Impact de la pandémie COVID-19 sur les évènements indésirables associés aux soins.

Since early 2020, the onset of the COVID-19 pandemic, physicians have continued to report adverse events associated with care. Patients also continued to participate in the hospital satisfaction surveys. To date, no study in France has measured the impact of the pandemic on adverse events and patient satisfaction. We looked at the characteristics of these adverse events in relation to the pandemic and put patients' feelings into perspective. A qualitative and observational retrospective study of the REX and MCO48 databases was carried out. The quantitative study of the REX database was supplemented by a qualitative analysis of the declarations. The adverse events more often affects middle-aged men aged 60 years, while deaths occur in older patients with more complex pathologies and more urgent management. The nature of these events is different depending on the reporting period: Those reported in the first wave are more urgent, occur less frequently in the operating room than in the emergency room, and are considered less preventable than those reported in the second wave. The latter are more similar to the events that usually occur. The implementation of effective barriers, particularly within the teams, has made it possible to reduce the impact of the second wave on the occurrence of these events, the role of communication seems essential. The overall patient satisfaction score as well as those for medical and paramedical care has increased, which may reflect patient solidarity with caregivers. The attitude of active resilience on the part of all actors has been a major element in risk management during this crisis and it is essential to capitalize on these collaborative processes for the future.

Quality indicators in hemodialysis: A 5-year experience of national campaigns in France.

BACKGROUND: End stage kidney disease (ESKD) is associated with increased morbidity and mortality. Hemodialysis (HD) is the main technique used for kidney replacement therapy. Dialyzed patients are expected to live less than one half as long as their counterparts without ESKD. Improving quality of care may help to improve mortality in this population. METHODS: The French National Authority for Health has carried out three consecutive national campaigns over 5 years for the assessment of quality indicators (QCI) during HD. QCI included anemia management, iron status evaluation, nutritional status assessment, and annual transplantation access. RESULTS: From 2013 to 2017, 227 health facilities participated, and 33,319 files were analyzed. Median age was 72 years old (IQR25-75 = 61-81), and 58.25% of patients were men. Median time in HD was 39.4 months (IQR25-75 = 20.7-72.7). Most of the patients underwent in-center HD (85.41%). Overweight and obese patients accounted, respectively, for 28.39% and 21.32%, and malnutrition was present in 38.61%. A contra-indication for renal transplantation was found in 68.3% of patients. All QCI improved over 5 years. CONCLUSION: Developing QCI based on guidelines is crucial to assure appropriate care of HD patients. Repeating campaigns over 5 years in France improves the quality of care among physicians.

Vers une nouvelle certification des établissements de santé pour 2020.

TOWARDS A NEW CERTIFICATION OF HEALTHCARE FACILITIES FOR 2020.: The accreditation process, now a certification process for healthcare facilities, has constantly evolved since 1999 in order to improve the quality and safety of care provided to patients. In order to meet demographic, epidemiological and social challenges, it needs to be revised again. The French National Health Authority board has fixed three main objectives for the 2020 version: to medicalise certification, simplify it and adapt it to hospital groups in the public and private sector.

La politique nationale des indicateurs de qualité et de sécurité des soins.

THE NATIONAL POLICY OF CARE QUALITY AND SAFETY INDICATORS: Care quality and safety indicators, piloted by the national health authority, are tools forming part of a global programme of improvement of quality and safety of care. The national scheme for measuring the quality and safety of care provides, for all healthcare facilities, dashboards for managing care quality and safety. Currently focused on the public and private hospital sector, it needs to evolve to widen its scope to include community care and the medical-social sector.

Hospital quality measures: are process indicators associated with hospital standardized mortality ratios in French acute care hospitals?

BACKGROUND: Results of associations between process and mortality indicators, both used for the external assessment of hospital care quality or public reporting, differ strongly across studies. However, most of those studies were conducted in North America or United Kingdom. Providing new evidence based on French data could fuel the international debate on quality of care indicators and help inform French policy-makers. The objective of our study was to explore whether optimal care delivery in French hospitals as assessed by their Hospital Process Indicators (HPIs) is associated with low Hospital Standardized Mortality Ratios (HSMRs). METHODS: The French National Authority for Health (HAS) routinely collects for each hospital located in France, a set of mandatory HPIs. Five HPIs were selected among the process indicators collected by the HAS in 2009. They were measured using random samples of 60 to 80 medical records from inpatients admitted between January 1st, 2009 and December 31, 2009 in respect with some selection criteria. HSMRs were estimated at 30, 60 and 90 days post-admission (dpa) using administrative health data extracted from the national health insurance information system (SNIIR-AM) which covers 77% of the French population. Associations between HPIs and HSMRs were assessed by Poisson regression models corrected for measurement errors with a simulation-extrapolation (SIMEX) method. RESULTS: Most associations studied were not statistically significant. Only two process indicators were found associated with HSMRs. Completeness and quality of anesthetic records was negatively associated with 30 dpa HSMR (0.72 [0.52-0.99]). Early detection of nutritional disorders was negatively associated with all HSMRs: 30 dpa HSMR (0.71 [0.54-0.95]), 60 dpa HSMR (0.51 [0.39-0.67]) and 90 dpa HSMR (0.52 [0.40-0.68]). CONCLUSION: In absence of gold standard of quality of care measurement, the limited number of associations suggested to drive in-depth improvements in order to better determine associations between process and mortality indicators. A smart utilization of both process and outcomes indicators is mandatory to capture aspects of the hospital quality of care complexity.

Mandatory national quality improvement systems using indicators: An initial assessment in Europe and Israel.

INTRODUCTION: Quality improvement systems (QIS) that are based on empirical performance assessment have increasingly been implemented as a mandatory part of health systems across countries. This study aims to describe national mandatory QIS in Europe in 2014. MATERIALS AND METHODS: Relevant national agencies for national mandatory QIS in Europe were identified through online searches and key informants. A questionnaire was compiled during a workshop with these agencies and filled out by representatives from these particular agencies. RESULTS: Agencies in charge of national mandatory QIS in seven countries (Denmark, France, Germany, Israel, Scotland, Sweden and Switzerland) were included in the study. An analysis of QIS revealed similarities, such as the use of routine data for performance assessment and the aim to hold healthcare providers accountable. Differences relate to the different forms of feedback systems and improvement mechanisms used. Trends include the development towards greater implementation of QIS within health systems, the inclusion of the patient's perspective in performance assessment, and experiments with pay for performance-related measures. CONCLUSION: On a country level, for health systems striving for newly implementing QIS it is recommended to start where routine data is available, add qualitative methodologies once the QIS is getting more complex, report performance data back to service providers and be patient centred. On the inter-country level exchange of information between agencies commissioned with implementing national QIS is very much needed for.

Hospital comparisons based on mortality: revisiting the choice of postadmission timeframe and evaluating the contribution of cause-of-death data, France, 2009.

BACKGROUND: In-hospital mortality is widely used to judge the quality of hospital care, but is biased by discharge patterns. Fixed-timeframe indicators have thus been recommended. However, the 30-day postadmission indicator may underestimate hospital-wide mortality, as patients dying in hospital >30 days after admission are considered as survivors. OBJECTIVES: To identify the most relevant timeframes and to assess the contribution of cause-of-death data. METHODS: The 2009 French hospital discharge database was linked to vital status records and to the causes of death register for 11.5 million hospital stays by beneficiaries of French general health insurance. Correlations and agreements between the 30-day hospital standardized mortality ratio (HSMR) and the in-hospital, 60-, 90-, 180-, and 365-day postadmission HSMRs were estimated. RESULTS: A total of 7.8%, 1.5%, and 0.5% of patients who died during their hospital stay were considered as survivors by the 30-, 60-, and 90-day HSMRs, respectively. The 30-day HSMR correlated strongly with the 60-day HSMR (Pearson coefficient=0.92), and their agreement on outlier status was excellent (κ coefficient=0.80). The association remained substantial at 90 days, but weakened at 180 days and even more so at 365 days. Regardless of the timeframe, exclusion of deaths likely due to independent causes barely modified the indicators. CONCLUSIONS: This nationwide study shows that 60- and 90-day HSMRs encompass in-hospital deaths better than the 30-day HSMR, while capturing the same interhospital variations. They should thus be preferred. The contribution of cause-of-death data to hospital-wide indicators seems negligible.

Development of kinomic analyses to identify dysregulated signaling pathways in cells expressing cytoplasmic PrP.

BACKGROUND: Dysregulated protein kinase signaling is involved in the pathogenesis of many chronic diseases. However, the dysregulated signaling pathways critical to prion pathogenesis remain incompletely characterized. Global analyses of signaling pathways may be useful to better characterize these pathways. We therefore set out to develop such global assays. To this end, we used as a model cytoplasmic mutants of the cellular prion protein (PrPC), which are toxic to N2a neuroblastoma cells. We tested the global assays for their sensitivity to detect changes in signaling pathways in cells expressing cytoplasmic PrP mutants. METHODS: We developed a targeted proteomics (kinomics) approach using multiplex Western blots to identify signaling pathways dysregulated in chronic neurological pathologies. We tested the approach for its potential ability to detect signaling changes in N2a cells expressing cytoplasmic PrP mutants. RESULTS: Multiplex Western blots were designed to quantitate the expression levels of 137 protein kinases in a single membrane and using only 1.2 mg of sample. The response of the blots was sensitive and linear to changes of 6% in protein levels. Hierarchical and functional clustering of the relative expression levels identified an mTOR signaling pathway as potentially dysregulated in N2a cells expressing cytoplasmic PrP. The mTOR signaling pathway regulates global protein synthesis, which is inhibited in cells expressing cytoplasmic PrP. The levels of proteins involved in the Akt1/p70S6K branch of mTOR signaling changed in synchrony with time of cytoplasmic PrP expression. Three kinases in this pathway, Akt, p70S6K, and eIF4B were in their inactive states, as evaluated by phosphorylation of their regulatory sites. CONCLUSION: The results presented are consistent with the previously reported inhibition of Akt/p70S6K/eIF4B signaling as mediating pathogenesis of cytoplasmic PrP. We conclude that the kinomic analyses are sensitive and specific to detect signaling pathways dysregulated in a simple in vitro model of PrP pathogenesis.

Can we simplify the hospital accreditation process? Predicting accreditation decisions from a reduced dataset of focus priority standards and quality indicators: results of predictive modelling.

OBJECTIVES: Accreditation in France relies on a mandatory 4-year cycle of self-assessment and a peer review of 82 standards, among which 14 focus priority standards (FPS). Hospitals are also required to measure yearly quality indicators (QIs-5 in 2010). On advice given by the accreditation committee of HAS (Haute Autorité en Santé), based on surveyors proposals and relying mostly on compliance to standards, accreditation decisions are taken by the board of HAS. Accreditation is still perceived by hospitals as a burdensome process and a simplification would be welcomed. The hypothesis was that a more limited number of criteria might give sufficient amount of information on hospitals overall quality level, appraised today by accreditation decisions. DESIGN: The accuracy of predictions of accreditation decisions given by a model, Partial Least Square-2 Discriminant Analysis (PLS2-DA), using only the results of FPS and QIs was measured. Accreditation decisions (full accreditation (A), recommendations or reservation (B), remit decision or non-accreditation (C)), results of FPS and QIs were considered qualitative variables. Stability was assessed by leave one out cross validation (LOOCV). SETTING AND PARTICIPANTS: All French 489 acute care organisations (ACO) accredited between June 2010 and January 2012 were considered, 304 of them having a rehabilitation care sector (RCS). RESULTS: Accuracy of prediction of accreditation decisions was good (89% of ACOs and 91% of ACO-RCS well classified). Stability of results appeared satisfactory when using LOOCV (87% of ACOs and 89% of ACO-RCS well classified). Identification of worse hospitals was correct (90% of ACOs and 97% of ACO-RCS predicted C were actually C). CONCLUSIONS: Using PLS2-DA with a limited number of criteria (QIs and FPS) provides an accurate prediction of accreditation decisions, especially for underperforming hospitals. This could support accreditation committees which give advices on accreditation decisions, and allow fast-track handling of 'safe' reports.

Hospital case volume and appropriate prescriptions at hospital discharge after acute myocardial infarction: a nationwide assessment.

BACKGROUND: In acute myocardial infarction, the relationship between volume and quality indicators (QIs) is poorly documented. Through a nationwide assessment of QIs at discharge repeated for 3 years, we aimed to quantify the relationship between volume and QIs in survivors after acute myocardial infarction. METHODS AND RESULTS: Almost all healthcare centers in France participated. Medical records were randomly selected. Data collection was performed by an independent group. QIs for acute myocardial infarction were defined by an expert consensus group as appropriate prescription at discharge of aspirin, clopidogrel, ß-blocker, statin, and an angiotensin-converting enzyme inhibitor in patients with left ventricular ejection fraction <0.40. A composite QI was calculated through the use of the all-or-none method. Volume was classified into 7 categories based on the number of admissions for acute myocardial infarctions in 2008 (centers with <10 acute myocardial infarctions were excluded). Odds ratios adjusted for age and sex with 95% confidence interval for volume categories were calculated by use of logistic regression for each QI. Temporal changes were tested in centers that participated in all 3 campaigns. A total of 46 390 records were examined: 18 159 in 2008, 12 837 in 2009, and 15 394 in 2010. Two hundred ninety-one centers were eligible for the temporal analysis. There was a significant increase between 2008 and 2009 in appropriate prescription of antiplatelet agents, ß-blockers, angiotensin-converting enzyme inhibitor, statins at discharge, and the composite indicator. Similarly, a significant increase was observed between 2009 and 2010 in appropriate prescription of angiotensin-converting enzyme inhibitor and ß-blockers and in the composite QI. Compared with a volume of >300, a significantly lower rate of all QIs was observed in centers with the lowest volume. Odds ratios progressively decreased with increasing volume. Despite a significant increase in the composite QI over the 3 years, a significant relationship persisted between volume and quality of care. CONCLUSIONS: Analysis of QIs at discharge demonstrates the existence of a relationship between volume and appropriate prescriptions at discharge. Centers with the highest volume perform better on quality measures than centers with lower volumes. Temporal analysis over 3 consecutive years confirms this relationship and shows that it persists despite improvement in QIs between 2008 and 2010.

Barriers to staff adoption of a surgical safety checklist.

OBJECTIVE: Implementation of a surgical checklist depends on many organisational factors and on socio-cultural patterns. The objective of this study was to identify barriers to effective implementation of a surgical checklist and to develop a best use strategy. SETTING: 18 cancer centres in France. DESIGN: The authors first assessed use compliance and completeness rates of the surgical checklist on a random sample of 80 surgical procedures performed under general or loco-regional anaesthesia in each of the 18 centres. They then developed a typology of the organisational and cultural barriers to effective checklist implementation and defined each barrier's contents using data from collective and semi-structured individual interviews of key staff, the results of an email questionnaire sent to the 18 centres, and direct observations over 20 h in two centres. RESULTS: The study consisted of 1440 surgical procedures, 1299 checklists, and 28 578 items. The mean compliance rate was 90.2% (0, 100). The mean completion rate was 61% (0, 84). 11 barriers to effective checklist implementation were identified. Their incidence varied widely across centres. The main barriers were duplication of items within existing checklists (16/18 centres), poor communication between surgeon and anaesthetist (10/18), time spent completing the checklist for no perceived benefit, and lack of understanding and timing of item checks (9/18), ambiguity (8/18), unaccounted risks (7/18) and a time-honoured hierarchy (6/18). CONCLUSIONS: Several of the barriers to the successful implementation of the surgical checklist depended on organisational and cultural factors within each centre. The authors propose a strategy for change for checklist design, use and assessment, which could be used to construct a feedback loop for local team organisation and national initiatives.

Suitability of three indicators measuring the quality of coordination within hospitals.

BACKGROUND: Coordination within hospitals is a major attribute of medical care and influences quality of care. This study tested the validity of 3 indicators covering two key aspects of coordination: the transfer of written information between professionals (medical record content, radiology exam order) and the holding of multidisciplinary team meetings during treatment planning. METHODS: The study was supervised by the French health authorities (COMPAQH project). Data for the three indicators were collected in a panel of 30 to 60 volunteer hospitals by 6 Clinical Research Assistants. The metrological qualities of the indicators were assessed: (i) Feasibility was assessed using a grid of 19 potential problems, (ii) Inter-observer reliability was given by the kappa coefficient () and internal consistency by Cronbach's alpha test, (iii) Discriminatory power was given by an analysis of inter-hospital variability using the Gini coefficient as a measure of dispersion. RESULTS: Overall, 19281 data items were collected and analyzed. All three indicators presented acceptable feasibility and reliability (, 0.59 to 0.97) and showed wide differences among hospitals (Gini, 0.08 to 0.11), indicating that they are suitable for making comparisons among hospitals. CONCLUSION: This set of 3 indicators provides a proxy measurement of coordination. Further research on the indicators is needed to find out how they can generate a learning process. The medical record indicator has been included in the French national accreditation procedure for healthcare organisations. The two other indicators are currently being assessed for inclusion.

A large ribonucleoprotein particle induced by cytoplasmic PrP shares striking similarities with the chromatoid body, an RNA granule predicted to function in posttranscriptional gene regulation.

The observation that PrP is present in the cytosol of some neurons and non-neuronal cells and that the N-terminal signal peptide is slightly inefficient has brought speculations concerning a possible function of the protein in the cytosol. Here, we show that cells expressing a cytosolic form of PrP termed cyPrP display a large juxtanuclear cytoplasmic RNA organelle. Although cyPrP spontaneously forms aggresomes, we used several mutants to demonstrate that the assembly of this RNA organelle is independent from cyPrP aggregation. Components of the organelle fall into three classes: mRNAs; proteins, including the RNAseIII family polymerase Dicer, the decapping enzyme Dcp1a, the DEAD-box RNA helicase DDX6, and the small nuclear ribonucleoprotein-associated proteins SmB/B'/N; and non-coding RNAs, including rRNA 5S, tRNAs, U1 small nuclear RNA, and microRNAs. This composition is similar to RNA granules or chromatoid bodies from germ cells, or planarian stem cells and neurons, which are large ribonucleoprotein complexes predicted to function in RNA processing and posttranscriptional gene regulation. The domain of PrP encompassing residues 30 to 49 is essential for the formation of the RNA particle. Our findings confirm the intriguing relation between PrP and RNA in cells, and underscore an unexpected function for cytosolic PrP: assembling a large RNA processing center which we have termed PrP-RNP for PrP-induced ribonucleoprotein particle.

How to limit the burden of data collection for Quality Indicators based on medical records? The COMPAQH experience.

BACKGROUND: Our objective was to limit the burden of data collection for Quality Indicators (QIs) based on medical records. METHODS: The study was supervised by the COMPAQH project. Four QIs based on medical records were tested: medical record conformity; traceability of pain assessment; screening for nutritional disorders; time elapsed before sending copy of discharge letter to the general practitioner. Data were collected by 6 Clinical Research Assistants (CRAs) in a panel of 36 volunteer hospitals and analyzed by COMPAQH. To limit the burden of data collection, we used the same sample of medical records for all 4 QIs, limited sample size to 80 medical records, and built a composite score of only 10 items to assess medical record completeness. We assessed QI feasibility by completing a grid of 19 potential problems and evaluating time spent. We assessed reliability (kappa coefficient) as well as internal consistency (Cronbach alpha coefficient) in an inter-observer study, and discriminatory power by analysing QI variability among hospitals. RESULTS: Overall, 23 115 data items were collected for the 4 QIs and analyzed. The average time spent on data collection was 8.5 days per hospital. The most common feasibility problem was misunderstanding of the item by hospital staff. QI reliability was good (kappa: 0.59-0.97 according to QI). The hospitals differed widely in their ability to meet the quality criteria (mean value: 19-85%). CONCLUSION: These 4 QIs based on medical records can be used to compare the quality of record keeping among hospitals while limiting the burden of data collection, and can therefore be used for benchmarking purposes. The French National Health Directorate has included them in the new 2009 version of the accreditation procedure for healthcare organizations.

Aggresomes do not represent a general cellular response to protein misfolding in mammalian cells.

BACKGROUND: Aggresomes are juxtanuclear inclusion bodies that have been proposed to represent a general cellular response to misfolded proteins in mammalian cells. Yet, why aggresomes are not a pathological characteristic of protein misfolding diseases is unclear. Here, we investigate if a misfolded protein inevitably forms aggresomes in mammalian cells. RESULTS: We show that a cytoplasmic form of the prion protein may form aggresomes or dispersed aggregates in different cell lines. In contrast to aggresomes, the formation of dispersed aggregates is insensitive to histone deacetylase 6 inhibitors and does not result in cytoskeleton rearrangements. Modulation of expression levels or proteasome inhibitors does not alter the formation of dispersed aggregates. CONCLUSION: Our results establish that aggresomes are not obligatory products of protein misfolding in vivo.

Prion protein aggresomes are poly(A)+ ribonucleoprotein complexes that induce a PKR-mediated deficient cell stress response.

In mammalian cells, cytoplasmic protein aggregates generally coalesce to form aggresomal particles. Recent studies indicate that prion-infected cells produce prion protein (PrP) aggresomes, and that such aggregates may be present in the brain of infected mice. The molecular activity of PrP aggresomes has not been fully investigated. We report that PrP aggresomes initiate a cell stress response by activating the RNA-dependent protein kinase (PKR). Activated PKR phosphorylates the translation initiation factor eIF2alpha, resulting in protein synthesis shut-off. However, other components of the stress response, including the assembly of poly(A)+ RNA-containing stress granules and the synthesis of heat shock protein 70, are repressed. In situ hybridization experiments and affinity chromatography on oligo(dT)-cellulose showed that PrP aggresomes bind poly(A)+ RNA, and are therefore poly(A)+ ribonucleoprotein complexes. These findings support a model in which PrP aggresomes send neuronal cells into untimely demise by modifying the cell stress response, and by inducing the aggregation of poly(A)+ RNA.

Aggregation of cellular prion protein is initiated by proximity-induced dimerization.

Prion diseases or transmissible spongiform encephalopathies (TSEs) are infectious and fatal neurodegenerative disorders in humans and animals. Pathological features of TSEs include the conversion of cellular prion protein (PrP(C)) into an altered disease-associated conformation generally designated PrP(Sc), abnormal deposition of PrP(Sc) aggregates, and spongiform degeneration of the brain. The molecular steps leading to PrP(C) aggregation are unknown. Here, we have utilized an inducible oligomerization strategy to test if, in the absence of any infectious prion particles, the encounter between PrP(C) molecules may trigger its aggregation in neuronal cells. A chimeric PrP(C) composed of one (Fv1) or two (Fv2) modified FK506-binding protein (Fv) fused with PrP(C) were created, and transfected in N2a cells. Similar to PrP(C), Fv1-PrP and Fv2-PrP were glycosylated, displayed normal localization, and anti-apoptotic function. When cells were treated with the dimeric Fv ligand AP20187, to induce dimerization (Fv1) or oligomerization (Fv2) of PrP(C), both dimerization and oligomerization of PrP(C) resulted in the de novo production, release and deposition of extracellular PrP aggregates. Aggregates were insoluble in non-ionic detergents and partially resistant to proteinase K. These findings demonstrate that homologous interactions between PrP(C) molecules may constitute a minimal and sufficient molecular event leading to PrP(C) aggregation and extracellular deposition.