Development and preliminary testing of Health Equity Across the AI Lifecycle (HEAAL): A framework for healthcare delivery organizations to mitigate the risk of AI solutions worsening health inequities.

The use of data-driven technologies such as Artificial Intelligence (AI) and Machine Learning (ML) is growing in healthcare. However, the proliferation of healthcare AI tools has outpaced regulatory frameworks, accountability measures, and governance standards to ensure safe, effective, and equitable use. To address these gaps and tackle a common challenge faced by healthcare delivery organizations, a case-based workshop was organized, and a framework was developed to evaluate the potential impact of implementing an AI solution on health equity. The Health Equity Across the AI Lifecycle (HEAAL) is co-designed with extensive engagement of clinical, operational, technical, and regulatory leaders across healthcare delivery organizations and ecosystem partners in the US. It assesses 5 equity assessment domains-accountability, fairness, fitness for purpose, reliability and validity, and transparency-across the span of eight key decision points in the AI adoption lifecycle. It is a process-oriented framework containing 37 step-by-step procedures for evaluating an existing AI solution and 34 procedures for evaluating a new AI solution in total. Within each procedure, it identifies relevant key stakeholders and data sources used to conduct the procedure. HEAAL guides how healthcare delivery organizations may mitigate the potential risk of AI solutions worsening health inequities. It also informs how much resources and support are required to assess the potential impact of AI solutions on health inequities.

Contraceptive Provision to Women With Intellectual and Developmental Disabilities Enrolled in Medicaid.

OBJECTIVE: To compare contraceptive provision to women with and without intellectual and developmental disabilities enrolled in North Carolina Medicaid. METHODS: Our retrospective cohort study used 2019 North Carolina Medicaid claims to identify women aged 15-44 years with and without intellectual and developmental disabilities at risk for pregnancy who were continuously enrolled during 2019 or had Family Planning Medicaid with at least one claim. We calculated the proportion in each cohort who received 1) most or moderately effective contraception, 2) long-acting reversible contraception, 3) short-acting contraception, and 4) individual methods. We classified contraceptive receipt by procedure type and disaggregated across sociodemographic characteristics. Adjusting for age, race, ethnicity, and urban or rural setting, we constructed logistic regression models to estimate most or moderately effective contraceptive provision odds by intellectual and developmental disability status and by level or type of intellectual and developmental disability. We performed subanalyses to estimate co-occurrence of provision and menstrual disorders. RESULTS: Among 9,508 women with intellectual and developmental disabilities and 299,978 without, a significantly smaller proportion with intellectual and developmental disabilities received most or moderately effective contraception (30.1% vs 36.3%, P <.001). With the exception of injectable contraception, this trend was consistent across all measures and remained statistically significant after controlling for race, ethnicity, age, and urban or rural status (adjusted odds ratio 0.75, 95% CI 0.72-0.79; P <.001). Among those who received most or moderately effective contraception, a significantly greater proportion of women with intellectual and developmental disabilities had co-occurring menstrual disorders (31.3% vs 24.3%, P <.001). CONCLUSION: These findings suggest disparities in contraceptive provision and potential differences in clinical indication by intellectual and developmental disability status. Future studies should investigate reasons for and barriers to contraceptive use among women with intellectual and developmental disabilities.

Recycling unused medications in hospitals is financially viable and good for the environment.

OBJECTIVES: Considerable pharmaceutical waste is generated in hospital settings which can be reduced by recycling of unused medications. We sought to determine the recycling practices as well as quantify the volume and the value of oral solid medications returned from nursing units to the pharmacy departments at three urban hospitals. METHODS: Unused oral solid medications were recycled at three sites and the net financial impact of this practice was calculated (cost recovered - labour costs). The results were extrapolated to all 21 hospitals within the health system. KEY FINDINGS: Recycling medications in 21 hospitals could divert ~461 000 units of medication from the incinerator, with an estimated net value of ~$415 000 per year. CONCLUSIONS: Recycling unused medications could save substantial amounts of money and reduce negative environmental impacts from disposal/incineration.

Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes are unclear. Senescing cells upregulate thrombomodulin-protease-activated receptor-1 (THBD-PAR1) signaling to remain viable. Vorapaxar blocks the activity of that pathway. We used vorapaxar to determine if and how THBD-PAR1 signaling promotes fibrosis progression in NASH. APPROACH AND RESULTS: We evaluated the THBD-PAR1 pathway in liver biopsies from patients with NAFLD. Chow-fed mice were treated with viral vectors to overexpress p16 in hepatocytes and induce replicative senescence. Effects on the THBD-PAR1 axis and regenerative capacity were assessed; the transcriptome of p16-overexpressing hepatocytes was characterized, and we examined how conditioned medium from senescent but viable (dubbed "undead") hepatocytes reprograms HSCs. Mouse models of NASH caused by genetic obesity or Western diet/CCl 4 were treated with vorapaxar to determine effects on hepatocyte senescence and liver damage. Inducing senescence upregulates the THBD-PAR1 signaling axis in hepatocytes and induces their expression of fibrogenic factors, including hedgehog ligands. Hepatocyte THBD-PAR1 signaling increases in NAFLD and supports sustained hepatocyte senescence that limits effective liver regeneration and promotes maladaptive repair. Inhibiting PAR1 signaling with vorapaxar interrupts this process, reduces the burden of 'undead' senescent cells, and safely improves NASH and fibrosis despite ongoing lipotoxic stress. CONCLUSION: The THBD-PAR1 signaling axis is a novel therapeutic target for NASH because blocking this pathway prevents accumulation of senescing but viable hepatocytes that generate factors that promote maladaptive liver repair.

Genetic analysis of daf-18/PTEN missense mutants for starvation resistance and developmental regulation during Caenorhabditis elegans L1 arrest.

Mutations in the well-known tumor suppressor PTEN are observed in many cancers. PTEN is a dual-specificity phosphatase that harbors lipid and protein-phosphatase activities. The Caenorhabditis elegans PTEN ortholog is daf-18, which has pleiotropic effects on dauer formation, aging, starvation resistance, and development. Function of 3 daf-18 point-mutants, G174E, D137A, and C169S, had previously been investigated using high-copy transgenes in a daf-18 null background. These alleles were generated based on their mammalian counterparts and were treated as though they specifically disrupt lipid or protein-phosphatase activity, or both, respectively. Here, we investigated these alleles using genome editing of endogenous daf-18. We assayed 3 traits relevant to L1 starvation resistance, and we show that each point mutant is essentially as starvation-sensitive as a daf-18 null mutant. Furthermore, we show that G174E and D137A do not complement each other, suggesting overlapping effects on lipid and protein-phosphatase activity. We also show that each allele has strong effects on nucleocytoplasmic localization of DAF-16/FoxO and dauer formation, both of which are regulated by PI3K signaling, similar to a daf-18 null allele. In addition, each allele also disrupts M-cell quiescence during L1 starvation, though D137A has a weaker effect than the other alleles, including the null. Our results confirm that daf-18/PTEN is important for promoting starvation resistance and developmental arrest and that it is a potent regulator of PI3K signaling, and they highlight challenges of using genetic analysis to link specific DAF-18/PTEN enzymatic activities to particular phenotypes.

Aging reduces liver resiliency by dysregulating Hedgehog signaling.

Older age is a major risk factor for damage to many tissues, including liver. Aging undermines resiliency and impairs liver regeneration. The mechanisms whereby aging reduces resiliency are poorly understood. Hedgehog is a signaling pathway with critical mitogenic and morphogenic functions during development. Recent studies indicate that Hedgehog regulates metabolic homeostasis in adult liver. The present study evaluates the hypothesis that Hedgehog signaling becomes dysregulated in hepatocytes during aging, resulting in decreased resiliency and therefore, impaired regeneration and enhanced vulnerability to damage. Partial hepatectomy (PH) was performed on young and old wild-type mice and Smoothened (Smo)-floxed mice treated with viral vectors to conditionally delete Smo and disrupt Hedgehog signaling specifically in hepatocytes. Changes in signaling were correlated with changes in regenerative responses and compared among groups. Old livers had fewer hepatocytes proliferating after PH. RNA sequencing identified Hedgehog as a top downregulated pathway in old hepatocytes before and after the regenerative challenge. Deleting Smo in young hepatocytes before PH prevented Hedgehog pathway activation after PH and inhibited regeneration. Gene Ontogeny analysis demonstrated that both old and Smo-deleted young hepatocytes had activation of pathways involved in innate immune responses and suppression of several signaling pathways that control liver growth and metabolism. Hedgehog inhibition promoted telomere shortening and mitochondrial dysfunction in hepatocytes, consequences of aging that promote inflammation and impair tissue growth and metabolic homeostasis. Hedgehog signaling is dysregulated in old hepatocytes. This accelerates aging, resulting in decreased resiliency and therefore, impaired liver regeneration and enhanced vulnerability to damage.

Renal allograft compartment syndrome: a review.

Renal allograft compartment syndrome (RACS) is the result of extrinsic compression resulting in graft dysfunction and loss due to ischaemia. A literature review was performed by computerized searches from the following data sources Medline, EMBASE, PubMed and Cochrane Library databases. Risk factors include size mismatch between graft and recipient. Intraoperative suspicion should be exercised if there is poor tissue turgor, cyanosis and loss of urine output upon fascial closure. Doppler ultrasound is the modality of choice amongst the literature to aid in diagnosis of RACS. From our study, the accepted form of treatment is early detection and appropriate surgical intervention. Nevertheless, it is clear from the paucity of literature that further investigation into this area of transplantation is necessary.

Hepatocyte activity of the cholesterol sensor smoothened regulates cholesterol and bile acid homeostasis in mice.

Cellular cholesterol is regulated by at least two transcriptional mechanisms involving sterol-regulatory-element-binding proteins (SREBPs) and liver X receptors (LXRs). Although SREBP and LXR pathways are the predominant mechanisms that sense cholesterol in the endoplasmic reticulum and nucleus to alter sterol-regulated gene expression, evidence suggests cholesterol in plasma membrane can be sensed by proteins in the Hedgehog (Hh) pathway which regulate organ self-renewal and are a morphogenic driver during embryonic development. Cholesterol interacts with the G-protein-coupled receptor Smoothened (Smo), which impacts downstream Hh signaling. Although evidence suggests cholesterol influences Hh signaling, it is not known whether Smo-dependent sterol sensing impacts cholesterol homeostasis in vivo. We examined dietary-cholesterol-induced reorganization of whole-body sterol and bile acid (BA) homeostasis in adult mice with inducible hepatocyte-specific Smo deletion. These studies demonstrate Smo in hepatocytes plays a regulatory role in sensing and feedback regulation of cholesterol balance driven by excess dietary cholesterol.

How to repair a donor renal vein injury with an inferior vena cava patch.

Shortage of supply of organs for donation means that every viable organ should be given the best chance possible for transplantation. As such, we present a method of renal vein reconstruction of a deceased donor kidney following injury during the organ recovery process.

Burnett's "Cocaine" for dandruff.

Joseph Burnett manufactured the diethyl ether used for William T.G. Morton's public demonstration of inhaled surgical anesthesia on October 16, 1846 (Ether Day). A later Burnett product was a hairdressing oil claimed to prevent baldness and dandruff. It contained cocoa-nut oil and was called Cocoaine. In 1902 and 1903, it was sometimes advertised as Burnett's Cocaine (rather than Cocoaine), possibly to emulate the economic success of coca-based beverages such as Vin Mariani and Coca-Cola. Coca leaves are now decocainized before use in preparation of Coca-Cola, and the recovered cocaine is used for scientific and dwindling medical purposes.

Beware the band adhesion: an unexpected cause of double obstruction following intraperitoneal kidney transplantation.

Small bowel obstruction (SBO) following intraperitoneal renal transplantation, either solitary or due to simultaneous pancreas-kidney transplantation, is a known complication. While SBO is most commonly due to adhesions, there have been documented cases of internal herniation following simultaneous pancreas-kidney transplantation with enteric drainage due to the formation of a mesenteric defect. We present a unique complication in which the transplant ureter has caused strangulation and necrosis of a length of small intestine. The transplant ureter was mistaken for a band adhesion and divided. Post-operative anuria signalled this difficult diagnosis. Subsequent re-look laparotomy and ureteric reimplantation with Boari flap were required. Therefore, it is important to consider the ureter as a cause of internal herniation in kidney transplant patients and recognize that a band adhesion within the pelvis may in fact be the transplant ureter, obstructing a loop of small intestine beneath its course.

Kety-Schmidt Application of Nitrous Oxide to Determine Cerebral Blood Flow.

In the 1940s, Seymour S. Kety and Carl F. Schmidt measured cerebral blood flow in awake humans by means of subanesthetic doses of inhaled nitrous oxide. The inhalation route obviated the need for an arterial injection of the indicator, and nitrous oxide had virtues of metabolic inertness, rapid diffusion through the blood-brain barrier, comparable blood and brain solubility, and ease of analytical detection. The technique was also applied to the heart. Follow-up work by Kety contributed to the development of brain scanning methods.

Accuracy of estimation of polyp size at colonoscopy.

BACKGROUND: The Cancer Council posits that the size of adenomas is a more robust marker of risk than histological characteristics. The purpose of our study is to assess the accuracy of estimation of polyp size at colonoscopy amongst different levels of endoscopists and compare this with histopathological size. METHODS: A retrospective review of prospectively collected data was performed. Specimens were included if they were (i) from patients aged 18 years or older, (ii) polyp obtained at colonoscopy, (iii) measured in quantitative units and (iv) the largest eligible polyp per patient. RESULTS: A total of 92 patients were included. Our results demonstrate that the relationship between the histological size of a polyp and an endoscopist's estimate depended upon seniority level (P = 0.001). Senior consultants tended to overestimate lesion size (P < 0.001), fellows/junior consultants tended to underestimate size (P = 0.010), whilst registrars' estimates demonstrated no systematic difference from histological size (P = 0.518). The ratio of a senior consultant's estimate of polyp size to histological size was on average 74% with their estimates ranging from 31% to 173%. The corresponding estimates are 123% (32-470%) for fellows/junior consultants and 107% (35-334%) for registrars. CONCLUSION: Our study demonstrates that senior consultants are more precise with more junior endoscopists having a great degree of variability in their practice. It is evident that there is a relationship between proceduralist experience and polyp size estimation. It is, therefore, important to consider the ways in which we can mitigate this learning curve and continue to develop technology to improve our accuracy.

Anesthesia and COVID-19: What We Should Know and What We Should Do.

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.

Production and evaluation of biosynthesized cellulose tubes as promising nerve guides for spinal cord injury treatment.

Spinal cord injury (SCI) is a central nervous disorder that can result in permanent motor and sensory damage due to a severed communication pathway. Although there is currently no effective treatment, nerve guide tubes have been used to bridge the injured stumps and act as drug delivery systems. In this study, biosynthesized cellulose (BC) nerve guides were prepared, and nerve growth factor (NGF)-a model growth factor-was incorporated into the tubular nerve guide in order to obtain a nerve guide/drug delivery system to assist the regeneration. To achieve this, Gluconacetobacter hansenii was cultivated in a special bioreactor to produce biosynthesized cellulose tubes (BCTs) in situ, and the physical and mechanical properties of the BCTs obtained from different cultivation time points were evaluated. Our results showed that the properties of the BCTs were comparable to those of the native human neural tissues, and that the NGF released from the BCTs was bioactive for at least 7 days as evaluated by PC12 cell cultures in vitro. In summary, this study evaluated the use of BCT as a drug releasing nerve guide, and our results showed that the BCT is an attractive strategy to enhance nerve regeneration after the SCI.

A Network Meta-Analysis to Compare the Efficacy of Steroid and Antiviral Medications for Facial Paralysis from Bell´s Palsy.

BACKGROUND: Facial paralysis is the most common cranial nerve injury. Bell's palsy is the name commonly used to describe an acute peripheral facial paralysis of unknown origin. The annual incidence of Bell's palsy is 20-30 cases per 100,000 persons, regardless of age and gender. OBJECTIVE: Our objective was to appraise the efficacy of steroid and antiviral treatments for facial paralysis. STUDY DESIGN: We conducted a network meta-analysis of studies of steroid and antiviral treatments for facial paralysis. SETTING: Second Hospital of Jilin University. METHODS: We performed a systematic search of PubMed and Embase databases to retrieve relevant studies. The efficacy outcome was overall recovery, measured in terms of the odds ratio (OR) and a corresponding 95% confidence interval (CI). The comprehensive ranking for each treatment with respect to overall recovery is presented as the value of the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 23 articles representing 4,623 patients were eligible for our study. In terms of overall recovery, no significant differences were found in the pairwise meta-analysis. From the results of the network meta-analysis, antiviral combined with steroid treatment was superior to placebo treatment (OR = 3.25; 95% CI, 1.23-8.61), but neither steroid nor antiviral therapy alone resulted in significant benefit compared with placebo. According to the SUCRA, antiviral combined with steroid treatment was the most effective, with a SUCRA value of 0.96, and the probability of ranking first was 90%. Only a small difference was observed between the efficacies of steroid and antiviral treatments (SUCRA values of 0.55 and 0.36, respectively), and they were both better than the placebo (SUCRA value of 0.134). LIMITATIONS: The major limitation of our study is that, due to the limited number of related studies in the last several years, we were not able to evaluate the safety of these therapies. CONCLUSIONS: Antiviral combined with steroid therapy is significantly better than antiviral or steroid therapy alone with respect to overall recovery, and the efficacies of single antiviral medications or single steroid treatments are nearly equal. In addition, all 3 therapies are more effective than placebo, according to the SUCRA values. KEY WORDS: Facial paralysis, Bell´s palsy, steroids, antiviral drugs, efficacy, overall recovery, network meta-analysis, SUCRA.

Cost Analysis of Initial Treatment With Endovascular Revascularization, Open Surgery, or Primary Major Amputation in Patients With Peripheral Artery Disease.

PURPOSE: To compare the total initial treatment costs for open surgery, endovascular revascularization, and primary major amputation within a single-payer healthcare system. METHODS: A multicenter, retrospective analysis was undertaken to evaluate 1138 patients with symptomatic peripheral artery disease (PAD) who underwent 1017 endovascular procedures, 86 open surgeries, and 35 major amputations between 2013 and 2016. A cost-mix analysis was performed on individual patient data generated for selected diagnosis-related groups. Mean costs are presented with the 95% confidence interval (CI). RESULTS: There was no intergroup difference in demographics or private health insurance status. However, the amputation group had a higher proportion of emergency procedures (68.6% vs 13.3% vs 27.9%, p<0.001) and critical limb ischemia (88.6% vs 35.9% vs 37.2%, p<0.001) compared with the endovascular therapy and open surgery groups, respectively. The endovascular revascularization group spent less time in hospital and used fewer intensive care unit (ICU) resources compared with the open surgery and major amputation groups (hospital length of stay: 3.4 vs 10.0 vs 20.2 days, p<0.01; ICU: 2.4 vs 22.6 vs 54.6 hours, p<0.01), respectively. While mean prosthetic and device costs were higher in the endovascular group [AUD$2770 vs AUD$1658 (open) and AUD$1219 (amputation), p<0.01], substantial disparities were observed in costs associated with longer operating theater times, length of stay, and ICU utilization, which resulted in significantly higher costs in the open and amputation groups. After adjusting for confounders, the AUD$18,396 (95% CI AUD$16,436 to AUD$20,356) mean cost per admission for the endovascular revascularization group was significantly less (p<0.001) than the open surgery (AUD$31,908, 95% CI AUD$28,285 to AUD$35,530) and major amputation groups (AUD$43,033, 95% CI AUD$37,706 to AUD$48,361). CONCLUSION: Endovascular revascularization procedures for PAD cost the health payer less compared with open surgery and primary amputation. While devices used to deliver contemporary endovascular therapy are more expensive, the reduction in bed days, ICU utilization, and related hospital resources results in a significantly lower mean total cost per admission for the initial treatment.