Enrollment Period Research Articles

Application of cognitive remediation in the world: new experiences from two schizophrenia rehabilitation centers in Togo and Benin

PurposePeople with schizophrenia in Sub-Saharan Africa often live in very difficult conditions, suffer important social isolation and usually do not receive any kind of treatment. In this context, some non-governmental initiatives have come to light, providing accommodation, food, primary healthcare, medications and, in some cases, education and rehabilitation. The aims of this study were to assess feasibility, effects, and acceptability of a Cognitive Remediation Therapy (CRT) intervention in the particular context of psychiatric rehabilitation in Togo and Benin.MethodsPatients diagnosed with schizophrenia accessing the “Saint Camille” association rehabilitation centers in Togo and Benin during the enrollment period were allocated consecutively with a 1:1 proportion to receive a manualized CRT intervention (46 one-hour sessions over 14 weeks) or continuing Treatment As Usual (TAU). The assessment included validated measures of cognitive performance and real-world functioning and was performed at baseline and at the conclusion of treatment.ResultsAll subjects that were invited into the study agreed to participate and completed the intervention, for a total of 36 participants. CRT produced greater improvements than TAU in processing speed, working memory, verbal memory, cognitive flexibility, and executive functions measures, with moderate to large effect sizes, in particular in processing speed and working memory domains.ConclusionsCRT represents a feasible and effective psychosocial intervention that can be implemented even in contexts with very limited resources, and could represent an important instrument to promote the rehabilitation process of people living with schizophrenia in low-income countries.

A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19

An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120–180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized, double-blind, placebo-controlled trial was conducted in Japanese COVID-19 patients with mild to moderate pneumonia. The number of study participants was set to be 50 in each arm. Even after extension of the enrollment period, the number of study participants did not reach the initially intended sample size, and 75 patients were enrolled in the study. The total oxygenation scale from Day 1 to Day 14 as the primary endpoint was 1.5 in the TM5614 group vs 4.0 in the placebo group (p = 0.22), and the number of days of oxygen administration required as the secondary endpoint was 2.0 days in the TM5614 group vs 3.5 days in the placebo group (p = 0.34). Further studies will be necessary to verify the efficacy of PAI-1 inhibition for the treatment of COVID-19 pneumonia.Clinical trial registration: Two studies were conducted: a prospective, multicenter, open-label phase II study at https://jrct.niph.go.jp (jRCT2021200018) (First registration date 18/08/2020) and a prospective, multicenter, randomized, double-blind, placebo-controlled, phase II study at https://jrct.niph.go.jp (jRCT2021210006) (First registration date 28/05/2021).

Prospective observational study to explore genes and proteins predicting efficacy and safety of brigatinib for ALK-gene rearranged non-small-cell lung cancer: study protocol for ABRAID study (WJOG11919L).

ALK-tyrosine kinase inhibitors (ALK-TKIs) are effective for treating non-small-cell lung cancer with ALK gene rearrangement; however, resistance is inevitable. Brigatinib is a unique ALK-TKI that is effective against many resistance mutations. However, data on factors associated with its efficacy and resistance mechanisms are limited. This study will evaluate the efficacy and safety of brigatinib in the real world and explore factors related to its efficacy, safety, and resistance mechanisms. Prospective observational study. This study is approved by the Ethics Committee of Wakayama Medical University. Written informed consent will be obtained from all patients before study-related procedures. This study comprises three cohorts. Cohorts A, B, and 0 will enroll patients receiving alectinib as the first ALK-TKI, receiving alectinib as the first ALK-TKI and subsequently cytotoxic agents and/or lorlatinib after alectinib, and without a history of ALK-TKI, respectively. Overall, 100, 30, and 50 patients will be enrolled in Cohorts A, B, and 0, respectively. Circulating tumor DNA before starting brigatinib and at disease progression will be analyzed in all cohorts using a hypersensitive next-generation sequencing (NGS) PGDx Elio plasma resolve panel. Serum protein levels will be analyzed using the Milliplex xMAP assay system with a Luminex 200 (Luminex, Austin, USA). The enrollment period is 31 months and the patients will be observed for 2 years after enrollment. Archived tissues will be collected for NGS analysis, gene expression analysis, and immunohistochemistry staining 1 year after completion of registration. Quality of life and safety evaluation using electronic patient-reported outcomes will be investigated. This study will elucidate predictors of ALK-TKI efficacy and resistance mechanisms and evaluate the efficacy and safety of brigatinib in a real-world setting. The results will provide crucial information for establishing treatment strategies, discovering novel biomarkers, and developing new therapeutic agents. UMIN000042439.

A MEDICAL AND NEUROPSYCHIATRIC MANAGEMENT SURVEY IN A BRAZILIAN COHORT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD).

Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions. • What is already known? • The prevalence and spectrum of neuropsychiatric co-morbidities varies among different epidemiologic studies. • What is new here? • Patients self report a high percentage of neuropsychiatric diseases but tend to better recognize central rather than peripheral nervous system disorders. • How can this study help patient care? • This study may guide practioners to educate IBD patients about their neuropsychiatric co-morbidities.

Metabolic syndrome risk among adolescents in the Deep South and the relationships with behavioral health, food insecurity, and physical activity.

A combination of physical and psychosocial risk factors put adolescents at risk for poor cardiometabolic health and chronic disease burden, often recognized as metabolic syndrome. The purposes of this study were to (1) identify the prevalence of metabolic syndrome risk among adolescents, utilizing the metabolic syndrome severity index, and (2) determine the relationship between metabolic syndrome risk and behavioral health, food insecurity, and physical inactivity among adolescents. A cross-sectional, descriptive, correlational design was deployed in an inner-city high school in the Deep South. An 8-month recruitment and enrollment period yielded a sample of 55 adolescents. A battery of measures included assessment of demographic data, anthropometric, cardiovascular, and psychosocial data. Utilizing these data elements, a progressive methodological approach was used to identify metabolic severity risk as a continuous variable for use in the adolescent population. All participants identified as African American/Black. Among them, 71% (N = 39) were female and an average age of 16 (SD = 1.3) years old, with 67.3% (N = 37) of the sample at risk for metabolic syndrome. There was not a statistically significant relationship between metabolic syndrome severity score and behavioral health risk, food insecurity, and physical inactivity in this sample. Future use of the continuous metabolic syndrome severity score may guide practice by utilizing longitudinal data to assess the trends of metabolic syndrome severity scores in relation to disease outcomes in adolescents. This may promote the identification of psychosocial and physical interrelationships with metabolic syndrome, thus improving overall health through the development of age-appropriate interventions.

Abstract A126: Differential survival among Medicare beneficiaries diagnosed with breast cancer in California

Abstract This study examines the differences in breast cancer survival among Medicare beneficiaries enrolled in either Traditional Medicare (TM) or Medicare Advantage (MA) plans during 1999-2017 in California. Medicare is federal health insurance for people of age 65 or older. Beneficiaries can choose between TM (directly administered by the Federal government) or MA (offered by private companies) plans. California (CA) has the largest number of Medicare beneficiaries of any state (6.6 million), nearly half (49%) of them enrolled in MA plans. Due to different management mechanisms, detailed claims data are not routinely submitted and available for MA enrollees as for TM, making objective assessment for the claimed MA advantages and effectiveness hard to find. Medicare beneficiaries often find it challenging to choose between TM and MA during the Medicare open enrollment period or make changes between these two types of plans. The National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) Program, routinely link its cancer registry data with Medicare to provide detailed information about Medicare beneficiaries aged 65 and older diagnosed with cancer. Using the SEER-Medicare linked data for the state of California (CA), we were able to compare the survival differences among Medicare beneficiaries with female breast cancer (BC) stratified by TM or MA enrollment in CA during 1999-2017. We identified a total of 189,517 women Medicare beneficiaries who had BC, of which 83,223 (43.9%) enrolled in TM and never had MA, while 106,294 (56.1%) ever enrolled in MA regardless of the length of MA coverage. Because Medicare enrollment is on monthly basis and enrollees may change plans during the annual open enrollment period each year. Therefore, among the MA enrollees, we found 61,006 (57.4%) who switched between MA and TM from time to time (MA switch), in contrast to 45,288 (42.6%) who were in MA for the entire study period (MA only). We calculated 5-year observed survival rates from all causes of death among these Medicare beneficiaries with BC, using Kaplan-Meier method. We found that MA switch group had the highest 5-year survival of 81.5% (95% CI: 81.2%-81.8%), followed by MA only (72.6%, 95% CI: 72.1%-73.0%) and TM (72.5%, 95% CI: 72.2%-72.8%) groups. The survival advantage of the MA switch group is evident across race/ethnicity. Asian MA switchers had the highest 5-year survival rate (87.3%) followed by Hispanic (83.3%), Non-Hispanic White (80.5%), and Non-Hispanic Black (75.9%). In a multivariate Cox proportional hazards regression analysis, controlling for sociodemographic and clinical characteristics (i.e., age at diagnosis, race and ethnicity, poverty indicator, summary stage of tumor, marital status, urbanization, and number of cancers), MA switch group displayed a statistically significant (α<0.05) mortality reduction of 25% as compared to the TM group. No significant differences between TM and MA only group was found. More informed and proactive Medicare beneficiaries are associated with the best health outcomes. Citation Format: Lihua Liu Liu, Ying Yan, Sue E. Kim. Differential survival among Medicare beneficiaries diagnosed with breast cancer in California [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A126.

“Pick a Plan and Roll the Dice”: A qualitative study of consumer experiences selecting a health plan in the non-group market

BackgroundFor consumers without access to employer-sponsored or public insurance, health plan choices in the non-group (individual) insurance market that do not meet consumer needs have the potential for negative downstream implications for health and financial well-being. ObjectiveThis qualitative interview study sought to understand consumers’ experiences and challenges with choosing a non-group health plan, among those who later had negative experiences with the plan they chose. MethodsWe conducted semi-structured telephone interviews with a purposive sample of 36 participants from a large regional health insurance carrier in three states who enrolled in non-group plans in 2017 (21 in Affordable Care Act (ACA) Marketplace plans and 15 enrolled off-Marketplace). Participants were included if they reported negative experiences using their plan after enrollment, such as higher-than-expected medical costs. Interviews explored challenges choosing a plan; information needed for choosing; usefulness of available tools; and preferred format for interventions to improve plan choice experiences. We analyzed interview transcripts using thematic content analysis. ResultsStudy participants reported experiencing substantial challenges to choosing an insurance plan. Key barriers included understanding insurance terms, finding relevant information, and making comparisons across plans. Participants valued the ability to make comparisons across carriers when using the Marketplace websites but were less satisfied with customer service. Suggestions for improvement included greater standardization of plans and language and availability of customized one-on-one assistance. ConclusionFindings from this study suggest that health plan selection in the non-group market presents challenges to consumers that may be addressed through enrollment assistance and improved presentation of information. Personalized assistance to find and choose coverage may lead to plan choices that better meet consumer needs and increase confidence choosing a plan in subsequent enrollment periods.

Cold Agglutinin Disease (CAD) Real-World Evidence (CADENCE) Registry: Update to the Study Design of the First International, Prospective CAD Registry

Cold agglutinin disease (CAD) is a rare chronic autoimmune hemolytic anemia (AIHA) characterized by classical complement pathway (CP)-mediated hemolysis. CAD is associated with a substantial disease burden negatively impacting quality of life (QoL), including severe fatigue, and increased risk of both thromboembolic events and early mortality. Due to the rarity of CAD, there is scarce information regarding its natural history, long-term impacts, and complications. Sutimlimab, a humanized monoclonal antibody that selectively inhibits the CP, is the first approved treatment for CAD. In the CARDINAL and CADENZA Phase 3 trials, sutimlimab reduced hemolysis, anemia, was generally well tolerated, and meaningfully improved QoL. The CADENCE Registry (NCT05791708) is a large international database of patients with CAD or cold agglutinin syndrome (CAS, a cold antibody-driven hemolytic anemia associated with an underlying condition). First launched in 2019, the first study patient was enrolled in 2022 following a COVID-19 pandemic-related hiatus. Presented here is an update on the current CADENCE protocol and study design. CADENCE is a multinational, multicenter, observational, prospective, longitudinal registry study enrolling patients ≥18 years of age diagnosed with CAD (diagnostic criteria: a monospecific direct antiglobulin test strongly positive for C3d and negative or weakly positive for immunoglobulin G and a cold agglutinin titer ≥1:64) or CAS (CAD diagnostic criteria, with causative infection, autoimmune disorder or overt malignancy). Exclusion criteria include patients with a diagnosis of warm or mixed AIHA and those actively participating in a CAD/CAS interventional trial. The main study objective is to better understand patient demographics, clinical characteristics, treatment patterns, healthcare resource utilization (HRU), natural history of disease, long-term clinical outcomes, and impact on patient QoL. A sutimlimab-treated cohort sub-study is ongoing to assess the real-world safety and effectiveness of sutimlimab in patients with CAD, fulfilling the regulatory commitment for a post-authorization safety study. The enrollment period is expected to last ~3 years and patients will be followed for 3 years after the last patient enrolled. Data collection will include both clinical assessments as per standard of care and patient-reported outcome (PRO) data collected at enrollment and at ~6-month interval follow-ups. Additional safety data will be collected for the sutimlimab cohort. The CADENCE Registry's first patient enrolled (after study restart) was in Q2 2022, with last patient's first visit expected in Q2 2025 and last patient's last visit expected in 2028 ( Figure). The registry will collect data on ~400 patients with CAD/CAS across ~90 sites in 8 countries: Austria, France, Germany, Italy, Japan, Spain, the UK, and the US. Among them, ≥30 patients with CAD treated with sutimlimab are expected to take part in the cohort study. Key data to be collected include clinical characteristics, disease complications, comorbidities, mortality, treatment regimens, HRU, and PROs. Biomarkers for hemolysis will be assessed, including lactate dehydrogenase, haptoglobin, total and indirect bilirubin. In the sutimlimab cohort, data will also be collected on adverse events (AEs), serious AEs, and AEs of special interest (serious infections, Raynaud's, arterial hypertension, autoimmune disorders, hypersensitivity/anaphylaxis, exposure in pregnancy, overdose). PRO measures include the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, the 36-item Short Form Health Survey (SF-36), and the CAD symptoms and impact questionnaire (CAD-SIQ), a novel 11-item questionnaire specifically designed for CAD. Interim analyses will occur annually. Final analyses will be performed at study end both at regional and global levels. As of July 13, 2023, 47 of 82 targeted sites have been activated, and 113 of 405 targeted patients (CAD/CAS) have been enrolled, including 13 sutimlimab-treated patients. CADENCE is the first global registry for patients with CAD and will help advance understanding of the natural history and disease process of this rare condition. This registry will also assess the long-term safety and effectiveness of sutimlimab in patients with CAD in a real-world setting, providing clinicians with data that may help improve treatment practices.

Prevalence and Proportion of Transcranial Doppler Screenings in a Population Children with Sickle Cell Disease and Association with Hydroxyurea Adherence

Sickle cell disease (SCD) is an inherited or genetic hemoglobinopathy in the United States and approximately 100,000 Americans are affected. The prevalence of stroke in unscreened children with sickle cell anemia (SCA) is 10% and can begin at infancy. National guidelines strongly recommend annual Transcranial Doppler (TCD) screenings as well as hydroxyurea (HU) administration in children with SS and Sβ o thalassemia (SCA) genotypes. The purpose of this project was to examine the prevalence and proportion of TCD screenings in North Carolina (NC) Medicaid enrollees and to identify associations with sociodemographic factors (age, sex, and rurality) and HU adherence. A longitudinal analysis of NC Medicaid claims data (2016-2019) was conducted for children with SCD ages 2-16 years. Prevalence of TCD screening claims was calculated to determine the number of children with TCD claims for each of the three, 12-month enrollment periods. The proportion of TCD screening claims was calculated based on NC Medicaid enrollees who had increasing TCD claims (0, 1, 2, or 3+) for 12, 24, and 36 months of Medicaid enrollment. HU adherence was measured using Proportion of Days Covered (PDC). HU PDC is a measure of HU prescription fills over 365 days within a 12-month period. HU PDC was used to categorize enrollees into good (≥80%), moderate (60-79%), or poor (<60%) adherence categories. Age (years) was declared as the age in years of each participant during each study observation period and was categorized into three groups: preschoolers (2-5 years), school aged (6-11 years), and adolescents (12-16 years). Rurality was identified by converting residential zip codes to rural/urban county codes (RUCC). An adjusted multivariable Poisson regression model was fit to assess the rate of TCD screenings by HU adherence while controlling for age, sex, and rurality. The prevalence of children with annual TCD screening claims ranged from 39.5% to 40.1%. The percentage of children with 2 or more TCD claims increased when they had extended months of NC Medicaid enrollment (10.5% at 12 months, 33.7% at 24 months, and 52.6% at 36 months). Overall, children with Good HU adherence were 2.48 (95% CI 2.00, 3.06) times more likely to have TCD claims than children with poor HU adherence. In conclusion, the prevalence of TCD screenings of children with SCD on NC Medicaid was extremely low. Children with better HU adherence and extended NC Medicaid enrollment time were associated with higher number of TCD screenings.

VOC-Free Status Among Patients with Sickle Cell Disease Following Allogeneic Hematopoietic Stem Cell Transplant: A Cohort Study of Medicaid Enrollees

Background: Sickle cell disease (SCD) is characterized by recurrent acute vaso-occlusive crises (VOCs), which diminish patient quality-of-life, contribute to end-organ damage and failure, and increase mortality. Currently, approved therapies for SCD are only partially effective and do not fully eliminate VOCs. Allogeneic hematopoietic stem cell transplant (HSCT) is the only known curative option for patients with SCD, however, HSCT is available to <20% of patients who have a matched sibling donor and is associated with significant risks, such as graft-versus-host disease. Autologous gene therapies that have the potential to provide a one-time functional cure to patients with SCD are currently in pivotal trials. The primary endpoint for these pivotal studies is the proportion of patients who become VOC-free for ≥12 months after treatment. Absence of VOCs for ≥12 months is expected to predict long-term efficacy. Given this, we evaluated patients with SCD in the national US Medicaid database who underwent allogeneic-HSCT to determine whether VOC-free status at 12 months was predictive of VOC-free status at 18 and 24 months after HSCT. Methods: A cohort of patients with SCD who had a record of allogeneic HSCT with at least 12 months of continuous Medicaid enrollment during 2000-2014 was identified. The date of HSCT was defined as the cohort entry date and the covariate assessment window was the 12 months continuous enrollment period preceding the cohort entry date. A VOC event was identified using ICD-9 diagnosis codes in hospitalization and ER visit claims for Hb-SS disease with crisis, other acute pain crisis, acute chest syndrome, priapism, and splenic sequestration. The cohort was further restricted to patients who had ≥24 months of follow-up after cohort entry to accurately assess VOC outcomes. Diagnosis codes associated with the delivery of healthcare and pharmacy claims were used to identify patient characteristics and outcomes of interest. Primary study outcome was the proportion of patients with no VOCs at 6 months, 12 months, 18 months, and 24 months after allogeneic HSCT. Results: During the study period, 44,685 patients with SCD were identified, out of whom 103 patients had undergone allogeneic HSCT, were enrolled for ≥12 months in the Medicaid program and had ≥24 months of follow-up after HSCT. Mean (SD) age was 10.3 (7.2) years, with 55.3% being male and majority (67%) Black. Patients had an average of 2.7 (SD, 7.9) VOC events during the 12-month period prior to HSCT. The most common (>10%) baseline comorbidities were chronic cardiac disease (42.7%), infections (36.9%), chronic pulmonary disease (31.1%), and acute chest syndrome (12.6%). Among the cohort of 103 patients who had undergone HSCT, 79% (n=81) were VOC-free by 12 months. Furthermore, among patients who were VOC-free at 12 months, 91% (n=74) were VOC-free at 18 months and 90% (n=73) were VOC-free at 24 months. Conclusions: This population-based study provides valuable information regarding long-term VOC-free status among patients with SCD who have undergone allogeneic HSCT in routine clinical care. Our findings suggest that patients with SCD who are VOC-free by 12 months post-HSCT are highly likely to stay VOC-free for longer durations (i.e. 18 and 24 months) after HSCT.

Prevalence of psychological distress and associated factors among patients undergoing comprehensive genomic profiling testing: protocol for a multicentre, prospective, observational study

IntroductionSince May 2019, comprehensive genomic profiling (CGP) has been covered by Japan’s health insurance system for patients with solid tumours that have progressed on standard chemotherapy, rare tumours or tumours...

One year clinical outcome of dual anti-platelet therapy with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm: A meta-analysis

BackgroundThe use of stents to treat un-ruptured intracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed to systematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm. MethodsOnline electronic databases were searched from June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis. ResultsFive studies with a total number of 893 participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants’ enrollment period ranged from the year 2009 to 2019. Our results showed that during a mean follow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 – 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associated with any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 – 1.50; P = 0.32) when compared to DAPT with clopidogrel. ConclusionAt one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, even though ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.

Repetitive LevosimenDan infusions fOR patients with advanced chronic heart failure in the vulnerable post-discharge period: the multinational randomized LeoDOR trial

Abstract Background Studies of the repetitive use of intravenous levosimendan suggested a beneficial effect in patients with advanced heart failure (HF). It was the aim of the LeoDOR trial to test the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute HF. Methods In this multicenter, double-blind, three-armed trial with an enrolment period from 3-2018 to 6-2021, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or placebo for a period of 12 weeks. Levosimendan was administered according to center preference either as 6-hour infusion at a rate of 0.2 mcg/kg/min every 2 weeks, or as 24-hour infusion at a rate of 0.1 mcg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank endpoint consisting of three hierarchical groups: Tier 1 = time to death or urgent heart transplantation or implantation of a ventricular assist device; Tier 2 = time to non-fatal HF requiring i.v. vasoactive therapy; Tier 3 = time-averaged proportional change in NTproBNP from baseline to week 14. Results Due to a forced interim interruption of the study as a result of the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat (mITT) analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm). Patient characteristics were well balanced between treatment and placebo arms (mean age 69.3±9.7 vs 67.9±10.1, proportion of women 22.6% vs 21.2%, HF-hospitalizations in previous 12 months 1.9±1.4 vs. 1.7±1.1, NTproBNP at baseline 4740 ng/L (IQR 2235 – 9016) vs 5380 ng/L (IQR 2287 – 8204). There were no marked differences regarding HF medication and implanted devices. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint (mean rank score 71.8 for the levosimendan group vs 75.1 for the placebo group; p = 0.65). However, there was a strong signal towards a higher incidence of the individual clinical components of the primary endpoint (tier 1 plus tier 2) in the levosimendan group vs the placebo group both after 14 weeks (HR 2.94, 95%CI 1.13–7.70; p = 0.028) and 26 weeks (HR 1.65 95%CI 0.87 – 3.12; p = 0.123). The number of investigator-reported adverse events during and immediately after drug application was 12.4% in the levosimendan group vs 11.8% in the placebo group (p = 0.905). Conclusion Our findings do not support the use of intermittent levosimendan to improve post-hospitalization clinical stability in patients who were recently hospitalized with HF and reduced LVEF. Further studies are warranted to find the correct use of levosimendan in advanced heart failure patients.

Clinical Utility Assessment of a Nursing Checklist Identifying Complex Care Needs Due to Inequities Among Ambulatory Patients With Cancer: Protocol for a Mixed Methods Study.

Disparities in cancer incidence, complex care needs, and poor health outcomes are largely driven by structural inequities stemming from social determinants of health. To date, no evidence-based clinical tool has been developed to identify newly diagnosed patients at risk of poorer outcomes. Specialist cancer nurses are well-positioned to ameliorate inequity of opportunity for optimal care, treatment, and outcomes through timely screening, assessment, and intervention. We designed a nursing complexity checklist (the "Checklist") to support these activities, with the ultimate goal of improving equitable experiences and outcomes of care. This study aims to generate evidence regarding the clinical utility of the Checklist. The primary objectives of this study are to provide qualitative evidence regarding key aspects of the Checklist's clinical utility (appropriateness, acceptability, and practicability), informed by Smart's multidimensional model of clinical utility. Secondary objectives explore the predictive value of the Checklist and concordance between specific checklist items and patient-reported outcome measures. This prospective mixed methods case series study will recruit up to 60 newly diagnosed patients with cancer and 10 specialist nurses from a specialist cancer center. Nurses will complete the Checklist with patient participants. Within 2 weeks of Checklist completion, patients will complete 5 patient-reported outcome measures with established psychometric properties that correspond to specific checklist items and an individual semistructured interview to explore Checklist clinical utility. Interviews with nurses will occur 12 and 24 weeks after they first complete a checklist, exploring perceptions of the Checklist's clinical utility including barriers and facilitators to implementation. Data describing planned and unplanned patient service use will be collected from patient follow-up interviews at 12 weeks and the electronic medical record at 24 weeks after Checklist completion. Descriptive statistics will summarize operational, checklist, and electronic medical record data. The predictive value of the Checklist and the relationship between specific checklist items and relevant patient-reported outcome measures will be examined using descriptive statistics, contingency tables, measures of association, and plots as appropriate. Qualitative data will be analyzed using a content analysis approach. This study was approved by the institution's ethics committee. The enrollment period commenced in May 2022 and ended in November 2022. In total, 37 patients with cancer and 7 specialist cancer nurses were recruited at this time. Data collection is scheduled for completion at the end of May 2023. This study will evaluate key clinical utility dimensions of a nursing complexity checklist. It will also provide preliminary evidence on its predictive value and information to support its seamless implementation into everyday practice including, but not limited to, possible revisions to the Checklist, instructions, and training for relevant personnel. Future implementation of this Checklist may improve equity of opportunity of access to care for patients with cancer. DERR1-10.2196/48432.

Virtual Reality Distraction Is No Better Than Simple Distraction Techniques for Reducing Pain and Anxiety During Pediatric Orthopaedic Outpatient Procedures: A Randomized Controlled Trial.

In-office procedures can be painful and anxiety-provoking for pediatric patients. Minimizing such pain and anxiety in children improves the patient experience and promotes a rewarding and productive patient-caregiver-provider relationship, which may for some young patients be their first memorable encounter with the healthcare system. Although virtual reality (VR) techniques have proven to be helpful in minimizing pain and anxiety during procedures in pediatric intensive care settings, it remains unclear how VR affects objective and subjective measures of pain and anxiety in children undergoing in-office orthopaedic procedures such as cast removal or percutaneous pin removal after fracture healing. Is a VR gaming simulation more effective than either of two forms of noninteractive visual distraction (VR goggles or tablet computer displaying a noninteractive video) for reducing (1) objective measures of pain and anxiety and (2) subjective measures of pain and anxiety in children undergoing in-office cast removal or percutaneous pin removal? This study was a randomized controlled trial with two parallel, separately analyzed cohorts: children undergoing in-office cast removal or in-office percutaneous pin removal at a single urban tertiary institution. We approached eligible patients who were scheduled to undergo outpatient cast or percutaneous pin removal and who met prespecified inclusion criteria. We enrolled until 105 patients were available for analysis in each of the cast removal and pin removal cohorts. Of note, the study institution was in an urban epicenter of the coronavirus-19 pandemic, and clinical research was paused sporadically, which resulted in a longer-than-expected enrollment period. In the cast removal cohort, all patients were eligible for inclusion and were enrolled and randomized into one of three groups: VR gaming simulation (n = 37), VR goggles with a noninteractive video (n = 36), or a tablet computer with the same noninteractive video (n = 40). Eleven percent (4), 8% (3), and 3% (1) withdrew from each of the three intervention groups, respectively. In the pin removal cohort, all patients were eligible for inclusion and were enrolled and randomized into the same three groups (37, 44, and 41 patients, respectively). In the pin removal group, 14% (5), 18% (8), and 10% (4) withdrew from each of the three intervention groups, respectively. In all, 235 patients were enrolled in the study and 210 patients (mean ± SD age 9 ± 3 years; 48% [100] girls) were included in the final analyses. There were no clinically important differences in age, gender, preprocedure pain, or anxiety among the intervention groups. Primary outcomes included preprocedure-to-maximum heart rate increase (objective measure) and preprocedure and postprocedure pain and anxiety using a VAS (subjective measures). One-way ANOVA and Bonferroni-adjusted pairwise comparisons were used to calculate between-group differences for the primary outcomes. There were no intervention-level groupwise differences between VR goggles with an interactive game, VR goggles with a noninteractive video, or the tablet computer with the same video in preprocedure-to-maximum heart rate increase in the cast removal cohort (18 ± 21 bpm versus 14 ± 11 bpm versus 20 ± 16 bpm, respectively; largest mean difference -6 bpm [95% CI -16 to 3]; p = 0.36) or pin removal cohort (27 ± 20 bpm versus 23 ± 12 bpm versus 24 ± 19 bpm, respectively; largest mean difference 4 bpm [95% CI -7 to 14]; p = 0.99). Similarly, there were no intervention-level groupwise differences in preprocedure to postprocedure VAS pain in the cast removal cohort (1 ± 1 versus 1 ± 2 versus 0 ± 2, respectively; largest mean difference 0 points [95% CI 0 to 1]; p = 0.89) or pin removal cohort (0 ± 3 versus 2 ± 3 versus 0 ± 3 points, respectively; largest mean difference 1 point [95% CI 0 to 3]; p = 0.13). Finally, there were no intervention-level groupwise differences between the same intervention groups in preprocedure to postprocedure VAS anxiety in the cast removal cohort (-2 ± 2 versus -1 ± 2 versus -1 ± 2 points, respectively; largest mean difference -1 point [95% CI -2 to 1]; p = 0.63) or pin removal cohort (-3 ± 3 versus -4 ± 4 versus -3 ± 3 points, respectively; largest mean difference -1 point [95% CI -2 to 1]; p = 0.99). During in-office cast and pin removal in pediatric patients, simple distraction techniques such as tablet video viewing are as effective as higher-fidelity VR headset video and interactive games in minimizing objective measures of procedural pain and subjective measures of pain and anxiety. Because of these findings and because of the associated costs, implementation logistics, and variable tolerance by young patients, widespread use of VR distraction techniques in the pediatric orthopaedic outpatient setting is unnecessary. Level I, therapeutic study.

Increased Utilization of Low-Dose CT for Lung Cancer Screening at an Arkansas Community Oncology Clinic

BackgroundLow-dose CT (LDCT) is underused in Arkansas for lung cancer screening, a rural state with a high incidence of lung cancer. The objective was to determine whether offering free LDCT increased the number of high-risk individuals screened in a rural catchment area. MethodsThere were 5,402 patients enrolled in screening at Highlands Oncology, a community oncology clinic in Northwest Arkansas, from 2013 to 2020. Screenings were separated into time periods: period 1 (10 months for-fee), period 2 (10 months free with targeted advertisements and primary care outreach), and period 3 (62 months free with only primary care outreach). In all, 5,035 high-risk participants were eligible for analysis based on National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Enrollment rates, incidence densities (IDs), Cox proportional hazard models, and Kaplan-Meier curves were performed to investigate differences between enrollment periods and high-risk groups. ResultsPatient volume increased drastically once screenings were offered free of charge (period 1 = 4.6 versus period 2 = 66.0 and period 3 = 69.8 average patients per month). Incidence density per 1,000 person-years increased through each period (IDPeriod 1 = 17.2; IDPeriod 2 = 20.8; IDPeriod 3 = 25.5 cases). Cox models revealed significant differences in lung cancer risk between high-risk groups (P = .012) but not enrollment periods (P = .19). Kaplan-Meier lung cancer-free probabilities differed significantly between high-risk groups (log-rank P = .00068) but not enrollment periods (log-rank P = .18). ConclusionsThis study suggests that eligible patients are more receptive to free LDCT screening, despite most insurances not having a required copay for eligible patients.

Outcomes of chronic total occlusion percutaneous coronary intervention from the RAIAN (RAjaie - Iran) registry

ObjectiveWhile most of the evidence in CTO interventions emerge from Western and Japanese studies, few data have been published up today from the Middle East. Objective of this study was to evaluate technical success rates and clinical outcomes of an Iranian population undergoing CTO PCI in a tertiary referral hospital. Moreover, we sought to evaluate the efficacy of our CTO teaching program. MethodsThis is a retrospective single-center cohort study including 790 patients who underwent CTO PCI performed by operators with different volumes of CTOs PCI performed per year. According to PCI result, all patients have been divided into successful (n = 555, 70.3 %) and unsuccessful (n = 235, 29.7 %) groups. Study endpoints were Major Adverse Cardiovascular Events and Health Status Improvement evaluated using the Seattle Angina Questionnaire at one year. ResultsA global success rate of 70 % for antegrade and 80 % for retrograde approach was shown despite the lack of some CTO-dedicated devices. During the enrollment period, the success rate increased significantly among operators with a lower number of CTO procedures per year. One-year MACE rate was similar in both successful and unsuccessful groups (13.5 % in successful and 10.6 % in unsuccessful group, p = 0.173). One year patients’ health status improved significantly only in successful group. ConclusionsNo significant differences of in-hospital and one-year MACE were found between the successful and unsuccessful groups. Angina symptoms and quality of life significantly improved after successful CTO PCI. The RAIAN registry confirmed the importance of operator expertise for CTO PCI success.

Study on the effect of 40 Hz non-invasive light therapy system. A protocol for a randomized, double-blinded, placebo-controlled clinical trial.

With no cure or effective treatment, the prevalence of patients with Alzheimer's disease (AD) is expected to intensify, thereby increasing the social and financial burden on society. Light-based 40 Hz brain stimulation is considered a novel treatment strategy for patients with AD that may alleviate some of this burden. The clinical trial ALZLIGHT will utilize a novel Light Therapy System (LTS). The LTS uses Invisible Spectral Flicker for non-invasive induction of 40 Hz neural activity. This protocol describes a trial evaluating the efficacy and safety of a light-based 40 Hz brain stimulation in patients with mild-to-moderate AD. 62 patients with mild-to-moderate AD will participate in a randomized, double-blinded, placebo-controlled, parallel-group, and single-center trial. The participants will partake in an enrollment period of 1 month, an intervention period of 6 months, and a 1.5-month post-interventional follow-up period. Prior to the baseline measurement (week 0), the patients will be randomized to either active or placebo intervention from baseline (week 0) to post-intervention follow-up (week 26). This protocol describes a randomized, double-blinded, placebo-controlled clinical trial that may increase the understanding of the effect of gamma oscillations in the human brain and how it could be utilized as a novel and important tool for the treatment of AD. The effect is measured through a large, multidisciplinary assessment battery.Clinical trial registration:www.ClinicalTrials.gov, (NCT05260177). Registered on March 2, 2022.

The effects of a structured communication tool in patients with medically unexplained physical symptoms: a cluster randomized trial

Medically Unexplained Physical Symptoms (MUPS) are prevalent among primary care patients and frequently lead to diminished quality of life, increased healthcare costs, and decreased work participation. We aimed to examine the effects of a work-focused structured communication tool based on cognitive-behavioral therapy in patients with MUPS. In a Norwegian two-arm cluster randomized trial, the effectiveness of the structured communication tool Individual Challenge Inventory Tool (ICIT) was compared to usual care for patients with MUPS using a two-arm cluster randomized design. Enrollment period was between March 7 and April 1, 2022. Ten groups (clusters) of 103 General Practitioners (GPs) were randomized to provide the ICIT or usual care for 11 weeks. Patients received two or more sessions with their GP, and outcomes were assessed individually. Primary outcome was patient-reported change in function, symptoms, and quality of life measured by the Patient Global Impression of Change (PGIC). Secondary outcomes included sick leave, work-related self-efficacy (RTW-SE), health-related quality of life (RAND-36), and patient experiences with consultants (PEQ). The trial was registered on ClinicalTrials.gov (NCT05128019). A total of 541 patients with MUPS were enrolled in the study. In the intervention group 76% (n=223) showed a significant overall improvement in function, symptoms, and quality of life as measured by the PGIC, compared to 38% (n=236) in the usual care group (mean difference-0.8 ([95% CI-1.0 to-0.6]; p<0.0001). At 11 weeks, the intervention group had a 27-percentage point decrease in sick leave (from 52.0 to 25.2), compared to 4-percentage point decrease (from 49.7 to 45.7) in the usual care group. Furthermore, compared to usual care, the intervention group reported significant improvements in work-related self-efficacy, health-related quality of life, and greater satisfaction with the communication during the consultations. No adverse events were reported. The implementation of the structured communication tool ICIT in primary care significantly improved patient outcomes and reduced sick leave among patients with MUPS. The study was funded by The Norwegian Research Fund for General Practice.

THU215 Treatment Of Childhood-onset Craniopharyngioma Patients Using Proton Beam Therapy Versus Photon-based Radiation Therapy In The Prospective Kraniopharyngeom 2007 Trial

Abstract Disclosure: C. Friedrich: None. S. Boekhoff: None. P. Sowithayasakul: None. M. Eveslage: None. J. Beckhaus: None. B. Bison: None. B. Timmermann: None. H.L. Muller: None. Proton beam therapy (PBT) compared to photon-based radiotherapy (XRT) offers the benefit to administer lower radiation doses to critical organs thereby possibly minimizing the risk of sequelae in patients with residual craniopharyngiomas (CP) after hypothalamus-sparing surgery. The validation in large CP patient cohorts is still pending. Of 290 childhood-onset CP patients included 2007-2019 in the prospective multicenter trial KRANIOPHARYNGEOM 2007, 99 (34%) received external RT (65% PBT, 35% XRT). Outcome was compared between the different groups in terms of overall (OS) and event-free survival (EFS), quality of life (QoL using PEDQOL), functional capacity (FMH), and auxological data (BMI and height SDS) one, three and five years after irradiation/CP diagnosis. PBT became the predominant irradiation technique during the study period (used in 23% and 77% of all irradiated patients registered within the first and second half of the enrollment period, respectively). PBT as well as XRT were associated with high (p&amp;lt;0.001) EFS (PBT: 0.917 ± 0.040; XRT: 0.940 ± 0.041) compared to non-RT (EFS: 0.669 ± 0.044). OS was similar in all groups. No differences between PBT, XRT and non-RT CP patients concerning functional capacity and anthropometric parameters (height SDS, BMI SDS) have been obtained. Only in the PEDQOL domain “physical function”, proxy-assessed QoL was lower one year after PBT when compared to XRT treated and non-irradiated CP patients. PBT is similar efficient in preventing relapses in childhood-onset CP patients. During follow-up, clinically relevant differences between PBT and XRT in terms of QoL, functional capacity and degree of obesity as a marker of hypothalamic syndrome were not detectable. While PBT is increasingly applied, studies on larger CP cohorts with longer follow-up after RT are warranted to analyze, whether it can prevent sequelae such as hypothalamic syndrome and severe obesity compared to XRT. Presentation: Thursday, June 15, 2023