Category: Nevin Manimala

Diabetes Metab J. 2024 Aug 19. doi: 10.4093/dmj.2023.0444. Online ahead of print.

ABSTRACT

BACKGROUND: We investigated the association between uterine leiomyoma (UL) and incident type 2 diabetes mellitus (T2DM) in young women.

METHODS: A nationwide population-based cohort study of 2,541,550 women aged between 20 and 40 years was performed using the National Health Information Database. Cox proportional hazards models were used to analyze the risk of incident T2DM according to the presence of UL and myomectomy.

RESULTS: The mean age was 29.70 years, and mean body mass index was 21.31 kg/m2. Among 2,541,550 participants, 18,375 (0.72%) women had UL. During a median 7.45 years of follow-up, 23,829 women (0.94%) were diagnosed with T2DM. The incidence of T2DM in women with UL (1.805/1,000 person-years) was higher than in those without UL (1.289/1,000 person-years). Compared with women without UL, women with UL had a higher risk of incident T2DM (hazard ratio, 1.216; 95% confidence interval [CI], 1.071 to 1.382). Women with UL who did not undergo myomectomy had a 1.505 times (95% CI, 1.297 to 1.748) higher risk for incident T2DM than women without UL. However, women with UL who underwent myomectomy did not have increased risk for incident T2DM.

CONCLUSION: Young women with UL were associated with a high risk of incident T2DM. In addition, myomectomy seemed to attenuate the risk for incident T2DM in young women with UL.

PMID:39159920 | DOI:10.4093/dmj.2023.0444

Math Biosci. 2024 Aug 17:109281. doi: 10.1016/j.mbs.2024.109281. Online ahead of print.

ABSTRACT

Investigating disease progression, transmission of infection and impacts of Multidrug Therapy (MDT) to inhibit demyelination in leprosy involves a certain amount of difficulty in terms of the in-built uncertain complicated and complex intracellular cell dynamical interactions. To tackle this scenario and to elucidate a more realistic, rationalistic approach of examining the infection mechanism and associated drug therapeutic interventions, we propose a four-dimensional ordinary differential equation-based model. Stochastic processes has been employed on this deterministic system by formulating the Kolmogorov forward equation introducing a transition state and the quasi-stationary distribution, exact distribution analysis have been investigated which allow us to estimate an expected time to extinction of the infected Schwann cells into the human body more prominently. Additionally, to explore the impact of uncertainty in the key intracellular factors, the stochastic system is investigated incorporating random perturbations and environmental noises in the disease dissemination, proliferation and reinfection rates. Rigorous numerical simulations validating the analytical outcomes provide us significant novel insights on the progression of leprosy and unravelling the existing major treatment complexities. Analytical experiments along with the simulations utilizing Monte-Carlo method and Euler-Maruyama scheme involving stochasticity predicts that the bacterial density is underestimated due to the recurrence of infection and suggests that maintaining a drug-efficacy rate in the range 0.6-0.8 would be substantially efficacious in eradicating leprosy.

PMID:39159890 | DOI:10.1016/j.mbs.2024.109281

Biosystems. 2024 Aug 17:105308. doi: 10.1016/j.biosystems.2024.105308. Online ahead of print.

ABSTRACT

Since 1996, circular codes in genes have been identified thanks to the development of 6 statistical approaches: trinucleotide frequencies per frame (Arquès and Michel, 1996), correlation functions per frame (Arquès and Michel, 1997), frame permuted trinucleotide frequencies (Frey and Michel, 2003, 2006), advanced statistical functions at the gene population level (Michel, 2015) and at the gene level (Michel, 2017). All these 3-frame statistical methods analyse the trinucleotide information in the 3 frames of genes: the reading frame and the 2 shifted frames. Notably, codon usage does not allow for the identification of circular codes (Michel, 2020). This has been a long-standing problem since 1996, hindering biologists’ access to circular code theory. By considering circular code conditions resulting from code theory, particularly the concept of permutation class, and building upon previous statistical work, a new statistical approach based solely on the codon usage, i.e. a 1-frame statistical method, surprisingly reveals the maximal C³ self-complementary trinucleotide circular code X in bacterial genes and in average (bacterial, archaeal, eukaryotic) genes, and almost in archaeal genes. Additionally, a new parameter definition indicates that bacterial and archaeal genes exhibit codon usage dispersion of the same order of magnitude, but significantly higher than that observed in eukaryotic genes. This statistical finding may explain the greater variability of codes in eukaryotic genes compared to bacterial and archaeal genes, an issue that has been open for many years. Finally, biologists can now search for new (variant) circular codes at both the genome level (across all genes in a given genome) and the gene level using only codon usage, without the need for analysing the shifted frames.

PMID:39159879 | DOI:10.1016/j.biosystems.2024.105308

J Med Internet Res. 2024 Aug 19;26:e48787. doi: 10.2196/48787.

ABSTRACT

BACKGROUND: Virtual reality (VR) in different immersive conditions has been increasingly used as a nonpharmacological method for managing chronic musculoskeletal pain.

OBJECTIVE: We aimed to assess the effectiveness of VR-assisted active training versus conventional exercise or physiotherapy in chronic musculoskeletal pain and to analyze the effects of immersive versus nonimmersive VR on pain outcomes.

METHODS: This systematic review of randomized control trials (RCTs) searched PubMed, Scopus, and Web of Science databases from inception to June 9, 2024. RCTs comparing adults with chronic musculoskeletal pain receiving VR-assisted training were included. The primary outcome was pain intensity; secondary outcomes included functional disability and kinesiophobia. Available data were pooled in a meta-analysis. Studies were graded using the Cochrane Risk-of-Bias Tool version 2.

RESULTS: In total, 28 RCTs including 1114 participants with some concerns for a high risk of bias were identified, and 25 RCTs were included in the meta-analysis. In low back pain, short-term outcomes measured post intervention showed that nonimmersive VR is effective in reducing pain (standardized mean difference [SMD] -1.79, 95% CI -2.72 to -0.87; P<.001), improving disability (SMD -0.44, 95% CI -0.72 to -0.16; P=.002), and kinesiophobia (SMD -2.94, 95% CI -5.20 to -0.68; P=.01). Intermediate-term outcomes measured at 6 months also showed that nonimmersive VR is effective in reducing pain (SMD -8.15, 95% CI -15.29 to -1.01; P=.03), and kinesiophobia (SMD -4.28, 95% CI -8.12 to -0.44; P=.03) compared to conventional active training. For neck pain, immersive VR reduced pain intensity (SMD -0.55, 95% CI -1.02 to -0.08; P=.02) but not disability and kinesiophobia in the short term. No statistical significances were detected for knee pain or other pain regions at all time points. In addition, 2 (8%) studies had a high risk of bias.

CONCLUSIONS: Both nonimmersive and immersive VR-assisted active training is effective in reducing back and neck pain symptoms. Our study findings suggest that VR is effective in alleviating chronic musculoskeletal pain.

TRIAL REGISTRATION: PROSPERO CRD42022302912; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=302912.

PMID:39159449 | DOI:10.2196/48787

J Med Internet Res. 2024 Aug 19;26:e47733. doi: 10.2196/47733.

ABSTRACT

BACKGROUND: Previous studies have demonstrated telemedicine to be an effective tool to complement rheumatology care and address workforce shortage. With the COVID-19 outbreak, telemedicine experienced a massive upswing. An earlier analysis revealed that the motivation of patients with rheumatic and musculoskeletal diseases to use telemedicine is closely connected to their disease. It remains unclear which factors are associated with patients’ motivation to use telemedicine in certain rheumatic and musculoskeletal diseases groups, such as rheumatoid arthritis (RA).

OBJECTIVE: This study aims to identify factors that determine the willingness to try telemedicine among patients diagnosed with RA.

METHODS: We conducted a secondary analysis of data from a German nationwide cross-sectional survey among patients with RA. Bayesian univariate logistic regression analysis was applied to the data to determine which factors were associated with willingness to try telemedicine. Predictor variables (covariates) studied individually included sociodemographic factors (eg, age, sex) and health characteristics (eg, health status). All the variables positively and negatively associated with willingness to try telemedicine in the univariate analyses were then considered for Bayesian model averaging analysis after a selection based on the variance inflation factor (≤ 2.5) to identify determinants of willingness to try telemedicine.

RESULTS: Among 438 surveyed patients in the initial study, 210 were diagnosed with RA (47.9%). Among them, 146 (69.5%) answered either yes or no regarding willingness to try telemedicine and were included in the analysis. A total of 22 variables (22/55, 40%) were associated with willingness to try telemedicine (region of practical equivalence %≤5). A total of 9 determinant factors were identified using Bayesian model averaging analysis. Positive determinants included desiring telemedicine services provided by a rheumatologist (odds ratio [OR] 13.7, 95% CI 5.55-38.3), having prior knowledge of telemedicine (OR 2.91, 95% CI 1.46-6.28), residing in a town (OR 2.91, 95% CI 1.21-7.79) or city (OR 0.56, 95% CI 0.23-1.27), and perceiving one’s health status as moderate (OR 1.87, 95% CI 0.94-3.63). Negative determinants included the lack of an electronic device (OR 0.1, 95% CI 0.01-0.62), absence of home internet access (OR 0.1, 95% CI 0.02-0.39), self-assessment of health status as bad (OR 0.44, 95% CI 0.21-0.89) or very bad (OR 0.47, 95% CI 0.06-2.06), and being aged between 60 and 69 years (OR 0.48, 95% CI 0.22-1.04) or older than 70 years (OR 0.38, 95% CI 0.16-0.85).

CONCLUSIONS: The results suggest that some patients with RA will not have access to telemedicine without further support. Older patients, those not living in towns, those without adequate internet access, reporting a bad health status, and those not owning electronic devices might be excluded from the digital transformation in rheumatology and might not have access to adequate RA care. These patient groups certainly require support for the use of digital rheumatology care.

PMID:39159448 | DOI:10.2196/47733

JMIR Med Inform. 2024 Aug 19;12:e50307. doi: 10.2196/50307.

ABSTRACT

BACKGROUND: Patient navigation interventions (PNIs) can provide personalized support and promote appropriate coordination or continuation of health and social care services. Online PNIs have demonstrated excellent potential for improving patient knowledge, transition readiness, self-efficacy, and use of services. However, the characteristics (ie, intervention type, mode of delivery, duration, frequency, outcomes and outcome measures, underlying theories or mechanisms of change of the intervention, and impact) of existing online PNIs to support the health and social needs of individuals with illness remain unclear.

OBJECTIVE: This scoping review of the existing literature aims to identify the characteristics of existing online PNIs reported in the literature.

METHODS: A scoping review based on the guidelines outlined in the Joanna Briggs Institute framework was conducted. A search for peer-reviewed literature published between 1989 and 2022 on online PNIs was conducted using MEDLINE, CINAHL, Embase, PsycInfo, and Cochrane Library databases. Two independent reviewers conducted 2 levels of screening. Data abstraction was conducted to outline key study characteristics (eg, study design, population, and intervention characteristics). The data were analyzed using descriptive statistics and qualitative content analysis.

RESULTS: A total of 100 studies met the inclusion criteria. Our findings indicate that a variety of study designs are used to describe and evaluate online PNIs, with literature being published between 2003 and 2022 in Western countries. Of these studies, 39 (39%) studies were randomized controlled trials. In addition, we noticed an increase in reported online PNIs since 2019. The majority of studies involved White females with a diagnosis of cancer and a lack of participants aged 70 years or older was observed. Most online PNIs provide support through navigation, self-management and lifestyle changes, counseling, coaching, education, or a combination of support. Variation was noted in terms of mode of delivery, duration, and frequency. Only a small number of studies described theoretical frameworks or change mechanisms to guide intervention.

CONCLUSIONS: To our knowledge, this is the first review to comprehensively synthesize the existing literature on online PNIs, by focusing on the characteristics of interventions and studies in this area. Inconsistency in reporting the country of publication, population characteristics, duration and frequency of interventions, and a lack of the use of underlying theories and working mechanisms to inform intervention development, provide guidance for the reporting of future online PNIs.

PMID:39159443 | DOI:10.2196/50307

J Phys Chem Lett. 2024 Aug 19:8697-8705. doi: 10.1021/acs.jpclett.4c01954. Online ahead of print.

ABSTRACT

In this work, we study the synthesis of glycine, the simplest amino acid, using ab initio molecular dynamics and enhanced sampling techniques to explore and quantify novel potential pathways. Our protocol integrates state-of-the-art machine learning approaches, allowing us to sample relevant chemical spaces more efficiently. We discover a novel “oxyglycolate path”, distinct from the “standard” Strecker mechanism, identify new intermediates, and provide a full thermodynamic characterization of all reaction steps. This alternative pathway aligns better with meteoritic and experimental observations, paving the way for further investigations. Integrating quantum accuracy and machine learning in prebiotic chemistry represents a methodological milestone advancing the exploration of life’s prebiotic origins.

PMID:39159425 | DOI:10.1021/acs.jpclett.4c01954

JCO Clin Cancer Inform. 2024 Aug;8:e2400094. doi: 10.1200/CCI.24.00094.

ABSTRACT

PURPOSE: No consensus about the effectiveness of prostate-specific antigen (PSA) screening exists among clinical guidelines, especially for the elderly. Randomized trials of PSA screening have yielded different results, partly because of variations in adherence, and it is unlikely that new trials will be conducted. Our objective was to estimate the effect of annual PSA screening on prostate cancer (PC) mortality in Medicare beneficiaries age 67-84 years.

METHODS: This is a large-scale, population-based, observational study of two screening strategies: annual PSA screening and no screening. We used data from 537,599 US Medicare (2001-2008) beneficiaries age 67-84 years who had a good life expectancy, no previous PC, and no PSA test in the 2 years before baseline. We estimated the 8-year PC mortality and incidence, treatments for PC, and treatment complications of PSA screening.

RESULTS: In men age 67-74 years, the estimated difference in 8-year risk of PC death between PSA screening and no screening was -2.3 (95% CI, -4.1 to -1.1) deaths per 1,000 men (a negative risk difference favors screening). Treatment complications were more frequent under PSA screening than under no screening. In men age 75-84 years, risk difference estimates were closer to zero.

CONCLUSION: Our estimates suggest that under conventional statistical criteria, annual PSA screening for 8 years is highly compatible with reductions of PC mortality from four to one fewer PC deaths per 1,000 screened men age 67-74 years. As with any study using real-world data, the estimates could be affected by residual confounding.

PMID:39159422 | DOI:10.1200/CCI.24.00094

J Clin Oncol. 2024 Aug 19:JCO2400427. doi: 10.1200/JCO.24.00427. Online ahead of print.

ABSTRACT

PURPOSE: The US Food and Drug Administration (FDA) approved capivasertib in combination with fulvestrant for adult patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced, or metastatic breast cancer (MBC) who have received at least one previous endocrine therapy and whose tumors harbor one or more phosphatidylinositol 3-kinase (PIK3CA)/AKT Serine/Threonine Kinase 1 (AKT1)/phosphatase and tensin homolog (PTEN) alterations, as detected by an FDA-approved test.

PATIENTS AND METHODS: Approval was based on CAPItello-291, a randomized, double-blind, multicenter trial of 708 patients with hormone receptor-positive, HER2-negative advanced or MBC, including 289 patients with PIK3CA/AKT1/PTEN tumor alterations. Patients were randomly assigned 1:1 to receive capivasertib 400 mg twice daily for 4 days per week with fulvestrant versus placebo with fulvestrant. Random assignment was stratified by presence of liver metastases, previous treatment with CDK4/6i, cyclin-dependent kinase four and six (CDK4/6) inhibitors, and geographical region.

RESULTS: A statistically significant progression-free survival (PFS) benefit was demonstrated in the overall population (hazard ratio [HR], 0.6 [95% CI, 0.51 to 0.71]); this result was driven by 289 patients in the biomarker-positive population (HR, 0.5 [95% CI, 0.37 to 0.68]). An exploratory analysis of investigator-assessed PFS in the 313 (44%) patients in the biomarker-negative population showed uncertain benefit (HR, 0.78 [95% CI, 0.60 to 1.01]). With capivasertib, more patients had Grade ≥3 toxicities. Key concerns included hyperglycemia (18% all-grade, 2.8% Grade ≥3), cutaneous toxicity (58% all-grade, 17% Grade ≥3), and diarrhea (72% all-grade, 9% Grade ≥3).

CONCLUSION: Capivasertib with fulvestrant was approved for patients whose tumors harbored PIK3CA/AKT1/PTEN alterations. Benefit-risk assessment in this subgroup was favorable based on a statistically significant and clinically meaningful improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in overall survival. By contrast, the benefit-risk was unfavorable in the biomarker-negative population.

PMID:39159418 | DOI:10.1200/JCO.24.00427

Neurology. 2024 Sep 10;103(5):e209746. doi: 10.1212/WNL.0000000000209746. Epub 2024 Aug 19.

ABSTRACT

BACKGROUND AND OBJECTIVES: Gender disparities have been demonstrated across several medical specialties, including neurology. Although women have comprised most of the child neurology trainees since 2007, it is not apparent whether this demographic shift is reflected in the Child Neurology Society (CNS) awards and leadership. This study aimed to evaluate the differences in gender representation among leadership positions and award recipients within the CNS. The primary outcome measure was the total number of board of director (BOD) positions or awards given by gender each year.

METHODS: A retrospective review of publicly available data was conducted on CNS members, post-training award recipients, and BOD positions, including nomination records, from 1972 to 2023. Data abstracted were restricted to gender to preserve member and nominee anonymity. Gender identification and consensus were determined through a combination of strategies and study members. Data analysis included descriptive statistics, Pearson χ² test, and the exact binomial test to compare gender proportions and the probability of being underrepresented in awards, leadership, and nominations over time. Data are presented according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

RESULTS: From 1972 to 2023, women represented 29% (44/152) of the BOD positions and 26% (61/236) of post-training award recipients presented by the CNS. Despite the increase in the proportion of women in child neurology, the overall gap in gender representation in leadership positions remains broadly stable. Only 13% (4/32) of CNS presidents have been women, a significant underrepresentation (95% CI 2.3%-52%, p < 0.004), although the representation of women in nonpresidential positions increased from 2003 to 2023. Women are also underrepresented as overall awardees (95% CI 12%-38%, p < 0.00001) except for the Philip R. Dodge Young Investigator Award, which is an investigator-initiated application.

DISCUSSION: Women remain underrepresented at the highest levels of recognition in child neurology despite representing most of the field. Reasons for disparities are known to be multifactorial and likely include gender bias and structural sexism. We present several discussion topics that seek to rationalize this disparity and provide suggestions for improving diversity, equity, and inclusion for leadership roles and awards.

PMID:39159414 | DOI:10.1212/WNL.0000000000209746