Cardiovascular disease healthcare trajectories: descriptions, similarities, mortality rates of heart failure in France.

AIMS: The primary objectives of this study were to analyse the nationwide healthcare trajectories of heart failure (HF) patients in France, 2 years after their first hospitalization, and to measure sequence similarities. Secondary objectives were to identify the association between trajectories and the risk of mortality. METHODS AND RESULTS: A retrospective, observational study was conducted using data extracted from the Echantillon Généraliste des Bénéficiaires database, covering the period from 1 January 2008 to 31 December 2018. Follow-up concluded upon death or at the end of the study. We developed a methodology specific to healthcare data by extracting frequent healthcare trajectories and measuring their similarity for use in a survival machine learning analysis. In total, 11 488 HF patients were included and followed up for an average of 2.9 ± 1.3 years. The mean age of the patients was 78.0 ± 13.2 years. The first-year mortality rate was 31.7% and increased to 78.8% at 5 years. Fifty per cent of patients experienced re-hospitalization for reasons related to cardiovascular diseases. We identified 1707 hospitalization sequences, and 21 sequences were associated with survival, while 15 sequences were linked to mortality. In all our models, age and gender emerged as the most significant predictors of mortality (permutation feature importance: 0.099 ± 0.00078 and 0.0087 ± 0.00018, respectively; weights could be interpreted in relative terms). Specifically, the age at initial hospitalization for HF was positively associated with mortality. Gender (male: 49.5%) was associated with poorer prognoses. Healthcare trajectories, including non-surgical device treatments, valve replacements, and atrial fibrillation ablation, were associated with a better prognosis (permutation feature importance: 0.0047 ± 0.00011, 0.0014 ± 0.000073, and 0.00095 ± 0.000097, respectively), except in cases where these invasive treatments preceded or followed hospitalization for cardiac decompensation. The predominant negative prognosis sequences were mostly those that included HF-related hospitalizations before or after other-related hospitalizations (permutation feature importance: 0.0007 ± 0.000091 and 0.00011 ± 0.000045, respectively). CONCLUSIONS: We highlight the value of healthcare trajectories on frequent hospitalization sequences, mortality, and prognosis and indicate the necessary prognostic value of HF re-hospitalization. Our work may be an essential tool for better identification of at-risk patients in order to increase and improve personalized care in the future.

Vitiligo patient population and disease burden in France: VIOLIN study results from the CONSTANCES cohort.

BACKGROUND: Vitiligo is a chronic autoimmune disease resulting in skin depigmentation. OBJECTIVES: This study assessed the prevalence, disease burden and treatment of vitiligo in France. METHODS: VIOLIN was a cross-sectional study nested in the national CONSTANCES cohort, which consists of randomly selected adults aged 18-69 years in France. In VIOLIN, longitudinal data were collected prospectively from 158,898 participants during 2012-2018 and linked to the National Health Data System (SNDS), a healthcare utilization database. Patients with physician-diagnosed vitiligo were matched (1:3) with control participants based on age, sex, geographic region, year of inclusion and skin phototype. Patients completed a questionnaire in 2022 to collect disease characteristics, disease burden and quality-of-life (QoL) data. RESULTS: Vitiligo prevalence was 0.71% (681/95,597) in 2018. The mean age in the vitiligo population was 51.2 years; 51.4% were women. Most patients (63%) were diagnosed before age 30 years, mainly by dermatologists (83.5%). Most patients (81.1%) had visible lesions (i.e. on face, hands). Vitiligo was limited to <10% of the body surface area (BSA) in 85.8% of patients. Comorbidities including thyroid disease (18.0% vs. 9.0%), psoriasis (13.7% vs. 9.7%), atopic dermatitis (12.4% vs. 10.3%), depression (18.2% vs. 14.6%) and alopecia areata (4.3% vs. 2.4%) were significantly more common in patients with vitiligo versus matched controls (n = 2043). QoL was significantly impaired in patients with >5% BSA involvement or visible lesions, particularly with ≥10% facial involvement. Vitiligo-specific instruments (i.e. Vitiligo Impact Patient scale and Vitiligo-specific QoL instrument) were more sensitive to QoL differences among subgroups versus general skin instruments, and generic instruments were least sensitive. Most patients (83.8%) did not receive any prescribed treatment. CONCLUSIONS: Patients with vitiligo in France have a high disease burden, particularly those with visible lesions or higher BSA involvement. Most patients are not receiving treatment, highlighting the need for new effective treatments and patient/physician education.

The Effectiveness of an App (Insulia) in Recommending Basal Insulin Doses for French Patients With Type 2 Diabetes Mellitus: Longitudinal Observational Study.

BACKGROUND: For patients with type 2 diabetes (T2D), calculating the daily dose of basal insulin may be challenging. Insulia is a digital remote monitoring solution that uses clinical algorithms to recommend basal insulin doses. A predecessor device was evaluated in the TeleDiab-2 randomized controlled trial, showing that a higher percentage of patients using the app achieved their target fasting blood glucose (FBG) level compared to the control group, and insulin doses were adjusted to higher levels without hypoglycemia. OBJECTIVE: This study aims to analyze how the glycemic control of Insulia users has evolved when using the app in a real-life setting in France. METHODS: A retrospective observational analysis of data collected through the device in adult French patients with T2D treated with basal insulin and oral antihyperglycemic agents using the system for ≥6 months was conducted. Analyses were descriptive and distinguished the results in a subpopulation of regular and compliant users of the app. Glycemic outcomes were estimated considering the percentage of patients who achieved their individualized FBG target between 5.5 and 6 months following the initiation of device use, the frequency of hypoglycemia resulting in a treatment change over the 6-month period of exposure, and the evolution of the average hemoglobin A1c (HbA1c) level over the same period. RESULTS: Of the 484 users, 373 (77.1%) performed at least one dose calculation. A total of 221 (59.2%) users were men. When app use started, the mean age, BMI, HbA1c, and basal insulin dose were 55.8 (SD 11.9) years, 30.6 (SD 5.9) kg/m2, 10.1% (SD 2.0%), and 25.5 (SD 15.8) IU/day, respectively. Over a median use duration of 5.0 (95% CI 3.8-5.7) months, patients used the system 5.8 (SD 1.6) times per week on average, and 73.4% of their injected doses were consistent with the app's suggested doses. Among regular and compliant user patients (n=91, ≥5 measurements/week and ≥80% adherence to calculated doses), 60% (55/91) achieved the FBG target (±5%) at 6 months (5.5-6 months) versus 51.5% (145/282) of the other patients (P=.15). There was an increase in the proportion of patients achieving their target FBG for regular and compliant users (+1.86% every 2 weeks) without clear improvement in other patients. A logistic model did not identify the variables that were significantly associated with this outcome among regular and compliant users. In the overall population, the incidence of reported hypoglycemia decreased simultaneously (-0.16%/month). Among 82 patients, the mean HbA1c decreased from 9.9% to 7.2% at 6 months. CONCLUSIONS: An improvement in glycemic control as measured by the percentage of patients reaching their FBG individualized target range without increasing hypoglycemic risk was observed in patients using the Insulia app, especially among regular users following the dose recommendations of the algorithm.

Plasma CD27, a Surrogate of the Intratumoral CD27-CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma.

PURPOSE: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear. EXPERIMENTAL DESIGN: Tumor tissue from 25 patients with ccRCC was assessed for the expression of CD27 and CD70 in situ using multiplex immunofluorescence. CD27+ T-cell phenotypes in tumors were analyzed by flow cytometry and their gene expression profile were analyzed by single-cell RNA sequencing then confirmed with public data. Baseline sCD27 was measured in 81 patients with renal cell carcinoma (RCC) treated with immunotherapy (35 for training cohort and 46 for validation cohort). RESULTS: In the tumor microenvironment, CD27+ T cells interacted with CD70-expressing tumor cells. Compared with CD27- T cells, CD27+ T cells exhibited an apoptotic and dysfunctional signature. In patients with RCC, the intratumoral CD27-CD70 interaction was significantly correlated with the plasma sCD27 concentration. High sCD27 levels predicted poor overall survival in patients with RCC treated with anti-programmed cell death protein 1 in both the training and validation cohorts but not in patients treated with antiangiogenic therapy. CONCLUSIONS: In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.

Management and Health Resource Use of Patients With Metastatic Renal Cell Carcinoma treated With Systemic Therapy Over 2014-2017 in France: A National Real-World Study.

BACKGROUND: The introduction of novel systemic therapies for metastatic renal cell carcinoma (mRCC) over the last decade has significantly improved patient outcomes. Little information is available on treatment modalities and outcomes in everyday practice. The objective of this study was to describe patient characteristics, treatment patterns, and healthcare resource use in mRCC patients receiving systemic therapy in France (2014-2017), using the nationwide claims database. PATIENTS AND METHODS: Patients with a diagnosis of RCC (ICD-10: C64) between 2009 and 2017 and receiving a first systemic treatment for mRCC between 2014 and 2017 were eligible. Patients were divided into two groups at diagnosis, Group A: metastatic RCC and Group B: localized RCC. RESULTS: 4,929 eligible patients were identified (Group A: 2638 patients, 53.5%; Group B: 2,291 patients,46.5%). Median age was 66 years and 73% were men. In patients with incident RCC (N = 3,425), 62.3% underwent nephrectomy (94.4% in Group B). Within the year following mRCC diagnosis, 86.5% were hospitalized at least once; among them 58.1% for RCC. Nearly 31% of patients underwent radiotherapy. First line treatment was sunitinib for 65% of patients and pazopanib for 24%. Twenty five percent and 10% of patients received 2 and 3 lines of systemic treatment, respectively. The 2-year survival rate after mRCC diagnosis was 44%, with median overall survival of 20 [95%CI: 19-21] months (14 and 28 in Group A and B). CONCLUSION: This study documented patient characteristics, treatment patterns and survival outcomes in mRCC patients receiving systemic therapy in France (2014-2017). Estimated survival rates were consistent with real-world studies from other countries.

Patterns of Use and Clinical Outcomes with Long-Acting Somatostatin Analogues for Neuroendocrine Tumors: A Nationwide French Retrospective Cohort Study in the Real-Life Setting.

INTRODUCTION: Long-acting somatostatin analogues such as lanreotide autogel (LAN) and octreotide long-acting release (OCT) are recommended as first-line treatment for patients with neuroendocrine tumors (NETs). However, only few real-world studies have compared the two medications. This retrospective, observational cohort study used a French claims database to compare patterns of use with LAN vs. OCT in patients with NETs. METHODS: Data on LAN and OCT patterns of use were obtained retrospectively from the National System of Health Data (SNDS), a national French claims database. Patients 18 years of age or older who initiated treatment for NETs between 2009 and 2016, and who received at least six subsequent dispensings of first-line LAN or OCT during the first year of treatment, were included. A subgroup analysis was performed on patients with gastroenteropancreatic (GEP)-NETs. RESULTS: Patients receiving LAN (n = 2327) vs. OCT (n = 2090) had greater median treatment duration (31.8 months vs. 22.1 months, respectively; p < 0.0001; log-rank test) and were less likely to discontinue treatment; adjusted hazard ratio (HR) 0.74 (95% confidence interval [CI] 0.69-0.80). In year 1, a significantly lower percentage of patients receiving LAN vs. OCT switched treatments (10.4% vs. 22.2%, respectively; p < 0.0001), received an average monthly dose per trimester above recommended dose (3.0% vs. 7.3%, respectively; p < 0.0001), and used rescue medication (3.1% vs. 10.0%, respectively; p < 0.0001). Dispensing of pancreatic enzymes was significantly higher in patients receiving LAN than OCT (16.4% vs. 13.9%, respectively). In the subgroup of patients with GEP-NETs, those receiving LAN (n = 1478) vs. OCT (n = 1278) had greater treatment duration and less treatment discontinuation, switching, dosage above the recommended dose, and rescue medication use, but no significant difference in dispensing of pancreatic enzymes or time to second-line treatment. CONCLUSION: These real-world data suggest potential clinical and economic advantages of LAN over OCT in the management of patients with NETs in the French population.

Conditional prescriptions of oral antihypertensive drugs for the management of hypertension urgencies in the inpatient setting: An observational study.

WHAT IS KNOWN AND OBJECTIVES: The management of hypertension urgencies during hospitalization may generally not necessitate urgent care. However, physicians frequently prescribe 'as needed' antihypertensive drugs for which administration is triggered by blood pressure thresholds. The lack of rationale for this hospital practice led us to study oral conditional antihypertensive (OCA) prescriptions. We aimed to estimate the prevalence of OCA prescriptions and to establish their characteristics. METHODS: In our institution, prescriptions are computerized. The study was retrospectively performed using a hospital clinical data warehouse over a 5-year period. RESULTS AND DISCUSSION: The prevalence of OCA prescriptions was 6.9% among subjects treated with an antihypertensive drug. The median duration of these prescriptions was 4 days, until the day of the patient discharge in 78.8% stays. The calcium channel inhibitors were the main (79.9%) pharmacological class prescribed, with mostly prescriptions of nicardipine. OCA prescriptions were associated with another antihypertensive medication in 58.8% of the prescriptions; for 19.3%, it was a medication belonging to the same pharmacological class than the OCA drug prescribed. Regarding the computerized drafting, 39.6% of the conditional prescriptions were considered uninterpretable. At least one administration by nurses concerned 65.1% of the OCA prescriptions. The mean SBP and DBP before the initiation of an OCA drug was 142.9 ± 28.2 and 75.8 ± 24.5 mm Hg, respectively, relative to 143.0 ± 24.9 and 77.6 ± 19.9 mm Hg after the initiation (P = .8 for SBP and P = .06 for DBP). WHAT IS NEW AND CONCLUSION: The originality of this study lies in the use of a clinical data warehouse to evaluate OCA prescriptions in hospital. These prescriptions are current, often uninterpretable and mostly ordered until patient discharge. Such drug orders could be associated with an increased risk of iatrogenic events and/or administration errors. This underlies the need for developing decision support tools and computerized protocols to manage hypertension urgencies.

Clinical and Pharmacological Aspects of Hospital-Acquired Acute Kidney Injuries Outside the Intensive Care Unit: A Phenome-Wide Association Study.

INTRODUCTION: Acute kidney injury (AKI) occurring in the hospital in noncritically ill patients involves a broad spectrum of clinical conditions and medical scenarios that are better appreciated by systematic association studies. METHODS: We extracted all diagnoses and drug prescriptions from an i2b2 clinical data warehouse for patients who stayed in an academic hospital between 2013 and 2017, and had at least two plasma creatinine measurements performed during the first week of their stay, and analyzed the association between AKI occurring outside the intensive care unit (ICU), as identified using the AKIN classification criteria, and International Classification of Diseases (ICD)-10 diagnosis codes and drug categories. RESULTS: 16,662 hospital stays for unique individuals were extracted. The prevalence of AKI outside the ICU was 8%, with a distribution of frequencies that greatly varied according to the departments. 4% of patients with AKI died during their hospital stay (OR 6.17, 95% CI [2.59-17.9]). ICD-10 diagnosis codes were related to infections, kidney cancer, heart failure, respiratory failure, and chronic kidney disease. Drugs targeting the renin angiotensin system and loop diuretics had the larger size effect on AKI. The ICD-10 code N17/"Acute kidney failure" was recorded in average in only 16% of the cases with AKI, and its frequency ranged from 0 to 80%, according to the hospital department; the lack of encoding did not impact mortality. CONCLUSION: A systematic search for the associations of AKI with prescribed drugs and medical diagnosis using a phenome-wide approach allows to describe in depth the epidemiology of AKI outside the ICU.

Hyperchloremia is not associated with AKI or death in septic shock patients: results of a post hoc analysis of the "HYPER2S" trial.

BACKGROUND: Recent data suggest that hyperchloremia induced by fluid resuscitation is associated with acute kidney injury (AKI) and mortality, particularly in sepsis. Experimental studies showed that hyperchloremia could affect organ functions. In patients with septic shock, we examined the relationship between serum chloride concentration and both renal function and survival. METHODS: Post hoc analysis of the "HYPER2S" trial database (NCT01722422) including 434 patients with septic shock randomly assigned for resuscitation with 0.9% or 3% saline. Metabolic parameters were recorded up to 72 h. Metabolic effects of hyperchloremia (> 110 mmol/L) were studied stratified for hyperlactatemia (> 2 mmol/L). Cox models were constructed to assess the association between chloride parameters, day-28 mortality and AKI. RESULTS: 413 patients were analysed. The presence of hyperlactatemia was significantly more frequent than hyperchloremia (62% versus 71% of patients, respectively, p = 0.006). Metabolic acidosis was significantly more frequent in patients with hyperchloremia, no matter the presence of hyperlactatemia, p < 0.001. Adjusted risk of AKI and mortality were not significantly associated with serum chloride, hyperchloremia, maximal chloremia and delta chloremia (maximal-H0 [Cl]). CONCLUSIONS: Despite more frequent metabolic acidosis, hyperchloremia was not associated with an increased risk for AKI or mortality. Trial registration ClinicalTrials.gov, identifier: NCT01722422, registered 2 November 2012.

Immediate Hypersensitivity to Contrast Agents: The French 5-year CIRTACI Study.

BACKGROUND: Iodinated and gadolinium-based contrast media (ICM; GBCM) induce immediate hypersensitivity (IH) reactions. Differentiating allergic from non-allergic IH is crucial; allergy contraindicates the culprit agent for life. We studied frequency of allergic IH among ICM or GBCM reactors. METHODS: Patients were recruited in 31 hospitals between 2005 and 2009. Clinical symptoms, plasma histamine and tryptase concentrations and skin tests were recorded. Allergic IH was diagnosed by intradermal tests (IDT) with the culprit CM diluted 1:10, "potentially allergic" IH by positive IDT with pure CM, and non-allergic IH by negative IDT. FINDINGS: Among 245 skin-tested patients (ICM = 209; GBCM = 36), allergic IH to ICM was identified in 41 (19.6%) and to GBCM in 10 (27.8%). Skin cross-reactivity was observed in 11 patients with ICM (26.8%) and 5 with GBCM (50%). Allergy frequency increased with clinical severity and histamine and tryptase concentrations (p < 0.0001). Cardiovascular signs were strongly associated with allergy. Non-allergic IH was observed in 152 patients (62%) (ICM:134; GBCM:18). Severity grade was lower (p < 0.0001) and reaction delay longer (11.6 vs 5.6 min; p < 0.001). Potentially allergic IH was diagnosed in 42 patients (17.1%) (ICM:34; GBCM:8). The delay, severity grade, and mediator release were intermediate between the two other groups. INTERPRETATION: Allergic IH accounted for < 10% of cutaneous reactions, and > 50% of life-threatening ones. GBCM and ICM triggered comparable IH reactions in frequency and severity. Cross-reactivity was frequent, especially for GBCM. We propose considering skin testing with pure contrast agent, as it is more sensitive than the usual 1:10 dilution criteria.