Prevalence of Fabry Disease in Patients on Dialysis in France.

Numerous prevalence studies on Fabry disease (FD, OMIM #301500) have been conducted in dialysis populations across the world with variable and controversial results. The FABRYDIAL study aimed to estimate the prevalence of FD in patients aged 18 to 74 years on chronic dialysis in France. This cross-sectional study was conducted in patients undergoing dialysis. One hundred and twenty-four dialysis centers participated. Patients with proven causes of nephropathy unrelated to FD were excluded. Alpha-galactosidase A activity was assayed in men, and both α-galactosidase A and lyso-Gb3 were assayed in women from dried blood spots. GLA gene sequencing was performed in case of abnormal values. If a variant was identified, a diagnosis validation committee was consulted for adjudication. Among the 6032 targeted patients, 3088 were included (73.6% of the eligible patients). Biochemical results were available for 2815 (1721 men and 1094 women). A genetic variant of GLA was identified in five patients: a benign c.937G>T/p.(Asp313Tyr) variant in two individuals, a likely benign c.427G>A/(p.Ala143Thr) variant, a likely benign c.416A>G/(p.Asn139Ser) variant, and a pathogenic c.1185dupG/p.Phe396Glyfs variant. Among the screened patients, the prevalence was 0.058% [0.010;0.328] in males, 0% [0.000;0.350] in females, and 0.035% [0.006;0.201] when both genders were pooled. Among all patients aged 18-74 years undergoing dialysis without a previously known cause of nephropathy unlinked to FD, the prevalence was 0.028% [0.006;0.121]. The prevalence of FD in a cohort of French dialysis patients was low. However, considering the prognostic impact of earlier diagnosis, signs of FD should be sought in patients with nephropathies of uncertain etiology.

Using intervention mapping to facilitate and sustain return-to work after breast cancer: protocol for the FASTRACS multicentre randomized controlled trial.

BACKGROUND: Women with breast cancer face many barriers to return to work (RTW) after their cancer. The main objective of the FASTRACS-RCT is to evaluate the impact of the FASTRACS (Facilitate and Sustain Return to Work after Breast Cancer) intervention on the sustainable RTW of breast cancer patients, 12 months after the end of active treatment. METHODS: FASTRACS-RCT is a prospective, national, multicentre, randomized, controlled and open-label study. A total of 420 patients with early breast cancer scheduled for surgery and (neo)adjuvant chemotherapy, will be randomly assigned (1:1 ratio) to: (i) the intervention arm comprising four steps over 6 months : Handing over the intervention tools; transitional medical consultation with the general practitioner (GP); pre-RTW visit with the company's occupational physician (OP); catch-up visit with a hospital-based RTW expert (if sick leave > 10 months) (ii) the control arm to receive usual care. The design of the FASTRACS intervention was informed by intervention mapping for complex interventions in health promotion planning, and involved patients and representatives of relevant stakeholders. Specific tools were developed to bridge the gap between the hospital, the GP, the OP and the workplace: a toolkit for breast cancer patients comprising a theory-based guide; specific checklists for the GP and the OP, respectively; and a theory-based guide for workplace actors (employer, manager, colleagues). The primary endpoint will associate sustainable RTW (full-time or part-time work at 50% or more of working time, for at least 28 consecutive days) and days off work. It will be assessed at 4, 8 and 12 months after the end of active oncological treatment. Secondary endpoints will include quality of life, anxiety, depression, RTW self-efficacy, physical activity, social support, job accommodations, work productivity, job status, and the usefulness and acceptability of the intervention's tools. DISCUSSION: FASTRACS-RCT will be supplemented by a realist evaluation approach aimed at understanding the influence of context in activating the intervention's mechanisms and effects. If the expected impact of the intervention is confirmed, the intervention will be adapted and scaled-up for other cancers and chronic diseases to better integrate healthcare and work disability prevention. TRIAL REGISTRATION: NCT04846972 ; April 15, 2021.

Feasibility of a screening and prevention procedure for risks associated with dysphagia in older patients in geriatric units: the DYSPHAGING pilot study protocol.

BACKGROUND: Dysphagia, particularly sarcopenic dysphagia, is frequent in frail older patients. Sarcopenic dysphagia is a swallowing disorder caused by sarcopenia, corresponding to a loss of muscle mass and strength. It frequently leads to inhalation and to the decrease of food intake, leading the patient to enter a vicious circle of chronic malnutrition and frailty. The awareness of the major health impacts of sarcopenic dysphagia is recent, explaining a low rate of screening in the population at risk. In this context, methods of prevention, evaluation and intervention of sarcopenic dysphagia adapted to the most at-risk population are necessary. METHODS: The DYSPHAGING (dysphagia & aging) pilot study is a prospective, multicentre, non-comparative study aiming to estimate the feasibility of an intervention on allied health professionals using the DYSPHAGING educational sheet designed to implement a two-step procedure 'screen-prevent' to mitigate swallowing disorders related to sarcopenic dysphagia. After obtaining oral consent, patients are screened using Eating Assessment Tool-10 Score. In case of a score≥2, procedures including positional manoeuvres during mealtimes, food and texture adaptation should be implemented. The primary endpoint of the study is the feasibility of this two-step procedure (screening-prevention measures) in the first 3 days after patient's consent.The study will include 102 patients, with an expected 10% rate of non-analysable patients. Participants will be recruited from acute geriatric wards, rehabilitation centres and long-term care units, with the hypothesis to reach a feasibility rate of 50% and reject a rate lower than 35%. ETHICS AND DISSEMINATION: The study protocol was approved according to French legislation (CPP Ile-de-France VII) on 15 February 2023. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05734586.

A cross-sectional study to evaluate hypovitaminosis C prevalence and risk factors in an acute geriatric unit in Lyon, France: the HYPO-VIT-C protocol.

INTRODUCTION: Vitamin C is an essential micronutrient playing crucial roles in human biology. Hypovitaminosis C is defined by a plasmatic ascorbemia below 23 µmol/L and is associated with numerous outcomes such as cardiovascular diseases, cancers or neurocognitive disorders. Numerous risk factors are common among older adults making them particularly susceptible to hypovitaminosis C. These risk factors include reduced vitamin intakes, higher vitamin metabolism related to polypathology, and iatrogeny because of polypharmacy. However, the precise prevalence of hypovitaminosis C and its risk factors are poorly documented within the geriatric population.A better knowledge of hypovitaminosis C prevalence and risk factor may lead to improving the vitamin C status among older people and prevent its consequences. METHOD AND ANALYSIS: To answer these questions, we designed a monocentric cross-sectional study in a population of older hospitalised patients in Lyon, France. A sample size of 385 patients was needed to estimate hypovitaminosis C prevalence. The study was proposed to all eligible patient aged more than 75 years old entering the participating acute geriatric unit. The plasmatic vitamin C status was systematically assessed for participating patients, and variables part of the medical and geriatric evaluation were collected. For patients with severe vitamin C depletion, an oral supplementation and a follow-up phone call were organised to ensure treatment completion and tolerance. ETHICS AND DISSEMINATION: The protocol has been approved by an independent national ethics committee and meets the methodological requirements. Final outcomes will be published in a peer-reviewed journal and disseminated through conferences. TRIAL REGISTRATION NUMBER: NCT05668663.

[Multidisciplinary Team Meeting dedicated to geriatric oncology: Decisions and four month follow-up]. / RCP dédiée à l'onco-gériatrie : décisions et suivi à quatre mois.

INTRODUCTION: MTDM dedicated to geriatric oncology are held at the E. Herriot hospital in Lyon. They bring together oncologist and geriatrician to optimize, through their complementary expertise, the care plan for elderly cancer patients. The aim is to demonstrate the value of these MTDMs and to describe the follow-up of oncological and geriatric recommendations. METHODS: This is a descriptive, prospective, non-interventional study analyzing the MTDMs dedicated to patients over 70years old with cancer. All patients underwent a comprehensive geriatric assessment (CGA) with a four-month follow-up. RESULTS: One hundred twenty-one patients were included with a G8 score≤14 (93 %), a slightly diminishing independence ADL<6 (36%) and IADL<4 (42%). The median CIRS-G is eight with on average, three geriatric syndromes/patient. Most cancers are non-metastatic. When oncological treatment is recommended (80 %), it is mostly curative (58 %). Geriatric recommendations were made for 75 % of patients. At four months, four patients were lost to follow-up and 34 died. No significant change in the dependency level was found. In 75 % of cases, at least one geriatric recommendation were followed and 77 % of oncological recommendations. CONCLUSION: The recommendations could be followed at four months; they were carried out in a comparable way whether they were oncological or geriatric. These MTDMs specializing in geriatric oncology appear to be beneficial in the geriatric oncology decision-making process. It is important to continue and strengthen this co-management.

Relationship between adverse drug reactions and unlicensed/off-label drug use in hospitalized children (EREMI): A study protocol.

INTRODUCTION: To date, few studies have shown a significant association between off-label drug use and adverse drug reactions (ADRs). The main aims of this study is to evaluate the relationship between adverse drug reactions and unlicensed or off-label drugs in hospitalized children and to provide more information on prescribing practice, the amplitude, consequences of unlicensed or off-label drug use in pediatric inpatients. METHODS: In this multicenter prospective study started from 2013, we use the French summaries of product characteristics in Theriaque (a prescription products guide) as a primary reference source for determining pediatric drug labeling. The detection of ADRs is carried out spontaneously by health professionals and actively by research groups using a trigger tool and patients' electronic health records. The causality between suspected ADRs and medication is evaluated using the Naranjo and the French methods of imputability independently by pharmacovigilance center. All suspected ADRs are submitted for a second evaluation by an independent pharmacovigilance experts. STRENGTH AND LIMITATIONS OF THIS STUDY: For our best knowledge, EREMI is the first large multicenter prospective and objective study in France with an active ADRs monitoring and independent ADRs validation. This study identifies the risk factors that could be used to adjust preventive actions in children's care, guides future research in the field and increases the awareness of physicians in off-label drug use and in detecting and declaring ADRs. As data are obtained through extraction of information from hospital database and medical records, there is likely to be some under-reporting of items or missing data. In this study the field specialists detect all adverse events, experts in pharmacovigilance centers assess them and finally only the ADRs assessed by the independent committee are confirmed. Although we recruit a high number of patients, this observational study is subject to different confounders.

Developing a Return to Work Intervention for Breast Cancer Survivors with the Intervention Mapping Protocol: Challenges and Opportunities of the Needs Assessment.

Return to work (RTW) is an important step for breast cancer survivors (BCSs). However, they face many barriers that affect particularly women with low socioeconomic status (SES). Health care, workplace, and insurance actors lack knowledge and collaborate poorly. No intervention to date has proven effective to reduce social disparities in employment after breast cancer. The intervention mapping (IM) protocol is being used in France to develop, implement, and evaluate an intervention to facilitate and sustain RTW after breast cancer [FAciliter et Soutenir le retour au TRAvail après un Cancer du Sein (FASTRACS) project]. The research question of this study was to elicit the needs for RTW after breast cancer from various stakeholders' point of view. The aim of this study was to describe the process and the preliminary results of the needs assessment of the FASTRACS project. Different methods were followed to (a) establish and work with a planning group and (b) conduct a needs assessment to create a logic model of the problem. A planning group was organized to gather the stakeholders with the research team. A review of the literature and indicators was conducted to identify the magnitude of the problem and the factors influencing RTW. A qualitative inquiry was conducted with 12 focus groups and 48 individual semi-structured interviews to explore the needs and experience of the stakeholders. The results of these tasks were the proposition of a charter of partnership to structure the participative process, a review of the scientific evidence and indicators, and the description by the stakeholders of their needs and experience. Many stakeholders disagreed with the concept of "early intervention." They advocated for a better support of BCSs during their RTW, emphasized as a process. Anticipation, intersectoral collaboration, and workplace accommodation were mentioned to fit the needs of the BCS and their environment. A logic model of the problem was elaborated from these data. The ability of the model to consider specific characteristics of women with low SES is discussed, with a view to developing the FASTRACS intervention through the next steps of the IM protocol.

Influence of donor age on islet isolation and transplantation outcome.

BACKGROUND: It has been suggested that the age of human organ donors might influence islet isolation and transplantation outcome in a negative way due to a decrease of in vivo function in islets isolated from older donors. METHODS: We retrospectively analyzed 332 islet isolations according to donor age. We determined isolation outcome by islet yields, transplantation rates, and [beta]-cell function in vitro. Transplanted patients were divided into two groups depending on donor age (n=25 and n=31 patients for <=45- and >45-year-old donors, respectively). We assessed islet graft function by C-peptide/glucose ratio, [beta] score, secretory units of islets in transplantation index, and insulin independence rate at 1, 6, and 12 months after transplantation. RESULTS: There was no difference in islet yields between the two groups (251,900+/-14,100 and 244,600+/-8400 islet equivalent for <=45- and >45-year-old donors, respectively). Transplantation rates and stimulation indices were similar in both groups as well. All islet graft function parameters were significantly higher at 1-month follow-up in patients who had received islets from younger donors. At 6-month follow-up after second or third injection and at 12-month follow-up, secretory units of islets in transplantation indices and C-peptide/glucose ratios were significantly higher in patients with donors aged 45 years or younger. CONCLUSIONS: These data suggest that, despite similar outcomes of the isolation procedure, islet graft function is significantly influenced by donor age. These results may have important consequences in the definition of pancreas allocation criteria.

Shared medical information: expectations of breast cancer patients.

UNLABELLED: Allowing cancer patients to hold medical records containing essential information for managing their disease may improve their satisfaction and the coordination of their medical care. OBJECTIVE: Our aim was to determine breast cancer patients' interest in and expectations of such medical records and the exchange of information during their treatment. METHODS: Eighty-six hospital physicians were selected to distribute an anonymous questionnaire to all of the breast cancer patients they saw in consultations. RESULTS: Out of 194 patients asked, 140 (72%) participated in the survey. Forty-eight percent were "highly satisfied", 47% were "quite satisfied" with their involvement in their treatment and 43% preferred to play a relatively passive role in decisions concerning treatments. When offered, 79% agreed to hold paper medical records containing test results, reports and letters. Many found these medical records to be useful and a possible means for improving communication. Others, however, expressed reservations concerning privacy or losing or forgetting the records. CONCLUSION: The principle of shared medical records could satisfy the majority of breast cancer patients. Experimenting with this concept in the field would enable practitioners to better determine the content of the records and how they can be used on a practical basis.

Expectations and strategies regarding islet transplantation: metabolic data from the GRAGIL 2 trial.

BACKGROUND: Whether islet transplantation should be aimed at restoring insulin independence or providing adequate metabolic control is still debated. The GRAGIL2 trial was designed as a phase 1-2 study where primary outcome was the rate of insulin independence, and secondary outcome was the success rate defined by a composite score based upon basal C-peptide, HbA1c, hypoglycemic events, and exogenous insulin needs. METHODS: C-peptide negative type 1 brittle diabetic patients experiencing severe hypoglycemia were eligible to receive a maximum of two islet preparations totalizing 10,000 IE/kg or more, with a threshold of 5,000 IE/kg for the first infusion, according to the Edmonton protocol, within the Swiss-French GRAGIL multicentric network. A sequential analysis with a triangular test was performed in every five patients after 6- and 12-month follow-up. Maximal inefficiency was set at 40% and minimal efficiency at 66%. RESULTS: From September 2003 to October 2005, 10 patients were included. Median waiting time was 6.7 months (first injection) and 9 weeks (second injection). All but one patient received 11,089+/-505 IE/kg: one received a single graft of 5398 IE/kg. At 6 months, insulin independence and composite success rates were 6 of 10 and 6 of 10, respectively. At 12 months, insulin independence was observed in 3 of 10 patients and success in 5 of 10 patients. CONCLUSION: Based upon our sequential analysis settings, islet transplantation failed to achieve the primary goal, insulin independence, but tended to succeed in reaching the secondary goal, successful metabolic control. Currently it appears to be a successful biological closed-loop glucose control method for brittle diabetes.

[Exchanges of medical information during the follow up of breast cancer patients: perceptions and expectations of the community- and the hospital based practitioners]. / Echanges d'informations médicales dans la prise en charge des patientes atteintes d'un cancer du sein: perceptions et attentes des médecins traitants de ville et des spécialistes hospitaliers.

The multidisciplinary dimension which imposes the follow up of patients suffering from breast cancer raises difficulties of communication between community and hospital practitioners. The aim of this study was to assess information needs and expectations when the general practitioners and private gynecologists on one hand, and the hospital practitioners on the other hand, exchange medical information in the follow up of patients suffering from breast cancer. This descriptive study included a sample of 225 general practitioners and 216 gynecologists in private practice, and 233 hospital practitioners in the Rhone-Alps French region. Response rate was respectively 68 % (153), 64 % (139) and 42 % (99). This study showed different perceptions on the frequency of shared documents (reports, letters) or phone calls according to the speciality. In spite of a strongly felt partnership, an expectation of change was found with notably the wish of a stronger implication in the follow up and the wish to receive numerous information concerning the patients. The community practitioners expected to be more aware of the stage of the cancer, the prognosis and the level of information given to the patients. The hospital specialists expected to be informed about psychological problems or comorbidity. Pending the generalization of an electronic shared medical records, the experiment of a patient-held records may help to fulfil these expectations.

Logistics and transplant coordination activity in the GRAGIL Swiss-French multicenter network of islet transplantation.

BACKGROUND: Since the Edmonton trial in 2000, increasing numbers of transplant centers have been implementing islet transplantation programs. Some institutions have elected to associate in multicenter networks, such as the Swiss-French GRAGIL (Groupe Rhin-Rhône-Alpes-Genève pour la Transplantation d'Ilots de Langerhans) consortium. METHODS: All pancreata offers to the University of Geneva Cell Isolation and Transplantation Center from within the network in 2002 and 2003 were reviewed. Islet preparations were attributed to the most suitable recipient on a centrally managed waiting list. All shipments were performed by ambulance in less than 5 hr. RESULTS: Over the period of study, 260 pancreata were offered, from a total of 1,304 cadaveric donors in the four allocation regions (20%). Fifty-two patients were on the waiting list at any time during this 2-year period. The percentage of organs offered varied in the range of 0.5% to 42%, depending on region of origin, with a correlation with number of patients on the waiting list in each region. Of these, 104 (40%) were accepted for processing. Ninety-two pancreata were actually processed, resulting in 42 islet preparations being transplanted. The number of international equivalents of transplanted preparations was 378,500+/-16,000 versus 165,400+/-15,400 (P<0.0001) for nontransplanted preparations. Total cold ischemia time was 6+/-0.3 hr for transplanted preparations versus 6.7+/-0.4 hr for nontransplanted preparations (not significant). CONCLUSIONS.: A high rate of pancreas offers, successful isolation, and islet transplantation can be achieved in multicenter networks such as GRAGIL. Such an approach can expand both the donor pool and the recipient population.

Influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients within the Swiss-French GRAGIL network.

BACKGROUND: The influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients was evaluated within the GRAGIL network. PATIENTS AND METHODS: From December 2001 to April 2003, 16 human pancreatic islet transplants were performed in 9 type 1 diabetic patients with an established kidney graft (functioning for at least 6 months) in four centers of the GRAGIL network. Islet isolation was performed in a core laboratory in Geneva, and the islet preparations were shipped by ambulance to each center for transplantation. One month after transplantation, the efficiency of the graft was assessed according to islet transportation time (ITT): ITT less than 2 hours (group 1, n=5), and ITT greater than 4.5 hours (group 2, n=4, mediant 5 hours). RESULTS: Primary graft dysfunction was observed in one patient in group 1 after one month. Two patients became insulin independent in groups 1 and 2. All other patients in both groups had a plasma C-peptide level greater than 0.5 ng/ml. The HbA1c level and the exogenous insulin needs decreased in both groups. CONCLUSIONS: ITT does not seem to influence the efficiency of pancreatic islet allotransplantation in type 1 diabetic patients. These results emphasize the scope for multicenter networks such as the GRAGIL group.