Patient- and physician-related risk factors for hyperkalaemia in potassium-increasing drug-drug interactions

Purpose: Hyperkalaemia due to potassium-increasing drug-drug interactions (DDIs) is a clinically important adverse drug event. The purpose of this study was to identify patient- and physician-related risk factors for the development of hyperkalaemia. Methods: The risk for adult patients hospitalised in the University Hospital Zurich between 1 December 2009 and 31 December 2011 of developing hyperkalaemia was correlated with patient characteristics, number, type and duration of potassium-increasing DDIs and frequency of serum potassium monitoring. Results: The 76,467 patients included in this study were prescribed 8,413 potentially severe potassium-increasing DDIs. Patient-related characteristics associated with the development of hyperkalaemia were pulmonary allograft [relative risk (RR) 5.1; p 48h: RR 1.6; p < 0.01). Conclusion: Strategies for reducing the risk of hyperkalaemia during potassium-increasing DDIs should consider both patient- and physician-related risk factors

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

A Changing Perspective for Treatment of Chronic Kidney Disease

Chronic kidney disease (CKD) has become an enormous worldwide health problem, both in developed and less developed countries. The incidence and prevalence of CKD is high, and is associated with increased mortality and morbidity. Of note, CKD is the 12th most common primary cause of death, accounting for about 1 million deaths per year worldwide. CKD and end-stage renal disease are characterized by the progressive development of a series of complications, such as anemia, hyperkalemia, hypervolemia, mineral and bone disorders (CKD-MBD), metabolic acidosis, hyperuricemia and wasting; all of these complications have been shown to be associated with adverse outcomes, and can contribute either individually or in association to the cardiovascular morbidity and mortality observed in CKD. While at this time CKD progression is not treated with high efficacy, new biomarkers of kidney fibrosis have become available in recent years and new treatments for kidney fibrosis and cell loss could become soon available. In addition recent progress in our understanding of CKD pathophysiology together with the development of novel therapeutic agents has led to a renewed attention on the treatment of CKD–associated metabolic complications which are now are amenable to therapeutic interventions. All these important issues are addressed in this volume

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents

This document was written with the intent to be a complete reference at the time of publication on the topic of managing hypertension in the elderly. This document has been developed as an expert consensus document by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), in collaboration with the American Academy of Neurology (AAN), the American College of Physicians (ACP), the American Geriatrics Society (AGS), the American Society of Hypertension (ASH), the American Society of Nephrology (ASN), the American Society for Preventive Cardiology (ASPC), the Association of Black Cardiologists (ABC), and the European Society of Hypertension (ESH). Expert consensus documents are intended to inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community

A review of the literature

Acute kidney injury is a heterogeneous disorder that is common in hospitalized patients and associated with short- and long-term morbidity and mortality, as well high healthcare costs. It is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. Approximately 70% of community-acquired cases of acute kidney injury are attributed to prerenal causes, which include severe hypotension, sepsis, dehydration, heart failure, liver failure, narrowing of renal arteries and exposure to a large number of drugs. Prerenal acute kidney injury results from glomerular hemodynamic alterations leading to reduced glomerular filtration rate with no parenchymal compromise. Autoregulatory mechanisms can partially compensate renal perfusion reduction in order to maintain glomerular filtration rate. Non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors and diuretics - a combination also known as “triple whammy” - can reduce the glomerular filtration rate and lead to prerenal acute kidney injury. A number of different mechanisms are involved, including inhibition of both prostaglandin-mediated control of glomerular afferent arteriolar tone and angiotensin control of efferent arteriolar tone, as well as volume depletion, all contributing to reduced renal plasma flow. This literature review intends to systematize the different pathophysiological mechanisms by which the different drugs promote prerenal acute kidney injury and, on the other hand, to compare the different groups of drugs in relation to their potential to induce prerenal acute kidney injury.A lesão renal aguda é um distúrbio heterogéneo, comum em pacientes hospitalizados, associado a elevada morbilidade e mortalidade a curto e longo prazo, assim como a elevados custos em saúde. É definida por uma diminuição rápida na taxa de filtração glomerular, durante um período de horas a dias, e pela incapacidade do rim para regular adequadamente a homeostase dos fluídos e eletrólitos, resultando na retenção de produtos azotados. Essa acumulação é acompanhada por distúrbios metabólicos, como acidose metabólica e hipercalemia, alterações no equilíbrio de fluídos corporais e efeitos em muitos outros sistemas orgânicos, dependendo da gravidade e da duração da disfunção renal. A gravidade da lesão varia de leve a grave e requer, em alguns casos, terapia de substituição da função renal. Ao longo dos anos, a ausência de consenso em relação aos critérios para a definição e classificação da lesão renal aguda fez emergir a necessidade de padronizar conceitos. Com o progresso do conhecimento médico diversos critérios foram propostos sendo que os mais recentes preconizam que a lesão renal aguda deve ser diagnosticada quando ocorre um aumento da creatinina sérica de pelo menos 0,3 mg/dL (num período de 48 horas) ou quando ocorre um aumento da creatinina sérica em 1,5 vezes em relação ao seu valor basal (documentada ou presumida a sua ocorrência nos 7 dias anteriores) ou ainda, quando for quantificado um volume de urina inferior a 0,5 ml/kg/h em 6 horas. Clinicamente, a lesão renal aguda pode ser dividida em três categorias principais: pré-renal, renal (ou intrínseca) e pós-renal. A forma pré-renal resulta de alterações hemodinâmicas glomerulares que conduzem à diminuição da perfusão renal, porém sem causar danos estruturais ao parênquima renal. A forma pós-renal é despoletada pela obstrução do fluxo urinário por massas intrínsecas ou extrínsecas, como cálculos ureterais ou tumores ginecológicos ou urológicos. Os restantes casos enquadram-se na forma renal, na qual várias estruturas do nefrónio são afetadas, incluindo glomérulos, túbulos, vasos ou interstício. Aproximadamente 70% dos casos de lesão renal aguda adquiridos na comunidade são atribuídos a causas pré-renais, as quais incluem hipotensão grave, sépsis, desidratação, insuficiência cardíaca, insuficiência hepática, estenose das artérias renais e exposição a um variado número de fármacos. Mecanismos autorregulatórios podem compensar parcialmente a redução da perfusão renal com o objetivo de manter uma taxa de filtração glomerular apropriada e de evitar o desenvolvimento de lesão renal aguda. Anti-inflamatórios não esteróides, inibidores do sistema renina-angiotensina e diuréticos - uma combinação conhecida como “triple whammy” - podem reduzir a taxa de filtração glomerular e conduzir a lesão renal aguda pré-renal. Vários mecanismos diferentes estão envolvidos, incluindo a inibição do controle mediado pelas prostaglandinas do tónus glomerular arteriolar aferente, a inibição do controle mediado pela angiotensina do tónus glomerular arteriolar eferente, bem como a depleção de volume, todos contribuindo para a redução do fluxo plasmático renal. Esta revisão da literatura pretende sistematizar os diferentes mecanismos fisiopatológicos pelos quais os diferentes fármacos promovem a lesão renal aguda pré-renal e, por outro lado, comparar os diferentes grupos de fármacos em relação ao seu potencial para induzir lesão renal aguda pré-renal

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents

This document was written with the intent to be a complete reference at the time of publication on the topic of managing hypertension in the elderly. This document has been developed as an expert consensus document by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), in collaboration with the American Academy of Neurology (AAN), the American College of Physicians (ACP), the American Geriatrics Society (AGS), the American Society of Hypertension (ASH), the American Society of Nephrology (ASN), the American Society for Preventive Cardiology (ASPC), the Association of Black Cardiologists (ABC), and the European Society of Hypertension (ESH). Expert consensus documents are intended to inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community

Suicide Screening In Primary Care With Patients Diagnosed With Depression

The purpose of this study was to evaluate healthcare providers\u27 compliance with the recommended 2009 ACCF/AHA guidelines for monitoring routine serum potassium levels in heart failure patients