Use of Voice-Based Conversational Artificial Intelligence for Basal Insulin Prescription Management Among Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Optimizing insulin therapy for patients with type 2 diabetes can be challenging given the need for frequent dose adjustments. Most patients receive suboptimal doses and do not achieve glycemic control. Objective: To examine whether a voice-based conversational artificial intelligence (AI) application can help patients with type 2 diabetes titrate basal insulin at home to achieve rapid glycemic control. Design, Setting, and Participants: In this randomized clinical trial conducted at 4 primary care clinics at an academic medical center from March 1, 2021, to December 31, 2022, 32 adults with type 2 diabetes requiring initiation or adjustment of once-daily basal insulin were followed up for 8 weeks. Statistical analysis was performed from January to February 2023. Interventions: Participants were randomized in a 1:1 ratio to receive basal insulin management with a voice-based conversational AI application or standard of care. Main Outcomes and Measures: Primary outcomes were time to optimal insulin dose (number of days needed to achieve glycemic control), insulin adherence, and change in composite survey scores measuring diabetes-related emotional distress and attitudes toward health technology and medication adherence. Secondary outcomes were glycemic control and glycemic improvement. Analysis was performed on an intent-to-treat basis. Results: The study population included 32 patients (mean [SD] age, 55.1 [12.7] years; 19 women [59.4%]). Participants in the voice-based conversational AI group more quickly achieved optimal insulin dosing compared with the standard of care group (median, 15 days [IQR, 6-27 days] vs >56 days [IQR, >29.5 to >56 days]; a significant difference in time-to-event curves; P = .006) and had better insulin adherence (mean [SD], 82.9% [20.6%] vs 50.2% [43.0%]; difference, 32.7% [95% CI, 8.0%-57.4%]; P = .01). Participants in the voice-based conversational AI group were also more likely than those in the standard of care group to achieve glycemic control (13 of 16 [81.3%; 95% CI, 53.7%-95.0%] vs 4 of 16 [25.0%; 95% CI, 8.3%-52.6%]; difference, 56.3% [95% CI, 21.4%-91.1%]; P = .005) and glycemic improvement, as measured by change in mean (SD) fasting blood glucose level (-45.9 [45.9] mg/dL [95% CI, -70.4 to -21.5 mg/dL] vs 23.0 [54.7] mg/dL [95% CI, -8.6 to 54.6 mg/dL]; difference, -68.9 mg/dL [95% CI, -107.1 to -30.7 mg/dL]; P = .001). There was a significant difference between the voice-based conversational AI group and the standard of care group in change in composite survey scores measuring diabetes-related emotional distress (-1.9 points vs 1.7 points; difference, -3.6 points [95% CI, -6.8 to -0.4 points]; P = .03). Conclusions and Relevance: In this randomized clinical trial of a voice-based conversational AI application that provided autonomous basal insulin management for adults with type 2 diabetes, participants in the AI group had significantly improved time to optimal insulin dose, insulin adherence, glycemic control, and diabetes-related emotional distress compared with those in the standard of care group. These findings suggest that voice-based digital health solutions can be useful for medication titration. Trial Registration: ClinicalTrials.gov Identifier: NCT05081011.

Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist.

Overactivation of the renin-angiotensin-aldosterone system (RAAS) has been shown to be pathologic in heart failure and albuminuric chronic kidney disease (CKD), triggering pro-inflammatory and pro-fibrotic cellular pathways. The standard of care in these disease states includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Mineralocorticoid receptor antagonists (MRAs) are also a mainstay in the treatment of heart failure with reduced ejection fraction; however, therapy is often limited by treatment-related hyperkalemia. In albuminuric CKD, the risk of hyperkalemia, acute kidney injury (AKI), and hypotension also remains significant. Finerenone is a novel non-steroidal MRA that may obviate some of these concerns and have therapeutic potential in additional patient populations. Finerenone was developed using the chemical structure of a dihydropyridine channel blocker but optimized to create a bulky MRA without any activity at the L-type calcium channel. It has several novel cellular mechanisms that may account for its ability to reduce cardiac hypertrophy and proteinuria more efficiently than an equinatriuretic dose of a steroidal MRA, while retaining anti-inflammatory and anti-fibrotic properties. Finerenone also has a lower rate of treatment-related hyperkalemia and AKI than steroidal MRAs with a smaller effect on systolic blood pressure, greatly expanding its therapeutic utility. The recently published FIGARO-DKD and FIDELIO-DKD trials demonstrate that treatment with finerenone in patients with type II diabetes and albuminuric CKD results in improved cardiovascular outcomes and a lower risk of CKD progression. Patients enrolled in these studies were already on maximally tolerated ACE inhibitor or angiotensin receptor blocker therapy. Trials investigating finerenone's therapeutic effect in patients with heart failure with preserved ejection fraction (HFpEF) and non-diabetic CKD, as well sodium-glucose cotransporter 2 (SGLT2) and finerenone combination therapy in patients with diabetic nephropathy, are ongoing.

Factors Associated With Emergency Department Discharge, Outcomes and Follow-Up Rates of Stable Patients With Lower Gastrointestinal Bleeding.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization. However, recent data suggest low-risk patients may be safely evaluated as an outpatient. Here, we compare stable LGIB patients discharged from the emergency department (ED) with those admitted, determine factors associated with discharge and 30-day outcomes, and evaluate follow-up rates amongst the discharged cohort. METHODS: A retrospective study of stable LGIB patients (heart rate < 100 beats/min, systolic blood pressure > 100 mm Hg and blood on rectal exam) who presented to the ED was conducted. Factors associated with discharge and rates of outpatient follow-up were determined in the discharged cohort. Therapeutic interventions and 30-day outcomes (including re-bleeding, re-admission and mortality rates) were compared between the admitted and discharged groups. RESULTS: Ninety-seven stable LGIB patients were reviewed, of whom 38% were discharged and characteristics associated with discharge included age (P < 0.001), lack of aspirin (P < 0.002) and anticoagulant (P < 0.004) use, higher index hemoglobin (P < 0.001) and albumin (P < 0.001), lower blood urea nitrogen (P < 0.001) and creatinine (P = 0.008), lower Oakland score (P < 0.001), lower Charlson Comorbidity Index (P < 0.001) and lack of transfusion requirements (P < 0.001). There was no statistical difference in 30-day re-bleeding, re-admission or mortality rates between admitted and discharged patients. Discharged patients had a 46% outpatient follow-up rate. CONCLUSIONS: While early discharge in low-risk LGIB patients appears to be safe and associated with a decrease in length of stay, further studies are needed to guide timely and appropriate outpatient evaluation.

SARS-CoV-2 Neutralization Resistance Mutations in Patient with HIV/AIDS, California, USA.

We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.

GPCR-ErbB transactivation pathways and clinical implications.

Cell surface receptors including the epidermal growth factor receptor (EGFR) family and G-protein coupled receptors (GPCRs) play quintessential roles in physiology, and in diseases, including cardiovascular diseases. While downstream signaling from these individual receptor families has been well studied, the cross-talk between EGF and GPCR receptor families is still incompletely understood. Including members of both receptor families, the number of receptor and ligand combinations for unique interactions is vast, offering a frontier of pharmacologic targets to explore for preventing and treating disease. This molecular cross-talk, called receptor transactivation, is reviewed here with a focus on the cardiovascular system featuring the well-studied GPCR receptors, but also discussing less-studied receptors from both families for a broad understanding of context of expansile interactions, repertoire of cellular signaling, and disease consequences. Attention is given to cell type, level of chronicity, and disease context given that transactivation and comorbidities, including diabetes, hypertension, coronavirus infection, impact cardiovascular disease and health outcomes.

Brown adipose tissue is associated with cardiometabolic health.

White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear1,2. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health.

Absence of Fibrosis and Inflammation by Cardiac Magnetic Resonance Imaging in Rheumatoid Arthritis Patients with Low to Moderate Disease Activity.

OBJECTIVE: The prevalence of heart failure is increased 2-fold in patients with rheumatoid arthritis (RA); this is not explained by ischemic heart disease or other risk factors for heart failure. We hypothesized that in patients with RA without known heart disease, cardiac magnetic resonance imaging (cMRI) would detect altered cardiac structure, function, and fibrosis. METHODS: We performed 1.5-T cMRI in 59 patients with RA and 56 controls frequency-matched for age, race, and sex, and compared cMRI indices of structure, function, and fibrosis [late gadolinium enhancement (LGE), native T1 mapping, and extracellular volume (ECV)] using Mann-Whitney U tests and linear regression, adjusting for age, race, and sex. RESULTS: Most patients with RA had low to moderate disease activity [28-joint count Disease Activity Score-C-reactive protein median 3.16, interquartile range (IQR) 2.03-4.05], and 49% were receiving anti-tumor necrosis factor agents. Left ventricular (LV) mass, LV end-diastolic and -systolic volumes indexed to body surface area, and LV ejection fraction and left atrial size were not altered in RA compared to controls (all p > 0.05). Measures of fibrosis were not increased in RA: LGE was present in 2 patients with RA and 1 control subject; native T1 mapping was similar comparing RA and control subjects, and ECV (median, IQR) was lower (26.6%, 24.7-28.5%) in patients with RA compared to control subjects (27.5%, 25.4-30.4%, p = 0.03). CONCLUSION: cMRI measures of cardiac structure and function were not significantly altered, and measures of fibrosis were similar or lower in RA patients with low to moderate disease activity compared to a matched control group.

Genetic Relatedness Among Shiga Toxin-Producing Escherichia coli Isolated Along the Animal Food Supply Chain and in Gastroenteritis Cases in Qatar Using Multilocus Sequence Typing.

INTRODUCTION: Pathogenic Escherichia coli has been listed among the most important bacteria associated with foodborne illnesses around the world. We investigated the genetic relatedness among Shiga toxin-producing E. coli (STEC) isolated along the animal food supply chain and from humans diagnosed with gastroenteritis in Qatar. METHODS: Samples were collected from different sources along the food supply chain and from patients admitted to the hospital with complaints of gastroenteritis. All samples were screened for the presence of E. coli O157:H7 and non-O157 STEC using a combination of bacterial enrichment and molecular detection techniques. A proportional sampling approach was used to select positive samples from each source for further multilocus sequence typing (MLST) analysis. Seven housekeeping genes described for STEC were amplified by polymerase chain reaction, sequenced, and analyzed by MLST. Isolates were characterized by allele composition, sequence type (ST) and assessed for epidemiologic relationship within and among different sources. Nei's genetic distance was calculated at the allele level between sample pools in each site downstream. RESULTS: E. coli O157:H7 occurred at a higher rate in slaughterhouse and retail samples than at the farm or in humans in our sampling. The ST171, an ST common to enterotoxigenic E. coli and atypical enteropathogenic E. coli, was the most common ST (15%) in the food supply chain. None of the genetic distances among the different sources was statistically significant. CONCLUSION: Enterohemorrhagic E. coli pathogenic strains are present along the supply chain at different levels and with varying relatedness. Clinical isolates were the most diverse, as expected, considering the polyclonal diversity in the human microbiota. The high occurrence of these food adulterants among the farm products suggests that implementation of sanitary measures at that level might reduce the risk of human exposure.

Optimized energy of spectral CT for infarct imaging: Experimental validation with human validation.

OBJECTIVES: Late contrast enhancement visualizes myocardial infarction, but the contrast to noise ratio (CNR) is low using conventional CT. The aim of this study was to determine if spectral CT can improve imaging of myocardial infarction. MATERIALS AND METHODS: A canine model of myocardial infarction was produced in 8 animals (90-min occlusion, reperfusion). Later, imaging was performed after contrast injection using CT at 90 kVp/150 kVpSn. The following reconstructions were evaluated: Single energy 90 kVp, mixed, iodine map, multiple monoenergetic conventional and monoenergetic noise optimized reconstructions. Regions of interest were measured in infarct and remote regions to calculate contrast to noise ratio (CNR) and Bhattacharya distance (a metric of the differentiation between regions). Blinded assessment of image quality was performed. The same reconstruction methods were applied to CT scans of four patients with known infarcts. RESULTS: For animal studies, the highest CNR for infarct vs. myocardium was achieved in the lowest keV (40 keV) VMo images (CNR 4.42, IQR 3.64-5.53), which was superior to 90 kVp, mixed and iodine map (p = 0.008, p = 0.002, p < 0.001, respectively). Compared to 90 kVp and iodine map, the 40 keV VMo reconstructions showed significantly higher histogram separation (p = 0.042 and p < 0.0001, respectively). The VMo reconstructions showed the highest rate of excellent quality scores. A similar pattern was seen in human studies, with CNRs for infarct maximized at the lowest keV optimized reconstruction (CNR 4.44, IQR 2.86-5.94). CONCLUSIONS: Dual energy in conjunction with noise-optimized monoenergetic post-processing improves CNR of myocardial infarct delineation by approximately 20-25%.