Nevin Manimala

JAMA Netw Open. 2023 Jul 3;6(7):e2321554. doi: 10.1001/jamanetworkopen.2023.21554.

ABSTRACT

IMPORTANCE: Blood-based measurements of total tau (T-tau) are commonly used to examine neuronal injury in patients with traumatic brain injury (TBI), but current assays do not differentiate between brain-derived tau (BD-tau) and tau produced in peripheral tissues. A novel assay for BD-tau has recently been reported that selectively quantifies nonphosphorylated tau of central nervous system origin in blood samples.

OBJECTIVES: To examine the association of serum BD-tau with clinical outcomes in patients with severe TBI (sTBI) and its longitudinal changes over 1 year.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted at the neurointensive unit at the Sahlgrenska University Hospital, Gothenburg, Sweden, between September 1, 2006, and July 1, 2015. The study included 39 patients with sTBI followed up for up to 1 year. Statistical analysis was performed between October and November 2021.

EXPOSURES: Serum BD-tau, T-tau, phosphorylated tau231 (p-tau231), and neurofilament light chain (NfL) measured on days 0, 7, and 365 after injury.

MAIN OUTCOMES AND MEASURES: Associations of serum biomarkers with clinical outcome and longitudinal change in sTBI. Severity of sTBI was evaluated using the Glasgow Coma Scale at hospital admission, while clinical outcome was assessed with the Glasgow Outcome Scale (GOS) at 1-year follow-up. Participants were classified as having a favorable outcome (GOS score, 4-5) or unfavorable outcome (GOS score, 1-3).

RESULTS: Among the 39 patients (median age at admission, 36 years [IQR, 22-54 years]; 26 men [66.7%]) in the study on day 0, the mean (SD) serum BD-tau level was higher among patients with unfavorable outcomes vs those with favorable outcomes (191.4 [190.8] pg/mL vs 75.6 [60.3] pg/mL; mean difference, 115.9 pg/mL [95% CI, 25.7-206.1 pg/mL]), while the other markers had smaller between-group mean differences (serum T-tau, 60.3 pg/mL [95% CI, -22.0 to 142.7 pg/mL]; serum p-tau231, 8.3 pg/mL [95% CI, -6.4 to 23.0 pg/mL]; serum NfL, -5.4 pg/mL [95% CI, -99.0 to 88.3 pg/mL]). Similar results were recorded on day 7. Longitudinally, baseline serum BD-tau concentrations showed slower decreases in the whole cohort (42.2% on day 7 [from 138.6 to 80.1 pg/mL] and 93.0% on day 365 [from 138.6 to 9.7 pg/mL]) compared with serum T-tau (81.5% on day 7 [from 57.3 to 10.6 pg/mL] and 99.0% on day 365 [from 57.3 to 0.6 pg/mL]) and p-tau231 (92.5% on day 7 [from 20.1 to 1.5 pg/mL] and 95.0% on day 365 [from 20.1 to 1.0 pg/mL]). These results did not change when considering clinical outcome, where T-tau decreased twice as fast as BD-tau in both groups. Similar results were obtained for p-tau231. Furthermore, the biomarker levels on day 365 were lower, compared with day 7, for BD-tau but not T-tau or p-tau231. Serum NfL had a different trajectory to the tau biomarkers, with levels increasing by 255.9% on day 7 compared with day 0 (from 86.8 to 308.9 pg/mL) but decreasing by 97.0% by day 365 vs day 7 (from 308.9 to 9.2 pg/mL).

CONCLUSIONS AND RELEVANCE: This study suggests that serum BD-tau, T-tau, and p-tau231 have differential associations with clinical outcome and 1-year longitudinal change in patients with sTBI. Serum BD-tau demonstrated utility as a biomarker to monitor outcomes in sTBI and can provide valuable information regarding acute neuronal damage.

PMID:37399012 | DOI:10.1001/jamanetworkopen.2023.21554

JAMA Netw Open. 2023 Jul 3;6(7):e2321644. doi: 10.1001/jamanetworkopen.2023.21644.

ABSTRACT

IMPORTANCE: The NASONE (Nasal Oscillation Post-Extubation) trial showed that noninvasive high-frequency oscillatory ventilation (NHFOV) slightly reduces the duration of invasive mechanical ventilation (IMV) in preterm infants, whereas NHFOV and noninvasive intermittent positive pressure ventilation (NIPPV) result in fewer reintubations than nasal continuous positive airway pressure (NCPAP). It is unknown whether NHFOV is similarly effective in extremely preterm neonates or in those with more severe respiratory failure (based on the duration of previous ventilation and CO2 levels).

OBJECTIVE: To clarify whether NHFOV is better than NIPPV and NCPAP in reducing the duration of IMV in extremely preterm neonates or those with severe respiratory failure.

DESIGN, SETTING, AND PARTICIPANTS: This study is a predefined secondary analyses of a multicenter randomized clinical trial that was performed at tertiary academic neonatal intensive care units (NICUs) in China. Participants included neonates enrolled in the NASONE trial between December 2017 and May 2021 and belonging to 3 predefined subgroups: (1) born at less than or equal to 28 weeks’ (plus 6 days) gestation, (2) invasively ventilated for more than 1 week from birth, and (3) with CO2 greater than 50 mm Hg before or in the 24 hours after extubation. Data analysis was performed in August 2022.

INTERVENTION: NCPAP, NIPPV, or NHFOV since the first extubation and until NICU discharge, with airway pressure higher in NHFOV than in NIPPV and than in NCPAP.

MAIN OUTCOMES AND MEASURES: The co-primary outcomes were total duration of IMV during the NICU stay, need for reintubation, and ventilator-free days calculated as per the original trial protocol. Outcomes were analyzed on an intention-to-treat basis as for the whole trial, and subgroup analyses followed the original statistical plan.

RESULTS: Among 1137 preterm infants, 455 (279 boys [61.3%]) were born at 28 weeks’ gestation or less, 375 (218 boys [58.1%]) underwent IMV for more than 1 week from birth, and 307 (183 boys [59.6%]) had CO2 greater than 50 mm Hg before or in the 24 hours after extubation. Both NIPPV and NHFOV were associated with significantly fewer reintubations (risk difference range, -28% [95% CI, -39% to -17%] to -15% [95% CI, -25% to -4%]; number needed to treat, 3-7 infants) and early reintubations (risk difference range, -24% [95% CI, -35% to -14%] to -20% [95% CI, -30% to -10%]) than NCPAP, and these reintubations were less frequently due to refractory hypoxemia. IMV was shorter in the NIPPV and NHFOV groups (mean difference range, -5.0 days [95% CI, -6.8 to -3.1 days] to -2.3 days [95% CI, -4.1 to -0.4 days]) than in the NCPAP group. Co-primary outcomes were not different between NIPPV and NHFOV; there was no significant interaction effect. Infants in the NHFOV group showed significantly less moderate-to-severe bronchopulmonary dysplasia than infants in the NCPAP group (range, -12% to -10%; number needed to treat, 8-9 infants) and better postextubation gas exchange in all subgroups. The 3 interventions were provided at different mean airway pressure and were equally safe.

CONCLUSIONS AND RELEVANCE: The subgroup analyses of extremely preterm or more ill infants confirm the results obtained in the whole population: NIPPV and NHFOV appeared equally effective in reducing duration of IMV compared with NCPAP.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03181958.

PMID:37399009 | DOI:10.1001/jamanetworkopen.2023.21644

Asian Bioeth Rev. 2023 Feb 7;15(3):241-258. doi: 10.1007/s41649-023-00241-w. eCollection 2023 Jul.

ABSTRACT

Evidence suggests a limited contribution to the total research output in leading obstetrics and gynaecology journals by researchers from the developing world. Editorial bias, quality of scientific research produced and language barriers have been attributed as possible causes for this phenomenon. The aim of this study was to understand the prevalence of editorial board members based out of low and lower-middle income countries in leading journals in the field of obstetrics and gynaecology. The top 21 journals in the field of obstetrics and gynaecology were selected based on their impact factor, SCImago ranking and literature search. The composition of the editorial boards of these journals was studied based on World Bank Income Criteria to understand the representation status of researchers from low and lower-middle income countries. A total of 1315 board members make up the editorial composition of leading obstetrics and gynaecology journals. The majority of these editors belong to high-income countries (n = 1148; 87.3%). Low (n = 6; 0.45%) and lower-middle income (n = 55; 4.18%) countries make up for a very minuscule proportion of editorial board members. Only a meagre 9 out of 21 journals have editorial board members from these countries (42.85%). Low and low-middle countries have poor representation in the editorial boards of leading obstetrics and gynaecology journals. Poor representation in research from these countries has grave consequences for a large proportion of the global population and multidisciplinary collaborative efforts must be taken to rapidly change this statistic with immediate effect.

PMID:37399006 | PMC:PMC9902818 | DOI:10.1007/s41649-023-00241-w

Lancet Rheumatol. 2023 Jul;5(7):e375-e385. doi: 10.1016/S2665-9913(23)00127-3. Epub 2023 May 31.

ABSTRACT

BACKGROUND: Studies on long-term consequences of COVID-19, commonly referred to as post-COVID condition, in patients with inflammatory rheumatic diseases are scarce and inconclusive. Furthermore, classifying patients with inflammatory rheumatic diseases as having post-COVID condition is complicated because of overlapping symptoms. Therefore, we investigated the risk of post-COVID condition and time until recovery, and compared the prevalence of symptoms seen in post-COVID condition, between patients with inflammatory rheumatic diseases and healthy controls, with and without a history of COVID-19.

METHODS: In this substudy we used data from an ongoing prospective cohort study in the Netherlands. All adult patients with inflammatory rheumatic diseases from the Amsterdam Rheumatology and Immunology Center in Amsterdam, the Netherlands, were invited to participate in the study between April 26, 2020, and March 1, 2021. All patients were asked, but not obliged, to recruit their own control participant of the same sex, of comparable age (< 5 years), and without an inflammatory rheumatic disease. Demographic and clinical data, including data on the occurrence of SARS-CoV-2 infections, were collected via online questionnaires. On March 10, 2022, all study participants received a questionnaire on the occurrence, onset, severity, and duration of persistent symptoms during the first 2 years of the COVID-19 pandemic, independent of their history of SARS-CoV-2 infection. Additionally, we prospectively monitored a subset of participants who had a PCR or antigen confirmed SARS-CoV-2 infection in the 2-month period surrounding the questionnaire in order to assess COVID-19 sequelae. In line with WHO guidelines, post-COVID condition was defined as persistent symptoms that lasted at least 8 weeks, started after the onset and within 3 months of a PCR or antigen-confirmed SARS-CoV-2 infection, and could not be explained by an alternative diagnosis. Statistical analyses included descriptive statistics, logistic regression analyses, logistic-based causal mediation analyses, and Kaplan-Meier survival analyses for time until recovery from post-COVID condition. In exploratory analyses, E-values were calculated to investigate unmeasured confounding.

FINDINGS: A total of 1974 patients with inflammatory rheumatic disease (1268 [64%] women and 706 [36%] men; mean age 59 years [SD 13]) and 733 healthy controls (495 [68%] women and 238 [32%] men; mean age 59 years [12]) participated. 468 (24%) of 1974 patients with inflammatory rheumatic disease and 218 (30%) of 733 healthy controls had a recent SARS-CoV-2 omicron infection. Of those, 365 (78%) of 468 patients with inflammatory rheumatic disease and 172 (79%) of 218 healthy controls completed the prospective follow-up COVID-19 sequelae questionnaires. More patients than controls fulfilled post-COVID condition criteria: 77 (21%) of 365 versus 23 (13%) of 172 (odds ratio [OR] 1·73 [95% CI 1·04-2·87]; p=0·033). The OR was attenuated after adjusting for potential confounders (adjusted OR 1·53 [95% CI 0·90-2·59]; p=0·12). Among those without a history of COVID-19, patients with inflammatory diseases were more likely to report persistent symptoms consistent with post-COVID condition than were healthy controls (OR 2·52 [95% CI 1·92-3·32]; p<0·0001). This OR exceeded the calculated E-values of 1·74 and 1·96. Recovery time from post-COVID condition was similar for patients and controls (p=0·17). Fatigue and loss of fitness were the most frequently reported symptoms in both patients with inflammatory rheumatic disease and healthy controls with post-COVID condition.

INTERPRETATION: Post-COVID condition after SARS-CoV-2 omicron infections was higher in patients with inflammatory rheumatic disease than in healthy controls based on WHO classification guidelines. However, because more patients with inflammatory rheumatic disease than healthy controls without a history of COVID-19 reported symptoms that are commonly used to define a post-COVID condition during the first 2 years of the pandemic, it is likely that the observed difference in post-COVID condition between patients and controls might in part be explained by clinical manifestations in the context of underlying rheumatic diseases. This highlights the limitations of applying current criteria for post-COVID condition in patients with inflammatory rheumatic disease, and suggests it might be appropriate for physicians to keep a nuanced attitude when communicating the long-term consequences of COVID-19.

FUNDING: ZonMw (the Netherlands organization for Health Research and Development) and Reade foundation.

PMID:37398978 | PMC:PMC10292827 | DOI:10.1016/S2665-9913(23)00127-3

Biol Sport. 2023 Jul;40(3):699-706. doi: 10.5114/biolsport.2023.119287. Epub 2022 Sep 22.

ABSTRACT

This study aimed to investigate the effect of a combined jump and sprint training program, two sessions a week for 6 weeks, on sprinting, change of directions (COD) and jumping performance in semi-professional soccer players. Twenty soccer players were enrolled in this randomized controlled trial (age 20 ± 2 years, body mass 74.3 ± 5.9 kg). Players were randomized into two groups such as training group (TG, n = 10 players) or control group (CG, n = 10 players). Physical tests were performed before and after 6 weeks of training such as sprint 10 m, sprint 30 m, 505-COD test and standing long jump (LJ). The two groups performed the same training except for the combined jump and sprint training performed twice a week by TG. After 6 weeks of training, between-group analysis reported statistical difference in favor of the TG in sprint 10 m (p = 0.015, η² = 0.295, large), sprint 30 m (p < 0.001, η² = 0.599, large), in 505-COD (p = 0.026, η² = 0.154, large), and LJ (p = 0.025, η² = 0.027, small). These data indicate that combined sprint and jump training, when performed twice a week, for the duration of 6 weeks, in addition to the regular team training, can improve specific physical performance in male soccer players. This study has shown that a volume increment of 10% after 3 weeks of training can be a suitable training dose progression and that a combination of 64-70 jumps and 675-738 m of sprinting training per session can yield benefits in sprint, COD and jump performance.

PMID:37398964 | PMC:PMC10286599 | DOI:10.5114/biolsport.2023.119287

Biol Sport. 2023 Jul;40(3):835-855. doi: 10.5114/biolsport.2023.121322. Epub 2022 Nov 22.

ABSTRACT

The purpose of this investigation is to estimate the global disease burden attributable to low physical activity (PA) in 204 countries and territories from 1990 to 2019 by age, sex, and Socio-Demographic Index (SDI). Detailed information on global deaths and disability-adjusted life years (DALYs) attributable to low PA were collected from the Global Burden of Disease Study 2019. The ideal exposure scenario of PA was defined as 3000-4500 metabolic equivalent minutes per week and low PA was considered to be less than this threshold. Age-standardization was used to improve the comparison of rates across locations or between time periods. In 2019, low PA seems to contribute to 0.83 million [95% uncertainty interval (UI) 0.43 to 1.47] deaths and 15.75 million (95% UI 8.52 to 28.62) DALYs globally, an increase of 83.9% (95% UI 69.3 to 105.7) and 82.9% (95% UI 65.5 to 112.1) since 1990, respectively. The age-standardized rates of low-PA-related deaths and DALYs per 100,000 people in 2019 were 11.1 (95% UI 5.7 to 19.5) and 198.4 (95% UI 108.2 to 360.3), respectively. Of all age-standardized DALYs globally in 2019, 0.6% (95% UI 0.3 to 1.1) may be attributable to low PA. The association between SDI and the proportion of age-standardized DALYs attributable to low PA suggests that regions with the highest SDI largely decreased their proportions of age-standardized DALYs attributable to low PA during 1990-2019, while other regions tended to have increased proportions in the same timeframe. In 2019, the rates of low-PA-related deaths and DALYs tended to rise with increasing age in both sexes, with no differences between males and females in the age-standardized rates. An insufficient accumulation of PA across the globe occurs together with a considerable public health burden. Health initiatives to promote PA within different age groups and countries are urgently needed.

PMID:37398951 | PMC:PMC10286621 | DOI:10.5114/biolsport.2023.121322

Biol Sport. 2023 Jul;40(3):899-918. doi: 10.5114/biolsport.2023.122479. Epub 2023 Feb 1.

ABSTRACT

Ice-hockey requires high acceleration and speed sprint abilities, but it is unclear what the distance characteristic is for measuring these capabilities. Therefore, this systematic meta-analysis aims to summarize the sprint reference values for different sprint distances and suggest the appropriate use of ice-hockey straight sprint testing protocols. A total of 60 studies with a pooled sample of 2254 males and 398 females aged 11-37 years were included. However, the pooled data for women was not large enough to permit statistical analysis. The sprint distance used for measuring the reported acceleration and speed was between 4-48 m. Increased test distance was positively associated with increased speed (r = 0.70) and negatively with average acceleration (r = -0.87). Forward skating sprint speed increases with the measured distance up to 26 m and do not differ much from longer distance tests, while acceleration decreases with a drop below 3 m/s at distances 15 m and longer. The highest acceleration (5.89 m/s² peak, 3.31 m/s² average) was achieved in the shortest distances up to 7 m which significantly differs from 8-14 m tests. The highest speed (8.1 m/s peak, 6.76 m/s average) has been recorded between 26-39 m; therefore, distances over 39 m are not necessary to achieve maximum speed. Considering match demands and most reported test distances, 6.1 m is the recommended distance for peak acceleration and 30 m for peak speed. The sprint time, acceleration, and speed of each individual and the number of skating strides should be reported in future studies.

PMID:37398950 | PMC:PMC10286618 | DOI:10.5114/biolsport.2023.122479

J Open Source Softw. 2023;8(82):4181. doi: 10.21105/joss.04181. Epub 2023 Feb 21.

ABSTRACT

Statistical causal inference of mixed exposures has been limited by reliance on parametric models and, until recently, by researchers considering only one exposure at a time, usually estimated as a beta coefficient in a generalized linear regression model (GLM). This independent assessment of exposures poorly estimates the joint impact of a collection of the same exposures in a realistic exposure setting. Marginal methods for mixture variable selection such as ridge/lasso regression are biased by linear assumptions and the interactions modeled are chosen by the user. Clustering methods such as principal component regression lose both interpretability and valid inference. Newer mixture methods such as quantile g-computation (Keil et al., 2020) are biased by linear/additive assumptions. More flexible methods such as Bayesian kernel machine regression (BKMR)(Bobb et al., 2014) are sensitive to the choice of tuning parameters, are computationally taxing and lack an interpretable and robust summary statistic of dose-response relationships. No methods currently exist which finds the best flexible model to adjust for covariates while applying a non-parametric model that targets for interactions in a mixture and delivers valid inference for a target parameter. Non-parametric methods such as decision trees are a useful tool to evaluate combined exposures by finding partitions in the joint-exposure (mixture) space that best explain the variance in an outcome. However, current methods using decision trees to assess statistical inference for interactions are biased and are prone to overfitting by using the full data to both identify nodes in the tree and make statistical inference given these nodes. Other methods have used an independent test set to derive inference which does not use the full data. The CVtreeMLE R package provides researchers in (bio)statistics, epidemiology, and environmental health sciences with access to state-of-the-art statistical methodology for evaluating the causal effects of a data-adaptively determined mixed exposure using decision trees. Our target audience are those analysts who would normally use a potentially biased GLM based model for a mixed exposure. Instead, we hope to provide users with a non-parametric statistical machine where users simply specify the exposures, covariates and outcome, CVtreeMLE then determines if a best fitting decision tree exists and delivers interpretable results.

PMID:37398941 | PMC:PMC10312067 | DOI:10.21105/joss.04181

J Migr Health. 2023 Jan 24;7:100164. doi: 10.1016/j.jmh.2023.100164. eCollection 2023.

ABSTRACT

BACKGROUND: Adolescent substance use is a significant issue which occurs during a critical period of life of youth. Perceived stress is a risk factor for adolescent substance use, and life events such as low family support, and community and familial turmoil often lead to ongoing feelings of stress and uncertainty. Similarly, structural factors such as poverty, local neighborhood disinvestment and disrepair, and exposure to racism and discrimination are linked to feelings of stress. The US-Mexico border region is favorable for drug smuggling. Such a context exacerbates stressful life events during adolescence and increases the risk of adolescent substance use. This study aims to investigate the impact family support has on substance use in adolescents living on either side of the U.S./Mexico border who self-reported high perceptions of disordered neighborhood stress, border community and immigration stress, or normalization of drug trafficking.

METHODS: This study used data from the cross-sectional BASUS survey. Logistic regression was used to study the association between family support and past 30-day use of alcohol, tobacco, marijuana, and any substance in a sample restricted to students who self-reported high perceptions of disordered neighborhood stress, border community and immigration stress, or normalization of drug trafficking.

RESULTS: Participants with low family support were at higher risk of using any substance compared to participants with high family support (aOR= 1.58, 95% CI: 1.02; 2.45). Similar results were found for alcohol (aOR= 1.79, 95% CI: 1.13, 2.83). While the odds of using tobacco were higher for those with low social support as compared to participants with higher social support, this association was not statistically significant (aOR = 1.74, 95% CI: 0.93, 3.27).

CONCLUSION: Prevention programs tailored to the U.S.-Mexico border region should emphasize strengthening family support as a preventive factor against adolescent substance use. Family support should be considered in school counseling assessments, healthcare screenings and other social services.

PMID:37398939 | PMC:PMC10313897 | DOI:10.1016/j.jmh.2023.100164

J Struct Biol X. 2023 Jun 2;7:100089. doi: 10.1016/j.yjsbx.2023.100089. eCollection 2023.

ABSTRACT

Correlation functions play an important role in the theoretical underpinnings of many disparate areas of the physical sciences: in particular, scattering theory. More recently, they have become useful in the classification of objects in areas such as computer vision and our area of cryoEM. Our primary classification scheme in the cryoEM image processing system, EMAN2, is now based on third order invariants formulated in Fourier space. This allows a factor of 8 speed up in the two classification procedures inherent in our software pipeline, because it allows for classification without the need for computationally costly alignment procedures. In this work, we address several formal and practical aspects of such multispectral invariants. We show that we can formulate such invariants in the representation in which the original signal is most compact. We explicitly construct transformations between invariants in different orientations for arbitrary order of correlation functions and dimension. We demonstrate that third order invariants distinguish 2D mirrored patterns (unlike the radial power spectrum), which is a fundamental aspects of its classification efficacy. We show the limitations of 3rd order invariants also, by giving an example of a wide family of patterns with identical (vanishing) set of 3rd order invariants. For sufficiently rich patterns, the third order invariants should distinguish typical images, textures and patterns.

PMID:37398937 | PMC:PMC10314203 | DOI:10.1016/j.yjsbx.2023.100089