Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999-2000). Groupe de Recherche Rhin Rhĵne Alpes Genève pour la transplantation d'Ilots de Langerhans

Aims/hypothesis. Improvements in islet transplantation require clinical series large enough to implement controlled new strategies. The goal of this study was to demonstrate the feasibility of a multicentre network for islet transplantation in Type I (insulin-dependent) diabetic patients. Methods. The five centres (Besançon, Geneva, Grenoble, Lyon, Strasbourg) of the GRAGIL network allow pancreas procurement, recipient recruitment, transplantation procedure and follow-up. Islet isolation is, however, performed in one single laboratory (Geneva). Pancreata were procured in each of the five centres and transported to Geneva with an ischaemia time of less than 8 hours. Islets were isolated using a standard automated method. If the islet number was too low for a graft ( < 6000 Islet-equivalent /kg), islets were cultured up to 12 days until another isolation was possible. Islets were transplanted by percutaneous transhepatic intraportal injection. Immunosuppression consisted of cyclosporine, mycophenolate mofetil, steroids and an anti-interleukin 2 receptor antibody. Results. From March 1999 to June 2000, 56 pancreata procurements were performed with an average yield of 234 500 islet-equivalent, with 32 preparations over 200 000 islet-equivalent. Ten C-peptide negative Type I diabetic patients (5 men and 5 women, median age 44 years, median diabetes duration 29 years) with an established kidney graft ( > 6 months) received 9030 ± 1090 islet-equivalent/kg with a median purity of 63 %. The number of pancreata required for each graft was 1 (n = 5) or 2 (n = 5). At the completion of a 12 month follow-up, we observed 0 % primary nonfunction, 50 % graft survival and 20 % insulin-independence. Conclusions/interpretation. This study demonstrates the interest and the feasibility of a multicentre collaboration in human islet transplantation. [Diabetologia (2001) 44: 859–864]     

Predictive medicine: outcomes,challenges and opportunities in the Synergy-COPD project

Background

Chronic Obstructive Pulmonary Disease (COPD) is a major challenge for healthcare. Heterogeneities in clinical manifestations and in disease progression are relevant traits in COPD with impact on patient management and prognosis. It is hypothesized that COPD heterogeneity results from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering.

Objectives

To assess the potential of systems medicine to better understand non-pulmonary determinants of COPD heterogeneity. To transfer acquired knowledge to healthcare enhancing subject-specific health risk assessment and stratification to improve management of chronic patients.

Method

Underlying mechanisms of skeletal muscle dysfunction and of co-morbidity clustering in COPD patients were explored with strategies combining deterministic modelling and network medicine analyses using the Biobridge dataset. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was done (ICD9-CM data from Medicare, 13 million people). A targeted network analysis using the two studies: skeletal muscle dysfunction and co-morbidity clustering explored shared pathways between them.

Results

(1) Evidence of abnormal regulation of pivotal skeletal muscle biological pathways and increased risk for co-morbidity clustering was observed in COPD; (2) shared abnormal pathway regulation between skeletal muscle dysfunction and co-morbidity clustering; and, (3) technological achievements of the projects were: (i) COPD Knowledge Base; (ii) novel modelling approaches; (iii) Simulation Environment; and, (iv) three layers of Clinical Decision Support Systems.

Conclusions

The project demonstrated the high potential of a systems medicine approach to address COPD heterogeneity. Limiting factors for the project development were identified. They were relevant to shape strategies fostering 4P Medicine for chronic patients. The concept of Digital Health Framework and the proposed roadmap for its deployment constituted relevant project outcomes.

     

ETPOD (European Training Program on Organ Donation): a successful training program to improve organ donation

Advanced training of healthcare professionals active in organ donation is highlighted as a major means to overcome organ shortage. The objective of this study was to improve donation rates in the selected European target areas (TAs) by providing an advanced training program. A prospective intervention study was conducted in 25 TAs with active donor programs from 17 European countries, between 2007 and 2009. A training program based on collaborative methodology was designed at three different professional levels (health workers awareness, junior transplant coordinators, managers). Courses evaluation scores and donation figures in each TA were collected and compared before and after intervention. Courses with new developed training tools were implemented reaching out 3286 healthcare professionals. Feed‐back questionnaires revealed a high degree of satisfaction among participants (average of 4.35 on a 1–5 scale). The number of utilized donors in the TAs increased from 15.7 ± 14.3 (95% CI: 9.8–21.6) to 20.0 ± 17.1 (95% CI: 13–27.1) (P = 0.014) and the number of organs recovered increased from 49.7 ± 48.5 (95% CI: 29.6–69.7) to 59.3 ± 52.1 (95% CI: 37.8–80.8) (P = 0.044). The European Training Program on Organ Donation is a successful training program, achieving a significant increase in organ donation figures.     

Variation in costs of cone beam CT examinations among healthcare systems

Objectives

To analyse the costs of cone beam CT (CBCT) in different healthcare systems for patients with different clinical conditions.

Methods

Costs were calculated for CBCT performed in Cluj (Romania), Leuven (Belgium), Malmö (Sweden) and Vilnius (Lithuania) on patients with (i) a maxillary canine with eruption disturbance, (ii) an area with tooth loss prior to implant treatment or (iii) a lower wisdom tooth planned for removal. The costs were calculated using an approach based on the identification, measurement and valuation of all resources used in the delivery of the service that combined direct costs (capital equipment, accommodation, labour) with indirect costs (patients'' and accompanying persons'' time, “out of pocket” costs for examination fee and visits).

Results

The estimates for direct and indirect costs varied among the healthcare systems, being highest in Malmö and lowest in Leuven. Variation in direct costs was mainly owing to different capital costs for the CBCT equipment arising from differences in purchase prices (range €148 000–227 000). Variation in indirect costs were mainly owing to examination fees (range €0–102.02).

Conclusions

Cost analysis provides an important input for economic evaluations of diagnostic methods in different healthcare systems and for planning of service delivery. Additionally, it enables decision-makers to separate variations in costs between systems into those due to external influences and those due to policy decisions. A cost evaluation of a dental radiographic method cannot be generalized from one healthcare system to another, but must take into account these specific circumstances.     

Investigating confounding in network‐based test‐negative design influenza vaccine effectiveness studies—Experience from the DRIVE project

Background: Establishing a large study network to conduct influenza vaccine effectiveness (IVE) studies while collecting appropriate variables to account for potential bias is important; the most relevant variables should be prioritized. We explored the impact of potential confounders on IVE in the DRIVE multi‐country network of sites conducting test‐negative design (TND) studies. Methods: We constructed a directed acyclic graph (DAG) to map the relationship between influenza vaccination, medically attended influenza infection, confounders, and other variables. Additionally, we used the Development of Robust and Innovative Vaccines Effectiveness (DRIVE) data from the 2018/2019 and 2019/2020 seasons to explore the effect of covariate adjustment on IVE estimates. The reference model was adjusted for age, sex, calendar time, and season. The covariates studied were presence of at least one, two, or three chronic diseases; presence of six specific chronic diseases; and prior healthcare use. Analyses were conducted by site and subsequently pooled. Results: The following variables were included in the DAG: age, sex, time within influenza season and year, health status and comorbidities, study site, health‐care‐seeking behavior, contact patterns and social precautionary behavior, socioeconomic status, and pre‐existing immunity. Across all age groups and settings, only adjustment for lung disease in older adults in the primary care setting resulted in a relative change of the IVE point estimate >10%. Conclusion: Our study supports a parsimonious approach to confounder adjustment in TND studies, limited to adjusting for age, sex, and calendar time. Practical implications are that necessitating fewer variables lowers the threshold for enrollment of sites in IVE studies and simplifies the pooling of data from different IVE studies or study networks.     

Cancer and Risk of COVID-19 Through a General Community Survey

Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.