Restrictive Criteria Research Articles

Barriers and facilitators to discussion of cancer clinical trials: A qualitative study.

e18588 Background: NCCN guidelines indicate that cancer clinical trials (CCTs) are the best management for patients with cancer. However, only 5% of patients enroll in CCTs. Few studies have examined oncology providers’ perceptions of the barriers and facilitators to discussing CCTs. Methods: This qualitative study was part of the ASCO-ACCC Initiative to Increase Racial and Ethnic Diversity in Clinical Trials. A convenience sample of 10 U.S oncology providers participated in this sub-study. Their perceived barriers and facilitators to discussion of CCTs at the provider, patient, system, and CCTs levels were examined. To achieve triangulation, each provider reviewed 5 recent patient encounters to identify actual barriers and facilitators using chart-stimulated recall (CSR). Results: Nine participants were oncologists and 1 was a clinical research coordinator; 5 were female; 4 were White; 3 were Asian and 3 were Black. The table shows the most cited barriers and facilitators to discussion of CCTs, and the number of interviews in which those barriers or facilitators was mentioned. Barriers were patients’ negative attitudes and lack of knowledge of CCTs, provider assumptions about patients, lack of time to discuss CCTs and restrictive CCT eligibility criteria. Facilitators were having a CCT workforce, systematically discussing CCTs with all patients, patients requiring new treatment options or were aware of CCTs, and electronic medical record (EMR) strategies. CSR validated the most cited barriers and facilitators except patient negative attitudes and system barriers and facilitators. Conclusions: Many of the barriers to discussing CCTs are addressable with the cited facilitators (e.g. assumptions can be addressed by systematically discussing CCTs with all patients; lack of time to discuss CCTs can be addressed by a robust CCT workforce; restrictive CCT criteria can be broadened). A larger study is needed to further generalize and validate the findings. [Table: see text]

Overall survival of patients with BRAF-mutant metastatic colorectal cancer treated with encorafenib-cetuximab in a real-world nationwide study in the Netherlands.

3589 Background: Approximately 10-15% of patients with metastatic colorectal cancer (mCRC) have BRAFV600E mutated tumors. Encorafenib plus cetuximab (EC) combination treatment was approved following the results of the randomized phase III BEACON trial and is currently recommended for all pretreated patients with BRAFV600E-mutant mCRC. Selection of patients in randomized controlled trials is based on restrictive eligibility criteria and often not representative of the patient population in daily clinical practice. Complementary real-world effectiveness studies can improve knowledge on the generalizability of trial results, and support decision making in clinical practice. Methods: This population-based study included all mCRC patients in the Netherlands treated with EC since approval in October 2020 until June 2022. Individual patient data and original pathology reports were collected. Primary endpoint was overall survival (OS), defined as time from EC initiation until death by any cause, analyzed by Kaplan-Meier curves. WebPlotDigitizer was used to reconstruct the Kaplan-Meier survival curve of the BEACON trial. Uni- and multivariable analyses were performed. Subgroup analyses were conducted for patients who would have been eligible for the BEACON trial based on key eligibility criteria: BRAFV600E mutation, 1-2 prior regimens, world health organization performance status (WHO PS) of 0-1, normal neutrophil count, absence of brain metastases, no prior RAS/RAF/MEK treatment, and no concurrent malignancies. Results: 155 patients were included with a median follow-up time of 11.1 months. Patient characteristics differed from BEACON in mean age (64 versus 60 years), primary tumor sidedness (69% versus 50% right-sided) and WHO PS (23% versus 51% WHO 0). Median OS of the total real-world cohort was 6.6 months (95% CI: 6.0-8.3) and differed significantly from BEACON (9.3 months; 95% CI: 8.0-11.3; p = 0.003). 35% of real-world patients treated with EC would not have been eligible for the BEACON trial, showing an inferior median OS of 6.0 months (95% CI: 4.6-9.2) compared to 7.0 months (95% CI: 6.4-9.8) in trial eligible real-world patients. WHO PS was independently associated with poor survival in multivariable analysis. Patients with WHO PS≥2 had a median OS of 3.9 months (95% CI: 2.4-NA) with a hazard rate of 2.5 (95% CI: 1.1-5.5; p = 0.003). Conclusions: This largest to date - unselected - population-based cohort of mCRC patients treated with EC showed an efficacy-effectiveness gap for OS. These outcomes should be considered in clinical practice for treatment decision making. Omitting EC for subgroups demonstrating very short OS, such as patients with WHO PS ≥2, needs to be considered. Further research is warranted to adapt treatment guidelines towards a more personalized approach for patients with BRAFV600E-mutated mCRC.

0342 Are Clinical Trials for Insomnia Recruiting Real World Patients?

Abstract Introduction Studies that have resulted in recent approval of hypnotics for chronic insomnia disorder (CID) have extremely restrictive inclusion criteria. We sought to determine how many patients seen in a sleep medicine clinic would be eligible to participate in these trials in order to assess the generalizability of these findings to clinical populations. Methods Six-hundred and twenty-eight patients were screened to identify 100 patients who were ≥18 years old, had a diagnosis of CID, and were prescribed a hypnotic medication at a sleep medicine clinic in a quaternary level healthcare center. Information regarding age, sex, body mass index, comorbid diagnoses, sleep schedule, medications, alcohol/tobacco/illicit drug use, caffeine intake, as well as Epworth Sleepiness Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index scores were abstracted. These data were compared against the inclusion and exclusion criteria for recent regulatory Phase III trials of orexin receptor antagonists (suvorexant, lemborexant, daridorexant). Results Of the 100 patients with CID (mean age=56.2 years; 57% female), only 3 patients met eligibility criteria for inclusion. A majority of patients (80%) would have been excluded due to a prior/concurrent trial of cognitive behavioral therapy for insomnia. If this criterion was set aside, only 11 patients would have been eligible to participate. The remaining top reasons for potential exclusion from the regulatory trials were: presence of medical comorbidities (36%), daytime napping (33%), and sleep apnea (30%). Conclusion A very small number of patients with CID seen in a clinical setting met eligibility criteria for clinical trials of hypnotic medications resulting in regulatory approval. This substantially limits the generalizability of findings from these trials and restricts our ability to determine the efficacy of these drugs in clinical populations. Future trials should enroll patients with less restrictive criteria to help determine the effectiveness of these medications in real world settings. Support (if any)

Visual impairment due to retinopathy of prematurity and concomitant disabilities in the Netherlands

AimDetermine incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant disabilities between 2009 and 2018 in the Netherlands and compare data to four former similar studies. Secondly, monitor if infants were missed for ROP-screening since the adoption of stricter, risk factor guided criteria (2013). MethodsRetrospective inventory on anonymous data of infants diagnosed with ROP from Dutch visual impairment-institutes. Data including: best corrected visual acuity, ROP-treatment and concomitant disabilities: bronchopulmonary dysplasia, behavioral abnormalities, epilepsy, hearing deficit, developmental delay, cerebral palsy and cerebral visual impairment. During the study period, lower age limit for neonatal life support (2010) and higher oxygen saturation targets (2014) were implemented. ResultsRecords of 53 infants were analyzed. Visual impairment incidence due to ROP was 2.02 per 100.000 live births (2000–2009: 1.84, p = 0.643). Compared to earlier periods (1975–2000), a significant decrease was observed. The incidence of concomitant disabilities remained stable. Mean gestational age (GA) continued to decrease to 26.6 ± 1.9 weeks (2000–2009: 27.4 ± 2.0 weeks, p = 0.047). All patients met the screening inclusion criteria. ConclusionThe incidence of visual impairment due to ROP and concomitant disabilities between 2009 and 2018 has not increased, despite lower GA and higher oxygen saturation targets. None of the infants were missed for ROP screening following introduction of more restricted screening inclusion criteria.

Examining Exclusion Criteria in Advanced Prostate Cancer Clinical Trials: An Assessment of recommendations From the American Society Of Clinical Oncology and Friends of Cancer Research

PurposeEligibility criteria illustrate the characteristics of the study population and promote the safety of participants. However, overreliance on restrictive eligibility criteria may limit the generalizability of outcomes. As a result, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) issued statements to curtail these challenges. In this study, we aimed to assess restrictiveness in eligibility criteria across advanced prostate cancer clinical trials. Materials and MethodsWe identified all phase I, II, and III advanced prostate cancer clinical trials between June 30, 2012, and June 30, 2022, through Clinicaltrials.gov. We evaluated whether a clinical trial excluded, conditionally included, or did not report 4 common criteria: brain metastases, prior or concurrent malignancies, HIV infection, and hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. Performance status (PS) criteria were recorded based on the Eastern Cooperative Oncology Group (ECOG) scale. ResultsOut of 699 clinical trials within our search strategy, 265 (37.9%) trials possessed all the required data and were included in our analysis. The most common excluded condition of our interest was brain metastases (60.8%), followed by HIV positivity (46.4%), HBV/HCV positivity (46.0%), and concurrent malignancies (15.5%). Additionally, 50.9% of clinical trials only included patients with ECOG PS 0 to 1. HIV and HBV/HCV infection were exclusion criteria of 22 (80.8%) and 19 (73.1%) immunotherapy trials, respectively. ConclusionPatients with brain metastases, prior or concurrent malignancies, HIV infection, HBV/HCV infection, or low-functioning PS were overly restricted from participating in advanced prostate clinical trials. Advocating for broader criteria may ameliorate generalizability.

Spatial modelling the location choice of large-scale solar photovoltaic power plants: Application of interpretable machine learning techniques and the national inventory

The optimum site selection of solar photovoltaics power plant across a given geographic space is usually assessed by using the geographic information system based multi-criteria decision making methods with various restriction criteria, while such evaluation results vary with criteria weights and are difficult to be validated in real life practices. To address this issue, this paper uses a national inventory dataset of large-scale solar photovoltaics installations (the land coverage area ≥ 1 hm2) to investigate the spatial location choices of solar power plants with the aids of interpretable machine learning techniques. A total of 21 geospatial conditioning factors of solar energy development are considered. The location choices of solar photovoltaics installation are then modeled with the multi-Layer perceptron, random forest, extreme gradient boosting models for each land cover type (e.g. cropland, forest, grassland, and barren). The SHapley additive explanation and variable importance measure methods are adopted to identify key criteria and their influences on the solar photovoltaics installation location selection. Results indicate that the random forest model presented the better performance among three machine learning models. The relative importance of conditioning factors revealed that the vegetation index and distance to power grid were always the most important predictors of solar photovoltaics installation location. Furthermore, topographical factors and transportation convenience may have a moderate impact on the spatial distribution of solar photovoltaics power stations. Unexpectedly, most of resources endowment and socio-economic factors play a negligible role in determining the optimal siting of solar power farms. Simulated solar photovoltaics installations probability maps illustrated that the most suitable regions account for 4.6 % of China’s total land area. The evidence-based method proposed in this research can not only help identify suitable solar photovoltaics farm locations in terms of various decision-making criterion, but also provide a robust planning tool for sustainable development of solar energy sources.

A perspective: Challenges and opportunities of a novel national dental benefit.

In Canada, the federal government launched the interim Canada Dental Benefit (CDB) on December 1, 2022, to support access to dental care for children <12 years. The interim benefit shows government's assurance to develop a long-term national dental care program. The benefit will be a cash transfer through Canada's revenue services agency, ranging from $260 to $650 annually. This perspective examines the federal initiative and reflects on its strengths and challenges to learn lessons, which can support the long-term solution that is being currently planned. This article outlines a number of positive aspects as well as challenges from the perspectives of varied stakeholders; the feasibility of the application process; remaining potential gaps due to restricted eligibility criteria; possible effects of unrestricted oral health care services and reimbursement rates; valuing of patient autonomy; guidelines for the expansion of the program to other populations; and remaining barriers to oral health care access are analyzed. The CDB is cause for excitement for the Canadian population because it is an opportunity to reduce affordability barriers to accessing dental care. That said, it is important to discuss anticipated challenges and indirect consequences, particularly through the lens of equity, to support the new CDB and the proposed national dental care program in achieving the much-awaited goal of putting the mouth back into the body.

Risk of adverse perinatal outcomes in pregnancies with “small” fetuses not meeting Delphi consensus criteria for fetal growth restriction

Previous research endeavors examining the association between clinical characteristics, sonographic indices, and the risk of adverse perinatal outcomes in pregnancies complicated by fetal growth restriction have been hampered by a lack of agreement regarding its definition. In 2016, a consensus definition was reached by an international panel of experts via the Delphi procedure, but as it currently stands, this has not been endorsed by all professional organizations. This study aimed to assess whether an independent association exists between estimated fetal weight and/or abdominal circumference of <10th percentile and adverse perinatal outcomes when consensus criteria for growth restriction are not met. Data were derived from a passive prospective cohort of singleton nonanomalous pregnancies at a single academic tertiary care institution (2010-2022) that fell into 3 groups: (1) consecutive fetuses that met the Delphi criteria for fetal growth restriction, (2) small-for-gestational-age fetuses that failed to meet the consensus criteria, and (3) fetuses with birthweights of 20th to 80th percentile randomly selected as an appropriately grown (appropriate-for-gestational-age) comparator group. This nested case-control study used 1:1 propensity score matching to adjust for confounders among the 3 groups: fetal growth restriction cases, small-for-gestational-age cases, and controls. Our primary outcome was a composite: perinatal demise, 5-minute Apgar score of <7, cord pH of ≤7.10, or base excess of ≥12. Pregnancy characteristics with a P value of <.2 on univariate analyses were considered for incorporation into a multivariable model along with fetal growth restriction and small-for-gestational-age to evaluate which outcomes were independently predictive of adverse perinatal outcomes. Overall, 2866 pregnancies met the inclusion criteria. After propensity score matching, there were 2186 matched pairs, including 511 (23%), 1093 (50%), and 582 (27%) patients in the small-for-gestational-age, appropriate-for-gestational-age, and fetal growth restriction groups, respectively. Moreover, 210 pregnancies (10%) were complicated by adverse perinatal outcomes. None of the pregnancies with small-for-gestational-age OR appropriate-for-gestational-age fetuses resulted in perinatal demise. Twenty-three of 511 patients (5%) in the small-for-gestational-age group had adverse outcomes based on 5-minute Apgar scores and/or cord gas results compared with 77 of 1093 patients (7%) in the appropriate-for-gestational-age group (odds ratio, 0.62; 95% confidence interval, 0.39-1.00). Furthermore, 110 of 582 patients (19%) with fetal growth restriction that met the consensus criteria had adverse outcomes (odds ratio, 3.08; 95% confidence interval, 2.25-4.20), including 34 patients with perinatal demise or death before discharge. Factors independently associated with increased odds of adverse outcomes included chronic hypertension, hypertensive disorders of pregnancy, and early-onset fetal growth restriction. Small-for-gestational age was not associated with the primary outcome after adjustment for 6 other factors included in a model predicting adverse perinatal outcomes. The bias-corrected bootstrapped area under the receiver operating characteristic curve for the model was 0.72 (95% confidence interval, 0.66-0.74). The bias-corrected bootstrapped area under the receiver operating characteristic curve for a 7-factor model predicting adverse perinatal outcomes was 0.72 (95% confidence interval, 0.66-0.74). This study found no evidence that fetuses with an estimated fetal weight and/or abdominal circumference of 3rd to 9th percentile that fail to meet the consensus criteria for fetal growth restriction (based on Doppler waveforms and/or growth velocity of ≥32 weeks) are at increased risk of adverse outcomes. Although the growth of these fetuses should be monitored closely to rule out evolving growth restriction, most cases are healthy constitutionally small fetuses. The management of these fetuses in the same manner as those with suspected pathologic growth restriction may result in unnecessary antenatal testing and increase the risk of iatrogenic complications resulting from preterm or early term delivery of small fetuses that are at relatively low risk of adverse perinatal outcomes.

AGNs in the CALIFA survey: X-ray detection of nuclear sources

ABSTRACT A complete demographic of active galactic nuclei (AGNs) is essential to understand the evolution of the Universe. Optical surveys estimate the population of AGNs in the local Universe to be of ∼ 4 per cent. However, these results could be biased towards bright sources, not affected by the host galaxy attenuation. An alternative method for detecting these objects is through the X-ray emission. In this work, we aim to complement the AGN population of the optical CALIFA survey (941 sources), by using X-ray data from Chandra, which provides the best spatial resolution to date, essential to isolate the nuclear emission from the host galaxy. We study a total of 138 sources with available data. We find 34 new bona fide AGNs and 23 AGN candidates, which could increase the AGN population to 7–10 per cent among the CALIFA survey. X-rays are particularly useful for low-luminosity AGNs since they are excluded by the criterion of large equivalent width of the $\rm {H\alpha }$ emission line when applied to optical selections. Indeed, placing such a restrictive criteria might cause a loss of up to 70 per cent of AGN sources. X-ray detected sources are preferentially located in the right side of the [${\mathrm{O}}\, {\small {\rm III}}$ ]/Hβ versus [${\mathrm{N}}\, {\small {\rm II}}$ ]/Hα diagram, suggesting that this diagram might be the most reliable at classifying AGN sources. Our results support the idea that multiwavelength studies are the best way to obtain a complete AGN population.

Characteristics of sudden death by clinical criteria.

Sudden death is a leading cause of deaths nationally. Definitions of sudden death vary greatly, resulting in imprecise estimates of its frequency and incomplete knowledge of its risk factors. The degree to which time-based and coronary artery disease (CAD) criteria impacts estimates of sudden death frequency and risk factors is unknown. Here, we apply these criteria to a registry of all-cause sudden death to assess its impact on sudden death frequency and risk factors. The sudden unexpected death in North Carolina (SUDDEN) project is a registry of out of-hospital, adjudicated, sudden unexpected deaths attended by Emergency Medical Services. Deaths were not excluded by time since last seen or alive or by prior symptoms or diagnosis of CAD. Common criteria for sudden death based on time since last seen alive (both 24 hours and 1 hour) and prior diagnosis of CAD were applied to the SUDDEN case registry. The proportion of cases satisfying each of the 4 criteria was calculated. Characteristics of victims within each restrictive set of criteria were measured and compared to the SUDDEN registry. There were 296 qualifying sudden deaths. Application of 24 hour and 1 hour timing criteria compared to no timing criteria reduced cases by 25.0% and 69.6%, respectively. Addition of CAD criteria to each timing criterion further reduced qualifying cases, for a total reduction of 81.8% and 90.5%, respectively. However, characteristics among victims meeting restrictive criteria remained similar to the unrestricted population. Timing and CAD criteria dramatically reduces estimates of the number of sudden deaths without significantly impacting victim characteristics.

Evaluating posttraumatic stress in young adult cancer survivors: Implications of revised DSM-5 traumatic event criteria.

The Diagnostic and Statistical Manual for Psychiatric Diagnoses (DSM-5) significantly narrowed conditions under which life-threatening illnesses meet qualifying traumatic event (QTE) criteria for posttraumatic stress disorder (PTSD). To investigate the impact of this change on identification of PTSD in young adult cancer survivors (YACS), we compared prevalence of QTE exposure using DSM-5 and earlier DSM-IV criteria. The Structured Clinical Interview for the DSM-5 (SCID-5) was customized for study goals and administered to a convenience sample of 250 YACS ages 18-40 followed at a single cancer center. The SCID-5 was well-tolerated by participants and estimated duration was brief (33min; range 12-75). Only 35 interviews (14%) presented complex scoring questions. 168 participants (67.2%) identified cancer as their "most stressful or traumatic experience." Applying DSM-IV criteria, 227 YACS (90.8%) reported any QTEs; prevalence was significantly reduced following more restrictive DSM-5 QTE criteria, with only 124 YACS (49.6%) reporting ≥1 QTE (z=-9.68, p<0.001). The SCID-5 can be successfully adapted to assess QTEs in YACS following both DSM-IV and DSM-5 criteria. DSM-5 criteria significantly limit prevalence of QTE exposures compared with DSM-IV. As the majority of YACS identify cancer as their most stressful life event, it is critically important to investigate its impact on their psychological functioning. Until more is known about how PTSD symptoms may arise after cancer, clinicians and researchers should adapt PTSD assessments to systematically evaluate the role of cancer as a traumatic event that may lead to PTSD symptoms in YACS.

Abstract 5538: Prevalence of factors serving as common cancer clinical trial eligibility criteria by race and ethnicity

Abstract Background: Racial/ethnic minority patients remain underrepresented in clinical trials potentially due to restrictive trial eligibility criteria that disproportionally affect minority cancer patients. Objective: To examine the prevalence of existing medical conditions and abnormal lab values that commonly serve as clinical trial eligibility criteria among cancer patients by race and ethnicity. Methods: A cross-sectional analysis was conducted among patients new to Moffitt Cancer Center in 2011-2021 with multiple myeloma (n=3,967), breast (n=14,348), lung (n=10,492), and prostate (n=7,823) cancers. Demographics, existing medical conditions, and lab values were obtained from the Electronic Health Record, whereas history of cancer and metastatic disease at diagnosis were obtained from the Cancer Registry. Prevalence of medical conditions and abnormal lab values were reported among all patients and compared by race groups (White, Black, Hispanic, and other races) using age-adjusted logistic regression. For factors with prevalence higher than 5%, stratified analysis was conducted with respect to cancer type and adjusted for multiple comparisons. Results: Compared to White patients, Black (B) and Hispanic (H) patients were found to have higher prevalence of diabetes (OR [odds ratio] = 2.26 [B]/1.40 [H]), organ transplantation (OR=1.58 [B]/1.77 [H]), hepatitis (OR=1.74 [B]/1.48 [H]), HIV (OR=4.25 [B]/1.92 [H]), and abnormal creatinine value (OR=1.77 [B]/1.23 [H]). In addition, Black patients were more likely to have hypertension (OR=1.41) while patients of other races were more likely to be diabetic (OR=1.36). Similar patterns were observed across cancer types. Conclusion: Restrictive cancer clinical trial eligibility criteria may post a structural barrier that disproportionately impact racial/ethnic minority patients. Investigators should consider leveraging real-world data to define and design appropriate trial eligibility criteria. Prevalence of factors commonly included as clinical trial eligibility by race/ethnicity. Factors All White Black Hispanic Other Prevalence (%) % % OR (95% CI) % OR (95% CI) % OR (95% CI) Diabetes 6.30 5.90 10.00 2.26 (1.97-2.58) 6.50 1.40 (1.20-1.63) 6.50 1.36 (1.07-1.70) Chronic obstructive pulmonary disease 10.30 11.40 6.20 0.61 (0.52-0.72) 6.10 0.61 (0.52-0.71) 5.90 0.57 (0.44-0.72) Hypertension 18.00 18.50 19.80 1.41 (1.27-1.55) 13.40 0.87 (0.78-0.97) 13.50 0.84 (0.71-1.00) Heart condition 3.00 3.10 2.60 1.10 (0.86-1.39) 2.00 0.80 (0.61-1.03) 1.80 0.70 (0.44-1.05) Organ transplant 0.90 0.90 1.40 1.58 (1.11-2.20) 1.50 1.77 (1.28-2.41) 0.40 0.46 (0.16-1.00) Autoimmune disease 2.50 2.60 2.10 0.84 (0.63-1.09) 1.90 0.78 (0.59-1.01) 2.20 0.90 (0.60-1.30) Hepatitis 0.70 0.70 1.20 1.74 (1.17-2.49) 1.00 1.48 (0.99-2.15) 0.40 0.60 (0.21-1.30) HIV infection 0.30 0.20 0.90 4.25 (2.62-6.74) 0.40 1.92 (1.01-3.40) 0.20 0.71 (0.12-2.30) History of any cancer 15.90 17.20 10.30 0.69 (0.60-0.78) 10.30 0.69 (0.61-0.77) 10.90 0.71 (0.59-0.85) Metastasis at diagnosis 21.20 21.40 22.60 1.13 (1.02-1.24) 19.80 0.96 (0.87-1.05) 18.60 0.88 (0.75-1.02) Abnormal neutrophil count 19.70 20.10 20.20 1.00 (0.86-1.16) 16.60 0.79 (0.67-0.93) 18.20 0.89 (0.69-1.13) Abnormal creatinine 14.00 13.50 19.30 1.77 (1.57-1.99) 14.10 1.23 (1.08-1.39) 13.40 1.13 (0.93-1.38) Abnormal glomerular filtration rate 14.00 13.50 22.40 2.32 (1.99-2.70) 11.20 1.07 (0.88-1.30) 10.10 0.91 (0.66-1.22) Abnormal bilirubin 2.40 2.50 2.40 1.02 (0.69-1.45) 2.40 1.03 (0.70-1.46) 2.40 0.99 (0.52-1.69) Abnormal aspartate aminotransferase 9.40 9.40 9.20 0.88 (0.72-1.07) 9.70 0.92 (0.76-1.12) 8.50 0.82 (0.59-1.12) Citation Format: Yayi Zhao, Rossybelle P. Amorrortu, Rachel Howard, Kedar S. Kirtane, Susan T. Vadaparampil, Dana E. Rollison. Prevalence of factors serving as common cancer clinical trial eligibility criteria by race and ethnicity. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5538.

Lost in transition? Community residential facility staff and stakeholder perspectives on previously incarcerated older adults’ transitions into long-term care

BackgroundEstablishing an effective continuum of care is a pivotal part of providing support for older populations. In contemporary practice; however, a subset of older adults experience delayed entry and/or are denied access to appropriate care. While previously incarcerated older adults often face barriers to accessing health care services to support community reintegration, there has been limited research on their transitions into long-term care. Exploring these transitions, we aim to highlight the challenges of securing long-term care services for previously incarcerated older adults and shed light on the contextual landscape that reinforces the inequitable care of marginalized older populations across the care continuum.MethodsWe performed a case study of a Community Residential Facility (CRF) for previously incarcerated older adults which leverages best practices in transitional care interventions. Semi-structured interviews were conducted with CRF staff and community stakeholders to determine the challenges and barriers of this population when reintegrating back into the community. A secondary thematic analysis was conducted to specifically examine the challenges of accessing long-term care. A code manual representing the project themes (e.g., access to care, long-term care, inequitable experiences) was tested and revised, following an iterative collaborative qualitative analysis (ICQA) process.ResultsThe findings indicate that previously incarcerated older adults experience delayed access and/or are denied entry into long-term care due to stigma and a culture of risk that overshadow the admissions process. These circumstances combined with few available long-term care options and the prominence of complex populations already in long-term care contribute to the inequitable access barriers of previously incarcerated older adults seeking entry into long-term care.ConclusionsWe emphasize the many strengths of utilizing transitional care interventions to support previously incarcerated older adults as they transition into long-term care including: 1) education & training, 2) advocacy, and 3) a shared responsibility of care. On the other hand, we underscore that more work is needed to redress the layered bureaucracy of long-term care admissions processes, the lack of long-term care options and the barriers imposed by restrictive long-term care eligibility criteria that sustain the inequitable care of marginalized older populations.

Rational Use of Microbiological Tests in the Diagnosis of Central Nervous System Infections Using Restrictive Criteria: a Retrospective Study

Central nervous infections, mostly represented by meningitis and encephalitis, remain a diagnostic challenge despite substantial advances in microbiological tools in recent years. Meanwhile, extensive microbiological workups, which often prove to be irrelevant retrospectively, continue to be processed on a large scale, therefore leading to unnecessary costs. The main goal of this study was to evaluate a systematic approach enabling more rational use of microbiological tools in the setting of community-acquired central nervous system infection diagnosis. In this single-center descriptive study, the modified Reller criteria were retrospectively extended to all neuropathogens tested in cerebrospinal fluid (CSF) samples with the FilmArray meningitis/encephalitis panel (BioFire Diagnostics, LLC) and bacterial culture. The inclusion period was 30 months. In total, 1,714 fluid (CSF) samples analyzed from 1,665 patients over 2 and a half years were reported. According to the retrospective application of the modified Reller criteria, microbiological testing was considered unnecessary in 544 CSF samples. Fifteen positive microbiological results were found among these samples, interpreted either as inherited chromosomally integrated human herpesvirus 6 (HHV-6), a false-positive result, or a true microbial detection without clinical relevance. No CNS infection case would have been missed if these analyses were not carried out, while about one-third of all meningitis/encephalitis multiplex PCR panels would have been saved. Our retrospective analysis suggests that the modified Reller criteria could be safely applied to all microbiological tests performed in CSF, thereby saving substantial costs. IMPORTANCE Microbiological testing in general and in the setting of central nervous system (CNS) infection in particular are often excessive, leading to superfluous laboratory work and costs. In this regard, restrictive criteria, named Reller criteria, have been developed to reduce unnecessary CSF herpes simplex virus 1 (HSV-1) PCR testing when suspecting encephalitis. These criteria were then adapted for increased safety to become the modified Reller criteria. This retrospective study aims at evaluating the safety of these criteria when applied to CSF microbiological testing in general, including multiplex PCR, direct examination, and bacterial culture. The postulate was that a CNS infection can be excluded if none of these criteria is present. According to our data set, no CNS infection would have been missed if the modified Reller criteria would have been applied to save microbiological tests. This study therefore proposes a simple way to reduce unnecessary microbiological testing in the context of CNS infection suspicion.

Legal certainty compliance analysis of measures aimed at spread prevention of coronavirus disease

Acute respiratory disease COVID-19 has caused unprecedented restrictions on human rights since the end of World War II. Restrictive measures to prevent the spread of coronavirus disease have been introduced almost worldwide. However, like any restriction of human rights, such measures must comply with the principle of proportionality. One of the main requirements is that the restriction must be prescribed by law and comply with the legal certainty. This requirement stipulates that any restrictions on human rights, including restrictive measures aimed at preventing the spread of coronavirus disease must be prescribed by law, adopted in the form and manner prescribed by current legislation and international human rights standards, promulgated in the manner prescribed by law, understood by ordinary citizens, predictable and obviously enforced. In this paper, the question of compliance with the legal certainty criteria of restrictions, implemented measures to prevent the spread of coronavirus disease in Ukraine and some other countries are considered. The question whether the measures aimed at preventing the spread of coronavirus were prescribed by law, adopted in the form and manner prescribed by applicable law and international human rights standards, were promulgated in the manner prescribed by law, were clear to ordinary citizens, predictable and obviously enforced is analyzed. However, the analysis of restrictive measures aimed at preventing the spread of coronavirus disease introduced in Ukraine raises several questions about the form of such restrictions. Firstly, no special law has been passed on this issue. Secondly, all restrictions were introduced by resolutions of the Cabinet of Ministers of Ukraine bylaws with an obvious excess of authority. Moreover, the official publication of the introduction of restrictive measures aimed at preventing the spread of coronavirus disease took place the day before, on the day, or even the day after the introduction of restrictive measures aimed at preventing the spread of coronavirus disease.

Development of a nurse-led decision counseling program for improving hepatocellular carcinoma screening: A typology-guided feasibility study

ObjectiveHepatocellular carcinoma (HCC) is frequently diagnosed late. Although ultrasound-based HCC screening is recommended, its effectiveness is restricted by underutilization. This study aimed to develop a nurse-led decision counseling program used to improve HCC screening in patients with hepatitis B and to evaluate its feasibility in terms of process, resources, management, and cultural acceptance. MethodsThe nurse-led decision counseling program was developed following the Medical Research Council framework and the preventive health model. Its components were informed by a systematic review and a qualitative study that had explored empirical HCC screening barriers. Guided by typology of Tickle-Degnen, a feasibility study was conducted among twenty eligible patients with hepatitis B, who were randomized to receive the intervention plus usual care or usual care only. Multisets of feasibility data were collected from interviews, field notes, and minutes of discussions with participants, family members, and clinical specialists. ResultsThe program consists of health education, tailored information, values clarification exercises, and exploring and addressing barriers, which help to achieve informed and value-based HCC screening utilization. Feasibility assessments identified and improved process issues, such as restrictive inclusion criteria and cultural challenges, including (1) default mistrust, (2) discrimination and confidentiality concerns, (3) cultural reluctance to open discussions about HCC screening, and (4) social influence under a collectivist culture. ConclusionsThe study informs an innovative feasibility typology for nursing interventions and contributes to a promising, feasible, and culturally relevant intervention to improve HCC screening and prevent advanced diagnosis in hepatitis B-induced HCC in China and other hepatitis B-prevalent Asian countries. Trial registrationClinicaltrials.gov: NCT04659005.

Commercial health plans use of patient subgroup restrictions: An analysis of orphan and US Food and Drug Administration-expedited programs.

BACKGROUND: Health plans apply utilization management criteria to guide their enrollees' access to prescription drugs. Patient subgroup restrictions (ie, clinical prerequisites for drug coverage) are a form of utilization management that have not been thoroughly investigated. OBJECTIVE: To examine the frequency with which large US commercial health plans impose patient subgroup restrictions beyond the US Food and Drug Administration (FDA) label in their coverage policies for orphan drugs and for drugs included in 1 or more FDA-expedited programs. To determine how consistently these patient subgroup restrictions align with eligibility criteria specified in each drug's pivotal clinical trial(s). METHODS: The Tufts Medical Center Specialty Drug Evidence and Coverage (SPEC) database was used, which includes coverage policies issued by 17 large US commercial health plans. SPEC contained 3,786 orphan drug policies and 4,027 FDA-expedited drug policies (current as of December 2020). SPEC data on plans' patient subgroup restrictions were assessed for the first objective. Each patient subgroup restriction was benchmarked against the corresponding eligibility criteria for a drug's pivotal clinical trial(s) for the second objective. To do so, the "Clinical Studies" section of the drug's FDA label was reviewed or, if necessary, the published manuscript describing the drug's pivotal trial(s). Patient subgroup restrictions were categorized as follows: (1) "consistent," the restriction and trial eligibility criterion are equivalent; (2) "same measure, more stringent," the restriction and trial eligibility criteria depend on the same measure, but the plan coverage is more restrictive; (3) "same measure, less stringent," the restriction and trial eligibility criteria depend on the same measure, but the plan coverage is less restrictive; and (4) "not consistent," the restriction and trial eligibility criteria depend on different measures. RESULTS: Health plans imposed patient subgroup restrictions in 20.2% of orphan drug policies (frequency varied by health plan, 11.7%-36.6%), and in 21.8% of FDA-expedited drug policies (frequency varied by health plan, 11.1%-47.9%). Of the 936 patient subgroup restrictions in orphan drug policies, 60.3% were categorized as consistent; 7.3% as same measure, more stringent; 12.0% as same measure, less stringent; and 20.5% as not consistent. Of the 1,070 patient subgroup restrictions in FDA-expedited drug policies, 57.5% were categorized as consistent; 6.7% as same measure, more stringent; 16.0% as same measure, less stringent; and 19.8% as not consistent. CONCLUSIONS: Patient subgroup restrictions for orphan drugs and FDA-expedited programs varied substantially across health plans, potentially resulting in inconsistent access to a given therapy across the approved patient population. Patient subgroup restrictions tend to be consistent with eligibility criteria specified in pivotal clinical trials. DISCLOSURES: This study was funded by Sarepta Therapeutics, Inc. Alexa C Klimchak and Lauren E Sedita are employees of Sarepta Therapeutics, Inc., and may own stock/options in the company.

Perfusion imaging in acute ischaemic stroke – the beginning of the end?

Endovascular thrombectomy (EVT) for large vessel occlusion in acute ischaemic stroke is the standard of care when initiated within 6 hours of stroke onset, and is performed between 6-24 hours using advanced neuroimaging (CT perfusion or MR imaging) for patients who meet the strict imaging selection criteria. However, adherence to the restrictive imaging criteria recommended by current guidelines is impeded in many parts of the world, including the UK, by resource constraints and limited access to advanced neuroimaging in the emergency setting. Furthermore, recent randomised and non-randomised studies have demonstrated that patients selected without advanced neuroimaging (with non-contrast CT and CT angiography only) using less restrictive imaging criteria for EVT eligibility beyond 6 hours from onset still benefited from EVT treatment, thereby increasing the proportion of patients eligible for EVT and widening the potential treatment impact at a population level. Hence, current guidelines should be updated expeditiously to reflect the level I evidence in support of more liberal imaging selection criteria for patients presenting with acute ischaemic stroke due to a large vessel occlusion.

Predictive index for adverse perinatal outcome in pregnancies complicated by fetal growth restriction.

To develop and validate an index predictive of adverse perinatal outcome (APO) in pregnancies meeting the consensus-based criteria for fetal growth restriction (FGR) endorsed by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). This was a retrospective analysis of consecutive singleton non-anomalous gestations meeting the ISUOG-endorsed criteria for FGR at a single tertiary care center from November 2010 to August 2020. The dataset was divided randomly into a development set (two-thirds) and a validation set (one-third). The primary composite APO comprised one or more of: perinatal demise, Grade III-IV intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), seizures, hypoxic ischemic encephalopathy (HIE), necrotizing enterocolitis (NEC), sepsis, bronchopulmonary dysplasia (BPD) and length of stay in the neonatal intensive care unit (NICU) > 7 days. Regression analysis incorporated clinical factors readily available at the time of FGR diagnosis. The sum of β coefficient-based weights yielded an index score, the performance of which was assessed in the validation set. Score cut-offs were selected to identify 'high-risk' and 'low-risk' ranges for which positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR-) likelihood ratios were calculated. Of the 875 consecutive pregnancies that met the criteria for FGR and were included in the study cohort, 405 (46%) were complicated by one or more components of the composite APO, including 54 (6%) perinatal deaths, 22 (3%) neonates with Grade III-IV IVH and/or PVL, nine (1%) with seizures and/or HIE, 91 (10%) with BPD, 57 (7%) with sepsis, 21 (2%) with NEC, and 361 (41%) who remained in the NICU > 7 days. In addition, 270 (31%) pregnancies were delivered by Cesarean section for non-reassuring fetal status, 43 (5%) were admitted to the NICU for < 7 days, 79 (9%) had 5-min Apgar score < 7, 125/631 (20%) had a cord gas pH ≤ 7.1 and 35/631 (6%) had a base excess ≥ 12 mmol/L. The predictive index we developed included seven factors available at the time of FGR diagnosis: hypertensive disorder of pregnancy (HDP) (+8 points), chronic hypertension without HDP (+4 points), gestational age ≤ 32 weeks (+5 points), absent or reversed end-diastolic flow in the umbilical artery (+8 points), prepregnancy body mass index ≥ 35 kg/m2 (+3 points), isolated abdominal circumference < 3rd percentile (-4 points) and non-Hispanic black race (-2 points). The bias-corrected bootstrapped (1000 replicates) area under the receiver-operating-characteristics curve (AUC) of the predictive index for composite APO in the validation group was 0.88 (95% CI, 0.84-0.92), which was similar to that in the development group (AUC, 0.86 (95% CI, 0.82-0.89); P = 0.34). In the total cohort, 40% of pregnancies had a low-risk index score (≤ 2), associated with a NPV of 85% (95% CI, 81-88%) and a LR- of 0.21 (95% CI, 0.16-0.27), and 23% had a high-risk index score (≥ 10), associated with a PPV of 96% (95% CI, 93-98%) and a LR+ of 27.36 (95% CI, 14.33-52.23). Of the remaining pregnancies that had an intermediate-risk score, 50% were complicated by composite APO. An easy-to-use index incorporating seven clinical factors readily available at the time of FGR diagnosis is predictive of APO and may prove useful in counseling and management of pregnancies meeting the ISUOG-endorsed criteria for FGR. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Effects of Part D Star Ratings on racial and ethnic disparities in health care costs

BackgroundRacial/ethnic minorities are less likely than non-Hispanic White (White) patients to be included in the Medicare Part D Star Ratings measure assessment due to the restrictive inclusion criteria for the measures. ObjectiveThis paper examined the effects of racial/ethnic disparities in the measure assessment in Part D Star Ratings on disparities in healthcare costs among patients with Alzheimer's disease and related dementias (ADRD). MethodsThis cross-sectional study analyzed 2017 Medicare data. Proportions of Beneficiaries with ADRD were categorized into the included and excluded groups based on the inclusion criteria for the calculation of medication adherence measures in Star Ratings. Outcomes included costs for medications, physician visits, emergency room (ER) visits, and total costs. A generalized linear model was employed to compare costs across racial/ethnic groups. To explore the differential disparities in healthcare costs between the 2 groups, interaction terms between dummy variables for being excluded from the measure calculation and racial/ethnic minorities were included in the models. ResultsThe patterns of racial/ethnic disparities in healthcare costs found in this study were generally consistent with expectations, with some exceptions. For example, compared with White patients, in the hyperlipidemia cohort, the physician visit cost for Black patients among the included group was 31% lower (cost ratio or CR = 0.69, 95% CI = 0.67–0.72); in the hypertension cohort, the hospitalization cost for Blacks among the excluded group was 15% higher (CR = 1.15, 95% CI = 1.12–1.19). More importantly, exclusion from measurement assessments was associated with differential cost disparities. For example, compared with individuals included in the measure assessment for hypertension, the Black-White disparities in costs for hospitalization and total healthcare were 30% higher (CR = 1.30, 95% CI = 1.26–1.34), and 10% higher (CR = 1.10; 95% CI = 1.08–1.12), respectively, among the excluded group. ConclusionsMedicare Part D Star Ratings may be associated with aggravated racial/ethnic disparities in healthcare costs in the Medicare Part D population.