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Nevin Manimala Statistics

Whole-Exome Sequencing Analyses Support a Role of Vitamin D Metabolism in Ischemic Stroke

Stroke. 2023 Feb 10. doi: 10.1161/STROKEAHA.122.040883. Online ahead of print.

ABSTRACT

BACKGROUND: Ischemic stroke (IS) is a highly heritable trait, and genome-wide association studies have identified several commonly occurring susceptibility risk loci for this condition. However, there are limited data on the contribution of rare genetic variation to IS.

METHODS: We conducted an exome-wide study using whole-exome sequencing data from 152 058 UK Biobank participants, including 1777 IS cases. We performed single-variant analyses for rare variants and gene-based analyses for loss-of-function and deleterious missense rare variants. We validated these results through (1) gene-based testing using summary statistics from MEGASTROKE-a genome-wide association study of IS that included 67 162 IS cases and 454 450 controls, (2) gene-based testing using individual-level data from 1706 IS survivors, including 142 recurrent IS cases, enrolled in the VISP trial (Vitamin Intervention for Stroke Prevention); and (3) gene-based testing against neuroimaging phenotypes related to cerebrovascular disease using summary-level data from 42 310 UK Biobank participants with available magnetic resonance imaging data.

RESULTS: In single-variant association analyses, none of the evaluated variants were associated with IS at genome-wide significance levels (P<5×10-8). In the gene-based analysis focused on loss-of-function and deleterious missense variants, rare genetic variation at CYP2R1 was significantly associated with IS risk (P=2.6×10-6), exceeding the Bonferroni-corrected threshold for 16 074 tests (P<3.1×10-6). Validations analyses indicated that CYP2R1 was associated with IS risk in MEGASTROKE (gene-based test, P=0.003), with IS recurrence in the VISP trial (gene-based test, P=0.001) and with neuroimaging traits (white matter hyperintensity, mean diffusivity, and fractional anisotropy) in the UK Biobank neuroimaging study (all gene-based tests, P<0.05).

CONCLUSIONS: Because CYP2R1 plays an important role in vitamin D metabolism and existing observational evidence suggests an association between vitamin D levels and cerebrovascular disease, our results support a role of this pathway in the occurrence of IS.

PMID:36762557 | DOI:10.1161/STROKEAHA.122.040883

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Telehealth equivalence of the Montreal cognitive assessment (MoCA): Results from the Emory healthy brain study (EHBS)

J Am Geriatr Soc. 2023 Feb 10. doi: 10.1111/jgs.18271. Online ahead of print.

ABSTRACT

BACKGROUND: We investigated potential differences between in-person cognitive testing and video telehealth administration of the Montreal Cognitive Assessment (MoCA). In addition to the MoCA, the Patient Health Questionnaire-8 (PHQ-8) and Generalized Anxiety Disorder-7 (GAD-7) were administered.

METHODS: MoCA scores from participants in the Emory Health Brain Study (EHBS) were contrasted based upon whether they were administered the MoCA in the standard face-to-face (F2F) assessment setting (n = 1205) or using a video telehealth administration (n = 491). All EHBS participants were self-reported to be cognitively normal.

RESULTS: MoCA scores did not differ across administration method (F2F MoCA = 26.6, SD = 2.4; telehealth MoCA = 26.5, SD = 2.4). The 95% confidence interval for difference in administration was small (CI = -0.16 to 0.34). When examining MoCA domain scores, administration differences were either associated with no statistically significant effect, or if present due to large sample sizes, were associated with small effects and differences <0.5 point. Telehealth patients reported slightly lower PHQ-8 scores (F2F PHQ-8 = 2.0, SD = 2.5; telehealth PHQ-8 = 1.6, SD = 2.1), although these scores are well within the normal range. No group difference in GAD-7 scores was present (F2F GAD-7 = 1.4, SD = 2.4; telehealth PHQ-8 = 1.4, SD = 2.4).

DISCUSSION: This report with its large sample size and between subject cohort provides complementary evidence to smaller test-retest studies, further supporting equivalence of MoCA telehealth testing to F2F MoCA administration. These findings provide additional reassurance that administration mode does not introduce systematic performance differences for MoCA test administration, thereby permitting telehealth MoCA testing to be applied confidently for both clinical and research applications.

PMID:36762513 | DOI:10.1111/jgs.18271

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Factors associated with perioperative mortality after late open conversion for failed endovascular aortic repair

J Cardiovasc Surg (Torino). 2023 Feb 10. doi: 10.23736/S0021-9509.22.12491-2. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to perform a systematic review about the clinical and technical aspects of late open conversion for failed endovascular aortic repair (EVAR) of abdominal aortic aneurysms (AAA), and to investigate if the need for suprarenal aortic cross clamping, graft infection, urgent procedures, endoleaks and aortic rupture were associated with an increase of 30-days (perioperative) mortality.

EVIDENCE ACQUISITION: A literature search was conducted on PubMed using the words “open conversion endovascular” on December 29th, 2021. Studies included randomized controlled trials, cohort studies, and case series of patients submitted to open conversion that were performed at least 1 month after the initial EVAR for AAA, reporting about 30-days mortality after surgery. A meta-analysis was performed to explore the association of suprarenal aortic cross clamping, graft infection, urgent procedures, endoleaks and aortic rupture with 30-days postoperative mortality using log odds ratios (ORs), with STATA/MP 17.0 (Stata Corp. 2021, LLC). Two-sided P values less than 0.05 were considered statistically significant.

EVIDENCE SYNTHESIS: The search retrieved 985 results on PubMed from 1994 to 2021. Among them, 40 papers were included in the study for the systematic review, and 5 of them for the meta-analysis. A total of 2297 patients from 1992 to 2020 were submitted to open conversion after a median of 40.4 months from the initial EVAR. Endoleak was the most frequent cause of open conversion (76.3%). Perioperative mortality was 23.5% for urgent and 5.3% for elective conversions. At meta-analysis, urgent procedures and aortic rupture were both associated with higher perioperative mortality (OR 5.27, 95% CI 2.90-9.57 and OR 5.61, 95% CI 3.09-10.19 respectively). Similarly, patients with infections and who needed suprarenal aortic clamping were at higher risk of 30-days postoperative death (OR 3.74, 95% CI 1.96-7.13) and OR 2.23, 95% CI 1.24-4.02), while the presence of a preoperative endoleaks was not associated with a higher 30-days mortality.

CONCLUSIONS: Late open conversion after EVAR of AAA is burdened by a perioperative mortality rate of 23.5% for urgent and 5.3% for elective cases. Urgent treatment, presence of aortic rupture or infection, and the need for suprarenal aortic cross clamping were associated with increased perioperative mortality, while the presence of an endoleak did not affect perioperative mortality.

PMID:36762507 | DOI:10.23736/S0021-9509.22.12491-2

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Clonidine for preventing emergence agitation in infants (PREVENT AGITATION II). Protocol and statistical analysis plan

Acta Anaesthesiol Scand. 2023 Feb 10. doi: 10.1111/aas.14212. Online ahead of print.

ABSTRACT

BACKGROUND: Emergence agitation is a common clinical condition in children. Symptoms pertaining to the spectrum of early postoperative negative behavior typically occur upon emergence from anesthesia. Clonidine is an effective adjunctive agent for the prevention of emergence agitation in children, but evidence in the smallest age groups is sparse We aim to investigate the efficacy and safety of an intraoperative bolus of intravenous clonidine for preventing emergence agitation in children 3-12 months of age.

METHODS: This is a randomized, placebo-controlled, double-blind trial. We will enroll 320 patients aged 3-12 months who have been scheduled for general anesthesia maintained with sevoflurane and opioid. The randomization is parallel and stratified by age group, sex, and site. The investigational medicinal product will be administered intravenously approximately 20 minutes before the anticipated end of the surgical procedure. The intervention is clonidine 3 mcg/kg and placebo is isotonic saline in a corresponding volume.

RESULTS: The primary outcome is the incidence of emergence agitation as assessed on the Watcha scale i.e., any Watcha score > 2 during participants’ stay in the post-anesthetic care unit. Secondary outcomes are the proportion of participants with postoperative pain, with postoperative nausea and vomiting, and a composite safety outcome. Statistical analysis will be conducted according to the Statistical Analysis Plan with the intention-to-treat population for our primary analyses.

CONCLUSION: The PREVENT AGITATION II trial will contribute valuable knowledge on efficacy for the prevention of emergence agitation and safety in infants.

TRIAL REGISTRATION: EudraCT number: 2020-005409-26, clinicaltrials.gov: NCT05091242.

PMID:36762465 | DOI:10.1111/aas.14212

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Long term oncological outcomes for minimally invasive surgery versus open surgery for colon cancer – A population-based nationwide study with a non-inferiority design

Colorectal Dis. 2023 Feb 10. doi: 10.1111/codi.16512. Online ahead of print.

ABSTRACT

AIM: The study aimed to compare five-year overall survival in a national cohort of patients undergoing curative abdominal resection for colon cancer by minimally invasive surgery (MIS) or open (OPEN) technique.

METHODS: All patients diagnosed between 2010 and 2016 in Sweden with pathological UICC stage I-III colon cancer localized in the cecum, ascending colon, hepatic flexure or sigmoid colon, and those who underwent curative right sided hemicolectomy, sigmoid resection or high anterior resection by MIS or OPEN were included. Patients were identified in the Swedish Colorectal Cancer Registry from which all data was retrieved. The analyses were performed as intention-to-treat and the relationship between surgical technique (MIS or OPEN) and overall mortality within five years was analysed. For the primary research question a non-inferiority hypothesis was assumed with a statistical power of 90%, a one-side type I error of 2.5%, and a non-inferiority margin of 2%. For the secondary analyses, multilevel survival regression models with the patients matched by propensity scores were employed, adjusted for patient- and tumuor-related variables.

RESULTS: A total of 11605 pathological UICC cancer stage I-III patients were included with 3297 MIS (28.4%) and 8308 OPEN (71.6%) and were followed until December 31, 2020. The primary analysis demonstrated superiority for MIS compared to OPEN. The multilevel survival regression analyses confirmed that five-year overall survival was higher in MIS with a hazard ratio (HR) of 0.874 (95% confidence interval (CI): 0.791-0.965), and if excluding pT4, outcome was similar, with a HR of 0.847 (95% CI: 0.756-0.948).

CONCLUSION: This observational study demonstrated that MIS was favourable to OPEN with regard to five-year overall survival. These results support the use of laparoscopic colon cancer surgery in routine practise.

PMID:36762443 | DOI:10.1111/codi.16512

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The Role of Pre-Treatment Traumatic Stress Symptoms in Adolescent Substance Use Treatment Outcomes

Subst Use Misuse. 2023 Feb 10:1-9. doi: 10.1080/10826084.2023.2177960. Online ahead of print.

ABSTRACT

Background: Prominent theories suggest that individuals with co-occurring traumatic stress symptoms (TSS) and substance use (SU) may be less responsive to SU treatment compared to those with SU only. However, empirical findings in adult samples are mixed, and there has been limited work among adolescents. This study assesses the association between TSS and SU treatment outcomes among trauma-exposed adolescents, using statistical methods to reduce potential confounding from important factors such as baseline SU severity. Method: 2,963 adolescents with lifetime history of victimization received evidence-based SU treatment in outpatient community settings. At baseline, 3- and 6-months, youth were assessed using the Global Appraisal of Individual Needs Traumatic Stress Scale and the Substance Frequency Scale. Propensity score weighting was used to mitigate potential confounding due to baseline differences in sociodemographic characteristics and SU across youth with varying levels of TSS. Results: Propensity score weighting successfully balanced baseline differences in sociodemographic factors and baseline SU across youth. Among all youth, mean SU was lower at both 3- and 6- month follow-up relative to baseline, indicating declining use. After adjusting for potential confounders, we observed no statistically significant relationship between TSS and SU at either 3- or 6-month follow-up. Conclusions: Based on this investigation, conducted among a large sample of trauma-exposed youth receiving evidence-based outpatient SU treatment, baseline TSS do not appear to be negatively associated with SU treatment outcomes. However, future research should examine whether youth with TSS achieve better outcomes through integrative treatment for both SU and TSS.

PMID:36762441 | DOI:10.1080/10826084.2023.2177960

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Sleep Apnea in Children With Down Syndrome

Pediatrics. 2023 Feb 10:e2022058771. doi: 10.1542/peds.2022-058771. Online ahead of print.

ABSTRACT

OBJECTIVE: The authors of this study aimed to evaluate the use of polysomnography (PSG) in children with Down syndrome (DS) between ages 0 and 7 years, to assess the prevalence and severity of obstructive sleep apnea (OSA) and associated comorbidities, and to describe interventions used for OSA.

METHODS: A retrospective cohort study was performed at Cincinnati Children’s Hospital Medical Center for children with DS born between 2013 and 2019. Data were extracted from the electronic medical record, including demographics, age at PSG, PSG results, and interventions after an abnormal PSG. Statistical analysis included unadjusted bivariate association testing and multivariable logistic regression modeling to investigate associations with OSA severity.

RESULTS: Among 397 patients in the cohort, 59% (n = 235) had a documented PSG and 94% (n = 221) had an abnormal study with 60% (n = 141) demonstrating moderate or severe OSA. There was an inverse relationship between age and OSA severity (P < .001). In a multiple regression model, OSA severity was associated with increased rates of failure to thrive (P < .01), aspiration (P = .02), and laryngomalacia (P < .01). After medical or surgical intervention, 73% of patients experienced the resolution of OSA or an improvement in OSA severity.

CONCLUSION: In this study of pediatric patients with DS, OSA was identified most frequently in the first year of life. In addition, to prompt evaluation of symptomatic infants, our data support earlier PSG screening for patients requiring neonatal ICU care and those with feeding difficulties, airway abnormalities, and/or pulmonary hypertension given their increased risk for severe OSA.

PMID:36762410 | DOI:10.1542/peds.2022-058771

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Development a prediction model for identifying bacterial meningitis in young infants aged 29-90 days: a retrospective analysis

BMC Pediatr. 2023 Feb 9;23(1):69. doi: 10.1186/s12887-022-03813-1.

ABSTRACT

BACKGROUND: The early diagnosis and treatment of bacterial meningitis (BM) in young infants was very critical. But, it was difficult to make a definite diagnosis in the early stage due to nonspecific clinical symptoms. Our objectives were to find the risk factors associated with BM and develop a prediction model of BM especially for young infants.

METHODS: We retrospectively reviewed the clinical data of young infants with meningitis between January 2011 and December 2020 in Children’s Hospital of Soochow University. The independent risk factors of young infants with BM were screened using univariate and multivariate logistic regression analyses. The independent risk factors were used to construct a new scoring model and compared with Bacterial Meningitis Score (BMS) and Meningitis Score for Emergencies (MSE) models.

RESULTS: Among the 102 young infants included, there were 44 cases of BM and 58 of aseptic meningitis. Group B Streptococcus (22, 50.0%) and Escherichia coli (14, 31.8%) were the main pathogens of BM in the young infants. Multivariate logistic regression analysis identified procalcitonin (PCT), cerebrospinal fluid (CSF) glucose, CSF protein as independent risk factors for young infants with BM. We assigned one point for CSF glucose ≤ 1.86 mmol/L, two points were assigned for PCT ≥ 3.80 ng/ml and CSF protein ≥ 1269 mg/L. Using the not low risk criterion (score ≥ 1) with our new prediction model, we identified the young infantile BM with 100% (95% CI 91.9%-100%) sensitivity and 60.3% (95% CI 46.4%-72.9%) specificity. Compared with BMS and MSE model, our prediction model had larger area under receiver operating characteristic curve and higher specificity, the differences were statistically significant.

CONCLUSION: Our new scoring model for young infants can facilitate early identification of BM and has a better performance than BMS and MSE models.

PMID:36759812 | DOI:10.1186/s12887-022-03813-1

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Migrant and native women’s perceptions of prenatal care communication quality: the role of host-country language proficiency

BMC Public Health. 2023 Feb 9;23(1):295. doi: 10.1186/s12889-023-15154-4.

ABSTRACT

BACKGROUND: Despite the potentially significant impact of women-prenatal care provider communication quality (WPCQ) on women’s perinatal health, evidence on the determinants of those perceptions is still lacking, particularly among migrant women.

METHODS: We aimed to examine the effect of women’s host-country language proficiency on their perceived WPCQ. We analyzed the data of 1210 migrant and 1400 native women who gave birth at Portuguese public hospitals between 2017 and 2019 and participated in the baMBINO cohort study. Migrants’ language proficiency was self-rated. Perceived WPCQ was measured as a composite score of 9 different aspects of self-reported communication quality and ranged from 0 (optimal) to 27.

RESULTS: A high percentage of women (29%) rated communication quality as “optimal”. Zero-inflated regression models were fitted to estimate the association between language proficiency and perceived WPCQ. Women with full (aIRR 1.35; 95% CI 1.22,1.50), intermediate (aIRR 1.41; 95% CI 1.23,1.61), and limited (aIRR 1.72; 95% CI 1.45,2.05) language proficiencies were increasingly more likely to have lower WPCQ when compared to natives.

CONCLUSIONS: Facilitating communication with migrant women experiencing language barriers in prenatal care could provide an important contribution to improving prenatal care quality and addressing potential subsequent disparities in perinatal health outcomes.

PMID:36759808 | DOI:10.1186/s12889-023-15154-4

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Which is the best femoral implant in children with osteogenesis imperfecta? a retrospective cohort study of 783 procedures

BMC Musculoskelet Disord. 2023 Feb 9;24(1):110. doi: 10.1186/s12891-023-06222-2.

ABSTRACT

BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary genetic disorder characterized by bone fragility and extremity deformities. The surgical management for long-bone fractures and deformities in OI remains a challenge. We aimed to compare clinical outcomes after femoral surgery splinted with the telescopic rod, the plate and screws, the elastic nail and the non-elongating rod in setting of OI.

METHODS: A retrospective cohort study included 783 femoral procedures (mean age 6.00 (interquartile range (IQR) 5.00) years, 335 (42.8%) females) was conducted, and individuals were categorized into four groups according to implants. After verifying comparability among the groups, revision rate and implant survival period were compared among the Sillence types and the same comparison were made among four groups within each Sillence type. The incidence of refractures, deformities, and implant-related complications were also compared among the four groups.

RESULTS: There were no significant differences in demographic information among the four groups in terms of sex (p = 0.101), laterality (p = 0.587), Sillence type (p = 0.122), and postoperative follow-up period (p = 0.214). In total, children with Sillence type III had the highest revision rate and the shortest implant survival period; children with Sillence type I had the lowest revision rate and the longest implant survival period; and children with Sillence type IV had the revision rate and the implant survival period between those observed in Sillence types I and III. In Sillence types III and IV, the telescopic rod had lower revision rate (III 24.8%; IV 20.9%) compared to the plate (III 97.2%, p<0.001; IV 80.3%, p<0.001), the elastic nail (III 100.0%, p=0.019; IV 73.9%, p<0.001) and the non-elongating rod (III 65.0%, p<0.001; IV46.9%, p<0.001); the median implant survival period of the telescopic rod (III 48.00 (IQR 28.50) months; IV 43.00 (33.00) months) is longer than the plate (III 11.00 (9.00) months, p<0.001; IV 19.00 (20.00) months, p<0.001), the elastic nail (III 45.00 (37.75) months, p=1.000; IV 19.00 (35.00) months, p=0.028) and the non-elongating rod (III 39.00 (31.75) months, p=0.473; IV 38.50 (29.75) months, p=1.000).A similar trend was observed in Sillence type I (p = 0.063, p = 0.003; respectively). In addition, the incidence of refracture (15.5%), deformity (2.8%) and implant-related complications (23.1%) were also statistically lower in the telescopic rod group.

CONCLUSION: In our cohort, lower revision rate and longer implant survival period were observed in telescopic rod group. This was mainly due to the significant lower incidence of refracture, deformity and implant-related complications with the use of telescopic rod.

PMID:36759791 | DOI:10.1186/s12891-023-06222-2