[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.

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.

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.

[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.

[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).

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%.

Optimizing the outcome of pregnancy in obese women: from pregestational to long-term management.

The obesity epidemic is of some concern in women of reproductive age. Maternal obesity is associated with many pregnancy complications, especially gestational diabetes and hypertensive disorders of pregnancy. Delivery in obese women is characterized by a high caesarean-section rate and an increased risk of anaesthetic and postoperative complications. Weight retention after birth may increase the risk of type 2 diabetes in the long term. Foetal risks include macrosomia, malformations and increased perinatal mortality, with the long-term infant health marked by a higher risk of obesity and metabolic disorders. Optimal management includes preconception counselling, pregravid weight-loss programmes, monitoring of gestational weight gain, repeated screening for pregnancy complications and long-term follow-up to minimize the social and economic consequences of pregnancy in overweight women.

Abdominal obesity is associated with ineffective control of cardiovascular risk factors in primary care in France.

AIM: Insufficient control of cardiovascular risk factors is observed in primary care. The goal of the present study was to evaluate the association of abdominal obesity with achievement of treatment targets for HbA(1c), LDL cholesterol, triglycerides, HDL cholesterol and blood pressure in primary care. METHODS: In this cross-sectional observational epidemiological study, primary-care practitioners completed a questionnaire covering demographic and socioeconomic data, medical history, drug treatment, and clinical and biological characteristics for 3351 patients (1630 men and 1721 women). Therapeutic targets were HbA(1c) <7%, LDL cholesterol <1.6g/L, triglycerides <1.5 g/L and SBP/DBP <140/90 mmHg. Multivariate analyses were performed to assess the relationship between waist circumference and a lack of cardiovascular risk-factor control. RESULTS: The patients' mean ages were 58+/-14 years and 55+/-16 years for men and women, respectively. A large waist circumference was positively and significantly (P<0.0001 for all) associated with diabetes, hypercholesterolaemia, hypertriglyceridaemia, low HDL cholesterol and hypertension. The prevalence of patients not achieving therapeutic targets increased across waist-circumference quartiles. For treated patients, the odds ratios (95% CI) (adjusted for age, gender, education, smoking status and medical specialty) for not achieving treatment targets were 17.6 (2.2-142) for triglycerides, 2.8 (1.3-6.1) for HbA(1c) and 1.4 (0.9-2.0) for blood pressure on comparisons with extreme quartiles of waist-circumference distribution. CONCLUSION: In primary care, a lack of control of triglycerides, HbA(1c) and, to a lesser extent, blood pressure increases with waist circumference independently of confounders. This suggests that abdominal obesity is associated of poor results in the treatment of diabetes and hypertriglyceridaemia.

Artificial beta-cell: clinical experience toward an implantable closed-loop insulin delivery system.

AIM: Restoration of long-term normal blood glucose control in diabetic patients supports the elaboration of an artificial beta cell. The possibility of implantation of the three crucial components of such a system (insulin delivery device, glucose sensor and controller) is analyzed. METHODS: The Long-Term Sensor System project, aiming at a fully implantable artificial beta cell, assessed the feasibility of glucose control by the combined implantation of a pump for peritoneal insulin delivery and a central intravenous glucose sensor close to the right atrium, connected via a subcutaneous lead. It was initiated in 10 Type 1 diabetic patients in our clinic from 2000. Data obtained during this experience are reviewed and confronted to reported closed-loop trials using other approaches. RESULTS: No significant complication related to prolonged implantation of intravenous sensors occurred and the combined implants were well tolerated. Glucose measurement by the intravenous sensors correlated well with meter values (r=0.83-0.93, with a mean absolute deviation of 16.5%) and accuracy has been sustained for an average duration of 9 months. Uploading of pump electronics by algorithms designed for closed-loop insulin delivery allowed in-patient 48 hour-trials aiming at automated glucose control. Glucose control was similar to that reported by investigations combining subcutaneous sensors to wearable pumps for subcutaneous insulin infusion. The benefits of more physiological insulin kinetics due to intra-peritoneal delivery have been hampered by the slow response time of intravenous sensors. CONCLUSION: Although the concept of a fully implantable artificial beta cell has been validated as feasible, the limited performance in achieving glucose control requests improvements in the sensor structure to increase its longevity and decrease sensor delay.

Accuracy of continuous subcutaneous glucose monitoring with the GlucoDay in type 1 diabetic patients treated by subcutaneous insulin infusion during exercise of low versus high intensity.

AIM: The GlucoDay allows continuous glucose monitoring by subcutaneous microdialysis in sedentary conditions. To validate it when glycaemia may undergo rapid and dramatic changes, we investigated its accuracy during two exercise sessions with markedly different glucose disposal rates. METHODS: Nine male diabetic patients, aged 32-61, treated by insulin pumps, first underwent a standard maximal exercise-test designed for determining the maximal oxygen consumption and the first ventilatory threshold (Vt1). Then two 30 min steady-state workloads at 15% below and 15% above the Vt1 were performed in random order with the GlucoDay, and measurement of CHO oxidation rates was made by indirect calorimetry. RESULTS: CHO oxidation during exercise at +15% Vt1 was higher (+943.5 mg/min, ie +45.5%, P<0.01) than during exercise at -15% Vt1 No hypoglycaemia occurred. Due to breakages of 39% of subcutaneous probes, eleven steady-state sessions in 7 subjects allowed to compare 141 paired glucose (sensor vs. venous) determinations. The Clarke error grid situates 92.9% of glucose values within the A zone and 6.4% within the B zone, while only one pair of values (0.7%) falls in the D zone. Venous glucose tended to decrease more rapidly than sensor glucose during exercise. Bland-Altman plots evidence for a few cases of underestimation of venous glucose at high intensity. CONCLUSIONS: This study showed satisfactory accuracy of the GlucoDay during exercise. A slight lag time in sensor values likely explains a few discrepancies that do not appear as clinically meaningful. Reduction of probe fragility and confirmed sensor accuracy in hypoglycaemia would further support applicability of GlucoDay at exercise.

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.

Prevention of insulin aggregation by dicarboxylic amino acids during prolonged infusion.

The dicarboxylic amino acids, aspartic and glutamic acid, at their isoelectric pH, reduced aggregation of insulin solutions in vitro for 16 days during continuous agitation at 37 degrees C. Unprotected insulin solutions, when infused via a 14-day implantable infusion device in diabetic Chinese hamsters, controlled plasma glucose levels for only 2 days, followed by escape coincident with insulin aggregation. However, when insulin solutions were protected with glutamic acid, euglycemia was maintained for the 14-day life of the device.

Glucagon immunoreactivity and antidiabetic action of somatostatin in the totally duodeno-pancreatectomized and gastrectomized human.

Ten patients who had been totally duodeno-pancreatectomized and totally (N = 1) or partially gastrectomized (N = 9) for chronic pancreatitis (N = 9) or pancreatic carcinoma (N = 1) were investigated. None had a measurable basal level of either plasma C-peptide or a C-peptide response to i.v. glucagon. Immunoreactive glucagon (IRG) was present in all patients, and the mean level (69 +/- 8 pg/ml) was not significantly different from the mean observed in normal subjects (81 +/- 16 pg/ml). Plasma IRG was unequivocally stimulated by arginine in 2 of the 10 subjects. The effect of somatostatin on plasma glucose and IRG during an oral glucose tolerance test was studied in 5 of the 10 patients. The effects of somatostatin on spontaneous hyperglycemia, plasma growth hormone, and IRG after withdrawal of insulin treatment was studied in 4 patients. Somatostatin blunted both the hyperglycemic and paradoxical IRG responses to the glucose challenge, and reduced the spontaneous rise of blood glucose that occurred after insulin withdrawal. This latter effect was not related to clear-cut changes in plasma growth hormone or in IRG. These data confirm the existence of circulating IRG in pancreatectomized patients and demonstrate the presence of circulating IRG in a completely gastrectomized and pancreatectomized patient. The somatostatin-induced improvement in glucose tolerance in the oral glucose tolerance test seems to be related to a reduction of the paradoxical IRG response. In contrast, the inhibition by somatostatin of the rise in blood glucose which occurs after insulin withdrawal does not seem to be mediated through IRG or growth hormone.

Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome.

To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and IRS-2 genes in insulin resistance, we explored the genomic DNA in women with polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)] 3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct sequencing. Whereas no novel mutations were found in these genes, gene-dosage effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h plasma glucose for the Gly1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was more prevalent in insulin-resistant patients compared with non-insulin-resistant individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031, respectively). A multivariate model that included BMI as a variable revealed significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P < 0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of both IRS variants than in those with IRS-2 mutations only or those with wild-type variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS.

Comparative effect of captopril and nifedipine in normotensive patients with incipient diabetic nephropathy.

In these studies, the effect of a 6-wk treatment by placebo, the calcium-channel blocker nifedipine, or the converting-enzyme inhibitor captopril was assessed in normotensive patients with insulin-dependent diabetes and incipient nephropathy. In response to captopril and nifedipine, arterial pressure decreased slightly and to a similar extent. These drugs resulted in opposite effects on urinary excretion of albumin [i.e., increase in urinary albumin excretion (UAE) by 40% during nifedipine treatment and decrease by 40% during captopril treatment]. No change in UAE was observed in the placebo group. This observation of opposite changes in UAE in the presence of a similar fall in arterial pressure suggests that the effects of captopril and nifedipine on UAE result from some difference in their intrarenal action. The data do not present recommendations for the use or disuse of captopril or nifedipine in such a group of patients and do not allow extrapolation to hypertensive diabetic subjects well controlled by other conventional antihypertensive agents.

Complications of the pump pocket may represent a significant cause of incidents with implanted systems for intraperitoneal insulin delivery.

OBJECTIVE: To increase awareness of adverse events associated with the use of programmable implantable pumps (PIPs). CASES: There were 7 cases of complications associated with the pump-pocket among 40 patients treated by PIP, and we searched for risk factors. RESULTS: Seven of 40 type I diabetic patients treated by PIP presented severe complications of the pump-pocket, resulting in five definitive explanations and nine other surgical interventions. The lesions included an exudative reaction in the pump-pocket and a skin retraction or atrophy, which were complicated by skin erosion in five patients. Coagulase-negative staphylococcus was identified in the pump-pocket in four patients, including three cases of skin erosion. No specific risk of local complications could be attributed to age, sex, duration of diabetes, body mass index, presence of retinopathy or peripheral neuropathy, HbA1c level since implantation, depth of implantation in the abdominal wall, or duration of experience with PIP. Usual physical activity corresponding to > 2,000 kcal energy expenditure per week, estimated by a questionnaire, appeared to be the only identified significant risk factor. CONCLUSIONS: From these results, we suggest that physical activity should be limited to moderate exercise and exclude vigorous efforts in diabetic patients treated by PIP to avoid an increased risk of complications at the implantation site.

Comparative analysis of soluble porcine and human insulin (Novo) using the artificial pancreas.

The porcine-extracted monocomponent insulins and human insulin (Novo) obtained by enzymatic conversion of porcine insulin had similar effects on glycemia balance when compared by means of an artificial pancreas during two 48-h studies 2 or 3 days apart. There was no significant difference between the maximum and minimum blood glucose circadian variations, the glycemic drops, and the Schlichtkrull coefficient. The speed of increase and decrease of glycemia during meals was slightly slower with human insulins than with porcine insulins, but the difference was not significant. Although comparable, the insulin requirements (per gram of ingested carbohydrate) were proportionately greater in the morning than during the rest of the day; the baseline requirements were also similar, but showed a trend toward increase during the day with both insulins.

Insulin underdelivery from implanted pumps using peritoneal route. Determinant role of insulin pump compatibility.

OBJECTIVE: To evaluate the incidence and investigate determinants of insulin underdelivery events occurring with implanted pumps using peritoneal route from a 103 patient-year experiment. RESEARCH DESIGN AND METHODS: Of the MiniMed (MIP 2001) pumps implanted in 47 type I diabetic patients, 70 were refilled quarterly with four successive batches (A, B, C, D) of U400 Hoechst 21 PH neutral insulin during a 3-year study period. Any reduction of insulin flow rate > 15% was considered as abnormal insulin delivery. Diagnosis of the cause of underdelivery was established according to the response to the following steps: 1) 0.01 mol/l NaOH rinse of pump circuits to solubilize insulin aggregates, 2) surgical examination and replacement of blocked catheters, and 3) postsurgical 0.01 mol/l NaOH rinse of pump. Step 2 was selected first if the increase of insulin requirements or reduction of flow rate were > 50%. Relative contributions of insulin and the implanted system to underdelivery events were analyzed. RESULTS: There were 76 episodes of insulin underdelivery that occurred during the study, resulting in an incidence of 74 events per 100 patient-years. Of 52 NaOH pump rinses, 30 restored normal flow rate. Surgery, performed after rinse failure (n = 22) or as the first step (n = 24), disclosed catheter blockages due to tip obstructions in 28 cases and omental encapsulations in 18 other cases. Five combined severe reductions of pump flow rate requiring pump replacements were diagnosed during surgery, and additional NaOH rinses had to be performed after catheter change in 12 other cases. Analysis of the incidence of underdelivery events indicated that both pump- and catheter-related problems were significantly increased while implanted systems infused batches B, C, and D versus batch A (P < 0.01), whereas the duration of pump implantation had no significant influence. CONCLUSIONS: Underdelivery events constitute serious limiting obstacles to prolonged peritoneal insulin infusion from implanted pumps. Progress in insulin pump compatibility is expected to reduce their occurrence and, thus, to improve the feasibility of this treatment.