Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

Acetaminophen causes neurodevelopmental injury in susceptible babies and children: no valid rationale for controversy.

Despite the worldwide acceptance of acetaminophen (APAP) as a necessary medicine in pediatrics, evidence that early exposure to APAP causes neurodevelopmental injury in susceptible babies and children has been mounting for over a decade. The evidence is diverse and includes extensive work with laboratory animals, otherwise unexplained associations, factors associated with APAP metabolism, and limited studies in humans. Although the evidence has reached an overwhelming level and was recently reviewed in detail, controversy persists. This narrative review evaluates some of that controversy. Evidence from the pre- and postpartum periods was considered to avoid controversy raised by consideration of only limited evidence of risks during the prepartum period. Among other issues, the association between APAP use and the prevalence of neurodevelopmental disorders was considered. A systematic review revealed that the use of APAP in the pediatric population was never tracked carefully; however, historical events that affected its use were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Moreover, problems with the exclusive reliance on results of meta-analyses of large datasets with limited time frames of drug exposure were reviewed. Furthermore, the evidence of why some children are susceptible to APAPinduced neurodevelopmental injuries was examined. We concluded that available evidence demonstrates that early exposure to APAP causes neurodevelopmental injury in susceptible babies and small children.

Wastewater-Informed Digital Advertising as a COVID-19 Geotargeted Neighborhood Intervention: Jefferson County, Kentucky, 2021-2022.

We sought to deliver a geotargeted digital health advertising intervention. We assessed risk of community infection through an integrated public health and wastewater rubric and delivered advertisements between November 2021 and April 2022 in Louisville, Kentucky. The average daily click-through rates for the campaigns were 0.19%, 0.15%, and 0.13%. Results show potential for digital public health interventions that are geographically anchored to subcity sewersheds and community interest and willingness to engage with targeted wastewater-themed public health messaging. (Am J Public Health. 2024;114(1):34-37. https://doi.org/10.2105/AJPH.2023.307439).

The Carolina hysterectomy cohort (CHC): a novel case series of reproductive-aged hysterectomy patients across 10 hospitals in the US south.

BACKGROUND: Hysterectomy is a common surgery among reproductive-aged U.S. patients, with rates highest among Black patients in the South. There is limited insight on causes of these racial differences. In the U.S., electronic medical records (EMR) data can offer richer detail on factors driving surgical decision-making among reproductive-aged populations than insurance claims-based data. Our objective in this cohort profile paper is to describe the Carolina Hysterectomy Cohort (CHC), a large EMR-based case-series of premenopausal hysterectomy patients in the U.S. South, supplemented with census and surgeon licensing data. To demonstrate one strength of the data, we evaluate whether patient and surgeon characteristics differ by insurance payor type. METHODS: We used structured and abstracted EMR data to identify and characterize patients aged 18-44 years who received hysterectomies for non-cancerous conditions between 10/02/2014-12/31/2017 in a large health care system comprised of 10 hospitals in North Carolina. We used Chi-squared and Kruskal Wallis tests to compare whether patients' socio-demographic and relevant clinical characteristics, and surgeon characteristics differed by patient insurance payor (public, private, uninsured). RESULTS: Of 1857 patients (including 55% non-Hispanic White, 30% non-Hispanic Black, 9% Hispanic), 75% were privately-insured, 17% were publicly-insured, and 7% were uninsured. Menorrhagia was more prevalent among the publicly-insured (74% vs 68% overall). Fibroids were more prevalent among the privately-insured (62%) and the uninsured (68%). Most privately insured patients were treated at non-academic hospitals (65%) whereas most publicly insured and uninsured patients were treated at academic centers (66 and 86%, respectively). Publicly insured and uninsured patients had higher median bleeding (public: 7.0, uninsured: 9.0, private: 5.0) and pain (public: 6.0, uninsured: 6.0, private: 3.0) symptom scores than the privately insured. There were no statistical differences in surgeon characteristics by payor groups. CONCLUSION: This novel study design, a large EMR-based case series of hysterectomies linked to physician licensing data and manually abstracted data from unstructured clinical notes, enabled identification and characterization of a diverse reproductive-aged patient population more comprehensively than claims data would allow. In subsequent phases of this research, the CHC will leverage these rich clinical data to investigate multilevel drivers of hysterectomy in an ethnoracially, economically, and clinically diverse series of hysterectomy patients.

PS1/gamma-secretase acts as rogue chaperone of glutamate transporter EAAT2/GLT-1 in Alzheimer's disease.

The recently discovered interaction between presenilin 1 (PS1), a catalytic subunit of γ-secretase responsible for the generation of amyloid-ß(Aß) peptides, and GLT-1, the major glutamate transporter in the brain (EAAT2 in the human) may provide a mechanistic link between two important pathological aspects of Alzheimer's disease (AD): abnormal Aßoccurrence and neuronal network hyperactivity. In the current study, we employed a FRET-based approach, fluorescence lifetime imaging microscopy (FLIM), to characterize the PS1/GLT-1 interaction in its native environment in the brain tissue of sporadic AD (sAD) patients. There was significantly less interaction between PS1 and GLT-1 in sAD brains, compared to tissue from patients with frontotemporal lobar degeneration (FTLD), or non-demented age-matched controls. Since PS1 has been shown to adopt pathogenic "closed" conformation in sAD but not in FTLD, we assessed the impact of changes in PS1 conformation on the interaction. Familial AD (fAD) PS1 mutations which induce a "closed" PS1 conformation similar to that in sAD brain and gamma-secretase modulators (GSMs) which induce a "relaxed" conformation, reduced and increased the interaction, respectively. This indicates that PS1 conformation seems to have a direct effect on the interaction with GLT-1. Furthermore, using biotinylation/streptavidin pull-down, western blotting, and cycloheximide chase assays, we determined that the presence of PS1 increased GLT-1 cell surface expression and GLT-1 homomultimer formation, but did not impact GLT-1 protein stability. Together, the current findings suggest that the newly described PS1/GLT-1 interaction endows PS1 with chaperone activity, modulating GLT-1 transport to the cell surface and stabilizing the dimeric-trimeric states of the protein. The diminished PS1/GLT-1 interaction suggests that these functions of the interaction may not work properly in AD.

An Analysis of Written and Numeric Scores in End-of-Rotation Forms from Three Residency Programs.

Introduction: End-of-Rotation Forms (EORFs) assess resident progress in graduate medical education and are a major component of Clinical Competency Committee (CCC) discussion. Single-institution studies suggest EORFs can detect deficiencies, but both grades and comments skew positive. In this study, we sought to determine whether the EORFs from three programs, including multiple specialties and institutions, produced useful information for residents, program directors, and CCCs. Methods: Evaluations from three programs were included (Program 1, Institution A, Internal Medicine: n = 38; Program 2, Institution A, Anesthesia: n = 9; Program 3, Institution B, Anesthesia: n = 11). Two independent researchers coded each written comment for relevance (specificity and actionability) and orientation (praise or critical) using a standardized rubric. Numeric scores were analyzed using descriptive statistics. Results: 4869 evaluations were collected from the programs. Of the 77,434 discrete numeric scores, 691 (0.89%) were considered "below expected level." 71.2% (2683/3767) of the total written comments were scored as irrelevant, while 3217 (85.4%) of total comments were scored positive and 550 (14.6%) were critical. When combined, 63.2% (n = 2379) of comments were scored positive and irrelevant while 6.5% (n = 246) were scored critical and relevant. Discussion: <1% of comments indicated below average performance; >70% of comments scored irrelevant. Critical, relevant comments were least frequently observed, consistent across all 3 programs. The low rate of constructive feedback and the high rate of irrelevant comments are inadequate for a CCC to make informed decisions. The consistency of these findings across programs, specialties, and institutions suggests both local and systemic changes should be considered.

Features of Effective Clinical Competency Committees.

Background: The Clinical Competency Committee (CCC) provides accountability to the general public that physicians completing a training program have achieved competence. CCC processes and features that best identify resident outcomes along a developmental spectrum are not well described. Objective: This study sought to describe CCC features associated with effective and efficient CCC performance. Methods: The study was conducted as part of the 2022 Council of Academic Family Medicine Educational Research Alliance survey of family medicine residency program directors. The survey assessed CCC methods, policies, faculty development, structure, and overall CCC time required. The outcomes were identification of residents along a spectrum of development, from failing to exceeding expectations. Ordinal logistic regressions were used to explore the relationship between CCC characteristics and CCC outcomes. Results: The response rate was 43.3% (291 of 672). Eighty-nine percent (258 of 291) of program directors reported their CCC is successful in identifying residents not meeting expectations; 69.3% (201 of 290) agree their CCC identifies residents who are exceeding expectations. Programs with written policies for synthesizing data (OR=2.53; 95% CI 1.22-5.22; P=.012) and written policies for resident feedback (OR=19.91; 95% CI 3.72-106.44; P<.001) were more likely to report successfully identifying residents below expectations. Programs whose members spent fewer than 3 hours per 6-month interval on CCC meetings were less likely to report being able to identify failing residents (OR=0.37; 95% CI 0.19-0.72; P=.004). Conclusions: This survey of family medicine program directors suggests that formal policies, faculty development, and adequate time for CCC faculty are associated with an effective CCC, especially if goals beyond "identifying failure" are desired.

Encapsulated Calcified Hematoma Mimicking a Cardiac Tumor, Diagnosed 25 Years Post-Traumatic Injury.

A 45-year-old man presented with nonspecific symptoms caused by a mass compressing the right ventricle. Cardiac computed tomography accurately predicted the operative and pathologic appearance of the mass, and the final diagnosis of an encapsulated cardiac hematoma was confirmed by pathologic examination. This condition is infrequent and mimics a cardiac tumor. (Level of Difficulty: Advanced.).

Generative AI as a Tool for Environmental Health Research Translation.

One valuable application for generative artificial intelligence (AI) is summarizing research studies for non-academic readers. We submitted five articles to Chat Generative Pre-trained Transformer (ChatGPT) for summarization, and asked the article's author to rate the summaries. Higher ratings were assigned to more insight-oriented activities, such as the production of eighth-grade reading level summaries, and summaries highlighting the most important findings and real-world applications. The general summary request was rated lower. For the field of environmental health science, no-cost AI technology such as ChatGPT holds the promise to improve research translation, but it must continue to be improved (or improve itself) from its current capability.

The APOE-TOMM40 Humanized Mouse Model: Characterization of Age, Sex, and PolyT Variant Effects on Gene Expression.

BACKGROUND: The human chromosome 19q13.32 is a gene rich region and has been associated with multiple phenotypes, including late onset Alzheimer's disease (LOAD) and other age-related conditions. OBJECTIVE: Here we developed the first humanized mouse model that contains the entire TOMM40 and APOE genes with all intronic and intergenic sequences including the upstream and downstream regions. Thus, the mouse model carries the human TOMM40 and APOE genes and their intact regulatory sequences. METHODS: We generated the APOE-TOMM40 humanized mouse model in which the entire mouse region was replaced with the human (h)APOE-TOMM40 loci including their upstream and downstream flanking regulatory sequences using recombineering technologies. We then measured the expression of the human TOMM40 and APOE genes in the mice brain, liver, and spleen tissues using TaqMan based mRNA expression assays. RESULTS: We investigated the effects of the '523' polyT genotype (S/S or VL/VL), sex, and age on the human TOMM40- and APOE-mRNAs expression levels using our new humanized mouse model. The analysis revealed tissue specific and shared effects of the '523' polyT genotype, sex, and age on the regulation of the human TOMM40 and APOE genes. Noteworthy, the regulatory effect of the '523' polyT genotype was observed for all studied organs. CONCLUSION: The model offers new opportunities for basic science, translational, and preclinical drug discovery studies focused on the APOE genomic region in relation to LOAD and other conditions in adulthood.

Ethnoracial Differences in Premenopausal Hysterectomy: The Role of Symptom Severity.

OBJECTIVE: To evaluate whether greater symptom severity can explain higher hysterectomy rates among premenopausal non-Hispanic Black compared with White patients in the U.S. South rather than potential overtreatment of Black patients. METHODS: Using electronic health record data from 1,703 patients who underwent hysterectomy in a large health care system in the U.S. South between 2014 and 2017, we assessed symptom severity to account for differences in hysterectomy rates for noncancerous conditions among premenopausal non-Hispanic Black, non-Hispanic White, and Hispanic patients. We used Poisson generalized linear mixed modeling to estimate symptom severity (greater than the 75th percentile on composite symptom severity scores of bleeding, bulk, or pelvic pain) as a function of race-ethnicity. We calculated prevalence ratios (PRs). We controlled for factors both contra-indicating and contributing to hysterectomy. RESULTS: The overall median age of non-Hispanic White (n=1,050), non-Hispanic Black (n=565), and Hispanic (n=158) patients was 40 years. The White and Black patients were mostly insured (insured greater than 95%), whereas the Hispanic patients were often uninsured (insured 58.9%). White and Black patients were mostly treated outside academic medical centers (nonmedical center: 63.7% and 58.4%, respectively); the opposite was true for Hispanic patients (nonmedical center: 34.2%). Black patients had higher bleeding severity scores compared with Hispanic and White patients (median 8, 7, and 4 respectively) and higher bulk scores (median 3, 1, and 0, respectively), but pain scores differed (median 3, 5, and 4, respectively). Black and Hispanic patients were disproportionately likely to have severe symptoms documented on two or more symptoms (referent: not severe on any symptoms) (adjusted PR [Black vs White] 3.02, 95% CI 2.29-3.99; adjusted PR [Hispanic vs White] 2.61, 95% CI 1.78-3.83). Although Black and Hispanic patients were more likely to experience severe symptoms, we found no racial and ethnic differences in the number of alternative treatments attempted before hysterectomy. CONCLUSION: We did not find evidence of overtreatment of Black patients. Our findings suggest potential undertreatment of Black and Hispanic patients with uterine-sparing alternatives earlier in their disease progression.

Artificial intelligence using a deep learning versus expert computed tomography human reading in calcium score and coronary artery calcium data and reporting system classification.

BACKGROUND: Artificial intelligence (AI) applied to cardiac imaging may provide improved processing, reading precision and advantages of automation. Coronary artery calcium (CAC) score testing is a standard stratification tool that is rapid and highly reproducible. We analyzed CAC results of 100 studies in order to determine the accuracy and correlation between the AI software (Coreline AVIEW, Seoul, South Korea) and expert level-3 computed tomography (CT) human CAC interpretation and its performance when coronary artery disease data and reporting system (coronary artery calcium data and reporting system) classification is applied. METHODS: A total of 100 non-contrast calcium score images were selected by blinded randomization and processed with the AI software versus human level-3 CT reading. The results were compared and the Pearson correlation index was calculated. The CAC-DRS classification system was applied, and the cause of category reclassification was determined using an anatomical qualitative description by the readers. RESULTS: The mean age was age 64.5 years, with 48% female. The absolute CAC scores between AI versus human reading demonstrated a highly significant correlation (Pearson coefficient R  = 0.996); however, despite these minimal CAC score differences, 14% of the patients had their CAC-DRS category reclassified. The main source of reclassification was observed in CAC-DRS 0-1, where 13 were recategorized, particularly between studies having a CAC Agatston score of 0 versus 1. Qualitative description of the errors showed that the main cause of misclassification was AI underestimation of right coronary calcium, AI overestimation of right ventricle densities and human underestimation of right coronary artery calcium. CONCLUSION: Correlation between AI and human values is excellent with absolute numbers. When the CAC-DRS classification system was adopted, there was a strong correlation in the respective categories. Misclassified were predominantly in the category of CAC = 0, most often with minimal values of calcium volume. Additional algorithm optimization with enhanced sensitivity and specificity for low values of calcium volume will be required to enhance AI CAC score utilization for minimal disease. Over a broad range of calcium scores, AI software for calcium scoring had an excellent correlation compared to human expert reading and in rare cases determined calcium missed by human interpretation.

Subcoronal inflatable penile prosthesis implantation: indications and outcomes.

BACKGROUND: While implantation of an inflatable penile prosthesis (IPP) is commonly performed via infrapubic or penoscrotal approaches, the subcoronal (SC) approach for IPP implantation may safely and reliably allow for additional reconstructive procedures through a single incision. AIM: The aim of this study is to report outcomes, including complications, of the SC approach and to determine common characteristics of patients undergoing the SC approach. METHODS: A retrospective chart review from May 11, 2012, to January 31, 2022, was performed at a single, tertiary care institution to identify patients with IPP implantation via the SC approach. OUTCOMES: Postoperative information was reviewed and extracted from all clinic notes available following the date of IPP implantation in the electronic medical record, detailing any complications including wound complications, need for revision or removal, device malfunction, and infections. RESULTS: Sixty-six patients had IPP implantation via the SC approach. Median follow-up duration was 29.4 (interquartile range 14.9-50.1) months. One (1.8%) patient had a simple wound complication. Two (3.6%) experienced postoperative infection of the prosthesis, which resulted in explantation of the device. One of these infected prostheses later experienced partial glans necrosis. Revision for mechanical failure or unsatisfactory cosmetic result was performed in 3 (7.3%) IPPs placed via a SC incision. CLINICAL IMPLICATIONS: The SC approach for implantation of IPP is safe and feasible with low complication and revision rates. It offers urologists an alternative to the classic infrapubic and penoscrotal approaches, both of which would require a second incision for additional reconstructive procedures required to adequately address deformities associated with severe Peyronie's disease. Therefore, urologists who treat these specialized populations of men may benefit from having the SC approach in their array of techniques for IPP implantation. STRENGTHS AND LIMITATIONS: The limitations of this study include its retrospective nature, risk of selection bias, lack of comparison groups, and sample size. This study reports on early experience with the SC approach performed by a single high-volume reconstructive surgeon, who treats a specialized population of patients requiring complex repair during implantation of an IPP, particularly those with Peyronie's disease. CONCLUSION: The SC incision for IPP implantation has low rates of complications and remains our approach of choice for IPP implantation in patients with severe Peyronie's disease, including curvatures >60°, severe indentation with hinge, and grade 3 calcification, which are unlikely to respond adequately to manual modeling alone.

Single-cell multi-scale footprinting reveals the modular organization of DNA regulatory elements.

Cis-regulatory elements control gene expression and are dynamic in their structure, reflecting changes to the composition of diverse effector proteins over time1-3. Here we sought to connect the structural changes at cis-regulatory elements to alterations in cellular fate and function. To do this we developed PRINT, a computational method that uses deep learning to correct sequence bias in chromatin accessibility data and identifies multi-scale footprints of DNA-protein interactions. We find that multi-scale footprints enable more accurate inference of TF and nucleosome binding. Using PRINT with single-cell multi-omics, we discover wide-spread changes to the structure and function of candidate cis-regulatory elements (cCREs) across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Activity segmentation using the co-variance across cell states identifies "sub-cCREs" as modular cCRE subunits of regulatory DNA. We apply this single-cell and PRINT approach to characterize the age-associated alterations to cCREs within hematopoietic stem cells (HSCs). Remarkably, we find a spectrum of aging alterations among HSCs corresponding to a global gain of sub-cCRE activity while preserving cCRE accessibility. Collectively, we reveal the functional importance of cCRE structure across cell states, highlighting changes to gene regulation at single-cell and single-base-pair resolution.

Generative AI as a Tool for Environmental Health Research Translation.

Generative artificial intelligence, popularized by services like ChatGPT, has been the source of much recent popular attention for publishing health research. Another valuable application is in translating published research studies to readers in non-academic settings. These might include environmental justice communities, mainstream media outlets, and community science groups. Five recently published (2021-2022) open-access, peer-reviewed papers, authored by University of Louisville environmental health investigators and collaborators, were submitted to ChatGPT. The average rating of all summaries of all types across the five different studies ranged between 3 and 5, indicating good overall content quality. ChatGPT’s general summary request was consistently rated lower than all other summary types. Whereas higher ratings of 4 and 5 were assigned to the more synthetic, insight-oriented activities, such as the production of a plain language summaries suitable for an 8 th grade reading level and identifying the most important finding and real-world research applications. This is a case where artificial intelligence might help level the playing field, for example by creating accessible insights and enabling the large-scale production of high-quality plain language summaries which would truly bring open access to this scientific information. This possibility, combined with the increasing public policy trends encouraging and demanding free access for research supported with public funds, may alter the role journal publications play in communicating science in society. For the field of environmental health science, no-cost AI technology such as ChatGPT holds the promise to improve research translation, but it must continue to be improved (or improve itself) from its current capability.

Exploring the Great Divide: Comparing Professional Development Satisfaction and Opportunities of Program Coordinators at Academic Medical Centers and Community-Based Programs.

INTRODUCTION: Program coordinators (PCs) need to maintain flexibility and evolve professionally with rapid changes in accreditation, specialty requirements, and policies. The Accreditation Council for Graduate Medical Education recommends professional development for PCs. This mixed-methods study explored professional development opportunities and current practices of PCs at community and academic programs. METHODS: A survey was administered to the Chicago Area Medical Education Group members to elicit attitudes and opinions regarding professional development availability. RESULTS: A total of 109 participants (eligible = 178) completed surveys. 97.2% (n = 105, N = 108) of respondents indicated that development is necessary for being a great coordinator. PCs at community-based programs report lower attendance at national conferences and less satisfaction with professional development opportunities than their academic-based institution counterparts. 28.5% of the community-based coordinators are dissatisfied with opportunities compared with 7% of the academic-based coordinators. 37.7% of the community coordinators (compared with 2.9% academic) report a lack of development activities by their program or graduate medical education. Only half of the PCs report discussing professional development with their program director. However, institutional supports were regarded as facilitators to satisfaction. CONCLUSIONS: Despite recommendations for regular professional development, this study finds only half of the PCs regularly discuss professional development and finds disparities in opportunities between those in community versus academic settings.

The Dangers of Acetaminophen for Neurodevelopment Outweigh Scant Evidence for Long-Term Benefits.

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment.

A collaborative care package for depression comorbid with chronic physical conditions in South Africa.

INTRODUCTION: A task-sharing collaborative care model for integrated depression care for South Africa's burgeoning primary health care population with chronic conditions was developed and tested through two pragmatic cluster randomized controlled trials. One trial focused on patients with hypertension and was located in one district where a collaborative care model was co-designed with district stakeholders. The other trial, focused on patients on antiretroviral treatment, was located in the same district site, with the addition of a second neighbouring district, without adaptation of the original model. This paper describes the package used to implement this model, and implementation outcomes across the two sites, and summarises lessons and challenges. METHODS: The Template for Intervention Description and Replication (TIDieR) framework, adapted for complex health systems interventions, was used to describe components of the package. Additional elements of 'modifications made' and 'actual implementation' introduced in the 'Getting messier with TIDieR' framework, were used to describe implementation outcomes in terms of reach, adoption and implementation across the two trial districts. RESULTS: In the absence of a co-design process to adapt the model to the context of the second site, there was less system level support for the model. Consequently, more project employed human resources were deployed to support training of primary care nurses in identification and referral of patients with depression; and supervise co-located lay counsellors. Referrals to co-located lay counselling services were more than double in the second site. However, uptake of counselling sessions was greater in the first site. This was attributed to greater in-vivo supervision and support from existing mental health specialists in the system. There was greater reliance on online supervision and support in the second site where geographical distances between clinics were larger. CONCLUSION: The need for in-country co-designed collaborative care models, and 'implementation heavy' implementation research to understand adaptations required to accommodate varying in-country health system contexts is highlighted.

Serial analysis of coronary artery disease progression by artificial intelligence assisted coronary computed tomography angiography: early clinical experience.

BACKGROUND: Studies have shown that quantitative evaluation of coronary artery plaque on Coronary Computed Tomography Angiography (CCTA) can identify patients at risk of cardiac events. Recent demonstration of artificial intelligence (AI) assisted CCTA shows that it allows for evaluation of CAD and plaque characteristics. Based on publications to date, we are the first group to perform AI augmented CCTA serial analysis of changes in coronary plaque characteristics over 13 years. We evaluated whether AI assisted CCTA can accurately assess changes in coronary plaque progression, which has potential clinical prognostic value in CAD management. CASE PRESENTATION: 51-year-old male with hypertension, hyperlipidemia and family history of myocardial infarction, underwent CCTA exams for anginal symptom evaluation and CAD assessment. 5 CCTAs were performed between 2008 and 2021. Quantitative atherosclerosis plaque characterization (APC) using an AI platform (Cleerly), was performed to assess CAD burden. Total plaque volume (TPV) change-over-time demonstrated decreasing low-density non-calcified plaque (LD-NCP) with increasing overall NCP and calcified-plaque (CP). Examination of individual segments revealed a proximal-LAD lesion with decreasing NCP over-time and increasing CP. In contrast, although the D2/D1/ramus lesions showed increasing stenosis, CP, and total plaque, there were no significant differences in NCP over-time, with stable NCP and increased CP. Remarkably, we also consistently visualized small plaques, which typically readers may interpret as false positives due to artifacts. But in this case, they reappeared each study in the same locations, generally progressing in size and demonstrating expected plaque transformation over-time. CONCLUSIONS: We performed the first AI augmented CCTA based serial analysis of changes in coronary plaque characteristics over 13 years. We were able to consistently assess progression of plaque volumes, stenosis, and APCs with this novel methodology. We found a significant increase in TPV composed of decreasing LD-NCP, and increasing NCP and CP, with variations in the evolution of APCs between vessels. Although the significance of evolving APCs needs to be investigated, this case demonstrates AI-based CCTA analysis can serve as valuable clinical tool to accurately define unique CAD characteristics over time. Prospective trails are needed to assess whether quantification of APCs provides prognostic capabilities to improve clinical care.