The ETHICA study (part I): elderly's thoughts about intensive care unit admission for life-sustaining treatments.

PURPOSE: To assess preferences among individuals aged ≥80 years for a future hypothetical critical illness requiring life-sustaining treatments. METHODS: Observational cohort study of consecutive community-dwelling elderly individuals previously hospitalised in medical or surgical wards and of volunteers residing in nursing homes or assisted-living facilities. The participants were interviewed at their place of residence after viewing films of scenarios involving the use of non-invasive mechanical ventilation (NIV), invasive mechanical ventilation (IMV), and renal replacement therapy after a period of invasive mechanical ventilation (RRT after IMV). Demographic, clinical, and quality-of-life data were collected. Participants chose among four responses regarding life-sustaining treatments: consent, refusal, no opinion, and letting the physicians decide. RESULTS: The sample size was 115 and the response rate 87 %. Mean participant age was 84.8 ± 3.5 years, 68 % were female, and 81 % and 71 % were independent for instrumental activities and activities of daily living, respectively. Refusal rates among the elderly were 27 % for NIV, 43 % for IMV, and 63 % for RRT (after IMV). Demographic characteristics associated with refusal were married status for NIV [relative risk (RR), 2.9; 95 % confidence interval (95 %CI), 1.5-5.8; p = 0.002] and female gender for IMV (RR, 2.4; 95 %CI, 1.2-4.5; p = 0.01) and RRT (after IMV) (RR, 2.7; 95 %CI, 1.4-5.2; p = 0.004). Quality of life was associated with choices regarding all three life-sustaining treatments. CONCLUSIONS: Independent elderly individuals were rather reluctant to accept life-sustaining treatments, especially IMV and RRT (after IMV). Their quality of life was among the determinants of their choices.

Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients.

Determining the optimal dose of warfarin for frail elderly patients is a challenging task because of the low dose requirements in such patients, the wide interindividual variability of response, and the associated risk of bleeding. The objective of this study was to address the influence of 13 common variations in eight genes on the maintenance dose of warfarin in a cohort of frail elderly inpatients. For our study, we enrolled 300 Caucasian subjects who were hospital inpatients, with a mean age of 86.7 +/- 6 years. In addition to age, genetic variants of VKORC1, CYP2C9, CYP4F2, and EPHX1 were found to be significant predictor variables for the maintenance dose of warfarin, explaining 26.6% of dose variability. Among 132 patients in whom warfarin therapy was initiated with the same low-dose regimen, we studied the relative influences of genetic and nongenetic factors. The time to first international normalized ratio (INR) > or =2 was influenced by VKORC1 and CYP2C9 genotypes (P = 0.0003 and P = 0.0016, respectively); individuals with multiple variant alleles were at highest risk for overanticoagulation (INR >4) (odds ratio, 12.8; 95% confidence interval, 2.73-60.0). In this special population of frail elderly patients with multiple comorbidities and polypharmacy, we demonstrated the main impact of genetic factors on warfarin response.

[Transfusion in clinical practice in geriatric wards]. / Enquête transversale sur la transfusion dans les services de gériatrie.

PURPOSE: In the absence of specific recommendations on blood transfusion in elderly subjects, we carried out a survey to assess transfusion practices in geriatric medicine. METHODS: A descriptive, national, cross-sectional survey was conducted in 14 French geriatric departments (12 teaching hospitals and two general hospitals). In each department, five patients receiving transfusions were randomly selected in order to analyze their characteristics, the indications of blood transfusion, the criteria for and the methods of transfusion compared with Afssaps recommendations on transfusion thresholds. RESULTS: Data were analyzed for 70 patients (mean age 86+/-7 years, sex ratio female to male 1.8, with an average of five+/-two pathologies and six+/-three treatments). The indicators of poor tolerance included confusion (23 %), somnolence (22 %), acute heart failure (17 %) or coronary heart disease (16 %), and differed from the Afssaps criteria in the majority of cases. The transfusion threshold that were considered in the absence of poor tolerance (45 % of transfusions) differed from that recommended by Afssaps in 26 % of cases. The main adverse event in transfusion recipients was heart failure. CONCLUSION: When criteria for poor anaemia tolerance or transfusion thresholds are considered, transfusion practices in geriatric subjects have specific features. Further studies are needed to validate the appropriateness of the practices described in this survey.

[Inappropriateness of hospital use in two acute geriatrics department: description of the phenomenon and analysis of risk factors]. / Non-pertinence hospitalière dans deux services de gériatrie aiguë: description du phénomène et étude des facteurs de risque.

BACKGROUND: Inappropriateness of hospital use occurs when a gap between the patient's needs and the level of care delivered exists. Taking into account the improvement of number of acute geriatric care, it appears relevant to study the rate and causes of inappropriate hospital use in this context. METHODS: All patients in two services of acute geriatrics were included: medical and socioeconomic data were collected, the appropriateness of each day of their hospitalization was evaluated using the French version of the Appropriateness Evaluation Protocol and the inappropriate days' Causes Analysis Protocol. Risk factors of having at least one inappropriate day occurring during the stay were searched using relevant statistical tests. A logistic regression model assessed influence of independent variables on the risk of inappropriateness. RESULTS: Only the existence of cognitive impairment and the department where the hospitalization takes place were found to be risk factors of inappropriateness. The ranking of inappropriateness according to the causes is the same in the two services, yet with statistically different rates, in particular for causes related to waiting for admission in subacute or long-term care institutional network and for a service provided outside the hospital where the patient was admitted. In the two departments, over 25% of the inappropriate days were related to a patient's or his family's choice. CONCLUSION: Access to subacute or long-term care institution is the first cause of inappropriate hospital use in the two departments. The importance of the rate of inappropriate days related to a choice of the patient or his family was probably a Geriatric specificity. Furthermore, in view of reducing the inappropriate hospital use, attention should be particularly paid on patients with cognitive impairment.

[Acute pulmonary infections in elderly patients in institutions]. / Infections pulmonaires aiguës chez les patients âgés en institution.

The high incidence of lower lung infections in elderly subjects in institutions is responsible for an increase in mortality both as the result of the infection itself and of the deterioration of pre-existing conditions. The multiple pathology of these elderly patients living in institutions necessitates particularly detailed diagnosis and management. While the pneumococcus remains the predominant organism the percentage of infections with staphylococci and Gram negative bacteria is higher than among younger subjects. The initial severity should be assessed by clinical and pathological criteria in the same way as the response to treatment. Transfer to hospital is often necessary. Among preventative measures anti-influenzal and anti-pneumococcal vaccines are recommended and reimbursed at 100%.

[Acute pulmonary infections in elderly patients in institutions]. / Infections pulmonaires aiguës chez les patients âgés en institution.

The high incidence of lower lung infections in elderly subjects in institutions is responsible for an increase in mortality both as the result of the infection itself and of the deterioration of pre-existing conditions. The multiple pathology of these elderly patients living in institutions necessitates particularly detailed diagnosis and management. While the pneumococcus remains the predominant organism the percentage of infections with staphylococci and Gram negative bacteria is higher than among younger subjects. The initial severity should be assessed by clinical and pathological criteria in the same way as the response to treatment. Transfer to hospital is often necessary. Among preventative measures anti-influenzal and anti-pneumococcal vaccines are recommended and reimbursed at 100%.

[Monitoring of tinzaparin in a ten day treatment dose in elderly patients]. / Surveillance d'un traitement par la tinzaparine à dose curative pendant dix jours chez le sujet âgé.

PURPOSE: Renal impairment, which is frequently observed in elderly patients, raises the question of low molecular weight heparins treatment dose adjustment in this population. Thus, we conducted a prospective study to determine whether tinzaparin, administered subcutaneously at treatment dose (175 anti-Xa IU/kg) once daily for 10 days, does accumulate in patients older than 70 years of age. METHODS: Accumulation criteria were an increase of plasma anti-Xa and anti-IIa levels determined prior to the first injection and on days 2, 5, 7 and 10. The characteristics of the 30 consecutive included patients receiving tinzaparin at treatment dose (six men, 24 women) were: age 87.0 +/- 5.9 years (range: 71-96 years), body weight: 62.7 +/- 14.6 kg (range: 38-90 kg) and creatinine clearance 40.6 +/- 15.3 mL/min (range: 20-72 mL/min). RESULTS: None of the patients required a dose adjustment of tinzaparin over the 10-day treatment period. Anti-Xa and anti-IIa activity levels on day 2 were 0.66 +/- 0.20 IU/mL (range: 0.26-1.04 IU/mL) and 0.33 +/- 0.10 IU/mL (range: 0.18-0.55 IU/mL), respectively. These levels did not significantly change over the 10 days. These results favor the absence of the accumulation effect of tinzaparin. There was no correlation between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. Concerning the side-effects, only one minor hematoma at the injection site was reported. CONCLUSION: Tinzaparin may thus be administered in older patients with renal impairment, at a treatment dose (175 anti-Xa IU/kg/d) for a 10-day treatment period, without accumulation effect nor hemorrhagic side-effect in patients with creatinine clearance greater than 20 mL/min.

Elderly patients treated with tinzaparin (Innohep) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days.

Since low molecular weight heparins (LMWH) are partly eliminated by renal excretion, their pharmacodynamic profile may be modified in very elderly patients with age-related renal impairment. The aim of this prospective study was to determine whether tinzaparin (Innohep) 175 anti-Xa IU/kg administered subcutaneously once daily over 10 days does accumulate in hospital patients greater than 70 years of age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined prior to the first injection (day 0), and then, at peak level i.e. 5 h after the second injection (day 2) and subsequently on days 5, 7 and 10. Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs at a curative dose for acute thromboembolic disease were included. Patients' characteristics (mean +/- SD) were: age 87.0+/-5.9 years (range 71-96), body weight 62.7+/-14.6 kg (range 38-90) and creatinine clearance 40.6+/-15.3 mL/min (range 20-72). The mean actual dose of tinzaparin delivered was 174.8 anti-Xa IU/kg. Since no patient had an anti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixed over 10 days. Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66+/-0.20 IU/mL (range 0.26-1.04) and 0.33+/-0.10 IU/mL (range 0.18-0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1. APTT ratios (patient/control) were strongly correlated with anti-IIa activity (p <0.01). There was no progressive increase of the anti-Xa and anti-IIa activities after repeated administration of tinzaparin over the 10 day treatment period. No correlation was found between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. No major bleeding occurred during the study and only one minor haematoma at the injection site was reported. No thrombo-embolic complication or death occurred. Tinzaparin may thus be administered safely at a treatment dose (175 anti-Xa IU/kg) in older patients with age-related renal impairment. Neither dose adjustment, nor serial anti-Xa activity monitoring seems to be required in patients with creatinine clearance above 20 mL/min during the first ten day treatment.

Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients.

OBJECTIVE: To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group. METHODS: A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings. RESULTS: Forty-seven men and 38 women, with a mean +/- SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. CONCLUSION: This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent.

[Impact of hospital infection on medical expenditures in a continuing care and rehabilitation service at a geriatric hospital]. / Impact de l'infection nosocomiale sur les consommations médicales en service de soins de suite et réadaptation dans un hôpital gériatrique.

The costs of medical expenditures such as drugs, medical devices (MD), biological assays and nurses workload, were measured, before and after the onset of nosocomial infection (NI), in rehabilitation care departments of a 1000-beds geriatric teaching hospital. Data were collected retrospectively in medical records and nursing records. Nurse's workload was measured by the French indicator "Soins Infirmiers Personnalisé à la Personne Soignée" (SIIPS). A week before and a week after the diagnosis of hospital-acquired infection, medical consumptions were compared. During the study 38 of the 206 patients admitted in rehabilitation care wards presented hospital-acquired infection. Data were collected for 31 of these 38 patients. Nosocomial infections are associated with an increased pharmaceutical dispensing: medication (mainly antibiotics) and medical device's cost; and an increased nurse's workload. This study suggests that infection surveillance may be helpful to a better understanding of pharmaceutical dispensing variation in geriatric rehabilitation care departments.

Treatment of glomerulonephritis in microscopic polyangiitis and Churg-Strauss syndrome. Indications of plasma exchanges, Meta-analysis of 2 randomized studies on 140 patients, 32 with glomerulonephritis.

UNLABELLED: Although plasma exchanges (PE) have no added benefit in the treatment of vasculitides of the polyarteritis nodosa (PAN) group with steroids (CS) +/- cyclophosphamide (CY), this has not been demonstrated in patients presenting with glomerulonephritis (GN). We therefore reanalyzed the records of microscopic polyangiitis (MPA) or Churg-Strauss syndrome (CSS) patients presenting with GN. PATIENTS AND METHODS: Patients were included consecutively in 2 randomized trials: a) comparing CS vs CS + PE (n = 78) and b) comparing CS + pulse CY +/- PE in PAN and CSS with factors of poor prognosis (n = 62); 9-12 PE/patient were performed. RESULTS: 32 patients, 18 men and 14 women, presented with GN, 28 MPA and 4 CSS, mean age 53.2 +/- 17 years. Clinical/biological manifestations before treatment were comparable in both groups: weight loss 84.4%, fever 62.5%, mononeuritis multiplex 62.5%, purpura 28.1%, GI tract involvement 43.8%, arthritis 37.5%, asthma 12.5%, CNS manifestations 9.4%; cardiac involvement 9.4%; mean creatininemia was 303 +/- 286 mumol/l, proteinuria > 0.5 g/l or 1g/d was found in every case, microscopic hematuria in 20/32 patients, leukocyturia in 12/32. Eight out of/16 were ANCA-positive, ELISA detected anti-MPO antibodies in 5 and anti-PR3 in 3. HBV infection was never observed. After 1 year of treatment, creatininemia decreased from 374.4 +/- 352 to 290 +/- 352 mumol/l in the PE group and from 287 +/- 292 to 170 +/- 67 in the non PE group (NS). Six patients of the PE group and 2 of the non-PE group were dialyzed at onset of treatment. Four of the 6 PE patients and 1 of the 2 not treated with PE were off dialysis 1 year later. In addition 1 patient from the PE group developed a flare with renal failure and required chronic dialysis. The 5-year survival was higher in the PE group (4 deaths/19) than in the non PE group (7/13). The survival curve was 74% in the PE group vs 54% in the non-PE group (NS). CONCLUSION: This study confirms that PE have no added benefit in the treatment of GN in MPA and CSS.

[Bacterial resistance and management of nosocomial infections: relations to hematology]. / Résistance bactérienne et prise en charge des infections nosocomiales: quelle réflexion en hématologie?

Because they receive many infected patients with various degrees of immunosuppression, the haematology departments have a high consumption of antibiotics. The possible relationship between antibiotic consumption and bacterial resistance is discussed in many specialities, especially for some classes like quinolones. This possible relationship has to be evocated in haematology where patients are at high risk of severe sepsis because of neutropenia. In Henri Mondor hospital, we studied the evolution of bacterial susceptibility and of antibiotic consumption in the haematology unit on a 6 year period. We found that this susceptibility was finally stable over time. The main factors which may influence the evolution of the bacterial susceptibility in our study, and in the literature are discussed.

Evolution of bacterial susceptibility to antibiotics during a six-year period in a haematology unit.

A knowledge of the bacterial ecology of a haematology unit should help in the management of the febrile patient with or without neutropenia. We studied the prevalence and the susceptibility profiles of bacteria isolated during a six-year period among patients hospitalized in a 44-bed haematology unit. Antibiotic use over this period was also studied. The most prevalent bacteria were coagulase-negative staphylococci (CNS) (35.1%), Escherichia coli (11.4%), Staphylococcus aureus (9.9%), Enterococcus spp. (8.2%), and Pseudomonas aeruginosa (7.5%). The susceptibility of CNS to oxacillin decreased from 67-44% over six years, while that of enterobacteriaceae to amoxycillin and piperacillin was reduced by about 50%. P. aeruginosa susceptibility to ceftazidime remained remarkably stable at around 90%, despite extensive empirical use. Imipenem and ciprofloxacin were used restrictively and ceftazidime-resistant P. aeruginosa remained susceptible to these two agents in most cases. Our antibiotic policy was found to be compatible with the frequency of the bacterial strains isolated in our department and with their susceptibility profiles.