Self-reported Adverse Events Research Articles

High-load strength training compared with standard care treatment in young adults with joint hypermobility and knee pain: study protocol for a randomised controlled trial (the HIPEr-Knee study)

IntroductionPatients with generalised joint hypermobility, including knee hypermobility (GJHk), often experience knee pain and are typically managed with low-intensity strength training and/or proprioceptive training as part of standard care. However,...

Associations among claims-based care fragmentation, self-reported gaps in care coordination, and self-reported adverse events

BackgroundFragmentation of care (that is, the use of multiple ambulatory providers without a dominant provider) may increase the risk of gaps in communication among providers. However, it is unclear whether people with fragmented care (as measured in claims) perceive more gaps in communication among their providers. It is also unclear whether people who perceive gaps in communication experience them as clinically significant (that is, whether they experience adverse events that they attribute to poor coordination).MethodsWe conducted a longitudinal study using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including a survey on perceptions of healthcare (2017–2018) and linked fee-for-service Medicare claims (for the 12 months prior to the survey) (N = 4,296). We estimated correlation coefficients to determine associations between claims-based and self-reported numbers of ambulatory visits and ambulatory providers. We then used logistic regression to determine associations between claims-based fragmentation (measured with the reversed Bice-Boxerman Index [rBBI]) and self-reported gaps in care coordination and, separately, between claims-based fragmentation and self-reported adverse events that the respondent attributed to poor coordination.ResultsThe correlation coefficient between claims-based and self-report was 0.37 for the number of visits and 0.38 for the number of providers (p < 0.0001 for each). Individuals with high fragmentation by claims (rBBI ≥ 0.85) had a 23% increased adjusted odds of reporting any gap in care coordination (95% CI 3%, 48%) and, separately, a 61% increased adjusted odds of reporting an adverse event that they attributed to poor coordination (95% CI 11%, 134%).ConclusionsMedicare beneficiaries with claims-based fragmentation also report gaps in communication among their providers. Moreover, these gaps appear to be clinically significant, with beneficiaries reporting adverse events that they attribute to poor coordination.

A cross-sectional study of self-reported dietary supplement use, associated factors, and adverse events among young adults in Kuwait

BackgroundDietary supplements (DS) are commonly used to improve overall health status and correct nutritional deficiencies. However, with the global rise in DS use, there is an increased risk of misuse and/or excessive use leading to toxicity and adverse events (AE). Research on DS use and DS-related AE is limited in Kuwait. This study aimed to explore the prevalence of DS use, its associated factors, and reported AE in a population of young adults.MethodsA cross-sectional study was carried out using an online self-administered questionnaire. Non-probabilistic sampling was used via multiple social media platforms. Logistic regression analysis was performed to assess the association between sociodemographic, lifestyle characteristics and health status with DS use and AE.ResultsThe prevalence of DS use was 68.24%. DS use was found to be associated with age (odds ratio [OR] = 1.07, 95% confidence interval [CI] 1.03–1.13; p-value [p] = < 0.001) and being female (OR = 1.55, 95% CI 1.01–2.41; p = 0.047). AE related to DS use were found to be associated with having respiratory disorders (asthma) (OR = 2.09, 95% CI 1.07–4.05; p = 0.029) and digestive disorders (OR = 3.22, 95% CI 1.24–8.35; p = 0.016).ConclusionThe study findings provide valuable insights into current DS use in young adults in Kuwait, which may enable the strategic development of targeted interventions and health promotion awareness campaigns. Furthermore, they emphasize the necessity of implementing regulations and policies to effectively manage DS use and monitor AE reporting in Kuwait.

Gaps in the coordination of care for people living with dementia.

One-third of people living with dementia (PLWD) have highly fragmented care (i.e., care spread across many ambulatory providers without a dominant provider). It is unclear whether PLWD with fragmented care and their caregivers perceive gaps in communication among the providers involved and whether any such gaps are perceived as benign inconveniences or as clinically meaningful, leading to adverse events. We sought to determine the frequency of perceived gaps in communication (coordination) among providers and the frequency of self-reported adverse events attributed to poor coordination. We conducted a cross-sectional study in the context of a Medicare accountable care organization (ACO) in New York in 2022-2023. We included PLWD who were attributed to the ACO, had fragmented care in the past year by claims (reversed Bice-Boxerman Index ≥0.86), and were in a pragmatic clinical trial on care management. We used an existing survey instrument to determine perceptions of care coordination and perceptions of four adverse events (repeat tests, drug-drug interactions, emergency department visits, and hospital admissions). ACO care managers collected data by telephone, using clinical judgment to determine whether each survey respondent was the patient or a caregiver. We used descriptive statistics to summarize results. Of 167 eligible PLWD, surveys were completed for 97 (58.1%). Of those, 88 (90.7%) reported having >1 ambulatory visit and >1 ambulatory provider and were thus at risk for gaps in care coordination and included in the analysis. Of those, 23 respondents were patients (26.1%) and 64 were caregivers (72.7%), with one respondent's role missing. Overall, 57% of respondents reported a problem (or "gap") in the coordination of care and, separately, 18% reported an adverse event that they attributed to poor care coordination. Gaps in coordination of care for PLWD are reported to be very common and often perceived as hazardous.

Air travel in patients suffering from pulmonary hypertension-A prospective, multicentre study.

The PEGASUS study is the first multicentric and prospective assessment of the safety of air travel flying in pulmonary hypertension (PH) (NCT03051763). Data of air travel from 60 patients with PH was available. No severe adverse events occurred. Nine patients self-reported mild adverse events during flight (13%), while after landing, 12 patients reported events (20%). Solely one patient (2%) had an adverse event leading to medical consultation. In patients with PH and World Health Organization functional classes II and III, air travel was safe.

Efficacy and Safety of Xylitol Nasal Irrigation after Functional Endoscopic Sinus Surgery: A Randomized Controlled Study

Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body’s own innate bactericidal mechanisms. It also provides anti-adhesive effects against both Streptococcus pneumoniae and Haemophilus influenza. This study was performed to evaluate the efficacy and safety of xylitol nasal irrigation in the postoperative care of functional endoscopic sinus surgery (FESS). Patients with chronic rhinosinusitis who received FESS were recruited and randomly assigned to two groups at one month post-surgery. Thirty-five patients in the xylitol group received 400 mL of 5% xylitol nasal irrigation daily for 2 months, while another 35 in the normal saline (NS) group received 400 mL of NS nasal irrigation daily for 2 months. Prior to FESS, as well as before and after nasal irrigation, sinonasal symptoms were assessed through the 22-item Sino-Nasal Outcome Test Questionnaire. The patients also underwent an endoscopic examination while undergoing nasal function tests, and a cytokine measurement of the nasal lavage and a bacterial culture from the middle meatus were performed. The safety of the nasal irrigation was assessed through any self-reported adverse events, the Eustachian Tube Dysfunction Patient Questionnaire and the eustachian tube function test. The endoscopic scores and olfactory threshold significantly decreased after xylitol irrigation when compared with those before irrigation. The prevalence of Staphylococcus aureus in the nasal secretions also decreased significantly after xylitol irrigation. The amounts of Interleukin-5 and Interleukin-17A were significantly increased in the nasal lavage after xylitol irrigation. No side effects, including those related to eustachian tube function, were seen after nasal irrigation in both groups. Our results showed that xylitol nasal irrigation was both beneficial and safe during the postoperative care of FESS.

Social Determinants of Health Mediate Racial Disparities in Cardiovascular Disease in Men With Prostate Cancer

BackgroundCardiovascular disease (CVD) is a significant cause of morbidity and mortality in men with prostate cancer; however, data on racial disparities in CVD outcomes are limited. ObjectivesWe quantified the disparities in CVD according to self-identified race and the role of the structural social determinants of health in mediating disparities in prostate cancer patients. MethodsA retrospective cohort study of 3,543 prostate cancer patients treated with systemic androgen deprivation therapy (ADT) between 2008 and 2021 at a quaternary, multisite health care system was performed. The multivariable adjusted association between self-reported race (Black vs White) and incident major adverse cardiovascular events (MACE) after ADT initiation was evaluated using cause-specific proportional hazards. Mediation analysis determined the role of theme-specific and overall social vulnerability index (SVI) in explaining the racial disparities in CVD outcomes. ResultsBlack race was associated with an increased hazard of MACE (HR: 1.38; 95% CI: 1.16-1.65; P < 0.001). The association with Black race was strongest for incident heart failure (HR: 1.79; 95% CI: 1.32-2.43), cerebrovascular disease (HR: 1.98; 95% CI: 1.37-2.87), and peripheral artery disease (HR: 1.76; 95% CI: 1.26-2.45) (P < 0.001). SVI, specifically the socioeconomic status theme, mediated 98% of the disparity in MACE risk between Black and White patients. ConclusionsBlack patients are significantly more likely to experience adverse CVD outcomes after systemic ADT compared with their White counterparts. These disparities are mediated by socioeconomic status and other structural determinants of health as captured by census tract SVI. Our findings motivate multilevel interventions focused on addressing socioeconomic vulnerability.

Safety profile and effects on the peripheral immune response of fecal microbiota transplantation in clinically healthy dogs.

Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated. Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs. Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors. Prospective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR. No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention. Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.

Survival and safety analysis of COVID-19 vaccine in Chinese patients with non-small cell lung cancer.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused a worldwide challenging and threatening pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccines in Non-Small Cell Lung Cancer (NSCLC) patients. Patient self-reported adverse events related to vaccines were recorded by follow-up through a uniform questionnaire. Survival analysis was performed by Kaplan-Meier method. A multivariate analysis was performed by the Cox proportional hazard regression model to determine the effect of each variable on the survival of lung cancer patients. A total of 860 patients with NSCLC on treatment were enrolled. Mean age was 57 years in patients with early stage group and 62 years in advanced stage group. The vaccination rate was 71.11% for early-stage patients and 19.48% for advanced-stage patients; most of them (86.5%) received the COVID-19 inactivated virus (Vero cell) vaccine (Coronavac; Sinovac). The most common systemic adverse reaction was weakness. The main reason for vaccine refusal in those unvaccinated patients was concern about the safety of vaccination in the presence of a tumor and undergoing treatment (56.9% and 53.4%). The 1-year disease-free survival (DFS) rate was 100% for vaccinated and 97.4% for unvaccinated early-stage patients. Then we compared the progression-free survival (PFS) of vaccinated (median PFS 9.0 months) and unvaccinated (median PFS 7.0 months) advanced stage patients (p = 0.815). Advanced NSCLC patients continued to be divided into groups receiving radio-chemotherapy, immunotherapy, and targeted therapy, with no statistical difference in PFS between the groups (p > 0.05). The median overall survival (OS) of vaccinated patients was 20.5 months, and that of unvaccinated patients was 19.0 months (p = 0.478) in advanced NSCLC patients. COVID-19 vaccination is safe for Chinese NSCLC patients actively receiving different antitumor treatments without increasing the incidence of adverse reactions, and vaccination does not affect cancer patient survival.

Short-term effects of Pilates-based exercise on upper limb strength and function in people with Parkinson's disease

BackgroundPeople with Parkinson's disease (PD) have impaired upper limb motor coordination, limiting the execution of activities of daily living. This study investigated the feasibility and safety of a short-term Pilates-based exercise program in the treatment of upper limb motor coordination for people with PD. MethodsFifteen patients – n (%) 4 women/11 men (27/73), median [interquartile range] age 66 [9] years – participated in this quasi-experimental (before-and-after) clinical trial. Patients underwent a 6-week (30 min/day, 3 days/week) Pilates exercise program using Reformer, Cadillac, Chair, and Barrel equipment. Feasibility was evaluated by adherence to the program and the ability to perform the exercises including progressions on difficulty. Safety was evaluated based on self-reported adverse events. Clinical and functional trends before and after the intervention were also computed regarding handgrip strength (HGS), fine motor coordination (9 Hole Peg Test; 9HPT), bradykinesia (Movement Disorder Society – Unified Parkinson's disease Rating Scale; MDS-UPDRS), and upper limb functionality (Test D'évaluation des Membres Supérieurs des Personnes Âgées, TEMPA). ResultsOf the 18 Pilates sessions, exercise adherence was 100%. The only adverse event observed was mild muscle pain. Pre-post differences were observed only for body bradykinesia and hypokinesia (1.0 [0.0] vs. 0.0 [1.0] s, adjusted p = 0.048). ConclusionsA short-term Pilates-based exercise program in the treatment of upper limb muscle strength, manual dexterity, bradykinesia, and functionality is feasible and safe for people with PD. Changes in upper limb bradykinesia encourage randomized clinical trials.

Effect of a Novel Training Program in Patients With Chronic Shoulder Pain Based on Implicit Motor Learning: Pilot and Feasibility Study.

Implicit motor learning has been shown to be effective for learning sports-related motor skills. It facilitates automaticity of movements and thereby improves performance in multitasking and high-pressure environments. Motor learning to develop motor skills and neuroplastic capacities is not sufficiently incorporated in musculoskeletal rehabilitation. Especially in patients with chronic pain conditions like shoulder pain this approach might benefit over traditional exercise programs. The aim of this study was to investigate the feasibility and clinical outcome of a new implicit motor learning exercise program in a group of patients with chronic shoulder pain. Pilot and feasibility cohort study. Twenty-six patients with chronic shoulder pain performed a 6-week home exercise program with weekly remote follow up by a physiotherapist. The program comprised five exercises designed to challenge overall body balance, simultaneously engaging the upper limbs in a range of reaching tasks. The tasks included reaching above the head, at and below waist level, in various directions. No instructions on correct performance were provided to foster external focus. Feasibility was assessed by (1) recruitment rate, (2) follow up rate, (3) subjective experience, (4) self-reported adverse events and (5) self-reported adherence of subjects. Clinical effects of the program were assessed with (1) the Shoulder Pain and Disability Index (SPADI), (2) the Auto-Constant score, (3) the numeric rating scale (NRS) at rest and at night, (4) the patient specific functional scale (PSFS), (5) the avoidance endurance questionnaire (AEQ), (6) patient acceptable symptom state (PASS) and (7) a global rating of change (GROC). The study protocol was feasible in terms of follow up rate (16w for 28 patients), exercise adherence (77.1%± 29.41), and adverse events (no serious, 5 light adverse events). Statistically significant improvements were observed for SPADI (p<0.001), NRS at rest (p=0.033), at night (p=0.29), PSFS (p<0.001) and PASS (p<0.001) after only six weeks training. This study reveals promising results of another way of looking at exercise for patients with chronic shoulder pain. Both feasibility and clinical effects of the program on pain and function was acceptable. Future studies should incorporate a control group, provide longer follow up and include objective measurements. 2b.

Safety of Janssen Ad26.COV.S and Astra Zeneca AZD1222 COVID-19 Vaccines among Mobile Phone Users in Malawi: Findings from a National Mobile-Based Syndromic Surveillance Survey, July 2021 to December 2021

The safety profiles of the Ad26.COV2.S and AZD1222 COVID-19 vaccines have not been described in the general population in Malawi. We present self-reported adverse events (AE) following the receipt of these vaccines in Malawi as part of a national syndromic surveillance survey. We conducted phone-based syndromic surveillance surveys among adults (≥18 years) with verbal consent. We used secure tablets through random digit dialing to select mobile phone numbers and collected data electronically. Survey questions included whether the respondent had received the COVID-19 vaccines, whether they had experienced any AE following vaccination, and the severity of the AE. We used multivariable analysis to identify factors associated with self-reported AE post-COVID-19 vaccination. A total of 11,924 (36.0%) out of 33,150 respondents reported receiving at least one dose of either Ad26.COV2.S or AZD1222 between July–December 2021; of those, 65.1% were female. About 49.2% of the vaccine recipients reported at least one AE, 90.6% of which were mild, and 2.6% were severe. Higher education level and concern about the safety of COVID-19 vaccines were associated with AE self-report (Adjusted Odds Ratio [AOR] 2.63 [95% CI 1.96–3.53] and 1.44, [95% CI 1.30–1.61], respectively), while male gender and older age were associated with reduced likelihood of AE self-report (AORs 0.81, [95% CI 0.75–0.88], 0.62 [95% CI 0.50–0.77], respectively). Ad26.COV2.S and AZD1222 vaccines are well-tolerated, with primarily mild and few severe AE among adults living in Malawi. Self-reporting of AE following COVID-19 vaccination is associated with gender, age, education, and concern about the safety of the vaccines. Recognizing these associations is key when designing and implementing COVID-19 vaccination communication messages to increase vaccination coverage.

A web-based genome-wide association study reveals the susceptibility loci of common adverse events following COVID-19 vaccination in the Japanese population

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. To prevent its spread, mRNA-based vaccines made by Pfizer/BioNTech (BNT162b1) and Moderna (mRNA-1273) have been widely used, including in Japan. Various adverse events have been reported following the COVID-19 mRNA vaccination, with differences observed among individuals. However, analyses of the genetic background associated with the susceptibility to side effects have been limited. In the present study, we performed genome-wide association studies (GWAS) for self-reported adverse events of the COVID-19 mRNA vaccination in 4545 Japanese individuals and identified 14 associated loci. Among these, 6p21 was associated with 37.5 °C or higher fever, 38 °C or higher fever, and muscle pain. HLA allele association analysis revealed that various HLA alleles were associated with the adverse effects; HLA-DQA1*03:01 and HLA-A*11:01 were more reliably associated with the adverse effects. Our results may enable the preparation and management of adverse effects by identifying the susceptibility to these adverse events. Furthermore, we obtained valuable data that may lead to a better understanding of the mechanisms of action of the COVID-19 mRNA vaccines.

Self-reported adverse events within the seven days following the Spikevax® (Moderna) vaccination

ObjectiveContinuous monitoring of COVID-19 vaccines safety may provide additional information to health care professionals and the general population. The aim of the present study was to analyze the local and systemic adverse events following the administration of the Spikevax® (Moderna) vaccine, and to identify the factors related to greater reactogenicity. MethodUsing a telephone survey, we interviewed 331 recipient of the Spikevax® vaccine (50.2% men; Meanage = 46.4). Participants characteristics, prior COVID-19 infection and Local and systemic adverse events within seven days following the first and second vaccine doses were asked. ResultsInjection site pain, fatigue and headache were the most common adverse events. The prevalence and intensity of local events was higher after the first dose, while systemic events were higher in the second one. Most adverse events were mild/moderate; 1.2% of participants needed hospitalization or emergency room visit. Women and participants aged 18-55 years were more likely to experience greater reactogenicity, participants with prior COVID-19 infection had more systemic events after the first dose, and participants with chronic diseases other than hypertension reported fewer systemic adverse events following the second dose. ConclusionsOur results are consistent with previous studies, identifying women, people aged 18-55 years and those with previous COVID-19 infection as those who experienced the greatest reactogenicity to the vaccine. A relationship was also found between reactogenicity and suffering from a chronic disease other than hypertension.

COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series

ObjectiveTo assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease.MethodsWe conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid...

A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study)

ObjectivesWe evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines. MethodsFluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant’s scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected daily for seven days following each visit.The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number. ResultsOverall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one.Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] −0.03 to 0.27) and 13% (95%CrI −0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI −0.29 to 0.41) and −4% (95%CrI −0.30 to 0.23), respectively. ConclusionAdverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses.Clinical trial registration: ACTRN12621001063808.

Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors.

Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known. RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skåne University Hospital, Lund and Malmö, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed. Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a ≥4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination. The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population. ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038.

Efficacy and safety of the endothelin-1 receptor antagonist macitentan in epicardial and microvascular vasospasm; a proof-of-concept study

BackgroundTreatment of patients diagnosed with angina due to epicardial or microvascular coronary artery spasm (CAS) is challenging because patients often remain symptomatic despite conventional pharmacological therapy. In this prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept study, we compared the efficacy and safety of macitentan, a potent inhibitor of the endothelin-1 receptor, to placebo in symptomatic patients with CAS despite background pharmacological treatment. MethodsPatients with CAS diagnosed by invasive spasm provocation testing with >3 anginal attacks per week despite pharmacological treatment were considered for participation. Participants received either 10 mg of macitentan or placebo daily for 28 days as add-on treatment. After a wash-out period patients were crossed over to the alternate treatment arm. The primary endpoint was the difference in anginal burden calculated as [1] the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1–10); and [2] the frequency of angina attacks * severity during medication use compared to the run-in phase. Results28 patients of whom 22 females (79%) and a mean age of 55.3 ± 7.6 completed the entire study protocol (epicardial CAS n = 19 (68), microvascular CAS n = 9 (32)). Change in both indices of anginal burden were not different during treatment with add-on macitentan as compared to add-on placebo (duration*severity: −9 [−134 78] vs −45 [−353 11], p = 0.136 and frequency*severity: −1.7 [−5.8 1.2] vs −1.8 [−6.2 0.3], p = 0.767). The occurrence and nature of self-reported adverse events were closely similar between the treatment phase with macitentan and placebo. ConclusionIn patients with angina due to epicardial or microvascular CAS despite background pharmacological treatment, 28 days of add-on treatment with the ET-1 receptor antagonist, macitentan 10 mg daily, did not reduce anginal burden compared to add-on treatment with placebo.Trial Registrationhttps://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.

Diabetes, gaps in care coordination, and preventable adverse events.

To compare the frequency of self-reported gaps in care coordination and self-reported preventable adverse events among adults with vs without diabetes. Cross-sectional analysis of REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants 65 years and older who completed a survey on health care experiences in 2017-2018 (N = 5634). We analyzed the association of diabetes with self-reported gaps in care coordination and with preventable adverse events. Gaps in care coordination were assessed using 8 validated questions. Four self-reported adverse events were studied (drug-drug interactions, repeat medical tests, emergency department visits, and hospitalizations). Respondents were asked if they thought these events could have been prevented with better communication among providers. Overall, 1724 (30.6%) participants had diabetes. Among participants with and without diabetes, 39.3% and 40.7%, respectively, reported any gap in care coordination. The adjusted prevalence ratio (aPR) for any gap in care coordination for participants with vs without diabetes was 0.97 (95% CI, 0.89-1.06). Any preventable adverse event was reported by 12.9% and 8.7% of participants with and without diabetes, respectively. The aPR for any preventable adverse event for participants with vs without diabetes was 1.22 (95% CI, 1.00-1.49). Among participants with and without diabetes, the aPRs for any preventable adverse event associated with any gap in care coordination were 1.53 (95% CI, 1.15-2.04) and 1.50 (95% CI, 1.21-1.88), respectively (P comparing aPRs = .922). Interventions to improve quality of care for patients with diabetes could incorporate patient-reported gaps in care coordination to aid in preventing adverse events.

Completion rates and trends of the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) across 14 oncology clinical trials.

1579 Background: With growing emphasis on patient-centered regulatory decision making, there is a greater need to incorporate the patient’s voice in oncology clinical trials. Regulatory guidelines outline core patient-reported outcomes (PROs) to include which can inform risk/benefit evaluation. Self-reported symptomatic adverse events (AE) form part of these core PROs, with the new 2023 draft FDA guidance acknowledging the benefits of including them to enhance the assessment of tolerability in early phase dose optimization trials. Given the clinical symptoms and disease burden in oncology, patient burden needs to be thoughtfully considered when incorporating PROs into trials. We assessed trends and feasibility of electronic data collection for symptomatic AEs by analyzing completion compliance and time to complete the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) across 14 oncology trials. Methods: All PRO-CTCAE were collected electronically on Clario Tablets. Operational data for completion status (completed or missed) and duration of time to complete the PRO-CTCAE in seconds was extracted. Completion rates over time were examined overall and for every 3-month interval (quarters Q1 to Q9+). The median was selected for analyses of time to complete to account for skewness. Results: The sample included 14 studies across Phase I-III trials across a range of cancers including multiple myeloma, mesothelioma and cancers of the lung, prostate, head/neck, gastric, breast, and ovary. Study durations were 24 weeks and up. The PRO-CTCAE form was completed 13,122 times and missed in 1,182 instances, giving an overall completion rate of 91.7%. On average, 25 questions (range 5-47) covered an average of 13 symptoms (range: 4-25). Completion rate was not associated with the number of questions asked or time since enrollment. The overall median time to complete the PRO-CTCAE was 82s (study-specific median range: 24s to 276s). Examining time to completion as a function of the number of questions revealed a significant positive association, such that each additional question added 5.2 seconds to the time it took to complete the assessment. Conclusions: Completion compliance was high for PRO-CTCAE and remained high regardless of study length and the number of questions included in the PRO-CTCAE form. This suggests that electronic PRO-CTCAE is a feasible solution for collecting self-reported symptomatic AEs. Although time to complete the form increased with the number of questions, results suggest that including a higher number of PRO-CTCAE questions does not negatively impact compliance rate. Our data showing high completion rates may also reflect the benefits of electronic PROs in reducing patient burden and enhancing data quality, as acknowledged by regulatory agencies.