Large-scale Observational Studies Research Articles

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.

Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Jet lag: an underestimated factor in reduced physical performance in athletes

Jet lag is a common issue affecting most athletes traveling across at least 2 time zones, particularly when traveling eastward. Observational studies on over 114,000 game matches have established that traveling teams had a statistically significant higher rate of game losses. Jet lag manifests not only in a decline in athletes' physical performance but also affects cognitive abilities, attention span, and subjective feelings of fatigue. Melatonin can be a very important supplement in helping to regulate the circadian rhythm. Other recommended methods include phototherapy, appropriate meal timing, and sedative medications. This paper aims to gather the latest clinical research assessing athletes' predisposition to jet lag symptoms, large-scale retrospective observational studies evaluating this phenomenon, and discusses the functioning of the circadian rhythm, methods for alleviating jet lag symptoms, and its manifestations.

Association Between IV Contrast Media Exposure and Acute Kidney Injury in Patients Requiring Emergency Admission: A Nationwide Observational Study in Japan.

This study aimed to elucidate the association between IV contrast media CT and acute kidney injury (AKI) and in-hospital mortality among patients requiring emergency admission. In this retrospective observational study, we examined AKI within 48 hours after CT, renal replacement therapy (RRT) dependence at discharge, and in-hospital mortality in patients undergoing contrast-enhanced CT or nonenhanced CT. We performed 1:1 propensity score matching to adjust for confounders in the association between IV contrast media use and outcomes. Subgroup analyses were performed according to age, sex, diagnosis at admission, ICU admission, and preexisting chronic kidney disease (CKD). This study used the Medical Data Vision database between 2008 and 2019. This database is Japan's largest commercially available hospital-based claims database, covering about 45% of acute-care hospitals in Japan, and it also records laboratory results. None. The study included 144,149 patients with (49,057) and without (95,092) contrast media exposure, from which 43,367 propensity score-matched pairs were generated. Between the propensity score-matched groups of overall patients, exposure to contrast media showed no significant risk of AKI (4.6% vs. 5.1%; odds ratio [OR], 0.899; 95% CI, 0.845-0.958) or significant risk of RRT dependence (0.6% vs. 0.4%; OR, 1.297; 95% CI, 1.070-1.574) and significant benefit for in-hospital mortality (5.4% vs. 6.5%; OR, 0.821; 95% CI, 0.775-0.869). In subgroup analyses regarding preexisting CKD, exposure to contrast media was a significant risk for AKI in patients with CKD but not in those without CKD. In this large-scale observational study, IV contrast media was not associated with an increased risk of AKI but concurrently showed beneficial effects on in-hospital mortality among patients requiring emergency admission.

Reassessment of pioglitazone and bladder cancer based on FAERS database

ABSTRACT Background The association between pioglitazone (PLZ) and bladder cancer (BC) remains controversial in several randomized control trials, meta-analyses of multiple prospective studies, and large-scale observational studies. Research design and methods Adverse event (AE) data from 1 January 2004 to 31 March 2024 were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis were applied to quantify the signals of PLZ related BC. Results In total, 17,627,524 AE reports were recorded in the FAERS database, of which 1366 were PLZ-related BCs. More male than female patients were reported. The median age of patients was 70 years old. The peak in the annual report occurred in 2011. A total of 602 AEs reported time to onset (TTO) and the median TTO was 1023 days. In this study, BC and BC recurrence were strong signal, whereas BC stage 0 (with cancer in situ), stage ii and iii were weak signals. Conclusions This study comprehensively demostrated the PLZ-induced risk of BC in patients with diabetes mellitus using the FAERS database. The results demonstrated that the patients treated with PLZ were more likely to develop BC. The male and aging attributed more cases to BC-related reports of PLZ treated patients.

Single point insulin sensitivity estimator index for identifying metabolic syndrome in US adults: NHANES 2017-march 2020

PurposeSingle Point Insulin Sensitivity Estimator (SPISE) index was recently introduced as a reliable indirect indicator of insulin resistance, applicable to large population-based research. Here, we aimed to 1) examine racial/ethnic differences in SPISE index among US adults, 2) compare predictive power of SPISE index for metabolic syndrome (MetSyn) by race/ethnicity, and 3) evaluate its predictive power for MetSyn against other well-known IR indices including Triglyceride/HDL-C, Triglyceride-glucose index, homeostatic model assessment for insulin resistance, and inverse fasting insulin. MethodsA total of 2168 adults (814 white, 690 black, and 664 Hispanic) from NHANES 2017-March 2020 Pre-Pandemic Data was analyzed in this study. MetSyn was defined by the AHA/NHLBI criteria. SPISE index and insulin resistance indices were calculated by using physical and cardiometabolic parameters. ResultsSPISE index was lowest in Hispanic, followed by black and white, with no difference between white vs. black. The area under the curve of receiver operating characteristics of SPISE index for predicting MetSyn was highest in white (88 %), followed by Hispanic (86 %) and black (82 %) (P < 0.05 vs. black), with optimal cutoffs of 5.03, 4.84, and 4.89, respectively. In the total cohort, the predictive power of the SPISE index for MetSyn was 85 %, higher than the other insulin resistance indices (all P < 0.05). ConclusionsSPISE index outperforms various insulin resistance indices for predicting MetSyn in US adults, signifying its potential in large-scale observational studies. Race/ethnicity should be stratified when using the SPISE index as its predictive power and cutoffs for predicting MetSyn vary by race/ethnicity.

Sun Exposure Characteristics among the Indian Population Who Are at Risk for Type 2 Diabetes Mellitus: A Population-Based Cross-Sectional Study

Abstract Background and Aim: Evidence suggests a beneficial effect of sun exposure on type 2 diabetes mellitus (DM). However, little is known about the characteristics of sun exposure among DM patients or individuals at risk of developing DM. The aim of this study was to analyze the sun exposure behaviors of individuals diagnosed with DM and those susceptible to developing DM within a semi-urban community in North India. Materials and Methods: A population-based cross-sectional study was conducted in northern India with 494 participants aged 25–60, with or without DM. The participants’ sun exposure characteristics were assessed through a sunlight exposure questionnaire, and total sun exposure in a day was computed using the veritable sun exposure (VSE) index. Fasting blood sugar, anthropometric measurements, and demographic details were also collected. Results: The study had 56.5% female participants, and 9.1% of the participants had DM. The VSE of the study participants ranged from 0.01 to 0.81, with a mean of 0.15 (±0.14) and a median of 0.10, indicating that more than half of the study samples had less than 10% h/day of sunlight exposure. The use of sunscreen, gender, and disease status all influenced VSE. Our data suggest that the characteristics of sun exposure among Indians significantly deviate from standard recommendations. Conclusion: Our results propose a need for evidence-based guidelines and policies that promote awareness about sun exposure among DM patients as well as those at risk of developing DM. Nevertheless, these findings need to be validated through large-scale observational studies.

Real-World Effectiveness of Nirmatrelvir in Protecting Long COVID for Outpatient Adult Patients - A Large-Scale Observational Cohort Study from the RECOVER Initiative.

Paxlovid has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30-180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 1, 2023, and among which 165,256 were treated with Paxlovid within 5 days since infection and 307,922 were not treated with Paxlovid or other COVID-19 treatments. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). Paxlovid treatment was associated with reduced risk of all-cause death (HR, 0.53, 95% CI 0.46 to 0.60; risk reduction 0.23 events per 100 persons, 95% CI 0.19 to 0.28) and hospitalization (HR, 0.70, 95% CI 0.68 to 0.73; risk reduction 2.37 events per 100 persons, 95% CI 2.19 to 2.56) in the post-acute phase. For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. Overall, high-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.

Antibiotic treatment to prevent pediatric acute otitis media infectious complications: A meta-analysis.

Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of antibiotics versus watchful waiting have focused on symptom resolution and RCTs, limiting the assessment of serious, rare complications. We sought to evaluate these complications by including observational studies. RCTs and observational studies that compared antibiotics to placebo or watchful waiting for pediatric clinician diagnosed AOM were identified [PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, and Web of Science] and reviewed for meta-analysis. Two reviewers independently extracted study characteristics, patient characteristics, and outcomes. We assessed publication bias, study bias with ROBINS-1 and RoB-2 and used random-effects models to assess treatment effects. 24 studies were included. Antibiotics decreased the risk of acute mastoiditis [incidence 0.02%, RR 0.48, 95% CI 0.40-0.59; NNT 5,368]. This protective effect may be underestimated because of misclassification of non-suppurative conditions as AOM. Intracranial complications remained too rare to assess. Antibiotics markedly increased the risk of adverse effects [incidence 10.5%, RR 1.49, 1.27-1.73; NNH 23]. Studies used non-specific criteria for acute mastoiditis, potentially underestimating treatment effects. Prompt antibiotic therapy reduces the risk for some AOM complications. The NNT to prevent serious, rare complications is high, while the NNH is relatively low. Large-scale population-based observational studies using real-world datasets with validated measures of severe complications are needed to improve understanding of risk factors for serious AOM complications, facilitate more selective antibiotic therapy, and optimize individual outcomes and public health.

Development of disease-modifying therapies against Alzheimer's disease.

To successfully develop disease-modifying therapies (DMT) against Alzheimer's disease (AD), it is important to target the mild stage of the disease, before the pathological changes progress and dementia symptoms are fully manifested. To this end, the AD Neuroimaging Initiative (ADNI), a large-scale observational study, was initiated in the U.S. with the goal of development of DMT that are effective in the early stages of mild cognitive impairment (MCI) by utilizing imaging and biomarkers. In Japan, J-ADNI enrolled and followed up 537 patients, mainly with MCI, and established a platform for evaluation including amyloid PET, and demonstrated a high similarity in the clinical course of amyloid-positive MCI (prodromal AD) in Japan and the U.S. In 2023, the anti-Aβ antibody lecanemab successfully completed a Phase III clinical trial for early AD (prodromal AD + mild AD dementia) and was granted regulatory approval and made available both in the US and Japan. Also, phase III trial of donanemab was completed successful. The J-TRC study was initiated in Japan as a "trial ready cohort (TRC)" consisting of participants who met the eligibility criteria for participation in preclinical and prodromal AD trials. Based on such a platform, the development of DMT for AD will progress more rapidly in the future.

Prognostic and predictive value of ctDNA-based MRD and actionable biomarkers in patients with resectable colorectal cancer: CIRCULATE-Japan GALAXY.

3609 Background: The role of biomarker-guided therapy for resectable colorectal cancer (CRC) remains unestablished. Circulating tumor DNA (ctDNA) has emerged as a minimally invasive biomarker for detecting molecular residual disease (MRD) and predicting recurrence. Tumor-informed ctDNA testing offers the advantage of tumor sequencing and MRD detection in a single workflow, suggesting its potential for facilitating integration of biomarker-guided therapy into perioperative treatment. Methods: GALAXY, a large-scale prospective observational study, monitored post-surgical ctDNA MRD status in patients with clinical stage II to IV or relapsed CRC (UMIN000039205). Tumor tissue and matched normal DNA were processed for whole-exome sequencing (WES) to identify and track patient-specific somatic single nucleotide variants (SNVs), for ctDNA detection in the associated patients’ plasma samples. Actionable biomarkers having OncoKB therapeutic levels 1-3 were explored and identified separately from the Signatera test (through WES data). Results: Of the 4,590 patients enrolled between May 2020, and October 2022, 2,695 who were not enrolled in randomized trials and had available WES data were included in this analysis. Identified actionable biomarkers included RAS/ BRAF wild-type in 1,369 (50.8%) patients, tumor mutational burden (TMB) high in 256 (10.3%), MSI high in 236 (9.5%), BRAF V600E in 176 (6.5%), KRAS G12C in 61 (2.3%), ERBB2 amplification in 47 (1.7%), TP53 Y220C in 33 (1.2%), NTRK1/ 2/ 3 fusion in 1 (0.04%), and RET fusion in 1 (0.04%). ctDNA positivity during the MRD window (2 to 10 weeks post-surgery) varied from 5.1% in those with TMB high and MSI high to 29.8% in those with ERBB2 amplification. ERBB2 amplification was the only actionable biomarker significantly associated with ctDNA positivity during the MRD window (odds ratio 2.20). Positive ctDNA MRD status correlated with significantly worse DFS across all actionable biomarkers, with hazard ratios ranging from 8.46 for TP53 Y220C to 5.53e+8 for BRAF V600E. In MSI high disease, recurrence was observed in only 3 of 225 (1.3%) patients with negative ctDNA compared to 5 of 12 (41.7%) with positive ctDNA during the MRD window. Adjustment by the propensity score revealed that adjuvant chemotherapy provided survival benefits in ctDNA-positive patients with pathological stage II and III disease across various biomarkers. In patients with one or more actionable mutations selected among the16-plex of the ctDNA MRD assay, those variants were detected at time of disease recurrence. Conclusions: Our study highlights the importance of ctDNA-based MRD as both a prognostic and predictive tool for CRC across different actionable biomarkers. These findings suggest the potential of MRD-driven targeted therapeutic strategies for CRC with specific actionable biomarkers. Clinical trial information: UMIN000039205.

Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study protocol KCSG AL-22–09

BackgroundNext-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform.MethodsThe KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment.DiscussionThis pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers.Trial registrationNCT05525858.

Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study.

: A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

Long-term follow-up results of facial nerve schwannoma with good facial nerve function: a multicenter study.

Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H-B) grade, of which two patients deteriorated from H-B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H-B grade according to tumor size at the time of diagnosis or change in tumor size. We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function.

Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence.

Inhaled nitric oxide (NO) has been used in pediatric and adult perioperative cardiac intensive care for over three decades. NO is a cellular signaling molecule that induces smooth muscle relaxation in the mammalian vasculature. Inhaled NO has the unique ability to exert its vasodilatory effects in the pulmonary vasculature without any hypotensive side-effects in the systemic circulation. In patients undergoing cardiac surgery, NO has been reported in numerous studies to exert beneficial effects on acutely lowering pulmonary artery pressure and reversing right ventricular dysfunction and/or failure. Yet, various investigations failed to demonstrate significant differences in long-term clinical outcomes. The authors, serving as an advisory board of international experts in the field of inhaled NO within pediatric and adult cardiac surgery, will discuss how the existing scientific evidence can be further improved. We will summarize the basic mechanisms underlying the clinical applications of inhaled NO and how this translates into the mandate for inhaled NO in cardiac surgery. We will move on to the popular use of inhaled NO and will talk about the evidence base of the use of this selective pulmonary vasodilator. This review will elucidate what kind of clinical and biological barriers and gaps in knowledge need to be solved and how this has impacted in the development of clinical trials. The authors will elaborate on how the optimization of inhaled NO therapy, the development of biomarkers to identify the target population and the definition of response can improve the design of future large clinical trials. We will explain why it is mandatory to gain an international consensus for the state of the art of NO therapy far beyond this expert advisory board by including the different major players in the field, such as the different medical societies and the pharma industry to improve our understanding of the real-life effects of inhaled NO in large scale observational studies. The design for future innovative randomized controlled trials on inhaled NO therapy in cardiac surgery, adequately powered and based on enhanced biological phenotyping, will be crucial to eventually provide scientific evidence of its clinical efficacy beyond its beneficial hemodynamic properties.

A novel measure to summarize blood transfusion practice during critical illness.

Large-scale observational studies have summarized transfusion practice using traditional measures of central tendency (e.g., the mean hemoglobin concentration at the time of transfusion). However, the mean hemoglobin concentration fails to identify specific hemoglobin concentration thresholds that drive practice. In the following brief report, we propose a novel measure of "practice discontinuity" that identifies specific practice-defining hemoglobin thresholds. We used the PINC AI Database (2016-2022) to identify adult patients admitted to an intensive care unit with at least one hemoglobin concentration measurement. For each day that hemoglobin was measured, we identified whether the patient received a red blood cell transfusion using hospital charge codes. We defined the "practice discontinuity" measure as the hemoglobin concentration at which there was the largest increase in transfusion use going from a higher to an incrementally lower hemoglobin concentration. We also calculated the mean and median pretransfusion hemoglobin concentrations. We identified 1,298,367 patients and 4,905,839 patient-days for inclusion. RBC transfusion occurred in a total of 530,654 (10.8%) patient-days. The overall pre-transfusion mean and median hemoglobin concentrations were 8.4 and 8.0 g/dL, respectively. The practice discontinuity measure identified 7.0 g/dL as the hemoglobin concentration at which transfusion use increased the most, from 46.6% of patient-days at a concentration of 7.0 g/dL to 74.8% of patient-days at a concentration of 6.9 g/dL. We propose that future studies of red blood cell transfusion practice consider inclusion of the practice discontinuity measure to more fully summarize clinical practice.

Abstract 14: Post-Traumatic Stress Disorder Symptoms and Physical Activity Behavior After Hospitalization for Suspected Acute Coronary Syndromes

Background: An acute coronary syndrome (ACS) related event can induce post-traumatic stress disorder (PTSD), and post-ACS PTSD is associated with a greater risk for secondary clinical outcomes among ACS survivors. While moderate-vigorous physical activity (MVPA) has been shown to reduce the risk of adverse outcomes after ACS, its impact on PTSD symptoms remains largely unknown. There is a notable absence of empirical evidence, especially from large-scale observational cohort studies with device-based measures of physical activity, on this topic. Aim: To investigate the relationship between physical activity behaviors over the first month post-discharge with PTSD symptoms at one month among patients with suspected ACS. Methods: Patients (n = 434, 48.6% female, 62.6±12.4yrs) evaluated for ACS in the emergency department were fitted with a GENEActiv wrist accelerometer in-hospital and wore the device on their non-dominant wrist for 30 days post-discharge to measure MVPA. Presence and severity of PTSD symptoms were assessed at 1-month follow-up using the PCL-5. Multilevel structural equation modeling was used to simultaneously 1) fit a linear growth curve (GC) model to patients’ 30-day trajectories of MVPA and 2) predict total PTSD symptoms from a) mean daily MVPA, b) average daily change in MVPA (GC slope), and c) covariates (age, biological sex, education, and Charlson Comorbidity Index). Results: Patients engaged in an average of 20.8 (95% CI: 18.4, 23.3, p &lt; 0.001) minutes of MVPA per day. MVPA levels increased at an average rate of 0.11 mins/day (95% CI: 0.05, 0.16, p &lt; 0.001) over the 30 days post-discharge. There was substantial between-patient variability in both average MVPA minutes (SD = 26.0) and daily rate of change in MVPA minutes (SD = 0.38). The daily rate of change in MVPA was significantly associated with 1-month PTSD symptoms (β per 0.5 mins/day difference in daily rate of change in MVPA minutes = -4.5 points on the PCL-5; 95% CI: -6.5, -2.5, p &lt; 0.001), controlling for the above-mentioned covariates. The association between average MVPA minutes and PCL-5 score was small and not statistically significant (β = 0.02; 95% CI: -0.04, 0.07, p = 0.60). Conclusion: PTSD symptoms appear to be mitigated in patients whose MVPA minutes increased over the 30 days post-discharge, whereas no evident association was observed between PTSD symptoms and average daily MVPA minutes. These findings suggest that progressively increasing MVPA by as little as .5 mins/day (i.e., ~1 SD above the mean rate of increase) within the immediate first month post-discharge, as opposed to maintaining a consistent daily average of MVPA, may impede the development of PTSD symptoms in ACS survivors.

H. pylori infection and osteoporosis: a large-scale observational and mendelian randomization study

PurposeThere is controversy concerning the relationship between Helicobacter pylori (H. pylori) infection and osteoporosis. This study is to examine the causal relationship between H. pylori infection and osteoporosis and to analyze the potential mechanism underlying the relationship.MethodsThe clinical data of H. pylori infection and bone mineral density from patients or physical examiner with good general condition in our hospital between September 2019 and September 2020 were retrospectively collected. The relationship between H. pylori infection and osteoporosis was compared and analyzed, using logistic regression to examine the potential mechanism underlying the association. To investigate the causal effects of H. pylori infection and osteoporosis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis.ResultsA total of 470 patients were positive for H. pylori, with a detection rate of 52.22%. It was found that age, SBP, FPG, DBP, ALB, LDL-C, hs-CRP, and OC were positively correlated with osteoporosis, while negative correlations were observed with BMI, LYM, ALB, TP, TG, HDL-C, SCr, UA, and VitD. After stratified analysis of sex and age, it was found that there was a significant correlation between H. pylori infection and osteoporosis. The levels of SBP, ALP, FPG, LDL-C, hs-CRP, and OC in both H. pylori-positive group and osteoporosis group were higher than those in the H. pylori-negative group while the levels of BMI, ALB, TP, HDL-C, SCr, UA, and VitD in the positive group were significantly lower than those in the negative group. Logistic regression analyses with gender and age showed that ALB, FPG, HDL-C, and VitD were common risk factors for osteoporosis and H. pylori infection. In the MR analysis, the IVW results found a positive effect of H. pylori infection on osteoporosis (OR = 1.0017, 95% CI: 1.0002–1.0033, P = 0.0217). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of osteoporosis on H. pylori infection.ConclusionOur study provides evidence for causal effects of H. pylori infection on osteoporosis. H. pylori may affect osteoporosis through serum albumin, high-density lipoprotein, fasting blood glucose and vitamin D.

The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies

Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative ‘backbone’ of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.

Comparative estimation of the effects of antihypertensive medications on schizophrenia occurrence: a multinational observational cohort study

BackgroundThe association between antihypertensive medication and schizophrenia has received increasing attention; however, evidence of the impact of antihypertensive medication on subsequent schizophrenia based on large-scale observational studies is limited. We aimed to compare the schizophrenia risk in large claims-based US and Korea cohort of patients with hypertension using angiotensin-converting enzyme (ACE) inhibitors versus those using angiotensin receptor blockers (ARBs) or thiazide diuretics.MethodsAdults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia.Results5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99–1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78–1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71–1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05–1.43]).ConclusionsThe risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years.

Antenatal corticosteroid administration is associated with lower risk of severe ROP in preterm twin infants

IntroductionRobust evidence revealed the impact of antenatal corticosteroid (ACS) administration on lower mortality and short-term neonatal outcomes in singleton preterm infants. We aimed to investigate the impact of ACS therapy on morbidity and mortality in preterm twin infants. MethodsWe conducted this retrospective single-center study from to the records of twin babies of 24–30 weeks of gestation admitted to the neonatal intensive care unit. The study population was grouped based on the exposure to ACS 1–7 days before birth as received or not. Groups were compared regarding in-hospital mortality and neonatal outcomes. ResultsData from 160 twin infants were analyzed. Of those, 102 (64 %) were administered ACS. The median (IQR) gestational age and birth weight of the whole cohort were 28 (27–29) weeks and 1060 (900–1240) g, respectively. ACS administration was associated with a significant decline in respiratory distress syndrome (RDS), requirement ≥2 doses of surfactant, severe intraventricular hemorrhage (IVH), early-onset sepsis (EOS), and retinopathy of prematurity (ROP) requiring treatment (p < 0.05). Logistic regression analysis revealed that gestational age (OR 0.29 95 % CI 0.14–0.62; p = 0.001), ACS administration (OR 0.14 95 % CI 0.03–0.85; p = 0.032), and time to achieve full enteral feeding (OR 1.16 95 % CI 1.03–1.31; p = 0.019) were independently associated with the risk of severe ROP. ConclusionThe reduction in the risk of severe ROP besides RDS, severe IVH, and EOS among preterm twins who received ACS was remarkable in our study similar to the trials conducted in preterm singletons. However, large-scale prospective observational studies are required to reveal the efficacy of ACS in preterm twins.