Effects of respiratory isolation for tuberculosis to reduce community-based transmission: a systematic review.

BACKGROUND: Respiratory isolation of people with pulmonary tuberculosis (TB), including after treatment initiation, is used to prevent community-based transmission; yet guidelines on duration are limited and implementation is heterogeneous. This systematic review synthesized evidence on respiratory isolation for TB to inform National TB Coalition of America guidelines. METHODS: After searching six databases, eight reviewers screened and extracted data in duplicate on effects of respiratory isolation compared to no isolation or masking. Studies were stratified by outcomes: TB infection or disease in contacts, mortality, hospitalization duration, patient and health system costs, and impact on mental health or stigma. We used a convergent integrated approach to synthesize quantitative and qualitative findings and assess limitations. RESULTS: Seventeen studies were included. There were limited data directly comparing isolation to non-isolation interventions, including effects after treatment initiation. One randomized controlled trial suggested treatment in a sanatorium versus at home did not affect TB incidence in contacts. Modelling studies suggest isolation may reduce transmission, but relied on various assumptions, and isolation was implemented alongside other interventions. Descriptive, mixed-methods, and qualitative studies described adverse impacts of isolation on employment, education, food/housing security, and mental health due to transmission fears, stigma and social isolation. Impacts were compounded in marginalized groups including indigenous and incarcerated persons. CONCLUSION: Data to support current isolation practices, particularly after effective treatment initiation, to reduce TB transmission in communities are limited. Public health guidance should weigh the negative impacts on people with TB against decreased community transmission to make evidence-based decisions about respiratory isolation.

Geographic Variation and Environmental Predictors of Nontuberculous Mycobacteria in Laboratory Surveillance, Virginia, USA, 2021-20231.

Because epidemiologic and environmental risk factors for nontuberculous mycobacteria (NTM) have been reported only infrequently, little information exists about those factors. The state of Virginia, USA, requires certain ecologic features to be included in reports to the Virginia Department of Health, presenting a unique opportunity to study those variables. We analyzed laboratory reports of Mycobacterium avium complex (MAC) and M. abscessus infections in Virginia during 2021-2023. MAC/M. abscessus was isolated from 6.19/100,000 persons, and 2.37/100,000 persons had MAC/M. abscessus lung disease. M. abscessus accounted for 17.4% and MAC for 82.6% of cases. Saturated vapor pressure was associated with MAC/M. abscessus prevalence (prevalence ratio 1.414, 95% CI 1.011-1.980; p = 0.043). Self-supplied water use was a protective factor (incidence rate ratio 0.304, 95% CI 0.098-0.950; p = 0.041). Our findings suggest that a better understanding of geographic clustering and environmental water exposures could help develop future targeted prevention and control efforts.

A qualitative study of recruitment strategies: Perspectives from older adults living with diabetes.

AIMS: There is a need to increase representation of diverse older adults in health-related qualitative research to better understand and improve chronic disease care over the lifespan. Our aim was to elicit perspectives about research recruitment among a diverse sample of older adults with diabetes participating in a qualitative study. METHODS: Older adults with diabetes and caregivers were recruited through purposive sampling for semi-structured interviews focused on diabetes self care. Six questions were used to explore recruitment strategies and recommendations for engaging older adults in research. We analysed interview transcripts using descriptive analysis to identify themes related to engaging older adults in research studies. RESULTS: Seventeen older adults with diabetes and three caregivers participated (N = 20). Descriptive analysis revealed four themes: (1) Recruitment of older adults requires varied strategies to overcome barriers to engagement and participation; (2) Building and leveraging personal relationships is central to successful recruitment; (3) Transparent communication about the research process and value of the study is needed to inform and motivate older adults to participate; and (4) Research offers a connection to a broader community: sharing, learning and helping others. CONCLUSIONS: We found four main themes related to the complexity of recruiting older adults for research studies. These insights may inform more effective, equitable and inclusive recruitment efforts targeted at older adults in the future.

Supporting the 'lived expertise' of older adults with type 1 diabetes: An applied focus group analysis to characterize barriers, facilitators, and strategies for self-management in a growing and understudied population.

INTRODUCTION: There is a growing number of older adults (≥65 years) who live with type 1 diabetes. We qualitatively explored experiences and perspectives regarding type 1 diabetes self-management and treatment decisions among older adults, focusing on adopting care advances such as continuous glucose monitoring (CGM). METHODS: Among a clinic-based sample of older adults ≥65 years with type 1 diabetes, we conducted a series of literature and expert informed focus groups with structured discussion activities. Groups were transcribed followed by inductive coding, theme identification, and inference verification. Medical records and surveys added clinical information. RESULTS: Twenty nine older adults (age 73.4 ± 4.5 years; 86% CGM users) and four caregivers (age 73.3 ± 2.9 years) participated. Participants were 58% female and 82% non-Hispanic White. Analysis revealed themes related to attitudes, behaviours, and experiences, as well as interpersonal and contextual factors that shape self-management and outcomes. These factors and their interactions drive variability in diabetes outcomes and optimal treatment strategies between individuals as well as within individuals over time (i.e. with ageing). Participants proposed strategies to address these factors: regular, holistic needs assessments to match people with effective self-care approaches and adapt them over the lifespan; longitudinal support (e.g., education, tactical help, sharing and validating experiences); tailored education and skills training; and leveraging of caregivers, family, and peers as resources. CONCLUSIONS: Our study of what influences self-management decisions and technology adoption among older adults with type 1 diabetes underscores the importance of ongoing assessments to address dynamic age-specific needs, as well as individualized multi-faceted support that integrates peers and caregivers.

Management of iatrogenic ascending aortic dissection after percutaneous intervention of chronic total occlusion.

BACKGROUND: This study highlights the prevalence and conservative management strategies of iatrogenic ascending aortic dissection after percutaneous intervention (PCI) of chronic total occlusion (CTO). METHODS: Retrospective analysis on patients who underwent CTO PCI from one medical center from 2020 to 2022 was performed by two operators. Data was obtained from the Prospective Global Registry for the Study of CTO database. RESULTS: Out of 318 patients, there were six reported cases of iatrogenic ascending aortic dissection. The causes of dissection included guiding catheter trauma, antegrade injection, two retrograde injection, and two cases of balloon rupture after lithotripsy. IVUS-guided stenting of the coronary back to the origin to seal the entry of the dissection flap occurred in two patients. All patients had a conservative management approach. No patient had to undergo urgent surgery. CONCLUSION: While the incidence remains rare, complications, including aortic dissection, are more frequent in CTO PCI as compared to non-CTO PCI. IVUS can be used to complete coronary intervention so long as the patient remains clinically and hemodynamically stable. Patients should have formal imaging with either transesophageal echocardiogram or computed tomography angiography. The outcomes of patients who experience iatrogenic aortic dissection during CTO PCI with stable coronary disease seem to be better than in patients with acute coronary syndrome.

Validation of the BCIS CHIP Score in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The complex high-risk indicated percutaneous coronary intervention (CHIP) score is a tool developed using the British Cardiovascular Intervention Society (BCIS) database to define CHIP cases and predict in-hospital major adverse cardiac or cerebrovascular events (MACCE). AIM: To assess the validity of the CHIP score in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We evaluated the performance of the CHIP score on 8341 CTO PCIs from the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) performed at 44 centers between 2012 and 2023. RESULTS: In our cohort, 7.8% (n = 647) of patients had a CHIP score of 0, 50.2% (n = 4192) had a CHIP score of 1-2, 26.2% (n = 2187) had a CHIP score of 3-4, 11.7% (n = 972) had a CHIP score of 5-6, 3.3% (n = 276) had a CHIP score of 7-8, and 0.8% (n = 67) had a CHIP score of 9+. The incidence of MACCE for a CHIP score of 0 was 0.6%, reaching as high as 8.7% for a CHIP score of 9+, confirming that a higher CHIP score is associated with a higher risk of MACCE. The estimated increase in the risk of MACCE per one score unit increase was 100% (95% confidence interval [CI]: 65%-141%). The AUC of the CHIP score model for predicting MACCE in our cohort was 0.63 (95% CI: 0.58-0.67). There was a positive correlation between the CHIP score and the PROGRESS-CTO MACE score (Spearman's correlation: 0.37; 95% CI: 0.35-0.39; p < 0.001). CONCLUSIONS: The CHIP score has modest predictive capacity for MACCE in CTO PCI.

Chronic total occlusion percutaneous coronary intervention of anomalous coronary arteries: insights from the PROGRESS CTO registry.

BACKGROUND: There is limited information about the frequency and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in anomalous coronary arteries (ACA). METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of CTO PCI in ACA among 14,173 patients who underwent 14,470 CTO PCIs at 46 US and non-US centers between 2012 and 2023. RESULTS: Of 14,470 CTO PCIs, 36 (0.24%) were CTO PCIs in an ACA. ACA patients had similar baseline characteristics as those without an ACA. The type of ACA in which the CTO lesion was found were as follows: anomalous origin of the right coronary artery (ARCA) (17, 48.5%), anomalous origin of left circumflex coronary artery (9, 25.7%), left anterior descending artery and left circumflex artery with separate origins (4, 11.4%), anomalous origin of the left anterior descending artery (2, 5.7%), dual left anterior descending artery (2, 5.7%) and woven coronary artery 1 (2.8%). The Japan CTO score was similar between both groups (2.17 ± 1.32 vs 2.38 ± 1.26, p = 0.30). The target CTO in ACA patients was more likely to have moderate/severe tortuosity (44% vs 28%, p = 0.035), required more often use of retrograde approach (27% vs 12%, p = 0.028), and was associated with longer procedure (142.5 min vs 112.00 min [74.0, 164.0], p = 0.028) and fluoroscopy (56 min [40, 79 ml] vs 42 min [25, 67], p = 0.014) time and higher contrast volume (260 ml [190, 450] vs 200 ml [150, 300], p = 0.004) but had similar procedural (91.4% vs 85.6%, p = 0.46) and technical (91.4% vs 87.0%, p = 0.59) success. No major adverse cardiac events (MACE) were seen in ACA patients (0% [0] vs 1.9% [281] in non-ACA patients, p = 1.00). Two coronary perforations were reported in ACA CTO PCI (p = 0.7 vs. non-ACA CTO PCI). CONCLUSIONS: CTO PCI of ACA comprise 0.24% of all CTO PCIs performed in the PROGRESS CTO registry and was associated with higher procedural complexity but similar technical and procedural success rates and similar MACE compared with non-ACA CTO PCI.

Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells - United States, 2023.

During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed.

Use of systems thinking and adapted group model building methods to understand patterns of technology use among older adults with type 1 diabetes: a preliminary process evaluation.

BACKGROUND: A growing number of older adults (ages 65+) live with Type 1 diabetes. Simultaneously, technologies such as continuous glucose monitoring (CGM) have become standard of care. There is thus a need to understand better the complex dynamics that promote use of CGM (and other care innovations) over time in this age group. Our aim was to adapt methods from systems thinking, specifically a participatory approach to system dynamics modeling called group model building (GMB), to model the complex experiences that may underlie different trajectories of CGM use among this population. Herein, we report on the feasibility, strengths, and limitations of this methodology. METHODS: We conducted a series of GMB workshops and validation interviews to collect data in the form of questionnaires, diagrams, and recordings of group discussion. Data were integrated into a conceptual diagram of the "system" of factors associated with uptake and use of CGM over time. We evaluate the feasibility of each aspect of the study, including the teaching of systems thinking to older adult participants. We collected participant feedback on positive aspects of their experiences and areas for improvement. RESULTS: We completed nine GMB workshops with older adults and their caregivers (N = 33). Each three-hour in-person workshop comprised: (1) questionnaires; (2) the GMB session, including both didactic components and structured activities; and (3) a brief focus group discussion. Within the GMB session, individual drawing activities proved to be the most challenging for participants, while group activities and discussion of relevant dynamics over time for illustrative (i.e., realistic but not real) patients yielded rich engagement and sufficient information for system diagramming. Study participants liked the opportunity to share experiences with peers, learning and enhancing their knowledge, peer support, age-specific discussions, the workshop pace and structure, and the systems thinking framework. Participants gave mixed feedback on the workshop duration. CONCLUSIONS: The study demonstrates preliminary feasibility, acceptability, and the value of GMB for engaging older adults about key determinants of complex health behaviors over time. To our knowledge, few studies have extended participatory systems science methods to older adult stakeholders. Future studies may utilize this methodology to inform novel approaches for supporting health across the lifespan.

Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study.

Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled. Serum and urine samples were collected over 24 h. Rifampin serum concentrations were measured using validated liquid chromatography-tandem mass spectrometry, and total exposure (area under the concentration-time curve) over 24 h (AUC0-24) was determined through noncompartmental analysis. The Sunahara method was used to extract total rifamycins, and rifampin urine excretion was measured by spectrophotometry. An analysis of 58 eligible participants, including 15 (26%) with type 2 diabetes mellitus, demonstrated that urine spectrophotometry accurately identified subtarget rifampin AUC0-24 at 0-4, 0-8, and 0-24 h. The area under the receiver operator characteristic curve (AUC ROC) values were 0.80 (95% CI 0.67-0.90), 0.84 (95% CI 0.72-0.94), and 0.83 (95% CI 0.72-0.93), respectively. These values were comparable to the AUC ROC of 2 h serum concentrations commonly used for therapeutic monitoring (0.82 [95% CI 0.71-0.92], P = 0.6). Diabetes status did not significantly affect the AUC ROCs for urine in predicting subtarget rifampin serum exposure (P = 0.67-0.92). Spectrophotometric measurement of urine rifampin excretion within the first 4 or 8 h after dosing is a simple and cost-effective test that accurately predicts rifampin underexposure. This test provides critical information for optimizing tuberculosis treatment outcomes by facilitating appropriate dose adjustments.

A Cost Analysis of Rethink the Strip: De-implementing a Low-value Practice in Primary Care.

BACKGROUND: Routine self-monitoring of blood glucose is a low-value practice that provides limited benefit for patients with non-insulin-treated type 2 diabetes mellitus. OBJECTIVES: We estimated the costs of Rethink the Strip (RTS), a multistrategy approach to the de-implementation of self-monitoring of blood glucose in primary care. RESEARCH DESIGN: RTS was conducted among 20 primary care clinics in North Carolina. We estimated the non-site-based and site-based costs of the 5 RTS strategies (practice facilitation, audit and feedback, provider champions, educational meetings, and educational materials) from the analytic perspective of an integrated health care system for 12 and 27-month time horizons. Material costs were tracked through project records, and personnel costs were assessed using activity-based costing. We used nationally based wage estimates. RESULTS: Total RTS costs equaled $68,941 for 12 months. Specifically, non-site-based costs comprised $16,560. Most non-site-based costs ($11,822) were from the foundational programming and coding updates to the electronic health record data to develop the audit and feedback reports. The non-site-based costs of educational meetings, practice facilitation, and educational materials were substantially lower, ranging between ~$400 and $1000. Total 12-month site-based costs equaled $2569 for a single clinic (or $52,381 for 20 clinics). Educational meetings were the most expensive strategy, averaging $1401 per clinic. The site-based costs for the 4 other implementation strategies were markedly lower, ranging between $51 for educational materials and $555 for practice facilitation per clinic. CONCLUSIONS: This study provides detailed cost information for implementation strategies used to support evidence-based programs in primary care clinics.

Twist2-expressing cells reside in human skeletal muscle and are responsive to aging and resistance exercise training.

Skeletal muscle is maintained and repaired by sub-laminar, Pax7-expressing satellite cells. However, recent mouse investigations have described a second myogenic progenitor population that resides within the myofiber interstitium and expresses the transcription factor Twist2. Twist2-expressing cells exclusively repair and maintain type IIx/b muscle fibers. Currently, it is unknown if Twist2-expressing cells are present in human skeletal muscle and if they function as myogenic progenitors. Here, we perform a combination of single-cell RNA sequencing analysis and immunofluorescence staining to demonstrate the identity and localization of Twist2-expressing cells in human skeletal muscle. Twist2-expressing cells were identified to be anatomically and transcriptionally comparable to fibro-adipogenic progenitors (FAPs) and lack expression of typical satellite cell markers such as Pax7. Comparative analysis revealed that human and mouse Twist2-expressing cells were highly transcriptionally analogous and resided within the same anatomical structures in vivo. Examination of young and aged skeletal muscle biopsy samples revealed that Twist2-positive cells are more prevalent in aged muscle and increase following 12-weeks of resistance exercise training (RET) in humans. However, the quantity of Twist2-positive cells was not correlated with indices of muscle mass or muscle fiber cross-sectional area (CSA) in young or older muscle, and their abundance was surprisingly, negatively correlated with CSA and myonuclear domain size following RET. Taken together, we have identified cells expressing Twist2 in human skeletal muscle which are responsive to aging and exercise. Further examination of their myogenic potential is warranted.

Muscle injury induces a transient senescence-like state that is required for myofiber growth during muscle regeneration.

Cellular senescence is the irreversible arrest of normally dividing cells and is driven by the cell cycle inhibitors Cdkn2a, Cdkn1a, and Trp53. Senescent cells are implicated in chronic diseases and tissue repair through their increased secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Here, we use spatial transcriptomics and single-cell RNA sequencing (scRNAseq) to demonstrate that cells displaying senescent characteristics are "transiently" present within regenerating skeletal muscle and within the muscles of D2-mdx mice, a model of Muscular Dystrophy. Following injury, multiple cell types including macrophages and fibrog-adipogenic progenitors (FAPs) upregulate senescent features such as senescence pathway genes, SASP factors, and senescence-associated beta-gal (SA-ß-gal) activity. Importantly, when these cells were removed with ABT-263, a senolytic compound, satellite cells are reduced, and muscle fibers were impaired in growth and myonuclear accretion. These results highlight that an "acute" senescent phenotype facilitates regeneration similar to skin and neonatal myocardium.

Impact of preprocedural anemia on in-hospital and follow-up outcomes of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The impact of preprocedural anemia on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 8633 CTO PCIs performed at 39 US and non-US centers between 2012 and 2023. Anemia was defined as a hemoglobin level of <13 g/dL in men and <12 g/dL in women. RESULTS: Anemia was present in 1652 (19%) patients undergoing CTO PCI. Anemic patients had a higher incidence of comorbidities, such as diabetes mellitus, hypertension, dyslipidemia, heart failure, cerebrovascular disease, and peripheral arterial disease. CTOs in anemic patients were more likely to have complex angiographic characteristics, including smaller diameter, longer length, moderate to severe calcification, and moderate to severe proximal tortuosity. Anemic patients required longer procedure (119 vs. 107 min; p < 0.001) and fluoroscopy (45 vs. 40 min; p < 0.001) times but received similar contrast volumes. Technical success was similar between the two groups. In-hospital major adverse cardiac events (MACE) rates were higher in patients with anemia; however, this association was no longer significant after adjusting for confounding factors. Baseline anemia was independently associated with follow-up MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.07-2.49; p = 0.023) and all-cause mortality (adjusted HR: 3.03; 95% CI: 1.41-6.49; p = 0.004). CONCLUSIONS: Preprocedural anemia is associated with more comorbidities, higher lesion complexity, longer procedure times, and higher follow-up MACE and mortality after CTO PCI.

Same day discharge versus overnight observation following chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: Same day discharge (SDD) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We evaluated the clinical, angiographic, and procedural characteristics of patients discharged the same day versus those kept for overnight observation in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO, NCT02061436). RESULTS: Of the 7181 patients who underwent CTO PCI, 943 (13%) had SDD. The SDD rate increased from 3% in 2015 to 21% in 2022. Patients with SDD were less likely to have a history of heart failure (21% vs. 26%, p = 0.005), chronic lung disease (10% vs. 15%, p = 0.001), or anemia (12% vs. 19%, p < 0.001). Technical success (87% vs. 88%, p = 0.289) was similar, but in-hospital major adverse cardiovascular events (0.0% vs. 0.4%, p = 0.041) were lower in SDD. In multivariable logistic regression analysis, prior myocardial infarction odds ratio (OR): 0.71 (95% confidence interval [CI]: 0.59-0.87, p = 0.001), chronic lung disease OR: 0.64 (95% CI: 0.47-0.88, p = 0.006), and increasing procedure time OR: 0.93 (95% CI: 0.91-0.95, p < 0.001, per 10-min increase) were associated with overnight observation, while radial-only access OR: 2.45 (95% CI: 2.03-2.96, p < 0.001) had the strongest association with SDD. In the SDD, 2 (0.4%) of 514 patients were readmitted, due to retroperitoneal bleeding (n = 1) and ischemic stroke (n = 1). CONCLUSION: The overall frequency of SDD after CTO PCI was 13% and has been increasing over time. SDD is feasible in select patients following CTO PCI, and radial-only access had the strongest association with SDD.

Real-world decision-making in the management of patients presenting with major bleeding on rivaroxaban: the Auckland regional experience.

BACKGROUND: Rivaroxaban is used increasingly as an oral anticoagulant; however, a specific reversal agent is not currently available in the Australasian setting. There is also variation across international consensus guidelines regarding advice on the management of bleeding. AIMS: To review the real-world management of rivaroxaban-associated major bleeding across the public hospitals of New Zealand's largest city. METHODS: A retrospective cohort analysis was performed of patients prescribed rivaroxaban who presented to four metropolitan hospital Emergency Departments between 1 August 2018 and 31 May 2021 with major bleeding as defined by the International Society on Thrombosis and Haemostasis. RESULTS: One hundred and twelve patients were identified, accounting for 115 major bleeding presentations. Upper gastrointestinal (34%) and intracranial (31%) bleeding sites were most common. Procedural intervention was required in 44% of patients. Haemostatic management involved tranexamic acid (TXA) in 26%, prothrombin complex concentrate (PCC) in 55% (dose range 1000-6000 IU or 10-65 IU/kg), vitamin K in 16% and fresh frozen plasma in 1%. Rivaroxaban was discontinued permanently following 56 (49%) events, switched to another anticoagulant in 24 (21%) and withheld in 30 (26%) from 2 days to 3 months (median 8.5 days). All-cause mortality at 90 days after bleeding was 17% (19 patients), and the incidence of combined venous and arterial thrombotic events was 10%. CONCLUSIONS: There is considerable heterogeneity in the acute clinical management of patients presenting with rivaroxaban-related major bleeding. The use of PCC and dosage administered is inconsistent. TXA was utilised in only approximately one-quarter of all cases. Evidence-based guidance for treating rivaroxaban-related bleeding would improve the management of these patients and potentially improve clinical outcomes.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Disparities in Food Security and Glycemic Control Among People with Type 2 Diabetes During the COVID-19 Pandemic.

Background: Little is known about the differing impacts of food insecurity on HbA1c by race in type 2 diabetes (T2D). Predictions around increased food insecurity from COVID-19 exacerbating racial disparities led us to estimate its prevalence and associations with HbA1c by race during the COVID-19 pandemic. Methods: Data came from medical records and surveys among a clinic-based sample of T2D patients. Linear regression models estimated associations between food insecurity and HbA1c and between change in food insecurity and change in HbA1c. Likelihood ratio tests and examination of stratum-specific estimates assessed effect modification by race. Results: Our sample was 59% White, 59% female, and mean age was 60.8 ± 12.6. During the pandemic, food insecurity prevalence and HbA1c were significantly (p < .05) higher among non-Whites (39%, 8.4% ± 2.1) compared to Whites (15%, 7.8% ±1.6). HbA1c among those who were very food insecure was 1.00% (95% CI: 0.222, 1.762, p = .01) higher than those who were food secure. Those with increased food insecurity had a 0.58% (95% CI: 0.024, 1.128, p = .04) higher HbA1c increase than among those experiencing no change. No effect modification was detected. Limitations: Convenience sampling in an endocrinology clinic, recall bias, and inadequate power may underlie null effect modification results. Conclusion: Although effect modification was not detected, racial disparities in HbA1c and food insecurity warrant further investigation. These disparities, combined with the significant impact of food insecurity on HbA1c, suggest that prioritization of resources to high-risk populations should be considered early during public emergencies to minimize short- and long-term health consequences.

Identification of underexplored mesenchymal and vascular-related cell populations in human skeletal muscle.

Skeletal muscle repair and maintenance are directly and indirectly supported by interstitial cell populations such as vascular cells and fibro-adipogenic progenitors (FAPs), a subset of which express Twist2 and possess direct myogenic potential. Furthermore, work in rodents has highlighted the potential of pericytes to act as progenitor cells, giving rise to muscle cells and transdifferentiating into endothelial cells. However, less is understood about these populations in human skeletal muscle. Here, we performed single-cell RNA sequencing (scRNAseq) on ∼2,000 cells isolated from the human semitendinosus muscle of young individuals. This demonstrated the presence of a vascular-related cell type that expressed pericyte and pan-endothelial genes that we localized to large blood vessels within skeletal muscle cross sections and termed endothelial-like pericytes (ELPCs). RNA velocity analysis indicated that ELPCs may represent a "transition state" between endothelial cells and pericytes. Analysis of published scRNAseq data sets revealed evidence for ELPCs in trunk and heart musculature, which showed transcriptional similarity. In addition, we identified a subset of FAPs expressing TWIST2 mRNA and protein. Human TWIST2-expressing cells were anatomically and transcriptionally comparable to mouse Twist2 cells as they were restricted to the myofiber interstitium, expressed fibrogenic genes but lacked satellite cell markers, and colocalized with the FAPs marker PDGFRα in human muscle cross sections. Taken together, these results highlight the complexity of stromal cells residing in human skeletal muscle and support the utility of scRNAseq for discovery and characterization of poorly described cell populations.

A Co-Association of Streptococcus mutans and Veillonella parvula/dispar in Root Caries Patients and In Vitro Biofilms.

Root caries in geriatric patients is a growing problem as more people are maintaining their natural teeth into advanced age. We determined the levels of various bacterial species previously implicated in root caries disease or health using quantitative real-time PCR in a pilot study of 7 patients with 1 to 4 root caries lesions per person. Levels of 12 different species on diseased roots compared to healthy (contralateral control) roots were measured. Four species were found at significantly higher levels on diseased roots (Streptococcus mutans, Veillonella parvula/dispar, Actinomyces naeslundii/viscosus, and Capnocytophaga granulosa) compared across all plaque samples. The level of colonization by these species varied dramatically (up to 1,000-fold) between patients, indicating different patients have different bacteria contributing to root caries disease. Neither of the two species previously reported to correlate with healthy roots (C. granulosa and Delftia acidovorans) showed statistically significant protective roles in our population, although D. acidovorans showed a trend toward higher levels on healthy teeth (P = 0.08). There was a significant positive correlation between higher levels of S. mutans and V. parvula/dispar on the same diseased teeth. In vitro mixed biofilm studies demonstrated that co-culturing S. mutans and V. parvula leads to a 50 to 150% increase in sucrose-dependent biofilm mass compared to S. mutans alone, depending on the growth conditions, while V. parvula alone did not form in vitro biofilms. The presence of V. parvula also decreased the acidification of S. mutans biofilms when grown in artificial saliva and enhanced the health of mixed biofilms.