Feasibility of Prone Positioning for Brain-injured Patients with Severe Acute Respiratory Distress Syndrome: A Systematic Review and Pilot Study (ProBrain).

BACKGROUND: Prone position is a key component to treat hypoxemia in patients with severe acute respiratory distress syndrome. However, most studies evaluating it exclude patients with brain injuries without any medical evidence. METHODS: This study includes a systematic review to determine whether brain-injured patients were excluded in studies evaluating prone position on acute respiratory distress syndrome; a prospective study including consecutive brain-injured patients needing prone position. The primary endpoint was the evaluation of cerebral blood flow using transcranial Doppler after prone positioning. Secondary outcomes were intracranial pressure, cerebral perfusion pressure, and tissue oxygen pressure. RESULTS: From 8,183 citations retrieved, 120 studies were included in the systematic review. Among them, 90 studies excluded brain-injured patients (75%) without any justification, 16 included brain-injured patients (4 randomized, 7 nonrandomized studies, 5 retrospective), and 14 did not retrieve brain-injured data. Eleven patients were included in the authors' pilot study. No reduction of cerebral blood flow surrogates was observed during prone positioning, with diastolic speed values (mean ± SD) ranging from 37.7 ± 16.2 cm/s to 45.2 ± 19.3 cm/s for the right side (P = 0.897) and 39.6 ± 18.2 cm/s to 46.5 ± 21.3 cm/s for the left side (P = 0.569), and pulsatility index ranging from 1.14 ± 0.31 to 1.0 ± 0.32 for the right side (P = 0.145) and 1.14 ± 0.31 to 1.02 ± 0.2 for the left side (P = 0.564) before and during prone position. CONCLUSIONS: Brain-injured patients are largely excluded from studies evaluating prone position in acute respiratory distress syndrome. However, cerebral blood flow seems not to be altered considering increasing of mean arterial pressure during the session. Systematic exclusion of brain-injured patients appears to be unfounded, and prone position, while at risk in brain-injured patients, should be evaluated on these patients to review recommendations, considering close monitoring of neurologic and hemodynamic parameters.

Incidence and survival of transthyretin amyloid cardiomyopathy from a French nationwide study of in- and out-patient databases.

BACKGROUND: Precise data about ATTR-CM incidence rates at national level are scarce. Consequently, this study aimed to estimate the annual incidence and survival of transthyretin amyloid cardiomyopathy (ATTR-CM) in France between 2011 and 2019 using real world data. We used the French nationwide exhaustive data (SNDS database) gathering in- and out-patient claims. As there is no specific ICD-10 marker code for ATTR-CM, diagnosis required both amyloidosis (identified by E85. ICD-10 code or a tafamidis meglumine delivery) and a cardiovascular condition (identified by ICD-10 or medical procedure codes related to either heart failure, arrhythmias, conduction disorders or cardiomyopathies), not necessarily reported at the same visit. Patients with probable AL-form of amyloidosis or probable AA-form of amyloidosis were excluded. RESULTS: Between 2011 and 2019, 8,950 patients with incident ATTR-CM were identified. Incidence rates increased from 0.6 / 100,000 person-years in 2011 to 3.6 / 100,000 person-years in 2019 (p < 0.001), reaching 2377 new cases in 2019. Sex ratios (M/F) increased from 1.52 in 2011 to 2.23 in 2019. In 2019, median age at diagnosis was 84.0 years (85.5 for women and 83.5 for men). Median survival after diagnosis was 41.9 months (95% CI [39.6, 44.1]). CONCLUSIONS: This is the first estimate of nationwide ATTR-CM incidence in France using comprehensive real-world databases. We observed an increased incidence over the study period, consistent with an improvement in ATTR-CM diagnosis in recent years.

Personalized Reimbursement Model (PRM) program: A real-world data platform of cancer drugs use to improve and personalize drug pricing and reimbursement in France.

OBJECTIVE: This article describes the Personalized Reimbursement Model (PRM) program methodology, limitations, achievement and perspectives in using real-world data of cancer drugs use to improve and personalize drug pricing and reimbursement in France. MATERIALS AND METHODS: PRM platform aggregates Electronic Pharmacy Records (EPR) data from French medical centers (PRM centers) to build retrospective cohorts of patients treated with injectable cancer drugs in a hospital setting. Data extracted on January 1st, 2020, from breast cancer (BC) patients who received trastuzumab, trastuzumab emtansin or pertuzumab since January 1st, 2011, and from lung cancer (LC) patients who received bevacizumab or atezolizumab since January 1st, 2015, enabled recovering their injectable cancer drugs history from diagnosis date until December 30th, 2019, and served as dataset for assessment. RESULTS: 123 PRM centers provided data from 30,730 patients (25,660 BC and 5,070 LC patients respectively). Overall, 20,942 (82%) of BC and 4,716 (93%) of LC patients were analyzed. Completion rate was above 98% for patients characteristics, diagnostic and treatment related data. PRM centers cover 48% and 33% of BC and LC patients in-hospital therapeutic management in France, respectively. Distribution of BC and LC patients therapeutic management, by medical center category and geographic location, was similar in PRM centers to all French medical centers, ensuring the representativeness of the PRM platform. CONCLUSION: PRM Platform enabled building a national database generating on demand Real-World Evidence based on EPR. This enabled the first performance-based risk-sharing arrangements based on PRM data, between the CEPS and Roche, for atezolizumab cancer immunotherapy in metastatic non-small cell lung cancer indication.

Cerebrovascular Ischemic Events in Patients With Takayasu Arteritis.

BACKGROUND: Takayasu arteritis (TA) is a large vessel vasculitis that may complicate with cerebrovascular ischemic events. The objective was to describe clinical and vascular features of TA patients with cerebrovascular ischemic events and to identify risk factors for these events. METHODS: We analyzed the prevalence and type of stroke/transient ischemic attack (TIA), factors associated with cerebrovascular ischemic events, and stroke-free survival in a large cohort fulfilling the American College of Rheumatology or Ishikawa criteria of TA. RESULTS: Among 320 patients with TA (median age at diagnosis, 36 [25-47] years; 261 [86%] women), 63 (20%) had a stroke (n=41; 65%) or TIA (n=22; 35%). Ischemic event localized in the carotid territory for 55 (87%) patients and the vertebral artery territory in 8 (13%) patients. Multiple stenosis were observed in 33 (52%) patients with a median number of stenosis of 2 (minimum, 0 to maximum, 11), and aneurysms were observed in 10 (16%) patients. A history of stroke or TIA before TA diagnosis (hazard ratio [HR], 4.50 [2.45-8.17]; P<0.0001), smoking (HR, 1.75 [1.01-3.02]; P=0.05), myocardial infarction history (HR, 0.21 [0.05-0.89]; P=0.039), thoracic aorta involvement (HR, 2.05 [1.30-3.75]; P=0.023), time from first symptoms to diagnosis >1 year (HR, 2.22 [1.30-3.80]; P=0.005), and aspirin treatment (HR, 1.82 [1.04-3.19]; P=0.035) were associated with cerebrovascular ischemic event. In multivariate analysis, time from first symptoms to TA diagnosis >1 year (HR, 2.16 [1.27-3.70]; P=0.007) was independently associated with cerebrovascular ischemic events in patients with TA. The HR for cerebrovascular ischemic event in patients who already experienced a stroke/TIA was 5.11 (2.91-8.99; P<0.0001), compared with those who had not. CONCLUSIONS: Carotid stroke/TIA is frequent in TA. We identified factors associated with cerebrovascular ischemic events.

Checkpoint inhibitor treatment induces an increase in HbA1c in nondiabetic patients.

Immunotherapy greatly improves clinical outcomes in treated patients with cancer. However, the long-lasting immune response and long duration of therapy could induce long-term adverse effects owing to the chronic inflammation induced. Type 2 diabetes is now recognized as an inflammatory disease. In addition, immunotherapy is concerned with increase in the production of tumor necrosis factor-α, interleukin-2, and interferon-γ, which are involved in the inflammatory process. Based on these observations, we hypothesized that anti-programmed cell death-1 (anti-PD-1) and/or anticytotoxic T-lymphocyte-associated protein-4 therapy could contribute to type 2 diabetes genesis in treated patients. Therefore, to evaluate this hypothesis, we studied HbA1c levels during follow-up in patients treated with anti-PD-1 and/or anticytotoxic T-lymphocyte-associated protein-4 therapy. A prospective and observational study was performed in an oncodermatology department (Saint-Louis Hospital, Paris, France) from March 2015 to February 2017. Sixty-two patients meeting the inclusion criteria were enrolled. Forty-three patients had paired HbA1c measurements during their follow-up period and were analyzed. The median follow-up was 3 months. We noted an increase in HbA1c levels from 5.3% [interquartile range (IQR): 5.1-5.5; range: 4.5-6.2) to 5.45% (IQR: 5.2-5.7; range: 4.7-6.2; P=0.037). This observation was confirmed in the subgroup of patients who did not receive concomitant glucocorticoids; their median HbA1c levels increased from 5.3% (IQR: 5.1-5.5; range: 4.7-6.2) to 5.5% (IQR: 5.2-5.7; range: 4.7-6.3; P=0.025). Variables such as age, BMI, and sex were not associated with the HbA1c level increase, but a tendency toward rising HbA1c levels was observed in treatments longer than 12 months. This study demonstrates that treatment with anti-PD-1 antibodies may impair glucose metabolism, as measured by increasing HbA1c levels.