0
selected
-
1.
The role of Neurochemicals, Stress Hormones and Immune System in the Positive Feedback Loops between Diabetes, Obesity and Depression.
Wilson, JB, Epstein, M, Lopez, B, Brown, AK, Lutfy, K, Friedman, TC
Frontiers in endocrinology. 2023;:1224612
Abstract
Type 2 diabetes mellitus (T2DM) and depression are significant public health and socioeconomic issues. They commonly co-occur, with T2DM occurring in 11.3% of the US population, while depression has a prevalence of about 9%, with higher rates among youths. Approximately 31% of patients with T2DM suffer from depressive symptoms, with 11.4% having major depressive disorders, which is twice as high as the prevalence of depression in patients without T2DM. Additionally, over 80% of people with T2DM are overweight or obese. This review describes how T2DM and depression can enhance one another, using the same molecular pathways, by synergistically altering the brain's structure and function and reducing the reward obtained from eating. In this article, we reviewed the evidence that eating, especially high-caloric foods, stimulates the limbic system, initiating Reward Deficiency Syndrome. Analogous to other addictive behaviors, neurochemical changes in those with depression and/or T2DM are thought to cause individuals to increase their food intake to obtain the same reward leading to binge eating, weight gain and obesity. Treating the symptoms of T2DM, such as lowering HbA1c, without addressing the underlying pathways has little chance of eliminating the disease. Targeting the immune system, stress circuit, melatonin, and other alterations may be more effective.
-
2.
Effects of home confinement on mental health and lifestyle behaviours during the COVID-19 outbreak: insights from the ECLB-COVID19 multicentre study.
Ammar, A, Trabelsi, K, Brach, M, Chtourou, H, Boukhris, O, Masmoudi, L, Bouaziz, B, Bentlage, E, How, D, Ahmed, M, et al
Biology of sport. 2021;38(1):9-21
-
-
-
Free full text
Plain language summary
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the respiratory syndrome coronavirus 2 (SARS-CoV-2). To curb the spread of the 2020 pandemic, social distancing, self-isolation and nationwide lockdown measures were put in place. These measures along with hygiene care are recognized as the most effective ways to curb the spread of disease. However; the weakening of social contacts can result in anxiety, frustration, panic attacks, loss or sudden increase of appetite, insomnia, depression, mood swings, delusions, fear, sleep disorders, and suicidal/domestic violence. The purpose of the study is to provide scientific data to help identify risk factors for the psychosocial strain during the COVID-19 outbreak. The study is an international cross-disciplinary online survey and was circulated in April 2020. 1047 replies were analysed from this preliminary phase. The results show a significant difference in all tested parameters and therefore reveal a large burden for mental wellbeing combined with a tendency towards an unhealthy lifestyle during, compared to before, the confinement enforced by the COVID-19 pandemic. These results highlight the importance for policy makers to consider strategies to promote wellbeing during future confinements.
Abstract
Although recognised as effective measures to curb the spread of the COVID-19 outbreak, social distancing and self-isolation have been suggested to generate a burden throughout the population. To provide scientific data to help identify risk factors for the psychosocial strain during the COVID-19 outbreak, an international cross-disciplinary online survey was circulated in April 2020. This report outlines the mental, emotional and behavioural consequences of COVID-19 home confinement. The ECLB-COVID19 electronic survey was designed by a steering group of multidisciplinary scientists, following a structured review of the literature. The survey was uploaded and shared on the Google online survey platform and was promoted by thirty-five research organizations from Europe, North Africa, Western Asia and the Americas. Questions were presented in a differential format with questions related to responses "before" and "during" the confinement period. 1047 replies (54% women) from Western Asia (36%), North Africa (40%), Europe (21%) and other continents (3%) were analysed. The COVID-19 home confinement evoked a negative effect on mental wellbeing and emotional status (P < 0.001; 0.43 ≤ d ≤ 0.65) with a greater proportion of individuals experiencing psychosocial and emotional disorders (+10% to +16.5%). These psychosocial tolls were associated with unhealthy lifestyle behaviours with a greater proportion of individuals experiencing (i) physical (+15.2%) and social (+71.2%) inactivity, (ii) poor sleep quality (+12.8%), (iii) unhealthy diet behaviours (+10%), and (iv) unemployment (6%). Conversely, participants demonstrated a greater use (+15%) of technology during the confinement period. These findings elucidate the risk of psychosocial strain during the COVID-19 home confinement period and provide a clear remit for the urgent implementation of technology-based intervention to foster an Active and Healthy Confinement Lifestyle AHCL).
-
3.
Resistant Hypertension and the Pivotal Role for Mineralocorticoid Receptor Antagonists: A Clinical Update 2016.
Epstein, M, Duprez, DA
The American journal of medicine. 2016;(7):661-6
Abstract
True resistant hypertension must be distinguished from apparent resistant hypertension, of which important causes include medication nonadherence, illicit drug use, and alcoholism. Ambulatory blood pressure monitoring should be considered to rule out white coat hypertension. The pathogenesis is multifactorial, but the 2 pivotal factors include volume excess and the myriad effects of aldosterone. Aldosterone increases vascular tone because of endothelial dysfunction and enhances the pressor response to catecholamines. It also plays a crucial role in vascular remodeling of small and large arteries. Aldosterone also promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure. Because aldosterone has been demonstrated to modulate baroreflex resetting, in cases of severe hypertension, there would be fewer compensatory mechanisms available to offset the blood pressure elevation.
-
4.
The Unappreciated Role of Extrarenal and Gut Sensors in Modulating Renal Potassium Handling: Implications for Diagnosis of Dyskalemias and Interpreting Clinical Trials.
Epstein, M, Lifschitz, MD
Kidney international reports. 2016;(1):43-56
Abstract
In addition to the classic and well-established "feedback control" of potassium balance, increasing investigative attention has focused on a novel and not widely recognized complementary regulatory paradigm for maintaining potassium homeostasis-the "feed-forward control" of potassium balance. This regulatory mechanism, initially defined in rumen, has recently been validated in normal human subjects. Studies are being conducted to determine the location for this putative potassium sensor and to evaluate potential signals, which might increase renal potassium excretion. Awareness of this more updated integrative control mechanism for potassium homeostasis is ever more relevant today, when the medical community is increasingly focused on the challenges of managing the hyperkalemia provoked by renin-angiotensin-aldosterone system inhibitors (RAASis). Recent studies have demonstrated a wide gap between RAASi prescribing guidelines and real-world experience and have highlighted that this gap is thought to be attributable in great part to hyperkalemia. Consequently we require a greater knowledge of the complexities of the regulatory mechanisms subserving potassium homeostasis. Sodium polystyrene sulfonate has long been the mainstay for treating hyperkalemia, but its administration is fraught with challenges related to patient discomfort and colonic necrosis. The current and imminent availability of newer potassium binders with better tolerability and more predictive dose-response potassium removal should enhance the management of hyperkalemia. Consequently it is essential to better understand the intricacies of mammalian colonic K+ handling. We discuss colonic transport of K+ and review evidence for potassium (BK) channels being responsible for increased stool K+ in patients with diseases such as ulcerative colitis.
-
5.
New approaches to hyperkalemia in patients with indications for renin angiotensin aldosterone inhibitors: Considerations for trial design and regulatory approval.
Zannad, F, Rossignol, P, Stough, WG, Epstein, M, Alonso Garcia, Mde L, Bakris, GL, Butler, J, Kosiborod, M, Berman, L, Mebazaa, A, et al
International journal of cardiology. 2016;:46-51
Abstract
Hyperkalemia is a common clinical problem, especially in patients with chronic kidney disease, diabetes mellitus, or heart failure. Treatment with renin angiotensin aldosterone system inhibitors exacerbates the risk of hyperkalemia in these patients. Concern about hyperkalemia can result in the failure to initiate, suboptimal dosing, or discontinuation of renin angiotensin aldosterone system inhibitor therapy in patients; effective treatments for hyperkalemia might mitigate such undertreatment. New treatments for hyperkalemia in development may offer better efficacy, tolerability and safety profiles than do existing approved treatments. These compounds might enable more eligible patients to receive renin angiotensin aldosterone system inhibitor therapy or to receive renin angiotensin aldosterone system inhibitors at target doses. The evidence needed to support a treatment claim (reduction in serum potassium) differs from that needed to support a prevention claim (preventing hyperkalemia to allow renin angiotensin aldosterone system inhibitor treatment). Thus, several issues related to clinical trial design and drug development need to be considered. This paper summarizes and expands upon a discussion at the Global Cardiovascular Clinical Trialists 2014 Forum and examines methodologic considerations for trials of new potassium binders for the prevention and management of hyperkalemia in patients with renin angiotensin aldosterone system inhibitor indications.
-
6.
Recent advances in pharmacological treatments of hyperkalemia: focus on patiromer.
Epstein, M, Pitt, B
Expert opinion on pharmacotherapy. 2016;(10):1435-48
Abstract
INTRODUCTION Hyperkalemia is a common electrolyte disorder, especially among patients with chronic kidney disease (CKD), diabetes mellitus, or heart failure, and is associated with a significantly increased risk for all-cause mortality. Hyperkalemia remains a vexing and challenging problem for clinicians, particularly in the management of patients with chronic kidney disease and congestive heart failure. Several observational and retrospective studies have reported a large gap between recommendations in guidelines and real-world practice in the implementation of RAASi therapies. RAASi treatment regimens are frequently down-titrated or discontinued following hyperkalemia events, with consequent worse outcomes than patients who remain on maximum doses. AREAS COVERED This review covers the preclinical and clinical studies that led to the approval of patiromer for the treatment of hyperkalemia. A literature search on patiromer was carried out using the PubMed database up to December 2015. EXPERT OPINION Recently, patiromer was approved by the FDA as the first new potassium binder for the treatment of hyperkalemia in over 50 years. Based on the results of phase II and phase III studies, we conclude that patiromer is a well-tolerated and predictable medication to consistently and safely reduce serum potassium levels and to sustain normokalemia for periods up to 52 weeks in patients with diverse underlying diseases including congestive heart failure, and chronic kidney disease. Future research questions that should be evaluated are: the role of patiromer in treating hyperkalemia and the potential to thereby allow the optimal management of resistant hypertension and the use of high dose MRAs in patients with acute decompensated heart failure. Additional research is also warranted in the potential safety benefits of reducing potassium fluctuations in patients on hemodialysis as a result of treatment of hyperkalemia with patiromer.
-
7.
Hyperkalemia constitutes a constraint for implementing renin-angiotensin-aldosterone inhibition: the widening gap between mandated treatment guidelines and the real-world clinical arena.
Epstein, M
Kidney international supplements. 2016;(1):20-28
Abstract
Recent studies have reported a large gap between the forceful and assertive recommendations in the guidelines and real-world practice in the use of renin-angiotensin-aldosterone inhibitors (RAASi) therapies. A comprehensive, retrospective analysis of a large database of electronic medical records (>7 million patients) was undertaken to evaluate 3 pivotal concerns: (i) whether RAASi are being prescribed according to treatment guidelines, (ii) what happens to RAASi prescriptions after hyperkalemia events, and (iii) what the clinical outcomes are in patients whose RAASi are discontinued or who are prescribed at doses lower than the guidelines recommend. The results indicate that a substantial gap exists between guideline recommendations and real-world prescribing patterns for RAASi. Among patients with cardiorenal comorbidities for which RAASi are recommended by the guidelines, more than one-half were prescribed lower-than-recommended doses, and approximately 14% to 16% discontinued RAASi therapy. RAASi prescribing patterns may be altered by the development of hyperkalemia. Moderate-to-severe hyperkalemia events were followed by down-titration or discontinuation of RAASi therapy in nearly one-half of all patients on maximal dose and by discontinuation in nearly one-third of patients on submaximal dose. This analysis highlights the challenge behind RAASi prescribing decisions, balancing the risk of provoking hyperkalemia with the benefits to reducing cardiorenal morbidity and mortality. Patients who are known to derive the greatest benefit from these drugs (chronic kidney disease patients with concomitant diabetes mellitus or heart failure) are the same patients who are at highest risk of developing hyperkalemia. These observations constitute a "call to action" to develop newer treatment modalities to lower serum potassium and to achieve and sustain normokalemia long-term.
-
8.
Resistant Hypertension: Insights on Evaluation and Management in the Post-SPRINT (Systolic Blood Pressure Intervention Trial) Era.
Townsend, RR, Epstein, M
Hypertension (Dallas, Tex. : 1979). 2016;(5):1073-1080
-
9.
Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future.
Rossignol, P, Legrand, M, Kosiborod, M, Hollenberg, SM, Peacock, WF, Emmett, M, Epstein, M, Kovesdy, CP, Yilmaz, MB, Stough, WG, et al
Pharmacological research. 2016;(Pt A):585-591
Abstract
Hyperkalemia is a common electrolyte disorder, especially in chronic kidney disease, diabetes mellitus, or heart failure. Hyperkalemia can lead to potentially fatal cardiac dysrhythmias, and it is associated with increased mortality. Determining whether emergency therapy is warranted is largely based on subjective clinical judgment. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) aimed to evaluate the current knowledge pertaining to the emergency treatment of hyperkalemia. The INI-CRCT developed a treatment algorithm reflecting expert opinion of best practices in the context of current evidence, identified gaps in knowledge, and set priorities for future research. We searched PubMed (to August 4, 2015) for consensus guidelines, reviews, randomized clinical trials, and observational studies, limited to English language but not by publication date. Treatment approaches are based on small studies, anecdotal experience, and traditional practice patterns. The safety and real-world effectiveness of standard therapies remain unproven. Prospective research is needed and should include studies to better characterize the population, define the serum potassium thresholds where life-threatening arrhythmias are imminent, assess the potassium and electrocardiogram response to standard interventions. Randomized, controlled trials are needed to test the safety and efficacy of new potassium binders for the emergency treatment of severe hyperkalemia in hemodynamically stable patients. Existing emergency treatments for severe hyperkalemia are not supported by a compelling body of evidence, and they are used inconsistently across institutions, with potentially significant associated side effects. Further research is needed to fill knowledge gaps, and definitive clinical trials are needed to better define optimal management strategies, and ultimately to improve outcomes in these patients.
-
10.
Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics.
Epstein, M, Calhoun, DA
Journal of clinical hypertension (Greenwich, Conn.). 2011;(9):644-8
-
-
Free full text
-
Abstract
KEY POINTS AND PRACTICAL RECOMMENDATIONS • Mineralocorticoid receptor (MR) antagonists (aldosterone blockers) provide effective antihypertensive treatment, especially in low-renin and salt-sensitive forms of hypertension, including resistant hypertension. • Newer, more selective MR antagonists (eg, eplerenone) have fewer of the progestational and antiandrogenic effects than spironolactone, enhancing tolerability and potentially improving adherence to therapy. • MR antagonists provide an additional benefit in the treatment of heart failure when combined with angiotensin-converting enzyme inhibitors, digoxin, and loop diuretics. • Other potassium-sparing diuretics (amiloride or triamterene) are generally prescribed for essential hypertension as a fixed-dose combination with hydrochlorothiazide. • The dose range for spironolactone with resistant hypertension is between 25 mg/d and 50 mg/d, and eplerenone is an appropriate alternative if spironolactone is not tolerated because of sexual side effects. • In general, the combined use of spironolactone and adequate doses of a thiazide diuretic or a thiazide-like agent such as chlorthalidone for the treatment of resistant hypertension maximizes efficacy and reduces the risk of spironolactone-induced hyperkalemia.