Tag: nevin manimala

JAMA Netw Open. 2022 Oct 3;5(10):e2234425. doi: 10.1001/jamanetworkopen.2022.34425.

ABSTRACT

IMPORTANCE: Communication and adoption of modern study design and analytical techniques is of high importance for the improvement of clinical research from observational data.

OBJECTIVE: To compare a modern method for statistical inference, including a target trial emulation framework and doubly robust estimation, with approaches common in the clinical literature, such as Cox proportional hazards models.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used longitudinal electronic health record data for outcomes at 28-days from time of hospitalization within a multicenter New York, New York, hospital system. Participants included adult patients hospitalized between March 1 and May 15, 2020, with COVID-19 and not receiving corticosteroids for chronic use. Data were analyzed from October 2021 to March 2022.

EXPOSURES: Corticosteroid exposure was defined as more than 0.5 mg/kg methylprednisolone equivalent in a 24-hour period. For target trial emulation, exposures were corticosteroids for 6 days if and when a patient met criteria for severe hypoxia vs no corticosteroids. For approaches common in clinical literature, treatment definitions used for variables in Cox regression models varied by study design (no time frame, 1 day, and 5 days from time of severe hypoxia).

MAIN OUTCOMES AND MEASURES: The main outcome was 28-day mortality from time of hospitalization. The association of corticosteroids with mortality for patients with moderate to severe COVID-19 was assessed using the World Health Organization (WHO) meta-analysis of corticosteroid randomized clinical trials as a benchmark.

RESULTS: A total of 3298 patients (median [IQR] age, 65 [53-77] years; 1970 [60%] men) were assessed, including 423 patients who received corticosteroids at any point during hospitalization and 699 patients who died within 28 days of hospitalization. Target trial emulation analysis found corticosteroids were associated with a reduced 28-day mortality rate, from 32.2%; (95% CI, 30.9%-33.5%) to 25.7% (95% CI, 24.5%-26.9%). This estimate is qualitatively identical to the WHO meta-analysis odds ratio of 0.66 (95% CI, 0.53-0.82). Hazard ratios using methods comparable with current corticosteroid research range in size and direction, from 0.50 (95% CI, 0.41-0.62) to 1.08 (95% CI, 0.80-1.47).

CONCLUSIONS AND RELEVANCE: These findings suggest that clinical research based on observational data can be used to estimate findings similar to those from randomized clinical trials; however, the correctness of these estimates requires designing the study and analyzing the data based on principles that are different from the current standard in clinical research.

PMID:36190729 | DOI:10.1001/jamanetworkopen.2022.34425

JAMA Intern Med. 2022 Oct 3. doi: 10.1001/jamainternmed.2022.4333. Online ahead of print.

ABSTRACT

IMPORTANCE: Cataract surgery in the US is routinely performed with anesthesia care, whereas anesthesia care for other elective, low-risk, outpatient procedures is applied more selectively.

OBJECTIVE: To identify predictors of anesthesia care in Medicare beneficiaries undergoing cataract surgery and evaluate anesthesia care for cataract surgery compared with other elective, low-risk, outpatient procedures.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective observational cohort study included Medicare beneficiaries 66 years or older who underwent cataract surgery in 2017. The data were analyzed from August 2020 through May 2021.

INTERVENTIONS (FOR CLINICAL TRIALS) OR EXPOSURES (FOR OBSERVATIONAL STUDIES): Anesthesia care during elective, low-risk, outpatient procedures.

MAIN OUTCOMES AND MEASURES: Prevalence of anesthesia care during cataract surgery compared with other low-risk procedures; association of anesthesia care with patient, clinician, and health system characteristics; and proportion of patients experiencing a systemic complication within 7 days of cataract surgery compared with patients undergoing other low-risk procedures.

RESULTS: Among 36 652 cataract surgery patients, the mean (SD) age was 74.7 (6.1) years; 21 690 (59.2%) were female; 2200 (6.6%) were Black and 32 049 (87.4%) were White. Anesthesia care was more common among patients undergoing cataract surgery compared with patients undergoing other low-risk procedures (89.8% vs range of <1% to 70.2%). Neither the patient’s age (adjusted odds ratio, 1.01; 95% CI, 1.00-1.02; P = .01) nor Charlson Comorbidity Index (CCI) score (CCI of ≥3: adjusted odds ratio, 1.06; 95% CI, 0.95-1.18; P = .28; reference, CCI score of 0-1) was strongly associated with anesthesia care for cataract surgery, but a model comprising a single variable identifying the ophthalmologist predicted anesthesia care with a C statistic of 0.96. Approximately 6.0% of ophthalmologists never used anesthesia care, 76.6% always used anesthesia care, and 17.4% used it for only a subset of patients. Fewer cataract surgery patients experienced systemic complications within 7 days (2833 [7.7%]), even when limited to patients of ophthalmologists who never used anesthesia care (108 [7.4%]), than patients undergoing other low-risk procedures (range, 13.2%-52.2%).

CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that systemic complications occurred less frequently after cataract surgery compared with other elective, low-risk, outpatient procedures during which anesthesia care was less commonly used. Anesthesia care was not associated with patient characteristics, such as older age or worse health status, but with the ophthalmologists’ usual approach to cataract surgery sedation. The study findings suggest an opportunity to use anesthesia care more selectively in patients undergoing cataract surgery.

PMID:36190717 | DOI:10.1001/jamainternmed.2022.4333

Ann Med. 2022 Dec;54(1):2710-2724. doi: 10.1080/07853890.2022.2122551.

ABSTRACT

INTRODUCTION: This article reports the results of a study conducted to assess the mediating effects of grit and learning agility on the relationship between academic burnout and learning engagement among undergraduate students.

METHODS: A cross-sectional survey was conducted using a self-report questionnaire. Undergraduate students (N = 344) were recruited from one university in South Korea (58.0% female; average age 21.43) to complete assessments of academic burnout, grit, learning agility, and learning engagement. Data were analysed using descriptive statistics, Pearson’s correlation coefficient, hierarchical regression and bootstrapping to verify the multiple parallel mediation effect.

RESULTS: We found that the direct effect of academic burnout on learning engagement (B= -0.26, p<.001) and the indirect effect of academic burnout as mediated by learning agility (B= -0.13; 95% CI, -0.20∼-0.06) were significant. This finding confirmed that 33.3% of the total effect of academic burnout on learning engagement was the result of indirect effects via learning agility.

CONCLUSION: These results indicate the necessity of developing an educational programme that focuses not only on reducing academic burnout but also on improving learning agility to increase undergraduate students’ learning engagement. This study contributes to the development of a curriculum aimed at increasing the effectiveness of university education, promoting learning engagement, and reducing academic burnout.KEY MESSAGEOur study reports that academic burnout has both a direct effect on learning engagement and an indirect effect via learning agility. Learning agility mediates the relationship between academic burnout and learning engagement among undergraduate students.Although grit has been reported by many previous studies to mediate the relationship between the tendency to pursue happiness and the willingness to continue learning and effectively improving one’s academic achievement and ability, our study did not find any mediating effect via grit in this context.

PMID:36190716 | DOI:10.1080/07853890.2022.2122551

JAMA Neurol. 2022 Oct 3. doi: 10.1001/jamaneurol.2022.3157. Online ahead of print.

ABSTRACT

IMPORTANCE: Racial and ethnic groups with higher rates of clinical Alzheimer disease (AD) are underrepresented in studies of AD biomarkers, including amyloid positron emission tomography (PET).

OBJECTIVE: To compare amyloid PET positivity among a diverse cohort of individuals with mild cognitive impairment (MCI) or dementia.

DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS), a single-arm multisite cohort study of Medicare beneficiaries who met appropriate-use criteria for amyloid PET imaging between February 2016 and September 2017 with follow-up through January 2018. Data were analyzed between April 2020 and January 2022. This study used 2 approaches: the McNemar test to compare amyloid PET positivity proportions between matched racial and ethnic groups and multivariable logistic regression to assess the odds of having a positive amyloid PET scan. IDEAS enrolled participants at 595 US dementia specialist practices. A total of 21 949 were enrolled and 4842 (22%) were excluded from the present analysis due to protocol violations, not receiving an amyloid PET scan, not having a positive or negative scan, or because of small numbers in some subgroups.

EXPOSURES: In the IDEAS study, participants underwent a single amyloid PET scan.

MAIN OUTCOMES AND MEASURES: The main outcomes were amyloid PET positivity proportions and odds.

RESULTS: Data from 17 107 individuals (321 Asian, 635 Black, 829 Hispanic, and 15 322 White) with MCI or dementia and amyloid PET were analyzed between April 2020 and January 2022. The median (range) age of participants was 75 (65-105) years; 8769 participants (51.3%) were female and 8338 (48.7%) were male. In the optimal 1:1 matching analysis (n = 3154), White participants had a greater proportion of positive amyloid PET scans compared with Asian participants (181 of 313; 57.8%; 95% CI, 52.3-63.2 vs 142 of 313; 45.4%; 95% CI, 39.9-50.9, respectively; P = .001) and Hispanic participants (482 of 780; 61.8%; 95% CI, 58.3-65.1 vs 425 of 780; 54.5%; 95% CI, 51.0-58.0, respectively; P = .003) but not Black participants (359 of 615; 58.4%; 95% CI, 54.4-62.2 vs 333 of 615; 54.1%; 95% CI, 50.2-58.0, respectively; P = .13). In the adjusted model, the odds of having a positive amyloid PET scan were lower for Asian participants (odds ratio [OR], 0.47; 95% CI, 0.37-0.59; P < .001), Black participants (OR, 0.71; 95% CI, 0.60-0.84; P < .001), and Hispanic participants (OR, 0.68; 95% CI, 0.59-0.79; P < .001) compared with White participants.

CONCLUSIONS AND RELEVANCE: Racial and ethnic differences found in amyloid PET positivity among individuals with MCI and dementia in this study may indicate differences in underlying etiology of cognitive impairment and guide future treatment and prevention approaches.

PMID:36190710 | DOI:10.1001/jamaneurol.2022.3157

JAMA Neurol. 2022 Oct 3. doi: 10.1001/jamaneurol.2022.3094. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with dementia may be at an increased suicide risk. Identifying groups at greatest risk of suicide would support targeted risk reduction efforts by clinical dementia services.

OBJECTIVES: To examine the association between a dementia diagnosis and suicide risk in the general population and to identify high-risk subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This was a population-based case-control study in England conducted from January 1, 2001, through December 31, 2019. Data were obtained from multiple linked electronic records from primary care, secondary care, and the Office for National Statistics. Included participants were all patients 15 years or older and registered in the Office for National Statistics in England with a death coded as suicide or open verdict from 2001 to 2019. Up to 40 live control participants per suicide case were randomly matched on primary care practice and suicide date.

EXPOSURES: Patients with codes referring to a dementia diagnosis were identified in primary care and secondary care databases.

MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) were estimated using conditional logistic regression and adjusted for sex and age at suicide/index date.

RESULTS: From the total sample of 594 674 patients, 580 159 (97.6%) were controls (median [IQR] age at death, 81.6[72.0-88.4] years; 289 769 male patients [50.0%]), and 14 515 (2.4%) died by suicide (median [IQR] age at death, 47.4 [36.0-59.7] years; 10 850 male patients [74.8%]). Among those who died by suicide, 95 patients (1.9%) had a recorded dementia diagnosis (median [IQR] age at death, 79.5 [67.1-85.5] years; median [IQR] duration of follow-up, 2.3 [1.0-4.4] years). There was no overall significant association between a dementia diagnosis and suicide risk (adjusted OR, 1.05; 95% CI, 0.85-1.29). However, suicide risk was significantly increased in patients diagnosed with dementia before age 65 years (adjusted OR, 2.82; 95% CI, 1.84-4.33), in the first 3 months after diagnosis (adjusted OR, 2.47; 95% CI, 1.49-4.09), and in patients with dementia and psychiatric comorbidity (adjusted OR, 1.52; 95% CI, 1.21-1.93). In patients younger than 65 years and within 3 months of diagnosis, suicide risk was 6.69 times (95% CI, 1.49-30.12) higher than in patients without dementia.

CONCLUSIONS AND RELEVANCE: Diagnostic and management services for dementia, in both primary and secondary care settings, should target suicide risk assessment to the identified high-risk groups.

PMID:36190708 | DOI:10.1001/jamaneurol.2022.3094

JAMA Pediatr. 2022 Oct 3. doi: 10.1001/jamapediatrics.2022.3611. Online ahead of print.

ABSTRACT

IMPORTANCE: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).

OBJECTIVE: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.

EXPOSURE: Administration of steroids within 2 days of admission.

MAIN OUTCOMES AND MEASURES: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.

RESULTS: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.

CONCLUSIONS AND RELEVANCE: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

PMID:36190706 | DOI:10.1001/jamapediatrics.2022.3611

JAMA Pediatr. 2022 Oct 3. doi: 10.1001/jamapediatrics.2022.3456. Online ahead of print.

ABSTRACT

IMPORTANCE: The risk and benefits of COVID-19 vaccination during pregnancy are under investigation. Pooled evidence regarding neonatal and maternal outcomes in association with COVID-19 vaccination during pregnancy is scarce.

OBJECTIVE: To evaluate the association between COVID-19 vaccination during pregnancy and peripartum outcomes.

DATA SOURCES: PubMed and EMBASE databases were searched on April 5, 2022. Language restrictions were not applied.

STUDY SELECTION: Prospective trials and observational studies comparing the individuals who received at least 1 COVID-19 vaccination during pregnancy with those who did not and reporting the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, neonatal intensive care units (NICU) admission, and intrauterine fetal death (IFD).

DATA EXTRACTION AND SYNTHESIS: Two independent investigators extracted relevant data from each study. Odds ratios (ORs) were calculated using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines.

MAIN OUTCOMES AND MEASURES: The primary outcomes were the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, NICU admission, and IFD. The secondary outcomes were maternal outcomes, including maternal SARS-CoV-2 infection, cesarean delivery, postpartum hemorrhage, and chorioamnionitis.

RESULTS: Nine observational studies involving 81 349 vaccinated (mean age, 32-35 years) and 255 346 unvaccinated individuals during pregnancy (mean age, 29.5-33 years) were included. COVID-19 vaccination during pregnancy was associated with lower risk of NICU admission (OR, 0.88; 95% CI, 0.80-0.97) and IFD (OR, 0.73; 95% CI, 0.57-0.94), whereas there was no statistically significant association with preterm birth (OR, 0.89; 95% CI, 0.76-1.04), small for gestational age (OR, 0.99; 95% CI, 0.94-1.04), and low Apgar score (OR, 0.94; 95% CI, 0.87-1.02). COVID-19 vaccination during pregnancy was associated with a lower risk of maternal SARS-CoV-2 infection (OR, 0.46; 95% CI, 0.22-0.93), whereas it was not associated with increased risk of cesarean delivery (OR, 1.05; 95% CI, 0.93-1.20), postpartum hemorrhage (OR, 0.95; 95% CI, 0.83-1.07), and chorioamnionitis (OR, 0.95; 95% CI, 0.83-1.07).

CONCLUSIONS AND RELEVANCE: COVID-19 vaccination during pregnancy was not associated with an increase in the risk of peripartum outcomes, was associated with a decreased risk of NICU admission, IFD, and maternal SARS-CoV-2 infection. Thus, COVID-19 vaccination should be encouraged for pregnant individuals.

PMID:36190704 | DOI:10.1001/jamapediatrics.2022.3456

Mol Neurobiol. 2022 Oct 3. doi: 10.1007/s12035-022-03054-4. Online ahead of print.

ABSTRACT

Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which are tPA-BDNF pathways proteins and are thought to play a role in synaptic pruning, as a possible endophenotype of schizophrenia. Forty drug-naïve patients with first-episode psychosis (FEP) matched for age, gender, and level of education, 40 unaffected siblings (UAS) of patients with FEP, and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH, and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway as well as the pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiate FEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the HCs with statistically significant differences between all 3 groups. The plasma level of pro-BDNF in the HC group was similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ and this imbalance could be an endophenotype of the disease.

PMID:36190691 | DOI:10.1007/s12035-022-03054-4

J Magn Reson Imaging. 2022 Aug 17. doi: 10.1002/jmri.28391. Online ahead of print.

ABSTRACT

BACKGROUND: Dual-phenotype hepatocellular carcinoma (DPHCC) is highly aggressive and difficult to distinguish from hepatocellular carcinoma (HCC).

PURPOSE: To develop and validate clinical and radiomics models based on contrast-enhanced MRI for the preoperative diagnosis of DPHCC.

STUDY TYPE: Retrospective.

POPULATION: A total of 87 patients with DPHCC and 92 patients with non-DPHCC randomly divided into a training cohort (n = 125: 64 non-DPHCC; 61 DPHCC) and a validation cohort (n = 54: 28 non-DPHCC; 26 DPHCC).

FIELD STRENGTH/SEQUENCE: A 3.0 T; dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging sequence.

ASSESSMENT: In the clinical model, the maximum tumor diameter and hepatitis B virus (HBV) were independent risk factors of DPHCC. In the radiomics model, a total of 1781 radiomics features were extracted from tumor volumes of interest (VOIs) in the arterial phase (AP) and portal venous phase (PP) images. For feature reduction and selection, Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were used. Clinical, AP, PP, and combined radiomics models were established using machine learning algorithms (support vector machine [SVM], logistic regression [LR], and logistic regression-least absolute shrinkage and selection operator [LR-LASSO]) and their discriminatory efficacy assessed and compared.

STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Chi-square test, regression analysis, receiver operating characteristic curve (ROC) analysis, Pearson correlation analysis, the Delong test. A P value < 0.05 was considered statistically significant.

RESULTS: In the validation cohort, the combined radiomics model (area under the curve [AUC] = 0.908, 95% confidence interval [CI]: 0.831-0.985) showed the highest diagnostic performance. The AUCs of the PP (AUC = 0.879, 95% CI: 0.779-0.979) and combined radiomics models were significantly higher than that of clinical model (AUC = 0.685, 95% CI: 0.526-0.844). There were no significant differences in AUC between AP or PP radiomics model and combined radiomics model (P = 0.286, 0.180 and 0.543).

CONCLUSION: MRI radiomics models may be useful for discriminating DPHCC from non-DPHCC before surgery.

EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

PMID:36190656 | DOI:10.1002/jmri.28391

J Clin Psychol Med Settings. 2022 Oct 3. doi: 10.1007/s10880-022-09912-6. Online ahead of print.

ABSTRACT

American Indian (AI) mothers experience high rates of postpartum depression (PPD). We evaluated the factor structure of the Edinburgh Postnatal Depression Scale (EPDS) among AI mothers from a rural AI serving health system. We also investigated potential associations between EPDS scores and selected psychosocial factors (n = 315). Exploratory Factor Analysis (n = 157) showed that a one-factor structure best fits the data. A Confirmatory Factor Analysis was then conducted to examine the fit of the one-factor model (n = 158). Goodness-of-fit statistics showed overall poor model fit (RMSEA = .13) which may be suggestive of an indicator of depression among Natives not detected by the EPDS. Results of the multiple regression analysis were non-significant. The findings demonstrated that while the EPDS measured aspects of PPD, there may be additional aspects of depression specific to the AI women in our sample not captured by the EPDS. Limitations and directions for future research are discussed.

PMID:36190607 | DOI:10.1007/s10880-022-09912-6