Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer.

BACKGROUND: Older patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older. PATIENTS AND METHODS: Patients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS). RESULTS: 102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75-91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status. CONCLUSION: Normal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL.

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results.

Background: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population. Patients and methods: Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria. Results: About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT). Conclusion: Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.

[Once weekly L-thyroxine treatment in non-compliance: A case report]. / Prise hebdomadaire de L-thyroxine dans un cas de non-observance du traitement substitutif.

INTRODUCTION: The non-adherence to substitutive treatment by L-thyroxine is the main cause of the discordance between high thyrotropin values and high doses of the drug. OBSERVATION: In a 36-year-old patient with post-surgery hypothyroidism, thyrotropin values ranged between 100 and 400 mUI/L, although daily replacement therapy included 300 µg of L-thyroxine and 75 µg of L-triiodothyronine. The oral loading test with L-thyroxine was normal and thyrotropin serum level returned to normal values under weekly oral administration of 1000 µg L-thyroxine. CONCLUSION: The strategy of non-adherence treatment in hypothyroidism is well defined with oral testing of L-thyroxine, followed by oral or parenteral weekly administration of the drug. The L-thyroxine oral test is the gold standard for diagnosis after eliminating of the other conventional causes: drug interactions or digestive malabsorption. L-thyroxine treatment should be discussed on a case-by-case basis, either daily under surveillance or once weekly oral or parenteral high dose.

Assessment of Glycemic Control in Nursing Home Residents with Diabetes.

OBJECTIVE: To describe glycemic control in nursing home residents with diabetes and to evaluate the relevance of HbA1c in the detection of hypoglycemia risk. DESIGN AND METHODS: Diabetes treatment, geriatric assessment, blood capillary glucose (n= 24,682), and HbA1c were collected from medical charts of 236 southern France nursing home residents during a 4-month period. Glycemic control was divided into four categories: tight, fair, and moderate or severe chronic hyperglycemia using the High Blood Glucose Index or the analysis of blood glucose frequency distribution. Hypoglycemia episodes were identified by medical or biological records. RESULTS: Glucose control was tight in 59.3 % and fair in 19.1 % of the residents. Chronic exposure to hyperglycemia was observed in 21.6 % of the residents (severe in 9.7 % and moderate in 11.9 %). Hypoglycemia was noticed in 42/236 (17.8%), in all categories of glycemic control. Relative hypoglycemia risk was significantly (P = 0.0095) higher in residents with moderate chronic hyperglycemia compared with those with tight control. The majority of residents with hypoglycemia (39/42) or chronic hyperglycemia (45/51) were insulin-treated. The relative risk of hypoglycemia was not significantly associated with HbA1c values. CONCLUSION: Hypoglycemia risk in nursing home residents is observed in all categories of glycemic control. In tight control, the potency of antidiabetic treatment should be reduced. In chronic hyperglycemia, diet and treatment should be reevaluated in order to reduce glucose variability. HbA1c is not sufficient for hypoglycemia risk detection; capillary blood glucose monitoring is warranted for nursing homes residents with diabetes.

Opportunistic autoimmunity secondary to cancer immunotherapy (OASI): An emerging challenge.

With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists. Within irAEs, we propose to individualize the induced autoimmunity by the term "Opportunistic Autoimmunity Secondary to Cancer Immunotherapy" (OASI). The aims of this article are (1) to present the different available checkpoint inhibitors and the OASIs reported with these treatments and (2) to propose practical recommendations for diagnosis, pre-therapeutic assessment and management of OASIs. The need for predictive biomarkers of OASIs occurrence will also be discussed.

[Statin and cardiovascular diseases after 75 years]. / Statine et pathologies cardiovasculaires après 75 ans.

Statin prescription in persons older than 75 years or with frailty signs raises questions on the role of cholesterol in the genesis of atherosclerosis in this population, on the benefit of this treatment in primary or secondary prevention, and on their side effects in a context of multiple pathology and multiple medications. These questions are approached with the available literature data for this population. In secondary prevention, statin prescription is recommended whatever the age although intensive treatment should be avoided. In primary prevention, in the absence of consensus, their prescription depends on both geriatric and cardiovascular risk assessment.

Characteristics and information searched for by French patients with systemic lupus erythematosus: A web-community data-driven online survey.

INTRODUCTION: To provide information about the needs of patients with systemic lupus erythematosus (SLE) using Carenity, the first European online platform for patients with chronic diseases. METHODS: At one year after its creation, all posts from the Carenity SLE community were collected and analysed. A focused cross-sectional online survey was performed. RESULTS: The SLE community included 521 people (93% females; mean age: 39.8 years). Among a total of 6702 posts, 2232 were classified according to disease-related topics. The 10 most common topics were 'lupus and …' either 'treatment', 'fatigue', 'entourage', 'sun exposure', 'diagnosis', 'autoimmune diseases', 'pregnancy', 'contraception', 'symptoms' or 'sexuality'. 112 SLE patients participated in the online survey. At the time of diagnosis, only 17 (15%) patients had heard of SLE and 84 (75%) expressed a need for more information on outcomes (27%), treatments (27%), daily life (14%), patients' associations (11%), symptoms (8%), the disease (8%) and psychosocial aspects (7%). When treatment was initiated, 48 patients (43%) would have liked more information about side effects (46%), long-term effects (21%), treatment duration/cessation (12.5%) and type (10%) and mechanism of action (8%) of treatments. All participants except one had used the internet to find information about SLE. Sources of information included healthcare providers (51%/61%/67%), journals/magazines (7%/12%/6%), lupus Websites (51%/77%/40%), web forums/blogs (34%/53%/19%), patients' associations (11%/23%/9%) accessed at 'just before diagnosis', 'just after diagnosis' and 'before treatment initiation'. CONCLUSIONS: Online patient communities provide original unbiased information that can help improve provision of information to SLE patients.

Effects of haptic supplementation on postural stability in unilateral vestibular loss patients.

The effects of haptic supplementation on postural stability during upright standing with vision were investigated in 11 unilateral vestibular loss (UVL) patients and compared to 12 age-marched controls. All the participants were instructed to grip a fixed or mobile stick. In the mobile conditions, the lower extremity of the stick was in contact with a slippery or a rough surface. Postural stability was assessed by the root mean square (RMS) and the velocity of the center of foot pressure (CoP) displacements in both antero-posterior (AP) and medio-lateral (ML) directions. Results showed that RMS was larger in UVL patients than in aged-matched participants in AP direction. However, in the mobile stick conditions, only the rough surface improved postural stability. In addition, RMS was more sensitive to haptic supplementation than CoP velocity. The present study confirms the importance of haptic information in the multi-sensory (re) weighting process underlying postural control in UVL patients.

[Tetanus risk assessment in the older outpatients: Usefulness of the "Tétanos Quick Stick ®"?]. / Évaluation du risque tétanique chez les sujets âgés en médecine ambulatoire: intérêt du "Tétanos Quick Stick ®"?

INTRODUCTION: Tetanus is a serious disease, which could be potentially lethal. All cases are observed in patients inadequately immunized. The immunochromatographic tests (including Tetanos quick Stick(®) [TQS]) have demonstrated their efficiency in emergency setting. The aim of our study was to assess the usefulness of these tests in elderly outpatients seen in ambulatory settings. MATERIALS: This prospective study included patients aged 65 years and over who presented to the outpatients' clinic of the Gerontologic Departmental Center (Marseille). A TQS and a self-administered questionnaire to assess risk factors for tetanus were performed. RESULTS: One hundred and twenty-two patients were studied. The prevalence of positive TQS was 66%. Patients have an average of 2.5 risk factors for tetanus. Negative TQS was observed in 35% of patients who had seen their general practitioner for a wound during the previous year. CONCLUSION: Elderly patients accumulate several risk factors regardless of age and lifestyle. While physicians are familiar with the vaccine recommendations, they are often faced with the difficulty of assessing patient's status based only on the patient's interview, which is frequently not reliable. The implementation of immunochromatographic tests in general practice could help physicians in the management of patients at risk for tetanus.

Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Société Française de Gériatrie et de Gérontologie) Workshop--Athens January 20-21, 2012.

UNLABELLED: Frailty tends to be considered as a major risk for adverse outcomes in older persons, but some important aspects remain matter of debate. OBJECTIVES: The purpose of this paper is to present expert's positions on the main aspects of the frailty syndrome in the older persons. PARTICIPANTS: Workshop organized by International Association of Gerontology and Geriatrics (IAGG), World Health Organization (WHO) and Société Française de Gériatrie et de Gérontologie (SFGG). RESULTS: Frailty is widely recognized as an important risk factor for adverse health outcomes in older persons. This can be of particular value in evaluating non-disabled older persons with chronic diseases but today no operational definition has been established. Nutritional status, mobility, activity, strength, endurance, cognition, and mood have been proposed as markers of frailty. Another approach calculates a multidimensional score ranging from "very fit" to "severely frail", but it is difficult to apply into the medical practice. Frailty appears to be secondary to multiple conditions using multiple pathways leading to a vulnerability to a stressor. Biological (inflammation, loss of hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors (isolation, financial situation) are involved in the vulnerability process. In clinical practice, detection of frailty is of major interest in oncology because of the high prevalence of cancer in older persons and the bad tolerance of the drug therapies. Presence of frailty should also be taken into account in the definition of the cardiovascular risks in the older population. The experts of the workshop have listed the points reached an agreement and those must to be a priority for improving understanding and use of frailty syndrome in practice. CONCLUSION: Frailty in older adults is a syndrome corresponding to a vulnerability to a stressor. Diagnostic tools have been developed but none can integrate at the same time the large spectrum of factors and the simplicity asked by the clinical practice. An agreement with an international common definition is necessary to develop screening and to reduce the morbidity in older persons.

[Thyroid in the elderly (part 2)]. / La thyroïde de la personne âgée (partie 2).

Aging is associated with an increased prevalence of thyroid diseases. The diagnosis of overt hypothyroidism and hyperthyroidism may be difficult since they are often pauci- or monosymptomatic. Subclinical forms of thyroid diseases, in particular hypothyroidism, are even more frequent. Therapeutic abstention with regular follow-up is usually recommended in hypothyroidism. Radical treatment is usually preferred for subclinical hyperthyroidism since heart complications may be severe. Increased prevalence of benign and malignant nodules is observed in the elderly. The prognosis of thyroid cancer is less favorable than in adults, due to a higher proportion of histological types with a worse evolution. Whatever the thyroid disease, diagnosis and treatment modalities should be adapted to the age and general conditions of the patient. Contradictory results have been reported on the relationship between thyroid status and neuromuscular and cognitive alterations linked to aging.

[Thyroid in the elderly (Part 1)]. / La thyroïde de la personne âgée (Partie 1).

Aging is associated with changes in thyroid function at several levels of regulation. Thyroid hormones levels are usually within the lower part of normal values reported in the general population. Two changes in aging are of clinical importance: a shift in the distribution of TSH levels, the 97.5th percentile of the TSH distribution being within 6 µUI/ml after 70 years and within 7.5 µUI/ml in subjects older than 80 instead of 4.5 µU/ml in the general population, and an increased prevalence of thyroid nodularity, requiring reliable and non-invasive methods of investigation in older people. Lastly, aging may be associated with comorbidities, high risk of drug interactions and under nutrition, which may make difficult the interpretation of laboratory data and in some cases induce iatrogenic thyroid diseases. Considering the high prevalence of the thyroid diseases in older patients and a better understanding of the physiopathological hormonal variations with the ageing, it seemed useful to propose a review to help the clinician in the care of these situations.

[Cost-effectiveness of drugs modifications for inpatients hospitalised in acute care geriatric units]. / Impact de la modification des prescriptions chez les sujets âgés hospitalisés en service de court séjour gériatrique en termes de coût.

PURPOSE: Polypharmacy in the elderly increases the risk of adverse drug reactions and leads to increased medical costs. There is little data currently available on drug modification and cost reduction during hospitalization in a geriatric unit. The aims of this study were to analyse drug modification during hospitalization in a geriatric care unit and to evaluate the repercussions in terms of cost reduction. METHODS: This monocentric study included 691 patients over a period of 3.5 years. The drugs and their daily costs were counted and classified (10 classes, 37 subclasses) upon admission and upon discharge. The modifications in the number of drugs in each class and subclass, as well as their costs, were analysed. Predictive factors in drug modification between admission and discharge were investigated. RESULTS: Our study showed a significant decrease in the number of drugs (mean ± standard error [SE], 5.2±0.11 to 4.5±0.07), as well as in the daily medical costs (4.4±0.18 to 3.67±0.12 €) between admission and discharge. The higher the number of drugs was upon admission, the greater the reduction was upon discharge. Cardiovascular, metabolic, analgesic and pulmonary drugs were significantly reduced, whereas gastrointestinal and anti-osteoporotic treatments increased. Diabetes, adverse drug events and the one-leg balance were predictive factors in drug modification. CONCLUSION: Hospitalization in a geriatric unit allows a re-evaluation of drug management with a significant reduction in the number and cost of treatments between admission and discharge. Given the multiple consequences of polypharmacy and its serious financial impact, research to develop optimal care of the elderly and to improve medication intervention is warranted.

Impact of an all-oral capecitabine and vinorelbine combination regimen on functional status of elderly patients with advanced solid tumours: A multicentre pilot study of the French geriatric oncology group (GERICO).

BACKGROUND: Elderly metastatic cancer patients typically have short life expectancy and frequently suboptimal treatment. Goals of therapy should include preservation of functional status as well as clinical response. For elderly patients, oral chemotherapy could be a valuable strategy, avoiding the constraints and risks of intravenous drugs. METHODS: This study assessed effect of an all-oral combination of capecitabine and vinorelbine on functional status (measured by basic Activities of Daily Living [ADL]), toxicity, efficacy and compliance in patients ≥70 years with advanced breast, prostate or lung cancer. RESULTS: Eighty patients were enrolled. After three cycles, 81.8% of patients had stabilised or improved ADL, and 8.6% and 42.9% had a response or stabilised disease. Compliance was excellent (68.8%). The most common grade 3-4 toxicities were haematological (17.9%) and gastrointestinal (7.7%). CONCLUSION: In elderly cancer patients, an all-oral combination of capecitabine and vinorelbine maintains functional status, is well tolerated, and provides good disease control.

[Adverse drug events in hospitalized elderly patients in a geriatric medicine unit: study of prevalence and risk factors]. / Accidents iatrogènes médicamenteux chez le sujet âgé hospitalisé en court séjour gériatrique : étude de prévalence et des facteurs de risques.

INTRODUCTION: In the elderly, both the presence of a multiple pathology and multiple medication have been shown to be frequent risk factors for adverse drug events. However, a few studies only have included parameters of standardized geriatric assessment for the purpose of identifying other risk factors. Our study compared the parameters of standard geriatric assessment, in the presence or absence of adverse drug events and evaluated the prevalence of adverse drug events in elderly inpatients, the symptoms, and the drugs involved. METHODS: A total of 823 patients were studied during a two-year period. Two groups of patients were identified, according to the presence or absence of an adverse drug event. Eight fields of geriatric assessment were compared: comorbidities, number of drugs, functional status, nutritional status, mobility, mood, neurosensory disorders, and cognition. For patients who experienced an adverse drug event, we also analyzed the drugs involved and the symptoms of the adverse drug events. RESULTS: One hundred and twelve patients (13.6%) aged 82 years+/-7.5 experienced 144 adverse drug events. Significant differences between the two groups were observed in the following: symptoms of depression, problems of mobility, risk of malnutrition (respectively p=0.001, p=0.002, p=0.007), the female sex, number of drugs, number of comorbidities, and the administration of diuretics. Cardiovascular (23.2%), psychotropic (17.9%) and anti-infectious (17%) medicines were the most frequently involved. The symptoms that occurred most frequently were orthostatic hypotension (14.6%), gastrointestinal disorders (12.5%), and neuropsychological (10.4%) disorders. CONCLUSION: Elderly patients with multiple pathology and multiple medication are at high risk for adverse drug events. Other lesser known factors, such as depression, problems of mobility, and malnutrition must be researched, as they are evidence of the underlying the frailty of the elderly population.