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Clinicians' perspectives of a care coordination model for children with medical complexity
Get PDFBackground: The Indiana Complex Care Coordination Collaborative (IC4) is a statewide initiative designed to enhance care for children with medical complexity (CMC) by embedding nurse care coordinators within clinical practices. This study explored clinicians' perspectives on how these coordinators influenced care delivery.
Methods: Fourteen clinicians from six participating medical systems completed semi-structured interviews. Discussions focused on the impact of care coordinators on workflow, patient care, clinician workload, and the medical home experience. Transcripts were analyzed using an inductive approach to identify key themes and insights.
Results: Clinicians consistently described care coordinators as central to improving communication and access for families, serving as a reliable point of contact, and facilitating smoother interactions with the healthcare system. They noted that care coordinators helped organize patient information, enabling focused and efficient clinical encounters. This support reduced administrative burden and allowed clinicians to prioritize patient needs more effectively. Additionally, care coordinators played a vital role in educating staff, advocating for families, and addressing both medical and non-medical concerns. While clinicians emphasized the value of care coordination, they also highlighted the need for clearer role definitions and adequate training to ensure coordinators are fully integrated and utilized appropriately.
Conclusion: Clinicians reported that embedded care coordinators significantly enhanced the quality, efficiency, and responsiveness of care for CMC. Their perspectives underscore the importance of structured, well-supported care coordination to improve clinical practice and patient outcomes
Tackling No-Show Rates: Addressing Barriers in a Free Clinic's Attendance
No full textProblem Statement:
Health disparities persist due to social determinants of health impacting appointment no-show rates at the Matthew 25 clinic.
Rationale:
Addressing health disparities has been at the forefront of challenges faced in the medical field. Social determinants of health (SDOH) have a significant impact on patient populations, often contributing to health disparities (1). SDOH refers to environmental factors that contribute to one’s overall health and longevity (2,3). It is estimated that SDOH account for 50% of the variation in health outcomes. Intervening on factors that contribute to poor SDOH could have a profound impact on many lives. Matthew 25, a free clinic in Fort Wayne, IN, serves a large immigrant population and natives who are of a low socioeconomic status. While the clinic helps to bridge the gap in healthcare by providing free healthcare services, it is hypothesized that SDOH are influencing the quality of care the clinic can provide. This study’s objective is to evaluate the effectiveness of the proposed survey model on increasing healthcare accessibility by observing its effects on rate of missed appointments.
Methods:
This was a single-center prospective questionnaire-based research project designed to determine the reasons for missed appointments and what resources can assist in reducing the no-show rate. This study was approved by the Indiana University Institutional Review Board. Participants included patients scheduled for appointments from November 2023 to the end of December 2023. Inclusion criteria were patients aged 18 and above who had at least one scheduled appointment during the study period. Any patient under the age of 18 years, who communicates exclusively in any language other than English or Spanish, or has substantial cognitive impairment was excluded. The data was stored on a Microsoft Excel Spreadsheet. The ultimate objective of this project was to implement interventions that would mitigate the no-show rate at Matthew 25.
The survey was administered by clinic staff, including volunteers and nurses, at the conclusion of each patient's visit prior to discharge. A verbal explanation of the intention of the study was given to potential participants before they completed the questionnaire. To encourage participation, the questionnaire was designed to be anonymous. The instrument comprised of ten questions. Completed surveys were securely stored at the clinic in a designated folder until the data was digitized, after which the physical questionnaires were disposed of securely.
Results:
A total of 64 participants completed the survey, shedding light on the primary reasons for missing appointments at Matthew 25. The most common reason was work obligations (19 participants, 29.7%), followed by simply forgetting (17 participants, 26.6%). Lack of transportation affected 10 participants (15.6%), while 5 participants (7.8%) cited lack of childcare. Seven respondents (10.9%) identified the absence of a translator as a significant barrier, and 4 (6.3%) selected "Other" reasons. A smaller percentage (3.1%) reported fear or anxiety about attending the clinic.
A second survey, with 149 responses, assessed preferred reminder times. Results showed 14% preferred reminders 1 day prior, 38% preferred 2 days prior, 43% opted for 1 week before, and 5% wanted a reminder 1 month in advance.
No-show rates did not significantly change within the first three months after posting informational materials, possibly due to insufficient time for patients to schedule follow-up visits. A newer Spanish-language poster was recently added, but its effects are still being evaluated.
These findings emphasize the importance of addressing social determinants of health on a community level, such as employment conflicts, transportation, and language barriers, to reduce no-show rates and improve healthcare access. Additionally, increasing patient awareness through multilingual outreach efforts, like the newly introduced Spanish-language poster, may further enhance attendance rates over time.
Potential Impact:
The survey highlighted common barriers that prevented patients from attending their appointments, allowing us to create English and Spanish posters with information about free services to help patients become more aware of the resources that, ideally, would make it simpler to attend appointments.
References:
1. Phelan JC, Link BG, Tehranifar P. Social conditions as fundamental causes of health inequalities: theory, evidence, and policy implications. J Health Soc Behav. 2010;51 Suppl:S28-S40. doi:10.1177/0022146510383498
2. Chang CD. Social Determinants of Health and Health Disparities Among Immigrants and their Children. Curr Probl Pediatr Adolesc Health Care. 2019;49(1):23-30. doi:10.1016/j.cppeds.2018.11.009
3. Adler NE, Newman K. Socioeconomic disparities in health: pathways and policies. Health Aff (Millwood). 2002;21(2):60-76. doi:10.1377/hlthaff.21.2.6
Proto‐Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer
No full textBackground:
Mutational landscape is prognostic in colorectal cancer (CRC). Rat sarcoma (RAS) oncogenes, such as KRAS and NRAS, with driver mutations, portend poor survival outcomes, whereas pathologic mutations in HRAS are extremely rare, and their prognostic value remains uncertain.
Methods:
This retrospective study analyzed the Oncology Research Information Exchange Network (ORIEN) alliance tumor RNA‐Seq data in Stages II and III CRC to investigate the association between RAS gene expression and survival outcomes.
Results:
High transcript levels of HRAS were associated with superior overall survival (OS). The high HRAS‐associated OS benefit was most pronounced in patients with right‐sided primary expressing low KRAS transcript levels in the absence of pathologic KRAS mutations.
Conclusions:
Contrary to the notion that RAS family genes are proto‐oncogenic, this study demonstrates that high HRAS transcript levels are associated with superior OS in Stages II and III CRC. The potential of HRAS as a prognostic biomarker should be explored further
Targeting hepatocyte-specific SLC2A8 blocks hepatic steatosis and dissociates TCA cycle flux inhibition from glutamine anaplerosis
No full textBackground: Excess TCA cycle and glutamine anaplerosis are hallmarks of metabolic dysfunction-associated steatotic liver disease and steatohepatitis. Blocking glutamine metabolism attenuates metabolic dysfunction-associated steatohepatitis. However, inhibiting TCA cycle flux by blocking plasma membrane carbohydrate transport is limited by the ubiquitous tissue distribution, function, and homology among the SLC2A family of facilitative carbohydrate transporters, and the potential for carbohydrate blockade to invoke or exacerbate glutamine anaplerosis. Here, we quantify alterations in hepatocyte carbon flux, define the broader metabolic consequences of hepatocyte-specific GLUT8/SLC2A8 inhibition, and delineate the antisteatotic efficacy of a novel small-molecule GLUT8-selective inhibitor.
Methods: We generated mice with floxed SLC2A8 alleles and expressed hepatocyte-specific Cre by breeding these mice with albumin-Cre transgenic mice, or by administering AAV8 encoding hepatocyte-specific iCre. We performed stable-isotope glucose, fructose, and glutamine metabolic labeling in isolated GLUT8WT and GLUT8LKO hepatocytes and performed metabolic phenotyping in lean and diet-induced obese GLUT8WT and GLUT8LKO mice. Finally, we performed high-throughput screening to identify a GLUT8-selective inhibitor, which we characterized using in vitro models of triglyceride accumulation.
Results: Hepatocyte-specific SLC2A8 deletion reduced diet-induced hepatic and peripheral fat accumulation and increased thermogenesis during ZT12-24 (eg, the dark phase). It also disrupted TCA cycle flux without inducing compensatory glutamine utilization. High-throughput screening identified a small-molecule, GLUT8-selective inhibitor, P20, which blocked hepatocyte TG accumulation and inflammation in in vitro steatotic and inflammatory models.
Conclusions: Deleting the hepatocyte carbohydrate transporter GLUT8 suppresses TCA cycle flux without inducing compensatory glutamine anaplerosis. The net effect of this is liver protection against multiple forms of dietary insult. Given that selective pharmacological GLUT8 inhibition is feasible, GLUT8 may be a viable target to abate metabolic dysfunction-associated steatohepatitis and other complications of obesity
The feasibility of pharmacokinetic‐based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial
No full textPharmacokinetic (PK)-guided dosing of hydroxyurea for children with sickle cell anaemia (SCA) could optimize dosing and improve outcomes, but its feasibility has not been demonstrated in low-resource settings where the majority of affected children live. Alternative Dosing And Prevention of Transfusions (ADAPT) is a prospective trial evaluating blood transfusions and the feasibility of determining PK-guided, hydroxyurea maximum tolerated doses (MTD) for children with SCA in Uganda, using portable high-performance liquid chromatography (HPLC) and a novel PK software programme (HdxSim). ADAPT enrolled 106 participants, and 100% completed PK testing. PK-guided doses were generated for 78%, of which 38% were within the protocol-defined range. Accurately, measuring serum hydroxyurea concentrations via HPLC and the potential for hydroxyurea degradation impacted the feasibility. Ensuring that people with SCA globally have access to hydroxyurea is imperative, and improving treatment strategies requires ongoing innovation including PK-guided dosing
High-throughput Amplicon Sequencing Optimization for Downstream Prediction Purposes
No full textIUPUIAlongside short tandem repeat (STR) typing, forensic DNA phenotyping (FDP) can enhance forensic DNA analysis by inferring externally visible characteristics and biogeographical ancestry from single-nucleotide polymorphisms (SNPs). This project involves the optimization of a high-throughput amplicon sequencing assay targeting ~2,000 SNPs associated with pigmentation, facial morphology, and ancestry. Over 400 samples were processed through a genotyping pipeline involving DNA extraction, library preparation with a modified version of a commerical FDP assay, MiSeq FGx sequencing, genotype calling, and quality and ancestry inference assessments. The substantial dataset produced with this project will supply downstream applications in pigmentation and facial morphology prediction modeling. This work also advances FDP toward wide-scale integration into forensic laboratories and demonstrates how SNP-based genotyping can extend investigative leads when traditional STR matching is insufficient
Aversion‐resistant alcohol seeking in the human laboratory
No full textBackground: Aversion-resistant, or "compulsive," drinking is well-studied as a preclinical model of alcohol use disorder. Human studies have largely relied on subjective self-report of aversion-resistant drinking. The goal of this study was to develop and test a behavioral model of aversion-resistant alcohol seeking in the human laboratory, facilitating translational research on this important risk factor.
Methods: A sample of 84 adults aged 21-55 (mean age = 32.2 years, 54.8% female, 58.3% white) who endorsed heavy alcohol use (mean AUDIT = 11.3, SD = 5.6) completed an interview/screening session and two counterbalanced progressive-ratio intravenous alcohol self-administration sessions, one in which alcohol seeking was paired with aversive and the other neutral stimuli (each beginning with a 40-min alcohol prime of 60 mg/dL). Study hypotheses were preregistered at clinicaltrials.gov (Study Details-Human Alcohol Seeking Despite Aversion-ClinicalTrials.gov, ID NCT03648840).
Results: Contrary to hypotheses, across the whole sample, cumulative lifetime drinking did not relate specifically to aversion-resistant alcohol seeking; rather, those with more extensive drinking histories worked more for alcohol across both sessions. A parallel growth curve model analysis found that less of an alcohol-prime-associated increase in stimulation was related to more aversion-resistant alcohol seeking.
Conclusions: These data suggest that aversion-resistant alcohol seeking may stem from the blunted stimulating effects of alcohol, consistent with the low-level response theory driving excessive alcohol seeking, or from acquired tolerance from drinking. This human model of aversion-resistant alcohol seeking can be paired with preclinical models to explore and evaluate new clinical treatment targets
Kinetically Controlled aza-Michael/Epimerization Cascade Enables a Scalable Total Synthesis of Putative (+)-Fumigaclavine F
No full textThe first total syntheses of putative (+)-fumigaclavine F (seven pots, 16% overall yield, 400 mg scale) and its proposed biosynthetic precursor (seven pots, 21% overall yield, 400 mg scale) have been achieved. The stereochemistry of both was unambiguously verified via XRD. The synthesis features a decagram-scale asymmetric intramolecular Mannich reaction, followed by an aza-Michael/epimerization cascade that constructs the cis-fused tetracyclic scaffold. The synthesis provides an excellent approach to probe the bioactivity of clavine alkaloids
Quantifying and Contextualizing Radiation Doses in Common Pediatric Medical Imaging Examinations
No full textObjective: To provide organ and effective radiation doses for common pediatric imaging examinations, which may help clinicians understand site-specific cancer risk, compare exposure across imaging modalities, and make informed care decisions.
Study design: Within a large multicenter retrospective cohort, imaging utilization and associated radiation doses were estimated for children enrolled from birth into one of six US health care systems. Doses are described for examinations performed from 2012 to 2017. For computed tomography (CT), doses were estimated using examination-level technical parameters, patient height and weight, and Monte Carlo simulations. For fluoroscopy, angiography, nuclear medicine, and radiography, dose maps were developed by patient age, sex, size, and year through Monte Carlo simulations using technical parameters collected from patient examinations. The mean dose and standard deviation (SD) were calculated for each examination type, and each modality's contribution to the cohort's cumulative effective dose was calculated.
Results: Eight hundred thirty-five thousand six hundred forty-three imaging examinations in 278 909 patients are included. Radiographs were the most commonly performed exam but made up 6% of radiation dose exposure. CT exams made up 4% of imaging exams but accounted for 80% of exposure. Head CT was the most common CT exam (44% of all CT). For head CT, the average radiation dose to the bone marrow (associated with hematologic cancer risk) was 9.8 mGy (SD = 6.7) and to the brain (associated with brain cancer risk) was 39 mGy (SD = 14.8).
Conclusions: CT radiation doses to the bone marrow and brain fell within ranges associated with increased hematologic and brain cancer risk, and are highest in the youngest children
The PKCι-β-arrestin2 axis disrupts SORLA retrograde trafficking, driving its degradation and amyloid pathology in Alzheimer's disease
No full textBackground: Variants of SORL1 have been associated with both late and early onset of Alzheimer's disease (AD). SORL1 encodes the sorting-related receptor with A repeat (SORLA) protein, which belongs to the VPS10 receptor family. SORLA protects against AD pathogenesis through its sorting function, and reduced SORLA levels have been consistently observed in sporadic AD. Although the importance of SORLA in AD pathogenesis is well recognized, how it can be targeted for AD treatment remains to be established, owing to the inadequate understanding of its regulation by intracellular signaling.
Methods: We employed combined biochemical, cell biological, and pharmacological approaches to investigate how SORLA trafficking and stability are regulated. Additionally, we used an AD mouse model, postmortem tissue samples, and iPSC-derived neurons to examine the functional outcomes of this regulation.
Results: We identified a novel direct interaction between SORLA and β-arrestin2 (βARR2), which impedes the interaction of SORLA with the retromer complex, thus reducing the retrograde trafficking of SORLA. βARR2 promotes the interaction between SORLA and the ESCRT0 complex, leading to the lysosomal localization and degradation of SORLA. We also found that PKCι/λ induces SORLA phosphorylation and enhances its interaction with βARR2, promoting SORLA degradation. Importantly, blocking PKCι/λ with auranofin disrupts the SORLA-βARR2 interaction, elevates SORLA levels, decreases amyloidogenic processing of APP, and improves cognition in the AppNL-G-F/NL-G-F AD mouse model. Furthermore, PKCι is hyperactive in human AD brains, and auranofin reduces Aβ production in AD iPSC-derived neurons through increasing SORLA levels.
Conclusion: Our study reveals the PKCι/λ-βARR2 axis as a key molecular mechanism that disrupts SORLA retrograde trafficking and drives its degradation. Our findings represent the first evidence that SORLA levels can be pharmacologically manipulated through blocking PKCι/λ to reduce Aβ production and alleviate AD-related phenotypes. Notably, repurposing auranofin, an FDA-approved drug for rheumatoid arthritis, may offer the potential for AD treatment