Tag: pubmed

Public Health Rep. 2022 Jul 16:333549221110300. doi: 10.1177/00333549221110300. Online ahead of print.

ABSTRACT

OBJECTIVES: The impact and risk of SARS-CoV-2 transmission from asymptomatic and presymptomatic hosts remains an open question. This study measured the secondary attack rates (SARs) and relative risk (RR) of SARS-CoV-2 transmission from asymptomatic and presymptomatic index cases as compared with symptomatic index cases.

METHODS: We used COVID-19 test results, daily health check reports, and contact tracing data to measure SARs and corresponding RRs among close contacts of index cases in a cohort of 12 960 young adults at the University of Notre Dame in Indiana for 103 days, from August 10 to November 20, 2020. Further analysis included Fisher exact tests to determine the association between symptoms and COVID-19 infection and z tests to determine statistical differences between SARs.

RESULTS: Asymptomatic rates of transmission of SARS-CoV-2 were higher (SAR = 0.19; 95% CI, 0.14-0.24) than was estimated in prior studies, producing an RR of 0.75 (95% CI, 0.54-1.07) when compared with symptomatic transmission. In addition, the transmission rate associated with presymptomatic cases (SAR = 0.25; 95% CI, 0.21-0.30) was approximately the same as that for symptomatic cases (SAR = 0.25; 95% CI, 0.19-0.31). Furthermore, different symptoms were associated with different transmission rates.

CONCLUSIONS: Asymptomatic and presymptomatic hosts of SARS-CoV-2 are a risk for community spread of COVID-19, especially with new variants emerging. Moreover, typical symptom checks may easily miss people who are asymptomatic or presymptomatic but still infectious. Our study results may be used as a guide to analyze the spread of SARS-CoV-2 variants and help inform appropriate public health measures as they relate to asymptomatic and presymptomatic cases.

PMID:35848117 | DOI:10.1177/00333549221110300

Am Surg. 2022 Jul 18:31348221091937. doi: 10.1177/00031348221091937. Online ahead of print.

ABSTRACT

The purpose of this study was to identify the population of pediatric patients who arrive without signs of life and describe outcomes using a national database.Patients eighteen and younger with no signs of life were pulled from the National Trauma Database (NTDB) from the years 2007-2016. A total of N = 7503 patients were separated into two cohorts for comparison. Subset analysis was also conducted for patients undergoing a thoracotomy. Statistical analysis was performed on the collected data. Over the 9-year period most patients died in the ED or hospital (95.7%), very few patients were discharged home (1.3%), and ED thoracotomies were performed rarely (9%) with most patients dying (97%).Arrival to the trauma bay without signs of life is associated with a dismal prognosis. Clinical judgment must be carefully applied to choose the small number of patients who would benefit from an aggressive approach.

PMID:35848107 | DOI:10.1177/00031348221091937

Eur J Drug Metab Pharmacokinet. 2022 Jul 18. doi: 10.1007/s13318-022-00773-w. Online ahead of print.

ABSTRACT

BACKGROUND: Lucitanib is an oral, potent, selective inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1‒3, fibroblast growth factor receptors 1‒3, and platelet-derived growth factor receptors alpha/beta.

OBJECTIVE: We aimed to develop a population pharmacokinetics (PopPK) model for lucitanib in patients with advanced cancers.

METHODS: PopPK analyses were based on intensive and sparse oral pharmacokinetic data from 5 phase 1/2 clinical studies of lucitanib in a total of 403 patients with advanced cancers. Lucitanib was administered at 5‒30 mg daily doses as 1 of 2 immediate-release oral formulations: a film-coated tablet or a hard gelatin capsule.

RESULTS: Lucitanib pharmacokinetics were best described by a 2-compartment model with zero-order release into the dosing compartment, followed by first-order absorption and first-order elimination. Large between-subject pharmacokinetic variability was partially explained by body weight. No effects of demographics or tumor type on lucitanib pharmacokinetics were observed. The model suggested that the formulation impacted release duration (tablet, 0.243 h; capsule, 0.814 h), but the effect was not considered clinically meaningful. No statistically significant effects were detected for concomitant cytochrome P450 (CYP) 3A4 inhibitors or inducers, CYP2C8 or P-glycoprotein inhibitors, serum albumin, mild/moderate renal impairment, or mild hepatic impairment. Concomitant proton pump inhibitors had no clinically significant effect on lucitanib absorption.

CONCLUSIONS: The PopPK model adequately described lucitanib pharmacokinetics. High between-subject pharmacokinetic variability supports a safety-based dose-titration strategy currently being used in an ongoing clinical study of lucitanib to optimize drug exposure and clinical benefit.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01283945, NCT02053636, ISRCTN23201971, NCT02202746, NCT02109016.

PMID:35844029 | DOI:10.1007/s13318-022-00773-w

J Egypt Natl Canc Inst. 2022 Jul 18;34(1):30. doi: 10.1186/s43046-022-00133-4.

ABSTRACT

OBJECTIVE: Glioblastoma Multiforme (GBM), a devastating the most common primary malignant intracranial brain tumors. In India, the incidence of this malignancy is escalating, however, there are very few studies on this tumor entity from Indian population. The present study sought to investigate the prevalence and prognostic significance of Signal Transducer and Activator of Transcription 3 (STAT3) gene expression in GBM patients from Western India.

METHOD: STAT3 gene expression using real-time PCR was detected in total 55 GBM patients. The impact of STAT3 aberrant expression on progression-free survival (PFS) and overall (OS) was analysed using univariate and multivariate survival analysis. The data were analysed using SPSS statistical software and p value ≤0.05 was considered as significant.

RESULTS: The aberrant STAT3 expression was found in 85% (47/55) of patients with -1.12 fold change down-regulation in 49% (23/47) and 3.36 fold change up-regulation was noted in 51% (24/47) of patients. In wild type IDH tumors (n=30), down regulation and up regulation of STAT3 was noted in 63% and 27% of patients, respectively, whereas, for IDH mutant GBM tumors (n=25), the incidence of low expression and high expression of STAT3 was noted in 16% and 68% of patients, respectively. Thus, we found that incidence of STAT3 down regulation was significantly high in patients with IDH wild type tumors, whereas, in IDH mutant GBM tumors, the incidence of up-regulated STAT3 was significantly high (P=0.021, χ2=12.81, r=+0.310). In Kaplan-Meier univariate survival analysis, a part from age (P=0.006), tumor location (P=0.025), and KPS score (P=0.002), co-detection of STAT3 up regulation and presence of IDH mutation (P=0.030) remained significant prognostic factors for PFS and OS. In multivariate survival analysis also, co-detection of STAT3 high expression and presence of IDH mutation remained independent prognosticators for PFS (HR=6.45, 95% CI=1.32-31.40, P=0.021) and OS (HR=8.69, 95% CI=1.66-45.51, P=0.010).

CONCLUSION: For GBM tumors, STAT3 up-regulation and presence of IDH mutations together predicts better survival. This reflects unique molecular etiology for GBM patients. Therefore, they would be useful in the future for targeted therapy and for clinicians they would be useful for better patient management. However, study on a larger sample size is required for validation.

PMID:35844028 | DOI:10.1186/s43046-022-00133-4

Int Orthop. 2022 Jul 18. doi: 10.1007/s00264-022-05514-x. Online ahead of print.

ABSTRACT

PURPOSE: The proximal chevron osteotomy and the modified Lapidus arthrodesis are both procedures utilized for deformity correction in patients with severe symptomatic hallux valgus. The aim of the current study was to compare their biomechanical stability when using locking plate fixation.

METHODS: Twelve matched pairs of human anatomical lower leg specimens underwent on one side a proximal chevron osteotomy with a medial locking plate and on the other side a modified Lapidus arthrodesis with a plantar locking plate utilizing an interfragmentary compression screw. All specimens underwent bone mineral density (BMD) assessment and were tested in a servohydraulic load frame which applied a load on the centre of the metatarsal head over 1000 loading cycles with subsequently ultimate load testing. Displacement of the proximal and distal bone segment, ultimate load, and bending stiffness were analyzed.

RESULTS: Mean displacement of both procedures showed no statistically significant difference throughout all the loading cycles (0.213 ≤ p ≤ 0.834). The mean ultimate load of the proximal chevron osteotomy was 227.9 N (± 232.4) and of the modified Lapidus arthrodesis 162.9 N (± 74.6) (p = 0.754). The proximal chevron osteotomy (38.2 N/mm (± 24.9)) had a significantly higher bending stiffness compared to the modified Lapidus arthrodesis (17.3 N/mm (± 9.9)) (p = 0.009). There was no correlation between BMD and displacement in all loading cycles, ultimate load, and bending stiffness of either procedure (p > 0.05).

CONCLUSION: Although the bending stiffness of the chevron osteotomy was higher, there was no statistically significant difference between the surgical techniques in mean displacement and ultimate load. The BMD did not influence the overall stability of either reconstruction. Locking plate fixation increases the clinical value of the modified Lapidus arthrodesis by outweighing most of the biomechanical disadvantages in comparison to the proximal chevron osteotomy.

PMID:35844015 | DOI:10.1007/s00264-022-05514-x

Epigenetics Chromatin. 2022 Jul 18;15(1):26. doi: 10.1186/s13072-022-00458-3.

ABSTRACT

Embryonic development is dependent on the maternal supply of proteins through the oocyte, including factors setting up the adequate epigenetic patterning of the zygotic genome. We previously reported that one such factor is the epigenetic repressor SMCHD1, whose maternal supply controls autosomal imprinted expression in mouse preimplantation embryos and mid-gestation placenta. In mouse preimplantation embryos, X chromosome inactivation is also an imprinted process. Combining genomics and imaging, we show that maternal SMCHD1 is required not only for the imprinted expression of Xist in preimplantation embryos, but also for the efficient silencing of the inactive X in both the preimplantation embryo and mid-gestation placenta. These results expand the role of SMCHD1 in enforcing the silencing of Polycomb targets. The inability of zygotic SMCHD1 to fully restore imprinted X inactivation further points to maternal SMCHD1’s role in setting up the appropriate chromatin environment during preimplantation development, a critical window of epigenetic remodelling.

PMID:35843975 | DOI:10.1186/s13072-022-00458-3

BMC Cardiovasc Disord. 2022 Jul 17;22(1):318. doi: 10.1186/s12872-022-02760-0.

ABSTRACT

BACKGROUND: The increase of low-density lipoprotein cholesterol (LDL-C) is widely accepted as an important factor in the occurrence of atherosclerosis. In recent years, the guidelines have recommended non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for lipid-lowering therapy. But even as research on the relationship between LDL-C/HDL-C and atherosclerosis increases, it is still undetermined which index is most closely related to the severity of acute ST-segment elevation myocardial infarction (STEMI).

METHODS: 901 patients who received coronary angiography due to chest pain were selected. Among them, 772 patients with STEMI represented the test group, and 129 patients with basically normal coronary angiography represented the control group. Researchers measured fasting blood lipids and other indicators after admission, and determined the severity of coronary artery disease using the Gensini score.

RESULTS: LDL-C/HDL-C and non-HDL-C indexes were statistically different between the two patient groups. In the test group, total cholesterol (TC), triglycerides (TG), LDL-C, high density lipoprotein cholesterol (HDL-C), non-HDL-C, arteriosclerosis index (AI), and LDL-C/HDL-C all correlated with the patients’ Gensini score. After applying the stepwise method of multiple linear regression analysis (R² = 0.423, β = 0.518, p < 0.05), LDL-C/HDL-C had the most correlation with the patient’s Gensini score. ROC curve analysis suggested that LDL-C/HDL-C can predict whether patients with chest pain are STEMI (AUC: 0.880, 95% Cl: 0.847-0.912, p < 0.05). When cutoff value is 2.15, sensitivity is 0.845, and specificity is 0.202, LDL-C/HDL-C is an effective indicator for predicting whether patients with chest pain have STEMI.

CONCLUSION: Compared to ratios of non-HDL-C and LDL-C, the LDL-C/HDL-C ratio in patients with STEMI is more correlated with the severity of coronary artery disease. It can better evaluate the severity of coronary artery disease and better predict whether patients with chest pain are STEMI.

PMID:35843962 | DOI:10.1186/s12872-022-02760-0

BMC Cardiovasc Disord. 2022 Jul 17;22(1):319. doi: 10.1186/s12872-022-02769-5.

ABSTRACT

BACKGROUND: China has experienced a continuing increase in hypertension prevalence over the past few decades, especially in rural areas. The paper aims to examine the variation of urban-rural disparities in hypertension prevalence, awareness, treatment, and control among Chinese middle-aged and older adults between 2011 and 2015.

METHODS: Our team extracted data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey of residents aged 45 years and older. In this study, we used the 2011 wave and the 2015 wave of CHARLS. We calculated crude rates and age-adjusted rates of hypertension prevalence, awareness, treatment, and control for the general, urban, and rural populations in each wave and performed chi-square tests to examine urban-rural disparities. We used logistic regression to further confirm these disparities by controlling confounding factors in each wave. We then used generalized estimating equation (GEE) to further examine whether urban-rural disparities changed between 2011 and 2015.

RESULTS: We included 11,129 records in the 2011 wave and 8916 records in the 2015 wave in this study. The mean age was 59.0 years and 5359 (48.2%) participants were male in the 2011 wave. Age-adjusted hypertension prevalence, awareness, treatment, control, and control among treated in the total population were 38.5%, 70.6%, 59.2%, 27.4%, and 46.4% in 2015. Urban-rural disparities in the indicators mentioned above were 5.7%, 13.4%, 15.3%, 9.4% and 5.6% in 2011; which decreased to 4.8%, 2.7%, 5.2%, 4.9% and 3.8% in 2015. Urban-rural disparities in prevalence, awareness and treatment were statistically significant in 2011 but not significant in 2015 adjusted for confounding factors, yet control disparities were statistically significant in both waves. Finally, urban-rural disparities in awareness and treatment had narrowed from 2011 to 2015.

CONCLUSIONS: Awareness, treatment, and control rates were sub-optimal among both urban and rural adults. Prevention and management of hypertension among both urban and rural adults should be further strengthened. Awareness and treatment increased more rapidly among rural adults, indicating some achievement had been made in enhancing the healthcare system in rural areas. More efforts are needed in attaining urban-rural equity of healthcare services.

PMID:35843959 | DOI:10.1186/s12872-022-02769-5

BMC Med Inform Decis Mak. 2022 Jul 17;22(1):186. doi: 10.1186/s12911-022-01932-4.

ABSTRACT

BACKGROUND: Agile projects are statistically more likely to succeed then waterfall projects. The overall aim of this study was to explore the nursing staffs’ experiences with an agile development process, from its initial requirements to the deployment of its outcome of ICT solutions aimed at supporting discharge planning.

METHODS: An explorative design with quantitative and qualitative methods was used. Qualitative data was collected through seven focus group interviews. Quantitative data was collected via an ICT-system, and with an evaluation form submitted by fourteen registered nurses and nine district nurses.

RESULTS: Qualitative result of the experiences with the agile development process and its outcome resulted in one theme, four categories, and ten subcategories. The theme was found to be about time and timing, namely the amount of time for the different activities and the timing of activities within and between organisations. The agile development process increased the participants’ readiness for change by offering time to learn, practice, engage and reflect, and then adopt the ICT as a support to daily practice. Quantitative results showed a variated adoption of the ICT.

CONCLUSION: There is a need for time to prepare, understand and adopt new tools, services and procedures and a need for additional time to prepare, understand and adopt the new among individuals, collectives, organizations, and sometimes even between different collectives or organizations. The agile development process offered the end-users involvement through the development process, which gave them time to change it both individually and collectively. However, there is a need for close collaboration between the development project team and management to reach an organizational change that is timely for both the individual and the collective change. When time or timing fails in the development or implementation process, there is a huge risk of non-adoption of new tools, services, or procedures or among the end-users.

PMID:35843948 | DOI:10.1186/s12911-022-01932-4

BMC Infect Dis. 2022 Jul 17;22(1):623. doi: 10.1186/s12879-022-07601-1.

ABSTRACT

BACKGROUND: Pericardial disease can be a manifestation of infection and imaging can have a role in its diagnosis. coccidioidomycosis endemic fungal infection has been more frequently reported over the past few decades. Other than case reports or series, there has been no systemic study evaluating pericardial imaging findings in patients with coccidioidomycosis to the best of our knowledge. The purpose of this study was to evaluate intrathoracic computed tomographic (CT) imaging abnormalities in patients with coccidioidal infection with specific emphasis on the pericardium.

METHODS: Retrospective review of radiology reports and clinical chart review was performed to identify patients with coccidioidomycosis between January 2000 and September 2021 at our medical center. Diagnosis of infection was confirmed predominately with serology. Patients were excluded if a CT was not performed within 3 months of confirmed diagnosis date and if there was concomitant additional granulomatous or fungal infection. Chest CT was reviewed for pericardial and additional intrathoracic findings.

RESULTS: The final retrospective cohort consisted of 37 patients. Imaging findings included lung nodules (N = 33/37), consolidation (N = 25/37), mediastinal or hilar lymphadenopathy (N = 20/37) and pleural effusions (N = 13/37). Eleven of 37 patients (30%) had either trace pericardial fluid (N = 3/37) or small pericardial effusions (N = 8/37). One patient had pericardial enhancement/thickening and history of pericardial tamponade. No other patient had clinical pericarditis or pericardial tamponade. Pericardial calcifications were not seen in any patient. Pericardial effusion was statistically associated with presence of pleural effusion as 9/13 patients with pleural effusion had pericardial effusion versus 2/26 patients without pleural effusion had pericardial effusion (p < 0.001). Otherwise patients with and without pericardial imaging findings were similar in terms of demographics, comorbidities and other imaging findings.

CONCLUSION: Pulmonary parenchymal pathology is a common manifestation of coccidioidal infection. Most patients with coccidioidomycosis do not have pericardial imaging abnormalities on CT.

PMID:35843935 | DOI:10.1186/s12879-022-07601-1