Health resource use and costs of symptomatic knee and/or hip osteoarthritis.

BACKGROUND: Data on the economic consequences of hip and knee osteoarthritis (OA) are scarce. We aimed to estimate the annual direct and indirect costs for patients followed for hip and/or knee OA in the Knee and Hip Osteoarthritis Long term Assessment (KHOALA) cohort. METHODS: The KHOALA cohort, set up from 2007 to 2009, is a French multicenter study of 878 individuals with symptomatic knee/hip OA who were 40-75 years old. Resources used were collected annually for 5 years. Costs were assigned by using official sources and expressed in 2018 euros per patient. RESULTS: The mean annual total costs per patient over the 5-year study period were 2,180 ± 5,305€. The mean annual direct medical costs per patient were 2,120 ± 5,275€ and mean annual indirect costs per patient 180 ± 1,735€ for people of working age. Costs increased slightly over the study period. Drugs were the largest cost share, representing over 50% of all direct costs. However, the proportion attributable to OA drugs accounted for only 10.5% of drug costs. The second cost share was hospitalizations; hip and knee prosthetic surgery accounted for 27% of surgery hospitalization costs. Health professional visits were the third cost share, accounting for 3% of direct medical costs. The median costs induced could be as high as 2 billion €/year (IQR 0.7-4.3) in France. CONCLUSION: Hip and knee OA costs were substantial and increased over the study period in France. However, the costs attributable to OA represented only a small fraction of overall costs.

Screening for frailty in community-dwelling elderly subjects: Predictive validity of the modified SEGA instrument.

AIMS: To study the capacity of the SEGAm instrument to predict loss of independence among elderly community-dwelling subjects. METHODS: The study was performed in four French departments (Ardennes, Marne, Meurthe-et-Moselle, Meuse). Subjects aged 65 years or more, living at home, who could read and understand French, with a degree of autonomy corresponding to groups 5 or 6 in the AGGIR autonomy evaluation scale were included. Assessment included demographic characteristics, comprehensive geriatric assessment, and the SEGAm instrument at baseline. Subjects had follow-up visits at home at 6 and 12 months. During follow-up, vital status and level of independence were recorded. Logistic regression was used to study predictive validity of the SEGAm instrument. RESULTS: Among the 116 subjects with complete follow-up, 84 (72.4%) were classed as not very frail at baseline, 23 (19.8%) as frail, and 9 (7.8%) as very frail; 63 (54.3%) suffered loss of at least one ADL or IADL at 12 months. By multivariable analysis, frailty status at baseline was significantly associated with loss of independence during the 12 months of follow-up (OR=4.52, 95% CI=1.40-14.68; p=0.01). We previously validated the SEGAm instrument in terms of feasibility, acceptability, internal structure validity, reliability, and discriminant validity. CONCLUSIONS: This instrument appears to be a suitable tool for screening frailty among community-dwelling elderly subjects, and could be used as a basis to plan early targeted interventions for subjects at risk of adverse outcome.

Economic impact of lower-limb osteoarthritis worldwide: a systematic review of cost-of-illness studies.

OBJECTIVE: An overview of the economic consequences - overall costs as well as cost breakdown (direct and indirect) - of hip and knee osteoarthritis (OA) worldwide. METHODS: A systematic literature search of EMBASE, MEDLINE, Scopus and Cochrane databases for articles was performed independently by two rheumatologists who used the same predefined eligible criteria. Papers without abstracts and in languages other than English or French were excluded. Extracted costs were converted to an annual cost and to 2013 euros (€) by using the Consumer Price Index of the relevant countries and the 2013 Purchasing Power Parities between these countries and the European Union average. RESULTS: A total of 45 abstracts were selected, and 32 articles were considered for the review. The studied populations were heterogeneous: administrative, hospital and national health survey data. Annual total costs per patient ranged from 0.7 to 12 k€, direct costs per patient from 0.5 to 10.9 k€ and indirect costs per patient from 0.2 to 12.3 k€. The weighted average annual costs per patient living with knee and hip OA were 11.1, 9.5 and 4.4 k€ for total, direct and indirect costs, respectively. CONCLUSIONS: This review highlights the heterogeneity of studies and lack of methodologic consensus to obtain reliable cost-of-illness estimates for lower-limb OA. However, costs induced by the disease seem substantial and deserve to be more extensively explored.

Predictors of Long-Term Mortality in Oldest Old Patients (90+) Hospitalized to Medical Wards via the Emergency Department: The SAFES Cohort.

OBJECTIVES: To identify risk factors for long-term mortality in patients aged 90 years and over who are admitted to hospital through the emergency department. DESIGN: Prospective cohort study (SAFES cohort; Sujet Agé Fragile - Évaluation Suivi). SETTING: 8 university teaching hospitals and one regional, non-academic hospital in France. PARTICIPANTS: Among 1306 patients in the SAFES cohort, 291 patients aged 90 or over were included. MEASUREMENTS: At inclusion, we recorded socio-demographic data (age, sex, level of education, living alone or in an institution, number of children, presence of helper/caregiver), and data from geriatric evaluation (dependence status, risk of depression, dementia, delirium, nutritional status, walking disorders, risk of falls, comorbidities, risk of pressure sores). Vital status at 36 months was obtained from the treating physician, the general practitioner, administrative registers, or during follow-up consultations. RESULTS: Among 291 patients included, 190 (65.3%) had died at 36 months. Risk factors for mortality at 36 months identified by multivariate analysis were risk of malnutrition (HR 1.6, 95%CI 1.1-2.3, p=0.004) and delirium (HR 1.6, 95%CI 1.1-2.3, p=0.01). CONCLUSION: Risk of malnutrition and presence of delirium are risk factors for mortality at 36 months in subjects aged 90 years and over hospitalized through the emergency department.

Screening for frailty in elderly subjects living at home: validation of the Modified Short Emergency Geriatric Assessment (SEGAm) instrument.

OBJECTIVES: To validate the modified version of the Short Emergency Geriatric Assessment (SEGAm) frailty instrument in elderly people living at home. DESIGN: Longitudinal, prospective, multicentre study. SETTING: Four departments (Ardennes, Marne, Meurthe-et-Moselle, Meuse) in two French Regions (Champagne-Ardenne and Lorraine). PARTICIPANTS: Subjects aged 65 years or more, living at home, who could read and understand French, with a degree of autonomy corresponding to groups 5, or 6 in the AGGIR autonomy evaluation scale. MEASUREMENTS: Assessment included demographic characteristics, comprehensive geriatric assessment, and the SEGAm instrument. Psychometric validation was used to study feasibility and acceptability, internal structure validity, reliability, and discriminant validity of the SEGAm instrument. RESULTS: Between July 1st 2012 and March 31st 2013, 167 patients were included in the study. Averaged age was 77±7 years, the majority were women (70.7%). Feasibility and acceptability of the SEGAm instrument were excellent: we observed no refusal to participate, no drop-out during administration, no missing items, no ceiling or floor effects, and the administration time was short (5.0±3.5 min). By factor analysis, the instrument proved to be unidimensional. It showed good internal consistency (Cronbach's alpha coefficient: 0.68) and good test-retest (intra-class correlation: 0.88) at 7 days interval. Discriminant validity showed a significant difference, mainly for nutritional status, fall risk, dependency, mood and depression risk, and comorbidities. CONCLUSION: Based on these psychometric properties, the SEGAm appears to be an easy-to-use instrument that is particularly suitable for use in the community to identify frail elderly people who could benefit from early targeted interventions.

Automated radiosynthesis of N-succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB) for peptides and proteins radiolabeling for positron emission tomography.

Recently, silicon fluoride building blocks (SiFA) have emerged as valuable and promising tools to overcome challenges in the labeling of peptides and proteins for positron emission tomography (PET). Herein, we report a fully automated synthesis of N-succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB) by a commercially available Scintomics Hot Box 3 synthesis module, to be used as a prosthetic group for peptide and protein labeling. The drying of K2.2.2./K (18)F complex was performed according to the Munich method modified by our group (avoiding azeotropic drying) using oxalic acid to neutralize the base from the (18)F(-) containing QMA eluent. This K2.2.2./K (18)F complex was then used for SiFA (18)F-(19)F isotopic exchange followed by a fast purification by a solid-phase-extraction (SPE) to afford [(18)F]SiFB with an average preparative radiochemical yield (RCY) of 24±1% (non-decay corrected (NDC)) within a synthesis time of 30 min. The [(18)F]SiFB produced by automated synthesis was then used for the (18)F-labeling of rat serum albumin (RSA) as a proof of applicability.

Is obesity a marker of robustness in vulnerable hospitalized aged populations? Prospective, multicenter cohort study of 1 306 acutely ill patients.

BACKGROUND: The "obesity paradox" is poorly understood in vulnerable older hospitalized populations. OBJECTIVES: To prospectively analyze the impact of body mass index (BMI) and comorbidities on early (6-week), one- and two-year mortality. DESIGN: Prospective multicenter study with a two-year follow-up of old patients participating in the SAFES cohort study. SETTINGS: Nine university hospitals in France. PARTICIPANTS: Patients aged 75 or older hospitalized in medical divisions through the emergency department. MEASUREMENT: Inpatients' characteristics were obtained through a comprehensive geriatric assessment of inpatients, conducted in the first week of hospitalization. All-cause mortalities at 6-week, one- and two-year were determined using bivariable and multivariable Cox proportional hazard model. RESULTS: The SAFES cohort included 1,306 patients, aged 85±6 years, with a majority of women (65%). One- and two-year mortality were inversely associated with BMI ≥30 kg/m2 while early mortality was not, and positively associated with age, burden of comorbidities, walking disorders, level of dependency and presence of a dementia syndrome. Survival rates between patients in low (< 18.0 kg/m2) and intermediate (18-24.9 and 25-29.9 kg/m2) BMI categories were not significant. CONCLUSION: While our findings seem to confirm the reality of the "obesity paradox" in vulnerable older hospitalized population, the exact understanding of underlying mechanisms and even the truthfulness of this paradoxical relationship are still fraught with considerable methodological, epidemiological and metabolic challenges.

Relationship between anticholinergic drug use and one-year outcome among elderly people hospitalised in medical wards via emergency department: the SAFES cohort study.

AIM: To investigate the relationship between anticholinergic drug use and one-year outcome of elderly patients hospitalised via the emergency department. METHODS: Prospective, multicentre, cohort study of patients aged 75 years and older. Comprehensive geriatric evaluation was performed. We included in this analysis all patients for whom data on drug use was available. Anticholinergic drugs were coded using the online database "Thesorimed". One-year mortality and nursing home admission were analysed using a Cox model, with matching on the propensity to use anticholinergic drugs. RESULTS: In total, 1176 subjects were included in this analysis, average age 85±6 years, 65% women. Overall, 144 (12%) were taking at least one anticholinergic drug. Mortality and nursing home admission at one year were respectively 29% and 30% in the anticholinergic group, and 34% and 33% respectively in subjects not taking anticholinergic drugs. No significant relationship was observed between anticholinergic drug use and the main endpoints. CONCLUSION: Although we did not observed any statistically significant relationship between use of anticholinergic drugs and one-year outcome in elderly patients, the long-term use of anticholinergic drugs can have deleterious effects on memory and functional capacity, and therefore requires prescriptions to be reviewed regularly.

Toca 511 gene transfer and 5-fluorocytosine in combination with temozolomide demonstrates synergistic therapeutic efficacy in a temozolomide-sensitive glioblastoma model.

Toca 511 (vocimagene amiretrorepvec), an amphotropic retroviral replicating vector (RRV), can successfully and safely deliver a functional, optimized cytosine deaminase (CD) gene to tumors in orthotopic glioma models. This agent, in conjunction with subsequent oral extended-release 5-fluorocytosine (5-FC) (Toca FC), is currently under investigation in patients with recurrent high-grade glioma . Temozolomide (TMZ) with radiation is the most frequently used first-line treatment for patients with glioblastoma, the most common and aggressive form of primary brain cancer in adults. However, subsets of patients with certain genetic alterations do not respond well to TMZ treatment and the overall median survival for patients who respond remains modest, suggesting that combinatorial approaches may be necessary to significantly improve outcomes. We show that in vitro TMZ delays but does not prevent RRV spread, nor interfere with Toca 511+5-FC-mediated cell killing in glioma tumor cells, and in vivo there is no significant hematologic effect from the combination of 5-FC and the clinically relevant dose of TMZ. A synergistic long-term survival advantage is observed in mice bearing an orthotopic TMZ-sensitive glioma after Toca 511 administration followed by coadministration of TMZ and 5-FC. These results provide support for the investigation of this novel combination treatment strategy in patients with newly diagnosed malignant glioma.

Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model.

In the present study, we compared the therapeutic effect of tumor-selective retroviral replicating vectors (RRV) expressing the yeast cytosine deaminase (CD) delivered by convection-enhanced delivery (CED) or simple injection, followed by systemic administration of the pro-drug, 5-fluorocytosine (5-FC). Treatment with RRV-CD and systemic 5-FC significantly increased survival in rodent U87MG glioma model in comparison with controls (P<0.01). Interestingly, CED of RRV-CD followed by 5-FC further enhanced survival in this animal model in comparison with intra-tumoral injection of RRV-CD, followed by systemic 5-FC (P<0.05). High expression levels of Ki-67 were found in untreated tumors compared with treated. Untreated tumors were also much larger than treated. CED resulted in excellent distribution of RRV while only partial distribution of RRV was obtained after injection. Furthermore, RRV-CD and CD were also found in tumors from treated rats at study end points. These results demonstrated that RRV vectors may efficiently transduce and stably propagate in malignant human glioma, thereby achieving a significant in situ amplification effect after initial administration. We conclude that delivery of RRV into the glioma by CED provides much wider vector distribution than simple injection, and this correlated with better therapeutic outcomes.

Response shift effects on measuring post-operative quality of life among breast cancer patients: a multicenter cohort study.

PURPOSE: To characterize response shift effects in patients with breast cancer (BC). METHODS: The QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and at the end of the first hospitalization. We used the then-test approach to characterize changes in internal standards by calculating the mean difference between the then-test (retrospective measure) and pre-test baseline QoL assessments. The Ideal Scale Approach was also used to assess changes in standards by comparing health and QoL expectancies between baseline and the end of the first hospitalization. Successive Comparison Approach was used to assess changes in values through the longitudinal assessment of the relative importance of EuroQOL dimensions. RESULTS: The results of this study showed that recalibration RS effects occurred early after the first hospitalization for 6/15 dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss, diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects). Moreover, health and QoL expectancies changed between the baseline and the end of the first hospitalization, and changes in values were seen for the self-care and usual activities dimensions of the EuroQOL-EQ-5D. CONCLUSIONS: The occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC.

[Cost-effectiveness of lung volume reduction coil treatment in emphysema. STIC REVOLENS]. / Évaluation médico-économique de la réduction volumique endobronchique par spirales. STIC REVOLENS.

BACKGROUND: Medical therapeutic options for the treatment of emphysema remain limited. Lung volume reduction surgery is infrequently used because of its high morbi-mortality. Endobronchial lung volume reduction coil (LVRC(®), PneumRx, Mountain View, CA) treatment has been recently developed and has been shown to be feasible and associated with an acceptable safety profile, while resulting in improvements in dyspnea, exercise capacity and lung function. The objective of this study is to analyze the cost effectiveness of LVRC treatment in severe emphysema. METHODS: This prospective, multicenter study, randomized with a 1:1 ratio (LVRC vs conventional treatment) will include 100 patients who will be followed up for 1year. The primary outcome measure is the 6-month improvement of the 6-minute walk test: the percentage of patients showing an improvement of at least 54m will be compared between groups. A cost-effectiveness study will estimate the cost of LVRC treatment, the global cost of this therapeutic option and will compare the cost between patients treated by LVRC and by medical treatment alone. EXPECTED RESULTS: This study should allow validating the clinical efficacy of LVRC in severe emphysema. The cost-effectiveness study will assess the medical-economic impact of the LVRC therapeutic option.

Six-month outcome of elderly people hospitalized via the emergency department: the SAFES cohort.

BACKGROUND: The objective of the study was to identify factors predictive of 6-month institutionalization or mortality in frail elderly patients after acute hospitalization. METHODS: A prospective cohort of elderly subjects 75 years and older was set up in nine French teaching hospitals. Data obtained from a comprehensive geriatric assessment were used in a Cox model to predict 6-month institutionalization or mortality. Institutionalization was defined as incident admission either to a nursing home or other long-term care facility during the follow-up period. RESULTS: Crude institutionalization and death rates after 6 months of follow-up were 18% and 24%, respectively. Independent predictors of institutionalization were: living alone (HR=1.83; 95% CI=1.27-2.62) or a higher number of children (HR=0.86; 95% CI=0.78-0.96), balance problems (HR=1.72; 95% CI=1.19-2.47), malnutrition or risk thereof (HR=1.93; 95% CI=1.24-3.01), and dementia syndrome (HR=1.88; 95% CI=1.32-2.67). Factors found to be independently related to 6-month mortality were exclusively medical factors: malnutrition or risk thereof (HR=1.92; 95% CI=1.17-3.16), delirium (HR=1.80; 95% CI=1.24-2.62), and a high level of comorbidity (HR=1.62; 95% CI=1.09-2.40). Institutionalization (HR=1.92; 95% CI=1.37-2.71) and unplanned readmission (HR=4.47; 95% CI=3.16-2.71) within the follow-up period were also found as independent predictors. CONCLUSION: The main factors predictive of 6-month outcome identified in this study are modifiable by global and multidisciplinary interventions. Their early identification and management would make it possible to modify frail elderly subjects' prognosis favorably.

Rapid cognitive decline, one-year institutional admission and one-year mortality: analysis of the ability to predict and inter-tool agreement of four validated clinical frailty indexes in the SAFEs cohort.

OBJECTIVES: To evaluate the predictive ability of four clinical frailty indexes as regards one-year rapid cognitive decline (RCD - defined as the loss of at least 3 points on the MMSE score), and one-year institutional admission (IA) and mortality respectively; and to measure their agreement for identifying groups at risk of these severe outcomes. DESIGN: One-year follow-up and multicentre study of old patients participating in the SAFEs cohort study. SETTING: Nine university hospitals in France. PARTICIPANTS: 1,306 patients aged 75 or older (mean age 85±6 years; 65% female) hospitalized in medical divisions through an Emergency department. MEASUREMENTS: Four frailty indexes (Winograd; Rockwood; Donini; and Schoevaerdts) reflecting the multidimensionality of the frailty concept, using an ordinal scoring system able to discriminate different grades of frailty, and constructed based on the accumulation of identified deficits after comprehensive geriatric assessment conducted during the first week of hospital stay, were used to categorize participants into three different grades of frailty: G1 - not frail; G2 - moderately frail; and G3 - severely frail. Comparisons between groups were performed using Fisher's exact test. Agreement between indexes was evaluated using Cohen's Kappa coefficient. RESULTS: All patients were classified as frail by at least one of the four indexes. The Winograd and Rockwood indexes mainly classified subjects as G2 (85% and 96%), and the Donini and Schoevaerdts indexes mainly as G3 (71% and 67%). Among the SAFEs cohort population, 250, 1047 and 1,306 subjects were eligible for analyses of predictability for RCD, 1-year IA and 1-year mortality respectively. At 1 year, 84 subjects (34%) experienced RCD, 377 (36%) were admitted into an institutional setting, and 445 (34%) had died. With the Rockwood index, all subjects who experienced RCD were classified in G2; and in G2 and G3 when the Donini and Schoevaerdts indexes were used. No significant difference was found between frailty grade and RCD, whereas frailty grade was significantly associated with an increased risk of IA and death, whatever the frailty index considered. Agreement between the different indexes of frailty was poor with Kappa coefficients ranging from -0.02 to 0.15. CONCLUSION: These findings confirm the poor clinimetric properties of these current indexes to measure frailty, underlining the fact that further work is needed to develop a better and more widely-accepted definition of frailty and therefore a better understanding of its pathophysiology.

Predictors of institution admission in the year following acute hospitalisation of elderly people.

OBJECTIVES: The aim of the study was to identify factors related to institutionalisation within one-year follow up of subjects aged 75 or over, hospitalised via the emergency department (ED). DESIGN: Prospective multicentre cohort. SETTING: Nine French university teaching hospitals. PARTICIPANTS: One thousand and forty seven (1 047) non institutionalised subjects aged 75 or over, hospitalised via ED. A sub-group analysis was performed on the 894 subjects with a caregiver. MEASUREMENTS: Patients were assessed using Comprehensive Geriatric Assessment (CGA) tools. Cox survival analysis was performed to identify predictors of institutionalisation at one year. RESULTS: Within one year after hospital admission, 210 (20.1%) subjects were institutionalised. For the overall study population, age >85 years (HR 1.6; 95%CI 1.1-2.1; p=0.005), inability to use the toilet (HR 1.6; 95%CI 1.1-2.4; p=0.007), balance disorders (HR 1.6; 95%CI 1.1-2.1; p=0.005) and presence of dementia syndrome (HR 1.9; 95%CI 1.4-2.6; p<0.001) proved to be independent predictors of institutionalisation; while a greater number of children was inversely linked to institutionalisation (HR 0.8; 95%CI 0.7-0.9; p<0.001). Bathing was of borderline significance (p=.09). For subjects with a caregiver, initial caregiver burden was significantly linked to institutionalisation within one year, in addition to the predictors observed in the overall study population. CONCLUSIONS: CGA performed at the beginning of hospitalisation in acute medical wards is useful to predict institutionalisation. Most of the predictors identified can lead to targeted therapeutic options with a view to preventing or delaying institution admission.

Is the screening test of the French version of the dementia quality of life questionnaire indispensable?

The aim of this study was to evaluate the usefulness of the screening questions in the French version of the Dementia Quality of Life (DQoL) questionnaire. To assess the psychometric properties of the French DQoL, 155 patients with mild-to-moderate dementia were recruited. Here, we compared the psychometric properties of the instrument between patients who passed the screening test (n = 109) and the whole study population (n = 155). The French DQoL version showed a good test-retest reliability at a 2-week interval (0.95 ≤ intraclass correlation coefficients ≤ 1.0), and an average internal consistency (0.58 ≤ Cronbach's α ≤ 0.87) for the 2 study groups. Significant differences were observed in the 2 groups for 4 dimensions of the DQoL regarding dementia severity (Cornell scale), and for 3 dimensions evaluating depression (MMSE). Convergent validity with the Duke Health Profile revealed many significant correlations between dimensions not only in the 109 patients, but also in the whole study population. Our study demonstrated that patients who failed the screening procedure nonetheless seemed to be able to answer the DQoL questionnaire, the whole study group showing acceptable psychometric properties.

Early markers of prolonged hospital stay in demented inpatients: a multicentre and prospective study.

BACKGROUND: Dementia is a serious, chronic, and costly public health problem. Prior studies have described dementia as increasing length of hospital stay, but so far no explanations have been proposed. METHODS: To identify early markers for prolonged hospital stay in demented elderly inpatients, 178 community-dwelling or institutionalized subjects aged 75+, hospitalized through an emergency department in 9 teaching hospitals in France, were analyzed. Prolonged hospital stays were defined according a limit adjusted for Diagnosis Related Group. All patients underwent a comprehensive geriatric assessment at admission. Logistic regression multifactorial mixed model was performed. Center effect was considered as a random effect. RESULTS: Of the 178 stays, 52 were prolonged. Most concerned community-dwelling patients (86%). Multifactor analysis demonstrated that demographic variables had no influence on the length of stay, while diagnosis of delirium (OR 2.31; 95% CI 1.77 - 2.91), walking difficulties (OR 1.94; 95% CI 1.62 - 2.43) and report by the informal caregiver of moderate or severe burden (OR 1.52; 95% CI 1.19 - 1.86) or low social quality-of-life score (OR 1.25; 95% CI 1.03 - 1.40), according to the Zarit's Burden Inventory short scale (12 items) and the Duke's Health Profile respectively, were identified as early markers for prolonged hospital stays. CONCLUSION: At the time of the rising incidence of cognitive disorders, these results suggest that preventive approaches might be possible. In a hospital setting as well as in a community-dwelling population, more specific, specialized and coordinated care, using the expertise of multiple disciplines appears as a probable effective measure to limit prolonged hospital stay. Such approaches require (i) clear patient-oriented goal definition, (ii) understanding and appreciation of roles among various health care and social disciplines and, (iii) cooperation between partners in patient's management. However, the cost- and health-effectiveness of such approaches should be evaluated.

Post-polio syndrome and rehabilitation.

Post-polio syndrome (PPS) is the commonly affected term to describe the symptoms that may develop many years after acute paralytic poliomyelitis. The etiology of PPS is still unclear. An overuse of enlarged motor units is suspected causing denervation again due to distal degeneration of axons. Metabolic and functional changes has been described in muscle fibers of partially denervated muscles. Nevertheless, submaximal aerobic training and low intensity muscular strengthening have shown positive effects on muscular strength and cardiorespiratory system in patients affected by PPS. Aquatic therapy has a positive impact on pain and muscle function. In patients with severe fatigue, it is recommended to adapt the daily exercise routine to their specific case.

[Cancer genetics: estimation of the needs of the population in France for the next ten years]. / Oncogénétique : estimation des besoins de la population en France pour les dix ans à venir.

Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.

A brief review of radiation hormesis.

This paper reviews physical, experimental and epidemiological evidence for and against radiation hormesis and discusses implications with regards to radiation protection. The scientific community is still divided on the premise of radiation hormesis, with new literature published on a regular basis. The International Commission on Radiological Protection (ICRP) recommends the use of the Linear No Threshold (LNT) model, for planning radiation protection. This model states that the probability of induced cancer and hereditary effects increases with dose in a linear fashion. As a consequence, all radiation exposures must be justified and have a sufficient protection standard in place so that exposures are kept below certain dose limitations. The LNT model has sufficient evidence at high doses but has been extrapolated in a linear fashion to low dose regions with much less scientific evidence. Much experimentation has suggested discrepancies of this extrapolation at low doses. The hypothesis of radiation hormesis suggests low dose radiation is beneficial to the irradiated cell and organism. There is definite standing ground for the hormesis hypothesis both evolutionarily and biophysically, but experimental evidence is yet to change official policies on this matter. Application of the LNT model has important radiation protection and general human health ramifications, and thus it is important that the matter be resolved.