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Nevin Manimala Statistics

Polygenic risk score improves the accuracy of a clinical risk score for coronary artery disease

BMC Med. 2022 Nov 7;20(1):385. doi: 10.1186/s12916-022-02583-y.

ABSTRACT

BACKGROUND: The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. METHODS: An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine the risk prediction performance of pooled cohort equations, integrated polygenic risk score, and PRS-enhanced pooled cohort equation for incident CAD cases. The performance of each model was analyzed by discrimination and risk reclassification using a 7.5% threshold.

RESULTS: In the cohort of 272,307 individuals (mean age, 56.7 years) used to analyze predictive accuracy, there were 7036 incident CAD cases over a 12-year follow-up period. Model discrimination was tested for integrated polygenic risk score, pooled cohort equation, and PRS-enhanced pooled cohort equation with reported C-statistics of 0.640 (95% CI, 0.634-0.646), 0.718 (95% CI, 0.713-0.723), and 0.753 (95% CI, 0.748-0.758), respectively. Risk reclassification for the addition of the integrated polygenic risk score to the pooled cohort equation at a 7.5% risk threshold resulted in a net reclassification improvement of 0.117 (95% CI, 0.102 to 0.129) for cases and – 0.023 (95% CI, – 0.025 to – 0.022) for noncases [overall: 0.093 (95% CI, 0.08 to 0.104)]. For incident CAD cases, this represented 14.2% correctly reclassified to the higher-risk category and 2.6% incorrectly reclassified to the lower-risk category.

CONCLUSIONS: Addition of the integrated polygenic risk score for CAD to the pooled cohort questions improves the predictive accuracy for incident CAD and clinical risk classification in the White British from the UK Biobank. These findings suggest that an integrated polygenic risk score may enhance CAD risk prediction and screening in the White British population.

PMID:36336692 | DOI:10.1186/s12916-022-02583-y

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Nevin Manimala Statistics

Association of intergenerational relationships with cognitive impairment among Chinese adults 80 years of age or older: prospective cohort study

BMC Geriatr. 2022 Nov 7;22(1):838. doi: 10.1186/s12877-022-03529-y.

ABSTRACT

BACKGROUND: The oldest-old (aged 80 or older) are the most rapidly growing age group, and they are more likely to suffer from cognitive impairment, leading to severe medical and economic burdens. The influence of intergenerational relationships on cognition among Chinese oldest-old adults is not clear. We aim to examine the association of intergenerational relationships with cognitive impairment among Chinese adults aged 80 or older.

METHODS: This was a prospective cohort study, and data were obtained from the Chinese Longitudinal Healthy Longevity Survey, 14,180 participants aged 80 or older with at least one follow-up survey from 1998 to 2018. Cognitive impairment was assessed by the Chinese version of Mini Mental State Examination, and intergenerational relationships were assessed by getting main financial support from children, living with children or often being visited by children, and doing housework or childcare. We used time-varying Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of associations between intergenerational relationships and cognitive impairment.

RESULTS: We identified 5443 incident cognitive impairments in the 24-cut-off MMSE cohort and 4778 in the 18-cut-off MMSE cohort between 1998 and 2018. After adjusting for a wide range of confounders, the HR was 2.50 (95% CI: 2.31, 2.72) in the old who received main financial support from children, compared with those who did not. The HR was 0.89 (95% CI: 0.83, 0.95) in the oldest-old who did housework or childcare, compared with those who did not. However, there were no significant associations between older adults’ cognitive impairments and whether they were living with or often visited by their children. Our findings were consistent in two different MMSE cut-off values (24 vs. 18) for cognitive impairment.

CONCLUSIONS: Sharing housework or childcare for children showed a protective effect on older adults’ cognitive function, whereas having children provide primary financial support could increase the risk for cognitive impairments. Our findings suggest that governments and children should pay more attention to older adults whose main financial sources from their children. Children can arrange some easy tasks for adults 80 years of age or older to prevent cognitive impairments.

PMID:36336683 | DOI:10.1186/s12877-022-03529-y

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Nevin Manimala Statistics

Automatic segmentation of the great arteries for computational hemodynamic assessment

J Cardiovasc Magn Reson. 2022 Nov 7;24(1):57. doi: 10.1186/s12968-022-00891-z.

ABSTRACT

BACKGROUND: Computational fluid dynamics (CFD) is increasingly used for the assessment of blood flow conditions in patients with congenital heart disease (CHD). This requires patient-specific anatomy, typically obtained from segmented 3D cardiovascular magnetic resonance (CMR) images. However, segmentation is time-consuming and requires expert input. This study aims to develop and validate a machine learning (ML) method for segmentation of the aorta and pulmonary arteries for CFD studies.

METHODS: 90 CHD patients were retrospectively selected for this study. 3D CMR images were manually segmented to obtain ground-truth (GT) background, aorta and pulmonary artery labels. These were used to train and optimize a U-Net model, using a 70-10-10 train-validation-test split. Segmentation performance was primarily evaluated using Dice score. CFD simulations were set up from GT and ML segmentations using a semi-automatic meshing and simulation pipeline. Mean pressure and velocity fields across 99 planes along the vessel centrelines were extracted, and a mean average percentage error (MAPE) was calculated for each vessel pair (ML vs GT). A second observer (SO) segmented the test dataset for assessment of inter-observer variability. Friedman tests were used to compare ML vs GT, SO vs GT and ML vs SO metrics, and pressure/velocity field errors.

RESULTS: The network’s Dice score (ML vs GT) was 0.945 (interquartile range: 0.929-0.955) for the aorta and 0.885 (0.851-0.899) for the pulmonary arteries. Differences with the inter-observer Dice score (SO vs GT) and ML vs SO Dice scores were not statistically significant for either aorta or pulmonary arteries (p = 0.741, p = 0.061). The ML vs GT MAPEs for pressure and velocity in the aorta were 10.1% (8.5-15.7%) and 4.1% (3.1-6.9%), respectively, and for the pulmonary arteries 14.6% (11.5-23.2%) and 6.3% (4.3-7.9%), respectively. Inter-observer (SO vs GT) and ML vs SO pressure and velocity MAPEs were of a similar magnitude to ML vs GT (p > 0.2).

CONCLUSIONS: ML can successfully segment the great vessels for CFD, with errors similar to inter-observer variability. This fast, automatic method reduces the time and effort needed for CFD analysis, making it more attractive for routine clinical use.

PMID:36336682 | DOI:10.1186/s12968-022-00891-z

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Nevin Manimala Statistics

Effectiveness of D.A.R.E/Keepin’ it REAL bullying prevention program among Brazilian students

J Adolesc. 2022 Nov 6. doi: 10.1002/jad.12115. Online ahead of print.

ABSTRACT

INTRODUCTION: Given the growing scientific evidence on the detrimental effects of bullying, several prevention programs have been implemented internationally to prevent this behavior among students. Brazil’s Educational Program for Drug and Violence Resistance (PROERD) is an adaptation of US’ DARE/Keepin’ it REAL program, being the most widespread school-based prevention program in the country. However, it has been offered without any effectiveness evaluation. As such, this study evaluates the effectiveness of PROERD in reducing bullying perpetration and victimization among students.

METHODS: Two cluster randomized controlled trials were carried out with 4030 students (1727 5th graders and 2303 7th graders) in 30 public schools in São Paulo, Brazil. The intervention group attended 10 PROERD classes taught by trained police officers whereas the control group underwent no intervention. Data were collected by self-administered questionnaires using smartphones at two moments (baseline preintervention and 9-month follow-up). Multilevel analysis included two paradigms, complete cases (CC) and intention-to-treat (ITT), using Full Information Maximum Likelihood (FIML) and Multiple Imputation (MI). RESULTS AND CONCLUSION: Results show no statistical difference between groups, indicating lack of evidence on PROERD’s effectiveness in preventing bullying behaviors. The insufficient number of classes on bullying prevention and the lack of cultural adaptation may explain these unexpected results. New in-depth evaluation studies concerning the program’s components and process are needed.

PMID:36336666 | DOI:10.1002/jad.12115

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Is self-reported adherence a valid measure of glycaemic control among people living with diabetes in rural India? A cross-sectional analysis

Prim Care Diabetes. 2022 Nov 3:S1751-9918(22)00175-9. doi: 10.1016/j.pcd.2022.10.009. Online ahead of print.

ABSTRACT

BACKGROUND: Visual analogue scale (VAS) is one of the simplest to measure medication adherence. It has neither been widely used for Non communicable diseases (NCD) nor validated for in the Indian setting. We examined the validity of self-reported medication adherence measures in relation to HbA1C in a rural population with diabetes mellitus (DM).

METHODS: Participants with DM was administered VAS, Diabetes Self-Management Questionnaire (DMSQ) and assessed for missed pills. Descriptive statistics and logistic regression analysis were done.

RESULTS: We recruited 1347 participants and 84% of them reported being 100% adherent as per VAS and 83.8% stated that they did not miss any pills. However, 58.2% of participants who reported having 100% adherence had poor glycaemic control, as did 58.1% of those who did not miss any pills. None of the diabetic self-care measures was significantly associated with glycaemic control.

CONCLUSION: We found a lack of association between self-reported adherence measures and glycaemic control in participants with DM suggesting that self-reported adherence scales may not be valid in this population.

PMID:36336604 | DOI:10.1016/j.pcd.2022.10.009

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Sex differences in periprocedural and long-term outcomes following transcatheter left atrial appendage occlusion: A systematic review and meta-analysis

Cardiovasc Revasc Med. 2022 Oct 8:S1553-8389(22)00819-3. doi: 10.1016/j.carrev.2022.10.002. Online ahead of print.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is among the most common arrhythmias associated with an increased risk of cardioembolic phenomena, including stroke. Percutaneous left atrial appendage occlusion (LAAO) has proven beneficial in reducing stroke and mortality in patients with atrial fibrillation who have contraindications to anticoagulation. However, the sex differences in outcomes following LAAO have not been studied systematically.

METHODS: Electronic databases PUBMED, Embase, and Web of Science were systematically searched until March 2022 for studies evaluating patient outcomes following LAAO for AF. The primary outcomes of interest were the risks of periprocedural stroke, major bleeding, pericardial complications, and all-cause mortality. Secondary outcomes included stroke risks, major bleeding, device-related thrombus, cardiovascular and all-cause mortality on long-term follow-up. A random-effects model meta-analysis was conducted, and heterogeneity was assessed using the I-squared test.

RESULTS: Sixteen studies were included in the final analysis encompassing 111,775 patients, out of which 45,441 (40.7 %) were women. Women had a significantly higher risk of peri-procedural complications including all-cause mortality [relative risk (RR), 95 % confidence intervals (CI); RR 1.94, 95 % CI 1.40-2.69], stroke [RR 1.85, 95 % CI 1.29-2.67], major bleeding [RR 1.63, 95 % CI 1.08-2.44], and pericardial events [RR 1.80, 95 % CI 1.58-2.05]. However, there were no statistically significant differences between sexes in terms of risk of stroke, major bleeding, device-related thrombus, cardiovascular and all-cause mortality on long-term follow-up.

CONCLUSION: Among patients undergoing LAAO implantation, women were at higher risk of periprocedural complications than men. This risk was not significant on long-term follow-up.

PMID:36336589 | DOI:10.1016/j.carrev.2022.10.002

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Quality of life of Moroccan patients with celiac disease: Arabic translation, cross-cultural adaptation, and validation of the celiac disease questionnaire

Arab J Gastroenterol. 2022 Nov 3:S1687-1979(22)00061-2. doi: 10.1016/j.ajg.2022.06.009. Online ahead of print.

ABSTRACT

BACKGROUND AND STUDY AIMS: Celiac disease (CD) management is based on a lifelong gluten-free diet (GFD) that affects the quality of life (QoL) of patients with CD. Specific instruments have been used to evaluate this QoL, such as the CD-Questionnaire (CD-Q). This study aimed to translate, validate, and cross-culturally adapt the CD-Q in an Arabic version and then apply it to evaluate the QoL of Moroccan adult patients with CD.

PATIENTS AND METHODS: The Moroccan version of the CD-Q (M-CD-Q) was administered to 150 patients with CD, and 112 of them completed it. The reproducibility and reliability of the M-CD-Q were studied by the intraclass coefficient (ICC) and Cronbach’s α, respectively. Parametric and nonparametric tests, confirmatory factor analysis, and Spearman correlation were used for the statistical analysis performed by SPSS, and the goodness-of-fit test was determined using SPSS AMOS.

RESULTS: No difficulties were found during the translation and cultural adaptation of the CD-Q. Cronbach’s α showed good internal consistency. The retest showed excellent reproducibility (ICC > 0.4). The study of the psychometric properties of the M-CD-Q showed good acceptance, zero ceiling effect, and floor effect. The model fit was good [(root mean square error of approximation = 0.075 (<0.08) and χ2 = 509.04, p < 0.001]. The total scores showed a neutral QoL. This QoL was worse in the worries subscale, which is related to gluten-free products. The GFD did not improve the QoL of the examined samples.

CONCLUSION: The M-CD-Q is the first reliable and adapted instrument in an Arab country for the evaluation of QoL in patients with CD. CD negatively influences this QoL, especially items related to gluten-free products.

PMID:36336586 | DOI:10.1016/j.ajg.2022.06.009

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Dosimetric benefits of 3D-printed modulated electron bolus following lumpectomy and whole-breast radiotherapy for left breast cancer

Med Dosim. 2022 Nov 3:S0958-3947(22)00085-1. doi: 10.1016/j.meddos.2022.10.001. Online ahead of print.

ABSTRACT

Radiotherapy with electrons is commonly applied to the tumor bed after whole-breast radiotherapy following breast conservation surgery for breast cancer patients. However, the radiation dose to adjacent organs-at-risk (OARs) and conformity of planning target volume (PTV) cannot be optimized. In this study, we examine the feasibility of using modulated electron bolus (MEB) to improve PTV conformity and reduce the dose to these OARs. Twenty-seven patients with left breast cancer were retrospectively selected in this study. For each patient, a tangential photon plan in RayStation treatment planning system with prescription of 26 Gy in 5 fractions was created as base plan. Two electron plans, one without bolus and one with MEB using Adaptiiv software based on the PTV were created. Various dosimetric parameters of OARs including left lung, heart, left anterior descending artery (LAD) and ribs and the conformity indices of PTV of these 2 electron plans together with the base plans were compared. Statistically significant decreases in the dosimetric parameters (V5Gy, V10Gy, V20Gy, and mean dose) of the ipsilateral left lung and the heart were observed with MEB. The median maximum dose to the LAD and the ribs decreased by 6.2% and 4.5% respectively. The median conformity index was improved by 14.3% with median increases of monitor units by 1.7%. Our results show that MEB is feasible resulting in reduction of doses to the predefined OARs and an improved conformity of PTV. By using 3D printing, MEB might be considered as an alternative to conventional electron boost.

PMID:36336582 | DOI:10.1016/j.meddos.2022.10.001

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Nevin Manimala Statistics

Classic Timothy Syndrome Associated With Bilateral Border Digit Syndactyly: A Case Series

J Hand Surg Am. 2022 Nov 3:S0363-5023(22)00538-X. doi: 10.1016/j.jhsa.2022.09.003. Online ahead of print.

ABSTRACT

PURPOSE: Timothy syndrome (TS) is characterized by congenital long-QT arrhythmia and limb syndactyly. Patients who undergo syndactyly repair with undiagnosed TS may have their abnormal cardiac electrical activity unmasked during surgery. The purpose of this study was to detail the extremity phenotype seen in patients with TS, which may help hand surgeons in their preoperative assessment.

METHODS: This was a retrospective review of all patients with TS seen at our institution from 1998 to 2022. Descriptive statistics regarding their demographics, medical and surgical histories, and syndactyly phenotypes were obtained.

RESULTS: Seven patients (5 males and 2 females) with TS were seen at our institution for multidisciplinary evaluation (median age at presentation was 23 months). Six patients had finger syndactyly and 5 had toe syndactyly. One patient did not have any extremity syndactyly and was noted to have a specific TS mutation known to lack musculoskeletal abnormalities. All patients with finger syndactyly had border digit involvement, with 5 out of 6 patients displaying syndactyly of the middle-ring and ring-little finger web spaces. Toe syndactyly was more heterogeneous, with 1 patient lacking any lower extremity syndactyly and others having variable involvement of the second-third, third-fourth, and fourth-little toe web spaces. Complexity ranged from simple to complete. Four patients had intraoperative cardiac events leading to TS diagnoses after surgery.

CONCLUSIONS: Bilateral border digit hand syndactyly, with or without bilateral toe syndactyly, should raise concerns for TS and prompt further investigation into potential cardiac disease to avoid perioperative cardiac morbidity and mortality.

TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

PMID:36336572 | DOI:10.1016/j.jhsa.2022.09.003

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Electrocardiographic Measures of Repolarization Heterogeneity are not Predictive For Torsades De Pointes Among Undifferentiated Patients with Prolonged QTc: A Case Control Study

J Cardiovasc Electrophysiol. 2022 Nov 6. doi: 10.1111/jce.15735. Online ahead of print.

ABSTRACT

INTRODUCTION: Torsades de Pointes (TdP) is a potentially lethal polymorphic ventricular tachydysrhythmia associated with and caused by prolonged myocardial repolarization. However, prediction of TdP is challenging. We sought to determine if electrocardiographic myocardial repolarization heterogeneity is necessary and predictive of TdP.

METHODS: We performed a case control study of TdP at a large urban hospital. We identified cases based on a hospital center ECG database search for tracings from 1/2005 to 6/2019 with QTc>500, QRS<120, and HR<60, and a subsequent natural language search of electronic health records for the terms: TdP, polymorphic ventricular tachycardia, sudden cardiac death, and relevant variants. Controls were drawn in a 2:1 ratio to cases from a similar pool of ECGs, and matching for QTc, heart rate, sex, and age. We abstracted historical, laboratory, and ECG data using detailed written instructions and an electronic database. We included a second blinded data abstractor to test data abstraction and manual ECG measurement reliability. We used GE QT Guard software for automated repolarization measurements. We compared groups using unpaired statistics.

RESULTS: We included 75 cases and 150 controls. The number of current QTc prolonging medications and serum electrolytes were substantially the same between the two groups. We found no significant difference in measures of QT or T wave repolarization heterogeneity.

CONCLUSION: Electrocardiographic repolarization heterogeneity is not greater in otherwise unselected patients with QTc prolongation who suffer TdP and does not appear predictive of TdP. However, previous observations suggest specific repolarization characteristics may be useful for defined patient subgroups at risk for TdP. This article is protected by copyright. All rights reserved.

PMID:36335640 | DOI:10.1111/jce.15735