Predictive value of midtrimester universal cervical length screening based on parity

OBJECTIVES: To evaluate the effect of parity on performance characteristics of midtrimester cervical length (CL) in predicting spontaneous preterm birth (sPTB) before 37 weeks. METHODS: This was a retrospective cohort study of 13,508 women with no history of sPTB undergoing universal transvaginal CL screening at 17 to 23 weeks\u27 gestation from 2011 to 2016. Patients who declined screening or with unknown delivery outcomes were excluded. Areas under the receiver operator characteristic curves were used to assess and compare the predictive ability of CL screening for sPTB. The sensitivity, specificity, and positive and negative predictive values were estimated for specific CL cutoffs for prediction of sPTB. RESULTS: There were 20,100 patients, of whom 2087 (10%) declined screening and 4505 (22%) did not meet inclusion criteria. Of the remaining 13,508 patients, 43% were nulliparous. The incidence rates of sPTB were 6.5% in nulliparas and 4.9% in multiparas (P \u3c .001). The mean CLs were 39.9 mm in nulliparas and 41.8 mm in multiparas (P \u3c .001), and those of the first percentiles were 19.0 mm in nulliparas and 24.0 mm in multiparas. Cervical length was significantly more predictive of sPTB in nulliparas (area under the curve, 0.67; 95% confidence interval, 0.63-0.70; versus 0.61, 95% confidence interval, 0.57-0.63; P = .008). At CL cutoffs of 10, 15, 20, and 25 mm or less, the sensitivity was lower in multiparas, and the specificity was comparable between the groups. CONCLUSIONS: Midtrimester CL is less predictive of sPTB in multiparas compared to nulliparas. The poor predictive ability, especially in multiparas, calls into question the value of universal CL screening in this population

LIN28A expression reduces sickling of cultured human erythrocytes

Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed all members of the let-7 family of miRNAs. LIN28A-OE did not affect erythroblast differentiation or prevent enucleation, but it significantly reduced or ameliorated the sickling morphologies of the enucleated erythrocytes

Identification of beneficial and detrimental bacteria impacting sorghum responses to drought using multi-scale and multisystem microbiome comparisons

Drought is a major abiotic stress limiting agricultural productivity. Previous field-level experiments have demonstrated that drought decreases microbiome diversity in the root and rhizosphere. How these changes ultimately affect plant health remains elusive. Toward this end, we combined reductionist, transitional and ecological approaches, applied to the staple cereal crop sorghum to identify key root-associated microbes that robustly affect drought-stressed plant phenotypes. Fifty-three Arabidopsis-associated bacteria were applied to sorghum seeds and their effect on root growth was monitored. Two Arthrobacter strains caused root growth inhibition (RGI) in Arabidopsis and sorghum. In the context of synthetic communities, Variovorax strains were able to protect plants from Arthrobacter-caused RGI. As a transitional system, high-throughput phenotyping was used to test the synthetic communities. During drought stress, plants colonized by Arthrobacter had reduced growth and leaf water content. Plants colonized by both Arthrobacter and Variovorax performed as well or better than control plants. In parallel, we performed a field trial wherein sorghum was evaluated across drought conditions. By incorporating data on soil properties into the microbiome analysis, we accounted for experimental noise with a novel method and were able to observe the negative correlation between the abundance of Arthrobacter and plant growth. Having validated this approach, we cross-referenced datasets from the high-throughput phenotyping and field experiments and report a list of bacteria with high confidence that positively associated with plant growth under drought stress. In conclusion, a three-tiered experimental system successfully spanned the lab-to-field gap and identified beneficial and deleterious bacterial strains for sorghum under drought

Development of a complex intervention to promote appropriate prescribing and medication intensification in poorly controlled type 2 diabetes mellitus in Irish general practice

BACKGROUND: Poorly controlled type 2 diabetes mellitus (T2DM) can be seen as failure to meet recommended targets for management of key risk factors including glycaemic control, blood pressure and lipids. Poor control of risk factors is associated with significant morbidity, mortality and healthcare costs. Failure to intensify medications for patients with poor control of T2DM when indicated is called clinical inertia and is one contributory factor to poor control of T2DM. We aimed to develop a theory and evidence-based complex intervention to improve appropriate prescribing and medication intensification in poorly controlled T2DM in Irish general practice. METHODS: The first stage of the Medical Research Council Framework for developing and evaluating complex interventions was utilised. To identify current evidence, we performed a systematic review to examine the effectiveness of interventions targeting patients with poorly controlled T2DM in community settings. The Behaviour Change Wheel theoretical approach was used to identify suitable intervention functions. Workshops, simulation, collaborations with academic partners and observation of physicians were utilised to operationalise the intervention functions and design the elements of the complex intervention. RESULTS: Our systematic review highlighted that professional-based interventions, potentially through clinical decision support systems, could address poorly controlled T2DM. Appropriate intensification of anti-glycaemic and cardiovascular medications, by general practitioners (GPs), for adults with poorly controlled T2DM was identified as the key behaviour to address clinical inertia. Psychological capability was the key driver of the behaviour, which needed to change, suggesting five key intervention functions (education, training, enablement, environmental restructuring and incentivisation) and nine key behaviour change techniques, which were operationalised into a complex intervention. The intervention has three components: (a) a training program/academic detailing of target GPs, (b) a remote finder tool to help GPs identify patients with poor control of T2DM in their practice and (c) A web-based clinical decision support system. CONCLUSIONS: This paper describes a multifaceted process including an exploration of current evidence and a thorough theoretical understanding of the predictors of the behaviour resulting in the design of a complex intervention to promote the implementation of evidence-based guidelines, through appropriate prescribing and medication intensification in poorly controlled T2DM

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

Association of outpatient ACE inhibitors and angiotensin receptor blockers and outcomes of acute respiratory illness: a retrospective cohort study

Objectives Evaluate associations between ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs) and clinical outcomes in acute viral respiratory illness (AVRI).Design Retrospective cohort analysis of claims data.Setting The USA; 2018–2019 influenza season.Participants Main cohort: people with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI. Falsification cohort: parallel cohort receiving elective knee or hip replacement.Main outcome measures Main cohort: hospital admission, intensive care unit, acute respiratory distress (ARD), ARD syndrome and all-cause mortality. Falsification cohort: complications after surgery and all-cause mortality.Results The main cohort included 236 843 episodes of AVRI contributed by 202 629 unique individuals. Most episodes were in women (58.9%), 81.4% in people with Medicare Advantage and 40.3% in people aged 75+ years. Odds of mortality were lower in the ACEi (0.78 (0.74 to 0.83)) and ARB (0.64 (0.61 to 0.68)) cohorts compared with other HTN medications. On all other outcomes, people taking ARBs (but not ACEis) had a >10% reduction in odds of inpatient stays compared with other HTN medications.In the falsification analysis (N=103 353), both ACEis (0.89 (0.80 to 0.98)) and ARBs (0.82 (0.74 to 0.91)) were associated with decreased odds of complications compared with other HTN medications; ARBs (0.64 (0.47 to 0.87)) but not ACEis (0.79 (0.60 to 1.05)) were associated with lower odds of death compared with other HTN medications.Conclusions Outpatient use of ARBs was associated with better outcomes with AVRI compared with other medications for HTN. ACEis were associated with reduced risk of death, but with minimal or no reduction in risk of other complications. A falsification analysis conducted to provide context on the possible causal implications of these findings did not provide a clear answer. Further analysis using observational data will benefit from additional approaches to assess causal relationships between these drugs and outcomes in AVRI

Access to primary care and computed tomography use in the emergency department

Abstract Background The decision to obtain a computed tomography CT scan in the emergency department (ED) is complex, including a consideration of the risk posed by the test itself weighed against the importance of obtaining the result. In patients with limited access to primary care follow up the consequences of not making a diagnosis may be greater than for patients with ready access to primary care, impacting diagnostic reasoning. We set out to determine if there is an association between CT utilization in the ED and patient access to primary care. Methods We performed a cross-sectional study of all ED visits in which a CT scan was obtained between 2003 and 2012 at an academic, tertiary-care center. Data were abstracted from the electronic medical record and administrative databases and included type of CT obtained, demographics, comorbidities, and access to a local primary care provider (PCP). CT utilization rates were determined per 1000 patients. Results A total of 595,895 ED visits, including 98,001 visits in which a CT was obtained (16.4%) were included. Patients with an assigned PCP accounted for 55% of all visits. Overall, CT use per 1000 ED visits increased from 142.0 in 2003 to 169.2 in 2012 (p < 0.001), while the number of annual ED visits remained stable. CT use per 1000 ED visits increased from 169.4 to 205.8 over the 10-year period for patients without a PCP and from 118.9 to 142.0 for patients with a PCP. Patients without a PCP were more likely to have a CT performed compared to those with a PCP (OR 1.57, 95%CI 1.54 to 1.58; p < 0.001). After adjusting for age, gender, year of visit and number of comorbidities, patients without a PCP were more likely to have a CT performed (OR 1.20, 95% CI 1.18 to 1.21, p < 0.001). Conclusions The overall rate of CT utilization in the ED increased over the past 10 years. CT utilization was significantly higher among patients without a PCP. Increased availability of primary care, particularly for follow-up from the ED, could reduce CT utilization and therefore decrease costs, ED lengths of stay, and radiation exposure

Increased Computed Tomography Utilization in the Emergency Department and Its Association with Hospital Admission

Introduction: Our goal was to investigate trends in computed tomography (CT) utilization in emergency departments (EDs) and its association with hospitalization. Methods: We conducted an analysis of an administrative claims database of U.S. privately insured and Medicare Advantage enrollees. We identified ED visits from 2005 through 2013 and assessed for CT use, associated factors, and hospitalization after CT, along with patient demographics. We used both descriptive methods and regression models adjusted for year, age, sex, race, geographic region, and Hwang comorbidity score to explore associations among CT use, year, demographic characteristics, and hospitalization. Results: We identified 33,144,233 ED visits; 5,901,603 (17.8%) involved CT. Over time, CT use during ED visits increased 59.9%. CT use increased in all age groups but decreased in children since 2010. In propensity-matching analysis, odds of hospitalization increased with age, comorbidities, male sex, and CT use (odds ratio, 2.38). Odds of hospitalization over time decreased more quickly for patients with CT. Conclusion: CT utilization in the ED has increased significantly from 2005 through 2013. For children, CT use after 2010 decreased, indicating caution about CT use. Male sex, older age, and higher number of comorbidities were predictors of CT in the ED. Over time, odds of hospitalization decreased more quickly for patients with CT