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Nevin Manimala Statistics

Stochastic models allow improved inference of microbiome interactions from time series data

PLoS Biol. 2024 Nov 21;22(11):e3002913. doi: 10.1371/journal.pbio.3002913. Online ahead of print.

ABSTRACT

How can we figure out how the different microbes interact within microbiomes? To combine theoretical models and experimental data, we often fit a deterministic model for the mean dynamics of a system to averaged data. However, in the averaging procedure a lot of information from the data is lost-and a deterministic model may be a poor representation of a stochastic reality. Here, we develop an inference method for microbiomes based on the idea that both the experiment and the model are stochastic. Starting from a stochastic model, we derive dynamical equations not only for the average, but also for higher statistical moments of the microbial abundances. We use these equations to infer distributions of the interaction parameters that best describe the biological experimental data-improving identifiability and precision. The inferred distributions allow us to make predictions but also to distinguish between fairly certain parameters and those for which the available experimental data does not give sufficient information. Compared to related approaches, we derive expressions that also work for the relative abundance of microbes, enabling us to use conventional metagenome data, and account for cases where not a single host, but only replicate hosts, can be tracked over time.

PMID:39571000 | DOI:10.1371/journal.pbio.3002913

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Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study

PLoS Med. 2024 Nov 21;21(11):e1004435. doi: 10.1371/journal.pmed.1004435. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within 3 years of final menstrual period. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS Continuation Study reevaluated cognition, mood, and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion. We hypothesized that women randomized to transdermal estradiol (tE2) during early postmenopause would show cognitive benefits, while oral conjugated equine estrogens (oCEE) would show no effect, compared to placebo over the 10 years following randomization in the KEEPS trial.

METHODS AND FINDINGS: The KEEPS-Cog (2005-2008) was an ancillary study to the KEEPS (NCT00154180), in which participants were randomized into 3 groups: oCEE (Premarin, 0.45 mg/d), tE2 (Climara, 50 μg/d) both with micronized progesterone (Prometrium, 200 mg/d for 12 d/mo) or placebo pills and patch for 48 months. KEEPS Continuation (2017-2022), an observational, longitudinal cohort study of KEEPS clinical trial, involved recontacting KEEPS participants approximately 10 years after the completion of the 4-year clinical trial to attend in-person research visits. Seven of the original 9 sites participated in the KEEPS Continuation, resulting in 622 women of original 727 being invited to return for a visit, with 299 enrolling across the 7 sites. KEEPS Continuation participants repeated the original KEEPS-Cog test battery which was analyzed using 4 cognitive factor scores and a global cognitive score. Cognitive data from both KEEPS and KEEPS Continuation were available for 275 participants. Latent growth models (LGMs) assessed whether baseline cognition and cognitive changes during KEEPS predicted cognitive performance at follow-up, and whether mHT randomization modified these relationships, adjusting for covariates. Similar health characteristics were observed at KEEPS randomization for KEEPS Continuation participants and nonparticipants (i.e., women not returning for the KEEPS Continuation). The LGM revealed significant associations between intercepts and slopes for cognitive performance across almost all domains, indicating that cognitive factor scores changed over time. Tests assessing the effects of mHT allocation on cognitive slopes during the KEEPS and across all years of follow-up including the KEEPS Continuation visit were all statistically nonsignificant. The KEEPS Continuation study found no long-term cognitive effects of mHT, with baseline cognition and changes during KEEPS being the strongest predictors of later performance. Cross-sectional comparisons confirmed that participants assigned to mHT in KEEPS (oCEE and tE2 groups) performed similarly on cognitive measures to those randomized to placebo, approximately 10 years after completion of the randomized treatments. These findings suggest that mHT poses no long-term cognitive harm; conversely, it provides no cognitive benefit or protective effects against cognitive decline.

CONCLUSIONS: In these KEEPS Continuation analyses, there were no long-term cognitive effects of short-term exposure to mHT started in early menopause versus placebo. These data provide reassurance about the long-term neurocognitive safety of mHT for symptom management in healthy, recently postmenopausal women, while also suggesting that mHT does not improve or preserve cognitive function in this population.

PMID:39570992 | DOI:10.1371/journal.pmed.1004435

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Impact of Implementing Electronic Nursing Records on Quality and Safety Indicators in Care

Libyan J Med. 2024 Dec 31;19(1):2421625. doi: 10.1080/19932820.2024.2421625. Epub 2024 Nov 21.

ABSTRACT

Electronic Health Records (EHR) have been adopted to improve the quality of care. Despite the growing use of health information technology, nursing documentation remains a challenge. In Tunisia, the implementation of the Electronic Medical Record (EMR) system is gaining momentum as part of national initiatives to modernize healthcare. However, nursing documentation is still largely paper-based, and no studies in Tunisia have adressed this topic. This research aims to assess the effect of the Electronic Nursing Record (ENR) on the quality and safety of care indicators (QSCI). This is an interventional study structured in four phases: development, pre-implementation, implementation, and evaluation, integrating the principles of the ‘Standards for Reporting Implementation Studies’ (StaRI). A list of QSCI was defined and validated through a literature review and Delphi consensus. The impact of the ENR on these indicators was evaluated in a Tunisian university hospital through a quasi-experimental study. Indicators were measured before ENR, one month after, and six months after. Data analyses was conducted using SPSS with statistical tests. Initially, the study led to the identification and validation of seventeen QSCI. Subsequently, a quasi-experimental study was conducted to evaluate the impact of ENR implementation on these indicators. The results revealed a significant improvement in the intervention group (using ENR), particularly in the traceability of vital signs (p < 10⁻3) and infusion administration (p = 0.027). Conversely, the control group (using paper-based documentation) performed better in terms of traceability of inter-team handovers (95.1% compared to 71.9% for the intervention group). The electronic documentation system is seen as a major transformation in healthcare in many hospitals worldwide. Moreover, electronic nursing documentation is crucial for patient safety. Its implementation in our hospital revealed a positive impact of the ENR on certain aspects of care quality while highlighting gaps in inter-team handovers.

PMID:39570988 | DOI:10.1080/19932820.2024.2421625

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Comparing college students’ mood states among immersive virtual reality, non-immersive virtual reality, and traditional biking exercise

PLoS One. 2024 Nov 21;19(11):e0311113. doi: 10.1371/journal.pone.0311113. eCollection 2024.

ABSTRACT

OBJECTIVES: This study examined differences in young adults’ mood states during immersive virtual reality (VR), non-immersive VR, and traditional exercise biking sessions.

DESIGN: Repeated-measure study design.

METHODS: Forty-nine college students (34 females; Mage = 23.6 years) completed three separate 20-minute exercise biking sessions: (1) immersive VR biking using the PlayStation 4 + VirZoom VR bike; (2) non-immersive VR biking using the Gamercize bike + Xbox 360; and (3) traditional stationary biking using the Spirit Fitness XBU55. Participants’ mood states (anger, confusion, depression, fatigue, tension, and vigor) were assessed by using the Brunel Mood Scale after each session.

RESULTS: Statistically significant differences were observed between biking sessions for all components of mood [F (2, 96) = 3.84-278.56, p < 0.05, η2 = 0.07-0.85], except for tension (p > 0.05). Results indicated non-immersive VR biking yielded significantly higher anger compared to immersive VR biking; non-immersive VR biking yielded significantly higher confusion compared to immersive VR biking and traditional biking, respectively; immersive VR biking yielded significantly lower depression compared to traditional biking; both immersive VR biking and non-immersive VR biking yielded significantly lower fatigue compared to traditional biking; and immersive VR biking yielded significantly higher vigor compared to non-immersive VR biking) and traditional biking, respectively.

CONCLUSION: Findings suggested the immersive VR-based biking exercise may facilitate in reducing the negative feelings, such as anger, fatigue, depression, and improving positive feeling, such as vigor, among college students. The immersive VR-based exercise appeared to be a feasible approach for motivating college students participating in physical activity and improving overall mood states.

PMID:39570986 | DOI:10.1371/journal.pone.0311113

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Impact of climate and land use on the temporal variability of sand fly density in Sri Lanka: A 2-year longitudinal study

PLoS Negl Trop Dis. 2024 Nov 21;18(11):e0012675. doi: 10.1371/journal.pntd.0012675. Online ahead of print.

ABSTRACT

BACKGROUND: Leishmaniasis has emerged as an escalating public health problem in Sri Lanka, with reported cases increasing nearly three folds over past decade, from 1,367 in 2014 to 3714 cases in 2023. Phlebotominae sand flies are the vectors of leishmaniasis. Their density is known to be influenced by context-specific climatic and land use patterns. Thus, we aimed to investigate how these factors drive sand fly density across Sri Lanka.

METHODOLOGY/PRINCIPAL FINDINGS: We analysed monthly collections of sand flies (n = 38,594) and weather data from ten sentinel sites representing three main geo-climatic zones across Sri Lanka, over 24 months. Site-specific land use data was also recorded. The influence of climate and land use patterns on sand fly density across the sentinel sites were estimated using distributed lag non-linear models and machine learning. We found that climate played a major role on sand fly density compared to land use structure. Increase in rainfall and relative humidity at real time, and ambient temperature and soil temperature with a 2-month lag were associated with a statistically significant increase in sand fly density. The maximum relative risk (RR) observed was 3.76 (95% CI: 1.58-8.96) for rainfall at 120 mm/month, 2.14 (95% CI: 1.04-4.38) for relative humidity at 82% (both at real time). The maximum RR was 2.81 (95% CI: 1.09-7.35) for ambient temperature at 34.5°C, and 11.6 (95% CI, 4.38-30.76) for soil temperature (both at a 2-month lag). The real-time increase in ambient temperature, sunshine hours, and evaporation rate, however, reduced sand fly density homogeneously in all study settings. The high density of chena and coconut plantations, together with low density of dense forests, homesteads, and low human footprint values, positively influenced sand fly density.

CONCLUSIONS/SIGNIFICANCE: The findings improve our understanding of the dynamic influence of environment on sand fly densities and spread of leishmaniasis. This knowledge lays a foundation for forecasting of sand fly densities and designing targeted interventions for mitigating the growing burden of leishmaniasis among the most vulnerable populations, particularly in an era of changing climate.

PMID:39570981 | DOI:10.1371/journal.pntd.0012675

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Characteristics of melanoma in Mexicans seen at “La Raza” National Medical Center

Rev Med Inst Mex Seguro Soc. 2024 Nov 4;62(6):1-7. doi: 10.5281/zenodo.13306762.

ABSTRACT

BACKGROUND: Melanoma is the third most common type of skin cancer in Mexico and represents 75% of skin cancer deaths. Dermoscopy is a diagnostic tool that increases early detection of melanoma compared to naked eye examination.

OBJECTIVE: The aim of this study was to describe the clinical, dermoscopic and histological characteristics of patients with a confirmed diagnosis of cutaneous melanoma treated at the “La Raza” National Medical Center.

MATERIAL AND METHODS: A retrospective, descriptive and cross-sectional study was carried out from March 1998 to December 2013, with 187 histologically confirmed cases, considering: sex, age, skin phototype, history, topography of the lesion, dermoscopic pattern, metastasis at the time of diagnosis and histological subtype, Breslow index and Clark index, using the chi-square test as a non-parametric statistical method to analyze the data obtained.

RESULTS: Most patients had skin phototype III and the most affected location was the lower limb. Clinically, acral lentiginous melanomas and nodular melanomas were the most observed. The most common dermoscopic finding was the multicomponent pattern. Clinically and histologically, the most frequent subtype associated with metastasis was nodular melanoma. Acral lentiginous melanoma was more common among patients without metastasis.

CONCLUSIONS: Unfortunately, melanoma is still diagnosed in advanced stages in Mexico; for its early recognition, training in the use of dermoscopy and greater awareness about melanoma in the Mexican population must be encouraged.

PMID:39570666 | DOI:10.5281/zenodo.13306762

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Oncological Outcomes of Patients With Oral Potentially Malignant Disorders

JAMA Otolaryngol Head Neck Surg. 2024 Nov 21. doi: 10.1001/jamaoto.2024.3719. Online ahead of print.

ABSTRACT

IMPORTANCE: Understanding the clinical course and malignant transformation rate of oral potentially malignant disorders (OPMDs)-including oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus-is crucial for early detection and improved survival rates in patients with oral cancer.

OBJECTIVE: To evaluate the progression of oral cancer from OPMDs using a large US electronic medical database.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the University of California, San Francisco’s PatientExploreR database between January 1973 and March 2024. Patients with oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes and keywords. Demographics, tobacco and alcohol use, HIV status, and other known risk factors for oral cancer were recorded to identify factors associated with malignant transformation. Logistic regression and descriptive analyses were used.

EXPOSURE: Diagnosis of oral leukoplakia, oral erythroplakia, oral submucous fibrosis, or oral lichen planus.

MAIN OUTCOMES AND MEASURES: Incidence of oral cancer, malignant transformation rate, median time to progression, and associations between demographics and risk factors and the development of oral cancer.

RESULTS: Among 4 225 251 individuals in the database, 4371 were diagnosed with oral cancer (median [IQR] age, 63 [53-71] years; 2610 [59.9%] male; 0.1% of the cohort), and 110 (2.5%) had a preceding OPMD. Oral leukoplakia was found in 1124 patients, with 94 (8.4%) undergoing malignant transformation (median [IQR] time to progression, 25 [7-129] months). HIV-positive patients with oral leukoplakia were more likely to develop oral cancer (odds ratio, 3.80; 95% CI, 1.35-10.70). Of 22 patients with oral erythroplakia, 11 (50.0%) developed oral cancer (median [IQR] time to progression, 3.7 [0.2-334] months). Those who smoked tobacco with oral erythroplakia showed a higher malignant transformation rate (odds ratio, 3.75; 95% CI, 0.54-26.05). Of the 78 patients with oral submucous fibrosis, 4 (5.1%) underwent malignant transformation (median [IQR] time to progression, 36 [36-48] months). Only 1 patient with oral lichen planus developed oral cancer after 5 years.

CONCLUSIONS AND RELEVANCE: This cohort study showed that OPMDs have notable but varying propensities to progress to oral cancer. Early detection and monitoring of OPMDs are crucial for improving patient outcomes. However, the risk, etiopathogenesis, and clinical presentation vary for each OPMD and should, therefore, be considered distinct diseases.

PMID:39570632 | DOI:10.1001/jamaoto.2024.3719

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Sparse Neighbor Joining: rapid phylogenetic inference using a sparse distance matrix

Bioinformatics. 2024 Nov 21:btae701. doi: 10.1093/bioinformatics/btae701. Online ahead of print.

ABSTRACT

MOTIVATION: Phylogenetic reconstruction is a fundamental problem in computational biology. The Neighbor Joining (NJ) algorithm offers an efficient distance-based solution to this problem, which often serves as the foundation for more advanced statistical methods. Despite prior efforts to enhance the speed of NJ, the computation of the n 2 entries of the distance matrix, where n is the number of phylogenetic tree leaves, continues to pose a limitation in scaling NJ to larger datasets.

RESULTS: In this work, we propose a new algorithm which does not require computing a dense distance matrix. Instead, it dynamically determines a sparse set of at most O(n log n) distance matrix entries to be computed in its basic version, and up to O(n log 2n) entries in an enhanced version. We show by experiments that this approach reduces the execution time of NJ for large datasets, with a trade-off in accuracy.

AVAILABILITY AND IMPLEMENTATION: Sparse Neighbor Joining is implemented in Python and freely available at https://github.com/kurtsemih/SNJ.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39570613 | DOI:10.1093/bioinformatics/btae701

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Prenatal Diet and Infant Growth From Birth to Age 24 Months

JAMA Netw Open. 2024 Nov 4;7(11):e2445771. doi: 10.1001/jamanetworkopen.2024.45771.

ABSTRACT

IMPORTANCE: Being born either small for gestational age (SGA) or large for gestational age (LGA) and experiencing rapid or slow growth after birth are associated with later-life obesity. Understanding the associations of dietary quality during pregnancy with infant growth may inform obesity prevention strategies.

OBJECTIVE: To evaluate the associations of prenatal dietary quality according to the Healthy Eating Index (HEI) and the Empirical Dietary Inflammatory Pattern (EDIP) with infant size at birth and infant growth from birth to age 24 months.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from birthing parent-child dyads in 8 cohorts participating in the Environmental influences on Child Health Outcomes program between 2007 and 2021. Data were analyzed from March 2021 to August 2024.

EXPOSURES: The HEI and the EDIP dietary patterns.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were infant birth weight, categorized as SGA, reference range, or LGA, and infant growth from birth to ages 6, 12, and 24 months, categorized as slow growth (weight-for-length z score [WLZ] score difference <-0.67), within reference range (WLZ score difference -0.67 to 0.67), or rapid (WLZ score difference, >0.67).

RESULTS: The study included 2854 birthing parent-child dyads (median [IQR] maternal age, 30 [25-34] years; 1464 [51.3%] male infants). The cohort was racially and ethnically diverse, including 225 Asian or Pacific Islander infants (7.9%), 640 Black infants (22.4%), 1022 Hispanic infants (35.8%), 664 White infants (23.3%), and 224 infants (7.8%) with other race or multiple races. A high HEI score (>80), indicative of a healthier diet, was associated with lower odds of LGA (adjusted odds ratio [aOR], 0.88 [95% CI, 0.79-0.98]), rapid growth from birth to age 6 months (aOR, 0.80 [95% CI, 0.37-0.94]) and age 24 months (aOR 0.82 [95% CI, 0.70- 0.96]), and slow growth from birth to age 6 months (aOR, 0.65 [95% CI, 0.50-0.84]), 12 months (aOR, 0.74 [95% CI, 0.65-0.83]), and 24 months (OR, 0.65 [95% CI, 0.56-0.76]) compared with an HEI score 80 or lower. There was no association between high HEI and SGA (aOR, 1.14 [95% CI, 0.95-1.35]). A low EDIP score (ie, ≤63.6), indicative of a less inflammatory diet, was associated with higher odds of LGA (aOR, 1.24 [95% CI, 1.13-1.36]) and rapid infant growth from birth to age 12 months (aOR, 1.50 [95% CI, 1.18-1.91]) and lower odds of rapid growth to age 6 months (aOR, 0.77 [95% CI, 0.71-0.83]), but there was no association with SGA (aOR, 0.80 [95% CI, 0.51-1.25]) compared with an EDIP score of 63.6 or greater.

CONCLUSIONS AND RELEVANCE: In this cohort study, a prenatal diet that aligned with the US Dietary Guidelines was associated with reduced patterns of rapid and slow infant growth, known risk factors associated with obesity. Future research should examine whether interventions to improve prenatal diet are also beneficial in improving growth trajectory in children.

PMID:39570591 | DOI:10.1001/jamanetworkopen.2024.45771

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More vs Less Frequent Follow-Up Testing and 10-Year Mortality in Patients With Stage II or III Colorectal Cancer: Secondary Analysis of the COLOFOL Randomized Clinical Trial

JAMA Netw Open. 2024 Nov 4;7(11):e2446243. doi: 10.1001/jamanetworkopen.2024.46243.

ABSTRACT

IMPORTANCE: Although intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, evidence for a long-term survival benefit of more frequent testing is limited.

OBJECTIVE: To examine overall and colorectal cancer-specific mortality rates in patients with stage II or III colorectal cancer who underwent curative surgery and underwent high-frequency or low-frequency follow-up testing.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial with posttrial prespecified follow-up was performed in 23 centers in Sweden and Denmark. The original study enrolled 2509 patients with stage II or III colorectal cancer from Sweden, Denmark, and Uruguay (1 center) who received treatment from January 1, 2006, through December 31, 2010, and were followed up for up to 5 years. The participants from Sweden and Denmark were then followed up for 10 years through population-based health registries. The 53 patients from Uruguay were not included in the posttrial follow-up. Statistical analysis was performed from March to June 2024.

INTERVENTIONS: Patients were randomly allocated to follow-up testing with computed tomography (CT) scans and serum carcinoembryonic antigen (CEA) screening at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; 1227 patients), or at 12 and 36 months after surgery (low-frequency group, 1229 patients).

MAIN OUTCOMES AND MEASURES: The outcomes were 10-year overall mortality and colorectal cancer-specific mortality rates. Both intention-to-treat and per-protocol analyses were performed.

RESULTS: Of the 2555 patients who were randomly allocated, 2509 were included in the intention-to-treat analysis, of whom 2456 (97.9%) were included in this posttrial analysis (median age, 65 years [IQR, 59-70 years]; 1355 male patients [55.2%]). The 10-year overall mortality rate for the high-frequency group was 27.1% (333 of 1227; 95% CI, 24.7%-29.7%) compared with 28.4% (349 of 1229; 95% CI, 26.0%-31.0%) in the low-frequency group (risk difference, 1.3% [95% CI, -2.3% to 4.8%]). The 10-year colorectal cancer-specific mortality rate in the high-frequency group was 15.6% (191 of 1227; 95% CI, 13.6%-17.7%) compared with 16.0% (196 of 1229; 95% CI, 14.0%-18.1%) in the low-frequency group (risk difference, 0.4% [95% CI, -2.5% to 3.3%]). The same pattern resulted from the per-protocol analysis.

CONCLUSIONS AND RELEVANCE: Among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scans and CEA testing did not result in a significant reduction in 10-year overall mortality or colorectal cancer-specific mortality. The results of this trial should be considered as the evidence base for updating clinical guidelines.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00225641.

PMID:39570590 | DOI:10.1001/jamanetworkopen.2024.46243