Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions.

Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome. Methods: Patients diagnosed with type 1 primary hyperoxaluria (PH), enteric hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic (MTG) and metatranscriptomic (MTT) data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels. Results: A total of 38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha-diversity and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. MTT-based network analysis identified the most interactive bacterial network in patients with PH. Patients with EH had a decreased abundance of multiple major oxalate degraders. Conclusion: The composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria.

Sociobiome - Individual and neighborhood socioeconomic status influence the gut microbiome in a multi-ethnic population in the US.

Lower socioeconomic status (SES) is related to increased incidence and mortality due to chronic diseases in adults. Association between SES variables and gut microbiome variation has been observed in adults at the population level, suggesting that biological mechanisms may underlie the SES associations; however, there is a need for larger studies that consider individual- and neighborhood-level measures of SES in racially diverse populations. In 825 participants from a multi-ethnic cohort, we investigated how SES shapes the gut microbiome. We determined the relationship of a range of individual- and neighborhood-level SES indicators with the gut microbiome. Individual education level and occupation were self-reported by questionnaire. Geocoding was applied to link participants' addresses with neighborhood census tract socioeconomic indicators, including average income and social deprivation in the census tract. Gut microbiome was measured using 16SV4 region rRNA gene sequencing of stool samples. We compared α-diversity, ß-diversity, and taxonomic and functional pathway abundance by SES. Lower SES was significantly associated with greater α-diversity and compositional differences among groups, as measured by ß-diversity. Several taxa related to low SES were identified, especially an increasing abundance of Prevotella copri and Catenibacterium sp000437715, and decreasing abundance of Dysosmobacter welbionis in terms of their high log-fold change differences. In addition, nativity and race/ethnicity have emerged as ecosocial factors that also influence the gut microbiota. Together, these results showed that lower SES was strongly associated with compositional and taxonomic measures of the gut microbiome, and may contribute to shaping the gut microbiota.

Cost-effectiveness analysis of artificial intelligence-based diabetic retinopathy screening in rural China based on the Markov model.

This study assessed the cost-effectiveness of different diabetic retinopathy (DR) screening strategies in rural regions in China by using a Markov model to make health economic evaluations. In this study, we determined the structure of a Markov model according to the research objectives, which required parameters collected through field investigation and literature retrieval. After perfecting the model with parameters and assumptions, we developed a Markov decision analytic model according to the natural history of DR in TreeAge Pro 2011. For this model, we performed Markov cohort and cost-effectiveness analyses to simulate the probabilistic distributions of different developments in DR and the cumulative cost-effectiveness of artificial intelligence (AI)-based screening and ophthalmologist screening for DR in the rural population with diabetes mellitus (DM) in China. Additionally, a model-based health economic evaluation was performed by using quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios. Last, one-way and probabilistic sensitivity analyses were performed to assess the stability of the results. From the perspective of the health system, compared with no screening, AI-based screening cost more (the incremental cost was 37,257.76 RMB (approximately 5,211.31 US dollars)), but the effect was better (the incremental utility was 0.33). Compared with AI-based screening, the cost of ophthalmologist screening was higher (the incremental cost was 14,886.76 RMB (approximately 2,070.19 US dollars)), and the effect was worse (the incremental utility was -0.31). Compared with no screening, the incremental cost-effectiveness ratio (ICER) of AI-based DR screening was 112,146.99 RMB (15,595.47 US dollars)/QALY, which was less than the threshold for the ICER (< 3 times the per capita gross domestic product (GDP), 217,341.00 RMB (30,224.03 US dollars)). Therefore, AI-based screening was cost-effective, which meant that the increased cost for each additional quality-adjusted life year was merited. Compared with no screening and ophthalmologist screening for DR, AI-based screening was the most cost-effective, which not only saved costs but also improved the quality of life of diabetes patients. Popularizing AI-based DR screening strategies in rural areas would be economically effective and feasible and can provide a scientific basis for the further formulation of early screening programs for diabetic retinopathy.

A microbial causal mediation analytic tool for health disparity and applications in body mass index.

BACKGROUND: Emerging evidence suggests the potential mediating role of microbiome in health disparities. However, no analytic framework can be directly used to analyze microbiome as a mediator between health disparity and clinical outcome, due to the non-manipulable nature of the exposure and the unique structure of microbiome data, including high dimensionality, sparsity, and compositionality. METHODS: Considering the modifiable and quantitative features of the microbiome, we propose a microbial causal mediation model framework, SparseMCMM_HD, to uncover the mediating role of microbiome in health disparities, by depicting a plausible path from a non-manipulable exposure (e.g., ethnicity or region) to the outcome through the microbiome. The proposed SparseMCMM_HD rigorously defines and quantifies the manipulable disparity measure that would be eliminated by equalizing microbiome profiles between comparison and reference groups and innovatively and successfully extends the existing microbial mediation methods, which are originally proposed under potential outcome or counterfactual outcome study design, to address health disparities. RESULTS: Through three body mass index (BMI) studies selected from the curatedMetagenomicData 3.4.2 package and the American gut project: China vs. USA, China vs. UK, and Asian or Pacific Islander (API) vs. Caucasian, we exhibit the utility of the proposed SparseMCMM_HD framework for investigating the microbiome's contributions in health disparities. Specifically, BMI exhibits disparities and microbial community diversities are significantly distinctive between reference and comparison groups in all three applications. By employing SparseMCMM_HD, we illustrate that microbiome plays a crucial role in explaining the disparities in BMI between ethnicities or regions. 20.63%, 33.09%, and 25.71% of the overall disparity in BMI in China-USA, China-UK, and API-Caucasian comparisons, respectively, would be eliminated if the between-group microbiome profiles were equalized; and 15, 18, and 16 species are identified to play the mediating role respectively. CONCLUSIONS: The proposed SparseMCMM_HD is an effective and validated tool to elucidate the mediating role of microbiome in health disparity. Three BMI applications shed light on the utility of microbiome in reducing BMI disparity by manipulating microbial profiles. Video Abstract.

A microbial causal mediation analytic tool for health disparity and applications in body mass index.

Background: Emerging evidence suggests the potential mediating role of microbiome in health disparities. However, no analytic framework is available to analyze microbiome as a mediator between health disparity and clinical outcome, due to the unique structure of microbiome data, including high dimensionality, sparsity, and compositionality. Methods: Considering the modifiable and quantitative features of microbiome, we propose a microbial causal mediation model framework, SparseMCMM_HD, to uncover the mediating role of microbiome in health disparities, by depicting a plausible path from a non-manipulable exposure (e.g. race or region) to a continuous outcome through microbiome. The proposed SparseMCMM_HD rigorously defines and quantifies the manipulable disparity measure that would be eliminated by equalizing microbiome profiles between comparison and reference groups. Moreover, two tests checking the impact of microbiome on health disparity are proposed. Results: Through three body mass index (BMI) studies selected from the curatedMetagenomicData 3.4.2 package and the American gut project: China vs. USA, China vs. UK, and Asian or Pacific Islander (API) vs. Caucasian, we exhibit the utility of the proposed SparseMCMM_HD framework for investigating microbiome’s contributions in health disparities. Specifically, BMI exhibits disparities and microbial community diversities are significantly distinctive between the reference and comparison groups in all three applications. By employing SparseMCMM_HD, we illustrate that microbiome plays a crucial role in explaining the disparities in BMI between races or regions. 11.99%, 12.90%, and 7.4% of the overall disparity in BMI in China-USA, China-UK, and API-Caucasian comparisons, respectively, would be eliminated if the between-group microbiome profiles were equalized; and 15, 21, and 12 species are identified to play the mediating role respectively. Conclusions: The proposed SparseMCMM_HD is an effective and validated tool to elucidate the mediating role of microbiome in health disparity. Three BMI applications shed light on the utility of microbiome in reducing BMI disparity by manipulating microbial profiles.

Gender-common and gender-specific determinants of child dietary diversity in eight Asia Pacific countries.

Background: Optimal child feeding practices contribute to reducing child undernutrition in low- and middle-income countries. Minimum dietary diversity (MDD) is a key indicator of complementary feeding quality for children aged 6-23 months. We aimed to examine the gender-common and gender-specific factors associated with the failure to meet MDD in eight Asia Pacific countries. Methods: The study used data of children aged 6-23 months from the Demographic and Health Surveys (DHS) conducted in Afghanistan (n = 8410), Bangladesh (n = 2371), Nepal (n = 1478), Pakistan (n = 3490), Cambodia (n = 2182), Indonesia (n = 5133), Myanmar (n = 1379), and Timor-Leste (n = 2115). A total of 41 household, maternal, and child-level variables were examined for association with MDD using univariate and multivariable logistic regressions. All analyses accounted for the survey design and sampling weights. Results: Being aged 6-11 months, not receiving Vitamin A supplementation, low maternal education, belonging to a low wealth quintile, and having two or more young children in the household were factors related to the failure to meet MDD among both male and female children. Mothers' not watching TV or not being exposed to media at least once a week, delivery at home, young age, and engagement to non-agricultural work were only significant risk factors among female children. Non-professional delivery assistance, unsafe disposal of children's stool, tolerant attitudes towards domestic violence, and rural residence were significant factors only among male children. Conclusions: It is possible that male and female children in the region may consume food in various ways, because the factors for meeting MDD are not the same for different genders of children. It is advised to enhance dietary diversity in child nutrition programmes through gender-specific activities.

Leveraging Social Media to Increase Access to an Evidence-Based Diabetes Intervention Among Low-Income Chinese Immigrants: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Type 2 diabetes (T2D) in Chinese Americans is a rising public health concern for the US health care system. The majority of Chinese Americans with T2D are foreign-born older immigrants and report limited English proficiency and health literacy. Multiple social determinants of health limit access to evidence-based diabetes interventions for underserved Chinese immigrants. A social media-based diabetes intervention may be feasible to reach this community. OBJECTIVE: The purpose of the Chinese American Research and Education (CARE) study was to examine the potential efficacy of a social media-based intervention on glycemic control in Chinese Americans with T2D. Additionally, the study aimed to explore the potential effects of the intervention on psychosocial and behavioral factors involved in successful T2D management. In this report, we describe the design and protocol of the CARE trial. METHODS: CARE was a pilot randomized controlled trial (RCT; n=60) of a 3-month intervention. Participants were randomized to one of two arms (n=30 each): wait-list control or CARE intervention. Each week, CARE intervention participants received two culturally and linguistically tailored diabetes self-management videos for a total of 12 weeks. Video links were delivered to participants via WeChat, a free and popular social media app among Chinese immigrants. In addition, CARE intervention participants received biweekly phone calls from the study's community health workers to set goals related to T2D self-management and work on addressing goal-achievement barriers. Hemoglobin A1c (HbA1c), self-efficacy, diabetes self-management behaviors, dietary intake, and physical activity were measured at baseline, 3 months, and 6 months. Piecewise linear mixed-effects modeling will be performed to examine intergroup differences in HbA1c and psychosocial and behavioral outcomes. RESULTS: This pilot RCT study was approved by the Institutional Review Board at NYU Grossman School of Medicine in March 2021. The first participant was enrolled in March 2021, and the recruitment goal (n=60) was met in March 2022. All data collection is expected to conclude by November 2022, with data analysis and study results ready for reporting by December 2023. Findings from this pilot RCT will further guide the team in planning a future large-scale study. CONCLUSIONS: This study will serve as an important first step in exploring scalable interventions to increase access to evidence-based diabetes interventions among underserved, low-income, immigrant populations. This has significant implications for chronic care in other high-risk immigrant groups, such as low-income Hispanic immigrants, who also bear a high T2D burden, face similar barriers to accessing diabetes programs, and report frequent social media use (eg, WhatsApp). TRIAL REGISTRATION: ClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/ct2/show/NCT03557697. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42554.

Soluble Receptor for Advanced Glycation End Products (sRAGE) Isoforms Predict Changes in Resting Energy Expenditure in Adults with Obesity during Weight Loss.

Background: Accruing evidence indicates that accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) play a significant role in obesity and type 2 diabetes. The concentrations of circulating RAGE isoforms, such as soluble RAGE (sRAGE), cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE), collectively sRAGE isoforms, may be implicit in weight loss and energy compensation resulting from caloric restriction. Objectives: We aimed to evaluate whether baseline concentrations of sRAGE isoforms predicted changes (∆) in body composition [fat mass (FM), fat-free mass (FFM)], resting energy expenditure (REE), and adaptive thermogenesis (AT) during weight loss. Methods: Data were collected during a behavioral weight loss intervention in adults with obesity. At baseline and 3 mo, participants were assessed for body composition (bioelectrical impedance analysis) and REE (indirect calorimetry), and plasma was assayed for concentrations of sRAGE isoforms (sRAGE, esRAGE, cRAGE). AT was calculated using various mathematical models that included measured and predicted REE. A linear regression model that adjusted for age, sex, glycated hemoglobin (HbA1c), and randomization arm was used to test the associations between sRAGE isoforms and metabolic outcomes. Results: Participants (n = 41; 70% female; mean ± SD age: 57 ± 11 y; BMI: 38.7 ± 3.4 kg/m2) experienced modest and variable weight loss over 3 mo. Although baseline sRAGE isoforms did not predict changes in ∆FM or ∆FFM, all baseline sRAGE isoforms were positively associated with ∆REE at 3 mo. Baseline esRAGE was positively associated with AT in some, but not all, AT models. The association between sRAGE isoforms and energy expenditure was independent of HbA1c, suggesting that the relation was unrelated to glycemia. Conclusions: This study demonstrates a novel link between RAGE and energy expenditure in human participants undergoing weight loss.This trial was registered at clinicaltrials.gov as NCT03336411.

Epidemiological and clinical study of hip fracture in hospitalized elderly patients in Shanghai, China.

In this study, we attempted to determine the epidemiology and clinical characteristics of hip fracture in the elderly. We find that elderly people with hip fracture have multiple comorbidities and suffer numerous complications. INTRODUCTION: We attempted to explore the epidemiology and clinical characteristics of hip fracture in the elderly. METHODS: One thousand five hundred thirty-nine patients aged over 65 years were included in the retrospective study. From the medical records, information was gathered about pre-fracture conditions, as well as fracture type, surgical details, laboratory indicators, postoperative complications, length of stay, outcomes, and costs of hospitalization. Binary logistic regression was used to screen for potential risk factors for perioperative complications and postoperative death, and general linear models were used to determine factors that influenced the cost of surgical treatment. RESULTS: The average age of hip fracture patients in our study was 82.20 ± 6.82 years old, and the male-to-female ratio was 1:2.82. In 1356 patients who underwent hip surgery, the incidence of perioperative complications was 6.71% (91/1356), and the postoperative mortality rate was 1.11% (15/1356). Factors associated with perioperative complications were male sex, heart function class III or higher, serum albumin < 35 g/L, respiratory diseases, and perioperative blood transfusion (P < 0.05). Perioperative blood transfusion was an independent risk factor for postoperative death after hip fracture in the elderly (P < 0.05). The main factors that influenced hospitalization expenses related to elderly hip fracture patients were type of surgery, method of anesthesia, length of stay, perioperative complications, and outcomes (P < 0.05). CONCLUSIONS: Elderly people with hip fracture have multiple comorbidities and suffer numerous complications. Thus, randomized intervention studies should focus on prevention of complications that might be avoidable.

Teaching Hospitals and the Disconnect Between Technology Adoption and Comparative Effectiveness Research: The Case of the Surgical Robot.

The surgical robot, a costly technology for treatment of prostate cancer with equivocal marginal benefit, rapidly diffused into clinical practice. We sought to evaluate the role of teaching in the early adoption phase of the surgical robot. Teaching hospitals were the primary early adopters: data from the Healthcare Cost and Utilization Project showed that surgical robots were acquired by 45.5% of major teaching, 18.0% of minor teaching and 8.0% of non-teaching hospitals during the early adoption phase. However, teaching hospital faculty produced little comparative effectiveness research: By 2008, only 24 published studies compared robotic prostatectomy outcomes to those of conventional techniques. Just ten of these studies (41.7%) were more than minimally powered, and only six (25%) involved cross-institutional collaborations. In adopting the surgical robot, teaching hospitals fulfilled their mission to innovate, but failed to generate corresponding scientific evidence.

Patient ratings of case managers in a medical home: associations with patient satisfaction and health care utilization.

BACKGROUND: Case managers are employed in medical homes to coordinate care for clinically complex patients. OBJECTIVE: To measure the association of patient perceptions of case manager performance with overall satisfaction and subsequent health care utilization. DESIGN: Retrospective cohort study. SETTING: Integrated health system in Pennsylvania. PATIENTS: Members of the health system-owned health plan who 1) received primary care in the health system's clinics, 2) were exposed to clinic-embedded case managers, and 3) completed a survey of satisfaction with care. MEASUREMENTS: Survey assessment of case manager performance and overall satisfaction with care and claims-based assessment of case manager performance and subsequent hospitalizations or emergency department visits. Survey measures were dichotomized into very good versus less than very good. RESULTS: A total of 1755 patients (44%) completed the survey and 1415 met study criteria. Survey respondents who reported very good ratings of case manager performance across all items had a higher probability of reporting very good overall satisfaction with care (92.2% vs. 62.5%; P < 0.001) and had a lower incidence of subsequent emergency department visits (incidence rate ratio, 0.79 [95% CI, 0.64 to 0.98]; P = 0.029) but not hospitalizations (incidence rate ratio, 0.92 [CI, 0.75 to 1.11]; P = 0.37) up to 2 years after the survey compared with survey respondents who reported less-than-very good case manager performance on 1 or more questions on the survey. LIMITATIONS: Satisfaction data demonstrated substantial ceiling effects. Survey nonresponse may have introduced bias in the results. CONCLUSION: Patients' favorable perceptions of case managers are associated with higher overall satisfaction with care and may lower risk for future acute care use. PRIMARY FUNDING SOURCE: Robert Wood Johnson Foundation and the U.S. Department of Veterans Affairs.

Gold-catalyzed 1,2-acyloxy migration/intramolecular [3+2] 1,3-dipolar cycloaddtion cascade reaction: an efficient strategy for syntheses of medium-sized-ring ethers and amines.

A highly efficient strategy for the formation of medium-sized-ring ethers and amines based on a gold-catalyzed cascade reaction, involving enynyl ester isomerization and intramolecular [3+2] cyclization, has been developed. Various multisubstituted medium-sized-ring unsaturated ethers and amines were obtained through this transformation. This method represents one of the relatively few transition metal catalyzed intramolecular cycloaddition reactions for medium-sized ring synthesis.

Using cases to strengthen inference on the association between single nucleotide polymorphisms and a secondary phenotype in genome-wide association studies.

Case-control genome-wide association studies provide a vast amount of genetic information that may be used to investigate secondary phenotypes. We study the situation in which the primary disease is rare and the secondary phenotype and genetic markers are dichotomous. An analysis of the association between a genetic marker and the secondary phenotype based on controls only (CO) is valid, whereas standard methods that also use cases result in biased estimates and highly inflated type I error if there is an interaction between the secondary phenotype and the genetic marker on the risk of the primary disease. Here we present an adaptively weighted (AW) method that combines the case and control data to study the association, while reducing to the CO analysis if there is strong evidence of an interaction. The possibility of such an interaction and the misleading results for standard methods, but not for the AW or CO approaches, are illustrated by data from a case-control study of colorectal adenoma. Simulations and asymptotic theory indicate that the AW method can reduce the mean square error for estimation with a prespecified SNP and increase the power to discover a new association in a genome-wide study, compared to CO analysis. Further experience with genome-wide studies is needed to determine when methods that assume no interaction gain precision and power, thereby can be recommended, and when methods such as the AW or CO approaches are needed to guard against the possibility of nonzero interactions.