Nevin Manimala

J Eukaryot Microbiol. 2023 May 26:e12986. doi: 10.1111/jeu.12986. Online ahead of print.

ABSTRACT

Several automated molecular methods have emerged for distinguishing eukaryote species based on DNA sequence data. However, there are knowledge gaps around which of these single-locus methods is more accurate for the identification of microalgal species, such as the highly diverse and ecologically relevant diatoms. We applied genetic divergence, Automatic Barcode Gap Discovery for primary species delimitation (ABGD), Assemble Species by Automatic Partitioning (ASAP), Statistical Parsimony Network Analysis (SPNA), Generalized Mixed Yule Coalescent (GMYC) and Poisson Tree Processes (PTP) using partial cox1, rbcL , 5.8S+ITS2 , ITS1+5.8S+ITS2 markers to delineate species and compare to published polyphasic identification data (morphological features, phylogeny and sexual reproductive isolation) to test the resolution of these methods. ASAP, ABGD, SPNA and PTP models resolved species of Eunotia, Seminavis, Nitzschia, Sellaphora and Pseudo-nitzschia corresponding to previous polyphasic identification, including reproductive isolation studies. In most cases, these models identified diatom species in similar ways, regardless of sequence fragment length. GMYC model presented smallest number of results that agreed with previous published identification. Following the recommendations for proper use of each model presented in the present study, these models can be useful tools to identify cryptic or closely-related species of diatoms, even when the datasets have relatively few sequences.

PMID:37243408 | DOI:10.1111/jeu.12986

Clin Trials. 2023 May 26:17407745231177046. doi: 10.1177/17407745231177046. Online ahead of print.

ABSTRACT

BACKGROUND: Composite time-to-event endpoints are beneficial for assessing related outcomes jointly in clinical trials, but components of the endpoint may have different censoring mechanisms. For example, in the PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr adults (PREVENTABLE) trial, the composite outcome contains one endpoint that is right censored (all-cause mortality) and two endpoints that are interval censored (dementia and persistent disability). Although Cox regression is an established method for time-to-event outcomes, it is unclear how models perform under differing component-wise censoring schemes for large clinical trial data. The goal of this article is to conduct a simulation study to investigate the performance of Cox models under different scenarios for composite endpoints with component-wise censoring.

METHODS: We simulated data by varying the strength and direction of the association between treatment and outcome for the two component types, the proportion of events arising from the components of the outcome (right censored and interval censored), and the method for including the interval-censored component in the Cox model (upper value and midpoint of the interval). Under these scenarios, we compared the treatment effect estimate bias, confidence interval coverage, and power.

RESULTS: Based on the simulation study, Cox models generally have adequate power to achieve statistical significance for comparing treatments for composite outcomes with component-wise censoring. In our simulation study, we did not observe substantive bias for scenarios under the null hypothesis or when the treatment has a similar relative effect on each component outcome. Performance was similar regardless of if the upper value or midpoint of the interval-censored part of the composite outcome was used.

CONCLUSION: Cox regression is a suitable method for analysis of clinical trial data with composite time-to-event endpoints subject to different component-wise censoring mechanisms.

PMID:37243355 | DOI:10.1177/17407745231177046

Clin Infect Dis. 2023 May 27:ciad308. doi: 10.1093/cid/ciad308. Online ahead of print.

ABSTRACT

BACKGROUND: It is unclear whether the reporting quality of antiretroviral non-inferiority randomised controlled trials (ARV NI-RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year.

METHODS: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 antiretroviral regimens used for HIV treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 (RoB 2.0) tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarise data; statistical tests were two-sided, with significance defined as p<0.05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded.

RESULTS: We included 160 articles reporting 171 trials. 101 of 160 (63.1%) did not justify the non-inferiority margin (NIM) used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat (ITT) and per-protocol (PP) analyses, while 118 (73.8%) described missing data handling. Ten of 171 (5.9%) trials reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double blinded (28.1% vs. 10.3%, p=0.029), and to describe missing data handling (78.5% vs. 59.0%, p=0.021). Overall risk of bias was low in 96 of 160 studies (60.0%).

CONCLUSION: ARV NI-RCTs should improve NIM justification, reporting of ITT and PP analyses, and missing data handling to increase CONSORT adherence.

PMID:37243351 | DOI:10.1093/cid/ciad308

Subst Use Misuse. 2023 May 26:1-4. doi: 10.1080/10826084.2023.2215323. Online ahead of print.

ABSTRACT

Background: Investigating tobacco use and associated factors is essential to set priorities and health promotion strategies among adolescents. Several studies examined the relationship between this behavior and the psychosocial salutogenic construct Sense of Coherence (SOC), but the evidence is limited to adolescents in high-income countries. This study aimed to analyze the association between tobacco use and SOC among Brazilian adolescent students. Methods: A cross-sectional school-based survey was conducted in 2018. Dependent variables were categorical binary (Yes/No): (1) Smoking experimentation (at least one puff in a lifetime); (2) Current smoking (at least one cigarette smoked in the last 30 days); (3) Daily cigarette smoking; and (4) Experimentation with hookah and/or other tobacco products (at least once in a lifetime). Independent variable SOC was assessed with the SOC-13 item scale. Independent-samples t-Test and Logistic regression were used in the statistical analyses. Potential confounders were identified using a Directed Acyclic Graph. Results: Participants were 3034 adolescents aged 13-19. The mean SOC scores were higher among adolescents who answered no to each of the dependent variables than among those who answered yes (p < .05). In the regression analysis, those with higher SOC scores were less likely to report smoking experimentation, current use, daily use, and experimentation with hookah and/or other tobacco products, than those with lower SOC scores. The associations remained after controlling for sociodemographic and/or social-environmental factors. Conclusion: An inverse relationship between SOC and tobacco use was observed among Brazilian adolescent students.

PMID:37243349 | DOI:10.1080/10826084.2023.2215323

Ann Neurol. 2023 May 26. doi: 10.1002/ana.26710. Online ahead of print.

ABSTRACT

OBJECTIVES: The glymphatic function has not yet been explored in behavioral variant frontotemporal dementia (bvFTD). The spatial correlation between regional glymphatic function and bvFTD remain unknown.

METHOD: A total of 74 patients with bvFTD and 67 age- and sex-matched healthy controls (HCs) were selected from discovery dataset and replication dataset. All participant underwent neuropsychological assessment. Glymphatic measures including choroid plexus (CP) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling between blood-oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling), were compared between the two groups. Regional glymphatic function was evaluated by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, and posterior regions. BvFTD-related metabolic pattern was identified using spatial covariance analysis based on ^l8 F-FDG-PET.

RESULTS: Patients with bvFTD showed higher CP volume (P < 0.001); anterior and middle DTI-ALPS (P < 0.001); and weaker anterior BOLD-CSF coupling (P < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI-ALPS was negatively associated with the expression of the bvFTD-related metabolic pattern (r = -0.52, P = 0.034) and positively related with regional standardized uptake value ratios of ^l8 F-FDG-PET in bvFTD-related brain regions (r = 0.49-0.62, P range: 0.017-0.047). Anterior and middle glymphatic function were related to global cognition and disease severity.

INTERPRETATION: Our findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD. This article is protected by copyright. All rights reserved.

PMID:37243334 | DOI:10.1002/ana.26710

Viruses. 2023 Apr 25;15(5):1047. doi: 10.3390/v15051047.

ABSTRACT

Missing Funding […].

PMID:37243304 | DOI:10.3390/v15051047

Viruses. 2023 May 19;15(5):1199. doi: 10.3390/v15051199.

ABSTRACT

INTRODUCTION: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking.

METHODS: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate-multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed.

RESULTS: Overall, 331 subjects were included; their median (q1-q3) age was 71 (51-80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3-11%) and 14% (95%CI = 3-25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02-0.77) when compared with monotherapy.

CONCLUSIONS: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial.

PMID:37243285 | DOI:10.3390/v15051199

Viruses. 2023 May 11;15(5):1157. doi: 10.3390/v15051157.

ABSTRACT

Pulmonary arterial hypertension (PAH) is common in severe coronavirus disease 2019 (COVID-19) and worsens the prognosis. Sildenafil, a phosphodiesterase-5 inhibitor, is approved for PAH treatment but little is known about its efficacy in cases of severe COVID-19 with PAH. This study aimed to investigate the clinical efficacy of sildenafil in patients with severe COVID-19 and PAH. Intensive care unit (ICU) patients were randomly assigned to receive sildenafil or a placebo, with 75 participants in each group. Sildenafil was administered orally at 0.25 mg/kg t.i.d. for one week in a placebo-controlled, double-blind manner as an add-on therapy alongside the patient’s routine treatment. The primary endpoint was one-week mortality, and the secondary endpoints were the one-week intubation rate and duration of ICU stay. The mortality rate was 4% vs. 13.3% (p = 0.078), the intubation rate was 8% and 18.7% (p = 0.09), and the length of ICU stay was 15 vs. 19 days (p < 0.001) for the sildenafil and placebo groups, respectively. If adjusted for PAH, sildenafil treatment significantly reduced mortality and intubation risks: OR = 0.21 (95% CI: 0.05-0.89) and OR = 0.26 (95% CI: 0.08-0.86), respectively. Sildenafil demonstrated some clinical efficacy in patients with severe COVID-19 and PAH and should be considered as an add-on therapy in these patients.

PMID:37243243 | DOI:10.3390/v15051157

Viruses. 2023 May 9;15(5):1127. doi: 10.3390/v15051127.

ABSTRACT

Tenofovir has been hypothesized to be effective against COVID-19 and is available as two prodrugs, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), both part of antiretroviral therapy (ART) regimens. People living with human immunodeficiency virus (PLWH) might be at higher risk for COVID-19 progression; however, information about the impact of tenofovir on COVID-19 clinical outcomes remains controversial. The COVIDARE is a prospective observational multicentric study in Argentina. PLWH with COVID-19 were enrolled from September 2020 to mid-June 2022. Patients were stratified according to baseline ART into those with tenofovir (TDF or TAF) and those without. Univariate and multivariate analyses were performed to evaluate the impact of tenofovir vs. non-tenofovir-containing regimens on major clinical outcomes. Of the 1155 subjects evaluated, 927 (80%) received tenofovir-based ART (79% TDF, 21% TAF) whilst the remaining population was under non-tenofovir regimens. The non-tenofovir group had older age and a higher prevalence of heart and kidney disease. Regarding the prevalence of symptomatic COVID-19, tomographic findings, hospitalization, and mortality, no differences were observed. The oxygen therapy requirement was higher in the non-tenofovir group. In the multivariate analyses, a first model with adjustment for viral load, CD4 T-cell count, and overall comorbidities showed that oxygen requirement was associated with non-tenofovir ART. In a second model with adjustment by chronic kidney disease, tenofovir exposure was not statistically significant.

PMID:37243213 | DOI:10.3390/v15051127

Viruses. 2023 Apr 26;15(5):1058. doi: 10.3390/v15051058.

ABSTRACT

Early menopause (<45 years) has significant impacts on bone, cardiovascular, and cognitive health. Several studies have suggested earlier menopause for women living with HIV; however, the current literature is limited by reliance on self-report data. We determined age at menopause in women living with HIV and socio-demographically similar HIV-negative women based on both self-report of menopause status (no menses for ≥12 months) and biochemical confirmation (defined as above plus follicle-stimulating hormone level ≥ 25 IU/mL). Multivariable median regression models assessed factors associated with menopause age, controlling for relevant confounders. Overall, 91 women living with HIV and 98 HIV-negative women were categorized as menopausal by self-report, compared to 83 and 92 by biochemical confirmation. Age at menopause did not differ significantly between groups, whether based on self-report (median [IQR]: 49.0 [45.3 to 53.0] vs. 50.0 [46.0 to 53.0] years; p = 0.28) or biochemical confirmation (50.0 [46.0 to 53.0] vs. 51.0 [46.0 to 53.0] years; p = 0.54). In the multivariable model, no HIV-related or psychosocial variables were associated with earlier age at menopause (all p > 0.05). Overall, HIV status per se was not statistically associated with an earlier age at menopause, emphasizing the importance of comparing socio-demographically similar women in reproductive health and HIV research.

PMID:37243146 | DOI:10.3390/v15051058