Substantial Heterogeneity Research Articles

Determinants and Characteristics of Insulin Dose Requirements in Children and Adolescents with New-Onset Type 1 Diabetes: Insights from the INSENODIAB Study.

New-onset type 1 diabetes mellitus (T1D) in pediatric patients represents a clinical challenge for initial total daily insulin dosing (TIDD) due to substantial heterogeneity in practice and lack of consensus on the optimal starting dose. Our INSENODIAB (INsulin SEnsitivity in New Onset type 1 DIABetes) study is aimed at (1) exploring the influence of patient-specific characteristics on insulin requirements in pediatric patients with new-onset T1D; (2) constructing a predictive model for the recommended TIDD tailored to individual patient profiles; and (3) assessing potential associations between TIDD and patient outcomes at follow-up intervals of 3 and 12 months. We conducted a comprehensive analysis of medical records for children aged 6 months to 18 years, hospitalized for new-onset T1D from 2013 to 2022. The study initially involved multivariable regression analysis on a retrospective cohort (rINSENODIAB), incorporating baseline variables. Subsequently, we validated the model robustness on a prospective cohort (pINSENODIAB) with a significance threshold of 5%. The model accuracy was assessed by Pearson's correlation. Our study encompassed 103 patients in the retrospective cohort and 80 in the prospective cohort, with median TIDD at diagnosis of 1.1 IU/kg BW/day (IQR 0.5). The predictive model for optimal TIDD was established using baseline characteristics, resulting in the following formula: TIDD (IU/d) = ([0.09 × Age2] + [0.68 × %Weight Loss] + [28.60 × Veinous pH] - [1.03 × Veinous bicarbonates] + [0.81 × Weight] - 194.63). Validation of the model using the pINSENODIAB cohort demonstrated a significant Pearson correlation coefficient of 0.74. Notably, no significant correlation was observed between TIDD at diagnosis and partial remission markers (IDAA1C, C-peptide) at 3- and 12-months postdiagnosis time points. In the context of new-onset T1D in pediatric patients, we identified key influencing factors for determining optimal TIDD, including age, percentage of weight loss, weight, veinous pH, and bicarbonates. These findings have paved the way for the development of a dosing algorithm to potentially expedite glycemic control stabilization and facilitate a more individualized approach to treatment regimens.

Does the Mere Presence of a Smartphone Impact Cognitive Performance? A Meta-Analysis of the “Brain Drain Effect”

ABSTRACT A growing body of research investigates the general possibility that the mere presence of a smartphone might negatively impact cognitive performance, with some researchers posing the “brain drain” hypothesis which posits that smartphone presence will impair working memory capacity and fluid intelligence, but not sustained attention and response inhibition. To assess the strength of evidence for the claim that the mere presence of a smartphone can negatively impact cognitive performance, this study reports a systematic review and six meta-analyses (k = 56, n = 7093). Across cognitive functions, only a single statistically significant pooled effect was found. Working memory capacity was negatively impacted by the mere presence of a smartphone, while results for the remaining cognitive functions produced null summary effects. The analysis also finds that there is substantial methodological heterogeneity and generally poor statistical power in the domain. Overall, while the current meta-analysis provides limited support for a negative albeit smaller than theorized brain drain effect due to the mere presence of a smartphone, given methodological concerns, the extent to which the current body of literature can support or refute the hypothesis is limited.

Beyond Eosinophilic Esophagitis: Eosinophils in Gastrointestinal Disease-New Insights, "New" Diseases.

Functional dyspepsia (FD) is a highly prevalent disorder. Upper endoscopy is normal, and according to the Rome IV criteria, there is no established pathology. Data accumulated over the last 15 years has challenged the notion FD is free of relevant pathology, and in particular, increased duodenal eosinophils have been observed. Intestinal eosinophils play important roles in microbial defence, immune regulation, tissue regeneration and remodelling, and maintaining tissue homeostasis and metabolism; degranulation of eosinophils releases toxic granule products (e.g., major basic protein, eosinophil-derived neurotoxin) which can damage nerves. Normal cut-offs for eosinophil infiltration into the duodenum histologically are less than five eosinophils per high power field (<25 per five high power fields). In clinical practice there is evidence that pathologically increased intestinal eosinophils may often be overlooked. In a meta-analysis duodenal eosinophils were significantly increased in FD although there was substantial heterogeneity; degranulation of duodenal eosinophils was also significantly higher in FD without significant heterogeneity. In addition, increased duodenal permeability, systemic immune activation, and an altered mucosa-associated duodenal microbiome have been identified that may help explain why symptoms arise, often occur after food with exposure to food antigens, and typically fluctuate. Several potentially reversible risk factors for FD have now been identified. We evaluate the current evidence linking duodenal microinflammation and immune activation with FD and disorders of gut-brain interactions that overlap with FD. We propose a two-hit disease model for eosinophilic functional dyspepsia (EoFD) with management implications.

Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study

BackgroundA number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis.MethodsAn investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran’s Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings.ResultsA total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288–2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran’s Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP).ConclusionOur first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease’s treatment.

Expanding on cross-price elasticity: Understanding tobacco product demand and substitution from the cross-price purchase task.

We examine whether cigarettes serve as substitutes for electronic nicotine delivery systems (ENDS) among ENDS users and demonstrate methodological extensions of data from a cross-price purchase task to inform policies and interventions. During a clinical laboratory study, n = 19 exclusive ENDS users and n = 17 dual cigarette/ENDS users completed a cross-price purchase task with cigarettes available at a fixed price while prices of own-brand ENDS increased. We estimated cross-price elasticity using linear models to examine substitutability. We defined five additional outcomes: nonzero cross-price intensity (purchasing cigarettes if ENDS were free), constant null demand (not purchasing cigarettes at any ENDS price), cross-product crossover point (first price where participants purchased more cigarettes than ENDS), dual-demand score (percentage of prices where both products were purchased), and dual-use break point (minimum relative price to force complete substitution). The cross-price elasticity results indicated that cigarettes could serve as substitutes for ENDS among ENDS users on average, but this average effect masked substantial heterogeneity in profiles of demand (here, a measure of the drug's reinforcement potential). Policies and regulations that increase ENDS prices appear unlikely to steer most exclusive ENDS users toward cigarette use, as most would not purchase cigarettes at any ENDS price, but they could prompt some dual users to substitute cigarettes completely while others remain dual users. This heterogeneity in consumer responses suggests additional indices of cross-product demand are useful to characterize the anticipated and unanticipated effects of tobacco price policies more fully.

Assessment of active shooter preparedness in US hospital systems

Background: Active shooter events are horrific, unfortunate realities in American hospitals. Protecting patients and staff in an active shooter event is made more difficult in the cases of critically ill and otherwise immobile patients. Previous work has proposed theoretical mitigation strategies for active shooter events. This study assesses American hospitals’ current, active preparedness plans.&#x0D; Methods: This is a survey-based study with questionnaires distributed to leaders in American healthcare. The survey assessed current active shooter protocols with a particular emphasis on managing critically ill patients. Data were summarized with frequency and percentage.&#x0D; Results: The survey was distributed to 294 hospital systems across the United States, and representatives from 60 hospital systems responded. Ninety-eight percent of these hospital systems have an active shooter protocol; 24 percent report a plan to provide care for critically ill patients. Among those hospital systems with a plan for caring for immobile patients, substantial heterogeneity exists in the philosophy and implementation of these protocols. Additionally, 52 percent of hospital systems routinely practice response drills to active shooter events. Notably, hospital systems that had experienced an active shooter event in the past were more likely to practice implementing active shooter protocols.&#x0D; Conclusions: While most hospital systems have an active shooter protocol in place, these plans are infrequently practiced and generally do not include contingency arrangements for the sickest, immobile patients. The results from this study highlight a significant opportunity for improvement in American hospital safety procedures.

Populational pan-ethnic screening panel enabled by deep whole genome sequencing

Birth defect is a global threat to the public health systems. Mitigating neonatal anomalies is hampered by elusive molecular mechanisms of pathogenic mutations and poor subsequent translation into preventative measures. Applying appropriate strategies in China to promote reproductive health is particularly challenging, as the Chinese population compromises complex genomic diversity due to the inclusion of many ethnic groups with distinct genetic backgrounds. To investigate and evaluate the feasibility of implementing a pan-ethnic screening strategy, and guide future reproductive counselling, high-quality variants associated with autosome recessive (AR) diseases derived from the largest publicly available cohort of the Chinese population were re-analysed using a bottom-up approach. The analyses of gene carrier rates (GCRs) across distinct ethnic groups revealed that substantial heterogeneity existed potentially due to diverse evolutionary selection. The sampling population, sequencing coverage and underlying population structure contributed to the differential variants observed between ChinaMAP and the East Asian group in gnomAD. Beyond characteristics of GCR, potential druggable targets were additionally explored according to genomic features and functional roles of investigated genes, demonstrating that phase separation could be a therapeutic target for autosomal recessive diseases. A further examination of estimated GCR across ethnic groups indicated that most genes shared by at least two populations could be utilised to direct the design of a pan-ethnic screening application once sequencing and interpreting costs become negligible. To this end, a list of autosomal recessive disease genes is proposed based on the prioritised rank of GCR to formulate a tiered screening strategy.

Diverging labour market trajectories of Australian graduates from advantaged and disadvantaged social backgrounds: A longitudinal analysis of population‐wide linked administrative data

Despite mounting evidence that university participation enhances labour market prospects, there are growing concerns about its unequal returns. This study uses novel large‐scale linked administrative data covering the full population of individuals graduating from Australian universities over the 2005–11 period to examine the labour market trajectories of graduates from multiple disadvantaged social backgrounds (based on socio‐economic, migration and disability status, ethnicity and location) in comparison with their more advantaged peers, over a ten‐year observation window. The findings reveal substantial heterogeneity in the income and unemployment benefit receipt trajectories of graduates from different groups. This has important implications for labour market policies aimed at improving social equity.

Addressing uncertainty about the role of structured lifestyle modification for metabolic surgery patients

There is good evidence that structured lifestyle modification programmes improve health in patients with metabolic and cardiovascular disorders, but there is no specific evidence that they improve outcomes in patients undergoing metabolic or obesity surgery. Despite expert consensus guidelines stating this fact, some healthcare systems still compel patients to participate in a structured lifestyle modification programme prior to metabolic or obesity surgery.There is a well-established need for individualised multidisciplinary dietetic and physical activity care for metabolic and obesity surgery patients, and the benefits of intentional weight loss prior to surgery are well proven, but these are distinct from potentially harmful requirements for patients to undertake compulsory structured lifestyle programmes of fixed duration, frequency and intensity, which may delay surgery and reinforce obesity stigma.A critical step in rejuvenating metabolic surgery is to reframe patient participation in structured lifestyle modification programmes as an opportunity for education and empowerment, not as an indicator of motivation or suitability for metabolic surgery. Large, well-designed and adequately powered clinical trials are needed to address uncertainties in the evidence base for these programmes. Given genuine equipoise, they will need to determine whether “surgery plus lifestyle” is superior to “surgery plus placebo”. Moreover, they will need to determine the cost-effectiveness of these programmes and identify some of the factors giving rise to the substantial heterogeneity in responses to structured lifestyle modification.

State Reporting Requirements for Involuntary Holds, Court-Ordered Guardianship, and the US National Firearm Background Check System

Firearm violence is a leading cause of death in the US. There is broad public agreement that individuals at high risk of perpetrating violence should not be allowed to purchase or possess firearms. The National Instant Criminal Background Check System (NICS) is a national system intended to stop firearm purchases or possession by prohibited persons, but there is heterogeneity in how states interact with and report data to NICS. To examine variability in state requirements for NICS reporting for mental health prohibitions. This cross-sectional study in the US reviewed current statutes for all 50 states and the District of Columbia (enacted through the 2021 legislative session) regarding reporting mental health prohibitions to NICS or state systems. Data were analyzed from October 2022 to April 2023. For each state, the following were recorded: reliance on Federal Bureau of Investigation vs state point of contact for NICS checks; regulation requiring or allowing reporting to NICS for 3 hypothetical cases; and details on reporting responsibility and time frame. The number of NICS listings for adjudicated mental health reasons was obtained, and state rates per 1000 population were calculated. To compare states, we developed 3 hypothetical cases of individuals with risk of firearm violence, whether possibly temporary (involuntary commitment for decompensated psychosis, or involuntary short-term psychiatric hold for suicidal ideation) or chronic and progressive (court-appointed guardianship for dementia). A total of 39 states required and 5 allowed reporting to NICS for court-ordered, involuntary psychiatric hospitalization. Thirteen states required and 5 allowed reporting to NICS when a court determines an individual is mentally incompetent to manage their affairs (with or without guardianship). Two states required NICS reporting for short-term emergency psychiatric holds. Five states and the District of Columbia had no legislation explicitly requiring or allowing NICS reporting in the 3 scenarios. In this cross-sectional study of state laws, there was substantial heterogeneity in NICS reporting requirements and lack of clarity around processes. This raises questions about the ability of NICS to be used to block firearm purchases or possession by individuals with court-identified high risk of perpetrating violence toward themselves or others.

Hepatitis C infection seroprevalence in pregnant women worldwide: a systematic review and meta-analysis

Monitoring progress towards the WHO global target to eliminate hepatitis C virus (HCV) infection by 2030, entails reliable prevalence estimates for HCV infection in different populations. Little is known about the global burden of HCV infection in pregnant women. Here, for the first time to our knowledge, we estimated the global and regional seroprevalence of HCV antibody (Ab) and determinants in pregnant women. In this systematic review and meta-analysis study, we searched PubMed/MEDLINE, Web of Science, Embase, Scopus, and SciELO databases for peer-reviewed observational studies between January 1, 2000 and April 1, 2023, without language or geographical restrictions. Pooled global seroprevalence (and 95% confidence interval, CI) were estimated using random-effects meta-analysis and seroprevalences were categorised according to World Health Organization regions and subregions, publishing year, countries' income and human development index (HDI) levels. We used sensitivity analysis to assess the effect of four large sample size studies on pooled global prevalence through the "leave-one-out" method. We also investigated the association of potential risk factors with HCV seropositivity in pregnant women by subgroup and meta-regression analyses. The Protocol was registered in PROSPERO CRD42023423259. We included 192 eligible studies (208 datasets), with data for 148,509,760 pregnant women from 53 countries. The global seroprevalence of HCV Ab in pregnant women was 1.80% (95% CI, 1.72-1.89%) and 3.29% (3.01-3.57%) in overall and sensitivity analyses, respectively. The seroprevalence was highest in the Eastern Mediterranean region (6.21%, 4.39-8.29%) and lowest in the Western Pacific region (0.75%, 0.38-1.22%). Subgroup analysis indicated that the seroprevalence of HCV Ab among pregnant women was significantly higher for those with opioid use disorder (51.94%, 95% CI: 37.32-66.39) and HIV infection (4.34%, 95% CI: 2.21-7.06%) than for the general population of pregnant women (1.08%, 95% CI: 1.02-1.15%), as confirmed by multivariable meta-regression (p<0.001). A significant decreasing trend was observed with increasing human development index levels. Other important risk factors for HCV seropositivity included older age, lower educational levels, poly sexual activity, history of blood transfusion, hospitalization, surgery, abortion and sexual transmitted diseases, having scarification/tattoo or piercing, and testing hepatitis B positive. This meta-analysis showed relatively high burden of exposure to HCV infection (2.2-5.3 million) in pregnant women globally. However, due to substantial heterogeneity between studies, our estimates might be different than the true seroprevalence. Our findings highlighted the need to expand HCV screening for women of reproductive age or during pregnancy, particularly in countries with high prevalence; as well as for more studies that assess safety of existing therapeutic drugs during pregnancy or potentially support development of drugs for pregnant women. There was no funding source for this study.

Constructing a high-precision precipitation dataset on the data-limited Qinghai-Tibet Plateau

The primary constraint hindering a comprehensive understanding of the atmospheric, hydrological, and ecological dynamics on the Qinghai-Tibet Plateau (QTP) is the absence of highly accurate precipitation datasets. Given the limited availability of climate observations and the pronounced spatial disparities in this region, traditional interpolation techniques are ill-suited, necessitating the development of novel methods. In this study, we formulated a random forest model leveraging precipitation data from 209 climate stations and multisource satellite datasets spanning the period from 1960 to 2020. These datasets encompassed low spatial resolution TRMM precipitation products and high spatial resolution NDVI data. This model facilitated the creation of a monthly precipitation dataset at a 1 km resolution for the QTP. Our findings showed that (1) the prevailing precipitation datasets for the QTP exhibited notable deficiencies, characterized by low spatial precision (R² = 0.592, p = 0.015) and incongruent temporal trends when compared to observational data (NSE = 0.398); (2) by incorporating multisource satellite data, we achieved a substantial enhancement in precipitation accuracy. For instance, the introduction of NDVI led to a reduction in precipitation estimation errors by 7.9 mm and 15.4 mm in desert and nondesert regions, respectively. The inclusion of TRMM satellite precipitation data not only improved accuracy in areas with limited climate stations by more than 16 % but also reduced cumulative monthly errors by 46.8 mm, and (3) the precipitation dataset generated through this method displayed a 24.8 % increase in accuracy (R² = 0.84) compared to existing datasets for the QTP, aligning well with actual precipitation trends (NSE = 0.806). This study offers an effective approach for acquiring high-precision precipitation datasets in regions with limited meteorological stations and substantial spatial heterogeneity in precipitation patterns. Furthermore, our method significantly enhances the spatial heterogeneity of precipitation products, potentially serving as a model for the development of datasets in data-scarce areas.

Prediction of Clinical Precision Chemotherapy by Patient-Derived 3D Bioprinting Models of Colorectal Cancer and Its Liver Metastases.

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.

National estimate and associated factors of myopia among schoolchildren in Ethiopia: A systematic review and meta-analysis

IntroductionMyopia is a global public health concern that has a significant socioeconomic and psychological impact on schoolchildren. If Myopic patients are not detected early, they are exposed to retinal detachment, cataracts, and glaucoma. There have been previous studies conducted in Ethiopia, but there is significant inconsistency among studies. Hence, the aim of this study was to provide a single figure as well as associated factors for Myopia among Ethiopian schoolchildren. MethodThe national and international databases and gray literature were searched for important research articles. This review included school-based cross-sectional studies that were reported in English. The data were extracted using Microsoft word and exported to Stata™ Version 17.0 statistical software for further management and analysis .The presence of heterogeneity was checked using Cochrane Q test via fixed effects model and presented by forest plots with 95% CI. Due to the presence of substantial heterogeneity, I2 test using random effects model was computed to estimate the effect size. The existing heterogeneity among studies was explained by regional difference. To identify factors associated with myopia, meta regression was computed and significant factors was reported using OR with 95% CI. ResultsIn this systematic review and meta-analysis, 12 studies with a total of 9688 schoolchildren were included. The national estimate of myopia among schoolchildren in Ethiopia was 6.49% (95%CI: 4.86, 8.12). Having family history of myopia (OR: 9.18, 95%CI: 3.5,24.02) and being female (OR: 0.94, 95% CI: 0.50, 0.98) were the identified factors associated with myopia. ConclusionMyopia is one of the most prevalent childhood health condition in Ethiopia, which affects about one in every fourteen schoolchildren. Schoolchildren who had family history of myopia and being female were the identified risk factors of myopia among schoolchildren. Clinical and public engagement activities are needed to address the burden of myopia.

The Association of Psoriasis, Diabetes Mellitus, and Hypertension: A Meta-Analysis.

Psoriasis is a systemic disease affecting various organs; however, it is usually thought of as a skin disease. A multidisciplinary approach is needed for better outcomes. The current meta-analysis assessed the association between diabetes mellitus, high blood pressure, and psoriasis. We searched four databases, including Cochrane Library, PubMed, MEDLINE, and Google Scholar, for relevant articles using the following keywords: psoriasis, hypertension, high blood pressure, cardiovascular risk factors, and diabetes mellitus. The author's name, year, and country of publication, diabetes, and hypertension among patients with psoriasis and control subjects were collected and entered into a Microsoft Excel sheet. Out of 1209 articles retrieved, 903 articles remained after duplication removal. From the 82 full texts screened, only seven studies fulfilled the inclusion and exclusion criteria. Psoriasis was associated with diabetes and hypertension: odds ratio 1.38, 95% CI 1.17-1.64;P-value 0.0002, chi-square 224.93, and odds ratio 1.60, 95% CI 1.41-1.81,P-value 0.00001, chi-square 226.59, respectively. Substantial heterogeneity was observed (I2 for heterogeneity, 97%, P < 0.001). A broad approach is needed to address the associated comorbidities and select the appropriate therapeutic approach. Randomized controlled trials investigating the best drugs for the treatment of psoriasis and its associated cardiovascular risk factors are needed.

Current Clinical Evidence for Agents used in Acanthamoeba Keratitis: Systematic Literature Reviews

To describe the evidence for agents with anti-amoebic activity used to treat Acanthamoeba keratitis (AK), two systematic literature reviews (SLRs) were conducted of 1) clinical outcomes for patients with AK and 2) health economic outcomes for patients with AK or microbial keratitis (MK). The intervention of interest was any agent with anti-amoebic activity administered as eye-drops or orally. The main outcome was clinical resolution. Electronic databases (January 1992-July 2022), conference abstracts (2017-2022), and relevant websites were hand-searched. Risk of bias assessments used external assessment tools. A narrative synthesis was conducted. The clinical SLR (37 studies; 2043 patients) identified at least 20 studies reporting clinical resolution, best-corrected visual acuity, and corneal surgery; fewer studies reported other outcomes. Treatment regimes, outcome definitions and assessment timing varied markedly between studies. Studies classified as fair or poor quality appeared to underestimate the burden of AK compared with good quality studies. For health economic outcomes (15 studies; 1878 patients), very limited evidence in AK populations was found. In conclusion, there was a substantial amount of clinical evidence, but scarce economic evidence. Study quality and comparability challenges should be considered when estimating the impact of AK, with substantial between-study heterogeneity limiting options for robust evidence synthesis.

Maternal Nativity and Preterm Birth

Preterm birth is a major contributor to neonatal morbidity and mortality, and considerable differences exist in rates of preterm birth among maternal racial and ethnic groups. Emerging evidence suggests pregnant individuals born outside the US have fewer obstetric complications than those born in the US, but the intersection of maternal nativity with race and ethnicity for preterm birth is not well studied. To determine if there is an association between maternal nativity and preterm birth rates among nulliparous individuals, and whether that association differs by self-reported race and ethnicity of the pregnant individual. This was a nationwide, cross-sectional study conducted using National Center for Health Statistics birth registration records for 8 590 988 nulliparous individuals aged 15 to 44 years with singleton live births in the US from 2014 to 2019. Data were analyzed from March to May 2022. Maternal nativity (non-US-born compared with US-born individuals as the reference, wherein US-born was defined as born within 1 of the 50 US states or Washington, DC) in the overall sample and stratified by self-reported ethnicity and race, including non-Hispanic Asian and disaggregated Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Pacific Islander, Vietnamese, and other Asian), non-Hispanic Black, Hispanic and disaggregated Hispanic subgroups (Cuban, Mexican, Puerto Rican, and other Hispanic), and non-Hispanic White. The primary outcome was preterm birth (<37 weeks of gestation) and the secondary outcome was very preterm birth (<32 weeks of gestation). Of 8 590 988 pregnant individuals included (mean [SD] age at delivery, 28.3 [5.8] years in non-US-born individuals and 26.2 [5.7] years in US-born individuals; 159 497 [2.3%] US-born and 552 938 [31.2%] non-US-born individuals self-identified as Asian or Pacific Islander, 1 050 367 [15.4%] US-born and 178 898 [10.1%] non-US-born individuals were non-Hispanic Black, 1 100 337 [16.1%] US-born and 711 699 [40.2%] non-US-born individuals were of Hispanic origin, and 4 512 294 [66.1%] US-born and 328 205 [18.5%] non-US-born individuals were non-Hispanic White), age-standardized rates of preterm birth were lower among non-US-born individuals compared with US-born individuals (10.2%; 95% CI, 10.2-10.3 vs 10.9%; 95% CI, 10.9-11.0) with an adjusted odds ratio (aOR) of 0.90 (95% CI, 0.89-0.90). The greatest relative difference was observed among Japanese individuals (aOR, 0.69; 95% CI, 0.60-0.79) and non-Hispanic Black individuals (aOR, 0.74; 0.73-0.76) individuals. Non-US-born Pacific Islander individuals experienced higher preterm birth rates compared with US-born Pacific Islander individuals (aOR, 1.15; 95% CI, 1.04-1.27). Puerto Rican individuals born in Puerto Rico compared with those born in US states or Washington, DC, also had higher preterm birth rates (aOR, 1.07; 95% CI, 1.03-1.12). Overall preterm birth rates were lower among non-US-born individuals compared with US-born individuals. However, there was substantial heterogeneity in preterm birth rates across maternal racial and ethnic groups, particularly among disaggregated Asian and Hispanic subgroups.

Multidimensional progressive single-cell sequencing reveals cell microenvironment composition and cancer heterogeneity in lung cancer.

Despite substantial advances in cancer biology and treatment, the clinical outcomes of patients with lung cancer remain unsatisfactory. The tumor microenvironment (TME) is a potential target. Using single-cell RNA sequencing, we could distinguish eight distinct cell types in the lung cancer microenvironment, demonstrating substantial intratumoral heterogeneity in 19 different lung cancer tumor samples. Through the re-dimensional grouping of cancer-associated fibroblasts (CAFs), myeloid cells, epithelial cells, natural killer (NK) cells, and T cells, the difference in the TME of lung cancer was revealed. We discovered SFTPB, SFN, and KRT8 as possible predictive biomarkers for lung cancer by assessing the gene expression patterns in epithelial cells. Examining cell-to-cell communications showed a robust association between the quantity of matrix CAFs, epithelial cells, and macrophages in the thrombospondin signaling pathway. Additionally, we found that the amyloid precursor protein signaling pathway primarily originated from the matrix, and inflammatory cancer-associated endothelial and fibroblast cells showed a co-expression relationship with myeloid cells and B cells. Through cell-to-cell correlation analysis, we found positive regulation between NK cells, regulatory T cells, GZMB-CD8 T cells, and GZMK-CD8 T cells, which could play a role in developing immune TMEs. These findings support studies on cancer heterogeneity and add to our understanding of lung cancer's cellular microenvironment.

Alveolar Type 2 Epithelial Cell Organoids: Focus on Culture Methods.

Lung diseases rank third in terms of mortality and represent a significant economic burden globally. Scientists have been conducting research to better understand respiratory diseases and find treatments for them. An ideal in vitro model must mimic the in vivo organ structure, physiology, and pathology. Organoids are self-organizing, three-dimensional (3D) structures originating from adult stem cells, embryonic lung bud progenitors, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). These 3D organoid cultures may provide a platform for exploring tissue development, the regulatory mechanisms related to the repair of lung epithelia, pathophysiological and immunomodulatory responses to different respiratory conditions, and screening compounds for new drugs. To create 3D lung organoids in vitro, both co-culture and feeder-free methods have been used. However, there exists substantial heterogeneity in the organoid culture methods, including the sources of AT2 cells, media composition, and feeder cell origins. This article highlights the currently available methods for growing AT2 organoids and prospective improvements to improve the available culture techniques/conditions. Further, we discuss various applications, particularly those aimed at modeling human distal lung diseases and cell therapy.

Trends and site-level variation of novel cardiovascular medication utilization among patients admitted for heart failure or coronary artery disease in the US Veterans Affairs System: 2017-2021

We assessed trends in novel cardiovascular medication utilization in US Veterans Affairs (VA) for angiotensin receptor-neprilysin inhibitors (ARNI), sodium-glucose cotransporter-2 Inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA). We retrospectively identified cohorts from 114 VA hospitals with admission for prevalent 1) systolic heart failure (HF, N=82,375) or 2) coronary artery disease and diabetes (CAD+T2D, N=74,209). Site-level data for prevalent filled prescriptions were assessed at hospital admission, discharge, or within 6 months of discharge. Variability among sites was estimated with median odds ratios (mOR), and within-site Pearson correlations of utilization of each medication class were calculated. Site- and patient-level characteristics were compared by high-, mixed-, and low-utilizing sites. ARNI and SGTL2i use for HF increased from <5% to 20% and 21%, respectively, while SGTL2i or GLP-1 RA use for CAD+T2D increased from <5% to 30% from 2017 to 2021. Adjusted mOR and 95% confidence intervals for ARNI, SGTL2i for HF, and SGTL2i or GLP-1 RA for CAD+T2D were 1.73 (1.64-1.91), 1.72 (1.59-1.81), and 1.53 (1.45-1.62), respectively. Utilization of each medication class correlated poorly with use of other novel classes (Pearson <0.38 for all). Higher patient volume, number of beds, and hospital complexity correlated with high-utilizing sites. Utilization of novel medications has increased over time but remains suboptimal for US Veterans with HF and CAD+T2D, with substantial site-level heterogeneity despite a universal medication formulary and low out-of-pocket costs for patients. Future work should include further characterization of hospital- and clinician-level practice patterns to serve as targets to increase implementation.