Nevin Manimala

Am J Obstet Gynecol MFM. 2023 May 9:101012. doi: 10.1016/j.ajogmf.2023.101012. Online ahead of print.

ABSTRACT

BACKGROUND: Some data suggest an association between abnormal fetal fraction on noninvasive prenatal screen and adverse pregnancy outcomes including low birthweight, preeclampsia, and preterm birth in the absence of aneuploidy. These findings suggest that abnormal fetal fraction may be associated with placental pathologic processes in early gestation.

OBJECTIVE: The purpose of this study is to determine the independent association of fetal fraction on genetic noninvasive prenatal screen and histologic placental types.

STUDY DESIGN: This is a retrospective cohort study at a single institution between January 2017 and March 2021 of livebirths ≥ 24 weeks who had noninvasive prenatal screen (NIPS) and placental pathology results available. Results were stratified by trimester of NIPS. Clinical characteristics were compared by quartile of FF using chi square tests. Linear regression was used to model continuous FF as a function of 3 histologic types representing chronic placental injury- chronic inflammation, maternal vascular malperfusion (MVM), and fetal vascular malperfusion. Inverse probability weighting was used to account for selection bias in characteristics of patients with placental pathology examination.

RESULTS: 1,374 patients had NIPS in the first trimester and 262 in the second trimester. Preterm birth and hypertensive disorders of pregnancy were most common in the lowest quartile of FF. Chronic inflammation was associated with a 0.56 percentage point reduction in FF (95% CI: -0.95, -0.16) and MVM was associated with 0.48 percentage point reduction in FF (95% CI: -0.91, -0.04) in adjusted models. The association with MVM was no longer statistically significant after accounting for selection bias in placentas sent for pathologic examination. Second trimester FF was not associated with placental pathology.

CONCLUSION: Chronic inflammation is associated with lower first trimester FF even after accounting for selection bias. Higher fetal fraction in the second trimester was associated with fetal vascular pathology, although this association was no longer statistically significant after inverse probability weighting to account for selection bias. First trimester FF may be a biomarker of adverse outcomes associated with chronic inflammation.

PMID:37169285 | DOI:10.1016/j.ajogmf.2023.101012

Nucleic Acids Res. 2023 May 11:gkad325. doi: 10.1093/nar/gkad325. Online ahead of print.

ABSTRACT

The mpox virus (MPXV) is mutating at an exceptional rate for a DNA virus and its global spread is concerning, making genomic surveillance a necessity. With MpoxRadar, we provide an interactive dashboard to track virus variants on mutation level worldwide. MpoxRadar allows users to select among different genomes as reference for comparison. The occurrence of mutation profiles based on the selected reference is indicated on an interactive world map that shows the respective geographic sampling site in customizable time ranges to easily follow the frequency or trend of defined mutations. Furthermore, the user can filter for specific mutations, genes, countries, genome types, and sequencing protocols and download the filtered data directly from MpoxRadar. On the server, we automatically download all MPXV genomes and metadata from the National Center for Biotechnology Information (NCBI) on a daily basis, align them to the different reference genomes, generate mutation profiles, which are stored and linked to the available metainformation in a database. This makes MpoxRadar a practical tool for the genomic survaillance of MPXV, supporting users with limited computational resources. MpoxRadar is open-source and freely accessible at https://MpoxRadar.net.

PMID:37167010 | DOI:10.1093/nar/gkad325

Stat Methods Med Res. 2023 May 11:9622802231167435. doi: 10.1177/09622802231167435. Online ahead of print.

ABSTRACT

Dynamic treatment regimens (DTRs), also known as treatment algorithms or adaptive interventions, play an increasingly important role in many health domains. DTRs are motivated to address the unique and changing needs of individuals by delivering the type of treatment needed, when needed, while minimizing unnecessary treatment. Practically, a DTR is a sequence of decision rules that specify, for each of several points in time, how available information about the individual’s status and progress should be used in practice to decide which treatment (e.g. type or intensity) to deliver. The sequential multiple assignment randomized trial (SMART) is an experimental design widely used to empirically inform the development of DTRs. Sample size planning resources for SMARTs have been developed for continuous, binary, and survival outcomes. However, an important gap exists in sample size estimation methodology for SMARTs with longitudinal count outcomes. Furthermore, in many health domains, count data are overdispersed-having variance greater than their mean. We propose a Monte Carlo-based approach to sample size estimation applicable to many types of longitudinal outcomes and provide a case study with longitudinal overdispersed count outcomes. A SMART for engaging alcohol and cocaine-dependent patients in treatment is used as motivation.

PMID:37167008 | DOI:10.1177/09622802231167435

JMIR Form Res. 2023 May 11;7:e44831. doi: 10.2196/44831.

ABSTRACT

BACKGROUND: Misleading health claims are widespread in the media, and making choices based on such claims can negatively affect health. Thus, developing effective learning resources to enable people to think critically about health claims is of great value. Serious games can become an effective learning resource in this respect, as they can affect motivation and learning.

OBJECTIVE: This study aims to document how user insights and input can inform the concept and development of a serious game application in critical thinking about health claims in addition to gathering user experiences with the game application.

METHODS: This was a mixed methods study in 4 successive phases with both qualitative and quantitative data collected in the period from 2020-2022. Qualitative data on design and development were obtained from 4 unrecorded discussions, and qualitative evaluation data were obtained from 1 recorded focus group interview and 3 open-ended questions in the game application. The quantitative data originate from user statistics. The qualitative data were analyzed thematically, and user data were analyzed using nonparametric tests.

RESULTS: The first unrecorded discussion revealed that the students’ (3 participants’) assessment of whether a claim was reliable or not was limited to performing Google searches when faced with an ad for a health intervention. On the basis of the acquired knowledge of the target group, the game’s prerequisites, and the technical possibilities, a pilot of the game was created and reviewed question by question in 3 unrecorded discussions (6 participants). After adjustments, the game was advertised at the Oslo Metropolitan University, and 193 students tested the game. A correlation (r=0.77; P<.001) was found between the number of replays and total points achieved in the game. There was no demonstrable difference (P=.07) between the total scores of students from different faculties. Overall, 36.3% (70/193) of the students answered the evaluation questions in the game. They used words such as “fun” and “educational” about the experiences with the game, and words such as “motivating” and “engaging” related to the learning experience. The design was described as “varied” and “user-friendly.” Suggested improvements include adding references, more games and modules, more difficult questions, and an introductory text explaining the game. The results from the focus group interview (4 participants) corresponded to a large extent with the results of the open-ended questions in the game.

CONCLUSIONS: We found that user insights and inputs can be successfully used in the concept and development of a serious game that aims to engage students to think critically about health claims. The mixed methods evaluation revealed that the users experienced the game as educational and fun. Future research may focus on assessing the effect of the serious game on learning outcomes and health choices in randomized trials.

PMID:37166972 | DOI:10.2196/44831

JMIR Diabetes. 2023 May 11;8:e44295. doi: 10.2196/44295.

ABSTRACT

BACKGROUND: A very low-carbohydrate (VLC) nutritional strategy may improve glycemic control and weight loss in adults with type 2 diabetes (T2D). However, the supplementary behavioral strategies that might be able to improve outcomes using this nutritional strategy are uncertain.

OBJECTIVE: This study aims to compare the impact of adding 3 different supplementary behavioral strategies to a web-based VLC diet intervention. To our knowledge, this is the first trial to randomize participants to different frequencies of dietary self-monitoring.

METHODS: The study included 112 overweight adults with T2D (hemoglobin A_1c ≥6.5%) taking no antiglycemic medications or only metformin. They received a remotely delivered 12-month VLC diet intervention. Participants were randomly assigned through a full factorial 2×2×2 design to supplementary strategies: either daily or monthly dietary self-monitoring, either mindful eating training or not, and either positive affect skills training or not. Our research goal was to determine whether 3 different supplemental strategies had at least a medium effect size (Cohen d=0.5).

RESULTS: Overall, the VLC intervention led to statistically significant improvements in glycemic control (-0.70%, 95% CI -1.04% to -0.35%; P<.001), weight loss (-6.82%, 95% CI -8.57% to -5.08%; P<.001), and depressive symptom severity (Cohen d -0.67, 95% CI -0.92 to -0.41; P<.001). Furthermore, 30% (25/83) of the participants taking metformin at baseline reduced or discontinued their metformin. Only 1 Cohen d point estimate reached 0.5; daily (vs monthly) dietary self-monitoring had a worse impact on depressive symptoms severity (Cohen d=0.47, 95% CI -0.02 to 0.95; P=.06). None of the strategies had a statistically significant effect on outcomes. For changes in our primary outcome, hemoglobin A_1c, the daily (vs monthly) dietary self-monitoring impact was 0.42% (95% CI -0.28% to 1.12%); for mindful eating, it was -0.47% (95% CI -1.15% to 0.22%); and for positive affect, it was 0.12% (95% CI -0.57% to 0.82%). Other results for daily (vs monthly) dietary self-monitoring were mixed, suggesting an increase in weight (0.98%) and depressive symptoms (Cohen d=0.47), less intervention satisfaction (Cohen d=-0.20), more sessions viewed (3.02), and greater dietary adherence (Cohen d=0.24). For mindful eating, the results suggested a benefit for dietary adherence (Cohen d=0.24) and intervention satisfaction (Cohen d=0.30). For positive affect, the results suggested a benefit for depressive symptoms (Cohen d=-0.32), the number of sessions viewed (3.68), dietary adherence (Cohen d=0.16), and intervention satisfaction (Cohen d=0.25).

CONCLUSIONS: Overall, our results support the use of a VLC diet intervention in adults with T2D. The addition of monthly (not daily) dietary self-monitoring, mindful eating, and positive affect skills training did not show a definitive benefit, but it is worth further testing.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03037528; https://clinicaltrials.gov/ct2/show/NCT03037528.

PMID:37166961 | DOI:10.2196/44295

Nucleic Acids Res. 2023 May 11:gkad407. doi: 10.1093/nar/gkad407. Online ahead of print.

ABSTRACT

Microbiome studies have become routine in biomedical, agricultural and environmental sciences with diverse aims, including diversity profiling, functional characterization, and translational applications. The resulting complex, often multi-omics datasets demand powerful, yet user-friendly bioinformatics tools to reveal key patterns, important biomarkers, and potential activities. Here we introduce MicrobiomeAnalyst 2.0 to support comprehensive statistics, visualization, functional interpretation, and integrative analysis of data outputs commonly generated from microbiome studies. Compared to the previous version, MicrobiomeAnalyst 2.0 features three new modules: (i) a Raw Data Processing module for amplicon data processing and taxonomy annotation that connects directly with the Marker Data Profiling module for downstream statistical analysis; (ii) a Microbiome Metabolomics Profiling module to help dissect associations between community compositions and metabolic activities through joint analysis of paired microbiome and metabolomics datasets; and (iii) a Statistical Meta-Analysis module to help identify consistent signatures by integrating datasets across multiple studies. Other important improvements include added support for multi-factor differential analysis and interactive visualizations for popular graphical outputs, updated methods for functional prediction and correlation analysis, and expanded taxon set libraries based on the latest literature. These new features are demonstrated using a multi-omics dataset from a recent type 1 diabetes study. MicrobiomeAnalyst 2.0 is freely available at microbiomeanalyst.ca.

PMID:37166960 | DOI:10.1093/nar/gkad407

Psychol Addict Behav. 2023 May 11. doi: 10.1037/adb0000919. Online ahead of print.

ABSTRACT

OBJECTIVES: Problematic substance use is one of the most stigmatized health conditions leading research to examine how the labels and models used to describe it influence public stigma. Two recent studies examine whether beliefs in a disease model of addiction influence public stigma but result in equivocal findings-in line with the mixed-blessings model, Kelly et al. (2021) found that while the label “chronically relapsing brain disease” reduced blame attribution, it decreased prognostic optimism and increased perceived danger and need for continued care; however, Rundle et al. (2021) conclude absence of evidence. This study isolates the different factors used in these two studies to assess whether health condition (drug use vs. health concern), etiological label (brain disease vs. problem), and attributional judgment (low vs. high treatment stability) influence public stigma toward problematic substance use.

METHOD: Overall, 1,613 participants were assigned randomly to one of the eight vignette conditions that manipulated these factors. They completed self-report measures of discrete and general public stigma and an indirect measure of discrimination.

RESULTS: Greater social distance, danger, and public stigma but lower blame were ascribed to drug use relative to a health concern. Greater (genetic) blame was reported when drug use was labeled as a “chronically relapsing brain disease” relative to a “problem.” Findings for attributional judgment were either inconclusive or statistically equivalent.

DISCUSSION: The labels used to describe problematic substance use appear to impact discrete elements of stigma. We suggest that addiction is a functional attribution, which may explain the mixed literature on the impact of etiological labels on stigma to date. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37166945 | DOI:10.1037/adb0000919

Psychol Methods. 2023 Apr;28(2):339-358. doi: 10.1037/met0000567.

ABSTRACT

Empirical studies often demonstrate multiple causal mechanisms potentially involving simultaneous or causally related mediators. However, researchers often use simple mediation models to understand the processes because they do not or cannot measure other theoretically relevant mediators. In such cases, another potentially relevant but unobserved mediator potentially confounds the observed mediator, thereby biasing the estimated direct and indirect effects associated with the observed mediator and threatening corresponding inferences. Additionally, researchers may not know the extent to which their measures are reliable, and accordingly, measurement error may bias estimated effects and mislead statistical inferences. Given these threats, we explore how the omission of an unobserved mediator and/or using variables with measurement error biases estimates and affects inferences associated with the observed mediator. Then, building off Frank’s impact threshold for a confounding variable (ITCV), we propose a correlation-based sensitivity analysis. Lastly, we provide an R package ConMed to assess the robustness of mediation inferences given the omission of an unobserved, confounding mediator and/or measurement error. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37166933 | DOI:10.1037/met0000567

Georgian Med News. 2023 Mar;(336):123-125.

ABSTRACT

Contamination of certain drugs and foods with one of the most potent carcinogens/mutagens- nitrosamines, remains to be an issue and unresolved at present. The increased contamination of these mutagens in the most commonly used drugs in the human population doesn’t ceases to baffle clinicians, critics, public scholars, and analysts of the nitrosamine saga. The introduction of permissive determinations of the presence of carcinogens in drugs only reinforces doubts about the powerlessness of regulatory authorities in the face of the influence of powerful pharmaceutical cartels. The FDA’s encouraging promises of 2018 for strict control of carcinogens in sartans seems to have been permanently forgotten? By 2021, it was unthinkable that these carcinogens would be present in blood drugs and affected batches were immediately removed. Following alert checks confirming their post-existence in diabetes drugs, anti-smoking drugs, a number of antibiotics, ACE inhibitors, Sartans, thiazide diuretics, ranitidine, but probably a number of others, the decision has been taken to give the green light to their permissible availability. An availability that in all likelihood has the flavour of death. A “flavour” that has been confirmed in hundreds of international publications. Or in data from scientific papers submitted to regulatory regional units for verification and which remain sadly silent to this day. The “silent confirmation” and the lack of any adequate response in favour of public health are a sufficient further indicator of the attitude and position of the regulatory authorities. A position that should be changed. Starting from the mentioned facts and the data announced already in 2016/2017 of all-American data shared originally in American scientific journals, using their statistical estimates, we present the first case in the world literature of nodular melanoma and basal cell carcinoma occurring after taking perindopril. This intake turns out to be confirmatory one with respect to the statistics presented by Beatrice Nardone dating back to 2017. The potential pro-carcinogenic effects of both nitrosamines and the generic substance of perindopril are discussed.

PMID:37166894

Georgian Med News. 2023 Mar;(336):63-65.

ABSTRACT

A comparative analysis of clinical and laboratory parameters was carried out in 49 children. The patients were divided into 3 groups depending on the type of insulin they received. Group 1 included 20 children who used Insulin human (Insulatard), group 2 included 15 children using insulin Glargine, and group 3 included 14 children using insulin Detemir. All children using Detemir and Glargine used short acting insulin Aspart. Those using Insulin human (Insulatard) used Human insulin (rDNA, Actrapid) in addition. In all children, blood glucose, glycohemoglobin and cholesterol were determined by laboratory methods. Statistical calculations were carried out using a statistical package at a confidence level of p＜0.05. A significant difference was found between the mean values of glycohemoglobin and glucose of Glargine users and patients with using Insulin human (Insulatard) (p≺0.05). These indicators were lower in Glargine users. There is a positive correlation between doses of Regular insulin and Insulin human (Insulatard) with body weight and height. There is a positive correlation between dose of Detemir and body mass. However, no such relationship between Glargine, body mass and height was recorded. It was a negative correlation between its dose Glargine with glycohemoglobin and also between glucose and cholesterol using Glargine.

PMID:37166882