Advancing the Scientific Basis for Determining Death in Controlled Organ Donation After Circulatory Determination of Death.

In controlled organ donation after circulatory determination of death (cDCDD), accurate and timely death determination is critical, yet knowledge gaps persist. Further research to improve the science of defining and determining death by circulatory criteria is therefore warranted. In a workshop sponsored by the National Heart, Lung, and Blood Institute, experts identified research opportunities pertaining to scientific, conceptual, and ethical understandings of DCDD and associated technologies. This article identifies a research strategy to inform the biomedical definition of death, the criteria for its determination, and circulatory death determination in cDCDD. Highlighting knowledge gaps, we propose that further research is needed to inform the observation period following cessation of circulation in pediatric and neonatal populations, the temporal relationship between the cessation of brain and circulatory function after the withdrawal of life-sustaining measures in all patient populations, and the minimal pulse pressures that sustain brain blood flow, perfusion, activity, and function. Additionally, accurate predictive tools to estimate time to asystole following the withdrawal of treatment and alternative monitoring modalities to establish the cessation of circulatory, brainstem, and brain function are needed. The physiologic and conceptual implications of postmortem interventions that resume circulation in cDCDD donors likewise demand attention to inform organ recovery practices. Finally, because jurisdictionally variable definitions of death and the criteria for its determination may impede collaborative research efforts, further work is required to achieve consensus on the physiologic and conceptual rationale for defining and determining death after circulatory arrest.

Knowledge gaps in heart and lung donation after the circulatory determination of death: Report of a workshop of the National Heart, Lung, and Blood Institute.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.

Emergency Department Pediatric Readiness and Disparities in Mortality Based on Race and Ethnicity.

Importance: Presentation to emergency departments (EDs) with high levels of pediatric readiness is associated with improved pediatric survival. However, it is unclear whether children of all races and ethnicities benefit equitably from increased levels of such readiness. Objective: To evaluate the association of ED pediatric readiness with in-hospital mortality among children of different races and ethnicities with traumatic injuries or acute medical emergencies. Design, Setting, and Participants: This cohort study of children requiring emergency care in 586 EDs across 11 states was conducted from January 1, 2012, through December 31, 2017. Eligible participants included children younger than 18 years who were hospitalized for an acute medical emergency or traumatic injury. Data analysis was conducted between November 2022 and April 2023. Exposure: Hospitalization for acute medical emergency or traumatic injury. Main Outcomes and Measures: The primary outcome was in-hospital mortality. ED pediatric readiness was measured through the weighted Pediatric Readiness Score (wPRS) from the 2013 National Pediatric Readiness Project assessment and categorized by quartile. Multivariable, hierarchical, mixed-effects logistic regression was used to evaluate the association of race and ethnicity with in-hospital mortality. Results: The cohort included 633 536 children (median [IQR] age 4 [0-12] years]). There were 557 537 children (98 504 Black [17.7%], 167 838 Hispanic [30.1%], 311 157 White [55.8%], and 147 876 children of other races or ethnicities [26.5%]) who were hospitalized for acute medical emergencies, of whom 5158 (0.9%) died; 75 999 children (12 727 Black [16.7%], 21 604 Hispanic [28.4%], 44 203 White [58.2%]; and 21 609 of other races and ethnicities [27.7%]) were hospitalized for traumatic injuries, of whom 1339 (1.8%) died. Adjusted mortality of Black children with acute medical emergencies was significantly greater than that of Hispanic children, White children, and of children of other races and ethnicities (odds ratio [OR], 1.69; 95% CI, 1.59-1.79) across all quartile levels of ED pediatric readiness; but there were no racial or ethnic disparities in mortality when comparing Black children with traumatic injuries with Hispanic children, White children, and children of other races and ethnicities with traumatic injuries (OR 1.01; 95% CI, 0.89-1.15). When compared with hospitals in the lowest quartile of ED pediatric readiness, children who were treated at hospitals in the highest quartile had significantly lower mortality in both the acute medical emergency cohort (OR 0.24; 95% CI, 0.16-0.36) and traumatic injury cohort (OR, 0.39; 95% CI, 0.25-0.61). The greatest survival advantage associated with high pediatric readiness was experienced for Black children in the acute medical emergency cohort. Conclusions and Relevance: In this study, racial and ethnic disparities in mortality existed among children treated for acute medical emergencies but not traumatic injuries. Increased ED pediatric readiness was associated with reduced disparities; it was estimated that increasing the ED pediatric readiness levels of hospitals in the 3 lowest quartiles would result in an estimated 3-fold reduction in disparity for pediatric mortality. However, increased pediatric readiness did not eliminate disparities, indicating that organizations and initiatives dedicated to increasing ED pediatric readiness should consider formal integration of health equity into efforts to improve pediatric emergency care.

Association of Transport Time, Proximity, and Emergency Department Pediatric Readiness With Pediatric Survival at US Trauma Centers.

Importance: Emergency department (ED) pediatric readiness is associated with improved survival among children. However, the association between geographic access to high-readiness EDs in US trauma centers and mortality is unclear. Objective: To evaluate the association between the proximity of injury location to receiving trauma centers, including the level of ED pediatric readiness, and mortality among injured children. Design, Setting, and Participants: This retrospective cohort study used a standardized risk-adjustment model to evaluate the association between trauma center proximity, ED pediatric readiness, and in-hospital survival. There were 765 trauma centers (level I-V, adult and pediatric) that contributed data to the National Trauma Data Bank (January 1, 2012, through December 31, 2017) and completed the 2013 National Pediatric Readiness Assessment (conducted from January 1 through August 31, 2013). The study comprised children aged younger than 18 years who were transported by ground to the included trauma centers. Data analysis was performed between January 1 and March 31, 2022. Exposures: Trauma center proximity within 30 minutes by ground transport and ED pediatric readiness, as measured by weighted pediatric readiness score (wPRS; range, 0-100; quartiles 1 [low readiness] to 4 [high readiness]). Main Outcomes and Measures: In-hospital mortality. We used a patient-level mixed-effects logistic regression model to evaluate the association of transport time, proximity, and ED pediatric readiness on mortality. Results: This study included 212 689 injured children seen at 765 trauma centers. The median patient age was 10 (IQR, 4-15) years, 136 538 (64.2%) were male, and 127 885 (60.1%) were White. A total of 4156 children (2.0%) died during their hospital stay. The median wPRS at these hospitals was 79.1 (IQR, 62.9-92.7). A total of 105 871 children (49.8%) were transported to trauma centers with high-readiness EDs (wPRS quartile 4) and another 36 330 children (33.7%) were injured within 30 minutes of a quartile 4 ED. After adjustment for confounders, proximity, and transport time, high ED pediatric readiness was associated with lower mortality (highest-readiness vs lowest-readiness EDs by wPRS quartiles: adjusted odds ratio, 0.65 [95% CI, 0.47-0.89]). The survival benefit of high-readiness EDs persisted for transport times up to 45 minutes. The findings suggest that matching children to trauma centers with high-readiness EDs within 30 minutes of the injury location may have potentially saved 468 lives (95% CI, 460-476 lives), but increasing all trauma centers to high ED pediatric readiness may have potentially saved 1655 lives (95% CI, 1647-1664 lives). Conclusions and Relevance: These findings suggest that trauma centers with high ED pediatric readiness had lower mortality after considering transport time and proximity. Improving ED pediatric readiness among all trauma centers, rather than selective transport to trauma centers with high ED readiness, had the largest association with pediatric survival. Thus, increased pediatric readiness at all US trauma centers may substantially improve patient outcomes after trauma.

Extracorporeal cardiopulmonary resuscitation dissemination and integration with organ preservation in the USA: ethical and logistical considerations.

Use of extracorporeal membrane oxygenation (ECMO) in cardiopulmonary resuscitation, termed eCPR, offers the prospect of improving survival with good neurological function after cardiac arrest. After death, ECMO can also be used for enhanced preservation of abdominal and thoracic organs, designated normothermic regional perfusion (NRP), before organ recovery for transplantation. To optimize resuscitation and transplantation outcomes, healthcare networks in Portugal and Italy have developed cardiac arrest protocols that integrate use of eCPR with NRP. Similar dissemination of eCPR and its integration with NRP in the USA raise novel ethical issues due to a non-nationalized health system and an opt-in framework for organ donation, as well as other legal and cultural factors. Nonetheless, eCPR investigations are ongoing, and both eCPR and NRP are selectively employed in clinical practice. This paper delineates the most pressing relevant ethical considerations and proposes recommendations for implementation of protocols that aim to promote public trust and reduce conflicts of interest. Transparent policies should rely on protocols that separate lifesaving from organ preservation considerations; robust, centralized eCPR data to inform equitable and evidence-based allocations; uniform practices concerning clinical decision-making and resource utilization; and partnership with community stakeholders, allowing patients to make decisions about emergency care that align with their values. Proactively addressing these ethical and logistical challenges could enable eCPR dissemination and integration with NRP protocols in the USA, with the potential to maximize lives saved through both improved resuscitation with good neurological outcomes and increased organ donation opportunities when resuscitation is unsuccessful or not in accordance with individuals' wishes.

Replicability of proton MR spectroscopic imaging findings in mild traumatic brain injury: Implications for clinical applications.

PURPOSE: Proton magnetic resonance spectroscopy (1H MRS) offers biomarkers of metabolic damage after mild traumatic brain injury (mTBI), but a lack of replicability studies hampers clinical translation. In a conceptual replication study design, the results reported in four previous publications were used as the hypotheses (H1-H7), specifically: abnormalities in patients are diffuse (H1), confined to white matter (WM) (H2), comprise low N-acetyl-aspartate (NAA) levels and normal choline (Cho), creatine (Cr) and myo-inositol (mI) (H3), and correlate with clinical outcome (H4); additionally, a lack of findings in regional subcortical WM (H5) and deep gray matter (GM) structures (H6), except for higher mI in patients' putamen (H7). METHODS: 26 mTBI patients (20 female, age 36.5 ± 12.5 [mean ± standard deviation] years), within two months from injury and 21 age-, sex-, and education-matched healthy controls were scanned at 3 Tesla with 3D echo-planar spectroscopic imaging. To test H1-H3, global analysis using linear regression was used to obtain metabolite levels of GM and WM in each brain lobe. For H4, patients were stratified into non-recovered and recovered subgroups using the Glasgow Outcome Scale Extended. To test H5-H7, regional analysis using spectral averaging estimated metabolite levels in four GM and six WM structures segmented from T1-weighted MRI. The Mann-Whitney U test and weighted least squares analysis of covariance were used to examine mean group differences in metabolite levels between all patients and all controls (H1-H3, H5-H7), and between recovered and non-recovered patients and their respectively matched controls (H4). Replicability was defined as the support or failure to support the null hypotheses in accordance with the content of H1-H7, and was further evaluated using percent differences, coefficients of variation, and effect size (Cohen's d). RESULTS: Patients' occipital lobe WM Cho and Cr levels were 6.0% and 4.6% higher than controls', respectively (Cho, d = 0.37, p = 0.04; Cr, d = 0.63, p = 0.03). The same findings, i.e., higher patients' occipital lobe WM Cho and Cr (both p = 0.01), but with larger percent differences (Cho, 8.6%; Cr, 6.3%) and effect sizes (Cho, d = 0.52; Cr, d = 0.88) were found in the comparison of non-recovered patients to their matched controls. For the lobar WM Cho and Cr comparisons without statistical significance (frontal, parietal, temporal), unidirectional effect sizes were observed (Cho, d = 0.07 - 0.37; Cr, d = 0.27 - 0.63). No differences were found in any metabolite in any lobe in the comparison between recovered patients and their matched controls. In the regional analyses, no differences in metabolite levels were found in any GM or WM region, but all WM regions (posterior, frontal, corona radiata, and the genu, body, and splenium of the corpus callosum) exhibited unidirectional effect sizes for Cho and Cr (Cho, d = 0.03 - 0.34; Cr, d = 0.16 - 0.51). CONCLUSIONS: We replicated findings of diffuse WM injury, which correlated with clinical outcome (supporting H1-H2, H4). These findings, however, were among the glial markers Cho and Cr, not the neuronal marker NAA (not supporting H3). No differences were found in regional GM and WM metabolite levels (supporting H5-H6), nor in putaminal mI (not supporting H7). Unidirectional effect sizes of higher patients' Cho and Cr within all WM analyses suggest widespread injury, and are in line with the conclusion from the previous publications, i.e., that detection of WM injury may be more dependent upon sensitivity of the 1H MRS technique than on the selection of specific regions. The findings lend further support to the corollary that clinic-ready 1H MRS biomarkers for mTBI may best be achieved by using high signal-to-noise-ratio single-voxels placed anywhere within WM. The biochemical signature of the injury, however, may differ and therefore absolute levels, rather than ratios may be preferred. Future replication efforts should further test the generalizability of these findings.

Perceptions of the Healthcare System Among Black Men with Previously Undiagnosed Diabetes and Prediabetes.

OBJECTIVE: Given the significant disparities in diabetes burden and access to care, this study uses qualitative interviews of Black men having HbA1c levels consistent with previously undiagnosed diabetes or prediabetes to understand their perceptions of the healthcare system. RESEARCH DESIGN AND METHODS: We recruited Black men from Black-owned barbershops in Brooklyn, NY, who were screened using point-of-care HbA1c tests. Among those with HbA1c levels within prediabetes or diabetes thresholds, qualitative interviews were conducted to uncover prevalent themes related to their overall health status, health behaviors, utilization of healthcare services, and experiences with the healthcare system. We used a theoretical framework from the William and Mohammed medical mistrust model to guide our qualitative analysis. RESULTS: Fifty-two Black men without a prior history of diabetes and an HbA1c reading at or above 5.7% were interviewed. Many participants stated that their health was in good condition. Some participants expressed being surprised by their abnormal HbA1c reading because it was not previously mentioned by their healthcare providers. Furthermore, many of our participants shared recent examples of negative interactions with physicians when describing their experiences with the healthcare system. Finally, several participants cited a preference for incorporating non-pharmaceutical options in their diabetes management plans. CONCLUSION: To help alleviate the disparity in diabetes burden among Black men, healthcare providers should take a more active role in recognizing and addressing their own implicit biases, engage in understanding the specific healthcare needs and expectations of each patient, and consider emphasizing non-medication approaches to improve glycemic control.

Eye tracking for classification of concussion in adults and pediatrics.

Introduction: In order to obtain FDA Marketing Authorization for aid in the diagnosis of concussion, an eye tracking study in an intended use population was conducted. Methods: Potentially concussed subjects recruited in emergency department and concussion clinic settings prospectively underwent eye tracking and a subset of the Sport Concussion Assessment Tool 3 at 6 sites. The results of an eye tracking-based classifier model were then validated against a pre-specified algorithm with a cutoff for concussed vs. non-concussed. The sensitivity and specificity of eye tracking were calculated after plotting of the receiver operating characteristic curve and calculation of the AUC (area under curve). Results: When concussion is defined by SCAT3 subsets, the sensitivity and specificity of an eye tracking algorithm was 80.4 and 66.1%, The AUC was 0.718. The misclassification rate (n = 282) was 31.6%. Conclusion: A pre-specified algorithm and cutoff for diagnosis of concussion vs. non-concussion has a sensitivity and specificity that is useful as a baseline-free aid in diagnosis of concussion. Eye tracking has potential to serve as an objective "gold-standard" for detection of neurophysiologic disruption due to brain injury.

ED-Home: Pilot feasibility study of a targeted homelessness prevention intervention for emergency department patients with drug or unhealthy alcohol use.

BACKGROUND: Housing insecurity is prevalent among emergency department (ED) patients. Despite a surge of interest in screening for patients' social needs including housing insecurity, little research has examined ED social needs interventions. We worked together with government and community partners to develop and pilot test a homelessness prevention intervention targeted to ED patients with drug or unhealthy alcohol use. METHODS: We approached randomly sampled patients at an urban public hospital ED, May to August 2019. Adult patients were eligible if they were medically stable, not incarcerated, spoke English, had unhealthy alcohol or any drug use, and were not currently homeless but screened positive for risk of future homelessness using a previously developed risk screening tool. Participants received a three-part intervention: (1) brief counseling and referral to treatment for substance use delivered through a preexisting ED program; (2) referral to Homebase, an evidence-based community homelessness prevention program; and (3) up to three troubleshooting phone calls by study staff. Participants completed surveys at baseline and 6 months. RESULTS: Of 2183 patients screened, 51 were eligible and 40 (78.4%) participated; one later withdrew, leaving 39 participants. Participants were diverse in age, gender, race, and ethnicity. Of the 32 participants reached at 6 months, most said it was very or extremely helpful to talk to someone about their housing situation (n = 23, 71.9%) at the baseline ED visit. Thirteen (40.6%) said their housing situation had improved in the past 6 months and 16 (50.0%) said it had not changed. Twenty participants (62.5%) had made contact with a Homebase office. Participants shared ideas of how to improve the intervention. CONCLUSIONS: This pilot intervention was feasible and well received by participants though it required a large amount of screening to identify potentially eligible patients. Our findings will inform a larger future trial and may be informative for others seeking to develop similar interventions.

Targeting versus Tailoring Educational Videos for Encouraging Deceased Organ Donor Registration in Black-Owned Barbershops.

In the U.S., black men are at highest risk for requiring kidney transplants but are among those least likely to register for organ donation. Prior outreach used videos culturally targeted for Black communities, yet registration rates remain insufficient to meet demand. Therefore, we assessed whether generic versus videos culturally targeted or personally tailored based on prior organ donation beliefs differentially increase organ donor registration. In a randomized controlled trial, 1,353 participants in Black-owned barbershops viewed generic, targeted, or tailored videos about organ donation. Logistic regression models assessed the relative impact of videos on: 1) immediate organ donor registration, 2) taking brochures, and 3) change in organ donation willingness stage of change from baseline. Randomization yielded approximately equal groups related to demographics and baseline willingness and beliefs. Neither targeted nor tailored videos differentially affected registration compared with the generic video, but participants in targeted and tailored groups were more likely to take brochures. Targeted (OR = 1.74) and tailored (OR = 1.57) videos were associated with incremental increases in organ donation willingness stage of change compared to the generic video. Distributing culturally targeted and individually tailored videos increased organ donor willingness stage of change among Black men in Black-owned barbershops but was insufficient for encouraging registration.Abbreviations: CI - confidence interval; DMV - Department of Motor Vehicles; BOBs - Black-owned barbershops; ODBI - organ donation belief index; ODWS - organ donation willingness stage of change; OR - odds ratio.

Evaluating factors that influenced the successful implementation of an evidence-based neonatal care intervention in Chinese hospitals using the PARIHS framework.

BACKGROUND: Evidence based interventions (EBIs) can improve patient care and outcomes. Understanding the process for successfully introducing and implementing EBIs can inform effective roll-out and scale up. The Promoting Action on Research Implementation in Health Services (PARIHS) framework can be used to evaluate and guide the introduction and implementation of EBIs. In this study, we used kangaroo mother care (KMC) as an example of an evidence-based neonatal intervention recently introduced in selected Chinese hospitals, to identify the factors that influenced its successful implementation. We also explored the utility of the PARIHS framework in China and investigated how important each of its constructs (evidence, context and facilitation) and sub-elements were perceived to be to successful implementation of EBIs in a Chinese setting. METHOD: We conducted clinical observations and semi-structured interviews with 10 physicians and 18 nurses in five tertiary hospitals implementing KMC. Interview questions were organized around issues including knowledge and beliefs, resources, culture, implementation readiness and climate. We used directed content analysis to analyze the interview transcript, amending the PARIHS framework to incorporate emerging sub-themes. We also rated the constructs and sub-elements on a continuum from "low (weak)", "moderate" or "high (strong)" highlighting the ones considered most influential for hospital level implementation by study participants. RESULTS: Using KMC as an example, our finding suggest that clinical experience, culture, leadership, evaluation, and facilitation are highly influential elements for EBI implementation in China. External evidence had a moderate impact, especially in the initial awareness raising stages of implementation and resources were also considered to be of moderate importance, although this may change as implementation progresses. Patient experience was not seen as a driver for implementation at hospital level. CONCLUSION: Based on our findings examining KMC implementation as a case example, the PARIHS framework can be a useful tool for planning and evaluating EBI implementation in China. However, it's sub-elements should be assessed and adapted to the implementation setting.

T1 and T2 quantification using magnetic resonance fingerprinting in mild traumatic brain injury.

OBJECTIVES: To assess whether MR fingerprinting (MRF)-based relaxation properties exhibit cross-sectional and prospective correlations with patient outcome and compare the results with those from DTI. METHODS: Clinical imaging, MRF, and DTI were acquired in patients (24 ± 10 days after injury (timepoint 1) and 90 ± 17 days after injury (timepoint 2)) and once in controls. Patient outcome was assessed with global functioning, symptom profile, and neuropsychological testing. ADC and fractional anisotropy (FA) from DTI and T1 and T2 from MRF were compared in 12 gray and white matter regions with Mann-Whitney tests. Bivariate associations between MR measures and outcome were assessed using the Spearman correlation and logistic regression. RESULTS: Data from 22 patients (38 ± 12 years; 17 women) and 18 controls (32 ± 8 years; 12 women) were analyzed. Fourteen patients (37 ± 12 years; 11 women) returned for timepoint 2, while two patients provided only timepoint 2 clinical outcome data. At timepoint 1, there were no differences between patients and controls in T1, T2, and ADC, while FA was lower in mTBI frontal white matter. T1 at timepoint 1 and the change in T1 exhibited more (n = 18) moderate to strong correlations (|r|= 0.6-0.85) with clinical outcome at timepoint 2 than T2 (n = 3), FA (n = 7), and ADC (n = 2). High T1 at timepoint 1, and serially increasing T1, accounted for five of the six MR measures with the highest utility for identification of non-recovered patients at timepoint 2 (AUC > 0.80). CONCLUSION: T1 derived from MRF was found to have higher utility than T2, FA, and ADC for predicting 3-month outcome after mTBI. KEY POINTS: • In a region-of-interest approach, FA, ADC, and T1 and T2 all showed limited utility in differentiating patients from controls at an average of 24 and 90 days post-mild traumatic brain injury. • T1 at 24 days, and the serial change in T1, revealed more and stronger predictive correlations with clinical outcome at 90 days than did T2, ADC, or FA. • T1 showed better prospective identification of non-recovered patients at 90 days than ADC, T2, and FA.

Including Medical Footage and Emotional Content in Organ Donation Educational Videos for Latinx Viewers.

We assessed whether videos with medical footage of organ preservation and transplantation plus sad, unresolved, or uplifting stories differentially affect deceased organ donor registration among clients in Latinx-owned barbershops and beauty salons. In a 2 × 3 randomized controlled trial, participants (N = 1,696, mean age 33 years, 67% female) viewed one of six videos. The control portrayed a mother who received a kidney (uplifting), excluding medical footage. Experimental videos included medical footage and/or showed a mother waiting (unresolved) or sisters mourning their brother's death (sad). Regression models assessed relative impact of medical footage and storylines on: (1) registry enrollment, (2) donation willingness stage of change, and (3) emotions. Randomization yielded approximately equal groups relative to age, sex, education, religion, nativity, baseline organ donation willingness, beliefs, and emotions. Overall, 14.8% of participants registered. Neither medical footage, sad, nor unresolved stories differentially affected registration and changes in organ donation willingness. Sad and unresolved stories increased sadness and decreased positive affect by ~0.1 logits compared with the uplifting story. Educational videos about organ donation which excluded or included medical footage and varying emotional valence of stories induced emotions marginally but did not affect viewers' registration decisions differently. Heterogeneity of responses within video groups might explain the attenuated impact of including medical footage and varying emotional content. In future work, we will report qualitative reasons for participants' registration decisions by analyzing the free text responses from the randomized trial and data from semistructured interviews that were conducted with a subset of participants.

Optimizing Healthcare Through Digital Health and Wellness Solutions to Meet the Needs of Patients With Chronic Disease During the COVID-19 Era.

The COVID-19 pandemic exposed and exacerbated longstanding inefficiencies and deficiencies in chronic disease management and treatment in the United States, such as a fragmented healthcare experience and system, narrowly focused services, limited resources beyond office visits, expensive yet low quality care, and poor access to comprehensive prevention and non-pharmacological resources. It is feared that the addition of COVID-19 survivors to the pool of chronic disease patients will burden an already precarious healthcare system struggling to meet the needs of chronic disease patients. Digital health and telemedicine solutions, which exploded during the pandemic, may address many inefficiencies and deficiencies in chronic disease management, such as increasing access to care. However, these solutions are not panaceas as they are replete with several limitations, such as low uptake, poor engagement, and low long-term use. To fully optimize digital health and telemedicine solutions, we argue for the gamification of digital health and telemedicine solutions through a pantheoretical framework-one that uses personalized, contextualized, and behavioral science algorithms, data, evidence, and theories to ground treatments.

Global decrease in brain sodium concentration after mild traumatic brain injury.

The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients' sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated.