[After the COVID crisis, what solutions for the future nursing home?] / Rapport 22-02. Après la crise COVID, quelles solutions pour l'EHPAD de demain ?

The ageing of the population induces situations of large vulnerability and dependence. Home care usually remains the best response to comply with the person's wish, the family's desire, and the civil society's interest. However, there are circumstances where patient management in a nursing home (EHPAD) is the only solution. The present pandemic of coronavirus COVID-19 has highlighted the issue of EHPAD and their limitations to provide high quality care. To analyze the current position of EHPAD into the care chain and to understand difficulties to their functioning, it seems essential to seek out accelerated changes in the EHPAD since their establishment in 1999 and then in the light of the current crisis, propose possible solutions with a positive view of the role which each EHPAD will have to ensure for future.

[Renal cell carcinoma in the department of Hérault: Results over a 30 year period]. / Le cancer du rein dans le département de L'Hérault : résultats de 30 ans d'enregistrement.

OBJECTIVE: The objective of the study was to determine the specificities of renal cell carcinoma (RCC) in the department of Herault using the Herault Tumor Registry over 30 years. METHODS: Data of this study were obtained from the Herault cancer database. We analysed the evolution of RCC from 1987 to 2016, including the incidence, mortality, cancer pathology and staging at the moment of diagnosis. We compared our results with national and international data. RESULTS: We identified 3769 newly diagnosed RCC: 2628 in men (69,7%) and 1141 in women (30,3%). In 2016, RCC was the 8th most frequent cancer, both genders combined, the 7th most frequent cancer in men and the 11th in women. New cases of RCC increased by 4.2 in men and 3.3 in women over the study period. The number of localised forms increased by 9% over 20 years. In 2016, the probability of having a RCC before the age of 75 was of 2.11% for a man and of 0.62% for a woman. CONCLUSION: Over 30 years, the incidence rate of RCC increased in the department of Herault; however, mortality decreased over the same period. This analytical data should be improved by the development of the Registry of Herault Specialised in Onco-Urology (RHESOU). LEVEL OF EVIDENCE: 3.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

Evidence of a link between resting energy expenditure and bone remodelling, glucose homeostasis and adipokine variations in adolescent girls with anorexia nervosa.

UNLABELLED: Low bone mass is a consequence of anorexia nervosa (AN). This study assessed the effects of energy deficiency on various bone and hormonal parameters. The interrelationships between energy deficiency and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit demineralisation and hormonal alterations in AN patients. INTRODUCTION: Low areal bone mineral density (aBMD) is a well-known consequence of AN. However, the impact of reduced energy expenditure on bone metabolism is unknown. This study assessed the effects of energy deficiency on bone remodelling and its potential interactions with glucose homeostasis and adipose tissue-derived hormones in AN, a clinical model for reduced energy expenditure. METHODS: Fifty women with AN and 50 age-matched controls (mean age 18.1 ± 2.7 and 18.0 ± 2.1 years, respectively) were enrolled. aBMD was determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers, undercarboxylated osteocalcin (ucOC), parameters of glucose homeostasis, adipokines and growth factors were concomitantly evaluated. RESULTS: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, ucOC, glucose, insulin, HOMA-IR, leptin and IGF-1 were significantly reduced, whereas the bone resorption marker, leptin receptor (sOB-R) and adiponectin were elevated in AN compared with CON. In AN patients, REEm was positively correlated with weight, BMI, whole body (WB) fat mass, WB fat-free soft tissue, markers of bone formation, glucose, insulin, HOMA-IR, leptin and IGF-1 and negatively correlated with the bone resorption marker and sOB-R. Biological parameters, aBMD excepted, appeared more affected by the weight variation in the last 6 months than by the disease duration. CONCLUSIONS: The strong interrelationships between REEm and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit short- and long-term bone demineralisation and hormonal alterations in AN patients.

Operational Definition of Active and Healthy Ageing (AHA): A Conceptual Framework.

Health is a multi-dimensional concept, capturing how people feel and function. The broad concept of Active and Healthy Ageing was proposed by the World Health Organisation (WHO) as the process of optimizing opportunities for health to enhance quality of life as people age. It applies to both individuals and population groups. A universal Active and Healthy Ageing definition is not available and it may differ depending on the purpose of the definition and/or the questions raised. While the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has had a major impact, a definition of Active and Healthy Ageing is urgently needed. A meeting was organised in Montpellier, France, October 20-21, 2014 as the annual conference of the EIP on AHA Reference Site MACVIA-LR (Contre les Maladies Chroniques pour un Vieillissement Actif en Languedoc Roussillon) to propose an operational definition of Active and Healthy Ageing including tools that may be used for this. The current paper describes the rationale and the process by which the aims of the meeting will be reached.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Metabolic syndrome performs better than the individual factors in predicting renal graft outcome.

AIM: Individual components of the metabolic syndrome (MS), especially obesity and hypertension, have a deleterious effect on renal graft outcome. Whether MS is better than its individual components in predicting the decline of renal function is unknown. We studied the presence of MS and its individual components at 12 months post-transplantation according to the Adult Treatment Panel III classification and their influence on measured graft function. METHODS: A cohort of 322 patients who underwent transplantation between 1996 and 2003 and who agreed to have their glomerular filtration rate (GFR) measured by urinary clearance of technetium 99m (Tc*-DTPA) (measured GFR [mGFR]) at 3, 12, 48, 60, and 96 months after transplantation were included. The patients were followed up until patient death, graft loss, or December 2009 (mean follow-up: 3 ± 2.8 years). The linear mixed effect model for longitudinal repeated measures was applied. To compare MS versus its components we used the Akaike information Criterion (AIC) to determine the best model according to the Anderson and Burnham method. RESULTS: Univariate and multivariate analyses models using MS were more efficient than those using the individual components, which consisted of waist circumference, low high-density lipoprotein-cholesterol, hypertriglyceridemia, hyperglycemia, and systolic and diastolic blood pressure. The AIC was the lowest with MS models indicating better prediction on graft function than the individual components. CONCLUSION: MS is a better predictor of mGFR decline than its individual components. It is a valid and precious tool to assess outcomes.

[Management of adult's renal and ureteral stones. Update of the Lithiasis Committee of the French Association of Urology (CLAFU). General considerations]. / Prise en charge urologique des calculs rénaux et urétéraux de l'adulte. Mise au point du Comité Lithiase de l'Association Française d'Urologie (CLAFU). Aspects généraux.

The Lithiasis Committee of the French Association of Urology (CLAFU) aimed to update the current knowledge about urolithiasis. This update will be divided into four parts: 1) general considerations; 2) the management of ureteral stones; 3) the management of kidney stones; 4) metabolic assessment and medical treatment of urolithiasis. Recent technicals advances helped the urologists to improve stones management: new extracorporeal shockwave lithotripsy (ESWL) devices, new flexible ureterorenoscopes, development of laser fragmentation. ESWL, semi-rigid and flexible ureteroscopy and the percutaneous nephrolithotomy (PCNL) remain currently the main therapeutic options. The first part of this update deals with the description and classification of stones, preoperative assessment, post-operative management and clinical follow-up. Main criteria of therapeutic choices are stone location, stone composition and stone size. Stone composition is assessed with infrared spectrophotometry analysis and its hardness is correlated with U.H. density on CT scan assessment. Preoperative assessment consists in urinary cytobacteriological examine, urinary PH, blood creatininemia, hemostasis. Low-dose CT scan is recommended before urological treatment. The result of the treatment must be done 1 or 3 months later with plain abdominal film and ultrasonography. Medical management of urolithiasis will be based on stone composition, metabolic and nutritional evaluation. Treatment success is definited by absence of residual fragments. Annual follow-up is recommended and based either on plain abdominal film and ultrasonography or low-dose CT scan.

Continuous glucose monitoring after kidney transplantation in non-diabetic patients: early hyperglycaemia is frequent and may herald post-transplantation diabetes mellitus and graft failure.

OBJECTIVES: New onset of diabetes after transplantation (NODAT) is a known complication of renal transplantation, but early glycaemic status after transplantation has not been described prospectively. This study aimed to assess blood glucose (BG) levels immediately following kidney transplantation in non-diabetic subjects and to explore their relationship to later graft outcomes and NODAT occurrence. PATIENTS AND METHODS: Over a 9-month period, 43 consecutive non-diabetic patients who received a kidney transplant were prospectively investigated. During the first 4 days after transplantation, fasting BG was measured and the 24-h BG profile assessed by continuous glucose monitoring (CGM). Capillary BG was measured on hospital admittance and at least four times a day for CGM calibration thereafter. All adverse events were recorded, and fasting BG and HbA1c were assessed at 3, 6 and 12 months and at the last visit to our centre. RESULTS: Immediately following renal transplantation, capillary BG was 12.2 ± 3.8 mmol/L. On day 1 (D1), fasting BG was 9.9 ± 4.3 mmol/L and decreased to 6.0 ± 1.5 mmol/L on D3. The CGM-reported mean 24-h BG (mmol/L) was 10.2±2.4 on D1, 7.7 ± 1.3 on D2 and 7.5 ± 1.1 on D3. From D1 to D4, 43% of patients spent>12h/day with BG levels>7.7 mmol/L. While morbidity during the 3 months following transplantation appeared unrelated to BG, the first post-transplantation capillary BG measurement and fasting BG on D1 tended to be higher in patients who developed diabetes 3 months later. Tacrolimus treatment was associated with a higher incidence of dysglycaemia at 3 and 6 months. After a mean follow-up of 72 months, NODAT was frequently seen (18.6%), and was associated with tacrolimus medication (P<0.01) and a higher rate of renal transplantation failure (RR: 3.6, P<0.02). CONCLUSION: Hyperglycaemia appears to be a nearly constant characteristic immediately following transplantation in non-diabetic kidney recipients. Higher BG values could identify patients at risk for later post-transplant diabetes and graft failure.

Accuracy assessment of online glucose monitoring by a subcutaneous enzymatic glucose sensor during exercise in patients with type 1 diabetes treated by continuous subcutaneous insulin infusion.

AIM: Online continuous glucose monitoring (CGM) during physical exercise would be highly useful in patients with insulin-treated diabetes. For this reason, this study assessed whether such a goal could be reached with a subcutaneous 'needle-type' enzymatic sensor. METHODS: Ten patients (five women/five men), aged 51 ± 12 years, with type 1 diabetes for 24 ± 11 years treated by continuous subcutaneous insulin infusion (CSII) for more than 1 year (HbA1c: 7.5 ± 0.8%) performed a 30-min bout of exercise at a constant high-intensity load (15% above their individual ventilatory threshold) on a cycle ergometer. All patients wore a subcutaneous 'needle-type' enzymatic glucose sensor linked to a portable monitor (Guardian(®) RT, Medtronic-MiniMed, Northridge, CA, USA) that had been inserted the previous evening. Sensor calibration was performed against capillary blood glucose immediately before the exercise. CGM values were recorded every 5 min from T(-10) to T(+30), then every 10 min during the recovery period from T(+30) to T(+90). These recorded values were compared with blood glucose assays performed on simultaneously collected venous samples. RESULTS: Sensor functioning and tolerability raised no problems except for one sensor that could not be adequately calibrated. Data from this patient were excluded from the data analysis. An average blood glucose decrease of 63 ± 63 mg/dL (3.5 ± 3.5 mmol/L) (median decrease: 58 mg/dL [3.22 mmol/L]; range: -3 mg/dL [0.16 mmol/L] to 178 mg/dL [9.8 mmol/L]) occurred during exercise bouts, while CGM values decreased by 38 ± 49 mg/dL (2.11 ± 2.72 mmol/L) (median: 32 mg/dL [1.7 mmmol/L]; range: -15 mg/dL [0.83 mmol/L] to 58 mg/dL [3.22 mmol/L]). Cumulative paired glucose values (n = 135) could be analyzed. The correlation factor between CGM and blood glucose values was 0.957 with an intercept of 0.275. The mean difference between paired values according to Bland-Altman analysis was 10 ± 31 mg/dL (0.56 ± 1.72 mmol/L). Clarke error grid analysis showed 91% of paired points in A and B zones, while 0%, 9% and 0% of paired points were in the C, D and E zones, respectively. CONCLUSION: Blood glucose changes during intensive physical-exercise bouts performed by CSII-treated type 1 diabetes patients can be estimated with acceptable clinical accuracy by online CGM.

[Place of the flexible ureterorenoscopy first choice for the treatment of kidney stones. Survey results practice committee of the AFU lithiasis completed in 2011]. / Place de l'urétérorénoscopie souple en première intention pour le traitement des calculs du rein. Résultats de l'enquête de pratique du comité lithiase de l'AFU réalisée en 2011.

UNLABELLED: The flexible ureterorenoscopy coupled with photovaporisation LASER (USSR-L) for the treatment of kidney kidney is a modern tool whose place is under evaluation. METHODS: Its place has been assessed in France in 2010 by the Committee of urolithiasis of the French Association of Urology (CLAFU). A practice survey among 27 experts concerned the following decision criteria: comorbid patient's supposed nature of the calculation, anatomy of the urinary tract of the patient. This investigation has been proposed to calculate the size not exceeding 20mm, for a calculation of size greater than 20mm and for multiple calculations kidney. RESULTS: Fourteen experts responded. The criteria for the USSR-The first line were: morbid obesity (BMI>30), anticoagulation or anti platelet aggregation, calculations Hard (UH>1000, cystine stones), calculations within diverticular caliceal calculations below, the failure of a first treatment or the wish of the patient. CONCLUSION: The URS-SL was a first-line treatment validated regardless of size and number of kidney stones, when ESWL and PCNL were contraindicated or when their predictable results were poor (hard stones/morbid obesity/lower pole stones) or when stone access is difficult (intradiverticular). It was also the treatment of choice after the failure of a first treatment (ESWL/PCNL).

Towards an artificial pancreas at home.

AIM: To review the recent clinical research related to the development of an artificial pancreas and the current perspectives for its home use. METHODS: All clinical investigations assessing closed-loop insulin delivery systems in diabetic patients in the literature were collected and analyzed to identify any significant advances as well as bottlenecks. RESULTS: The development of an artificial pancreas for ambulatory use offering an optimal substitute for insulin secretion has shown promising evolution over the past decade. The accumulated improvements achieved on the performance of insulin pumps using subcutaneous and intraperitoneal routes, continuous glucose monitoring and algorithms driving insulin infusion according to glucose measurement have led to numerous clinical trials recently, albeit only in a hospital setting so far. The key obstacles to achieving permanent normal glucose control are related to the delay of insulin action when infused subcutaneously or, at a lesser extent, into the peritoneal cavity, and blood glucose estimation made by subcutaneous interstitial measurement. These time lags impair the reactivity of the system, and suggest a need to develop complex algorithms aiming at their compensation. So far, manual interventions are needed at times of food intake to prevent hyper- or hypoglycaemic excursions when insulin changes rapidly. CONCLUSION: The most recent models using subcutaneous insulin infusion and glucose measurements linked by predictive control algorithms offer sufficient effectiveness and safety to consider their forthcoming use at home, during the night as a first step.

Continuous glucose monitoring reduces both hypoglycaemia and HbA1c in hypoglycaemia-prone type 1 diabetic patients treated with a portable pump.

AIM: This study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and presenting with frequent hypoglycaemic episodes. METHODS: Thirteen patients with type 1 diabetes (diabetes duration: 25±15 years; CSII duration: 5.5±7.0 years), with more than six recorded capillary blood glucose (CBG) values <60 mg/dL, according to their metres for the past 14 days, were offered the permanent use of a CGM device (Guardian RT(®), Medtronic) plus ongoing self-monitoring of blood glucose (SMBG) for 12 weeks, followed by a 12-week crossover period of SMBG only, or vice versa. Glucose control, determined by recorded 14-day CBG values <60 mg/dL and HbA(1c) levels, and quality of life according to the Diabetes Quality of Life (DQOL) questionnaire, were assessed at baseline, and after 12- and 24-week follow-ups. RESULTS: Four patients withdrew from the study during the first period (of whom three were using CGM). In the nine study completers, the number of low CBG values decreased significantly from 13.9±9.2 to 7.6±6.8 (P=0.011) when patients used CGM, in either the initial or final trial period, while a decrease in HbA(1c) from 8.3±0.7 to 7.7±0.6% (P=0.049) was also observed, in contrast to the absence of any significant differences during the SMBG-only period. DQOL scores were also essentially unaffected. CONCLUSION: This pilot observational study supports the hypothesis that CGM use can significantly improve overall glucose control while reducing hypoglycaemic episodes in hypoglycaemia-prone type 1 diabetic patients treated by CSII.

[Cowden syndrome, or multiple hamartomatous tumor syndrome, in clinical endocrinology]. / Le syndrome de Cowden ou syndrome des hamartomes multiples en endocrinologie clinique.

Cowden syndrome (CS) is the prototypic PTEN hamartoma tumor syndromes (PHTS), rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. CS is characterized by association of macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, with increased risk for breast, thyroid and endometrial cancer. PTEN, which is located on chromosome 10q23, regulates negatively the prosurvival PI3K/Akt/mTOR pathway through a lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. CS diagnosis is clinical, based on the association of pathognomonic, major and minor criteria. The association in a patient with thyroid cancer, rarely with multinodular goiter, of typical dermatological manifestations, easily identifiable by clinical examination (papillomatous papules, acral keratoses, trichilemmomas), with a history of breast, endometrial, or renal cancer, or hamartomatous tumors presence, should alert the clinician. Clinical management of patients with CS is multidisciplinary, to include early and frequent screening, surveillance, and preventive care for associated malignancies. The development of antineoplastic agents targeting PI3K/Akt/mTOR pathway, such as rapamycin, may be the opportunity of treatment in PHTS and CS patients, for whom no specific medical treatment exist.

Attempt to improve glucose control in type 2 diabetic patients by education about real-time glucose monitoring.

The effectiveness of a specific educational programme involving the use of a real-time glucose-sensor system (Guardian RT) to improve glucose control was investigated in patients with poorly controlled type 2 diabetes despite insulin therapy. Ten patients participated in a randomized crossover study comparing two 3-month periods, during which glucose levels were monitored by either self-monitoring of blood glucose (SMBG) alone or by Guardian RT (restricted to 1 week per month) in addition to SMBG. Only four of the enrolled patients completed both periods, while dropouts were mainly due to technical difficulties in using the device. All six patients who completed the first 3-month period showed a reduction in glycated haemoglobin (HbA(1c)) level whatever the mode of glucose monitoring (study effect). A further reduction in HbA(1c) level was observed in two of the three patients using the Guardian RT during the second period. Less frequent symptomatic hypoglycaemic episodes were noted during the 3-month period with the device in the four patients who completed both study periods. These limited, but promising, results of this pilot study appear to justify the initiation of a larger study to assess the use of a real-time glucose sensor in carefully selected patients with type 2 diabetes.

Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France.

AIM: The objective of the present study was to investigate the genetic association of the fat-mass-and-obesity-associated (FTO) gene in obese women in the presence of the known influential role of the insulin receptor substrate 2 (IRS-2) gene. METHODS: This case-control study was carried out in the Languedoc-Roussillon region of France, and included lean control women (n=128), and women (n=119) of various degrees of obesity (body mass index [BMI] mean+/-S.D.: 39.3+/-7.4kg/m(2)) and a prevalence of 26.9% of the metabolic syndrome (MetS). For the FTO gene, genotyping was performed by sequence-specific oligonucleotide-polymerase chain reaction (SSO-PCR) on the single nucleotide polymorphism (SNP) rs1421085 (C/T) while, for IRS-2, the rs1805097 (G/A) corresponding to variant Gly1057Asp was genotyped by direct sequencing. RESULTS: The FTO gene (homozygous C/C) was significantly associated to both simple and morbid obesity (P<0.026 and P<0.0034, respectively), with odds-ratios (ORs) of 2.58 (95% CI: 1.1-6.0) and 4.1 (95% CI: 1.6-10.5), respectively, independent of IRS-2. MetS was also associated with FTO (P<0.032, OR: 3.1, 95% CI: 1.1-8.5), but not with IRS-2. Genotypes of FTO were correlated with insulin resistance, and homozygous C/C was positively correlated with an increase in insulin resistance over the value predicted by the increase in BMI. CONCLUSION: These data confirm the influential role of the FTO gene in obesity in the French female population and, in addition, revealed the role of FTO in insulin resistance and MetS. These effects appeared to be independent of IRS-2, which is directly involved in insulin action. This study may offer new insights into the genetic determinants of obesity and MetS in women.

Prevalence of diagnosed type 2 diabetes mellitus in the French general population: the INSTANT study.

AIMS: To estimate the prevalence of diagnosed type 2 diabetes mellitus in the French general population. Secondary objectives were to evaluate treatments and diabetic complications. METHODS: In this cross-sectional epidemiological survey, a representative sample of the French adult population was selected using a stratified quota method: 10,038 individuals were evaluated by a standardized face-to-face interview. The diagnosis of type 2 diabetes was determined on the basis of replies to six questions using a specific algorithm. Data were collected on risk factors, diabetes history, familial antecedents and diabetic complications. These patients also identified their treatments from an exhaustive list. RESULTS: The prevalence of type 2 diabetes was 5.08% in men and 4.11% in women, and rose progressively after the age of 50. Of these, 79 patients (13.4%) received no pharmacological treatment, 477 (80.9%) were taking an oral antidiabetic drug and 134 (22.7%) were taking insulin. Renal and ocular complications were reported by 6.8% and 21.0%, respectively, of the patients. Also, 10.4% had been hospitalized at some time of that year for a diabetes-related problem. The most frequently reported treatments were metformin and sulphonylureas, used by more than 50% of the patients. In addition, 380 patients (65.9%) claimed to be following a diet and 228 (39.2%) were consulting a dietitian. CONCLUSION: The prevalence of treated and untreated type 2 diabetes mellitus in France was 4.57%.