Prospective Monitoring of Newly Marketed Drugs in Frail Older Adults Using Real-World Databases

In recent years several new drugs have been approved for treatment of heart failure and type 2 diabetes. Despite their life-prolonging benefits, uptake of new drugs is often slow among older patients with frailty due to under-representation of frail older adults in pivotal clinical trials and concerns for adverse events. To optimize pharmacotherapy, timely evaluation of the drug benefits and risks is urgently needed. We propose a novel drug monitoring framework that prospectively evaluates the effectiveness and safety of newly marketed drugs for frail and non-frail patients in real-world databases. This framework utilizes a validated claims-based frailty index (CFI) (range: 0-1; frail if ≥0.20) to find early signals for effectiveness and safety of new drugs by updating the analysis at regular intervals as new data become available. In this symposium, we present early results of this prospective monitoring framework for 2 new drug classes using Medicare claims data from the approval date until the end of 2017: 1) angiotensin receptor-neprilysin inhibitor (ARNI) (approved in July 2015) for heart failure with reduced ejection fraction (HFrEF) and 2) sodium-glucose cotransporter-2 inhibitors (SGLT2i) (approved in March 2013) for type 2 diabetes. We first show the uptake of ARNI and SGLT2i over time among the eligible Medicare beneficiaries by clinical characteristics, including frailty. Subsequently we present the results of sequential cohort analysis for the effectiveness and safety results of ARNI and SGLT2i. After these presentations, the panel will discuss the strengths, limitations, and challenges of implementing our monitoring framework in real-world databases.

Continuous Electrical Monitoring in Patients with Arrhythmic Myocarditis: Insights from a Referral Center

Background. The incidence and burden of arrhythmias in myocarditis are under-reported. Objective. We aimed to assess the diagnostic yield and clinical impact of continuous arrhythmia monitoring (CAM) in patients with arrhythmic myocarditis. Methods. We enrolled consecutive adult patients (n = 104; 71% males, age 47 ± 11 year, mean LVEF 50 ± 13%) with biopsy-proven active myocarditis and de novo ventricular arrhythmias (VAs). All patients underwent prospective monitoring by both sequential 24-h Holter ECGs and CAM, including either ICD (n = 62; 60%) or loop recorder (n = 42; 40%). Results. By 3.7 ± 1.6 year follow up, 45 patients (43%) had VT, 67 (64%) NSVT and 102 (98%) premature ventricular complexes (PVC). As compared to the Holter ECG (average 9.5 exams per patient), CAM identified more patients with VA (VT: 45 vs. 4; NSVT: 64 vs. 45; both p < 0.001), more VA episodes (VT: 100 vs. 4%; NSVT: 91 vs. 12%) and earlier NSVT timing (median 6 vs. 24 months, p < 0.001). The extensive ICD implantation strategy was proven beneficial in 80% of the population. Histological signs of chronically active myocarditis (n = 73, 70%) and anteroseptal late gadolinium enhancement (n = 26, 25%) were significantly associated with the occurrence of VTs during follow up, even in the primary prevention subgroup. Conclusion. In patients with arrhythmic myocarditis, CAM allowed accurate arrhythmia detection and showed a considerable clinical impact.

Rotavirus Genotypes in Abuja, Nigeria

Introduction: Nigeria had planned to introduce the rotavirus vaccine in the National Immunisation Programme in 2014, but this has yet to be done. Nigeria has the continent's highest mortality due to diarrhoeal diseases with little information on specific, prevalent genotypes. Aim: The study's main objectives were to identify the predominant rotavirus genotypes and examine the effects of existing local vaccination programs on prevailing rotavirus genotypes and on preventing rotavirus diarrhoea. Methodology: A one-year prospective descriptive study of children under 5 with acute diarrhoea was conducted from June 2018 to May 2019. Children with acute diarrhoea attending Asokoro District Hospital, Abuja. Children without diarrhoea were also recruited as a control group. Rotavirus ELISA and RNA extraction were done with commercially available kits, and positive samples were subjected to RT-PCR and electrophoresis to determine VP7 (G) and VP4 (P) genotypes. Results: Rotavirus-ELISA was positive among 231 (17.8%) children with diarrhoea and 29 (2.2%) of controls, with November, December. The predominant VP7 genotypes was G1 (n=116, 50.2%) followed by G9 (n=66, 28.5%). Viral Protein, VP4 (P) was mostly P [8] (n=143, 74.8%) followed by P [4] (n=21, 10.9%). The predominant genotype combinations found were G1 P [8] (n=108, 46.7%), G9 P [8] (n=62, 26.8%), and G2 P [4] (n=18, 7.7%). Very few mixed infections were found in the study, 2 (0.8%). Among 94 unvaccinated children with rotavirus isolates that were genotyped, G1 P [8] (n=88, 49.4%) and G9 P [8] (n=43, 24.1%) were predominant. Among 32 vaccinated children, G1 P [8] (n=13, 40.2%) and G9 P [8] (n=9, 28.1%) were predominant. Conclusion: The emergence of new genotypes such as G 12 P [4] found in this study emphasize the need for continued prospective monitoring of rotavirus at the molecular level to detect new threats to vaccine programs in future.

Psychiatric polygenic risk scores: Child and adolescent psychiatrists' knowledge, attitudes, and experiences

Objective: Psychiatric polygenic risk scores (PRS) have the potential to transform aspects of psychiatric care and prevention, but there are concerns about their implementation. We sought to assess child and adolescent psychiatrists' (CAP) experiences, perspectives, and potential uses of psychiatric PRS. Methods: A survey of 960 US-based practicing CAP. Results: Most respondents (54%) believed psychiatric PRS are currently at least slightly useful and 87% believed they will be so in five years. Yet, 77% rated their knowledge of PRS as poor or very poor. Ten percent have had a patient/family bring PRS to them, and 25% would request PRS if a patient/caregiver asked. Respondents endorsed different actions in response to a hypothetical child with a top 5th percentile psychiatric PRS but no diagnosis: 48% would increase prospective monitoring of symptoms, 42% would evaluate for current symptoms, and 4% would prescribe medications. Most respondents were concerned that high PRS results could lead to overtreatment and negatively impact patients' emotional well-being. Conclusion: Findings indicate emerging use of psychiatric PRS within child and adolescent psychiatry in the US. Thus, it is critical to examine the ethical and clinical challenges that PRS may generate and begin efforts to promote their informed and responsible use.

Covid-19 as occupational disease in healthcare workers: a brief review of cases in the Clinical Hospital Centre Rijeka, Croatia

The coronavirus disease 19 (COVID-19) pandemic has had a tremendous impact on every facet of private life and work organisation in virtually all social and economic sectors worldwide. People who stand on the first line of defence are healthcare workers (HCWs) risking exposure to infected patients. However, even though they are often affected by COVID-19 and associated somatic and mental health problems, COVID-19 as a new illness was not immediately acknowledged as occupational disease. This is why several groups of HCWs contacted their occupational medicine physicians in 2020 with a request to register the infection with SARS-CoV-2 as occupational disease. In an attempt to support their appeals and show that hospital workers have a high occupational risk of COVID-19, this study presents COVID-19 incidence and symptoms in 100 employees working at 11 clinics of the Clinical Hospital Centre (CHC) Rijeka, Croatia from 1 June to end December 2020. All of them were infected with SARS-CoV-2 and took sick leave, which lasted 13.6±2.6 days in average. This study also looks into the role of occupational medicine physicians in prospective monitoring of acute and long-acting consequences of COVID-19 that might occur in HCWs.

A study on prospective monitoring of adverse drug reactions associated with hematinics at a tertiary care teaching hospital

Introduction: Adverse reactions are the documented hazards of drug treatment and they can happen with any class of drugs and several studies exposed that the incidence is increasing with blood and blood products. Objectives: The main aim of this study is to identify and analyze Adverse Drug Reactions with Hematinics in a tertiary care hospital. Methods: This prospective observational study was conducted for a period of 6 months. Results: A total of 29 ADRs were reported during the study period with a female high proportion (79.31%), more amounts of ADRs were from Obstetrics & Gynecology and General Medicine in which the mainly affected organ systems were the skin (86.20%) and the GIT (13.79%). The hematinics mostly accounted were Iron sucrose (44.82%) followed by ferric carboxy maltose (37.93%) and Iron dextran (17.24%) in which type B reactions were more compared to type A and 72.41% of them were unpredictable. The severity assessment revealed that the majority of them were moderate reactions (62.06%). Out of the reported reactions, 58.62% were definitely preventable and a causality assessment was done which showed that 68.96% of the reactions were probable, possible (20.68%) and conditional (10.34%). Most of the patients (65.51%) were treated with Antihistamines & corticosteroids, with only anti-histamines (24.13%) and no treatment (10.34%). Conclusions: The study concludes that Adverse Drug Reactions with Hematinics are increasing in recent days. Better vigilance is necessary for the implementation of safe and effective treatment with hematinics for each and individual patient.

Effect of monitoring surgical outcomes using control charts to reduce major adverse events in patients: cluster randomised trial

ObjectiveTo determine the effect of introducing prospective monitoring of outcomes using control charts and regular feedback on indicators to surgical teams on major adverse events in patients.DesignNational, parallel, cluster randomised trial embedding a difference-in-differences analysis.Setting40 surgical departments of hospitals across France.Participants155 362 adults who underwent digestive tract surgery. 20 of the surgical departments were randomised to prospective monitoring of outcomes using control charts with regular feedback on indicators (intervention group) and 20 to usual care only (control group).InterventionsProspective monitoring of outcomes using control charts, provided in sets quarterly, with regular feedback on indicators (intervention hospitals). To facilitate implementation of the programme, study champion partnerships were established at each site, comprising a surgeon and another member of the surgical team (surgeon, anaesthetist, or nurse), and were trained to conduct team meetings, display posters in operating rooms, maintain a logbook, and devise an improvement plan.Main outcome measuresThe primary outcome was a composite of major adverse events (inpatient death, intensive care stay, reoperation, and severe complications) within 30 days after surgery. Changes in surgical outcomes were compared before and after implementation of the programme between intervention and control hospitals, with adjustment for patient mix and clustering.Results75 047 patients were analysed in the intervention hospitals (37 579 before and 37 468 after programme implementation) versus 80 315 in the control hospitals (41 548 and 38 767). After introduction of the control chart, the absolute risk of a major adverse event was reduced by 0.9% (95% confidence interval 0.4% to 1.4%) in intervention compared with control hospitals, corresponding to 114 patients (70 to 280) who needed to receive the intervention to prevent one major adverse event. A significant decrease in major adverse events (adjusted ratio of odds ratios 0.89, 95% confidence interval 0.83 to 0.96), patient death (0.84, 0.71 to 0.99), and intensive care stay (0.85, 0.76 to 0.94) was found in intervention compared with control hospitals. The same trend was observed for reoperation (0.91, 0.82 to 1.00), whereas severe complications remained unchanged (0.96, 0.87 to 1.07). Among the intervention hospitals, the effect size was proportional to the degree of control chart implementation witnessed. Highly compliant hospitals experienced a more important reduction in major adverse events (0.84, 0.77 to 0.92), patient death (0.78, 0.63 to 0.97), intensive care stay (0.76, 0.67 to 0.87), and reoperation (0.84, 0.74 to 0.96).ConclusionsThe implementation of control charts with feedback on indicators to surgical teams was associated with concomitant reductions in major adverse events in patients. Understanding variations in surgical outcomes and how to provide safe surgery is imperative for improvements.Trial registrationClinicalTrials.gov NCT02569450.