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BMC Medicine Jul 2018Rates of emergency hospitalisations are increasing in many countries, leading to disruption in the quality of care and increases in cost. Therefore, identifying... (Review)
Review
BACKGROUND
Rates of emergency hospitalisations are increasing in many countries, leading to disruption in the quality of care and increases in cost. Therefore, identifying strategies to reduce emergency admission rates is a key priority. There have been large-scale evidence reviews to address this issue; however, there have been no reviews of medication therapies, which have the potential to reduce the use of emergency health-care services. The objectives of this study were to review systematically the evidence to identify medications that affect emergency hospital admissions and prioritise therapies for quality measurement and improvement.
METHODS
This was a systematic review of systematic reviews. We searched MEDLINE, PubMed, the Cochrane Database of Systematic Reviews & Database of Abstracts of Reviews of Effects, Google Scholar and the websites of ten major funding agencies and health charities, using broad search criteria. We included systematic reviews of randomised controlled trials that examined the effect of any medication on emergency hospital admissions among adults. We assessed the quality of reviews using AMSTAR. To prioritise therapies, we assessed the quality of trial evidence underpinning meta-analysed effect estimates and cross-referenced the evidence with clinical guidelines.
RESULTS
We identified 140 systematic reviews, which included 1968 unique randomised controlled trials and 925,364 patients. Reviews contained 100 medications tested in 47 populations. We identified high-to moderate-quality evidence for 28 medications that reduced admissions. Of these medications, 11 were supported by clinical guidelines in the United States, the United Kingdom and Europe. These 11 therapies were for patients with heart failure (angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, aldosterone receptor antagonists and digoxin), stable coronary artery disease (intensive statin therapy), asthma exacerbations (early inhaled corticosteroids in the emergency department and anticholinergics), chronic obstructive pulmonary disease (long-acting muscarinic antagonists and long-acting beta-2 adrenoceptor agonists) and schizophrenia (second-generation antipsychotics and depot/maintenance antipsychotics).
CONCLUSIONS
We identified 11 medications supported by strong evidence and clinical guidelines that could be considered in quality monitoring and improvement strategies to help reduce emergency hospital admission rates. The findings are relevant to health systems with a large burden of chronic disease and those managing increasing pressures on acute health-care services.
Topics: Adult; Emergency Service, Hospital; Hospitalization; Humans; Self Medication
PubMed: 30045724
DOI: 10.1186/s12916-018-1104-9 -
Clinical Science (London, England :... Jun 2018Endogenous digitalis-like factor(s), originally proposed as a vasoconstrictor natriuretic hormone, was discovered in fetal and neonatal blood accidentally because it...
Endogenous digitalis-like factor(s), originally proposed as a vasoconstrictor natriuretic hormone, was discovered in fetal and neonatal blood accidentally because it cross-reacts with antidigoxin antibodies (ADAs). Early studies using immunoassays with ADA identified the digoxin-like immuno-reactive factor(s) (EDLF) in maternal blood as well, and suggested it originated in the feto-placental unit. Mammalian digoxin-like factors have recently been identified as at least two classes of steroid compounds, plant derived ouabain (O), and several toad derived bufodienolides, most prominent being marinobufagenin (MBG). A synthetic pathway for MBG has been identified in mammalian placental tissue. Elevated maternal and fetal EDLF, O and MBG have been demonstrated in preeclampsia (PE), and inhibition of red cell membrane sodium, potassium ATPase (Na, K ATPase (NKA)) by EDLF is reversed by ADA fragments (ADA-FAB). Accordingly, maternal administration of a commercial ADA-antibody fragment (FAB) was tested in several anecdotal cases of PE, and two, small randomized, prospective, double-blind clinical trials. In the first randomized trial, ADA-FAB was administered post-partum, in the second antepartum. In the post-partum trial, ADA-FAB reduced use of antihypertensive drugs. In the second trial, there was no effect of ADA-FAB on blood pressure, but the fall in maternal creatinine clearance (CrCl) was prevented. In a secondary analysis using the pre-treatment maternal level of circulating Na, K ATPase (NKA) inhibitory activity (NKAI), ADA-FAB reduced the incidence of pulmonary edema and, unexpectedly, that of severe neonatal intraventricular hemorrhage (IVH). The fall in CrCl in patients given placebo was proportional to the circulating level of NKAI. The implications of these findings on the pathophysiology of the clinical manifestations PE are discussed, and a new model of the respective roles of placenta derived anti-angiogenic (AAG) factors (AAGFs) and EDLF is proposed.
Topics: Birth Weight; Blood Pressure; Cardenolides; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Ouabain; Placenta; Pre-Eclampsia; Pregnancy; Saponins
PubMed: 29930141
DOI: 10.1042/CS20171499 -
Drugs & Aging May 2018Residents of long-term care facilities (LTCFs) are at high risk of hospitalization. Medications are a potentially modifiable risk factor for hospitalizations. (Review)
Review
BACKGROUND
Residents of long-term care facilities (LTCFs) are at high risk of hospitalization. Medications are a potentially modifiable risk factor for hospitalizations.
OBJECTIVE
Our objective was to systematically review the association between medications or prescribing patterns and hospitalizations from LTCFs.
METHODS
We searched MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and International Pharmaceutical Abstracts (IPA) from inception to August 2017 for longitudinal studies reporting associations between medications or prescribing patterns and hospitalizations. Two independent investigators completed the study selection, data extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Tools.
RESULTS
Three randomized controlled trials (RCTs), 22 cohort studies, five case-control studies, one case-time-control study and one case-crossover study, investigating 13 different medication classes and two prescribing patterns were included. An RCT demonstrated that high-dose influenza vaccination reduced all-cause hospitalization compared with standard-dose vaccination (risk ratio [RR] 0.93; 95% confidence interval [CI] 0.88-0.98). Another RCT found no difference in hospitalization rates between oseltamivir as influenza treatment and oseltamivir as treatment plus prophylaxis (treatment = 4.7%, treatment and prophylaxis = 3.5%; p = 0.7). The third RCT found no difference between multivitamin/mineral supplementation and hospitalization (odds ratio [OR] 0.94; 95% CI 0.74-1.20) or emergency department visits (OR 1.05; 95% CI 0.76-1.47). Two cohort studies demonstrated influenza vaccination reduced hospitalization. Four studies suggested polypharmacy and potentially inappropriate medications (PIMs) increased all-cause hospitalization. However, associations between polypharmacy (two studies), PIMs (one study) and fall-related hospitalizations were inconsistent. Inconsistent associations were found between psychotropic medications with all-cause and cause-specific hospitalizations (11 studies). Warfarin, nonsteroidal anti-inflammatory drugs, pantoprazole and vinpocetine but not long-term acetylsalicylic acid (aspirin), statins, trimetazidine, digoxin or β-blockers were associated with all-cause or cause-specific hospitalizations in single studies of specific resident populations. Most cohort studies assessed prevalent rather than incident medication exposure, and no studies considered time-varying medication use.
CONCLUSION
High-quality evidence suggests influenza vaccination reduces hospitalization. Polypharmacy and PIMs are consistently associated with increased all-cause hospitalization.
Topics: Age Factors; Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Cross-Over Studies; Drug Prescriptions; Emergency Service, Hospital; Hospitalization; Humans; Inappropriate Prescribing; Long-Term Care; Nursing Homes; Polypharmacy
PubMed: 29582403
DOI: 10.1007/s40266-018-0537-3 -
PloS One 2018During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence.
RESULTS
28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%).
CONCLUSIONS
The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42016052935.
Topics: Aged; Amiodarone; Atrial Fibrillation; Atrial Flutter; Bias; Calcium Channel Blockers; Comorbidity; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Mortality; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Stroke; Treatment Outcome
PubMed: 29518134
DOI: 10.1371/journal.pone.0193924 -
Journal of the American Medical... Apr 2018Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the associations between cardiovascular medications and fall risk in older adults.
METHODS
Design: A systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, and PsycINFO. Key search concepts were "fall," "aged," "causality," and "medication." Studies that investigated cardiovascular medications as risk factors for falls in participants ≥60 years old or participants with a mean age of 70 or older were included. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratios (ORs) separately.
RESULTS
In total, 131 studies were included in the qualitative synthesis. Meta-analysis using adjusted ORs showed significant results (pooled OR [95% confidence interval]) for loop diuretics, OR 1.36 (1.17, 1.57), and beta-blocking agents, OR 0.88 (0.80, 0.97). Meta-analysis using unadjusted ORs showed significant results for digitalis, OR 1.60 (1.08, 2.36); digoxin, OR 2.06 (1.56, 2.74); and statins, OR 0.80 (0.65, 0.98). Most of the meta-analyses resulted in substantial heterogeneity that mostly did not disappear after stratification for population and setting. In a descriptive synthesis, consistent associations were not observed.
CONCLUSION
Loop diuretics were significantly associated with increased fall risk, whereas beta-blockers were significantly associated with decreased fall risk. Digitalis and digoxin may increase the risk of falling, and statins may reduce it. For the majority of cardiovascular medication groups, outcomes were inconsistent. Furthermore, recent studies indicate that specific drug properties, such as selectivity of beta-blockers, may affect fall risk, and drug-disease interaction also may play a role. Thus, studies addressing these issues are warranted to obtain a better understanding of drug-related falls.
Topics: Accidental Falls; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Female; Humans; Male; Middle Aged; Netherlands; Prevalence; Risk Assessment; Sex Factors; United Kingdom
PubMed: 29396189
DOI: 10.1016/j.jamda.2017.12.013 -
Journal of the American Heart... Dec 2017There is no consensus on the most effective and best tolerated first-line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is no consensus on the most effective and best tolerated first-line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta-analysis was to compare the efficacy, safety, and fetal-maternal tolerance of first-line monotherapies for fetal supraventricular tachycardia and atrial flutter.
METHODS AND RESULTS
A comprehensive search of several databases was conducted through January 2017. Only studies that made a direct comparison between first-line treatments of fetal tachyarrhythmia were included. Outcomes of interest were termination of fetal tachyarrhythmia, fetal demise, and maternal complications. Ten studies met inclusion criteria, with 537 patients. Overall, 291 patients were treated with digoxin, 137 with flecainide, 102 with sotalol, and 7 with amiodarone. Digoxin achieved a lower rate of supraventricular tachycardia termination compared with flecainide (odds ratio [OR]: 0.773; 95% confidence interval [CI], 0.605-0.987; I=34%). In fetuses with hydrops fetalis, digoxin had lower rates of tachycardia termination compared with flecainide (OR: 0.412; 95% CI, 0.268-0.632; I=0%). There was no significant difference in the incidence of maternal side effects between digoxin and flecainide groups (OR: 1.134; 95% CI, 0.129-9.935; I=80.79%). The incidence of maternal side effects was higher in patients treated with digoxin compared with sotalol (OR: 3.148; 95% CI, 1.468-6.751; I=0%). There was no difference in fetal demise between flecainide and digoxin (OR: 0.767; 95% CI, 0.140-4.197; I=44%).
CONCLUSIONS
Flecainide may be more effective treatment than digoxin as a first-line treatment for fetal supraventricular tachycardia.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Echocardiography; Female; Fetal Diseases; Fetal Therapies; Flecainide; Humans; Pregnancy; Prenatal Care; Prenatal Diagnosis
PubMed: 29246961
DOI: 10.1161/JAHA.117.007164 -
Heart, Lung & Circulation Mar 2018Current epidemiological data suggests that postoperative atrial fibrillation or atrial flutter (POAF) causes significant morbidity and mortality after cardiac surgery.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current epidemiological data suggests that postoperative atrial fibrillation or atrial flutter (POAF) causes significant morbidity and mortality after cardiac surgery. The literature for prophylactic management of POAF is limited, resulting in the lack of clear guidelines on management recommendations.
AIM
To examine the efficacy of prophylactic rate control agents in reducing the incidence of new-onset POAF in patients undergoing elective cardiac surgery.
METHODS
Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Medline were systematically searched for blinded randomised controlled studies (RCT) evaluating adults with no history of atrial fibrillation randomised to a pharmacological agent (either beta blocker, calcium channel blocker or digoxin), compared to placebo. Utilising Cochrane guidance, three reviewers screened, extracted and the quality of the evidence was assessed. We used a random effects meta-analysis to compare a rate-control agent with placebo.
RESULTS
Five RCTs (688 subjects, mean age 61±8.9, 69% male) were included. Beta blocker administration prior to elective cardiac surgery significantly reduced the incidence of POAF (OR 0.43, 95%Cl [0.30-0.61], I=0%) without significant impact on ischaemic stroke (OR 0.49, 95%Cl [0.10-2.44], I=0%), non-fatal myocardial infarction (OR 0.76, 95%Cl [0.08-7.44], I=0%), overall mortality (OR 0.83, 95%Cl [0.19-3.66], I=0%), or length of stay (mean -0.96days 95%Cl [-1.49 to -0.42], I=0%). An increased rate of bradycardic episodes was observed (OR 3.53, 95%Cl [1.22-10.23], I=0%).
CONCLUSIONS
This review suggests that selective administration of prophylactic oral beta blockers prior to elective cardiac surgery is safe and may reduce the incidence of POAF.
Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Cardiac Surgical Procedures; Global Health; Humans; Incidence; Postoperative Complications; Preoperative Care
PubMed: 29129562
DOI: 10.1016/j.hlc.2017.08.026 -
Prenatal Diagnosis Nov 2017Multiple transplacental medications can be used to treat fetal tachycardia. We sought to perform a systematic review and meta-analysis to determine whether digoxin,... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Multiple transplacental medications can be used to treat fetal tachycardia. We sought to perform a systematic review and meta-analysis to determine whether digoxin, flecainide, or sotalol was the most efficacious therapy for converting fetal tachycardia to sinus rhythm.
METHOD
We performed a systematic review and meta-analysis to compare digoxin, flecainide, or sotalol as first-line therapy for fetal tachycardia. Studies were identified by a search of PubMed (Medline), Web of Science, and Scopus.
RESULTS
There were 21 studies included. Flecainide (OR: 1.4, 95% CI: 1.1-2.0, I = 60%, P = 0.03) and sotalol (OR:1.4, 95% CI:1.1-2.0, I = 30%, P = 0.02) were superior to digoxin for conversion of fetal tachycardia to sinus rhythm. In those with hydrops, the benefit over digoxin was more notable for both flecainide (OR: 5.0, 95% CI: 2.5-10.0, I = 0%, P < 0.001) and sotalol (OR: 2.5, 95% CI: 1.7-5.0, I = 0%, P < 0.001). When limited to atrioventricular reentrant tachycardia, flecainide was superior to digoxin (OR:1.7, 95% CI:1.1-3.3, I = 62%, P = 0.03) and sotalol (OR:1.3, 95% CI:1.1-1.7, I = 0%, P = 0.01).
CONCLUSION
Digoxin should not be first-line therapy for fetal tachycardia, particularly in the presence of hydrops fetalis. Flecainide should be the first-line therapy of choice in atrioventricular reentrant tachycardia. Further study may identify further sub-populations responding differently.
Topics: Anti-Arrhythmia Agents; Digoxin; Female; Fetal Diseases; Fetal Therapies; Flecainide; Humans; Pregnancy; Sotalol; Tachycardia
PubMed: 28833310
DOI: 10.1002/pd.5144 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2017Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department... (Review)
Review
CONTEXT
Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available.
OBJECTIVE
This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article.
METHODS
A medical librarian created a systematic search strategy for Medline, subsequently translated to Embase, BIOSIS, PubMed, Web of Science, Cochrane, Database of Abstracts of Reviews of Effects (DARE), and the CENTRAL clinical trial register, all of which we searched from inception to 30 June 2016. Interventions included IO administration of selected antidotes. Articles included volunteer studies, poisoning, or other resuscitation contexts such as cardiac arrest, burns, dehydration, seizure, hemorrhagic shock, or undifferentiated shock. We considered all human studies and animal experiments to the exception of in vitro studies. Two reviewers independently selected studies, and a third adjudicated in case of disagreement. Three reviewers extracted all relevant data. Three reviewers evaluated the risk of bias and quality of the articles using specific scales according to each type of study design.
RESULTS
A total of 47 publications (46 articles and one abstract) met our inclusion criteria and described IO administration of 13 different antidotes. These included one case series and 21 case reports describing 26 patients, and 25 animal experiments. Of those, seven human case reports and four animal experiments specifically reported the use of antidotes in poisoning. Human case reports suggested favorable outcomes with IO use of atropine, diazepam, hydroxocobalamin, insulin, lipid emulsion, methylene blue, phentolamine, prothrombin complex concentrate, and sodium bicarbonate. Clinical outcomes varied according to the antidote used. The only reported adverse event was ventricular tachycardia following IO naloxone. Regarding the animal experiments, IO administration of lipid emulsion and of hydroxocobalamin showed improved survival in bupivacaine-poisoned rats and in cyanide-intoxicated swine, respectively. Animal data also suggested an equivalent bio-availability between IO and IV administration for atropine, calcium chloride, dextrose 50%, diazepam, methylene blue, pralidoxime, and sodium bicarbonate. Adverse effect reporting of fat emboli after IO administration of sodium bicarbonate, for example, was conflicting due to the significant heterogeneity in the timing of lung examination across studies.
CONCLUSION
The evidence supporting the use of IO route for the administration of antidotes in a context of poisoning is scarce. The majority of the evidence consists of case reports and animal experiments. Common antidotes such as acetylcysteine, fomepizole, and digoxin-specific antibody fragments have not been studied or reported with the use of the IO route. Despite the low-quality evidence available, IO access is a potential option for antidotal treatments in toxicological resuscitation when IV access is unavailable.
Topics: Animals; Antidotes; Humans; Infusions, Intraosseous; Poisoning; Resuscitation
PubMed: 28644688
DOI: 10.1080/15563650.2017.1337122 -
PloS One 2017Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies have investigated the anti-neoplastic properties of CGs since 1960s. Epidemiological studies concerning the association between CGs use and cancer risk yielded inconsistent results. We have performed a systematic review and meta-analysis to summarize the effects of CGs on cancer risk and mortality.
METHODS
PubMed, Scopus, Cochrane library, Medline and Web of Knowledge were searched for identifying relevant studies. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects model.
RESULTS
We included 14 case-control studies and 15 cohort studies published between 1976 and 2016 including 13 cancer types. Twenty-four studies reported the association between CGs and cancer risk and six reported the association between CGs and mortality of cancer patients. Using CGs was associated with a higher risk of breast cancer (RR = 1.330, 95% CI: 1.247-1.419). Subgroup analysis showed that using CGs increased the risk of ER+ve breast cancer but not ER-ve. Using CGs wasn't associated with prostate cancer risk (RR = 1.015, 95% CI: 0.868-1.87). However, CGs decreased the risk in long term users and showed a protective role in decreasing the risk of advanced stages. CGs use was associated with increased all-cause mortality (HR = 1.35, 95% CI: 1.248-1.46) but not cancer-specific mortality (HR = 1.075, 95% CI: 0.968-1.194).
CONCLUSION
The anti-tumor activity of CGs observed in pre-clinical studies requires high concentrations which can't be normally tolerated in humans. However, the estrogen-like activity of CGs could be responsible for increasing the risk of certain types of tumors.
Topics: Cardiac Glycosides; Female; Humans; Male; Neoplasms; Observational Studies as Topic; Risk Factors
PubMed: 28591151
DOI: 10.1371/journal.pone.0178611