Nevin Manimala

Ann Noninvasive Electrocardiol. 2021 Dec 29:e12929. doi: 10.1111/anec.12929. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate a new risk score for acute chest pain with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

METHODS: Patients who suffered from Chest pain and suspected NSTE-ACS were enrolled as subjects. Predictor variables had been analyzed, and a bootstrap technique was used to evaluate the internal validity of the model, and external validation had been assessed for a prospective cohort study.

RESULTS: Thousand five hundred and sixty-eight patients had been included in this study. Six predictor variables were found to be significant and were used to develop the model. The C-statistic of the model was 0.83, and internal validation revealed the stability of the model and the absence of over-optimism. Patients were given different triage recommendations, and the risk score was prospectively validated.

CONCLUSIONS: A risk score may be a suitable method for assessing the risk of major adverse cardiac events and aiding patient triage in emergency departments among patients with suspected NSTE-ACS.

PMID:34964535 | DOI:10.1111/anec.12929

J Magn Reson Imaging. 2021 Dec 29. doi: 10.1002/jmri.28038. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease with common musculoskeletal manifestations, notably reductions in bone quality. Bone marrow adipose tissue composition and quantity has been previously linked to bone quality and may play a role in SLE pathophysiology but has not been thoroughly studied.

PURPOSE: To use magnetic resonance spectroscopy (MRS) to investigate bone marrow adipose tissue quantity and composition in proximal femur subregions of untreated SLE patients compared to controls and treated patients.

STUDY TYPE: Prospective.

SUBJECTS: A total of 64 female subjects: 28 SLE, 15 glucocorticoid (GC)-treated SLE and 21 matched controls.

FIELD STRENGTH/SEQUENCE: Stimulated echo acquisition mode (STEAM) sequence at 3 T.

ASSESSMENT: MRS was performed at multiple echo times in the femoral neck and trochanter regions and fatty acids (FA) composition was computed.

STATISTICAL TESTS: Intergroup comparisons were carried out using ANOVA. A P value < 0.05 was considered statistically significant.

RESULTS: SLE patients had significantly higher saturated FA compared to controls in both the femoral neck (+0.12) and trochanter (+0.11), significantly lower monounsaturated FA in the trochanter compared to controls (-0.05), and significantly lower polyunsaturated FA in the femoral neck compared to both controls (-0.07) and SLE patients on GC therapy (-0.05).

DATA CONCLUSION: SLE patients have altered proximal femur marrow fat metabolism, which may reflect a manifestation of, or play a role in, the altered inflammatory response of these patients.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

PMID:34964533 | DOI:10.1002/jmri.28038

J Magn Reson Imaging. 2021 Dec 29. doi: 10.1002/jmri.28037. Online ahead of print.

ABSTRACT

BACKGROUND: Automated magnetic resonance imaging (MRI) volumetry is a promising tool to evaluate regional brain volumes in dementia and especially Alzheimer’s disease (AD).

PURPOSE: To compare automated methods and the gold standard manual segmentation in measuring regional brain volumes on MRI across healthy controls, patients with mild cognitive impairment, and patients with dementia due to AD.

STUDY TYPE: Systematic review and meta-analysis.

DATA SOURCES: MEDLINE, Embase, and PsycINFO were searched through October 2021.

FIELD STRENGTH: 1.0 T, 1.5 T, or 3.0 T.

ASSESSMENT: Two review authors independently identified studies for inclusion and extracted data. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).

STATISTICAL TESTS: Standardized mean differences (SMD; Hedges’ g) were pooled using random-effects meta-analysis with robust variance estimation. Subgroup analyses were undertaken to explore potential sources of heterogeneity. Sensitivity analyses were conducted to examine the impact of the within-study correlation between effect estimates on the meta-analysis results.

RESULTS: Seventeen studies provided sufficient data to evaluate the hippocampus, lateral ventricles, and parahippocampal gyrus. The pooled SMD for the hippocampus, lateral ventricles, and parahippocampal gyrus were 0.22 (95% CI -0.50 to 0.93), 0.12 (95% CI -0.13 to 0.37), and -0.48 (95% CI -1.37 to 0.41), respectively. For the hippocampal data, subgroup analyses suggested that the pooled SMD was invariant across clinical diagnosis and field strength. Subgroup analyses could not be conducted on the lateral ventricles data and the parahippocampal gyrus data due to insufficient data. The results were robust to the selected within-study correlation value.

DATA CONCLUSION: While automated methods are generally comparable to manual segmentation for measuring hippocampal, lateral ventricle, and parahippocampal gyrus volumes, wide 95% CIs and large heterogeneity suggest that there is substantial uncontrolled variance. Thus, automated methods may be used to measure these regions in patients with AD but should be used with caution.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

PMID:34964531 | DOI:10.1002/jmri.28037

Clin Transplant. 2021 Dec 29:e14576. doi: 10.1111/ctr.14576. Online ahead of print.

ABSTRACT

BACKGROUND: African-American (AA) has historically been associated with inferior graft survival after pancreas transplantation. However, with the improvement of immunosuppression and surgical technique, we hypothesized that the racial disparity has been neutralized.

METHODS: We analyzed data from the Scientific Registry of Transplant Recipients (1989-2018). Using Kaplan-Meier estimation and Cox proportional hazards regression, we examined the influence of race on pancreatic graft survival.

RESULTS: Before 2009, AA recipients had a higher risk of pancreatic graft failure after adjusting for confounding factors (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.08-1.24), but the risks for Hispanic and Asian recipients were both comparable to their Caucasian counterparts. However, the risk of pancreatic graft failure in AA recipients dropped to 1% and was no longer significant since 2009 (HR: 1.01, 95%CI: 0.88-1.16). Interestingly, donor race showed similar results. Furthermore, the concordance statistic of the complete pancreas donor risk index (including donor race) was 0.582, whereas the concordance did not change when donor race was eliminated from the model.

CONCLUSIONS: AA and other races have shown similar pancreatic graft survival in the modern era. Furthermore, donor racial disparity also seems neutralized; thus, donor race should not be considered as an indicator of pancreatic donor quality. This article is protected by copyright. All rights reserved.

PMID:34964519 | DOI:10.1111/ctr.14576

Stat Med. 2022 Jan 15;41(1):146-162. doi: 10.1002/sim.9227. Epub 2021 Oct 20.

ABSTRACT

Identifying transmission of hot spots with temporal trends is important for reducing infectious disease propagation. Cluster analysis is a particularly useful tool to explore underlying stochastic processes between observations by grouping items into categories by their similarity. In a study of epidemic propagation, clustering geographic regions that have similar time series could help researchers track diffusion routes from a common source of an infectious disease. In this article, we propose a two-stage scan statistic to classify regions into various geographic clusters by their temporal heterogeneity. The proposed scan statistic is more flexible than traditional methods in that contiguous and nonproximate regions with similar temporal patterns can be identified simultaneously. A simulation study and data analysis for a dengue fever infection are also presented for illustration.

PMID:34964513 | DOI:10.1002/sim.9227

Paediatr Perinat Epidemiol. 2021 Dec 29. doi: 10.1111/ppe.12847. Online ahead of print.

ABSTRACT

BACKGROUND: Severe maternal morbidity (SMM) is a key indicator of maternal health. Generally explored without distinction by the timing of the event, it mainly reflects postpartum SMM. Although antepartum (pre-labour) SMM presents specific challenges in its need to optimise the risk-benefit balance for both mother and foetus, its features remain inadequately explored.

OBJECTIVES: We explored risk factors of antepartum SMM and described adverse delivery and neonatal outcomes associated with antepartum SMM.

METHODS: We designed a population-based nested case-control study based on data from the EPIMOMS study (119 maternity hospitals of 6 French regions, 2012-2013, N = 182,309 deliveries in the source cohort). This study included all women with antepartum SMM (cases, n = 601) compared to a randomly selected sample of women who gave birth without SMM in the same hospitals (controls, n = 3651). Antepartum SMM risk factors were identified with multivariable logistic regression following imputations for missing data.

RESULTS: Antepartum SMM complicated 0.33% (95% confidence interval [CI] 0.30, 0.36) of pregnancies. Antepartum SMM risk factors were maternal age ≥35 years (adjusted odds ratio [OR] 1.55, 95% CI 1.22, 1.97), increased body mass index (OR for 5 kg/m² increase, 1.24, 95% CI 1.14, 1.36), maternal birth in sub-Saharan Africa (OR 1.80, 95% CI 1.29, 2.53), pre-existing medical condition (OR 2.56, 95% CI 1.99, 3.30), nulliparity (OR 2.26, 95% CI 1.83, 2.80), previous pregnancy-related hypertensive disorders (OR 4.94, 95% CI 3.36, 7.26), multiple pregnancy (OR 5.79, 95% CI 3.75, 7.26), irregular prenatal care (OR 1.86, 95% CI 1.27, 2.72). For women with antepartum SMM, preterm delivery, neonatal mortality and transfer to the neonatal intensive care unit were 10 times more frequent than for controls. Emergency caesarean and general anaesthesia were more frequent in women with antepartum SMM.

CONCLUSIONS: Antepartum SMM is rare but associated with increased rates of adverse delivery and neonatal outcomes.

PMID:34964499 | DOI:10.1111/ppe.12847

J Clin Pharmacol. 2021 Dec 29. doi: 10.1002/jcph.2021. Online ahead of print.

ABSTRACT

Astegolimab is a fully human immunoglobulin G2 monoclonal antibody (mAb) that binds to the ST2 receptor and blocks the interleukin-33 signaling. It was evaluated in patients with uncontrolled severe asthma in the Phase 2b study (Zenyatta) at doses of 70, 210, 490 mg subcutaneous every 4 weeks (Q4W) for 52 weeks. This work aimed to characterize astegolimab pharmacokinetics, identify influential covariates contributing to its inter-individual variability, and make a descriptive assessment of the exposure-response relationships. A population pharmacokinetic model was developed using data from 368 patients in the Zenyatta study. Predicted average steady-state concentration was used in the subsequent exposure-response analyses, which evaluated efficacy (asthma exacerbation rate) and biomarker endpoints including forced expiratory volume in 1 second, fraction exhaled nitric oxide, blood eosinophils, and soluble ST2. A two-compartment disposition model with first-order elimination and first-order absorption best described the astegolimab pharmacokinetics. The relative bioavailability for the 70 mg dose was 15.3% lower. Baseline body weight, estimated glomerular filtration rate, and eosinophils were statistically correlated with pharmacokinetic parameters, but only body weight had a clinically meaningful influence on the steady-state exposure (ratios exceeding 0.8-1.25). The exposure-response of efficacy and biomarkers were generally flat with a weak trend in favor of the highest dose/exposure. This study characterized astegolimab pharmacokinetics in patients with asthma and showed typical pharmacokinetic behavior as a mAb-based drug. The exposure-response analyses suggested the highest dose tested in the Zenyatta study (490 mg Q4W) performed close to the maximum effect, and no additional response may be expected above it. This article is protected by copyright. All rights reserved.

PMID:34964491 | DOI:10.1002/jcph.2021

Europace. 2021 Dec 29:euab298. doi: 10.1093/europace/euab298. Online ahead of print.

ABSTRACT

AIMS: Complexity of the ventricular tachycardia (VT) substrate and the size and thickness of infarction area border zones differ based on location of myocardial infarctions (MIs). These differences may translate into heterogeneity in the effectiveness of treatments. This study aims to examine the influence of infarct location on the effectiveness of VT ablation in comparison with escalated pharmacological therapy in patients with prior MI and antiarrhythmic drug (AAD)-refractory VT.

METHODS AND RESULTS: VANISH trial participants were categorized based on the presence or absence of an inferior MI scar. Inverse probability of treatment weighted Cox models were calculated for each subgroup. Of 259 randomized patients (median age 69.8 years, 7.0% women), 135 had an inferior MI and 124 had a non-inferior MI. Among patients with an inferior MI, no statistically significant difference in the composite primary outcome of all-cause mortality, appropriate implantable cardioverter-defibrillator (ICD) shock, and VT storm was detected between treatment arms [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (CI) 0.51-1.20]. In contrast, patients with non-inferior MIs had a statistically significant reduction in the incidence of the primary outcome with ablation (aHR 0.48, 95% CI 0.27-0.86). In a sensitivity analysis of anterior MI patients (n = 83), a trend towards a reduction in the primary outcome with ablation was detected (aHR 0.50, 95% CI 0.23-1.09).

CONCLUSION: The effectiveness of VT ablation versus escalated AADs varies based on the location of the MI. Patients with MI scars located only in non-inferior regions of the ventricles derive greater benefit from VT ablation in comparison to escalation of AADs in reducing VT-related events.

PMID:34964475 | DOI:10.1093/europace/euab298

Eur J Cardiovasc Nurs. 2021 Dec 29:zvab123. doi: 10.1093/eurjcn/zvab123. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac surgeries pose as an emotional experience for patients. Preoperative education is known to positively alter people’s perceptions, emotions, and mitigate surgical distress. However, this intervention’s effectiveness in improving perioperative outcomes among patients undergoing cardiac surgery lacked rigorous statistical synthesis and remains inconclusive.

AIMS: The aim was to synthesize the effectiveness of preoperative education on improving perioperative outcomes [anxiety, depression, knowledge, pain intensity, pain interference with daily activities, postoperative complications, length of hospitalization, length of intensive care unit (ICU) stay, satisfaction with the intervention and care, and health-related quality of life] among patients undergoing cardiac surgery.

METHODS: This systematic review and meta-analysis conducted a comprehensive search of nine electronic databases (PubMed, EMBASE, Scopus, MEDLINE, CINAHL, Cochrane CENTRAL, Web of Science, PsycINFO, and ERIC) and grey literature for randomized controlled trials examining the preoperative educational interventional effects on patients undergoing cardiac surgery from inception to 31 December 2020. The studies’ quality was evaluated using Cochrane Risk-of-Bias Tool 1 (RoB1). Meta-analyses via RevMan 5.4 software synthesized interventional effects.

RESULTS: Twenty-two trials involving 3167 participants were included. Preoperative education had large significant effects on reducing post-intervention preoperative anxiety (P = 0.02), length of ICU stay (P = 0.02), and improving knowledge (P < 0.00001), but small significant effect sizes on lowering postoperative anxiety (P < 0.0001), depression (P = 0.03), and enhancing satisfaction (P = 0.04).

CONCLUSIONS: This review indicates the feasibility of preoperative education in clinical use to enhance health outcomes of patients undergoing cardiac surgery. Future studies need to explore knowledge outcomes in-depth and more innovative technologies in preoperative education delivery.

PMID:34964470 | DOI:10.1093/eurjcn/zvab123

Hum Mol Genet. 2021 Nov 23:ddab341. doi: 10.1093/hmg/ddab341. Online ahead of print.

ABSTRACT

Mitochondrial DNA copy number (mtDNAcn) variation has been associated with increased risk of several human diseases in epidemiological studies. The quantification of mtDNAcn performed with real-time PCR is currently considered the de facto standard among several techniques. However, the heterogeneity of the laboratory methods (DNA extraction, storage, processing) used could give rise to results that are difficult to compare and reproduce across different studies. Several lines of evidence suggest that mtDNAcn is influenced by nuclear and mitochondrial genetic variability, however this relation is largely unexplored. The aim of this work was to elucidate the genetic basis of mtDNAcn variation. We performed a genome-wide association study (GWAS) of mtDNAcn in 6836 subjects from the ESTHER prospective cohort, and included, as replication set, the summary statistics of a GWAS that used 295 150 participants from the UK Biobank. We observed two novel associations with mtDNAcn variation on chromosome 19 (rs117176661), and 12 (rs7136238) that reached statistical significance at the genome-wide level. A polygenic score that we called mitoscore including all known single nucleotide polymorphisms explained 1.11% of the variation of mtDNAcn (p = 5.93 × 10-7). In conclusion, we performed a GWAS on mtDNAcn, adding to the evidence of the genetic background of this trait.

PMID:34964454 | DOI:10.1093/hmg/ddab341