Impact of spironolactone exposure on prostate cancer incidence amongst men with heart failure: A Pharmacoepidemiological study.

AIMS: Aldosterone has been found to influence cancer cell growth, cell cycle regulation and cell migration, including in prostate cancer cells. Spironolactone is an aldosterone antagonist used for managing chronic heart failure (HF) with known antiandrogenic effects. We examined the effect of spironolactone exposure amongst men with HF on the incidence of prostate cancer. METHODS: This retrospective cohort study utilized provincial clinical and administrative databases from the Manitoba Centre for Health Policy. Incident cases of prostate cancer were identified from the provincial cancer registry, and spironolactone exposure was quantified from pharmacare databases. A multivariable proportional hazards model was used to assess the time-dependent impact of spironolactone exposure on prostate cancer incidence. RESULTS: A total of 18 562 men with newly diagnosed HF from 2007 to 2015 with a median age of 72 years (interquartile range: 61-81) and a median follow-up from HF diagnosis to prostate cancer incidence of 2.7 years (interquartile range: 1.1-4.9) were included. A time-dependent multivariable analysis of spironolactone exposure following HF diagnosis found a reduced the risk of prostate cancer hazard ratio 0.55 (95% confidence interval 0.31-0.98, P = .043). CONCLUSION: Spironolactone exposure significantly reduced the incidence of prostate cancer amongst men with HF. These findings support the plausibility of aldosterone as a promoter of prostate cancer growth and development. Prospective clinical trials are warranted to further assess the role of spironolactone or other mineralocorticoid receptor antagonists as a means to prevent prostate cancer development or as an adjunctive measure to prostate cancer treatments.

Hyperkalemia in heart failure.

PURPOSE OF REVIEW: Hyperkalemia is increasingly prevalent in the heart failure population as more people live with heart failure and comorbid conditions such as diabetes and chronic kidney disease. Furthermore, renin-angiotensin-aldosterone (RAAS) inhibitors are a key component of clinical therapy in these populations. Until now, we have not had any reliable or tolerable therapies for treatment of hyperkalemia resulting in inability to implement or achieve target doses of RAAS inhibition. This review will focus on two new therapies for hyperkalemia: patiromer and sodium zirconium cyclosilicate (SZC). RECENT FINDINGS: Patiromer and SZC have been studied in heart failure and both agents have demonstrated the ability to maintain normokalemia for extended periods of time with improved side effect profiles than existing potassium binders such as sodium polystyrene sulfate, though no direct comparisons have occurred. SZC has also shown promise in the treatment of acute hyperkalemia with its quick onset of action. SUMMARY: Patiromer and SZC will be useful adjuncts in the clinical care of heart failure patients with hyperkalemia. These agents will allow clinicians to maintain patients on RAAS inhibitors and uptitrate their guideline directed medical therapy to target doses without the additional concern for recurrent hyperkalemia and its untoward effects.

Dexmedetomidine versus propofol sedation in reducing delirium among older adults in the ICU: A systematic review and meta-analysis.

BACKGROUND: Delirium is common in the ICU, with incidence rates reported to be upwards of 70%. Due to the significant morbidity and mortality associated with delirium, it is hypothesised that a delirium-free sedative agent will improve outcomes in older adults admitted to the ICU. OBJECTIVES: To assess if dexmedetomidine sedation is associated with a reduction in ICU delirium among older adults, and to evaluate its risks and benefits compared with propofol sedation. DESIGN: Systematic review of randomised controlled trials and cohort studies with meta-analyses. DATA SOURCES: Articles published from database inception to 8 April 2019 were retrieved from Medline, EMBASE, Evidence-based Medicine Reviews, International Pharmaceutical Abstracts, Scopus, ClinicalTrials.gov and WHO Trials. ELIGIBILITY: Studies were included if they compared dexmedetomidine sedation with propofol in the ICU, reported the incidence of delirium as an outcome and had a mean/median sample age of at least 60. Studies that examined dexmedetomidine and propofol use intra-operatively or as part of general anaesthesia were excluded. RESULTS: Dexmedetomidine sedation was associated with a lower incidence of delirium when compared with propofol: seven studies, n=1249; risk ratio 0.70; 95% confidence interval (CI) 0.52 to 0.95; P = 0.02. There was no statistically significant difference in the incidence of bradycardia: three studies, n=278; risk ratio 1.52; 95% CI 0.85 to 2.72; P = 0.16, and hypotension: six studies, n=867 patients; risk ratio 1.12; 95% CI 0.86 to 1.45; P = 0.42. Dexmedetomidine sedation did not reduce hospital length of stay, ICU length of stay or duration of mechanical ventilation compared with propofol. CONCLUSION: Compared with propofol, dexmedetomidine sedation in the ICU is associated with lower delirium incidence among older adults with no significant increase in adverse events. In older adult ICU patients at risk of developing delirium, sedation with dexmedetomidine should be considered. Further research is warranted to elucidate and explain the mechanisms underlying this process, and to confirm our findings with large, multicentre trials. TRIAL REGISTRATION: The study protocol has been registered in PROSPERO (CRD42018099339).

Treatment Outcomes for Right-Sided Endocarditis in Intravenous Drug Users: A Systematic Review and Analysis of Outcomes in a Tertiary Centre.

BACKGROUND: The increasing prevalence of intravenous drug users (IVDU) has resulted in higher incidence of right-sided infective endocarditis (RSIE). However, treatment guidelines for RSIE in IVDU are not well defined. The aim is to evaluate efficacy of different treatment strategies in reducing mortality and to describe treatment outcomes. METHODS: We systematically reviewed the literature using PubMed, Cochrane, CENTRAL, OvidEMBASE, Web of Science, and Medline databases to include prospective studies that compare mortality rates among IVDU with RSIE receiving isolated medical treatment versus those receiving medical-surgical treatment. In conjunction, analysis of 27 RSIE patients (including IVDU) treated at authors' institution was done to supplement the findings. Kaplan-Meier survival rates following hospital admission and cumulative incidence estimates for hospital re-admission were obtained. RESULTS: A total of nine studies (all with low or marginal risk of bias) met inclusion criteria. The prevalence of RSIE among IVDU with infective endocarditis varied from 34% to 100%. Seven studies compared medical versus medical-surgical therapy with less than 30% needing surgery. Mortality was higher in patients receiving surgical therapy. There were 27 RSIE (16 non-IVDU and 11 IVDU) analyzed at the authors' institution. Survival at 30 days, 1 year, and 3 years were 89%, 82%, and 78%, respectively, and repeat hospitalization for recurrent endocarditis were 8%, 17%, and 23%, respectively. CONCLUSIONS: There is paucity around optimal RSIE management strategy for IVDU that can decrease mortality. Surgical management of RSIE may be associated with increased mortality over medical management mainly due to advanced surgical indications.

Ketamine-based anesthesia improves electroconvulsive therapy outcomes: a randomized-controlled study.

BACKGROUND: Major depressive disorder (MDD) is a common and debilitating condition that can be challenging to treat. Electroconvulsive therapy (ECT) is currently the therapeutic gold standard for treatment-resistant MDD. We tested our hypothesis that ketamine-based anesthesia for ECT results in superior improvement in treatment-resistant MDD outcomes compared with propofol-based anesthesia. METHODS: Patients with treatment-resistant MDD were enrolled in a randomized clinical trial with assignment to ketamine- or propofol-based anesthesia arms. Using a modified intention-to-treat analysis, we compared the median number of ECT treatments required to achieve a 50% reduction (primary outcome) and a score ≤ 10 (secondary outcome) on the Montgomery-Asberg depression rating scale (MADRS) between anesthesia groups. RESULTS: The study was terminated as significant results were found after the first planned interim analysis with 12 patients in each of the ketamine (intervention) and propofol (control) groups. All ketamine patients achieved at least a 50% MADRS reduction after a median of two ECT treatments whereas ten propofol patients (83%) achieved the same outcome after a median of four ECT treatments. All ketamine patients and seven propofol patients (58%) achieved MDD remission (MADRS ≤ 10). Log rank tests showed that both time-to-50% reduction and remission differed significantly between groups. Adverse events and recovery time were similar between groups. CONCLUSIONS: In this early-terminated small-sized study, ketamine-based anesthesia compared with propofol-based anesthesia provided response and remission after fewer ECT sessions. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01935115). Registered 4 September 2013.

Safety and efficacy of low-dose intracoronary thrombolysis during primary percutaneous coronary intervention in patients with ST elevation myocardial infarction: A meta-analysis of randomized trials.

BACKGROUND: In patients with ST elevation myocardial infarction (STEMI), intracoronary thrombolysis (ICT) may reduce thrombotic burden and microvascular obstruction in the infarct-related artery. We performed a meta-analysis to evaluate the role of adjunctive low-dose ICT during primary percutaneous coronary intervention (PPCI) in improving clinical outcomes and indices of microvascular function. METHODS: We searched electronic databases (Cochrane, EMBASE, Medline; inception to October 2023) for randomized controlled trials (RCTs) evaluating the effects of adjunctive ICT in STEMI patients undergoing PPCI, compared with placebo or usual care. Study-level data on efficacy and safety outcomes were pooled using a fixed-effect model. The primary outcome was major adverse cardiovascular events (MACE). RESULTS: A total of 8 RCTs were included, comprising a total of 1,208 patients. Compared with placebo or usual care, ICT was associated with a trend towards lower MACE (11.3% vs. 15.1%; odds ratio [OR] 0.73, 95% confidence interval [CI] 0.51 to 1.04). Infarct size (mean difference [MD] -1.98, 95% CI -3.68 to -0.27; p=0.02), ST-segment resolution (MD: 6.06, 95% CI: 0.69 to 11.43; p=0.03) and corrected TIMI frame count (MD: -2.26, 95% CI: -4.03 to -0.48; p=0.01; I2=78%). The odds for major (0.7% vs. 0.7%; OR 0.94, 95% CI 0.24 to 3.7; p=0.93) and minor bleeding (7.7% vs. 4.3%; OR 1.81, 95% CI 0.87 to 3.76; p=0.11) were similar between the two groups. CONCLUSION: Adjunctive low-dose ICT during PPCI is safe, associated with a trend towards lower MACE, and may improve surrogate markers of microvascular function. These hypothesis-generating findings warrant validation in larger, adequately powered randomized trials.

Revising the Roles of Aldosterone in Vascular Physiology and Pathophysiology: From Electocortin to Baxdrostat.

Aldosterone was initially identified as a hormone primarily related to regulation of fluid and electrolyte homeostasis. However, over the past 20 years there has been an increasing appreciation of its role in regulation of vascular function and pathophysiology in the setting of hypertension, atherosclerosis, and heart failure. This review highlights recent advances in our understanding the biology of aldosterone as it relates to the pathophysiology and the management of vascular disease-especially related to hypertension. The review focuses on 3 key areas: 1) advances in our understanding of the cellular mechanisms by which aldosterone mediates its cellular effects, 2) identification of the hidden epidemic of aldosteronism as a mediator of hypertension, and 3) appreciating new therapeutic advances in the clinical pharmacology of aldosterone inhibition in cardiovascular and renal disease.

Barriers to Successful Discharge After Cardiac Surgery: A Focus Group Study and Cross-Sectional Survey.

At present, there is a lack of information on patient and caregiver values, and perceived priorities and barriers, to guide successful post-discharge recovery. This was a single center, multiple methods study that investigated patient, caregiver, and health care provider perceptions of the discharge process after cardiac surgery. Themes emerging from focus group discussions with patients and caregivers were used to develop surveys relating to values, barriers, and challenges relating to the discharge process. Thirty-two patients (n = 16) and caregivers (n = 16) participated in four separate focus groups. Four themes emerged from these discussions: (1) a lack of understanding about what the discharge process entails and when discharge is appropriate, (2) issues relating to the information provided to patients at the time of discharge, (3) participant experiences with the health care system, and (4) the experiences of caregivers. Seventy-eight patients, 34 caregivers, 53 nurses and/or other allied health professionals, and 8 surgeons completed the cross-sectional surveys. The most important component of the discharge process for patients and caregivers was "knowing what to do in an emergency." Health care providers less accurately identified what caregivers perceived as the most important aspects of the discharge process.Statements relating to informational barriers to discharge were the most discordant among patient and caregiver respondents. After discharge, patients and caregivers identified the need for longer-term follow up with the surgeon and more support in the community. Incorporation of patient and caregiver values to guide the post-cardiac surgery discharge process is essential to promote successful recovery.

Delirium definition influences prediction of functional survival in patients one-year postcardiac surgery.

BACKGROUND: Delirium after cardiac surgery is associated with prolonged intensive care unit (ICU) and hospital length of stay and elevated rates of mortality. The Society of Thoracic Surgery National Database (STS-ND) includes delirium in routine data collection but restricts its definition to hyperactive symptoms. The objective is to determine whether the Confusion Assessment Method for ICU (CAM-ICU), which includes hypo- and hyperactive symptoms, is associated with improved prediction of poor 1-year functional survival following cardiac surgery. METHODS: Clinical and administrative databases were used to determine the influence of postoperative delirium on 1-year poor functional survival, defined as being institutionalized or deceased at 1 year. Patients experiencing postoperative delirium using the STS-ND definition (2007-2009) were compared with patients with delirium identified by the CAM-ICU (2010-2012). A propensity score match was undertaken, and multivariable Cox proportional hazards regression models were generated to determine risk of poor 1-year functional survival. RESULTS: There were 2756 and 2236 patients in the STS-ND and CAM-ICU cohorts, respectively. Propensity matching resulted in a cohort of 1835 patients (82.1% matched). The overall rate of delirium in the matched study population was 7.6% in the STS-ND cohort and 13.0% in the CAM-ICU cohort (P < .001). Delirium in the CAM-ICU cohort was independently associated with poor 1-year functional survival (hazard ratio, 2.58; 95% confidence interval, 1.20-5.54; P = .02); delirium in the STS-ND cohort was not associated with poor 1-year functional survival (hazard ratio, 0.92; 95% confidence interval, 0.49-1.71; P = .79). CONCLUSIONS: A systematic screening tool identifies postoperative delirium with improved prediction of poor 1-year functional survival following cardiac surgery.

A Quality Improvement Initiative to Reduce Postoperative Delirium among Cardiac Surgery Patients.

Patients following cardiac surgery commonly experience post-operative delirium (POD) during their postoperative hospital stay. A multifaceted, specialty wide, quality improvement (QI) project was undertaken for patients experiencing POD. The goal was to develop a reduction in POD care bundle (rPOD-a structured patient care program) that encompasses efficient preoperative risk factor identification and a postoperative patient-care process to ensure early POD identification and treatment. The following steps were taken to implement the rPOD care bundle including: (a) Developing a quality driven, evidence-based guideline for the perioperative cardiac surgery health care team, (b) identifying and addressing local barriers to implementation, (c) selecting performance measures to assess intervention adherence and patient outcomes, and (d) ensuring that all patients receive the interventions through staff engagement and education, and regular project evaluation. Trends of process measures and quality improvement measures were examined. An increasing trend in the rate of postoperative delirium screening during implementation of rPOD intervention was demonstrated. This quality improvement study provides a bases for future postoperative delirium reduction interventions.

Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) after cardiac surgery is associated with longer hospital stay and increased in-hospital death and stroke, but its long-term implications remain incompletely understood. A systematic literature review was undertaken to investigate the impact of POAF on long-term death and stroke in adult patients who undergo cardiac operations. METHODS: Electronic databases (Cochrane, Embase, Ovid MEDLINE, and PubMed) were queried from inception to October 2018. Included studies compared long-term outcomes after cardiac operations in patients with and without POAF. Adjusted and unadjusted meta-analyses examined death, stroke, and major adverse cardiac and cerebrovascular events. Risk of bias was evaluated with the Newcastle-Ottawa Scale. RESULTS: The inclusion criteria were met by 32 studies describing 155,575 patients who had undergone cardiac operations. POAF occurred in 36,988 patients (23.7%). Meta-analysis of 10 studies (44,367 patients) demonstrated increased 1-year death in patients with POAF (odds ratio, 2.60; 95% confidence interval, 2-3.38; P < .01). Aggregate adjusted hazard of death (16 studies, n = 84,295) was also increased in patients with POAF (hazard ratio, 1.25; 95% confidence interval, 1.2-1.3; P < .01). CONCLUSIONS: This systematic review and meta-analysis identified an association between POAF and long-term death after cardiac surgery. More comprehensive POAF prevention and management, including more stringent follow-up for POAF recurrence after hospital discharge, may be indicated. The included studies used inconsistent definitions of POAF and variable exclusion criteria; however, estimates of heterogeneity are low. Differences in preoperative comorbidities, such as age, ejection fraction, and obesity, may not be fully accounted for in adjusted analyses. Future work is required to delineate mechanisms linking POAF and death in this population.

Delirium Prevention in Postcardiac Surgical Critical Care.

This review provides an overview for health care teams involved in the perioperative care of cardiac surgery patients. The intention is to summarize key determinants of delirium, its impact on short- and long-term outcomes as well as to discuss effective management strategies. The first component of this review examines the prevalence and the factors associated with an increased risk of postoperative delirium. A multitude of predisposing (eg, baseline vulnerability and comorbidities) and precipitating (eg, type of cardiac surgery and postoperative care) factors that contribute to the occurrence of delirium are discussed.

Neurocognitive Function and Fetal Alcohol Spectrum Disorder in Offenders with Mental Disorders.

Individuals with a history of offending behavior show high rates of mental disorder as well as fetal alcohol spectrum disorder (FASD). Neurocognitive impairments are common in both mental disorders and FASD and may interface with offending behavior. Understanding these impairments could effectively inform clinical considerations among this population. The purpose of this study was to characterize the life experiences and examine the neurocognitive profile of a group of adult forensic psychiatric outpatients. We also investigated potential differences between offenders with FASD and the rest of the sample. Data were collected on 45 subjects on numerous variables, including demographics, background information, offending histories, and comorbidities. Subjects also completed extensive neurocognitive testing. The sample was primarily male (82.2%) with a mean age of 42 years. There was a high prevalence of lifetime adversity and varied offense histories. Subjects showed the most significant neurocognitive impairment in executive function, visual memory (immediate and delayed recall), and full-scale IQ. The FASD group (n = 12) did not differ significantly from the No-FASD group (n = 33) on any background variables. The FASD group showed significantly lower neurocognitive scores in the areas of verbal IQ, full-scale IQ, working memory, processing speed, and expressive vocabulary.

Comprehensive Geriatric Assessment in the Management of Older Patients With Cardiovascular Disease.

Cardiovascular disease (CVD) disproportionately affects older adults. It is expected that by 2030, one in five people in the United States will be older than 65 years. Individuals with CVD now live longer due, in part, to current prevention and treatment approaches. Addressing the needs of older individuals requires inclusion and assessment of frailty, multimorbidity, depression, quality of life, and cognition. Despite the conceptual relevance and prognostic importance of these factors, they are seldom formally evaluated in clinical practice. Further, although these constructs coexist with traditional cardiovascular risk factors, their exact prevalence and prognostic impact remain largely unknown. Development of the right decision tools, which include these variables, can facilitate patient-centered care for older adults. These gaps in knowledge hinder optimal care use and underscore the need to rigorously evaluate the optimal constructs for providing care to older adults. In this review, we describe available tools to examine the prognostic role of age-related factors in patients with CVD.

"NEW" Prehabilitation: A 3-Way Approach to Improve Postoperative Survival and Health-Related Quality of Life in Cardiac Surgery Patients.

With advances in health care practices and delivery, the overall life expectancy of the Western population has increased. For those practitioners involved in the care of the patient with advanced cardiac disease, there has been a resultant higher prevalence of increasingly frail and older patients undergoing complex cardiac procedures. The higher rates of comorbid-associated higher vulnerability, with associated deconditioning, predisposes older, frail patients to poorer postoperative outcomes and a complicated recovery process after cardiac surgery. In addition, such patients experience inferior quality of life as a result of reduced ability to independently perform activities of daily living. During the preoperative waiting period, the cardiac symptoms and anxiety induces inactivity that in turn compounds the physical and mental deconditioning. To improve functional capacity and enhance postoperative recovery, prehabilitation, a component of the enhanced recovery after surgery model, might be of particular importance. In some studies, the preoperative improvement of the baseline physical, nutritional, and mental status has been reported to improve postoperative outcomes and enhance recovery after cardiac surgery. To address these domains, a 3-way approach to prehabilitation that is targeted toward improving nutritional status (N), exercise capacity (E) and worry reduction (W) (nutrition, exercise, and worry; "NEW" approach) might facilitate the perioperative management by ameliorating the postoperative outcomes and alleviating the surgical stress-related health deconditioning. In this review, the NEW approach and its potential benefits on postoperative outcomes as well as an implementation model (Promoting Action on Research Implementation in Health Services [PARiHS] framework) to aid institutional level implementation is described.