Real-life Management Research Articles

Réalité de la prise en charge de la maladie rénale chronique en néphrologie en France : étude de cohorte CKD-REIN

BackgroundTo be able to assess the impact of the bundled payment system on real-life management of patients with chronic kidney disease, an overview of patient-care management before its implementation is needed. Patients and methodsWe describe patterns of nephrology care over 3 years in 2835 patients with moderate to severe chronic kidney disease, who were followed-up from 2013 to 2019 in the CKD-REIN cohort study. Compliance with health authority guidelines during this period is also studied. ResultsAt baseline, patients’ mean age was 67 years, 65% were men, and 43% had chronic kidney disease stage 4 or 5. The mean number of nephrology visits increased from 1.1 to 2.7 per year, from chronic kidney disease stage 3A to stage 5. The minimum number of nephrology visits as recommended by health authorities was achieved in 84%, 63%, and 33% of patients with chronic kidney disease stages 3B, 4, and 5, respectively. In chronic kidney disease stages 4 and 5, only 34% and 40% of patients had seen a dietitian, and 33% and 54% had received information about treatment options, respectively. The average waiting time for a first appointment with a nephrologist was longer, 60 days and its duration shorter, 30 vs 38 to 40 minutes, in university hospitals compared with non-university hospitals and private clinics. ConclusionThe significant gap between received and recommended care reflects human resources and organizational limits in chronic kidney disease management in the nephrology setting. Improvements with bundled payment are expected.

Clinical Practice Audit on the Management of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in the Netherlands

IntroductionManaging complex and rare systemic autoimmune diseases such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can be challenging and is often accompanied by undesirable variations in clinical practice. Adequate understanding of clinical practice can help identify essential issues to improve the care for AAV patients. Therefore, we studied the real-life management and outcomes of AAV patients in the Netherlands.MethodsIn this cohort study, we investigated clinical practice in university and nonuniversity teaching hospitals with respect to patients with a clinical diagnosis of AAV. We retrospectively collected clinical data encompassing clinical variables, medication details, and outcome parameters.ResultsData of 230 AAV patients were collected in 9 Dutch hospitals. Of these, 167 patients (73%) were diagnosed with granulomatosis with polyangiitis, 54 (24%) with microscopic polyangiitis and 9 (4%) with eosinophilic granulomatosis with polyangiitis. One hundred sixty-six patients (72%) had generalized disease. The median year of diagnosis was 2013 (range 1987–2018). Besides steroids, oral cyclophosphamide was the most used drug (50%) for induction therapy and azathioprine (68%) for maintenance therapy. Adverse outcomes were major infections in 35%, major relapses in 23%, malignancy in 10%, major cardiovascular events in 8%, and end-stage renal disease in 7%.ConclusionOral cyclophosphamide was the most frequently used induction therapy, azathioprine for maintenance therapy; over time, the use of rituximab is increasingly employed. Major infection and relapses are the most prevalent adverse outcomes. This audit resulted in important indicators for treatment of AAV patients that can be implemented for future, national audits to improve the outcomes of AAV patients.

2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr. Jekyll and Mr. Hyde.

According to the updated International Myeloma Working Group criteria, smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by an M-component >3 g/dL, bone marrow plasma cell infiltration >10% and <60%, and absence of any myeloma-defining event. Active multiple myeloma is preceded by SMM, with a median time to progression of approximately 5 years. Cases of SMM range from the extremes of “monoclonal gammopathy of undetermined significance-like”, in which patients never progress during their lifetimes, to “early multiple myeloma”, in which transformation into symptomatic disease, based on genomic evolution, may be rapid and devastating. Such a “split personality” makes the prognosis and management of individual patients challenging, particularly with regard to the identification and possible early treatment of high-risk SMM. Outside of clinical trials, the conventional approach to SMM generally remains close observation until progression to active multiple myeloma. However, two prospective, randomized trials have recently demonstrated a significant clinical benefit in terms of time to progression, and of overall survival in one of the two studies, for some patients with higher-risk SMM treated with lenalidomide ± dexamethasone, raising the question of whether such an approach should be considered a new standard of care. In this paper, experts from the European Myeloma Network describe current biological and clinical knowledge on SMM, focusing on novel insights into its molecular pathogenesis, new prognostic scoring systems proposed to identify SMM patients at higher risk of early transformation, and updated results of completed or ongoing clinical trials. Finally, some practical recommendations for the real-life management of these patients, based on Delphi consensus methodology, are provided.

Non-occlusive mesenteric ischemia: Diagnostic challenges and perspectives in the era of artificial intelligence.

Acute mesenteric ischemia (AMI) is a severe condition associated with poor prognosis, ultimately leading to death due to multiorgan failure. Several mechanisms may lead to AMI, and non-occlusive mesenteric ischemia (NOMI) represents a particular form of AMI. NOMI is prevalent in intensive care units in critically ill patients. In NOMI management, promptness and accuracy of diagnosis are paramount to achieve decisive treatment, but the last decades have been marked by failure to improve NOMI prognosis, due to lack of tools to detect this condition. While real-life diagnostic management relies on a combination of physical examination, several biomarkers, imaging, and endoscopy to detect the possibility of several grades of NOMI, research studies only focus on a few elements at a time. In the era of artificial intelligence (AI), which can aggregate thousands of variables in complex longitudinal models, the prospect of achieving accurate diagnosis through machine-learning-based algorithms may be sought. In the following work, we bring you a state-of-the-art literature review regarding NOMI, its presentation, its mechanics, and the pitfalls of routine work-up diagnostic exams including biomarkers, imaging, and endoscopy, we raise the perspectives of new biomarker exams, and finally we discuss what AI may add to the field, after summarizing what this technique encompasses.

Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience.

BackgroundCutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR).MethodsMelanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors.ResultsThe median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62).ConclusionsThe nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study

BackgroundAnemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients’ quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece.MethodsThis study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively.ResultsA total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn’s disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%).ConclusionsThe frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to 4/5 of anemia IBD patients with the majority of them receiving iron intravenously.

Treatment Patterns, Effectiveness, and Satisfaction Among Patients with Type2 Diabetes Treated with Insulin in Saudi Arabia: Results of the RIMODIS Study.

IntroductionThe alarming increase in type 2 diabetes mellitus (T2DM) in Saudi Arabia is aggravated by increasing obesity, sedentary lifestyle, and population aging. The RIMODIS study aimed at describing the practices in the therapeutic management of patients with T2DM treated with different insulin regimens. MethodsThis national, multicenter, non-interventional, cross-sectional disease registry on the real-life therapeutic management of insulin-treated patients with T2DM in Saudi Arabia enrolled 3010 patients. It primarily aimed at describing treatment patterns, complications, and glycemia levels. Patients completed the diabetes treatment satisfaction questionnaire (DTSQ). Data on different treatment patterns were analyzed using chi-square or Fisher’s exact test. Outcomes were analyzed according to the different insulin regimen subgroups (basal versus premixed).ResultsOver 60% of patients were treated with premixed insulin and most patients were also prescribed oral antidiabetics (OADs). Patients on insulin alone seemed to achieve better glycated hemoglobin (HbA1c) control. Adding OADs to insulin slightly increased treatment satisfaction scores, with scores higher in patients on basal insulin compared to premixed insulin. Hypoglycemia was lower when adding OADs to insulin. Most patients showed high treatment adherence; however, two-thirds of study patients failed to achieve glycemic target levels. ConclusionMost patients are treated with a combination of insulin and OADs, associated with glycemic control and low incidence of hypoglycemia. However, we highlight suboptimal glycemic target achievement, underscoring the need to improve T2DM clinical management and promote healthier lifestyle among patients in Saudi Arabia.

Aminoglycosides in Critically Ill Septic Patients With Acute Kidney Injury Receiving Intermittent Hemodialysis: A Multicenter, Observational Study

PurposeData on aminoglycoside stewardship in critically ill septic patients with acute kidney injury (AKI) needing intermittent hemodialysis (IH) are scarce. The first objective of the study was to evaluate whether aminoglycoside administration occurs before vs after IH in the real-life management of critically ill septic patients with AKI needing IH. The second objective was to assess the delay in achieving a potential reinjection window for a second dose of aminoglycoside, which should be obtained with a postdialysis vs predialysis regimen. MethodsA post hoc observational analysis of a multicenter randomized trial of critically ill patients with AKI needing renal replacement therapy was conducted. Inclusion criteria consisted of any patients receiving IH for AKI during an antimicrobial therapy for a septic episode. FindingsAmong 206 of 341 septic patients (60%) receiving aminoglycosides, 90 underwent IH (46 with previous continuous renal replacement therapy and 44 without). Amikacin and gentamicin were administered for a mean (SD) of 2.2 (1.5) and 2.5 (2.1) days with mean (SD) doses of 20.6 (6.6) and 5.4 (2.5) mg/kg, respectively. In the 44 patients undergoing exclusive IH, aminoglycosides were administered in a predialysis in 53% of episodes versus 35% in a postdialysis schedule. The first Cmin target was obtained earlier with a predialysis vs postdialysis schedule (33.9 [14.2] hours vs 50.9 [12.2] hours, P = 0.009). ImplicationsDespite being less frequently used than a predialysis schedule, the postdialysis administration of aminoglycosides remains a regular practice in the intensive care unit. A predialysis schedule of administration in IH reduces the interval time to tolerable aminoglycoside redosing.

Diagnosis and management of non-clonal erythrocytosis remains challenging: a single centre clinical experience

Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb > 185 g/L and/or Hct > 0.52 in men and Hb > 165 g/L and/or Hct > 0.48 in women on two visits ≥ two months apart, thus confirming true erythrocytosis. Secondly, polycythaemia vera was excluded and secondary causes of erythrocytosis (SE) identified. Thirdly, idiopathic erythrocytosis patients (IE) were referred to next-generation sequencing for possible genetic background evaluation. Of the 116 patients, 75 (65%) are men and 41 (35%) women, with non-clonal erythrocytosis 34/116 (29%) had SE, 15/116 (13%) IE and 67/116 (58%) stayed incompletely characterized (ICE). Patients with SE were significantly older and had significantly higher Hb and Hct compared to patients with IE. Most frequently, SE was attributed to obstructive sleep apnoea and smoking. Phlebotomies were performed in 56, 53 and 40% of patients in the SE, IE, and ICE group, respectively. Approx. 70% of patients in each group received aspirin. Thrombotic events were registered in 12, 20 and 15% of SE, IE and ICE patients, respectively. Congenital erythrocytosis type 4 (ECYT4) was diagnosed in one patient. The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm.

DGeye: Probabilistic Risk Perception and Prediction for Urban Dangerous Goods Management

Recent years have witnessed the emergence of worldwide megalopolises and the accompanying public safety events, making urban safety a top priority in modern urban management. Among various threats, dangerous goods such as gas and hazardous chemicals transported through cities have bred repeated tragedies and become the deadly “bomb” we sleep with every day. While tremendous research efforts have been devoted to dealing with dangerous goods transportation (DGT) issues, further study is still in great need to quantify this problem and explore its intrinsic dynamics from a big data perspective. In this article, we present a novel system called DGeye , to feature a fusion between DGT trajectory data and residential population data for dangers perception and prediction. Specifically, DGeye first develops a probabilistic graphical model-based approach to mine spatio-temporally adjacent risk patterns from population-aware risk trajectories. Then, DGeye builds the novel causality network among risk patterns for risk pain-point identification, risk source attribution, and online risky state prediction. Experiments on both Beijing and Tianjin cities demonstrate the effectiveness of DGeye in real-life DGT risk management. As a case in point, our report powered by DGeye successfully drove the government to lay down gas pipelines for the famous Guijie food street in Beijing.

Topical Treatment of Premature Ejaculation: The Rise of Anesthetic Spray Formulations?

Topical anesthetics are one of the first line therapeutical options for men with premature ejaculation (PE). Real-life PE management often involves a range of interventions including systemic drug treatments (such as off-label and on-label selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, phosphodiesterase-5 inhibitors (PDE5Is)), topical anesthetic creams and sprays, and behavioral approaches. Among them, on-demand dapoxetine and lidocaine/prilocaine spray formulations are the only approved treatment options for lifelong PE. The earliest strategy to treat PE was based on the use of topical anesthetic agents. The rationale behind the use of anesthetics is that by reducing the glans penis sensitivity, the spinal and cerebral input of sexual arousal impulses may also be reduced. Oral SSRI proved to be effective to treat PE, but their high rate of side effects limit treatment adherence and both short and long term follow up data are lacking. Conversely, topical anesthetics have proved to increase ejaculatory latency, control, and sexual satisfaction in couple affected by PE with limited rates of adverse events. In this context, we aimed to perform a narrative review to summarize the most recent findings regarding the use of topical treatments for PE.

Real-Life Management of Central and Branch Retinal Vein Occlusion: A Seven-Year Follow-Up Study.

Retinal vein occlusion is the second most common retinal vascular pathology after diabetic retinopathy and a major cause of vision impairment. Nowadays, both central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) can be well-managed by intravitreal treatments. However, considering the long-life expectance of the patients, few data are present in the literature about the very long-term outcome of CRVO and BRVO. The present study was an interventional, retrospective analysis of the morphological and functional long-term outcome of CRVO and BRVO patients, followed in an Italian referral center. We collected data from 313 eyes (178 CRVO eyes and 135 BRVO eyes). Mean follow-up was 45 ± 25 months (range 12-84 months). Both CRVO and BRVO eyes experience a significant visual acuity improvement secondary to anti-vascular endothelial growth factor/dexamethasone treatments (from 0.57 ± 0.25 to 0.41 ± 0.24 LogMAR in CRVO and from 0.53 ± 0.42 to 0.30 ± 0.41 LogMAR in BRVO, respectively) (p < 0.01). Also, central macular thickness (CMT) resulted significant recovery at the end of the follow-up (from 585.54 ± 131.43 to 447.88 ± 245.07 μm in CRVO and from 585.54 ± 131.43 to 447.88 ± 245.07 μm in BRVO, respectively) (p < 0.01). CRVO eyes received a mean of 10.70 ± 4.76 intravitreal treatments, whereas BRVO underwent 9.80 ± 5.39 injections over the entire 7-year follow-up. Our analyses highlighted different time points indicating the best obtainable improvement. This was the first year for CRVO (12-month follow-up) and the second year for BRVO (24-month follow-up). After these two time points, both visual acuity and CMT resulted stable up to the end of the follow-up. Ischemia was associated with significantly worse outcome.

Management of LDL-cholesterol levels in patients with Diabetes Mellitus in Cardiology Practice: Real-life evidence of Under-treatment from the EPHESUS registry.

Effective treatment of high low-density lipoprotein cholesterol (LDL-C) levels has been shown to improve cardiovascular outcomes of patients with diabetes mellitus (DM). Herein, we aimed to provide insight to the real-life management of patients with DM in terms of LDL-C goal attainment and adherence to lipid management recommendations. Our objective was also to reveal the reasons of poor LDL-C goal attainment by assessing the perceptions of both physicians and patients. We compared the diabetic and non-diabetic patients from the database of a nationwide registry conducted in cardiology outpatient clinics with regard to the demographic characteristics, educational status, comorbidities, medications, laboratory parameters and LDL-C goal attainment. Also, both the patients and attending physicians were surveyed to analyse perceptions and awareness of hypercholesterolemia. Of the 1868 consecutively enrolled patients, 873 (47%) had DM. Proportion of patients on statins was significantly lower in patients with DM (67.8% vs 55.3%; P<.001). The proportion of patients who attained LDL-C targets were lower among the diabetic patients (17.8% vs 15%; P=.06). The most common causes of the discontinuation of statin therapy were negative media coverage about statins (32.1%), and recommendations of physicians to stop the lipid lowering therapy (29.6%). Analysis of the physician survey revealed that the physicians could determine the off-target patients accurately (negative predictive value 98.4%) while the positive predictive value (48.8%) was low. The reasons for not attaining the LDL-C goals in diabetic patients were not prescription of statins (38%) and inadequate (eg low-dose, non-adherent) statin (28.3%) dosages. In real-life clinical cardiology practice, diabetic patients are far below the recommended LDL-C treatment goals. High-intensity statin treatment in diabetic population is still avoided because of the concerns about polypharmacy and drug interactions. Also, the inertia of physicians and even cardiologists is probably a major cause of refraining of prescription of optimal statin dosages.

Consequences of representativeness bias on SHM-based decision-making

Judging the state of a bridge based on SHM observations is an inference process, which should be rationally carried out using a logical approach. However, it is often observed that real-life decision makers depart from this ideal model of rationality, judge and decide using common sense, and privilege fast and frugal heuristics to rational analytic thinking. For instance, confusion between condition state and safety of a bridge is one of the most frequently observed examples in bridge management. The aim of this paper is to describe mathematically this observed biased judgement, a condition that is broadly described by Kahneman and Tversky’s representativeness heuristic. Particularly, the paper examines how this heuristic affects the interpretation of data, providing a deeper understanding of the differences between a method affected by cognitive biases and the classical rational approach. Based on the literature review, three different models reproducing an individual behaviour distorted by representativeness are identified. These models are applied to the case of a transportation manager who wrongly judges a particular bridge unsafe simply because deteriorated, regardless its actual residual load-carrying capacity. It is demonstrated that the application of any of the three heuristic judgment models correctly predicts that the manager will mistakenly judge the bridge as unsafe based on the observed condition state. It is not objective of the paper to suggest that representativeness should be used instead of rational logic, however, understanding how real-life managers actually behave is of paramount importance when setting a general policy for bridge maintenance.

Real-Life Management Pathways for Chronic Peripheral Neuropathic Pain at Tertiary Pain Clinics in France.

Peripheral neuropathic pain (PNP) represents a major public health issue. Severe or refractory cases warrant tertiary multidisciplinary management, but little information is available about real-life care pathways. The primary objective of this cross-sectional, observational study was to investigate the pathways of patients with PNP consulting for the first time or followed for less than 1 year in French tertiary specialized pain clinics. PNP was diagnosed with the NeuPSIG algorithm. Data collected included demographics, pain characteristics, and details of management before and after the study visit (e.g., drug and non-drug treatment, nature of medical visits), as well as time to referral to a pain clinic and time to a diagnosis of PNP. Factors associated with delayed referral or diagnosis were analyzed with multivariate analysis. A total of 404 patients with PNP (age 55.8 ± 15.6 years, 60.3% females, 78.3% retired or unemployed, pain duration 43.4 ± 68.9 months) were enrolled by 84 pain specialists. Pain affected mainly the lower limbs (53.5%) and was predominantly related to surgery or trauma (59.4%). Primary care management was characterized by a high proportion of conventional analgesics (60.7%). Time to referral to a pain clinic was 43.4 ± 68.9 months since pain onset and 20.1 ± 39.4 months since the diagnosis of PNP. Delayed referral to a pain clinic was independently predicted by the clinical specialty of the referring doctor and by male gender. This study highlights the need for accessible guidance for non-pain specialists to improve their diagnostic and management skills and for faster referral of patients with PNP to tertiary pain clinics.

A convolutional neural network with transfer learning for automatic discrimination between low and high-grade synovitis: a pilot study.

Ultrasound-guided synovial tissue biopsy (USSB) may allow personalizing the treatment forpatients with inflammatory arthritis. To this end, the quantification of tissue inflammation in synovial specimens can be crucial to adopt proper therapeutic strategies. This study aimed at investigating whether computer vision may be of aid in discriminating the grade of synovitis in patients undergoing USSB. We used a database of 150 photomicrographs of synovium from patients who underwent USSB. For each hematoxylin and eosin (H&E)-stained slide, Krenn's score was calculated. After proper data pre-processing and fine-tuning, transfer learning on a ResNet34 convolutional neural network (CNN) was employed to discriminate between low and high-grade synovitis (Krenn's score < 5 or ≥ 5). We computed test phase metrics, accuracy, precision (true positive/actual results), and recall (true positive/predicted results). The Grad-Cam algorithm was used to highlight the regions in the image used by the model for prediction. We analyzed photomicrographs of specimens from 12 patients with arthritis. The training dataset included n.90 images (n.42 with high-grade synovitis). Validation and test datasets included n.30 (n.14 high-grade synovitis) and n.30 items (n.16 with high-grade synovitis). An accuracy of 100% (precision = 1, recall = 1) was scored in the test phase. Cellularity in the synovial lining and sublining layers was the salient determinant of CNNprediction. This study provides a proof of concept that computer vision with transfer learning is suitable for scoring synovitis. Integrating CNN-based approach into real-life patient management may improve the workflow between rheumatologists and pathologists.

Using over-the-label doses in real-life management of post-stroke spasticity with botulinum toxin type A: Treating more muscles to ensure success

Using over-the-label doses in real-life management of post-stroke spasticity with botulinum toxin type A: Treating more muscles to ensure success

Choosing the best algorithm among five thyroid nodule ultrasound scores: from performance to cytology sparing\u2014a single-center retrospective study in a large cohort

ObjectiveIncidental diagnosis of thyroid nodules, and therefore of thyroid cancer, has definitely increased in recent years, but the mortality rate for thyroid malignancies remains very low. Within this landscape of overdiagnosis, several nodule ultrasound scores (NUS) have been proposed to reduce unnecessary diagnostic procedures. Our aim was to verify the suitability of five main NUS.MethodsThis single-center, retrospective, observational study analyzed a total number of 6474 valid cytologies. A full clinical and US description of the thyroid gland and nodules was performed. We retrospectively applied five available NUS: KTIRADS, ATA, AACE/ACE-AME, EUTIRADS, and ACRTIRADS. Thereafter, we calculated the sensitivity, specificity, PPV, and NPV, along with the number of possible fine-needle aspiration (FNA) sparing, according to each NUS algorithm and to clustering risk classes within three macro-groups (low, intermediate, and high risk).ResultsIn a real-life setting of thyroid nodule management, available NUS scoring systems show good accuracy at ROC analysis (AUC up to 0.647) and higher NPV (up to 96%). The ability in FNA sparing ranges from 10 to 38% and reaches 44.2% of potential FNA economization in the low-risk macro-group. Considering our cohort, ACRTIRADS and AACE/ACE-AME scores provide the best compromise in terms of accuracy and spared cytology.ConclusionsDespite several limitations, available NUS do appear to assist physicians in clinical practice. In the context of a common disease, such as thyroid nodules, higher accuracy and NPV are desirable NUS features. Further improvements in NUS sensitivity and specificity are attainable future goals to optimize nodule management.Key Points• Thyroid nodule ultrasound scores do assist clinicians in real practice.• Ultrasound scores reduce unnecessary diagnostic procedures, containing indolent thyroid microcarcinoma overdiagnosis.• The variable malignancy risk of the “indeterminate” category negatively influences score’s performance in real-life management of thyroid lesions.

Real-life management of neovascular age-related macular degeneration (nAMD) in France: a nationwide observational study using retrospective claims data

Aims Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is standard care for neovascular age-related macular degeneration (nAMD), but the recommended monthly injection regimen is burdensome. Evidence suggests low injection/monitoring frequencies in clinical practice and suboptimal vision outcomes. This observational cohort study uses administrative claims data from the French national healthcare system to assess anti-VEGF treatment patterns and nAMD-specific healthcare resource demands and costs. Patients and methods nAMD patients ≥50 years initiating intravitreal ranibizumab, aflibercept or bevacizumab treatment (2014‒2015), and propensity score-matched non-nAMD patients (controls), were identified from the Echantillon Généraliste de Bénéficiaires database. Outcomes of interest included anti-VEGF treatment patterns, and healthcare resource utilization and associated costs of patients vis-à-vis controls over 24 months. Results Study patients (n = 355) received (mean) 5.2 and 2.4 anti-VEGF injections over 0‒12 and 12‒24 months, respectively. Most patients (79.0%) remained on their initial anti-VEGF agent; among treatment switchers, the most common transition was from ranibizumab to aflibercept. During follow-up, nAMD patients were more likely than controls to require ophthalmology visits (99.7% vs. 44.8%), ocular procedures (optical coherence tomography/angiography/fundoscopy) (96.9% vs. 27.2%), cataract surgery (13.0% vs. 6.7%), and medical transports (38.0% vs. 31.9%). Mean numbers of ophthalmology visits (25.1 vs. 1.2) and medical transports (6.0 vs. 3.5) were higher (p<.01) among nAMD patients. Total reimbursed costs were two-fold higher for nAMD patients than controls (mean €16,799 vs. €8,255) due to higher treatment costs (€6,847 vs. €1,156), medical fees (€1,858 vs. €295), hospital fees (€6,396 vs. €5,235), and transport costs (€358 vs. €259). Excess total healthcare cost was (mean) €5,279 and €7,918 over the first 12 and 24 months of treatment, respectively. Conclusions Current intravitreal anti-VEGF treatment and monitoring requirements place a considerable economic burden on the French healthcare system. New intravitreal therapies with extended dosing intervals and predictable efficacy might reduce demand for ophthalmology services.

Venetoclax Plus Hypomethylating Agents for Relapsed/Refractory Acute Myeloid Leukemia (AML) Is Safe and Manageable in the Outpatient Setting

JN and CP equally contributed Introduction In the setting of clinical trials Venetoclax (VEN) combined with hypomethylating agents (HMAs) has shown fair activity in R/R AML and impressive results in treatment-naïve elderly AML patients. However, no clear guidelines are available on real-life management, especially in the outpatient setting. This study involving R/R AML patients treated with VEN combined with HMAs aims to amelioratate physicians' knowledge about the administration of these regimens. Methods This is a single-center retrospective study involving AML patients treated with Venetoclax combined with HMAs. Data were collected in accordance with GCP and Helsinky declaration. Adverse events (AEs) were graded according to CTCAE v4.03. Survival is estimated with Kaplan-Meyer method. Results Thirty-one R/R AML patients have been treated with VEN plus HMAs from March 2018 to March 2020 and completed at least 1 therapy course (range 1-9, median 2, IQR 1.0 - 5.0) (Table 1: patients' characteristics). Seventeen out of 31 (54,8 %) had received intensive chemotherapy as induction therapy. Twenty-two patients (71 %) had already received HMAs therapy, of which 14/31 (45,2 %) as first and only previous line of therapy. VEN was combined with azacitidine in 13/31 (41,9%) and with decitabine in 18/31 patients (58.1 %). The majority of patients (22/31, 70,9%) received the first cycle as out-patients, special focus of our analysis. For clinical reasons, only 9 out of 31 (29,1 %) patients were hospitalized and were used as control. In the outpatients setting, VEN dose escalation was managed with at least a weekly laboratory and clinical monitoring and the drug was often increased more slowly to carefully prevent tumor lysis syndrome or other complications. Specifically, there has been a trend toward a ramp-up schedule different from that indicated in clinical trials in the outpatient setting in comparison with hospitalized patients (77,2 % vs 33,3 %). In term of safety, no cases of tumor lysis syndrome (TLS) and only 2 AEs were documented during ramp-up phase, both experienced by hospitalized patients. Seventeen AEs were documented during cycle 1, affecting more frequently hospitalized patients (77,9% vs 31,8 %). In the outpatient setting, the early 30-days and 60-days mortalities were 4,5 % (1/22) and 13,6 % (3/22), respectively, comparable to percentages documented in hospitalized subgroup (0% and 11,1%). Overall, with a median follow-up of 138 days (IQR 69 - 285), we reported 48 AEs, of which 28 were grade III-IV and the most common were hematological (13/28, 48,1 %) or infective (14/28, 51,8 %). Twenty out of 31 (64,5 %) patients reduced VEN dosage during treatment, of which 12/20 (60 %) due to occurring AEs, and remaining patients for azole coadministration. Eleven out of 31 (35,5 %) patients required hospitalization, specifically 3 out of 9 hospitalized patients (33,3 %) during the subsequent outpatient phase of treatment, and 8/22 (36,3 %) patients who underwent VEN therapy outpatient, of which only 2 during the first 28 days of treatment. Twenty-four and 5 AEs were followed by a VEN temporary (median duration 14 days, range 5-120) and permanent withdrawn, respectively. As for the rate of response, the Overall Response Rate (ORR) by VEN plus HMAs therapy in our R/R study population, defined as CR + CRi + HI, was 41,9 % (13/31), with a CR/CRi rate of 22,6 % (7/31). The median time to first response was 67.0 days (IQR 37.0 - 133.5) and the median duration of response was 131.0 days (IQR 89.0 - 151.0). Four out of 31 (12,9 %) patients received subsequent HSCT. The median OS was 285 days (95% C.I. 178 - 392), with no difference in OS between patients who underwent VEN plus HMAs outpatient and patients who underwent the first cycle hospitalized (p = 0,38). Conclusions With the limitations of a single-center retrospective study, our real-life data indicate that VEN plus HMAs is feasible in an outpatient management, without TLS or other limiting toxicities and with comparable early-mortality and toxicity profiles, even in the ramp-up phase and first therapeutic cycle. There was no significant impact of the outpatient management on treatment effectiveness, with data in line with published R/R AML cohorts. Further studies evaluating the clinical, social and economic impact of outpatient VEN-based treatments are highly warranted. Disclosures Papayannidis: Abbvie, Janssen, Novartis, Amgen, Pfizer:Membership on an entity's Board of Directors or advisory committees, Patents &amp; Royalties.Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive:Consultancy, Honoraria. OffLabel Disclosure: In R/R AML, available data regarding the combination of VEN plus HMAs come only from retrospective studies where VEN is administered as an off-label prescription due to its widespread approval for chronic lymphocytic leukemia due to promising results obtained in treatment-naive elderly AML patients