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Nevin Manimala Statistics

Preliminary Evaluation of a Novel Point of Care Diagnostic Device for Sports-Related Concussion

Clin J Sport Med. 2022 Nov 1;32(6):623-626. doi: 10.1097/JSM.0000000000001056. Epub 2022 Jul 6.

ABSTRACT

OBJECTIVE: Visinin-like protein 1 (VILIP-1) is a neuron-specific calcium sensor protein rapidly released into blood after mild traumatic brain injury (mTBI) and may be a suitable biomarker for identification of sports-related concussion (SRC). The objective of the study is to test if quantification of a specific post-translationally modified (ubiquitinated) form of VILIP-1 (ubVILIP-1) from a fingerstick blood sample using a point of care (POC) lateral flow device (LFD) can be used to rapidly identify athletes with SRC.

DESIGN: Prospective cohort study.

SETTING: Side-line blood collection at football, soccer, and volleyball games/practices.

PARTICIPANTS: Division I athletes with/without SRC.

MAIN OUTCOME MEASURES: Blood ubVILIP-1 concentrations.

RESULTS: Data collected over 2 athletic seasons from non-SRC athletes (controls) show a small but statistically significant elevation of ubVILIP-1 over an individual season for male athletes (P = 0.02) dependent on sport (P = 0.014) and no significant changes in ubVILIP-1 levels between seasons. For SRC athletes, the data show ubVILIP-1 levels substantially increase above baseline as soon as 30 minutes postdiagnosis with peak concentrations and times postinjury that vary based on injury severity.

CONCLUSION: Results of the study suggest quantification of blood ubVILIP-1 levels measured using an LFD may provide an objective identification of athletes with SRC, setting the stage for further study with a larger number of SRC patients.

PMID:36315821 | DOI:10.1097/JSM.0000000000001056

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Longitudinal Prediction of Ventricular Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Circ Arrhythm Electrophysiol. 2022 Oct 31:e011207. doi: 10.1161/CIRCEP.122.011207. Online ahead of print.

ABSTRACT

BACKGROUND: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator stratifies risk for incident sustained ventricular arrhythmias (VA) at the time of ARVC diagnosis. However, included risk factors change over time, and how well the ARVC risk calculator performs at follow-up is unknown.

METHODS: This was a retrospective analysis of patients with definite ARVC and without prior sustained VA. Risk factors for VA including age, nonsustained ventricular tachycardia, premature ventricular complex burden, T-wave inversions on electrocardiogram, cardiac syncope, right ventricular function, therapeutic medication use, and exercise intensity were assessed at the time of 2010 Task Force Criteria based ARVC diagnosis and upon repeat evaluations. Changes in these risk factors were analyzed over 5-year follow-up. The 5-year risk of VA was predicted longitudinally using (1) the baseline ARVC risk calculator prediction, (2) the ARVC risk prediction calculated using updated risk factors, and (3) time-varying Cox regression. Discrimination and calibration were assessed in comparison to observed VA event rates.

RESULTS: Four hundred eight patients with ARVC experiencing 132 primary VA events were included. Matched comparison of risk factors at baseline versus at 5 years of follow-up revealed decreased burdens of premature ventricular complexes (-1200/day) and nonsustained ventricular tachycardia (-14%). Presence of significant right ventricular dysfunction and number of T-wave inversions on electrocardiogram were unchanged. Observed risk for VA decreased by 13% by 5 years follow-up. The baseline ARVC risk calculator’s ability to predict 5-year VA risk worsened during follow-up (C statistics, 0.83 at diagnosis versus 0.68 at 5 years). Both the updated ARVC risk calculator (C statistics of 0.77) and time-varying Cox regression model (C statistics, 0.77) had strong discrimination. The updated ARVC risk calculator overestimated 5-year VA risk by an average of +6%.

CONCLUSION: Risk factors for VA in ARVC are dynamic, and overall risk for incident sustained VA decreases during follow-up. Up-to-date risk factor assessment improves VA risk stratification.

PMID:36315818 | DOI:10.1161/CIRCEP.122.011207

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Nevin Manimala Statistics

Advances and Applications of Polygenic Scores for Coronary Artery Disease

Annu Rev Med. 2022 Oct 31. doi: 10.1146/annurev-med-042921-112629. Online ahead of print.

ABSTRACT

Polygenic scores quantify inherited risk by integrating information from many common sites of DNA variation into a single number. Rapid increases in the scale of genetic association studies and new statistical algorithms have enabled development of polygenic scores that meaningfully measure-as early as birth-risk of coronary artery disease. These newer-generation polygenic scores identify up to 8% of the population with triple the normal risk based on genetic variation alone, and these individuals cannot be identified on the basis of family history or clinical risk factors alone. For those identified with increased genetic risk, evidence supports risk reduction with least two interventions, adherence to a healthy lifestyle and cholesterol-lowering therapies, that can substantially reduce risk. Alongside considerable enthusiasm for the potential of polygenic risk estimation to enable a new era of preventive clinical medicine is recognition of a need for ongoing research into how best to ensure equitable performance across diverse ancestries, how and in whom to assess the scores in clinical practice, as well as randomized trials to confirm clinical utility. Expected final online publication date for the Annual Review of Medicine, Volume 74 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:36315649 | DOI:10.1146/annurev-med-042921-112629

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Nevin Manimala Statistics

Risk factors for the presence and persistence of posttraumatic stress symptoms following traumatic brain injury in U.S. service members and veterans

J Trauma Stress. 2022 Oct 31. doi: 10.1002/jts.22892. Online ahead of print.

ABSTRACT

This study aimed to identify risk factors predictive of the presence and persistence of posttraumatic stress disorder (PTSD) symptom reporting following traumatic brain injury (TBI). Participants were 1,301 U.S. service members and veterans (SMVs) divided into four groups: uncomplicated mild TBI (mTBI; n = 543); complicated mild, moderate, severe, and penetrating TBI (n = 230); injured controls (n = 340); and noninjured controls (n = 188). We examined 25 factors related to demographic, injury-related, military-specific, treatment/health care need, and mental health/social support variables. Seven factors were statistically associated with the presence of DSM-IV-TR symptom criteria for PTSD: premorbid IQ, combat exposure, depression, social participation, history of mTBI, need for managing mood and stress, and need for improving memory and attention, p < .001 (51.3% variance). When comparing the prevalence of these risk factors in a longitudinal cohort (n = 742) across four PTSD trajectory groups (i.e., asymptomatic, improved, developed, persistent), a higher proportion of participants in the persistent PTSD group reported worse depression, a lack of social participation, and history of mTBI. Additionally, a higher proportion of participants in the persistent and developed PTSD groups reported the need for managing mood/stress and improving memory/attention. When considered simultaneously, the presence of ≥ 1 or ≥ 2 risk factors was associated with a higher proportion of participants in the developed and persistent PTSD groups, ps < .001. These risk factors may be useful in identifying SMVs at risk for the development and/or persistence of PTSD symptoms who may need intervention.

PMID:36315642 | DOI:10.1002/jts.22892

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Hate crime victimization and reporting within Miami’s queer Latine immigrant population

Law Hum Behav. 2022 Oct 31. doi: 10.1037/lhb0000505. Online ahead of print.

ABSTRACT

OBJECTIVES: This research examined hate crime victimization and crime reporting among Miami’s lesbian, gay, bisexual, transgender, and queer (LGBTQ) Latine immigrant population.

HYPOTHESES: Informed by the intersectionality perspective and the Cuban dominance thesis, I predicted that respondents would experience higher levels of victimization than what law enforcement data capture, yet the vast majority of these crimes would go unreported (Hypothesis 1); Respondents or third parties would be more likely to report victimization to police as crime severity increased (Hypothesis 2); and Cuban LGBTQ victims would be more likely to report crime than non-Cuban Latines (Hypothesis 3).

METHOD: Four hundred LGBTQ immigrant Latine individuals (age: M = 37.7 years, Cuban = 51.5%, transgender = 5.8%) in Miami completed face-to-face interviews through a three-stage venue-based sampling procedure.

RESULTS: Although 48% of screened respondents reported experiencing at least one incident of victimization within 5 years, they reported only 15% of these incidents to police (supporting Hypothesis 1). Increased violent and property crime were associated with markedly increased reporting (odds ratio [OR] = 5.44, p < .001), as was the use of a weapon (OR = 2.80, p < .01; supporting Hypothesis 2). Friends’ encouragement to report a crime was by far the strongest predictor of crime reporting (OR = 12.47, p < .001). Cuban Americans were less likely to report anti-LGBTQ hate crimes to the police, although this effect was not statistically significant after models accounted for documented and new immigrant measures of (supporting Hypothesis 3).

CONCLUSIONS: Hate crime victimization and underreporting were prevalent in this sample. Given the different crime-reporting outcomes for Cuban victims, it is important to examine victimization and crime reporting among the Latine population by country of origin. Queer networks and friends within the LGBTQ community may facilitate reporting crime and seeking help. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:36315640 | DOI:10.1037/lhb0000505

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Chemometric approach to the composition of flavonoid compounds and phenolic acids and antioxidant potential of Artemisia species from different habitats

Chem Biodivers. 2022 Oct 31. doi: 10.1002/cbdv.202200365. Online ahead of print.

ABSTRACT

Four Artemisia species from Serbia were selected for the study: A. annua L., A. absinthium L., A. vulgaris L. and A. scoparia Waldst. et Kit. because of the proven excellent action in treating certain medical conditions and diseases. A. absinthium L., A. vulgaris L., A. annua L. and A. scoparia Waldst. et Kit. collected from different habitats across Serbia (48 samples in total) were studied from the statistical aspect considering the phenolic and flavonoid contents, compositions, and antioxidant activities of methanol extracts in correlation with the soil type. The components were identified using HPLC (High Performance Liquid Chromatography), while antioxidant activities were determined by seven assays (TP (Total phenolic content), TF (Total flavonoid content), DPPH (2,2-diphenyl-1-picrylhydrazy) radical-based, ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical cation-based, FRAP (Ferric Reducing Antioxidant Power), TRP (Total Reducing Power), and CUPRAC (Cupric Reducing Antioxidant Capacity). The results were processed using five statistical methods (PCA (Principal Component Analysis), ANOVA (Analysis of Variance), MANOVA (Multivariate analysis of variance), DA (Discriminant analysis), and AHC (Agglomerative Hierarchical Clustering)). Principal component analysis enabled very well separation of the analyzed Artemisia species based on the content of total phenolics, total flavonoids, and the values obtained from antioxidant tests, but not on the individual compounds identified and quantified by HPLC. The MANOVA analyses showed that for A. scoparia and A. annua there was a significant effect of soil type on the total phenolics, total flavonoids, and antioxidant tests. In contrast, for A. vulgaris and A. absinthium, that effect was not significant. Additional MANOVA analyses showed a significant effect of soil type on phenolic and flavonoid compounds in the case of A. vulgaris, A. annua, and A. absinthium. The overall correct classification rate of all samples of four investigated Artemisia species by the discriminant analysis was 81.25% using the training sample and 72.92% the cross-validation results based on TP, TF, and antioxidant tests, but a much lower based on selected compounds identified and quantified by HPLC. MANOVA analyses based on particular Artemisia species show that soil is a significant factor affecting the measurable variables.

PMID:36315629 | DOI:10.1002/cbdv.202200365

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Systematic Review of Surgical Interventions for Inferior Turbinate Hypertrophy

Am J Rhinol Allergy. 2022 Oct 31:19458924221134555. doi: 10.1177/19458924221134555. Online ahead of print.

ABSTRACT

BACKGROUND: Various surgical interventions exist for treatment of inferior turbinate hypertrophy (ITH). Though mucosal-sparing techniques are generally preferred, there is lack of consensus on the optimal technique.

OBJECTIVE: This systematic review sought to evaluate the evidence for treatment of bilateral nasal obstruction via inferior turbinate reduction (ITR) and provide a meta-analysis of expected results of various techniques.

METHODS: PubMed, Scopus, Cochrane Library databases were queried to include articles describing surgical treatment for ITH. Exclusion criteria were concurrent nasal procedures or non-mucosal ITH. Primary outcomes included visual analog scale for nasal obstruction, nasal cavity volume by acoustic rhinometry, and resistance by anterior rhinomanometry. Subgroup analyses assessed outcomes by rhinitis diagnosis and length of follow-up, and radiofrequency ablation (RFA) was compared to microdebrider-assisted turbinoplasty (MAIT).

RESULTS: A total of 1870 studies were identified with 62 meeting inclusion criteria. Reported techniques included turbinectomy, submucosal resection, RFA, MAIT, laser, or electrocautery.All techniques demonstrated significant improvements in nasal obstruction using the visual analog scale. Further comprehensive physiologic data for RFA, MAIT, and laser was available and, compared to baseline, these techniques resulted in significant improvements in nasal resistance, nasal cavity volume, and nasal airflow. Six studies directly compared RFA and MAIT with statistically similar results on VAS, nasal cavity volume, and resistance with median follow-up time of 3.5 months. Assessment of VAS congestion over time reveals peak benefit is achieved between 3-6 months follow-up.

CONCLUSIONS: All reviewed ITR techniques improve patient-reported nasal obstruction. RFA and MAIT provide comparable improvements in patient-reported and physiologic nasal airflow outcomes and while benefits are sustained long-term, the peak benefit for both techniques appears to be achieved within the first year.

PMID:36315624 | DOI:10.1177/19458924221134555

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The number of cases, mortality and treatments of viral hemorrhagic fevers: A systematic review

PLoS Negl Trop Dis. 2022 Oct 31;16(10):e0010889. doi: 10.1371/journal.pntd.0010889. Online ahead of print.

ABSTRACT

BACKGROUND: Viral hemorrhagic fevers (VHFs) are a group of diseases, which can be endemo-epidemic in some areas of the world. Most of them are characterized by outbreaks, which, occur irregularly and are hard to predict. Innovative medical countermeasures are to be evaluated but due to the field specificities of emerging VHF, challenges arise when implementing clinical studies. To assess the state of the art around VHFs, we conducted a systematic review for all reports and clinical studies that included specific results on number of cases, mortality and treatment of VHFs.

METHODS: The search was conducted in January 2020 based on PRISMA guidelines (PROSPERO CRD42020167306). We searched reports on the WHO and CDC websites, and publications in three international databases (MEDLINE, Embase and CENTRAL). Following the study selection process, qualitative and quantitative data were extracted from each included study. A narrative synthesis approach by each VHF was used. Descriptive statistics were conducted including world maps of cases number and case fatality rates (CFR); summary tables by VHF, country, time period and treatment studies.

RESULTS: We identified 141 WHO/CDC reports and 126 articles meeting the inclusion criteria. Most of the studies were published after 2010 (n = 97 for WHO/CDC reports and n = 93 for publications) and reported number of cases and/or CFRs (n = 141 WHO/CDC reports and n = 88 publications). Results varied greatly depending on the outbreak or cluster and across countries within each VHF. A total of 90 studies focused on Ebola virus disease (EVD). EVD outbreaks were reported in Africa, where Sierra Leone (14,124 cases; CFR = 28%) and Liberia (10,678 cases; CFR = 45%) reported the highest cases numbers, mainly due to the 2014-2016 western Africa outbreak. Crimean-Congo hemorrhagic fever (CCHF) outbreaks were reported from 31 studies in Africa, Asia and Europe, where Turkey reported the highest cases number (6,538 cases; CFR = 5%) and Afghanistan the last outbreak in 2016/18 (293 cases; CFR = 43%). Regarding the 38 studies reporting results on treatments, most of them were non-randomized studies (mainly retrospective or non-randomized comparative studies), and only 10 studies were randomized controlled trials. For several VHFs, no specific investigational therapeutic option with strong proof of effectiveness on mortality was identified.

CONCLUSION: We observed that number of cases and CFR varied greatly across VHFs as well as across countries within each VHF. The number of studies on VHF treatments was very limited with very few randomized trials and no strong proof of effectiveness of treatment against most of the VHFs. Therefore, there is a high need of methodologically strong clinical trials conducted in the context of VHF.

PMID:36315609 | DOI:10.1371/journal.pntd.0010889

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Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis

Circulation. 2022 Nov;146(18):1383-1405. doi: 10.1161/CIRCULATIONAHA.122.061732. Epub 2022 Oct 31.

ABSTRACT

SGLT2 (sodium-glucose cotransporter 2) inhibitors produce a distinctive pattern of benefits on the evolution and progression of cardiomyopathy and nephropathy, which is characterized by a reduction in oxidative and endoplasmic reticulum stress, restoration of mitochondrial health and enhanced mitochondrial biogenesis, a decrease in proinflammatory and profibrotic pathways, and preservation of cellular and organ integrity and viability. A substantial body of evidence indicates that this characteristic pattern of responses can be explained by the action of SGLT2 inhibitors to promote cellular housekeeping by enhancing autophagic flux, an effect that may be related to the action of these drugs to produce simultaneous upregulation of nutrient deprivation signaling and downregulation of nutrient surplus signaling, as manifested by an increase in the expression and activity of AMPK (adenosine monophosphate-activated protein kinase), SIRT1 (sirtuin 1), SIRT3 (sirtuin 3), SIRT6 (sirtuin 6), and PGC1-α (peroxisome proliferator-activated receptor γ coactivator 1-α) and decreased activation of mTOR (mammalian target of rapamycin). The distinctive pattern of cardioprotective and renoprotective effects of SGLT2 inhibitors is abolished by specific inhibition or knockdown of autophagy, AMPK, and sirtuins. In the clinical setting, the pattern of differentially increased proteins identified in proteomics analyses of blood collected in randomized trials is consistent with these findings. Clinical studies have also shown that SGLT2 inhibitors promote gluconeogenesis, ketogenesis, and erythrocytosis and reduce uricemia, the hallmarks of nutrient deprivation signaling and the principal statistical mediators of the ability of SGLT2 inhibitors to reduce the risk of heart failure and serious renal events. The action of SGLT2 inhibitors to augment autophagic flux is seen in isolated cells and tissues that do not express SGLT2 and are not exposed to changes in environmental glucose or ketones and may be related to an ability of these drugs to bind directly to sirtuins or mTOR. Changes in renal or cardiovascular physiology or metabolism cannot explain the benefits of SGLT2 inhibitors either experimentally or clinically. The direct molecular effects of SGLT2 inhibitors in isolated cells are consistent with the concept that SGLT2 acts as a nutrient surplus sensor, and thus, its inhibition causes enhanced nutrient deprivation signaling and its attendant cytoprotective effects, which can be abolished by specific inhibition or knockdown of AMPK, sirtuins, and autophagic flux.

PMID:36315602 | DOI:10.1161/CIRCULATIONAHA.122.061732

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Effect of active tuberculosis on the survival of HIV-infected adult patients who initiated antiretroviral therapy at public hospitals of Eastern Ethiopia: A retrospective cohort study

PLoS One. 2022 Oct 31;17(10):e0277021. doi: 10.1371/journal.pone.0277021. eCollection 2022.

ABSTRACT

BACKGROUND: In resource-limited countries such as Ethiopia, tuberculosis is the major cause of morbidity and mortality among people living with the human immunodeficiency virus. In the era of antiretroviral therapy, the effect of tuberculosis on the survival of patients who are living with human immunodeficiency virus has been poorly understood in Ethiopia. Therefore, this study aimed to determine the effect of active tuberculosis on the survival of HIV-infected adult patients who initiated antiretroviral therapy in public hospitals in Eastern Ethiopia.

METHODS: An institution-based retrospective cohort study was conducted among 566 participants from January 1, 2014, to June 30, 2018. The collected data were entered into EpiData version 3.1 before being exported to Stata version 14 for analysis. A Cox proportional hazard model was used to determine the effect of active tuberculosis on the survival of HIV-infected adult patients who initiated antiretroviral therapy, and a p-value less than 0.05 and a 95% confidence level were used to declare statistical significance.

RESULT: Of the 566 patients included in the study, 76 died. The mortality rate was 11.04 per 100 person-years in tuberculosis co-infected patients, while it was 2.52 per 100 person-years in non-tuberculosis co-infected patients. The patients with tuberculosis co-infection had a 2.19 times higher hazard of death (AHR: 2.19; 95% CI: 1.17, 4.12) compared to those without tuberculosis. Advanced clinical stage, low CD4+ cell count, and previous episodes of an opportunistic infection other than tuberculosis were found to be independent predictors of mortality.

CONCLUSION: Co-infection with tuberculosis at antiretroviral therapy initiation increases the hazard of death approximately two-fold. Hence, we recommend key organizations to enhance the region’s collaborative interventional and preventative strategies for TB and HIV.

PMID:36315573 | DOI:10.1371/journal.pone.0277021