoring is considered the reference standard for out-of-office BP assessment, with home BP monitoring being an alternative when ambulatory BP monitoring is not available or tolerated. Compared with their counterparts with sustained normotension (ie, nonhypertensive BP levels in and outside the office setting), it is unclear whether adults with white-coat hypertension (ie, hypertensive BP levels in the office but not outside the office) have increased cardiovascular disease risk, whereas those with masked hypertension (ie, hypertensive BP levels outside the office but not in the office) are at substantially increased risk. In addition, high nighttime BP on ambulatory BP monitoring is associated with increased cardiovascular disease risk. Both oscillometric and auscultatory methods are considered acceptable for measuring BP in children and adolescents. Regardless of the method used to measure BP, initial and ongoing training of technicians and healthcare providers and the use of validated and calibrated devices are critical for obtaining accurate BP measurements.
Patients with gout and cardiovascular disease were assigned to receive febuxostat or allopurinol. At 32 months, there was no significant between-group difference in a composite cardiovascular end ...point, but all-cause and cardiovascular mortality were higher with febuxostat.
Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be ...restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension.
In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enrolled participants aged 18 years and older with chronic kidney disease (estimated glomerular filtration rate 25 to ≤45 mL/min per 1·73 m2) and uncontrolled resistant hypertension from 62 outpatient centres in ten countries (Bulgaria, Croatia, Georgia, Hungary, Ukraine, France, Germany, South Africa, the UK, and the USA). Patients meeting all eligibility criteria at the final screening visit were stratified by local serum potassium measurement (4·3 to <4·7 mmol/L vs 4·7 to 5·1 mmol/L) and history of diabetes. Participants were randomly assigned (1:1) with an interactive web response system to receive either placebo or patiromer (8·4 g once daily), in addition to open-label spironolactone (starting at 25 mg once daily) and their baseline blood pressure medications. Participants, the study team that administered treatments and measured blood pressure, and the investigators were masked to assigned treatment groups. Dose titrations were permitted after 1 week (patiromer) and 3 weeks (spironolactone). The primary endpoint was the between-group difference at week 12 in the proportion of patients on spironolactone. Efficacy endpoints and safety were assessed in all randomised patients (intention to treat). The study was registered with Clinicaltrials.gov, NCT03071263.
Between Feb 13, 2017, and Aug 20, 2018, we screened 574 patients. 295 (51%) of 574 patients met all inclusion criteria and were randomly assigned to spironolactone in addition to double-blind treatment with either placebo (n=148) or patiromer (n=147). At week 12, 98 (66%) of 148 patients in the placebo group and 126 (86%) of 147 patients in the patiromer group remained on spironolactone (between-group difference 19·5%, 95% CI 10·0–29·0; p<0·0001). Adverse events were mostly mild or moderate in severity and occurred in 79 (53%) of 148 patients in the placebo group and 82 (56%) of 147 patients in the patiromer group.
In patients with resistant hypertension and chronic kidney disease, patiromer enabled more patients to continue treatment with spironolactone with less hyperkalaemia. Persistent spironolactone enablement in this population of patients has clinical relevance for the treatment of resistant hypertension.
Relypsa, a Vifor Pharma Group Company.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a new class of antihyperglycemic agents that block renal sodium and glucose reabsorption and may reduce blood pressure (BP). We assessed ...the BP lowering ability of these agents using meta-analytic techniques. PubMed, SCOPUS, and Cochrane Central were searched through October 2013. We included fully published randomized controlled trials (RCTs) that evaluated SGLT2 inhibitors in patients with type-2 diabetes mellitus and reported change in systolic and/or diastolic BP. Subgroup analyses were performed for placebo-controlled trials and those with active controls. We also conducted meta-regression to assess for a dose-response effect, and whether baseline BP, changes in body weight, heart rate, and hematocrit were associated with the BP effects. Twenty-seven RCTs (n = 12,960 participants) were included. SGLT2 inhibitors significantly reduced both systolic BP (weighted mean difference, -4.0 mm Hg; 95% confidence interval, -4.4 to -3.5) and diastolic BP (weighted mean difference, -1.6 mm Hg; 95% confidence interval, -1.9 to -1.3) from baseline. Only canagliflozin had a significant dose-response relationship with SBP (P = .008). Significant reductions in body weight and hematocrit were seen with the SGLTs. SGLTs had no significant effect on the incidence of orthostatic hypotension (P > .05). SGLT2 inhibitors significantly reduce BP in patients with type 2 diabetes.
Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium ...channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. The antihypertensive drugs should be administered at maximum or maximally tolerated daily doses. RH also includes patients whose BP achieves target values on ≥4 antihypertensive medications. The diagnosis of RH requires assurance of antihypertensive medication adherence and exclusion of the “white-coat effect” (office BP above goal but out-of-office BP at or below target). The importance of RH is underscored by the associated risk of adverse outcomes compared with non-RH. This article is an updated American Heart Association scientific statement on the detection, evaluation, and management of RH. Once antihypertensive medication adherence is confirmed and out-of-office BP recordings exclude a white-coat effect, evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. If BP remains uncontrolled, referral to a hypertension specialist is advised.
Nonsteroidal mineralocorticoid receptor antagonists (MRAs) are a new class of drugs developed to address the medical need for effective and safer treatment to protect the kidney and the heart in ...patients with diabetic kidney disease (DKD). There are several drugs within this class at varying stages of clinical development. Finerenone is the first nonsteroidal MRA approved in the US for treating patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). In clinical studies, finerenone slowed CKD progression without inducing marked antihypertensive effects. Esaxerenone is a nonsteroidal MRA with proven blood pressure-lowering efficacy that is currently licensed in Japan for treating hypertension. There are also three other nonsteroidal MRAs in mid-to-late stages of clinical development. Here we overview evidence addressing pharmacological and clinical differences between the nonsteroidal MRAs and the steroidal MRAs spironolactone and eplerenone. First, we describe a framework that highlights the role of aldosterone-mediated pathological overactivation of the mineralocorticoid receptor and inflammation as important drivers of CKD progression. Second, we discuss the benefits and adverse events profile of steroidal MRAs, the latter of which are often a limiting factor to their use in routine clinical practice. Finally, we show that nonsteroidal MRAs differ from steroidal MRAs based on pharmacology and clinical effects, giving the potential to expand the therapeutic options for patients with DKD. In the recently completed DKD outcome program comprising two randomized clinical trials - FIDELIO-DKD and FIGARO-DKD - and the FIDELITY analysis of both trials evaluating more than 13,000 patients, the nonsteroidal MRA finerenone demonstrated beneficial effects on the kidney and the heart across a broad spectrum of patients with CKD and T2D. The long-term efficacy of finerenone on cardiac and renal morbidity and mortality endpoints, along with the anti-hypertensive efficacy of esaxerenone, widens the scope of available therapies for patients with DKD.
This review discusses a group of drugs called mineralocorticoid receptor antagonists (MRAs for short). Some people with diabetes develop kidney and heart problems because their body is producing too much steroid hormone. This causes a protein called the mineralocorticoid receptor inside kidney and heart cells to be overactive, causing excessive inflammation and damage. Over time these excesses can lead to loss of organ function. MRAs can block this effect on the mineralocorticoid receptor and so reduce associated kidney and heart problems. Older types of MRAs called steroidal MRAs have been used clinically for many years. They have side effects such as high blood potassium levels. Nonsteroidal MRAs are a newer type of MRA. Finerenone is the first nonsteroidal MRA approved by the United States' Food and Drug Administration for reducing kidney and heart damage in people with diabetic kidney disease. Two clinical studies involving more than 13,000 people with Diabetic Kidney Disease have completed. People in these studies who took finerenone had slower worsening of kidney disease and less heart and blood vessel damage compared with people who did not take finerenone (took placebo). Finerenone also has a lower risk of causing side effects compared with steroidal MRAs. Another type of nonsteroidal MRA is esaxerenone, which is currently only available in Japan. Other types of nonsteroidal MRAs are going through clinical trials so are not available for use yet. See Supplementary Figure 1 for an infographic version of this summary.
All national guidelines for the management of hypertension recommend angiotensin receptor blockers (ARBs) as an initial or add-on antihypertensive therapy. The eight available ARBs have variable ...clinical efficacy when used for control of hypertension. Additive blood pressure-lowering effects have been demonstrated when ARBs are combined with thiazide diuretics or dihydropyridine calcium channel blockers, augmenting hypertension control. Furthermore, therapeutic use of ARBs goes beyond their antihypertensive effects, with evidence-based benefits in heart failure and diabetic renal disease particularly among angiotensin-converting enzyme inhibitor-intolerant patients. On the other hand, combining renin-angiotensin system blocking agents, a formerly common practice among medical subspecialists focusing on the management of hypertension, has ceased, as there is not only no evidence of cardiovascular benefit but also modest evidence of harm, particularly with regard to renal dysfunction. ARBs are very well tolerated as monotherapy, as well as in combination with other antihypertensive medications, which improve adherence to therapy and have become a mainstay in the treatment of stage 1 and stage 2 hypertension.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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