A multifaceted risk management program to improve the reporting rate of patient safety incidents in primary care: a cluster-randomised controlled trial.

BACKGROUND: While patient safety incident reporting is of key importance for patient safety in primary care, the reporting rate by healthcare professionals remains low. This study aimed to assess the effectiveness of a risk management program in increasing the reporting rate within multiprofessional primary care facilities. METHODS: A nation-wide cluster-randomised controlled trial was performed in France, with each cluster defined as a primary care facility. The intervention included professional e-learning training, identification of a risk management advisor, and multidisciplinary meetings to address incident analysis. In the first observational period, a patient safety incident reporting system for professionals was implemented in all facilities. Then, facilities were randomised, and the program was implemented. Incidents were reported over the 15-month study period. Quasi-Poisson models were used to compare reporting rates. RESULTS: Thirty-five facilities (intervention, n = 17; control, n = 18) were included, with 169 and 232 healthcare professionals, respectively, involved. Overall, 7 out of 17 facilities carried out the entire program (41.2%), while 6 did not hold meetings (35.3%); 48.5% of professionals logged on to the e-learning website. The relative rate of incidents reported was 2.7 (95% CI = [0.84-11.0]; p = 0.12). However, a statistically significant decrease in the incident rate between the pre-intervention and post-intervention periods was observed for the control arm (HR = 0.2; 95% CI = [0.05-0.54]; p = 0.02), but not for the intervention arm (HR = 0.54; 95% CI = [0.2-1.54]; p = 0.23). CONCLUSION: This program didn't lead to a significant improvement in the patient safety incident reporting rate by professionals but seemed to sustain reporting over time. Considering that the program was fully implemented in only 41% of facilities, this highlights the difficulty of implementing such multidisciplinary programs in primary care despite its adaptation to the setting. A better understanding of how risk management is currently organized in these multiprofessional facilities is of key importance to improve patient safety in primary care. TRIAL REGISTRATIONS: The study has been registered at clinicaltrials.gov (NCT02403388) on 30 March 2015.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Zone-specific computer-aided diagnosis system aimed at characterizing ISUP ≥ 2 prostate cancers on multiparametric magnetic resonance images: evaluation in a cohort of patients on active surveillance.

PURPOSE: To assess a region-of-interest-based computer-assisted diagnosis system (CAD) in characterizing aggressive prostate cancer on magnetic resonance imaging (MRI) from patients under active surveillance (AS). METHODS: A prospective biopsy database was retrospectively searched for patients under AS who underwent MRI and subsequent biopsy at our institution. MRI lesions targeted at baseline biopsy were retrospectively delineated to calculate the CAD score that was compared to the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 score assigned at baseline biopsy. RESULTS: 186 patients were selected. At baseline biopsy, 51 and 15 patients had International Society of Urological Pathology (ISUP) grade ≥ 2 and ≥ 3 cancer respectively. The CAD score had significantly higher specificity for ISUP ≥ 2 cancers (60% [95% confidence interval (CI): 51-68]) than the PI-RADS score (≥ 3 dichotomization: 24% [CI: 17-33], p = 0.0003; ≥ 4 dichotomization: 32% [CI: 24-40], p = 0.0003). It had significantly lower sensitivity than the PI-RADS ≥ 3 dichotomization (85% [CI: 74-92] versus 98% [CI: 91-100], p = 0.015) but not than the PI-RADS ≥ 4 dichotomization (94% [CI:85-98], p = 0.104). Combining CAD findings and PSA density could have avoided 47/184 (26%) baseline biopsies, while missing 3/51 (6%) ISUP 2 and no ISUP ≥ 3 cancers. Patients with baseline negative CAD findings and PSAd < 0.15 ng/mL2 who stayed on AS after baseline biopsy had a 9% (4/44) risk of being diagnosed with ISUP ≥ 2 cancer during a median follow-up of 41 months, as opposed to 24% (18/74) for the others. CONCLUSION: The CAD could help define AS patients with low risk of aggressive cancer at baseline assessment and during subsequent follow-up.

Characterization of high-grade prostate cancer at multiparametric MRI: assessment of PI-RADS version 2.1 and version 2 descriptors across 21 readers with varying experience (MULTI study).

OBJECTIVE: To assess PI-RADSv2.1 and PI-RADSv2 descriptors across readers with varying experience. METHODS: Twenty-one radiologists (7 experienced (≥ 5 years) seniors, 7 less experienced seniors and 7 juniors) assessed 240 'predefined' lesions from 159 pre-biopsy multiparametric prostate MRIs. They specified their location (peripheral, transition or central zone) and size, and scored them using PI-RADSv2.1 and PI-RADSv2 descriptors. They also described and scored 'additional' lesions if needed. Per-lesion analysis assessed the 'predefined' lesions, using targeted biopsy as reference; per-lobe analysis included 'predefined' and 'additional' lesions, using combined systematic and targeted biopsy as reference. Areas under the curve (AUCs) quantified the performance in diagnosing clinically significant cancer (csPCa; ISUP ≥ 2 cancer). Kappa coefficients (κ) or concordance correlation coefficients (CCC) assessed inter-reader agreement. RESULTS: At per-lesion analysis, inter-reader agreement on location and size was moderate-to-good (κ = 0.60-0.73) and excellent (CCC ≥ 0.80), respectively. Agreement on PI-RADSv2.1 scoring was moderate (κ = 0.43-0.47) for seniors and fair (κ = 0.39) for juniors. Using PI-RADSv2.1, juniors obtained a significantly lower AUC (0.74; 95% confidence interval [95%CI]: 0.70-0.79) than experienced seniors (0.80; 95%CI 0.76-0.84; p = 0.008) but not than less experienced seniors (0.74; 95%CI 0.70-0.78; p = 0.75). As compared to PI-RADSv2, PI-RADSv2.1 downgraded 17 lesions/reader (interquartile range [IQR]: 6-29), of which 2 (IQR: 1-3) were csPCa; it upgraded 4 lesions/reader (IQR: 2-7), of which 1 (IQR: 0-2) was csPCa. Per-lobe analysis, which included 60 (IQR: 25-73) 'additional' lesions/reader, yielded similar results. CONCLUSIONS: Experience significantly impacted lesion characterization using PI-RADSv2.1 descriptors. As compared to PI-RADSv2, PI-RADSv2.1 tended to downgrade non-csPCa lesions, but this effect was small and variable across readers.

Effectiveness of seasonal malaria chemoprevention in three regions of Togo: a population-based longitudinal study from 2013 to 2020.

BACKGROUND: In 2012, the World Health Organization (WHO) recommended seasonal malaria chemoprevention (SMC) in areas of high seasonal transmission. Though implemented since 2013, the effectiveness of SMC in Togo was never evaluated. METHODS: This study concerned routine data from 2013 to 2020 mass SMC campaigns for children under five in all health facilities of three Regions of Togo. Treatment coverage, reasons for non-treatment, and SMC-attributable adverse reactions were analysed per year and treatment round. Random effect logistic models estimated SMC effectiveness per health district, year, and treatment round. RESULTS: The overall coverage was 98% (7,971,877 doses for 8,129,668 children). Contraindication was the main reason for non-administration. Over the study period, confirmed malaria cases decreased from 11,269 (1st round of 2016) to 1395 (4th round of 2020). Only 2,398 adverse reactions were reported (prevalence: 3/10,000), but no severe Lyell syndrome or Stevens-Johnson-type skin reaction. Compared to 2016, malaria prevalence decrease was estimated at 22.6% in 2017 (p < 0.001) and 75% in 2020 (p < 0.001). SMC effectiveness ranged from 76.6% (2nd round) to 96.2% (4th round) comparison with the 1st round. CONCLUSIONS: SMC reduced significantly malaria cases among children under five. The results reassure all actors and call for effort intensification to reach the WHO goals for 2030.

Feasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosis-related diabetes-PIM study: A multicenter phase 1-2 trial.

Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF), and restoring metabolic control in these patients may improve their management after lung transplantation. In this multicenter, prospective, phase 1-2 trial, we evaluate the feasibility and metabolic efficacy of combined pancreatic islet-lung transplantation from a single donor in patients with CFRD, terminal respiratory failure, and poorly controlled diabetes. Islets were infused via the portal vein under local anesthesia, 1 week after lung transplantation. At 1 year, the primary outcome was transplant success as evaluated by a composite score including four parameters (weight, fasting glycemia, HbA1c, and insulin requirements). Ten participants (age: 24 years [17-31], diabetes duration: 8 years [4-12]) received a combined islet-lung transplant with 2892 IEQ/kg [2293-6185]. Transplant success was achieved in 7 out of 10 participants at 1-year post transplant. Fasting plasma C-peptide increased from 0.91 µg/L [0.56-1.29] to 1.15 µg/L [0.77-2.2], HbA1c decreased from 7.8% [6.5-8.3] (62 mmol/mol [48-67]) to 6.7% [5.5-8.0] (50 mmol/mol [37-64]), with 38% decrease in daily insulin doses. No complications related to the islet injection procedure were reported. In this pilot study, combined pancreatic islet-lung transplantation restored satisfactory metabolic control and pulmonary function in patients with CF, without increasing the morbidity of lung transplantation.

Efficacy of careHPV™ human papillomavirus screening versus conventional cytology tests for the detection of precancerous and cancerous cervical lesions among women living with HIV-1 in Lao People's Democratic Republic.

BACKGROUND: In the Lao People's Democratic Republic (Lao PDR), cervical cancer is the third leading cause of women cancer. AIMS: The objective of this cross-sectional study was to compare the efficacy of careHPV™ test versus conventional Pap smear or Siriraj liquid-based cytology in the detection of cervical cancer in women living with human immunodeficiency virus type 1 (HIV-1). MATERIALS & METHODS: Overall, 631 women consented to participate. Four cervical specimens were taken for the purpose of conventional Pap smear, Siriraj liquid-based cytology, careHPV™ test, and HPV-16 genotyping. The exact McNemar test was used to compare the efficacy and diagnostic performance of the tests. RESULTS: Of the 631 women with follow-up, 331 were human papillomavirus (HPV) negative. High-grade squamous intraepithelial lesions were found in 37 women, biopsy-proven high-grade cervical intraepithelial neoplasia in 50 women, and invasive carcinoma in seven women. The proportion of women with high-grade cervical lesion or carcinoma detected after abnormal careHPV™ test was higher (6.02%; 95% confidence interval [CI]: 4.4-8.1) than that detected by conventional Pap smear (4.59%; 95% CI: 3.2-6.5). careHPV™ and HPV-16 genotyping had, respectively, the highest sensitivity (80.8%; 95% CI: 67.4-89.5) and specificity (92.2%; 95% CI: 89.8-94.2). HPV-16 was the most frequently detected genotype. CONCLUSIONS: careHPV™ test represents a screening option in Lao PDR, particularly in women living with HIV-1 because of higher prevalence of chronic HPV in this population.

Detection of ISUP ≥2 prostate cancers using multiparametric MRI: prospective multicentre assessment of the non-inferiority of an artificial intelligence system as compared to the PI-RADS V.2.1 score (CHANGE study).

INTRODUCTION: Prostate multiparametric MRI (mpMRI) has shown good sensitivity in detecting cancers with an International Society of Urological Pathology (ISUP) grade of ≥2. However, it lacks specificity, and its inter-reader reproducibility remains moderate. Biomarkers, such as the Prostate Health Index (PHI), may help select patients for prostate biopsy. Computer-aided diagnosis/detection (CAD) systems may also improve mpMRI interpretation. Different prototypes of CAD systems are currently developed under the Recherche Hospitalo-Universitaire en Santé / Personalized Focused Ultrasound Surgery of Localized Prostate Cancer (RHU PERFUSE) research programme, tackling challenging issues such as robustness across imaging protocols and magnetic resonance (MR) vendors, and ability to characterise cancer aggressiveness. The study primary objective is to evaluate the non-inferiority of the area under the receiver operating characteristic curve of the final CAD system as compared with the Prostate Imaging-Reporting and Data System V.2.1 (PI-RADS V.2.1) in predicting the presence of ISUP ≥2 prostate cancer in patients undergoing prostate biopsy. METHODS: This prospective, multicentre, non-inferiority trial will include 420 men with suspected prostate cancer, a prostate-specific antigen level of ≤30 ng/mL and a clinical stage ≤T2 c. Included men will undergo prostate mpMRI that will be interpreted using the PI-RADS V.2.1 score. Then, they will undergo systematic and targeted biopsy. PHI will be assessed before biopsy. At the end of patient inclusion, MR images will be assessed by the final version of the CAD system developed under the RHU PERFUSE programme. Key secondary outcomes include the prediction of ISUP grade ≥2 prostate cancer during a 3-year follow-up, and the number of biopsy procedures saved and ISUP grade ≥2 cancers missed by several diagnostic pathways combining PHI and MRI findings. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Comité de Protection des Personnes Nord Ouest III (ID-RCB: 2020-A02785-34). After publication of the results, access to MR images will be possible for testing other CAD systems. TRIAL REGISTRATION NUMBER: NCT04732156.

Combined model-based and deep learning-based automated 3D zonal segmentation of the prostate on T2-weighted MR images: clinical evaluation.

OBJECTIVE: To train and to test for prostate zonal segmentation an existing algorithm already trained for whole-gland segmentation. METHODS: The algorithm, combining model-based and deep learning-based approaches, was trained for zonal segmentation using the NCI-ISBI-2013 dataset and 70 T2-weighted datasets acquired at an academic centre. Test datasets were randomly selected among examinations performed at this centre on one of two scanners (General Electric, 1.5 T; Philips, 3 T) not used for training. Automated segmentations were corrected by two independent radiologists. When segmentation was initiated outside the prostate, images were cropped and segmentation repeated. Factors influencing the algorithm's mean Dice similarity coefficient (DSC) and its precision were assessed using beta regression. RESULTS: Eighty-two test datasets were selected; one was excluded. In 13/81 datasets, segmentation started outside the prostate, but zonal segmentation was possible after image cropping. Depending on the radiologist chosen as reference, algorithm's median DSCs were 96.4/97.4%, 91.8/93.0% and 79.9/89.6% for whole-gland, central gland and anterior fibromuscular stroma (AFMS) segmentations, respectively. DSCs comparing radiologists' delineations were 95.8%, 93.6% and 81.7%, respectively. For all segmentation tasks, the scanner used for imaging significantly influenced the mean DSC and its precision, and the mean DSC was significantly lower in cases with initial segmentation outside the prostate. For central gland segmentation, the mean DSC was also significantly lower in larger prostates. The radiologist chosen as reference had no significant impact, except for AFMS segmentation. CONCLUSIONS: The algorithm performance fell within the range of inter-reader variability but remained significantly impacted by the scanner used for imaging. KEY POINTS: • Median Dice similarity coefficients obtained by the algorithm fell within human inter-reader variability for the three segmentation tasks (whole gland, central gland, anterior fibromuscular stroma). • The scanner used for imaging significantly impacted the performance of the automated segmentation for the three segmentation tasks. • The performance of the automated segmentation of the anterior fibromuscular stroma was highly variable across patients and showed also high variability across the two radiologists.

Development and Validation of a Predictive Model of Hypovitaminosis D in General Adult Population: SCOPYD Study.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18-70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (<50 nmol/L) and 195 (7.8%) had severe deficiency (<25 nmol/L). The final model included sunlight exposure in the preceding week and during the last holidays, month of blood sampling, age, sex, body mass index, skin phototype, employment, smoking, sport practice, latitude, and VitD supplementation in preceding year. The area under the curve was 0.82 (95% CI (0.78; 0.85)) for severe deficiency. The model predicted severe deficiency with a sensitivity of 77.9% (95% CI (69.1; 85.7)) and a specificity of 68.3% (95% CI (64.8; 71.9)). We identified a set of predictors of severe VitD deficiency that are easy to collect in routine that may help to better target patients for serum 25(OH)D concentration determination.

Comparison of iohexol plasma clearance formulas vs. inulin urinary clearance for measuring glomerular filtration rate.

OBJECTIVES: The one-compartment iohexol plasma clearance has been proposed as a reliable alternative to renal inulin clearance. However, this method's performance depends on the formula used to calculate glomerular filtration rate (GFR). This study reports on performance comparisons between various mathematical formulas proposed for iohexol plasma clearance vs. inulin urinary clearance. METHODS: GFR was simultaneously determined by inulin and iohexol clearance in 144 participants (age: 10-84 years; glomerular filtration rate: 15-169 mL/min/1.73 m2). A retrospective cross-sectional study evaluated the performance of four formulas proposed to calculate plasma iohexol clearance (Brøchner-Mortensen, Fleming et al., Jødal-Brøchner-Mortensen, and Ng-Schwartz-Munoz). The performance of each formula was assessed using bias, precision (standard deviation of the bias), accuracy (percentage iohexol within 5, 10, and 15%), root mean square error, and concordance correlation coefficient vs. renal inulin clearance as reference. RESULTS: Regarding accuracy, there was no difference in root mean square error (RMSE), P5, P10, or P15 between the four formulas. The four concordance correlation coefficients (CCC) between the value from each formula and in-GFR were high and not significantly different. At in-GFR ≥90 mL/min/1.73 m2, Ng-Schwartz-Munoz formula performed slightly better than other formulas regarding median bias (-0.5; 95% CI [-3.0 to 2.0] and accuracy P15 (95.0; 95% CI [88.0-100.0]). CONCLUSIONS: The studied formulas were found equivalent in terms of precision and accuracy, but the Ng-Schwartz-Munoz formula improved the accuracy at higher levels of in-GFR.

A beat-by-beat cardiovascular index, CARDEAN, to titrate opioid administration in the setting of orthopaedic surgery: a prospective randomized trial.

To determine whether a beat-by-beat cardiovascular index (CARDEAN: cardiovascular depth of analgesia, Alpha-2 Ltd, Lyon, France) reduces the incidence of tachycardia in ASA I-III patients undergoing orthopaedic surgery. A total of 76 patients were prospectively randomized into (1) a control group or (2) the CARDEAN group, in which the nurse anaesthetist was blinded to CARDEAN application. In addition to conventional signs, an external observer instructed the nurse anaesthetist to administer sufentanil 0.1 µg kg-1 when the CARDEAN crossed a threshold (≥ 60). The primary outcome was the incidence of tachycardia (> 120% of reference heart rate, HR). Non-invasive blood pressure (BP), electrocardiogram (ECG), O2 saturation-photoplethysmography and the bispectral index (40 < BIS < 60) were monitored. HR and an estimation of beat-by-beat BP changes acquired from photoplethysmography and ECG were combined in an algorithm that detected hypertension followed by tachycardia (index scaled 0-100). Sufentanil 0.1 µg kg-1 was administered when tachycardia, hypertension or movement ("conventional signs") was observed. Data for 66 patients (27 with known hypertension) were analysed. In the CARDEAN group, (a) the dose of sufentanil was higher (control: 0.46 µg kg-1 100 min-1, CARDEAN: 0.57 µg kg-1 100 min-1, p = 0.016), (b) the incidence rates of tachycardia and untoward events were lower (respectively: - 44%; control: 2.52 events 100 min-1 [1.98-3.22]; CARDEAN: 1.42 [1.03-1.96], p = 0.005, hazard ratio: 0.56; movement, muscular contraction, or coughing: control: 0.74 events 100 min-1 [0.47-1.16]; CARDEAN: 0.31 [0.15-0.62], p = 0.038), and (c) extubation occurred more often in the operating room (control: 76.5%, CARDEAN: 97%, p = 0.016). CARDEAN-titrated opioid administration was associated with a higher dose of sufentanil, a reduction in tachycardia and earlier emergence in ASA I-III patients undergoing major orthopaedic surgery.

A key role for conservative treatment in the management of pituitary apoplexy.

PURPOSE: The management of pituitary apoplexy, a rare emergency neuroendocrine condition, is controversial. The aim of the present study is to compare the outcomes of patients with pituitary apoplexy managed either by a conservative or surgical approach. METHODS: A retrospective cohort study including patients diagnosed between 2007 and 2018 in a tertiary French university hospital. Pituitary Apoplexy Score (PAS) was retrospectively applied in the perspective of therapeutic decision support. RESULTS: Forty-six patients were treated for pituitary apoplexy either with conservative management (n = 27) or surgery (n = 19). At initial evaluation, visual field defects (VFD) and visual acuity impairment were more frequent in patients from the surgery group. At 1 year there were no statistical differences in the rates of complete/near-complete resolution of VFD (100 vs. 91.7%), visual acuity impairment (100 vs. 87.5%), and cranial nerve palsies (83.3 vs. 100%), between conservative and surgical treatment groups. There were more endocrine deficits at 1 year in the surgical group (p = 0.029). PAS (n = 41) was 3.4 on average in the early surgery group and 1.3 in the conservative treatment/delayed surgery group. Among patients with a score < 4, 31.3% were operated at first line and did not present better outcomes than patients managed conservatively. In all, 88.9% of patients with a score ≥ 4 underwent surgery. CONCLUSIONS: PAS may be a reliable parameter for defining therapeutic strategy. Patients with non-severe and nonprogressive neuro-ophthalmological deficits can be managed conservatively without negative impact on outcomes, thus surgery should be reserved only for those patients with a PAS ≥ 4.

Usefulness of Thoracic Aortic Calcium to Predict 1-Year Mortality After Transcatheter Aortic Valve Implantation.

In patients who underwent transcatheter aortic valve implantation (TAVI), vascular disease is associated with increased risk of mortality. Thoracic aortic calcification (TAC), an objective surrogate of vascular disease, could be a predictor of mortality after TAVI. We aimed to analyze the association between TAC burden and 1-year all-cause mortality in patients who underwent TAVI in a US population. From July 2015 through July 2017, a retrospective review of TAVI procedures was performed at Baylor Scott & White-The Heart Hospital, Plano, Texas. Patients were analyzed for comorbidities, cardiac risk factors, and 30-day and 1-year all-cause mortality. Restricted cubic splines analysis was used to define low, moderate, and high TAC categories. The association between TAC and survival was evaluated using unadjusted and adjusted Cox models. A total of 431 TAVI procedures were performed, of which TAC was measured in 374 (81%) patients. Median (interquartile range) age was 82 (77, 87) years, and 51% were male. Median (interquartile range) STS PROM was 5.6 (4.1, 8.2) %. Overall 30-day and 1-year all-cause mortality was 1% and 10%, respectively. TAC was categorized as low (<1.6 cm3), moderate (1.6 to 2.9 cm3), and high (>2.9 cm3). At 1 year, all-cause mortality was 16% in patients with high TAC compared with 6% in the low and moderate TAC categories (p = 0.008). Unadjusted and adjusted Cox regression analysis showed a significant increase in mortality for patients with high TAC compared with low TAC (hazard ratio 2.98, 95% confidence interval [1.34-6.63]), but not significant compared with moderate TAC group. TAC is a predictor of late mortality after TAVI. In conclusion, adding TAC to preoperative evaluation may provide an objective, reproducible, and potentially widely available tool that can help in shared decision-making.

High-dimensional propensity scores improved the control of indication bias in surgical comparative effectiveness studies.

OBJECTIVES: The objective of the study is to evaluate the performance of high-dimensional propensity scores (hdPSs) for controlling indication bias as compared with propensity scores (PSs) in surgical comparative effectiveness studies. STUDY DESIGN AND SETTING: Patients who underwent interventional transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) between 2013 and 2017 were included from the French nationwide hospitals. At each hospital level, matched pairs of patients who underwent TAVI and SAVR were formed using PSs, considering 20 patient baseline characteristics, and hdPSs, considering the same patient characteristics and 300 additional variables from procedure and diagnosis codes the year before surgery. We compared death, reoperation, and stroke up to 3 years between TAVI and SAVR using Cox or Fine and Gray models. RESULTS: Before matching, 12 of 20 patient characteristics were imbalanced between the included patients who underwent TAVI and SAVR. No significant imbalance persisted after matching with both methods. Hazard ratio of 1-year death, reoperation, and stroke was 1.3 [1.1; 1.4], 1.6 [1.1; 2.4], and 1.4 [1.2; 1.7] for TAVI relative to SAVR with PSs (n = 9,498 pairs) and 1.1 [1.0; 1.3], 1.3 [0.8; 2.0], and 1.3 [1.0; 1.6] with hdPSs (n = 7,157). CONCLUSION: HdPS estimations were more consistent with results seen in randomized controlled trials. The HdPS is a promising alternative for the PS to control indication bias in comparative studies of surgical procedures.

Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor.

BACKGROUND AND OBJECTIVE: Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of biallelic pathogenic MEFV variants. MEFV encodes pyrin, an inflammasome sensor. Using a kinase inhibitor, UCN-01, we recently identified that dephosphorylation of FMF-associated pyrin mutants leads to inflammasome activation. The aim of this study was to assess whether quantifying UCN-01-mediated inflammasome activation could discriminate FMF patients from healthy donors (HD) and from patients with other inflammatory disorders (OID). METHODS: Real-time pyroptosis and IL-1ß secretion were monitored in response to UCN-01 in monocytes from FMF patients (n=67), HD (n=71) and OID patients (n=40). Sensitivity and specificity of the resulting diagnostic tests were determined by receiver operating characteristic curve analyses. RESULTS: Inflammasome monitoring in response to UCN-01 discriminates FMF patients from other individuals. Pyroptosis assessment leads to a fast FMF diagnosis while combining pyroptosis and IL-1ß dosage renders UCN-01-based assays highly sensitive and specific. UCN-01-triggered monocytes responses were influenced by MEFV gene dosage and MEFV mutations in a similar way as clinical phenotypes are. CONCLUSIONS: UCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity.

Assessment of serological techniques for screening patients for COVID-19 (COVID-SER): a prospective, multicentric study.

INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated. METHODS AND ANALYSIS: We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04341142.

Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France.

OBJECTIVE: To determine the observed and expected incidence rates of paraneoplastic neurologic syndromes (PNSs) and autoimmune encephalitides (AEs) diagnosed in France between 2016 and 2018, we conducted a population-based epidemiologic study. METHODS: Observed incidence rates were stratified by sex, age groups, region of care, year of diagnosis, and disease subgroups. National expected incidence rates were calculated based on rates obtained in the area directly adjacent to the Reference Center using a mixed Poisson model and compared with observed incidence rates. RESULTS: Six hundred thirty-two patients with definite PNS or AE met the inclusion criteria. The observed incidence rate of definite PNS and AE in France was 3.2 per million person-years (CI95%: 2.9-3.4) compared with an expected incidence rate of 7.1 per million person-years (CI95%: 3.9-11.4). The national observed incidence rate for the antibody-positive AE subgroup increased from 1.4 per million person-years (CI95%: 1.2-1.7) in 2016 to 2.1 per million person-years (CI95%: 1.7-2.4) in 2018, thus surpassing the incidence rate of classical PNS (1.2 per million person-years [CI95%: 1.0-1.5]) of 2018. CONCLUSIONS: There was a significant widespread year-to-year increase in the incidence of diagnoses registered with the Reference Center for all subgroups of PNS and AE studied. The national observed incidence rate is likely underestimated due to underdiagnosis and underreporting.

The area between ROC curves, a non-parametric method to evaluate a biomarker for patient treatment selection.

Treatment selection markers are generally sought for when the benefit of an innovative treatment in comparison with a reference treatment is considered, and this benefit is suspected to vary according to the characteristics of the patients. Classically, such quantitative markers are detected through testing a marker-by-treatment interaction in a parametric regression model. Most alternative methods rely on modeling the risk of event occurrence in each treatment arm or the benefit of the innovative treatment over the marker values, but with assumptions that may be difficult to verify. Herein, a simple non-parametric approach is proposed to detect and assess the general capacity of a quantitative marker for treatment selection when no overall difference in efficacy could be demonstrated between two treatments in a clinical trial. This graphical method relies on the area between treatment-arm-specific receiver operating characteristic curves (ABC), which reflects the treatment selection capacity of the marker. A simulation study assessed the inference properties of the ABC estimator and compared them with other parametric and non-parametric indicators. The simulations showed that the estimate of the ABC had low bias, power comparable to parametric indicators, and that its confidence interval had a good coverage probability (better than the other non-parametric indicator in some cases). Thus, the ABC is a good alternative to parametric indicators. The ABC method was applied to data of the PETACC-8 trial that investigated FOLFOX4 versus FOLFOX4 + cetuximab in stage III colon adenocarcinoma. It enabled the detection of a treatment selection marker: the DDR2 gene.

Influence of trends in hospital volume over time on patient outcomes for high-risk surgery.

BACKGROUND: The "practice makes perfect" concept considers the more frequent a hospital performs a procedure, the better the outcome of the procedure. We aimed to study this concept by investigating whether patient outcomes improve in hospitals with a significantly increased volume of high-risk surgery over time and whether a learning effect existed at the individual hospital level. METHODS: We included all patients who underwent one of 10 digestive, cardiovascular and orthopaedic procedures between 2010 and 2014 from the French nationwide hospitals database. For each procedure, we identified three groups of hospitals according to volume trend (increased, decreased, or no change). In-hospital mortality, reoperation, and unplanned hospital readmission within 30 days were compared between groups using Cox regressions, taking into account clustering of patients within hospitals and potential confounders. Individual hospital learning effect was investigated by considering the interaction between hospital groups and procedure year. RESULTS: Over 5 years, 759,928 patients from 694 hospitals were analysed. Patients' mortality in hospitals with procedure volume increase or decrease over time did not clearly differ from those in hospitals with unchanged volume across the studied procedures (e.g., Hazard Ratios [95%] of 1.04 [0.93-1.17] and 1.08 [0.97-1.21] respectively for colectomy). Furthermore, patient outcomes did not improve or deteriorate in hospitals with increased or decreased volume of procedures over time (e.g., 1.01 [0.95-1.08] and 0.99 [0.92-1.05] respectively for colectomy). CONCLUSIONS: Trend in hospital volume over time did not appear to influence patient outcomes based on real-world data. TRIAL REGISTRATION: NCT02788331, June 2, 2016.