Electronic Case Report Form Research Articles

Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: A randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU).

After admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. In a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. Adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. In hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

Thoracic outlet syndrome (TROTS) registry: A study protocol for the primary upper extremity deep venous thrombosis section.

There is a lack of comprehensive and uniform data on primary upper extremity deep venous thrombosis (pUEDVT). pUEDVT includes venous thoracic outlet syndrome related upper extremity deep venous thrombosis (UEDVT) and idiopathic UEDVT. Research on these conditions has been hampered by their rarity, lack of uniform diagnostic criteria, and heterogeneity in therapeutic strategies. To improve current research data collection using input of all various pUEDVT treating medical specialists, we initiated the ThoRacic OuTlet Syndrome (TROTS) registry. The aim of the TROTS registry is to a) collect extensive data on all pUEDVT patients through a predefined protocol, b) give insight in the long term outcome using patient reported outcome measures, c) create guidance in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future research. The TROTS registry was designed as an international prospective longitudinal observational registry for data collection on pUEDVT patients. All pUEDVT patients, regardless of treatment received, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition, a survey containing general questions, a Health-related Quality of Life questionnaire (EQ-5D-5L), and Functional Disability questionnaire (Quick-DASH) will be sent periodically (at the time of inclusion, one and two years after inclusion, and every five years after inclusion) to the participant. The registry protocol was approved by the Medical Ethical Review Board and registered in the Netherlands Trial Register under Trial-ID NL9680. The data generated by the registry will be used for future research on pUEDVT and published in peer reviewed journals. TROTS registry data will be used to further establish the optimal management of pUEDVT and lay the foundation for future research and guidelines.

Fatigue visual analogue scale score correlates with quality of life in cancer patients receiving epoetin alfa (Sandoz) for chemotherapy-induced anaemia: The CIROCO study

PurposeAvailable tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. MethodsThis was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). ResultsThe study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. ConclusionTreatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.

Clinical Source Data Production and Quality Control in Real-world Studies: Proposal for Development of the eSource Record System.

An eSource generally includes the direct capture, collection, and storage of electronic data to simplify clinical research. It can improve data quality and patient safety and reduce clinical trial costs. There has been some eSource-related research progress in relatively large projects. However, most of these studies focused on technical explorations to improve interoperability among systems to reuse retrospective data for research. Few studies have explored source data collection and quality control during prospective data collection from a methodological perspective. This study aimed to design a clinical source data collection method that is suitable for real-world studies and meets the data quality standards for clinical research and to improve efficiency when writing electronic medical records (EMRs). On the basis of our group's previous research experience, TransCelerate BioPharm Inc eSource logical architecture, and relevant regulations and guidelines, we designed a source data collection method and invited relevant stakeholders to optimize it. On the basis of this method, we proposed the eSource record (ESR) system as a solution and invited experts with different roles in the contract research organization company to discuss and design a flowchart for data connection between the ESR and electronic data capture (EDC). The ESR method included 5 steps: research project preparation, initial survey collection, in-hospital medical record writing, out-of-hospital follow-up, and electronic case report form (eCRF) traceability. The data connection between the ESR and EDC covered the clinical research process from creating the eCRF to collecting data for the analysis. The intelligent data acquisition function of the ESR will automatically complete the empty eCRF to create an eCRF with values. When the clinical research associate and data manager conduct data verification, they can query the certified copy database through interface traceability and send data queries. The data queries are transmitted to the ESR through the EDC interface. The EDC and EMR systems interoperate through the ESR. The EMR and EDC systems transmit data to the ESR system through the data standards of the Health Level Seven Clinical Document Architecture and the Clinical Data Interchange Standards Consortium operational data model, respectively. When the implemented data standards for a given system are not consistent, the ESR will approach the problem by first automating mappings between standards and then handling extensions or corrections to a given data format through human evaluation. The source data collection method proposed in this study will help to realize eSource's new strategy. The ESR solution is standardized and sustainable. It aims to ensure that research data meet the attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available standards for clinical research data quality and to provide a new model for prospective data collection in real-world studies.

Over-prescription of short-acting β2-agonists for asthma in South Africa: Results from the SABINA III study.

Asthma medication prescription trends, including those of short-acting β2 -agonists (SABAs), are not well documented for South Africa (SA). To describe demographics, disease characteristics and asthma prescription patterns in the SA cohort of the SABA use IN Asthma (SABINA) III study. An observational, cross-sectional study conducted at 12 sites across SA. Patients with asthma (aged ≥12 years) were classified by investigator-defined asthma severity, guided by the Global Initiative for Asthma (GINA) 2017 recommendations, and practice type (primary/ specialist care). Data were collected using electronic case report forms. Overall, 501 patients were analysed - mean (standard deviation) age, 48.4 (16.6) years; 68.3% female - of whom 70.6% and 29.4% were enrolled by primary care physicians and specialists, respectively. Most patients were classified with moderate-to-severe asthma (55.7%; GINA treatment steps 3 - 5), were overweight or obese (70.7%) and reported full healthcare reimbursement (55.5%). Asthma was partly controlled/uncontrolled in 60.3% of patients, with 46.1% experiencing ≥1 severe exacerbations in the 12 months before the study visit. Overall, 74.9% of patients were prescribed ≥3 SABA canisters in the previous 12 months (over-prescription); 56.5% were prescribed ≥10 SABA canisters. Additionally, 27.1% of patients reported purchasing SABA over-the-counter (OTC); among patients with both SABA purchase and prescriptions, 75.4% and 51.5% already received prescriptions for ≥3 and ≥10 SABA canisters, respectively, in the preceding 12 months. SABA over-prescription and OTC purchase were common in SA, demonstrating an urgent need to align clinical practices with the latest evidence-based recommendations and regulate SABA OTC purchase to improve asthma outcomes. What the study adds. This study provides valuable insights into asthma medication prescription patterns, particularly SABAs, across SA. Collection of this real-world data in patients treated in primary and specialty care demonstrates that SABA over-prescription and SABA OTC purchase are common, even in patients with mild asthma. These findings will enable clinicians and policymakers to make targeted changes to optimise asthma outcomes across the country Implications of the findings. SABA over-prescription represents a major public health concern in SA. Healthcare providers and policymakers will need to work together to promote educational initiatives aimed at patients, pharmacists and physicians, align clinical practices with the latest evidence-based recommendations, improve access to affordable medications and regulate SABA purchase without prescription.

1110 PROGNOSTIC IMPACT OF SIGNIFICANT MITRAL REGURGITATION IN PATIENTS WITH SEVERE LOW FLOW, LOW GRADIENT AORTIC STENOSIS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT

Abstract Aim This study sought to determinate the prevalence, clinical impact, and clinical outcome of significant moderate-to-severe mitral regurgitation (MR) in patients with severe low flow, low gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR). Methods All consecutive patients with severe LFLG-AS undergoing TAVI in two high-volume Italian centres from 2013 to 2022 were prospectively included. LFLG-AS was defined as indexed aortic valve area (iAVA) ≤0.6 cm2/m2, mean transaortic gradient <40 mmHg and stroke volume index <36 ml/m2. LFLG-AS was classified as classical if left ventricular ejection fraction (LVEF) was <50%, and paradoxical in patients with preserved LVEF >50%. Demographic, clinical, instrumental, and procedural features were systematically collected by using an electronic case report form. MR severity was graded according to the current guidelines, and patients were categorized based on the MR severity at baseline in two groups: mild and moderate-to-severe MR. The primary study outcome was the composite of all-cause mortality and rehospitalization for worsening heart failure (HF) up to 1 year; secondary outcomes were the single components of the primary outcome. Results The study included 268 patients [81±6 years; 142 (53%) females]; moderate-to-severe MR was reported in 57 patients (21%). At baseline moderate-to-severe MR compared to those with mild MR showed statistically significant differences between age (p 0.008), female sex (p 0.007), hypertension (p 0.036), diabetes (p 0.001) atrial fibrillation/flutter (p 0.018) and chronic kidney disease (p 0.012). In the overall population, only one patient died during the hospitalization and at one-year follow-up, the primary outcome was reported in 49 patients (18%); all-cause death occurred in 26 (10%), and HF rehospitalization in 24 (9%). Regarding the two subgroups, Kaplan-Meier curves showed that survival free from the composite outcome was significantly lower in patients with moderate-to-severe MR compared to those with mild MR (Log Rank <0.001, Figure 1A). Survival free from all-cause mortality and HF rehospitalization was also significantly lower in patients with moderate-to-severe MR (Log-Rank <0.001 and Log-Rank=0.002, respectively; Figure 1B and 1C). Conclusion In this study, many patients with LFLG-AS undergoing TAVR had coexisting moderate-to-severe MR. TAVI confirmed a high safety profile, LFLG-AS patients showed a high incidence of adverse events up to 1 year, especially those with coexisting moderate-to-severe MR. Moderate-to-severe MR should be duly considered for better prognostic stratification and clinical management of these particular TAVR patients during follow-up. Figure 1

Modern thromboprophylaxis protocol based on guidelines applied in a respiratory intensive care unit: a single-center prospective cohort study

BackgroundCritically ill patients in intensive care units (ICUs) are at high risk of venous thromboembolism (VTE). This study aimed to explore the prophylaxis effect under a guideline-based thromboprophylaxis protocol among critically ill patients in a respiratory ICU.MethodsFor this single-center prospective cohort study, we followed the thromboprophylaxis protocol, which was drawn up based on relevant guidelines and Chinese experts’ advice. Clinical data were entered into an electronic case report form and analyzed. Multivariate logistic regression was conducted to explore independent risk factors of VTE event under this protocol.ResultsFrom August 1, 2014, to December 31, 2020, 884 patients underwent thromboprophylaxis according to this protocol; 10.5% of them received mechanical prophylaxis, 43.8% received pharmacological prophylaxis, and 45.7% received pharmacological combined with mechanical prophylaxis. The proportion of VTE events was 14.3% for patients who received the thromboprophylaxis protocol, of which 0.1% had pulmonary thromboembolism (PTE), 2.0% had proximal deep vein thrombosis (DVT), and 12.1% had isolated distal DVT. There was no significant difference between different thromboprophylaxis measures. Cirrhosis (OR 5.789, 95% CI [1.402, 23.894], P = 0.015), acute asthma exacerbation (OR 39.999, 95% CI [4.704, 340.083], P = 0.001), and extracorporeal membrane oxygenation treatment (OR 22.237, 95%CI [4.824, 102.502], P < 0.001) were independent risk factors for proximal DVT under thromboprophylaxis.ConclusionsThe thromboprophylaxis protocol based on guidelines applied in the ICU was practicable and could help decrease the proportion of PTE and proximal DVT events. The risk factors of VTE events happening under the thromboprophylaxis protocol require more attention.Trial registrationClinicalTrials.gov: NCT02213978.

IMbrave150: Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: An Exploratory Analysis of the Phase III Study

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) stage B disease. Methods: Patients with systemic treatment-naive unresectable HCC and Child-Pugh class A liver function were randomized 2:1 to receive 1,200 mg of atezolizumab plus 15 mg/kg of bevacizumab or 400 mg of sorafenib. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in the BCLC stage B subgroup. Patients in this analysis had BCLC stage B disease at baseline per electronic case report form. Secondary efficacy endpoints included the objective response rate (ORR) and change in the sum of longest diameters (SLD) of target lesions from baseline per IRF RECIST 1.1 and modified RECIST (mRECIST) for HCC. Results: Of 501 enrolled patients, 74 (15%) had BCLC stage B disease at baseline (atezolizumab + bevacizumab, n = 49; sorafenib, n = 24). For this group, median follow-up was 19.7 months. A trend toward improved OS and PFS per IRF RECIST 1.1 was observed with atezolizumab + bevacizumab versus sorafenib (OS: hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.29, 1.34; PFS: HR: 0.64; 95% CI: 0.36, 1.12). ORRs per IRF RECIST 1.1 and HCC mRECIST were 43% and 50% with atezolizumab + bevacizumab and 26% and 30% with sorafenib, respectively. Percentage change in SLD of target lesions from baseline per IRF RECIST 1.1 and HCC mRECIST showed durable responses with atezolizumab + bevacizumab treatment. Safety data were consistent with known profiles of atezolizumab and bevacizumab, as seen in the overall study population. Discussion/Conclusion: Efficacy benefits were observed with atezolizumab + bevacizumab in patients with baseline BCLC stage B disease, consistent with the intention-to-treat population.

Treatment Patterns, Tolerance, and Clinical Response of Chronic Phase Chronic Myeloid Leukemia (CML-CP) Patients (Including Those Harboring the T315I Mutation) Experiencing Multiple Tyrosine Kinase Inhibitor Failure: A Multi-Center Retrospective Chart Review Analysis

Background Despite the remarkable efficacy of adenosine triphosphate-competitive tyrosine kinase inhibitors (TKIs) for chronic phase chronic myeloid leukemia (CML-CP) treatment, about one-third of newly TKI-treated CML patients switch to an alternative TKI over time due to TKI-intolerance or -resistance. These patients currently represent a major clinical burden among patients previously exposed to TKIs. In addition, the presence of the BCR::ABL1 T315I mutation further complicates the clinical management of patients with CML-CP as the mutation is associated with worse prognosis. Objective The aim of this study is to describe "real-world” treatment patterns, clinical outcomes, and adverse events (AEs) in CML-CP patients receiving 3 or more lines of therapy (3L+) and those with the ABL1 T315I mutation. Methods A retrospective chart review study was conducted at 3 large clinical institutions for CML in France. De-identified demographic and clinical data for adult patients diagnosed with CML-CP and treated in 3L+ or harboring the T315I mutation between 2006 and 2021 were abstracted from medical charts using electronic case report form. Descriptive statistics were used to summarize patient characteristics, clinical outcomes during 3L treatment, and AEs. The Kaplan-Meier method was used to determine the cumulative incidence of patients with a major molecular response (MMR) or deep molecular response (DMR: MR4.0 or MR4.5). Results This study included 157 adult patients with CML-CP in 3L+ and 17 adult patients with the T315I mutation. In the 3L+ cohort (median age [interquartile range] at diagnosis, 56 [43-65] years; 44% female; Sokal scores: 22% low, 34% intermediate, 29% high, 15% unknown), 16% of patients had 5L+. In 1L (median duration: 23 [9-66] months), 80% of patients received imatinib. In 2L (median duration: 21 [6-41] months), almost 90% patients received either nilotinib or dasatinib. In 3L (median duration: 17 [5-47] months), TKIs received were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Treatment-free remission (TFR) was observed in 16 (10%) patients in 3L (median duration: 45 [22-64] months); the last reported treatments were dasatinib (n=10) and nilotinib (n=6) for these patients. Among the 16 patients in TFR, 5 (31%) were intolerant to 3L TKI. In 145 patients with documented responses in 3L, the rate of achieving MMR, MR4.0, and MR4.5 at 12 months was 42%, 27%, and 14%, respectively. AEs were documented in 139/157 patients (89%) in 3L. The median overall survival since 3L treatment initiation was 12 (8-16) years. The median number of AEs per patient was 2 in 3L; infections (18%) and asthenia (13%) were the most common AEs. Among patients harboring the ABL1 T315I mutation (median age at diagnosis, 52 [39-59] years; 24% female; Sokal scores: 6% low, 12% intermediate, 65% high, 18% unknown), 41% had 5L+. The T315I mutation was identified in 2L (N=6, 35%), 3L (N=5, 29%), 4L (N=4, 24%), and 5L (N=2, 12%). Median duration of the index line of treatment was 11 months. Ponatinib was the most common TKI used in these T315I+ patients (N=10, 59%) following the identification of the mutation. Other therapies included dasatinib (N=3, 18%), allogeneic stem cell transplant (N=2, 12%), and asciminib through compassionate use or clinical trial (N=2, 12%). Thrombocytopenia (18%) was the most common AE in patients with T315I mutation. The median OS since T315I identification was 5 (3-10) years. Conclusion In this analysis, CML-CP patients with at least 3 lines of treatment and patients harboring the T315I mutation switched up to 7 lines of therapy. In both 3L+ and T315I cohorts, patients switched between first-, second-, and third-generation TKIs (Figure 1). The most common reasons for treatment discontinuation in 1L, 2L, and 3L, including patients with T315I mutation were intolerance and resistance. Earlier lines of treatment lasted less than 2 years in CML-CP patients in 3L and less than 1 year in CML patients harboring the T315I mutation, indicating that there is a substantial unmet need for novel therapeutics with improved safety and efficacy profiles early in the treatment course. Figure 1. a. Sankey diagram for patients with chronic myeloid leukemia with at least three lines of treatment. b. Sankey diagram for patients with chronic myeloid leukemia with T315I mutation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Brazilian Real-Life Experience of Multiple Myeloma Patients: Final Results from the Mmybrave Multi-Center Study

Background: Despite incremental therapeutic improvements for patients (pt) with multiple myeloma (MM) over the past two decades, large discrepancies still exist worldwide in outcomes and in terms of access to novel agents and stem-cell transplantation (SCT). Moreover, the real-world effectiveness of novel therapies may not reflect pt profiles and outcomes from clinical trials. Management of MM in Brazil is subject to constraints that may impact clinical outcomes, and continual assessment of trends in treatment patterns and results in real life is warranted. Methods: The objective of MMyBRAve (NCT03506386) was to investigate the demographic and clinical characteristics, as well as the patterns of care and treatment results, for patients with MM treated at selected experienced hematology/oncology centers in Brazil. Eligible pts were aged ≥18 years and had been diagnosed with MM using contemporaneous IMWG criteria between 01/2008 and 12/2016. Demographic and clinical data were collected from institutional charts retrospectively between 06/2018 and 08/2019 using a dedicated electronic case report form. Treatment and patient evaluation were left to local standards of care. Baseline pt and disease characteristics, as well as treatment patterns, were analyzed descriptively. The overall survival (OS) was analyzed using the Kaplan-Meier method, and predictors of OS were explored using Cox proportional-hazards model. The OS was compared between subgroups defined according to selected baseline characteristics, eligibility to transplantation (Tx) at baseline, and type of institution (public vs private). Results: 17 institutions (Inst) contributed data from 943 pts, who had a mean age of 68.4 years (range, 29 to 103). Females comprised 46.3% of the pts, and 61.1% were reportedly White. Considering the 792 pts with information on immunoglobulin (Ig) isotype, 57.7% had IgG, 21.2% IgA, 16.9% light-chain only, non-secretory in 3.5%, and IgD, IgE or IgM in 0.6%. International Staging System (ISS) stage at diagnosis was I in 19.3%, II in 21.3%, III in 26.6%, and unknown in 32.8%. 491 (52.1%, 95% confidence interval [CI], 48.9% to 55.3%) pts were considered Tx-ineligible at baseline. 452 (47.9%, 95% CI, 44.7% to 51.1%) pts were considered Tx-eligible, and 250 (55.3% of 452; 95% CI, 50.6% to 60.0%) underwent Tx as part of frontline therapy. Overall, after a median follow-up of 63 months, the median OS was 70 months, with OS probabilities of 87% at 12 months, 78% at 24, 70% at 36, 62% at 48, and 55% at 60 months. Tx-ineligible pts were significantly older and had significantly higher levels of creatinine and lactic dehydrogenase (LDH), and more advanced ISS than Tx-eligible pts. Median OS times were 49 and 93 months for Tx-ineligible and Tx-eligible patients, with a hazard ratio (HR) of 0.52 favoring Tx-eligible (95% CI, 0.43 to 0.63; P<0.001). 519 pts came from public Inst, and 424 from private. The former had significantly lower levels of hemoglobin and significantly higher levels of creatinine, calcium and LDH, and more advanced ISS than pts from private Inst. Median OS in these two groups were 61 and 74 months, with a HR of 0.78 favoring pts from private Inst (95% CI, 0.64 to 0.94; P=0.010). Pts from public Inst were more likely to receive melphalan- or thalidomide-based frontline regimens, whereas those from private Inst were more likely to receive bortezomib in frontline. Other univariable baseline factors associated with OS were age, hemoglobin, creatinine, calcium, and Durie-Salmon stage. In multivariable analysis for factors associated with OS, all these remained significant, and so was Inst (HR=0.61, P=0.002). Although there was no significant difference in Tx eligibility between public and private Inst (46.1% vs 50.2%; P=0.224) or in the percentage of patients undergoing Tx (24.5% vs 29.0%; P=0.134), adding this variable to the multivariable model for OS suggested that it confounds the association between type of Inst and OS, since Tx eligibility became a stronger prognostic factor (HR=0.586, P<0.001) than type of Inst (HR=0.81, P=0.073). Conclusions: Comparing these results with those from previous studies, the OS of pts with MM is improving in Brazil. Discrepancies remain in OS for patients from public and private institutions. Although the reasons for this finding remain to be ascertained, differential access to novel therapies cannot be ruled out as a determining factor.

Predictive risk factors of phenoconversion in idiopathic REM sleep behavior disorder: the Italian study “FARPRESTO”

Most patients with idiopathic REM sleep behavior disorder (iRBD) will develop an overt α-synucleinopathy over time, with a rate of phenoconversion of 73.5% after 12 years from diagnosis. Several markers of phenoconversion were identified; however, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without standardized data collection methods. The risk FActoRs PREdictive of phenoconversion in idiopathic REM sleep behavior disorder: the Italian STudy (FARPRESTO) is a multicentric longitudinal retrospective and prospective study with a cohort of incident (prospective recruitment) and prevalent (retrospective recruitment) iRBD patients, whose primary aim is to stratify the risk of phenoconversion, through the systematic collection by means of electronic case report forms of different biomarkers. Secondary aims are to (1) describe the sociodemographic and clinical characteristics of patients with iRBD; (2) collect longitudinal data about the development of α-synucleinopathies; (3) monitor the impact of iRBD on quality of life and sleep quality; (4) assess the correlation between phenoconversion, cognitive performance, and loss of normal muscle atony during REM sleep; (5) identify RBD phenotypes through evaluating clinical, biological, neurophysiological, neuropsychological, and imaging biomarkers; and (6) validate vPSG criteria for RBD diagnosis. The FARPRESTO study will collect a large and harmonized dataset, assessing the role of different biomarkers providing a unique opportunity for a holistic, multidimensional, and personalized approach to iRBD, with several possible application and impact at different levels, from basic to clinical research, and from prevention to management. The FARPRESTO has been registered at clinicaltrials.gov (NCT05262543).

Sociodemographic Characteristics and Comorbidities of Patients With Long COVID and Persistent Olfactory Dysfunction

Determining the characteristics, type, and severity of olfactory dysfunction in patients with long COVID is important for the prognosis and potential treatment of the affected population. To describe the sociodemographic and clinical features of patients with long COVID who develop persistent olfactory dysfunction. This cross-sectional study, conducted at a rehabilitation center at a public university in the Amazon region of Brazil between September 9, 2020, and October 20, 2021, comprised 219 patients with long COVID and self-reported neurologic symptoms. Of these 219 patients, 139 received a diagnosis of chronic olfactory dysfunction, as confirmed by the Connecticut Chemosensory Clinical Research Center (CCCRC) test. Clinical diagnosis of long COVID. Electronic case report forms were prepared for the collection of sociodemographic and clinical data. Patients' sense of smell was evaluated via a CCCRC test, and the association of olfactory dysfunction with aspects of daily life was recorded using a questionnaire. Of the 219 patients included in the study, 164 (74.9%) were women, 194 (88.6%) were between 18 and 59 years of age (mean [SD] age, 43.2 [12.9] years), 206 (94.1%) had more than 9 years of education, and 115 (52.5%) had a monthly income of up to US $192.00. In the study group, 139 patients (63.5%) had some degree of olfactory dysfunction, whereas 80 patients (36.5%) had normosmia. Patients with olfactory dysfunction had a significantly longer duration of long COVID symptoms than those in the normosmia group (mean [SD], 242.7 [101.9] vs 221.0 [97.5] days; P = .01). Among patients with anosmia, there was a significant association between olfactory dysfunction and daily activities, especially in terms of impairment in hazard detection (21 of 31 patients [67.7%]), personal hygiene (21 of 31 patients [67.7%]), and food intake (21 of 31 patients [67.7%]). Univariable logistic regression analyses found that ageusia symptoms were associated with the occurrence of olfactory dysfunction (odds ratio [OR], 11.14 [95% CI, 4.76-26.07]; P < .001), whereas headache (OR, 0.41 [95% CI, 0.22-0.76]; P < .001) and sleep disorders (OR, 0.48 [95% CI, 0.26-0.92]; P = .02) showed an inverse association with the occurrence of olfactory dysfunction. Olfactory dysfunction is one of the most important long-term neurologic symptoms of COVID-19, with the highest prevalence seen among women, adults, and outpatients. Patients with olfactory dysfunction may experience persistent severe hyposmia or anosmia more than 1 year from the onset of symptoms, suggesting the possibility of the condition becoming a permanent sequela.

Quality of life, disease activity and preferences for administration routes in rheumatoid arthritis: a multicentre, prospective, observational study.

ObjectiveWe aimed to evaluate quality of life (QoL), disease activity, compliance to treatment, patient and physician preferences for route of administration (RoA), status of health and pain in RA patients starting advanced treatments or needing a switch, and the factors associated with patient preferences.MethodsA multicentre, prospective, observational and 1-year follow-up study was conducted, between 2015 and 2020, in adult RA patients using advanced treatments for the first time or needing a switch in their current treatments. All the data collected were entered into electronic case report forms. DAS in 28 joints with ESR [DAS28-4(ESR)], EuroQol 5-Dimensional Questionnaire (EQ-5D), HAQ Disability Index (HAQ-DI), Compliance Questionnaire for Rheumatology (CQR-19), Work Productivity and Activity Impairment Instrument (WPAI) and Patient Global Assessment-Visual Analogue Scale (PGA-VAS) questionnaires were used for longitudinal assessments.ResultsFour hundred and fifty-nine patients were enrolled. Three hundred and eight patients (67.1%) attended the final study visit at 12 months and were included for comparative analyses. Irrespective of RoA, the disease activity and QoL improved significantly at 12 months, whereas compliance worsened. At baseline and 12 months, EQ-5D and DAS28-4(ESR) scores were significantly correlated (P < 0.001). The WPAI scores changed significantly in favour of better outcomes over 12 months after initiation of advanced treatment or switching (P < 0.001). A higher proportion of patients preferred an oral RoA, in comparison to physicians (53.6% vs 31.4%; P < 0.001). Patient and physician RoA preferences were independent of gender, age, disease duration, advanced treatment type and the EQ-5D-3L, DAS28-4(ESR), HAQ-DI, PGA-VAS and CQR-19 scores at baseline.ConclusionThe oral route was more frequently preferred by patients compared with physicians, although patients’ preference rates showed a slight increase towards the end of the treatment, which might be an important factor for RA outcomes. Better control of disease activity and QoL were achieved at 12 months, regardless of RoA.

825P CemiplimAb-rwlc Survivorship and Epidemiology (CASE): A prospective study of the safety and efficacy of cemiplimab in patients (pts) with advanced cutaneous squamous cell carcinoma (CSCC) in a real-world setting

Cemiplimab is the first programmed cell death-1 inhibitor approved for the treatment of pts with locally advanced or metastatic CSCC who are not candidates for curative surgery or curative radiation. Here, we describe demographics, effectiveness, and safety results of cemiplimab in a general population of pts with advanced CSCC enrolled in the CASE study (NCT03836105). CASE is a real-world study evaluating the effectiveness, safety, disease evolution, survivorship, and quality of life of pts with advanced CSCC treated in 43 US academic and community centres. Pts had received cemiplimab 350 mg intravenously every 3 weeks per standard of care. Prospective data are captured using an electronic case report form and include demographics, disease characteristics, efficacy, and quality-of-life data. Investigator assessment of objective response rate (ORR), survival, and safety was conducted. Data collected between June 2019 and October 2021 are presented. Recruitment is ongoing. As of 1 Oct 2021, 188 pts were enrolled in the CASE study. Median age was 76.0 years (range, 33.0–98.0), 76.9% were male, 90.9% were White, and 36 (19.1%) were considered immunocompromised or immunosuppressed (IC/IS). Median duration of cemiplimab exposure for all pts was 22.1 weeks (quartile [Q] 1–Q3, 9.1–46.4; range, 0–117). Efficacy was evaluated in pts enrolled before Cycle 3 (n=164), when a clear treatment outcome could be established. ORR for the overall population was 42.1% (95% confidence interval [CI], 34.4–50.0) and for the IC/IS population (n=27) was 44.4% (95% CI, 25.5–64.7). Eight (4.3%) pts experienced a treatment-related serious adverse event and 47 (25.3%) experienced a treatment-related immune-related adverse event. Cemiplimab was generally well tolerated in IC/IS pts. In total, 95 (48.2%) pts discontinued treatment. At this timepoint, the safety, tolerability, and effectiveness of cemiplimab in this real-world study of pts with advanced CSCC were consistent with results observed in the registration clinical trial (NCT02383212, NCT02760498).

Acute care for patients exposed to a chemical attack: protocol for an international multicentric observational study

IntroductionThe use of weapons of mass destruction against civilian populations is of serious concern to public health authorities. Chemical weapons are of particular concern. A few studies have investigated medical...

Over-prescription of short-acting β2-agonists is associated with poor asthma outcomes: results from the African cohort of the SABINA III study

Background The extent of short-acting β2-agonist (SABA) overuse in Africa remains poorly documented. As part of the SABA use IN Asthma (SABINA) III study, we assessed SABA prescriptions/clinical outcomes in 3 African countries. Methods Data on disease characteristics/asthma treatments were collected from patients (≥12 years) using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma) and practice type (primary/specialist care). Multivariable regression models analyzed associations between SABA prescriptions and outcomes. Results Data from 1778 patients (mean age, 43.7 years) were analyzed. Most patients were female (62.4%) and had moderate-to-severe asthma (63.3%), with 57.1 and 42.9% of patients treated in specialist and primary care, respectively. Asthma was partly controlled/uncontrolled in 66.2% of patients, with 57.9% experiencing ≥1 severe exacerbation in the previous 12 months. Overall, 46.5% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (over-prescription); 26.2% were prescribed ≥10 canisters. SABAs were purchased over-the-counter by 32.6% of patients, of whom 79.3% had received SABA prescriptions; 71.9% and 40.1% for ≥3 and ≥10 canisters, respectively. Higher SABA prescriptions (vs. 1–2 canisters) were associated with increased incidence rate of severe exacerbations and lower odds of having at least partly controlled asthma (except 3–5 canisters). Conclusions Findings from this African cohort of the SABINA III study indicate that SABA over-prescription and SABA over-the-counter purchase are common and associated with poor asthma-related outcomes. This highlights the need for healthcare providers/policymakers to align clinical practices with the latest treatment recommendations.

Neural Net Modeling of Checkpoint Inhibitor Related Myocarditis and Steroid Response.

BackgroundSerious but rare side effects associated with immunotherapy pose a difficult problem for regulators and practitioners. Immune checkpoint inhibitors (ICIs) have come into widespread use in oncology in recent years and are associated with rare cardiotoxicity, including potentially fatal myocarditis. To date, no comprehensive model of myocarditis progression and outcomes integrating time-series based laboratory and clinical signals has been constructed. In this paper, we describe a time-series neural net (NN) model of ICI-related myocarditis derived using supervised machine learning.MethodsWe extracted and modeled data from electronic medical records of ICI-treated patients who had an elevation in their troponin. All data collection was performed using an electronic case report form, with approximately 300 variables collected on as many occasions as available, yielding 6000 data elements per patient over their clinical course. Key variables were scored 0–5 and sequential assessments were used to construct the model. The NN model was developed in MatLab and applied to analyze the time course and outcomes of treatments.ResultsWe identified 23 patients who had troponin elevations related to their ICI therapy, 15 of whom had ICI-related myocarditis, while the remaining 8 patients on ICIs had other causes for troponin elevation, such as myocardial infarction. Our model showed that troponin was the most predictive biomarker of myocarditis, in line with prior studies. Our model also identified early and aggressive use of steroid treatment as a major determinant of survival for cases of grade 3 or 4 ICI-related myocarditis.ConclusionOur study shows that a supervised learning NN can be used to model rare events such as ICI-related myocarditis and thus provide clinical insight into drivers of progression and treatment outcomes. These findings direct attention to early detection biomarkers and clinical symptoms as the best means of implementing early and potentially life-saving steroid treatment.

Inclusion of pregnant and breastfeeding women in nonobstetrical randomized controlled trials

There is an urgent need to prioritize and expedite the inclusion of pregnant and breastfeeding women in research. Characterizing trials that have successfully included these populations could inform the design and execution of future studies. In addition, up-to-date data on their inclusion in clinical research could assist in setting benchmarks, establishing targets, and monitoring progress toward more equitable inclusion. This study aimed to characterize the eligibility and enrollment of pregnant and breastfeeding women in randomized controlled trials evaluating interventions for nonobstetrical conditions experienced by, but not limited to, these populations. We developed a literature search in collaboration with an information specialist. We included randomized controlled trials published between 2017 and 2019 in the 5 highest-impact general medicine journals and the 3 highest-impact specialty journals in cardiovascular disease, critical care, general infectious diseases, HIV, and psychiatry. We included randomized controlled trials that evaluated screening, diagnosis, prevention, or treatment of nonobstetrical medical conditions. We excluded randomized controlled trials exclusively focused on males, pediatrics, geriatrics, oncology, or postmenopausal women, and publications reporting subgroup, pooled, or follow-up analyses of previously published randomized controlled trials. We screened titles and abstracts independently and in duplicate, with discrepancies resolved by a third reviewer. We entered data into a standardized electronic case report form. We reviewed study protocols, appendices, and trial registries for additional data. Of the 1333 randomized controlled trials, pregnant and breastfeeding women were eligible for 13 (1.0%) and 6 (0.5%), respectively. Pregnancy and breastfeeding eligibility criteria were not addressed in 383 of 1333 (28.7%) and 710 of 1333 (53.3%) randomized controlled trials, respectively. In total, 102 of 937 (10.9%) and 33 of 617 (5.3%) randomized controlled trials that explicitly excluded pregnant and breastfeeding women documented the rationale. Most studies excluding pregnant women (542/937; 57.8%) required at least 1 method of contraception and/or pregnancy testing as part of trial participation for women with reproductive capacity. Among the 13 randomized controlled trials that allowed inclusion of pregnant women, 3 restricted eligibility to specific trimesters. Two randomized controlled trials enrolled pregnant women after the first year of the study following interim review of safety results in nonpregnant participants. Four randomized controlled trials reported the number of pregnant women enrolled, which ranged from 0.7% to 3.4% of the study population. None of the studies reported on pregnancy or perinatal outcomes. Compared with randomized controlled trials that excluded pregnant women, those including them more commonly had an infectious disease focus (12/13 [92.3%] vs 270/937 [28.8%]; p<.0001), including HIV (5/13 [38.5%] vs 96/937 [10.2%]; p=.0079), enrolled participants in sub-Saharan Africa (5/13 [38.5%] vs 111/937 [11.8%]; p=.0143), and had exclusively nonindustry sponsorship (13/13 [100%] vs 559/937 [59.7%]; p=.0025); inclusion varied by study phase, randomization level, and intervention type. This study illustrates a major inequity in research involving pregnant and breastfeeding women. As new health challenges arise, including novel pandemics, and the research community mobilizes to develop therapies and innovate in patient care, it is crucial that pregnant and breastfeeding women not be left behind. Greater regulatory support, in the form of explicit requirements and incentives, will be needed to ensure these populations are integrated into the research agenda.

The German Cardiosurgery Atrial Fibrillation Registry: 1-Year Follow-up Outcomes.

This study of German Cardiosurgery Atrial Fibrillation (CASE-AF) registry aims to describe the 1-year outcomes of patients undergoing ablative procedures for atrial fibrillation (AF) in a cardiosurgical setting. Between January 2017 and April 2020, 17 German cardiosurgical units enrolled 1,000 consecutive patients undergoing concomitant or stand-alone ablation for AF. In-hospital and 1-year follow-up data were collected on web-based electronic case report forms. The protocol mandated telephone-based follow-up contact after 1 year. At 1-year follow-up (median, 14.5 months [12.6-18.2 months]), significant improvement (p < 0.0001) in baseline modified European Heart Rhythm Association Class I was reported in both concomitant and stand-alone patients. Follow-up examinations were completed in 97.9% of cases, and a sinus rhythm was reported in 60.2 and 63.6% of stand-alone and concomitant patients, respectively. Statistically significant factors determining late recurrence were female gender (p = 0.013), preoperative persistent AF (p < 0.0001), and presence of cardiac implantable electronic device (p = 0.011). All-cause mortality at 1 year was 1% (n = 1) in stand-alone patients and 6.7% (n = 58) in concomitant patients. Surgical ablation of AF is safe and provides satisfactory results at short-term follow-up, with significant improvement in patient symptoms. Adequate cardiac rhythm monitoring should be prioritized for higher quality data acquisition.

Management of Acute Coronary Syndrome Indonesia : Insight from One ACS Multicenter Registry

Background&#x0D; Acute coronary syndrome (ACS) is a life-threatening disorder which contributes to high morbidity and mortality in the world. Registry of ACS offers a great guidance for improvement and research. We collated a multicentre registry to gain information about demographic, management, and outcomes of ACS in Indonesia.&#x0D; Methods&#x0D; IndONEsia Acute Coronary Syndrome Registry (One ACS Registry) was a prospective nationwide multicenter registry with 14 hospitals participating in submitting data of ACS via standardized electronic case report form (eCRF). Between July 2018 and June 2019, 7634 patients with ACS were registered. This registry recorded baseline characteristics; onset, awareness, and transfer time; physical examination and additional test; diagnosis; in-hospital medications and intervention; complications; and in-hospital outcomes.&#x0D; Results&#x0D; Nearly half of patients (48.8%) were diagnosed with STE-ACS. Most prevalent risk factors were male gender, smoking, hypertension. Patients with NSTE-ACS tended to have more concomitant diseases including diabetes mellitus, dyslipidemia, prior AMI, HF, PCI, and CABG. Majority of ACS patients in our registry (89.4%) were funded by national health coverage. Antiplatelet, anticoagulant, antihypertensive, and statins were prescribed as 24-hours therapy and discharge therapy; however presription of potent P2Y12 inhibitor was low. More STE-ACS patients underwent reperfusion therapy than non-reperfusion (65.2% vs. 34.8%), and primary PCI was the most common method (45.7%). Only 21.8% STE-ACS patients underwent reperfusion strategy within 0-3 hours of onset. Invasive strategy performed in 17.6% of NSTE-ACS patients, and only 6.7% performed early (within &lt;24 hours). Patients underwent early invasive strategy had a shorter median LoS than late invasive strategy (P&lt;0.001). A shorter median LoS also found in intermediate and low risk patients. Mortality rate in our ACS patients was 8.9%; STE-ACS patients showed higher mortality than NSTE-ACS (11.7 vs. 6.2%).&#x0D; Conclusion&#x0D; Our registry showed a comparable proportion between STE- and NSTE-ACS patients, with male gender predominant in middle age. Both STE- and NSTE-ACS sharing the same risk factors. We need an improvement in referral time, especially in patients with STE-ACS. Evidence from our registry showed that there are two issues that need to be addressed in order to improve ACS outcomes: optimal and adequate medical treatment and invasive strategy.