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Nevin Manimala Statistics

Prediction of large-for-gestational age at 36 weeks’ gestation: two-dimensional vs three-Dimensional vs magnetic resonance imaging

Ultrasound Obstet Gynecol. 2023 Sep 19. doi: 10.1002/uog.27485. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the performance of two-dimensional ultrasound (2D-US) three-dimensional ultrasound (3D-US) and magnetic resonance imaging (MRI) at 36 weeks of gestation (WG) in the prediction of Large-for-Gestational-Age (LGA) fetuses defined as birthweight > 95th percentile in a high- and low-risk groups for macrosomia.

METHODS: This was a prospective observational study conducted between January 2017 and February 2019. Women with singleton pregnancy at 36 WG underwent simultaneously 2D-US, 3D-US, and MRI. By plotting the weight estimations and the birthweight on the growth curve, a percentile was obtained, and it was used for comparison. The study population was divided into high- and low-risk groups, according to at least one of the following risk factors: the presence of diabetes, suspicion of macrosomia during the third trimester (> 90th percentile at the ultrasound routine scan), obesity (body mass index, BMI, > 30 kg/m2 ), and excessive weight gain. The outcome was the measurement of the performance of each diagnostic modality in the prediction of birthweight > 95th percentile. Statistical analysis was performed by calculating the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive and negative predictive values for each modality.

RESULTS: Out of 988 patients, 965 were eligible: 533 (55.23%) in the high-risk group and 432 (44.77%) in the low-risk group. In the low-risk group, the AUCs were 0.982 for MRI, 0.964 for 2D-US, and 0.962 for 3D-US. No statistical significance was found among these three methods. In the high-risk group, the AUCs were 0.959 for MRI, 0.909 for 2D-US, and 0.894 for 3D-US. A statistically significant difference between MRI and both 2D-US (p = 0.002) and 3D-US (p = 0.002) was found. MRI had the highest sensitivity (65.79%) compared with both 2D-US (36.84%) and 3D-US (21.05%) ultrasound (p = 0.002 and p < 0.001, respectively). The 3D-US had the highest specificity (98.99%) compared to both methods (2D-US: 96.77%, p = 0.005, and MRI: 96.97%, p = 0.004).

CONCLUSION: At 36 WG, MRI performs better than 2D-US and 3D-US in predicting birthweight > 95th percentile at birth, especially in patients at high-risk for macrosomia, while 2D-US and 3D-US are comparable. For low-risk patients, the three modalities perform similarly. This article is protected by copyright. All rights reserved.

PMID:37725758 | DOI:10.1002/uog.27485

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Incremental yield of whole genome sequencing over chromosome microarray and exome sequencing for congenital anomalies in prenatal period and infancy: systematic review and meta-analysis

Ultrasound Obstet Gynecol. 2023 Sep 19. doi: 10.1002/uog.27491. Online ahead of print.

ABSTRACT

OBJECTIVE: Primarily to determine the incremental yield of Whole Genome Sequencing (WGS) over Chromosome Microarray Assessment (CMA) and/or Exome Sequencing (ES) in fetuses and infants with a congenital anomaly that was or could have been detectable on ultrasound prenatally. Secondly, to evaluate the turnaround time (TAT) and quantity of DNA required for testing using these pathways.

METHODS: OVID MEDLINE(R), EMBASE, Medline (Web of Science), Cochrane Library, and ClinicalTrials.gov databases were searched electronically (January 2010 to December 2022). Inclusion criteria were cohort studies including fetuses/infants with ≥n=3 cases of: (i) one or more congenital anomalies; (ii) an anomaly which was or would have been detectable on prenatal ultrasound and; (iii) exclusion of aneuploidy and pathogenic Copy Number Variants >50kb. Pooled incremental yield was determined using a random-effects model and heterogeneity was assessed statistically using Higgins’ I2 . Sub-analyses were performed based on pre- or postnatal presentation, multi-system anomalies and classification based upon NHS England prenatal (R21) ES inclusion criteria. PROSPERO 2022 CRD42022380483 RESULTS: Eighteen studies incorporating n=1284 cases were included, of which n=8 (44.4%) incorporating n=754 (58.7%) cases were prenatal cohorts and the remainder representing postmortem (postnatal evaluation), neonatal or infants with congenital structural anomalies. The incremental yield of WGS over QF-PCR/CMA was 26% (95% CI 18-36%, I2 =86%), 16% (9-24%, I2 =85%) and 39% (95%CI 27-51%, I2 =53%) for all, prenatal and postnatal cases. The incremental yields were optimal where sequencing was performed in line with NHS England prenatal ES criteria; 32% (22%-42%, I2 =70%). The incremental yield of Variants of Uncertain Significance (VUS) was 18% (95% CI 7-33%, I2 =74%). The yield of WGS over ES was non-significant at 1% (95% CI 0%-4%, I2 =47%). The pooled median TAT for WGS was 18 days (range: 1-912 days) and the quantity of DNA required for WGS versus CMA and ES was 100ng (±0) and 350ng (±50) p=0.03 respectively.

CONCLUSION: Whilst WGS investigation for congenital anomaly holds great promise, for the future, its’ incremental yield over ES is yet to be demonstrated. However, the laboratory pathway for WGS (compared to sequential QF-PCR/CMA/ES) requires less DNA with a potentially faster TAT. There was a relatively high rate of VUS. This article is protected by copyright. All rights reserved.

PMID:37725747 | DOI:10.1002/uog.27491

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Nevin Manimala Statistics

Automated Spot Counting in Microbiology

IEEE/ACM Trans Comput Biol Bioinform. 2023 Sep 19;PP. doi: 10.1109/TCBB.2023.3317339. Online ahead of print.

ABSTRACT

Biological samples are routinely analyzed for microbe concentration. The samples are diluted, loaded onto established host cell cultures, and incubated. If infectious agents are present in the samples, they form circular spots that do not contain the host cells. Each spot is assumed to be originated from a single microbial unit such as a bacterial colony forming unit or viral plaque forming unit. The undiluted sample concentration is estimated by counting the spots and back-calculating. Counting the number of spots by trained technicians is currently the gold standard but it is laborious, subjective, and hard to scale. This paper presents a new automated algorithm for spot counting, Localized and Sequential Thresholding (LoST). Validation studies showed that LoST performance was comparable with manual counting and outperformed several existing tools on images with overlapping spots. The LoST algorithm employs sequential thresholding through a two-stage segmentation and borrows information across all images from the same dilution series to fine-tune the count and identify right censoring. The algorithm increases the efficiency of the spot counting and the quality of the downstream analysis, especially when coupled with an appropriate statistical serial dilution model to enhance the undiluted sample concentration estimation procedure.

PMID:37725729 | DOI:10.1109/TCBB.2023.3317339

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Nevin Manimala Statistics

Sleep quality and duration: A key to life satisfaction among military students

Mil Psychol. 2023 Sep 19:1-11. doi: 10.1080/08995605.2023.2259778. Online ahead of print.

ABSTRACT

Military service is a demanding profession that requires high physical preparedness and mental endurance. At the same time, the demands of military duties often require early rising and shortened sleep duration. Such a reduction in sleep can reduce physical and mental performance, and these changes can be reflected in life satisfaction. For this reason, soldiers’ life satisfaction is a crucial variable for their success and long-term service. This study examined the relationship between sleep quality, sleep duration, and life satisfaction in military medical students. The results on 35 military students showed that greater sleep quality corresponded to greater life satisfaction; this relationship was moderate and significant (r = -460, p = .005). Notably, participants (n = 17) who began to wake up without the use of an alarm clock reported an average of 11% higher life satisfaction than the participants who woke to an alarm clock; this difference between participants was statistically significant (p = .011, Cohen’s d = .911). Pre- and post-intervention showed that sleep hygiene education could be a suitable solution to prevent sleep deprivation and positively impact life satisfaction. Our findings emphasize the importance of increased sleep hygiene education, especially in preparing future military officers and during military exercises. Prioritizing sleep hygiene in these ways can significantly increase soldiers’ life satisfaction.

PMID:37725691 | DOI:10.1080/08995605.2023.2259778

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Increased Neighborhood Deprivation Is Associated with Prolonged Hospital Stays After Surgical Fixation of Traumatic Pelvic Ring Injuries

J Bone Joint Surg Am. 2023 Sep 19. doi: 10.2106/JBJS.23.00292. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to understand the role of social determinants of health assessed by the Area Deprivation Index (ADI) on hospital length of stay and discharge destination following surgical fixation of pelvic ring fractures.

METHODS: A retrospective chart analysis was performed for all patients who presented to our level-I trauma center with pelvic ring injuries that were treated with surgical fixation. Social determinants of health were determined via use of the ADI, a comprehensive metric of socioeconomic status, education, income, employment, and housing quality. ADI values range from 0 to 100 and are normalized to a U.S. mean of 50, with higher scores representing greater social deprivation. We stratified our cohort into 4 ADI quartiles. Statistical analysis was performed on the bottom (25th percentile and below, least deprived) and top (75th percentile and above, most deprived) ADI quartiles. Significance was set at p < 0.05.

RESULTS: There were 134 patients who met the inclusion criteria. Patients in the most deprived group were significantly more likely to have a history of smoking, to self-identify as Black, and to have a lower mean household income (p = 0.001). The most deprived ADI quartile had a significantly longer mean length of stay (and standard deviation) (19.2 ± 19 days) compared with the least deprived ADI quartile (14.7 ± 11 days) (p = 0.04). The least deprived quartile had a significantly higher percentage of patients who were discharged to a resource-intensive skilled nursing facility or inpatient rehabilitation facility compared with those in the most deprived quartile (p = 0.04). Race, insurance, and income were not significant predictors of discharge destination or hospital length of stay.

CONCLUSIONS: Patients facing greater social determinants of health had longer hospital stays and were less likely to be discharged to resource-intensive facilities when compared with patients of lesser social deprivation. This may be due to socioeconomic barriers that limit access to such facilities.

LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:37725686 | DOI:10.2106/JBJS.23.00292

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Nevin Manimala Statistics

Potential missed diagnoses of Crohn’s disease in tertiary care: impact on drug utilization and healthcare facilities use

Eur J Gastroenterol Hepatol. 2023 Sep 18. doi: 10.1097/MEG.0000000000002642. Online ahead of print.

ABSTRACT

BACKGROUND: A missed diagnosis of Crohn’s disease (CD) can delay treatment initiation with consequences on disease course.

AIMS: To measure the possible impact of missed diagnoses on drug utilization and access to healthcare facilities in a real-world cohort of CD patients.

METHODS: This retrospective observational study has been conducted on the regional administrative databases of Tuscany (Italy). We included patients with a first record of CD diagnosis between 06/11/2011 and 06/30/2016. Possible missed diagnosis (exposure) was defined by hospital presentation for gastrointestinal symptoms consistent with CD diagnosis that occurred in the 7-60 months preceding CD diagnosis. We compared exposed and non-exposed patients by assessing time-free from biologic drugs and from Emergency Department (ED) or hospital access. Hazard ratio (HR) was calculated using Cox models.

RESULTS: Among 3342 CD patients, 584 (17.5%) had a possible missed diagnosis. A risk of being treated with biologic drugs [adjusted HR (aHR): 2.17, 95% CI: 1.75-2.71] and of access to ED or hospitalization (aHR: 1.59, 95% CI: 1.44-1.75) was observed in patients with a possible missed diagnosis as compared to those without.

CONCLUSION: Tertiary care caregivers should be trained in the identification of early CD symptoms, to timely identify CD diagnosis and optimize pharmacological treatment and disease management.

PMID:37724478 | DOI:10.1097/MEG.0000000000002642

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Nevin Manimala Statistics

Psychosocial Stressors at Work and Coronary Heart Disease Risk in Men and Women: 18-Year Prospective Cohort Study of Combined Exposures

Circ Cardiovasc Qual Outcomes. 2023 Sep 19:e009700. doi: 10.1161/CIRCOUTCOMES.122.009700. Online ahead of print.

ABSTRACT

BACKGROUND: Psychosocial stressors at work, like job strain and effort-reward imbalance (ERI), can increase coronary heart disease (CHD) risk. ERI indicates an imbalance between the effort and received rewards. Evidence about the adverse effect of combined exposure to these work stressors on CHD risk is scarce. This study examines the separate and combined effect of job strain and ERI exposure on CHD incidence in a prospective cohort of white-collar workers in Quebec, Canada.

METHODS: Six thousand four hundred sixty-five white-collar workers without cardiovascular disease (mean age, 45.3±6.7) were followed for 18 years (from 2000 to 2018). Job strain and ERI were measured with validated questionnaires. CHD events were retrieved from medico-administrative databases using validated algorithms. Marginal Cox models were used to calculate hazard ratios (HR) stratified by sex. Multiple imputation and inverse probability weights were applied to minimize potential threats to internal validity.

RESULTS: Among 3118 men, 571 had a first CHD event. Exposure to either job strain or ERI was associated with an adjusted 49% CHD risk increase (HR, 1.49 [95% CI, 1.07-2.09]). Combined exposure to job strain and ERI was associated with an adjusted 103% CHD risk increase (HR, 2.03 [95% CI, 1.38-2.97]). Exclusion of early CHD cases and censoring at retirement did not alter these associations. Among 3347 women, 265 had a first CHD event. Findings were inconclusive (passive job HR, 1.24 [95% CI, 0.80-1.91]; active job HR, 1.16 [95% CI, 0.70-1.94]; job strain HR, 1.08 [95% CI, 0.66-1.77]; ERI HR, 1.02 [95% CI, 0.72-1.45]).

CONCLUSIONS: In this prospective cohort study, men exposed to job strain or ERI, separately and in combination, were at increased risk of CHD. Early interventions on these psychosocial stressors at work in men may be effective prevention strategies to reduce CHD burden. Among women, further investigation is required.

PMID:37724474 | DOI:10.1161/CIRCOUTCOMES.122.009700

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Nevin Manimala Statistics

Evaluating Prognostic Value of Dynamics of Circulating Lactate Dehydrogenase in Colorectal Cancer Using Modeling and Machine Learning

Clin Pharmacol Ther. 2023 Sep 19. doi: 10.1002/cpt.3052. Online ahead of print.

ABSTRACT

Pre-treatment serum lactate dehydrogenase (LDH) levels have been associated with poor prognosis in several types of cancer, including metastatic colorectal cancer (mCRC). However, very few models link survival to longitudinal LDH measured repeatedly over time during treatment. We investigated the prognostic value of on-treatment LDH dynamics in mCRC. Using data from two large Phase III studies (2L and 3L+ mCRC settings, n = 824 and 210, respectively), we found that integrating longitudinal LDH data with baseline risk factors significantly improved survival prediction. Current LDH values performed best, enhancing discrimination ability (area under the receiver operating characteristic curve) by 4.5% ~ 15.4% and prediction accuracy (Brier score) by 3.9% ~ 15.0% compared to baseline variables. Combining all four longitudinal LDH markers further improved predictive performance. After controlling for baseline covariates and other longitudinal LDH indicators, current LDH levels remained a significant risk factor in mCRC, increasing mortality risk by over 90% (P < 0.001) in 2L patients and 60-70% (P < 0.01) in 3L+ patients per unit increment in current log(LDH). Machine learning techniques like functional principal component analysis (FPCA) extracted informative features from longitudinal LDH data, capturing over 99% of variability and allowing prediction of survival. Unsupervised clustering based on the extracted FPCA features stratified patients into three groups with distinct LDH dynamics and survival outcomes. Hence, our approaches offer a valuable and cost-effective way for risk stratification and improves survival prediction in mCRC using LDH trajectories.

PMID:37724436 | DOI:10.1002/cpt.3052

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Nevin Manimala Statistics

The frontooccipital interaction mechanism of high-frequency acoustoelectric signal

Cereb Cortex. 2023 Sep 18:bhad306. doi: 10.1093/cercor/bhad306. Online ahead of print.

ABSTRACT

Based on acoustoelectric effect, acoustoelectric brain imaging has been proposed, which is a high spatiotemporal resolution neural imaging method. At the focal spot, brain electrical activity is encoded by focused ultrasound, and corresponding high-frequency acoustoelectric signal is generated. Previous studies have revealed that acoustoelectric signal can also be detected in other non-focal brain regions. However, the processing mechanism of acoustoelectric signal between different brain regions remains sparse. Here, with acoustoelectric signal generated in the left primary visual cortex, we investigated the spatial distribution characteristics and temporal propagation characteristics of acoustoelectric signal in the transmission. We observed a strongest transmission strength within the frontal lobe, and the global temporal statistics indicated that the frontal lobe features in acoustoelectric signal transmission. Then, cross-frequency phase-amplitude coupling was used to investigate the coordinated activity in the AE signal band range between frontal and occipital lobes. The results showed that intra-structural cross-frequency coupling and cross-structural coupling co-occurred between these two lobes, and, accordingly, high-frequency brain activity in the frontal lobe was effectively coordinated by distant occipital lobe. This study revealed the frontooccipital long-range interaction mechanism of acoustoelectric signal, which is the foundation of improving the performance of acoustoelectric brain imaging.

PMID:37724433 | DOI:10.1093/cercor/bhad306

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Salivette® cortisol versus oropharyngeal swabbing for the detection of SARS-CoV-2 infection

Expert Rev Mol Diagn. 2023 Sep 19. doi: 10.1080/14737159.2023.2260308. Online ahead of print.

ABSTRACT

BACKGROUND: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by naso/oropharyngeal swabbing may expose healthcare workers to the virus and is technically challenging. The Salivette® is an alternative saliva-collection device with an oral cotton swab containing citric acid to stimulate saliva production, which may have an unpleasant taste. We present a pilot study comparing the Salivette® Cortisol (SC), which uses a synthetic swab without citric acid, against oropharyngeal swabbing for detection of SARS-CoV-2 by RT-qPCR.

RESEARCH DESIGN AND METHODS: Symptomatic SARS-CoV-2-positive patients were sampled at various timepoints. The number of patients positive/negative for SARS-CoV-2 in oropharyngeal swab and SC samples, and percentage testing true positive/true negative for SARS-CoV-2 from SC samples was determined. Positivity was defined by RT-qPCR amplification of 2/3 target SARS-CoV-2 N, ORF1 and S gene sequences.

RESULTS: SC demonstrated 100% specificity, 52.2% sensitivity and positive correlation with oropharyngeal swabbing for detection of the SARS-CoV-2 S gene. In later-stage disease, lower viral load was observed in SC samples compared with oropharyngeal swabs.

CONCLUSIONS: The SC may be an alternative for SARS-CoV-2 detection where naso/oropharyngeal swabbing is not feasible/available. This technique also confirms observations that detection of SARS-CoV-2 in the upper airway may vary due to viral load over the disease course.

TRIAL REGISTRATION: NCT04599959.

PMID:37724431 | DOI:10.1080/14737159.2023.2260308