Synaptic Plasticity Forms and Functions.

Synaptic plasticity, the activity-dependent change in neuronal connection strength, has long been considered an important component of learning and memory. Computational and engineering work corroborate the power of learning through the directed adjustment of connection weights. Here we review the fundamental elements of four broadly categorized forms of synaptic plasticity and discuss their functional capabilities and limitations. Although standard, correlation-based, Hebbian synaptic plasticity has been the primary focus of neuroscientists for decades, it is inherently limited. Three-factor plasticity rules supplement Hebbian forms with neuromodulation and eligibility traces, while true supervised types go even further by adding objectives and instructive signals. Finally, a recently discovered hippocampal form of synaptic plasticity combines the above elements, while leaving behind the primary Hebbian requirement. We suggest that the effort to determine the neural basis of adaptive behavior could benefit from renewed experimental and theoretical investigation of more powerful directed types of synaptic plasticity.

The Current Mismatch Between COVID-19 Clinical Trial Design and the Evolving Profile of Hospitalized Patients: A Retrospective Cohort Analysis.

Evaluating 100 adult coronavirus disease 2019 (COVID-19) patients at a Madrid hospital, we identified a mismatch between current clinical trial designs and the evolving profile of hospitalized patients. Most patients were ineligible due to design constraints, suggesting a need to rethink trial criteria for a more accurate representation of the hospitalized COVID-19 cohort.

Provider motivations and barriers to cancer clinical trial screening, referral, and operations: Findings from a survey.

BACKGROUND: Provider and institutional practices have been shown to have a large impact on cancer clinical trial enrollment. Understanding provider perspectives on screening for trial eligibility is necessary to improve enrollment. METHODS: A questionnaire about incentives, barriers, process tools, and infrastructure related to opening trials and referring patients to onsite and offsite trials was administered to diverse stakeholders, including professional societies, advocacy organizations, and industry networks. Descriptive statistics were used to summarize findings. RESULTS: Overall, 693 responses were received, primarily from physicians (42.7%) and nurses (35.6%) employed at hospital health systems (43.7%) and academic centers (36.5%). Approximately half (49.2%) screened all patients for onsite clinical trials with screening typically done by manual chart review (81.9%). The greatest incentive reported for offering trials was providing the best treatment options for patients (67.7%). Contracting and paperwork (48.5%) were the greatest barriers to opening more onsite trials. Offsite referrals were rare. CONCLUSIONS: Screening for trial eligibility is a largely manual and ad hoc process, with screening and referral to offsite trials occurring infrequently. Administrative and infrastructure barriers commonly prevent sites from opening more onsite trials. These findings suggest that automated trial screening tools built into workflows that screen in a site-agnostic manner could result in more frequent trial eligibility screening, especially for offsite trials. With recent momentum, in part in response to the COVID-19 pandemic, to improve clinical trial efficiencies and broaden access and participant diversity, implementing tools to improve screening and referral processes is timely and essential. PLAIN LANGUAGE SUMMARY: There are many factors that contribute to low adult enrollment in cancer clinical trials, but previous research has indicated that provider and institutional barriers are the largest contributors to low cancer clinical trial enrollment. In this survey, we sought to gain insight into cancer clinical trial enrollment practices from the perspective of health care providers such as physicians and nurses. We found that only approximately half of respondents indicated their institution systematically screens their patients for clinical trials and this process is manual and time consuming. Furthermore, we found that providers infrequently search for and refer patients to clinical trials at other sites. Creating better screening methods could improve enrollment in clinical trials.

Improved assessment of donor liver steatosis using Banff consensus recommendations and deep learning algorithms.

BACKGROUND & AIMS: The Banff Liver Working Group recently published consensus recommendations for steatosis assessment in donor liver biopsy, but few studies reported their use and no automated deep-learning algorithms based on the proposed criteria have been developed so far. We evaluated Banff recommendations on a large monocentric series of donor liver needle biopsies by comparing pathologists' scores with those generated by convolutional neural networks (CNNs) we specifically developed for automated steatosis assessment. METHODS: We retrospectively retrieved 292 allograft liver needle biopsies collected between January 2016 and January 2020 and performed steatosis assessment using a former intra-institution method (pre-Banff method) and the newly introduced Banff recommendations. Scores provided by pathologists and CNN models were then compared, and the degree of agreement was measured with the intraclass correlation coefficient (ICC). RESULTS: Regarding the pre-Banff method, poor agreement was observed between the pathologist and CNN models for small droplet macrovesicular steatosis (ICC: 0.38), large droplet macrovesicular steatosis (ICC: 0.08), and the final combined score (ICC: 0.16) evaluation, but none of these reached statistically significance. Interestingly, significantly improved agreement was observed using the Banff approach: ICC was 0.93 for the low-power score (p <0.001), 0.89 for the high-power score (p <0.001), and 0.93 for the final score (p <0.001). Comparing the pre-Banff method with the Banff approach on the same biopsy, pathologist and CNN model assessment showed a mean (±SD) percentage of discrepancy of 26.89 (±22.16) and 1.20 (±5.58), respectively. CONCLUSIONS: Our findings support the use of Banff recommendations in daily practice and highlight the need for a granular analysis of their effect on liver transplantation outcomes. IMPACT AND IMPLICATIONS: We developed and validated the first automated deep-learning algorithms for standardized steatosis assessment based on the Banff Liver Working Group consensus recommendations. Our algorithm provides an unbiased automated evaluation of steatosis, which will lay the groundwork for granular analysis of steatosis's short- and long-term effects on organ viability, enabling the identification of clinically relevant steatosis cut-offs for donor organ acceptance. Implementing our algorithm in daily clinical practice will allow for a more efficient and safe allocation of donor organs, improving the post-transplant outcomes of patients.

How to improve treatment-free remission eligibility in chronic myeloid leukaemia?

The achievement of treatment-free remission (TFR) has become a significant clinical end-point in the management of patients with chronic myeloid leukaemia (CML), providing an opportunity to discontinue therapy with tyrosine kinase inhibitors (TKIs) while maintaining deep molecular response (DMR). Early studies, such as the French STIM trial, have demonstrated that a portion of patients can maintain DMR after treatment cessation, with rates ranging from 40% to 50%, and most relapses occurring within the first 6 months. Key prognostic factors for successful TFR, including treatment duration, duration of DMR, risk scores, and transcript type, have been identified. Optimal patient selection for TFR remains a challenge, but recent research provides insights into potential strategies to increase TFR eligibility. Evidence suggests that early intervention switching to achieve optimal response, treatment combinations, proactive switch in the case of absence of DMR, dose-optimization and induction-maintenance approach can improve molecular responses and, consequently, enhance TFR eligibility. In this review, we report and discuss all the potential therapeutic strategies that may enhance eligibility for a first attempt at TFR, with a particular emphasis on potential future approaches.

A process to reanalyze clinical DNA sequencing data for biomarker matching in the Lung-MAP Master Protocol.

For cancer clinical trials that require central confirmation of tumor genomic profiling, exhaustion of tissue from standard-of-care testing may prevent enrollment. For Lung-MAP, a master protocol that requires results from a defined centralized clinical trial assay to assign patients to a therapeutic substudy, we developed a process to repurpose existing commercial vendor raw genomic data for eligibility: genomic data reanalysis (GDR). Molecular results for substudy assignment were successfully generated for 369 of the first 374 patients (98.7%) using GDR for Lung-MAP, with a median time from request to result of 9 days. During the same period, 691 of 791 (87.4%) tissue samples received successfully yielded results, in a median of 14 days beyond sample acquisition. GDR is a scalable bioinformatic pipeline that expedites reanalysis of existing data for clinical trials in which validated integral biomarker testing is required for participation.

Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

Assessing the efficiency of eligibility criteria for low-dose computed tomography lung screening in China according to current guidelines.

BACKGROUND: Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. METHODS: Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). RESULTS: Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45-49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35-39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P < 0.001). CONCLUSIONS: The I-ELCAP guideline has the highest eligibility rate for both males and females. But its actual efficiency ratio for those deemed eligible by the guideline was the lowest. Whereas the NCCN guideline has the highest ERe value for those deemed eligible by the guideline.

The relationship between community food environment around schools and student meal participation: the role of school CEP participation status.

BACKGROUND: Despite the many benefits of school meals, not all students participate. One reason students may not participate in school meals is because they instead purchase breakfast or lunch from food outlets located around schools that mostly carry unhealthy items. This study examined whether school participation in the Community Eligibility Provision (CEP), which allows qualifying schools to serve free meals to all students, moderated the association between the community food environment around schools and student meal participation. METHODS: This study employed a longitudinal repeated-measures design using school-level data collected between 2014 and 2020 within four low-income school districts (n = 126 schools) in the US. We obtained meal participation data from state records and created a measure characterizing the community food environment within 0.25 miles of schools (characterized as low-density of unhealthy food outlets vs. high-density of unhealthy food outlets) through a latent class analysis. Regression analysis estimated associations between community food environments, CEP participation, and participation rates in school breakfast and school lunch, assessed in separate models. RESULTS: While no moderating effect of school CEP status was observed for breakfast or lunch participation, school breakfast participation was predicted to be 4% lower in high-density food environments than in low-density environments (P-value = .049) among non-CEP schools, and there was no difference in participation by the community food environment among CEP-participating schools. Differences in breakfast participation by the community food environment among non-CEP schools were mostly attributable to middle/high schools, with participation predicted to be 10% lower in high-density environments than in low-density environments among non-CEP middle/high schools (P-value < .001), whereas such a difference in participation was not observed among non-CEP elementary schools. CONCLUSIONS: Negative associations between food environment around schools and school breakfast participation were observed only among middle and high schools not participating in CEP, suggesting that policy actions to increase access to free school meals may benefit students, particularly older children and adolescents.

Comparison of the characteristics of the population eligible for lung cancer screening under 2013 and population newly eligible under 2021 US Preventive Services Task Force recommendations.

PURPOSE: In 2021, the United States Preventive Services Task Force (USPSTF) revised their 2013 recommendations for lung cancer screening eligibility by lowering the pack-year history from 30+ to 20+ pack-years and the recommended age from 55 to 50 years. Simulation studies suggest that Black persons and females will benefit most from these changes, but it is unclear how the revised USPSTF recommendations will impact geographic, health-related, and other sociodemographic characteristics of those eligible. METHODS: This cross-sectional study employed data from the 2017-2020 Behavioral Risk Factor Surveillance System surveys from 23 states to compare age, gender, race, marital, sexual orientation, education, employment, comorbidity, vaccination, region, and rurality characteristics of the eligible population according to the original 2013 USPSTF recommendations with the revised 2021 USPSTF recommendations using chi-squared tests. This study compared those originally eligible to those newly eligible using the BRFSS raking-dervived weighting variable. RESULTS: There were 30,190 study participants. The results of this study found that eligibility increased by 62.4% due to the revised recommendations. We found that the recommendation changes increased the proportion of eligible females (50.1% vs 44.1%), Black persons (9.2% vs 6.6%), Hispanic persons (4.4% vs 2.7%), persons aged 55-64 (55.8% vs 52.6%), urban-dwellers(88.3% vs 85.9%), unmarried (3.4% vs 2.5%) and never married (10.4% vs 6.6%) persons, as well as non-retirees (76.5% vs 56.1%) Respondents without comorbidities and COPD also increased. CONCLUSION: It is estimated that the revision of the lung cancer screening recommendations decreased eligibility disparities in sex, race, ethnicity, marital status, respiratory comorbidities, and vaccination status. Research will be necessary to estimate whether uptake patterns subsequently follow the expanded eligibility patterns.

The economic argument for hepatitis B treatment simplification and expansion.

One component of decisions regarding hepatitis B virus (HBV) treatment simplification and expansion is the economic perspective. Literature was reviewed for studies which provide estimates for the economic impact of simplifying and expanding treatment eligibility. Eight published studies and four unpublished studies were included and all but one subset of one study found that expanding treatment criteria would result in programs that would be at minimum cost-effective and most often highly cost-effective.

Exclusion of older adults from randomized controlled trials in rheumatoid arthritis.

OBJECTIVES: To assess eligibility criteria that either explicitly or implicitly exclude older patients from randomized controlled trials (RCTs) in RA. METHODS: Our analysis included RCTs of pharmacological interventions registered with ClinicalTrials.gov and started between 2013 and 2022. Co-primary outcomes were proportions of trials with an upper age limit and the eligibility criteria indirectly increasing risk of the exclusion of older adults. RESULTS: A total of 143/290 (49%) trials had an upper age limit of 85 years or less. Multivariable analysis showed that the odds of an upper age limit were significantly lower in trials performed in the USA [adjusted odds ratio (aOR), 0.34; CI, 0.12-0.99; P = 0.04] and intercontinental trials (aOR, 0.4; CI, 0.18-0.87; P = 0.02). In total, 154/290 (53%) trials had at least one eligibility criterion implicitly excluding older adults. These included specific comorbidities (n = 114; 39%), compliance concerns (n = 67; 23%), and broad and vague exclusion criteria (n = 57; 20%); however, we found no significant associations between these criteria and trial characteristics. Overall, 217 (75%) trials either explicitly or implicitly excluded older patients; we also noted a trend towards increasing proportion of these trials over time. Only one trial (0.3%) enrolled solely patients aged 65 and older. CONCLUSION: Older adults are commonly excluded from RCTs in RA based on both age limits and other eligibility criteria. This seriously limits the evidence base for the treatment of older patients in clinical practice. Given the growing prevalence of RA in older adults, relevant RCTs should be more inclusive to them.

Transparency in Cognitive Training Meta-analyses: A Meta-review.

Meta-analyses often present flexibility regarding their inclusion criteria, outcomes of interest, statistical analyses, and assessments of the primary studies. For this reason, it is necessary to transparently report all the information that could impact the results. In this meta-review, we aimed to assess the transparency of meta-analyses that examined the benefits of cognitive training, given the ongoing controversy that exists in this field. Ninety-seven meta-analytic reviews were included, which examined a wide range of populations with different clinical conditions and ages. Regarding the reporting, information about the search of the studies, screening procedure, or data collection was detailed by most reviews. However, authors usually failed to report other aspects such as the specific meta-analytic parameters, the formula used to compute the effect sizes, or the data from primary studies that were used to compute the effect sizes. Although some of these practices have improved over the years, others remained the same. Moreover, examining the eligibility criteria of the reviews revealed a great heterogeneity in aspects such as the training duration, age cut-offs, or study designs that were considered. Preregistered meta-analyses often specified poorly how they would deal with the multiplicity of data or assess publication bias in their protocols, and some contained non-disclosed deviations in their eligibility criteria or outcomes of interests. The findings shown here, although they do not question the benefits of cognitive training, illustrate important aspects that future reviews must consider.

The impact of blood donation deferral strategies on the eligibility of men who have sex with men and other sexual risk behavior in Australia.

BACKGROUND: In Australia, a man cannot donate blood if he has had sex with another man within the past 3 months. However, this policy has been criticized as being discriminatory as it does not consider lower risk subgroups, and led to calls for modifications to the policy that more accurately distinguish risk among gay, bisexual, and other men who have sex with men (GBM). STUDY DESIGN AND METHODS: We used data from a nationally representative survey to estimate the proportion of GBM aged 18-74 years old who would be eligible to donate under current criteria and other scenarios. RESULTS: Among the 5178 survey participants, 155 (3.0%) were classified as GBM based on survey responses, Among the GBM, 40.2% (95% CI 28.0%-53.7%) were eligible to donate based on current criteria, and 21.0% (95% CI 14.5%-29.5%) were ineligible due to the 3 months deferral alone. Eligibility among GBM, all men, and the population increased as criteria were removed. Under the new Australian plasma donation criteria, 73.6% (95% CI 64.4%-81.1%) of GBM, 68.4% (95% CI 65.5%-71.2%) of all men, and 60.8% (95% CI 58.8%-62.8%) of the full population were estimated to be eligible. Only 16.1% (95% CI 8.6%-28.1%) of GBM knew that the male-to-male sex deferral period is 3 months. DISCUSSION: Changing the deferral criteria and sexual risk evaluation would lead to a higher proportion of GBM being eligible to donate blood. Knowledge of the current GBM deferral period is very low. Improved education about the current criteria and any future changes are required to improve blood donation rates.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Receipt of seasonal malaria chemoprevention by age-ineligible children and associated factors in nine implementation states in Nigeria.

BACKGROUND: As part of implementation quality standards, community distributors are expected to ensure that only age-eligible children (aged 3-59 months) receive seasonal malaria chemoprevention (SMC) medicines during monthly campaigns. There is uncertainty about the extent to which SMC medicines are administered to ineligible children. This study aimed to assess the magnitude of this occurrence, while exploring the factors associated with it across nine states where SMC was delivered in Nigeria during the 2022 round. METHODS: This analysis was based on data from representative end-of-round SMC household surveys conducted in nine SMC-implementing states in Nigeria. Data of 3299 age-ineligible children aged > 5 years and their caregivers were extracted from the survey dataset. Prevalence of receipt of SMC medicines by ineligible children was described by child-, caregiver- and SMC-related factors. Mixed-effects multivariable logistic regression models were fitted to explore the factors associated with ineligible receipt of SMC medicines. RESULTS: 30.30% (95% CI 27.80-32.90) of ineligible children sampled received at least one dose of SMC medicines in 2022, the majority (60.60%) of whom were aged 5-6 years while the rest were aged 7-10 years. There were lower odds of an age-ineligible child receiving SMC among caregivers who had knowledge of SMC age eligibility (OR: 0.53, 95% CI 0.37-0.77, p < 0.001), compared with those who were knowledgeable of age eligibility. Higher odds of receipt of SMC were found among age-ineligible children whose caregivers had higher confidence in the protective effect of SMC against malaria (OR: 2.01, 95% CI 1.07-3.72, p = 0.030), compared with those whose caregivers were less confident. Compared with ineligible children of younger caregivers (aged < 20 years), those whose caregivers were older had lower odds of receiving SMC than those whose caregivers were younger; with lower odds among children of caregivers aged 20-39 years (OR: 0.50, 95% CI 0.30-0.82, p = 0.006). CONCLUSIONS: This study contributes important evidence on the magnitude of the receipt of SMC medicines by age-ineligible children, while identifying individual and contextual factors associated with it. The findings provide potentially useful insights that can help inform and guide context-specific SMC implementation quality improvement efforts.

A Qualitative Study of Emergency Medicaid Programs From the Perspective of Hospital Stakeholders.

INTRODUCTION: Uninsured patients often have poor clinical outcomes associated with lower access to care. Hospital Presumptive Eligibility (HPE) provides up to 60-d emergency Medicaid coverage for uninsured, low-income patients. After obtaining 60-d HPE, patients must file for ongoing Medicaid to sustain coverage; however, navigating HPE approval is complex. We conducted a qualitative study to understand (1) stakeholder perspectives on the application process and workflow and (2) facilitators and barriers to HPE approval to understand process improvement opportunities. MATERIAL AND METHODS: We conducted semi-structured interviews between September-December 2021 with key stakeholders (social workers, financial counselors, case managers, and private third-party vendor representatives) involved in HPE coverage determination, screening, approval, and Medicaid sustainment at our institution. We performed a team-based thematic analysis to elicit factors influencing HPE screening and approval, and recommendations for process improvement. RESULTS: Study participants described the HPE application and Medicaid approval processes. Patient-level barriers included information disclosure and immigration status, inability to contact patients or next-of-kin, and knowledge gaps about insurance acquisition and sustainment. System-level barriers included technical challenges with the state HPE application portal, inadequate staffing for patient screening, and short emergency department stays that limited opportunities to initiate HPE. Stakeholders proposed improvements in education, patient outreach, and logistics. CONCLUSIONS: This qualitative study reveals the process of HPE approval and outlines barriers within HPE and Medicaid processing from the perspective of direct hospital stakeholders. We identified opportunities at the patient, hospital, and policy levels that could improve successful HPE application and approval rates.

Absolute neutrophil count clinical trial eligibility criteria for pediatric oncology phase I and phase I/II trials by sponsorship.

Normal absolute neutrophil count (ANC) variations, as seen with Duffy-null associated neutrophil count (DANC), are not accounted for in trial eligibility, which may contribute to racial enrollment disparities. We describe ANC eligibility for pediatric oncology phase I/II clinical trials according to primary sponsorship from 2010 to 2023 using ClinicalTrials.gov. Out of 438 trials, 20% were industry-sponsored. Total 17% of trials required ANC ≥1500 cells/µL for enrollment; however, industry-sponsored trials were significantly more likely to require ANC ≥1500 cells/µL than non-industry-sponsored trials (odds ratio 2.53, 95% confidence interval: 1.39-4.62; p < .001). These data suggest laboratory exclusion criteria are one possible mechanism for pediatric clinical trial enrollment disparities.

The American Association of Tissue Banks tissue donor screening for Mycobacterium tuberculosis-Recommended criteria and literature review.

After two multistate outbreaks of allograft tissue-transmitted tuberculosis (TB) due to viable bone, evidence-based donor screening criteria were developed to decrease the risk of transmission to recipients. Exclusionary criteria, commentary, and references supporting the criteria are provided, based on literature search and expert opinion. Both exposure and reactivation risk factors were considered, either for absolute exclusion or for exclusion in combination with multiple risk factors. A criteria subset was devised for tissues containing viable cells. Risk factors for consideration included exposure (e.g., geographic birth and residence, travel, homelessness, incarceration, healthcare, and workplace) and reactivation (e.g., kidney disease, liver disease, history of transplantation, immunosuppressive medications, and age). Additional donor considerations include the possibility of sepsis and chronic illness. Donor screening criteria represent minimal criteria for exclusion and do not completely exclude all possible donor TB risks. Additional measures to reduce transmission risk, such as donor and product testing, are discussed but not included in the recommendations. Careful donor evaluation is critical to tissue safety.

Evaluation of the implementation of a "Pediatric Feasibility Assessment for Transplantation" tool in children and adolescents at Red Cross War Memorial Children's Hospital, Cape Town, South Africa.

BACKGROUND: Kidney transplantation remains the treatment of choice for children with kidney failure (KF). In South Africa, kidney replacement therapy (KRT) is restricted to children eligible for transplantation. This study reports on the implementation of the Paediatric Feasibility Assessment for Transplantation (pFAT) tool, a psychosocial risk score developed in South Africa to support transparent transplant eligibility assessment in a low-resource setting. METHODS: Single-center retrospective descriptive analysis of children assessed for KRT using pFAT tool from 2015 to 2021. RESULTS: Using the pFAT form, 88 children (median [range] age 12.0 [1.1 to 19.0] years) were assessed for KRT. Thirty (34.1%) children were not listed for KRT, scoring poorly in all domains, and were referred for supportive palliative care. Fourteen of these 30 children (46.7%) died, with a median survival of 6 months without dialysis. Nine children were reassessed and two were subsequently listed. Residing >300 km from the hospital (p = .009) and having adherence concerns (p = .003) were independently associated with nonlisting. Of the 58 (65.9%) children listed for KRT, 40 (69.0%) were transplanted. One-year patient and graft survival were 97.2% and 88.6%, respectively. Only one of the four grafts lost at 1-year posttransplant was attributed to psychosocial issues. CONCLUSIONS: Short-term outcomes among children listed using the pFAT form are good. Among those nonlisted, the pFAT highlights specific psychosocial/socioeconomic barriers, over which most children themselves have no power to change, which should be systemically addressed to permit eligibility of more children and save lives.