Anticholinergic medications in patients admitted with cognitive impairment or falls (AMiCI). The impact of hospital admission on anticholinergic cognitive medication burden. Results of a multicentre observational study

What is known and objectiveDrugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. MethodsThis is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. Results and discussion21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naive patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR=1.82, 95% CI for OR: 1.36-2.45, P What is new and conclusionThere was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects.Peer reviewe

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

Objective: The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods: In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results: 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions: In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153)

Anticholinergic medications in patients admitted with cognitive impairment or falls (AMiCI). The impact of hospital admission on anticholinergic cognitive medication burden. Results of a multicentre observational study.

WHAT IS KNOWN AND OBJECTIVE: Drugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. METHODS: This is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. RESULTS AND DISCUSSION: 21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naïve patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR = 1.82, 95% CI for OR: 1.36-2.45, P < .001). WHAT IS NEW AND CONCLUSION: There was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

ObjectiveThe objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF).MethodsIn a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF.Results26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.ConclusionsIn ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153)

Body mass index and mortality in acutely decompensated heart failure across the world:a global obesity paradox

ObjectivesThis study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk.BackgroundObesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF.MethodsWe studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality.ResultsNormal-weight patients (BMI 18.5 to 25 kg/m2) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m2; p < 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p < 0.001). Notably, the “protective” association of BMI with mortality was confined to persons with older age (>75 years; hazard ratio [HR]: 0.82; p = 0.006), decreased cardiac function (ejection fraction <50%; HR: 0.85; p < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p = 0.004).ConclusionsA lower BMI is associated with age, disease severity, and a higher risk of death in acute decompensated HF. The “obesity paradox” is confined to older persons, with decreased cardiac function, less cardiometabolic illness, and recent-onset HF, suggesting that aging, HF severity/chronicity, and metabolism may explain the obesity paradox

Spearman correlation coefficients between biomarkers.

<p>All values were log transformed except serum creatinine (Screat) and blood urea nitrogen (BUN), NT-proBNP, N-terminal pro-brain natriuretic peptide; BNP, brain natriuretic peptide-BNP; eGFR, estimated glomerular filtration rate; pNGAL, plasma neutrophil gelatinase associated lipocalin; uNGAL, urine neutrophil gelatinase associated lipocalin; KIM-1, kidney injury molecule-1; NAG, urine N-acetyl-beta-D-glucosaminidase.</p><p>Spearman correlation coefficients between biomarkers.</p

Results of baseline biomarkers in patients who developed worsening renal function and those who did not.

<p>Amino-terminal pro-B type natriuretic peptide, NT-proBNP; B type natriuretic peptide, BNP; Estimated glomerular filtration rate, eGFR; Neutrophil gelatinase-associated lipocalin, NGAL, urine kidney injury molecule-1, KIM-1, urine N-acetyl-beta-D-glucosaminidase, NAG. Urine biomarkers are expressed per gram urinary creatinine.</p><p>Results of baseline biomarkers in patients who developed worsening renal function and those who did not.</p

Receiver operating curve of biomarkers of cardiac stretch (1A), renal function (1B) and renal injury (1C).

<p>Receiver operating curve of biomarkers of cardiac stretch (1A), renal function (1B) and renal injury (1C).</p

Logistic regression analysis for the primary endpoint of WRF.

<p>In univariable analysis, several candidates were significant predictors. Optimal cutoffs were determined using the value providing optimal sensitivity and specificity balance. Amino-terminal pro-B type natriuretic peptide, NT-proBNP; B type natriuretic peptide, BNP; Estimated glomerular filtration rate, eGFR; Neutrophil gelatinase-associated lipocalin, NGAL, urine kidney injury molecule-1, KIM-1, urine N-acetyl-beta-D-glucosaminidase, NAG; urine Cystatin C, uCyst C.</p><p>Logistic regression analysis for the primary endpoint of WRF.</p

Baseline characteristics of study subjects as a function of the subsequent development of WRF.

<p>Few differences between the groups existed.</p><p>Baseline characteristics of study subjects as a function of the subsequent development of WRF.</p