Muriel Rainfray

Predictors of Early Death Risk in Older Patients Treated With First-Line Chemotherapy for Cancer

PURPOSE Objective factors for making choices about the treatment of elderly patients with cancer are lacking. This investigation aimed to help physicians select appropriate treatments through the identification of factors that predict early death (< 6 months) after initiation of chemotherapy treatment. PATIENTS AND METHODS Previously untreated patients greater than 70 years of age who were scheduled for first-line chemotherapy for various types of cancer were included. Baseline abbreviated comprehensive geriatric assessment (aCGA), including the Mini-Mental State Exam, Timed Get Up and Go (GUG), Activities of Daily Living (ADL), Instrumental Activities in Daily Living (IADL), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS15), and comorbidities index (Cumulative Index Rating Scale-Geriatric), was carried out. Prognostic factors of early death were sought from aCGA results and traditional oncology measures. RESULTS A total of 348 patients were included across 12 centers in Southwest France (median age, 77.45 years; ratio of men to women, 1.47; advanced disease, 65%). Abnormal aCGA scores were observed for 18.1% of patients on the ADL, 73.0% of patients on the IADL, 24.1% of patients on the GUG, 19.0% of patients on the MMS, 44.0% of patients on the GDS15, and 64.9% of patients on the MNA. Advanced disease (odds ratio [OR], 3.9; 95% CI, [1.58 to 9.73]), a low MNA score (OR 2.77; 95% CI, [1.24 to 6.18]), male sex (OR, 2.40; 95% CI, [1.2 to 4.82]), and long GUG (OR, 2.55; 95% CI, [1.32 to 4.94] were associated with higher risk of early death. CONCLUSION In patients greater than 70 years of age with cancer, advanced disease, a low MNA score, and poor mobility predicted early death. We recommend that the MNA and GUG, performed by a trained nurse, be maintained as part of routine pretreatment workup in these patients to identify at-risk patients and to inform the decision-making process for chemotherapy.

Undernutrition in elderly patients with cancer: target for diagnosis and intervention.

In recent years, geriatricians and oncologists have worked together to evaluate elderly patients with cancer before and during treatment, to estimate the balance between the efficacy and safety of chemotherapy and to upgrade treatment in this population according to their comorbidity and physiological status. The clinical and biological factors of this population need to be assessed in multidisciplinary comprehensive geriatric assessment (CGA) in order to optimize treatment without inducing major adverse effects. We reviewed the nutritional aspects of this evaluation that highlight the impact of undernutrition on poor survival. In this paper we briefly describe tumoral cachexia (molecular and physiological), the impact of undernutrition on cancer prognosis (predictive factors), therapeutic effects of cancer on nutritional status, nutritional indicators (biological, anthropometric) and undernutrition in the elderly (specific needs of this population). The potential for nutritional intervention in geriatric oncology with regard to CGA is explored.

Functional Decline in Older Patients With Cancer Receiving First-Line Chemotherapy

PURPOSE To determine factors associated with early functional decline during first-line chemotherapy in older patients. PATIENTS AND METHODS Patients age ≥ 70 years receiving first-line chemotherapy for cancer were prospectively considered for inclusion across 12 centers in France. Functional decline was defined as a decrease of ≥ 0.5 points on the Activities of Daily Living (ADL) scale between the beginning of chemotherapy and the second cycle. Factors associated with functional decline were sought from pretreatment abbreviated comprehensive geriatric assessment, including ADL, Instrumental ADL (IADL), Mini-Nutritional Assessment (MNA), Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS15), and Timed Get Up and Go (GUG) test, and from comorbidities (Cumulative Illness Rating Scale-Geriatrics), MAX2 index, and baseline biologic and clinical information. RESULTS Of 364 included patients, 50 experienced functional decline (16.7%; median, 0.5 points). Abnormal preadmission performance status, IADL, GDS15, MMSE, GUG, and MNA were associated with increased likelihood of functional decline (univariate analysis). In the multivariate model adjusted for baseline ADL and MAX2 index, high baseline GDS (odds ratio [OR], 2.16; 95% CI, 1.09 to 4.30; P = .03) and low IADL scores (OR, 2.87; 95% CI, 1.06 to 7.79; P = .04) were independently associated with increased risk of functional decline. CONCLUSION Our results outline associations between baseline depression, instrumental dependencies, and early functional decline during chemotherapy for older patients. ADL should be sequentially evaluated early during treatment. Baseline evaluation of GDS15 and IADL may be proposed to anticipate this event.

Epidemiology and prognostic significance of chronic kidney disease in the elderly--the Three-City prospective cohort study.

BACKGROUND Little is known about normal kidney function level and the prognostic significance of low estimated glomerular filtration rate (eGFR) in the elderly. METHODS We determined age and sex distribution of eGFR with both the Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 8705 community-dwelling elderly aged ≥ 65 years and studied its relation to 6-year mortality. In a subsample of 1298 subjects examined at 4 years, we assessed annual eGFR decline and clinically relevant markers including microalbuminuria (3-30 mg/mmol creatinine) with diabetes, proteinuria ≥ 50 mg/mmol, haemoglobin <11 g/L or resistant hypertension despite three drugs. RESULTS Median (interquartile range) MDRD eGFR was 78 (68-89) mL/min/1.73 m(2) in men and 74 (65-83) in women; there were 79 (68-87) and 77 (67-85) for CKD-EPI eGFR, respectively. Prevalence of MDRD eGFR <60 mL/min/1.73 m(2) was 13.7% and of CKD-EPI eGFR was 12.9%. After adjustment for several confounders, only those with an eGFR <45 mL/min/1.73 m(2) had significantly higher all-cause and cardiovascular mortality than those with an eGFR of 75-89 mL/min/1.73 m(2) whatever the equation. In the subsample men and women with an MDRD eGFR of 45-59 mL/min/1.73 m(2), 15 and 13% had at least one clinical marker and 15 and 3% had microalbuminuria without diabetes, respectively; these percentages were 41 and 21% and 23 and 10% in men and women with eGFR <45, respectively. Mean MDRD eGFR decline rate was steeper in men than in women, 1.75 versus 1.41 mL/min/1.73 m(2)/year. CONCLUSIONS Moderately decreased eGFR is more often associated with clinical markers in men than in women. In both sexes, eGFR <45 mL/min/1.73 m(2) is related to poor outcomes. The CKD-EPI and the MDRD equations provide very similar prevalence and long-term risk estimates in this elderly population.

Health and aging in elderly farmers: the AMI cohort.

BackgroundThe health of the agricultural population has been previously explored, particularly in relation to the farming exposures and among professionally active individuals. However, few studies specifically focused on health and aging among elders retired from agriculture. Yet, this population faces the long-term effects of occupational exposures and multiple difficulties related to living and aging in rural area (limited access to shops, services, and practitioners). However, these difficulties may be counter-balanced by advantages related to healthier lifestyle, richer social support and better living environment. The general aim of the AMI cohort was to study health and aging in elderly farmers living in rural area through a multidisciplinary approach, with a main focus on dementia.Methods/designThe study initially included 1 002 participants, randomly selected from the Farmer Health Insurance rolls. Selection criteria were: being 65 years and older; living in rural area in Gironde (South-Western France); being retired from agriculture after at least 20 years of activity and being affiliated to the Health Insurance under own name. The study started in 2007, with two follow-up visits over 5 years. Baseline visits were conducted at home by a neuropsychologist then by a geriatrician for all cases suspected of dementia, Parkinson’s disease and depression (to confirm the diagnosis), and by a nurse for others. A large panel of data were collected through standardised questionnaires: complete neuropsychological assessment, material and social living environment, psychological transition to retirement, lifestyle (smoking, alcohol and diet), medications, disability in daily living, sensory impairments and some clinical measures (blood pressure, depression symptomatology, anxiety, visual test, anthropometry…). A blood sampling was performed with biological measurements and constitution of a biological bank, including DNA. Brain MRI were also performed on 316 of the participants. Finally, the three-year data on health-related reimbursements were extracted from the Health System database (medications, medical and paramedical consultations, biological examinations and medical devices), and the registered Long-Term Diseases (30 chronic diseases 100% covered by the Insurance System).DiscussionAMI is the first French longitudinal study on health and aging set up in a population of elderly farmers living in rural area through a multidisciplinary approach.

Evolution of Prevalence of Depressive Symptoms and Antidepressant Use Between 1988 and 1999 in a Large Sample of Older French People: Results from the Personnes Agées Quid Study

OBJECTIVES: To describe the evolution of prevalence of depressive symptoms and antidepressant use between 1988 and 1999 in a large representative sample of older community‐dwelling French people.

One-Year Incidence of Hyperosmolar States and Prognosis in a Geriatric Acute Care Unit

Background: Hyperosmolar syndromes are associated with high mortality rates, yet little is known about their incidence and their prognosis. Objective: To determine the 1-year incidence of hyperosmolar states and the prognostic factors for in-hospital and 1-year mortality. Method: A 6-month prospective cohort study was conducted in a 40-bed acute care geriatric unit and included all patients who developed plasma osmolarity of 320 mosm/l or greater. Age, sex and known cognitive impairment as possible risk factors of hyperosmolarity were assessed. In-hospital and 1-year mortality were calculated and risk factors for death among baseline patient characteristics were sought. Results: 48 (11) of the 436 inpatients in the study were identified as hyperosmolar. Diabetic hyperosmolarity was found in 8 patients. Cognitive impairment was a risk factor for hyperosmolarity (relative risk 2.39, 95% confidence interval 2.18–3.33, p < 0.001), but not age or sex. Infections were accompanied by hyperosmolarity in 30 (62.5). Thirty-five patients (72.9) were bed- or chair-ridden. In-hospital mortality was higher in hyperosmolar patients (35.4) than in the others (16.7%, p = 0.003). Causes of death were infection in 5 (29.4), terminal cachexia in 5, thrombosis in 3, gastric bleeding in 1, renal failure in 2 and heart failure in 1. Functional dependency for mobility was a risk factor for in-hospital mortality but not the degree of hyperosmolarity. One-year mortality was 68.7%. Functional dependency and pressure ulcers were independent predictors of 1-year mortality (p = 0.005 and p = 0.044, respectively). Conclusion: Hyperosmolar states occurred in cognitively impaired and dependent patients and resulted in high mortality rates at short and at mid-term. Mortality was related to functional dependency rather than to hyperosmolarity.

Metabolic clearance rate of immunoreactive vasopressin in man

Abstract. Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 μg AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty‐two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287·1 ml min‐1 (m2)‐1 and 219·3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.

Group and individual cognitive therapies in Alzheimer's disease: the ETNA3 randomized trial.

BACKGROUND Although non-drug interventions are widely used in patients with Alzheimers disease, few large scale randomized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out. ETNA3 trial compares the effect of cognitive training, reminiscence therapy, and an individualized cognitive rehabilitation program in Alzheimers disease to usual care. METHODS This is a multicenter (40 French clinical sites) randomized, parallel-group trial, with a two-year follow-up comparing groups receiving standardized programs of cognitive training (group sessions), reminiscence therapy (group sessions), individualized cognitive rehabilitation program (individual sessions), and usual care (reference group). Six hundred fifty-three outpatients with Alzheimers disease were recruited. The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years. Secondary outcomes were cognitive impairment, functional disability, behavioral disturbance, apathy, quality of life, depression, caregivers burden, and resource utilization. RESULTS No impact on the primary efficacy measure was evidenced. For the two group interventions (i.e. cognitive training and reminiscence), none of the secondary outcomes differed from usual care. The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidenced. CONCLUSIONS These findings challenge current management practices of Alzheimers patients. While cognitive-oriented group therapies have gained popularity, this trial does not show improvement for the patients. The individualized cognitive rehabilitation intervention provided clinically significant results. Individual interventions should be considered to delay institutionalization in Alzheimers disease.

Incidence sur un an et facteurs de risque des infections nosocomiales bactériennes dans un service de médecine interne gériatrique

PURPOSE Elderly inpatients are particularly exposed to the risk of nosocomial infections, thus the study of their risk factors and consequences is of interest. METHODS Among 1,565 subjects referred to a short-term geriatric unit, patients hospitalised for a year for an acute event and unable to move themselves were followed up for the occurrence of nosocomial infections. RESULTS Among these 402 immobilised patients (age: 86.3 +/- 7.6 years), 102 nosocomial infections occurred in 91 patients (22.6%), whereas the estimation of the incidence in the total hospitalised population (1,565 subjects, age: 85.1 +/- 6.2 years) was 9.4% (95% confidence interval [CI] 8.3-11.2). Forty-seven point seven percent of nosocomial infections were urinary tract nosocomial infections, 27.5% were lower respiratory nosocomial infections, 9.2% were cutaneous nosocomial infections, 7.3% were septicaemia and 8.2% were of unknown origin. The relative risk (RR) of NI linked to functional dependency for mobility was 5.5 (95% CI: 3.93-7.7, P < 0.001). Other risk factors were: for all nosocomial infections: cancer diagnosis (RR 1.1, 95% CI: 1.1-1.2, P = 0.01); and respectively for urinary tract NI: bladder indwelling (RR 4.8, 95% CI: 2.9-7.7, P < 0.001), pulmonary NI: swallowing disorders (RR 5.4, 95% CI: 2.8-10.5, P < 0.001); and septicaemia: venous catheter (RR 5.4, 95% CI: 1.3-23.3, P = 0.002). NI were associated with an increased length of stay (22.1 +/- 11.7 days in infected patients vs 16.3 +/- 9.5 days in immobilised non-infected subjects, P < 0.001). The mean length of stay for the 1,565 subjects was 10.3 +/- 7.6 days. Death was attributed to nosocomial infections in 13 subjects. In conclusion, functional dependency for mobility, bladder indwelling, venous catheter, swallowing disorders and diagnosis of cancer were risk factors for nosocomial infections in hospitalised elderly subjects in an acutecare setting.