Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial.

BACKGROUND: Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes. METHODS: We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. RESULTS: Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. CONCLUSION: BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. REGISTRATION: ClinicalTrials.gov identifier: NCT02986425. December 8, 2016.

Healthcare Costs and Health-Related Quality of Life in Older Multimorbid Patients After Hospitalization.

Objectives: We identified factors associated with healthcare costs and health-related quality of life (HRQoL) of multimorbid older adults with polypharmacy. Methods: Using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid older people) trial, we described the magnitude and composition of healthcare costs, and time trends of HRQoL, during 1-year after an acute-care hospitalization. We performed a cluster analysis to identify groups with different cost and HRQoL trends. Using multilevel models, we also identified factors associated with costs and HRQoL. Results: Two months after hospitalization monthly mean costs peaked (CHF 7'124) and HRQoL was highest (0.67). They both decreased thereafter. Age, falls, and comorbidities were associated with higher 1-year costs. Being female and housebound were negatively associated with HRQoL, while moderate alcohol consumption had a positive association. Being independent in daily activities was associated with lower costs and higher HRQoL. Conclusion: Although only some identified potential influences on costs and HRQoL are modifiable, our observations support the importance of prevention before health deterioration in older people with multimorbid illness and associated polypharmacy.

Association between diabetes overtreatment in older multimorbid patients and clinical outcomes: an ancillary European multicentre study.

BACKGROUND: Diabetes overtreatment is a frequent and severe issue in multimorbid older patients with type 2 diabetes (T2D). OBJECTIVE: This study aimed at assessing the association between diabetes overtreatment and 1-year functional decline, hospitalisation and mortality in older inpatients with multimorbidity and polypharmacy. METHODS: Ancillary study of the European multicentre OPERAM project on multimorbid patients aged ≥70 years with T2D and glucose-lowering treatment (GLT). Diabetes overtreatment was defined according to the 2019 Endocrine Society guideline using HbA1c target range individualised according to the patient's overall health status and the use of GLT with a high risk of hypoglycaemia. Multivariable regressions were used to assess the association between diabetes overtreatment and the three outcomes. RESULTS: Among the 490 patients with T2D on GLT (median age: 78 years; 38% female), 168 (34.3%) had diabetes overtreatment. In patients with diabetes overtreatment as compared with those not overtreated, there was no difference in functional decline (29.3% vs 38.0%, P = 0.088) nor hospitalisation rates (107.3 vs 125.8/100 p-y, P = 0.115) but there was a higher mortality rate (32.8 vs 21.4/100 p-y, P = 0.033). In multivariable analyses, diabetes overtreatment was not associated with functional decline nor hospitalisation (hazard ratio, HR [95%CI]: 0.80 [0.63; 1.02]) but was associated with a higher mortality rate (HR [95%CI]: 1.64 [1.06; 2.52]). CONCLUSIONS: Diabetes overtreatment was associated with a higher mortality rate but not with hospitalisation or functional decline. Interventional studies should be undertaken to test the effect of de-intensifying GLT on clinical outcomes in overtreated patients.

Palliative profile, one-year mortality and quality of life in older inpatients according to Be-PICT: a multicenter prospective cohort study.

BACKGROUND: A palliative care approach (PCA), including advanced care planning (ACP), should be considered for patients with limited life expectancy. The Belgian Palliative Care Indicators Tool (Be-PICT) has been released to help identify patients who may benefit from such approach. This study aimed at measuring 1-year mortality and describe the quality of life in older inpatients, according to baseline Be-PICT results. METHODS: Prospective multicentre cohort study in older patients (≥ 75 years) admitted at geriatrics and cardiology wards of four Belgian hospitals. The palliative profile was defined as a positive Be-PICT.1, defined by the presence of its three criteria, i.e. a negative physician's answer to the surprise question 'would you be surprised if this patient dies in the 6-12 next months?', ≥ 1 poor health indicator and ≥ 1 life-limiting condition. RESULTS: Of the 379 patients (50% aged ≥85 years; 51% female), 52 (14%) presented a palliative profile and 83 (23%) died within 1 year. Be-PICT.1 showed the following characteristics to predict 1-year mortality: sensitivity 0.54, specificity 0.83, positive and negative predictive values 0.48 and 0.86, positive and negative likelihood ratios 3.22 and 0.55. The patients with a palliative profile were at higher mortality risk (hazard ratio 4.79 p < 0.001) and 1-year mortality rate (45%). Not using the SQ allowed to improve sensitivity to include a larger number of patients who may benefit from ACP and PCA. CONCLUSIONS: Be-PICT.1 is a simple case-finding tool to identify older inpatients being at high mortality risk and candidates for ACP and PCA.

Comparison of 6 Mortality Risk Scores for Prediction of 1-Year Mortality Risk in Older Adults With Multimorbidity.

Importance: The most appropriate therapy for older adults with multimorbidity may depend on life expectancy (ie, mortality risk), and several scores have been developed to predict 1-year mortality risk. However, often, these mortality risk scores have not been externally validated in large sample sizes, and a head-to-head comparison in a prospective contemporary cohort is lacking. Objective: To prospectively compare the performance of 6 scores in predicting the 1-year mortality risk in hospitalized older adults with multimorbidity. Design, Setting, and Participants: This prognostic study analyzed data of participants in the OPERAM (Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People) trial, which was conducted between December 1, 2016, and October 31, 2018, in surgical and nonsurgical departments of 4 university-based hospitals in Louvain, Belgium; Utrecht, the Netherlands; Cork, Republic of Ireland; and Bern, Switzerland. Eligible participants in the OPERAM trial had multimorbidity (≥3 coexisting chronic diseases), were aged 70 years or older, had polypharmacy (≥5 long-term medications), and were admitted to a participating ward. Data were analyzed from April 1 to September 30, 2020. Main Outcomes and Measures: The outcome of interest was any-cause death occurring in the first year of inclusion in the OPERAM trial. Overall performance, discrimination, and calibration of the following 6 scores were assessed: Burden of Illness Score for Elderly Persons, CARING (Cancer, Admissions ≥2, Residence in a nursing home, Intensive care unit admit with multiorgan failure, ≥2 Noncancer hospice guidelines) Criteria, Charlson Comorbidity Index, Gagné Index, Levine Index, and Walter Index. These scores were assessed using the following measures: Brier score (0 indicates perfect overall performance and 0.25 indicates a noninformative model); C-statistic and 95% CI; Hosmer-Lemeshow goodness-of-fit test and calibration plots; and sensitivity, specificity, and positive and negative predictive values. Results: The 1879 patients in the study had a median (IQR) age of 79 (74-84) years and 835 were women (44.4%). The median (IQR) number of chronic diseases was 11 (8-16). Within 1 year, 375 participants (20.0%) died. Brier scores ranged from 0.16 (Gagné Index) to 0.24 (Burden of Illness Score for Elderly Persons). C-statistic values ranged from 0.62 (95% CI, 0.59-0.65) for Charlson Comorbidity Index to 0.69 (95% CI, 0.66-0.72) for the Walter Index. Calibration was good for the Gagné Index and moderate for other mortality risk scores. Conclusions and Relevance: Results of this prognostic study suggest that all 6 of the 1-year mortality risk scores examined had moderate prognostic performance, discriminatory power, and calibration in a large cohort of hospitalized older adults with multimorbidity. Overall, none of these mortality risk scores outperformed the others, and thus none could be recommended for use in daily clinical practice.

Cost-effectiveness of a structured medication review approach for multimorbid older adults: Within-trial analysis of the OPERAM study.

BACKGROUND: Inappropriate polypharmacy has been linked with adverse outcomes in older, multimorbid adults. OPERAM is a European cluster-randomized trial aimed at testing the effect of a structured pharmacotherapy optimization intervention on preventable drug-related hospital admissions in multimorbid adults with polypharmacy aged 70 years or older. Clinical results of the trial showed a pattern of reduced drug-related hospital admissions, but without statistical significance. In this study we assessed the cost-effectiveness of the pharmacotherapy optimisation intervention. METHODS: We performed a pre-planned within-trial cost-effectiveness analysis (CEA) of the OPERAM intervention, from a healthcare system perspective. All data were collected within the trial apart from unit costs. QALYs were computed by applying the crosswalk German valuation algorithm to EQ-5D-5L-based quality of life data. Considering the clustered structure of the data and between-country heterogeneity, we applied Generalized Structural Equation Models (GSEMs) on a multiple imputed sample to estimate costs and QALYs. We also performed analyses by country and subgroup analyses by patient and morbidity characteristics. RESULTS: Trial-wide, the intervention was numerically dominant, with a potential cost-saving of CHF 3'588 (95% confidence interval (CI): -7'716; 540) and gain of 0.025 QALYs (CI: -0.002; 0.052) per patient. Robustness analyses confirmed the validity of the GSEM model. Subgroup analyses suggested stronger effects in people at higher risk. CONCLUSION: We observed a pattern towards dominance, potentially resulting from an accumulation of multiple small positive intervention effects. Our methodological approaches may inform other CEAs of multi-country, cluster-randomized trials facing presence of missing values and heterogeneity between centres/countries.

Performance of a trigger tool for detecting drug-related hospital admissions in older people: analysis from the OPERAM trial.

BACKGROUND: identifying drug-related hospital admissions (DRAs) in older people is difficult. A standardised chart review procedure has recently been developed. It includes an adjudication team (physician and pharmacist) screening using 26 triggers and then performing causality assessment to determine whether an adverse drug event (ADE) occurred (secondary to an adverse drug reaction, overuse, misuse or underuse) and whether the ADE contributed to hospital admission (DRA). OBJECTIVE: to assess the performance of those triggers in detecting DRA. DESIGN: retrospective study using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people) trial. SETTINGS: four European medical centres. SUBJECTS: multimorbid (≥ 3 chronic medical conditions) older (≥ 70 years) inpatients with polypharmacy (≥ 5 chronic medications) were enrolled in the OPERAM trial (N = 2,008) and followed for 12 months. We included patients with ≥1 adjudicated hospitalisation during the follow-up. METHODS: the positive predictive value (PPV; number of DRAs identified by trigger/number of triggers) was calculated for each trigger and for the tool as a whole. RESULTS: of 1,235 hospitalisations adjudicated for 832 patients, 716 (58%) had at least one trigger; an ADE was identified in 673 (54%) and 518 (42%) were adjudicated as DRAs. The overall PPV of the trigger tool for detecting DRAs was 0.66 [0.62-0.69]. CONCLUSIONS: this tool performs well for identifying DRAs in older people. Based on our results, a revised version of the tool was proposed but will require external validation before it can be incorporated into research and clinical practice.

Prevalence of drug-drug interactions in older people before and after hospital admission: analysis from the OPERAM trial.

BACKGROUND: Drug-drug interactions (DDIs) are highly prevalent in older patients but little is known about prevalence of DDIs over time. Our main objective was to assess changes in the prevalence and characteristics of drug-drug interactions (DDIs) during a one-year period after hospital admission in older people, and associated risk factors. METHODS: We conducted a sub-study of the European OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people), which assessed the effects of a structured medication review (experimental arm) compared to usual care (control arm) on reducing drug-related hospital readmissions. All OPERAM patients (≥70 years, with multimorbidity and polypharmacy, hospitalized in four centers in Bern, Brussels, Cork and Utrecht between December 2016 and October 2018, followed over 1 year) who were alive at hospital discharge and had full medication data during the index hospitalization (at baseline i.e., enrolment at admission, and at discharge) were included. DDIs were assessed using an international consensus list of potentially clinically significant DDIs in older people. The point-prevalence of DDIs was evaluated at baseline, discharge, and at 2, 6 and 12 months after hospitalization. Logistic regression models were performed to assess independent variables associated with changes in DDIs 2 months after baseline. RESULTS: Of the 1950 patients (median age 79 years) included, 1045 (54%) had at least one potentially clinically significant DDI at baseline; point-prevalence rates were 58, 57, 56 and 57% at discharge, and 2, 6 and 12 months, respectively. The prevalence increased significantly from baseline to discharge (P < .001 [significant only in the control group]), then remained stable over time (P for trend .31). The five most common DDIs -all pharmacodynamic in nature- accounted for 80% of all DDIs and involved drugs that affect potassium concentrations, centrally-acting drugs and antithrombotics. At 2 months, DDIs had increased in 459 (27%) patients and decreased in 331 (19%). The main factor predictive of a change in the prevalence of DDIs was hyperpolypharmacy (≥10 medications). CONCLUSIONS: DDIs were very common; their prevalence increased during hospitalization and tended to remain stable thereafter. Medication review may help control this increase and minimize the risk of adverse drug events.

Trends in benzodiazepine receptor agonists use and associated factors in the Belgian general older population: analysis of the Belgian health interview survey data.

BACKGROUND: Benzodiazepine receptor agonists (BZRA), which include benzodiazepines and z-drugs, are commonly prescribed for insomnia and anxiety in older adults, and used often long term. Yet, the risk-benefit ratio of BZRA use in older adults may be unfavorable and many recommendations suggest avoidance or a maximal treatment duration of 4 weeks. The aim of this study was to describe trends of BZRA use in older adults and associated factors. METHODS: Using data from the Belgian Health Interview Survey in 2004 (n = 3594), 2008 (n = 2917), and 2013 (n = 2048), prevalence standardized for age, sex, and region were calculated to assess trends of BZRA use in people ⩾65 years. Analysis of associated factors to BZRA use was performed using a sub-sample of 2013 data for which variables assessing sleeping disorder and anxiety disorder were not missing (n = 1286). Variables from seven main topics were explored using multivariate logistic regression: socio-demographic factors, geriatric factors, comorbidities, subjective health and mental health indicators, social health indicators, medication use and healthcare services use. RESULTS: Overall, standardized prevalence of BZRA use decreased significantly between 2004 and 2013 [22% to 18%, prevalence difference (95% confidence interval, CI): -4.0% (-6.8; -1.3)]. Factors associated with BZRA use in multivariable analysis included female gender [adjusted odds ratio (aOR) (95%CI) : 1.62 (1.14; 2.29)], poor mental health [aOR (95%CI): 1.73 (1.13-2.63)] a fall in the past 12 months [aOR (95%CI): 1.52 (1.02; 2.26), reporting a sleeping disorder [aOR (95%CI): 1.92 (1.35; 2.72)], polypharmacy [aOR (95%CI): 2.51 (1.75; 3.60)], and trazodone use [aOR (95%CI): 4.05 (1.64; 10.21)]. CONCLUSION: Despite an encouraging decline observed from 2004 to 2013, BZRA use remained highly prevalent in Belgian older adults. Promotion of alternatives to BZRA in treatment of sleeping problems need to be continued. Among BZRA older users, women, the oldest (⩾85 years) and high-risk subgroups should be targeted in deprescribing interventions.

Benzodiazepine Use and Deprescribing in Belgian Nursing Homes: Results from the COME-ON Study.

BACKGROUND/OBJECTIVES: To describe the use and deprescribing of benzodiazepine receptor agonists (BZRAs) among nursing home residents (NHRs), to evaluate appropriateness of use and to identify factors associated with BZRA use and deprescribing. DESIGN: Posthoc analysis of the Collaborative Approach to Optimize Medication Use for Older People in Nursing Homes (COME-ON) study, a cluster controlled trial that evaluated the impact of a complex intervention on potentially inappropriate prescriptions (PIPs) in nursing homes (NHs). SETTING: A total of 54 NHs in Belgium. PARTICIPANTS: A total of 797 NHRs included in the study who had complete medical, clinical, and medication information at baseline and at the end of the study (month 15). MEASUREMENTS: Data were recorded by participating healthcare professionals. Reasons why BZRA use was considered as PIPs were assessed using the 2019 American Geriatrics Society Beers Criteria® and the Screening Tool of Older Persons' Prescriptions (STOPP) criteria, version 2. Deprescribing included complete cessation or decreased daily dose. We identified factors at the NHR, prescriber, and NH levels associated with BZRA use and BZRA deprescribing using multivariable binary and multinomial logistic regression, respectively. RESULTS: At baseline, 418 (52.4%) NHRs were taking a BZRA. The use of BZRA for longer than 4 weeks, with two or more other central nervous system active drugs, and in patients with delirium, cognitive impairment, falls, or fractures was found in more than 67% of BZRA users. Eight NHR-related variables and two prescriber-related variables were associated with regular BZRA use. Deprescribing occurred in 28.1% of BZRA users (32.9% in the intervention group and 22.1% in the control group). In addition to four other factors, dementia (odds ratio [OR] = 2.35; 95% confidence interval [CI] = [1.45-3.83]) and intervention group (OR = 1.74; 95% CI = 1.07-2.87) were associated with deprescribing. CONCLUSION: Use of BZRAs was highly prevalent, and reasons to consider it as PIP were frequent. Deprescribing occurred in one-fourth of NHRs, which is encouraging. Future interventions should focus on specific aspects of PIPs (ie, indication, duration, drug-drug and drug-disease interactions) as well as on nondementia patients.

Trends in multimorbidity and polypharmacy in the Flemish-Belgian population between 2000 and 2015.

OBJECTIVES: The aim of this paper was to describe the time trends in the prevalence of multimorbidity and polypharmacy in Flanders (Belgium) between 2000 and 2015, while controlling for age and sex. METHODS: Data were available from Intego, a Flemish-Belgian general practice-based morbidity registration network. The practice population between 2000 and 2015 was used as the denominator, representing a mean of 159,946 people per year. Age and gender-standardised prevalence rates were used for the trends of multimorbidity and polypharmacy in the total population and for subgroups. Joinpoint regression analyses were used to analyse the time trends and breaks in trends, for the entire population as well as for specific age and sex groups. RESULTS: Overall, in 2015, 22.7% of the population had multimorbidity, while the overall prevalence of polypharmacy was 20%. Throughout the study period the standardised prevalence rate of multimorbidity rose for both sexes and in all age groups. The largest relative increase in multimorbidity was observed in the younger age groups (up to the age of 50 years). The prevalence of polypharmacy showed a significant increase between 2000 and 2015 for all age groups except the youngest (0-25 years). CONCLUSION: For all adult age groups multimorbidity and polypharmacy are frequent, dynamic over time and increasing. This asks for both epidemiological and interventional studies to improve the management of the resulting complex care.

Potentially Inappropriate Prescribing in Belgian Nursing Homes: Prevalence and Associated Factors.

BACKGROUND/OBJECTIVES: Our aim was to describe the prevalence of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) in Belgian nursing homes and to identify characteristics of residents, general practitioners (GPs), and nursing homes (NHs) that are associated with the number of PIMs and PPOs. DESIGN: A cross-sectional study. SETTING: and Participants: Nursing home residents (NHRs), aged ≥65 years, not in palliative care were included in 54 Belgian NHs participating in the COME-ON study. MEASURES: Instances of PIMs were detected using a combination of the STOPP v2 and AGS 2015 Beers criteria. Instances of PPOs were detected using START v2. To assess factors associated with the number of PIMs and PPOs, a multivariate binomial negative regression analysis was performed. RESULTS: A total of 1410 residents, with a median age of 87 years, was included. The median number of medications taken was 9. PIMs were detected in 88.3% of NHRs and PPOs in 85.0%. Use of benzodiazepines (46.7%) and omission of vitamin D (51.5%) were the most common PIM and PPO, respectively. The factor most strongly associated with increased PIMs was the use of 5 to 9 drugs or ≥10 drugs [relative risk (RR) (95% confidence interval [CI]: 2.27 (1.89, 2.76) and 4.04 (3.37, 4.89), respectively]. The resident's age was associated with both decreased PIMs and increased PPOs. PIMs and PPOs were also associated with some NH characteristics, but not with GP characteristics. CONCLUSION: Implications: The high prevalence of PIMs and PPOs remains a major challenge for the NH setting. Future interventions should target in priority residents taking at least 10 medications and/or those taking psychotropic drugs. Future studies should explore factors related to organizational and prescribing culture. Moreover, special attention must be paid to the criteria used to measure inappropriate prescribing, including criteria relative to underuse.

Factors associated with Prolonged Inaction in the hypoglycaemic treatment in people with non-insulin dependent Type 2 Diabetes and elevated glycated haemoglobin: A registry-based cohort study.

AIMS: To assess factors associated with Prolonged Inaction (PI) in insulin-naïve patients with Type 2 Diabetes Mellitus (T2DM). PI was defined as the absence of treatment initiation or intensification for ≥12 months despite HbA1c >7% (53mmol/mol). METHODS: A retrospective cohort study was conducted based on data from Intego, a Flemish General Practice registry. The study period ranged from January 1, 2006 to December 31, 2013. Patients with insulin therapy before the start of the study period were excluded from the analysis. A mixed effects logistic regression was used to assess the association of PI with the presence of co-morbidities, co-medications, process parameters and bio-clinical parameters. RESULTS: In a population of 2265 patients with T2DM, 578 insulin-naive patients presented with an HbA1c >7% (53mmol/mol) for ≥12 months. Median follow-up was 1.2 years, median age 67 years, 55% were male. PI was present in 340 patients (59%) and associated with moderate to severe Chronic Kidney Disease, absence of a mental health disorder, less frequent HbA1c measurements, lower HbA1c values and a smaller number of co-medications. CONCLUSIONS: PI is highly prevalent in primary care, particularly in patients with less complex disease status and with less intensive follow-up.

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

OBJECTIVES: Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. METHODS: A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS2 [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS2 and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. RESULTS: Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. CONCLUSION: Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse.

Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study.

CONTEXT: The long-term mortality in adults treated with recombinant GH during childhood has been poorly investigated. Recently released data from the French part of the European Union Safety and Appropriateness of GH treatments in Europe (EU SAGhE) study have raised concerns on the long-term safety of GH treatment. OBJECTIVE: To report preliminary data on long-term vital status and causes of death in patients with isolated GH deficiency or idiopathic short stature or born small for gestational age treated with GH during childhood, in Belgium, The Netherlands, and Sweden. DESIGN: Data were retrieved from national registries of GH-treated patients and vital status from National Population Registries. Causes of death were retrieved from a National Cause of Death Register (Sweden), Federal and Regional Death Registries (Belgium), or individual patient records (The Netherlands). PATIENTS: All patients diagnosed with isolated GH deficiency or idiopathic short stature or born small for gestational age started on recombinant GH during childhood from 1985-1997 and who had attained 18 yr of age by the end of 2010 were included. Vital status was available for approximately 98% of these 2,543 patients, corresponding to 46,556 person-years of observation. MAIN OUTCOME MEASURE: Vital status, causes of death, age at death, year of death, duration of GH treatment, and mean GH dose during treatment were assessed. RESULTS: Among 21 deaths identified, 12 were due to accidents, four were suicides, and one patient each died from pneumonia, endocrine dysfunction, primary cardiomyopathy, deficiency of humoral immunity, and coagulation defect. CONCLUSIONS: In these cohorts, the majority of deaths (76%) were caused by accidents or suicides. Importantly, none of the patients died from cancer or from a cardiovascular disease.

Coronary artery calcification: a strong predictor of cardiovascular events in renal transplant recipients.

BACKGROUND: Coronary artery calcification (CAC) independently predicts cardiovascular events (CVE) in the general population. Whether this applies to renal transplant recipients (RTR) is unknown. This prospective study assessed the prognostic impact of CAC on CVE in RTR. METHODS: We followed up a published cohort of 281 prevalent RTR. At baseline, 16-slice chest spiral computerized tomography scan was performed and classical as well as CKD-related risk factors were recorded. Major CVE (MCVE) was defined as cardiovascular death, myocardial infarction, stroke or transient ischaemic attack. All CVE (ACVE) included MCVE and revascularizations. Prognostic factors were assessed by univariate and multivariate Cox regression. RESULTS: During 2.3 ± 0.5 years of follow-up, 16 patients died from CV (n = 8) or non-CV causes (n = 8). Thirty-one RTR developed at least one CVE (first CVE cardiac in 15, peripheral in 12 and cerebrovascular in 4) for a total of 36 CVE. Thirty-month CV survival, MCVE-free survival and ACVE-free survival was 96.4, 93.9 and 87.9%, respectively. By multivariate analysis, the independent predictors of ACVE were CAC score (hazards ratios [HR] = 1.40 [1.12; 1.75] for a 2.72-fold increase in CAC, P < 0.003) and history of CVE (HR = 2.76 [1.21; 6.39], P < 0.02). CONCLUSION: Our study shows for the first time that CAC is a strong independent predictor of CVE in RTR.