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The prognostic significance of DDIT4 in endometrial cancer

Cancer Biomark. 2023 May 24. doi: 10.3233/CBM-220368. Online ahead of print.

ABSTRACT

BACKGROUND: Despite extensive research on endometrial cancer and tumor hypoxic microenvironment, there are no reports exploring the role of DDIT4 in endometrial cancer.

OBJECTIVE: This study aimed to elucidate the significance of DDIT4, as a prognostic biomarker for endometrial cancer by immunohistochemical staining and statistical analysis.

METHODS: Four endometrial cancer cells were cultured under normoxia and hypoxia, and the differentially expressed genes were examined using RNA-seq. Immunohistochemical staining for DDIT4 and HIF1A was performed in 86 patients with type II endometrial cancer treated at our hospital, and their correlation with other clinicopathological factors and the prognostic role was analyzed using statistical methods.

RESULTS: The expression analysis of hypoxia-inducible genes using four types of endometrial cancer cells revealed that DDIT4 was among the 28 genes that were upregulated in all cells. Based on our results of immunohistochemistry of DDIT4 expression in endometrial cancer tissues, univariate and multivariate analyses based on COX regression analysis showed that high DDIT4 expression significantly correlated to favorable prognosis in both progression-free survival and overall survival. Limited to recurrent cases, metastasis to only lymph nodes was significantly related to high DDIT4 expression, whereas metastasis to other parenchymal organs was significantly dominant in patients with low DDIT4 expression.

CONCLUSIONS: The expression of DDIT4 enables to predict survival and recurrence in type II endometrial cancer.

PMID:37302026 | DOI:10.3233/CBM-220368

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Australian medical radiation practitioners perspectives of continuing professional development: An online cross-sectional study

J Med Radiat Sci. 2023 Jun 10. doi: 10.1002/jmrs.691. Online ahead of print.

ABSTRACT

INTRODUCTION: Continuing professional development (CPD) is mandatory for registered Australian medical radiation practitioners (MRPs) to maintain competence in their respective scopes of practice. The aim of this study was to explore MRPs attitudes, opinions and satisfaction towards CPD activities offered by the Australian Society of Medical Imaging and Radiation Therapy (ASMIRT).

METHODS: An online cross-sectional survey was emailed to 6398 ASMIRT members and included questions on: demographics, ASMIRT CPD activities, learning mode preferences, barriers and perceptions of CPD outcomes. Data were analysed using descriptive statistics and chi-square tests.

RESULTS: The survey was completed by 1018 MRPs. While MRPs were satisfied with face-to-face CPD quality (n = 540, 58.1%) and provision (n = 492, 55.3%), they were dissatisfied with the quantity of online CPD activities (n = 577, 65.1%) delivered by ASMIRT. Online learning was the most preferred mode of CPD delivery (n = 749, 74.2%), followed by face-to-face (n = 643, 64.0%) and collaborative learning (n = 539, 53.4%). Younger participants (19-35 years) had positive opinions regarding ASMIRT CPD activities and outcomes. Access to professional development leave (PDL) supported achievement of mandatory CPD requirements (P < 0.001). Lack of time, lack of access and workload were the highest ranked barriers preventing CPD participation. Rural/remote MRPs were dissatisfied with availability (P = 0.023), access (P < 0.001) and adequacy of ASMIRT provided CPD (P < 0.01) and were more likely to encounter barriers to CPD participation (P < 0.001).

CONCLUSIONS: Many MRPs experienced barriers which prevented them from participating in CPD. Provision of more online CPD activities by ASMIRT and access to PDL can assist. Future improvements will ensure MRPs remain motivated to engage in CPD to improve clinical skills, patient safety and health outcomes.

PMID:37301987 | DOI:10.1002/jmrs.691

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Process and costs for readiness to safely implement immediate kangaroo mother care: a mixed methods evaluation from the OMWaNA trial at five hospitals in Uganda

BMC Health Serv Res. 2023 Jun 10;23(1):613. doi: 10.1186/s12913-023-09624-z.

ABSTRACT

BACKGROUND: Preterm birth complications result in > 1 million child deaths annually, mostly in low- and middle-income countries. A World Health Organisation (WHO)-led trial in hospitals with intensive care reported reduced mortality within 28 days among newborns weighing 1000-1799 g who received immediate kangaroo mother care (iKMC) compared to those who received standard care. Evidence is needed regarding the process and costs of implementing iKMC, particularly in non-intensive care settings.

METHODS: We describe actions undertaken to implement iKMC, estimate financial and economic costs of essential resources and infrastructure improvements, and assess readiness for newborn care after these improvements at five Ugandan hospitals participating in the OMWaNA trial. We estimated costs from a health service provider perspective and explored cost drivers and cost variation across hospitals. We assessed readiness to deliver small and sick newborn care (WHO level-2) using a tool developed by Newborn Essential Solutions and Technologies and the United Nations Children’s Fund.

RESULTS: Following the addition of space to accommodate beds for iKMC, floor space in the neonatal units ranged from 58 m2 to 212 m2. Costs of improvements were lowest at the national referral hospital (financial: $31,354; economic: $45,051; 2020 USD) and varied across the four smaller hospitals (financial: $68,330-$95,796; economic: $99,430-$113,881). In a standardised 20-bed neonatal unit offering a level of care comparable to the four smaller hospitals, the total financial cost could be in the range of $70,000 to $80,000 if an existing space could be repurposed or remodelled, or $95,000 if a new unit needed to be constructed. Even after improvements, the facility assessments demonstrated broad variability in laboratory and pharmacy capacity as well as the availability of essential equipment and supplies.

CONCLUSIONS: These five Ugandan hospitals required substantial resource inputs to allow safe implementation of iKMC. Before widespread scale-up of iKMC, the affordability and efficiency of this investment must be assessed, considering variation in costs across hospitals and levels of care. These findings should help inform planning and budgeting as well as decisions about if, where, and how to implement iKMC, particularly in settings where space, devices, and specialised staff for newborn care are unavailable.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02811432 . Registered: 23 June 2016.

PMID:37301974 | DOI:10.1186/s12913-023-09624-z

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Using machine learning to develop a clinical prediction model for SSRI-associated bleeding: a feasibility study

BMC Med Inform Decis Mak. 2023 Jun 11;23(1):105. doi: 10.1186/s12911-023-02206-3.

ABSTRACT

INTRODUCTION: Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding.

METHODS: The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features (n = 88) were selected with clinicians’ input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models.

RESULTS: There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632-0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs.

CONCLUSIONS: We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction.

PMID:37301967 | DOI:10.1186/s12911-023-02206-3

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Disinfection of 3D-printed surgical guides using virgin coconut oil (in vitro study)

BMC Oral Health. 2023 Jun 10;23(1):379. doi: 10.1186/s12903-023-03092-x.

ABSTRACT

BACKGROUND/OBJECTIVE: Disinfection of a 3D-printed surgical guide is of utmost importance as it comes into contact with hard and soft tissue during implant placement so it poses a potential risk of pathogenic transmission. Methods used for disinfection in the surgical field should be reliable, practical, and safe for the instruments and the patients. The objectives of this study were to compare the antimicrobial potential of 100% Virgin Coconut Oil, 2% Glutaraldehyde, and 70% Ethyl Alcohol used to decontaminate 3D-printed surgical guides.

MATERIALS AND METHODS: Thirty identical surgical guides were printed and cut into two halves (N = 60). Both halves were then contaminated with a defined amount of human saliva samples (2 ml). The first half (n = 30) was sub-grouped into three study groups which were immersed in one of the three disinfectants for 20 min as follows; group VCO was immersed in 100% Virgin Coconut Oil, group GA was immersed in 2% Glutaraldehyde, and group EA was immersed in 70% Ethyl Alcohol. The second half (n* = 30) was sub-grouped into three control groups which were immersed in sterile distilled water as follows group VCO*, group GA*, and group EA*. The microbial count was expressed as colony-forming units per plate and the comparison of the antimicrobial potential of the three tested disinfectants between the three study and three control groups was done using the One-Way ANOVA test.

RESULTS: The culture results of three study groups revealed no bacterial growth with the highest % of reduction in the mean microbial count of the oral microorganisms (about100%) and an uncountable bacterial growth was shown between the three control groups (more than 100 CFU/plate) representing the baseline of the oral microorganisms. Therefore; statistically significant differences were found between the three control and three study groups (P < .001).

CONCLUSION: The antimicrobial potential of Virgin Coconut Oil was comparable and equivalent to Glutaraldehyde and Ethyl Alcohol with a significant inhibitory action against oral pathogens.

PMID:37301954 | DOI:10.1186/s12903-023-03092-x

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Two-port dry vitrectomy for rhegmatogenous retinal detachment: a pilot study

Eye (Lond). 2023 Jun 10. doi: 10.1038/s41433-023-02617-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of a new surgical technique for the management of primary rhegmatogenous retinal detachment (RRD), consisting of localized PPV near the retinal break(s), without infusion line, associated with a drainage of subretinal fluid and cryoretinopexy.

METHODS: Multicentric prospective study conducted at the University Hospital of Cagliari and IRCCS Fondazione Policlinico Universitario A. Gemelli, Roma. Twenty eyes affected by RRD with the causative retinal break(s) in the superior meridians were enrolled between February 2022 and June 2022. Patients with cataract ≥3, aphakia, significant posterior capsule opacification, giant retinal tears, retinal dialysis, history of trauma and PVR ≥C2 were excluded. All eyes underwent a two-port 25-gauge PPV with localized removal of the vitreous surrounding retinal break(s), followed by 20% SF6 injection and cryopexy. The surgical time was recorded for each procedure. Best-corrected visual acuity (BCVA) was measured at baseline and postoperative 6 months.

RESULTS: Primary anatomic success at 6 months was achieved by 85% of patients. No complications occurred, except for three (15%) retinal re-detachments. The average surgical time was 8.61 ± 2.16 min. Overall, the difference between pre- and last postoperative mean BCVA was statistically significant (p = 0.02).

CONCLUSIONS: Two-port dry PPV demonstrated safety and efficacy for the treatment of RRD, reaching an 85% of anatomical success rate. Although further studies are necessary to confirm the efficacy and long-term benefit of this treatment, we believe that this surgical technique could be considered a valid and safe alternative for the management of primary RRD.

PMID:37301938 | DOI:10.1038/s41433-023-02617-6

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Bayesian risk prediction model for colorectal cancer mortality through integration of clinicopathologic and genomic data

NPJ Precis Oncol. 2023 Jun 10;7(1):57. doi: 10.1038/s41698-023-00406-8.

ABSTRACT

Routine tumor-node-metastasis (TNM) staging of colorectal cancer is imperfect in predicting survival due to tumor pathobiological heterogeneity and imprecise assessment of tumor spread. We leveraged Bayesian additive regression trees (BART), a statistical learning technique, to comprehensively analyze patient-specific tumor characteristics for the improvement of prognostic prediction. Of 75 clinicopathologic, immune, microbial, and genomic variables in 815 stage II-III patients within two U.S.-wide prospective cohort studies, the BART risk model identified seven stable survival predictors. Risk stratifications (low risk, intermediate risk, and high risk) based on model-predicted survival were statistically significant (hazard ratios 0.19-0.45, vs. higher risk; P < 0.0001) and could be externally validated using The Cancer Genome Atlas (TCGA) data (P = 0.0004). BART demonstrated model flexibility, interpretability, and comparable or superior performance to other machine-learning models. Integrated bioinformatic analyses using BART with tumor-specific factors can robustly stratify colorectal cancer patients into prognostic groups and be readily applied to clinical oncology practice.

PMID:37301916 | DOI:10.1038/s41698-023-00406-8

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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

Nat Commun. 2023 Jun 10;14(1):3453. doi: 10.1038/s41467-023-38951-2.

ABSTRACT

Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.

PMID:37301908 | DOI:10.1038/s41467-023-38951-2

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The interactive effects of extreme temperatures and PM2.5 pollution on mortalities in Jiangsu Province, China

Sci Rep. 2023 Jun 10;13(1):9479. doi: 10.1038/s41598-023-36635-x.

ABSTRACT

Exposure to extreme temperatures or fine particles is associated with adverse health outcomes but their interactive effects remain unclear. We aimed to explore the interactions of extreme temperatures and PM2.5 pollution on mortalities. Based on the daily mortality data collected during 2015-2019 in Jiangsu Province, China, we conducted generalized linear models with distributed lag non-linear model to estimate the regional-level effects of cold/hot extremes and PM2.5 pollution. The relative excess risk due to interaction (RERI) was evaluated to represent the interaction. The relative risks (RRs) and cumulative relative risks (CRRs) of total and cause-specific mortalities associated with hot extremes were significantly stronger (p < 0.05) than those related to cold extremes across Jiangsu. We identified significantly higher interactions between hot extremes and PM2.5 pollution, with the RERI range of 0.00-1.15. The interactions peaked on ischaemic heart disease (RERI = 1.13 [95%CI: 0.85, 1.41]) in middle Jiangsu. For respiratory mortality, RERIs were higher in females and the less educated. The interaction pattern remained consistent when defining the extremes/pollution with different thresholds. This study provides a comprehensive picture of the interactions between extreme temperatures and PM2.5 pollution on total and cause-specific mortalities. The projected interactions call for public health actions to face the twin challenges, especially the co-appearance of hot extremes and PM pollution.

PMID:37301905 | DOI:10.1038/s41598-023-36635-x

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Manganese in residential drinking water from a community-initiated case study in Massachusetts

J Expo Sci Environ Epidemiol. 2023 Jun 10. doi: 10.1038/s41370-023-00563-9. Online ahead of print.

ABSTRACT

BACKGROUND: Manganese (Mn) is a metal commonly found in drinking water, but the level that is safe for consumption is unknown. In the United States (U.S.), Mn is not regulated in drinking water and data on water Mn concentrations are temporally and spatially sparse.

OBJECTIVE: Examine temporal and spatial variability of Mn concentrations in repeated tap water samples in a case study of Holliston, Massachusetts (MA), U.S., where drinking water is pumped from shallow aquifers that are vulnerable to Mn contamination.

METHODS: We collected 79 residential tap water samples from 21 households between September 2018 and December 2019. Mn concentrations were measured using inductively coupled plasma mass spectrometry. We calculated descriptive statistics and percent of samples exceeding aesthetic (secondary maximum containment level; SMCL) and lifetime health advisory (LHA) guidelines of 50 µg/L and 300 µg/L, respectively. We compared these concentrations to concurrent and historic water Mn concentrations from publicly available data across MA.

RESULTS: The median Mn concentration in Holliston residential tap water was 2.3 µg/L and levels were highly variable (range: 0.03-5,301.8 µg/L). Mn concentrations exceeded the SMCL and LHA in 14% and 12% of samples, respectively. Based on publicly available data across MA from 1994-2022, median Mn concentration was 17.0 µg/L (N = 37,210; range: 1-159,000 µg/L). On average 40% of samples each year exceeded the SMCL and 9% exceeded the LHA. Samples from publicly available data were not evenly distributed between MA towns or across sampling years.

IMPACT STATEMENT: This study is one of the first to examine Mn concentrations in drinking water both spatially and temporally in the U.S. Findings suggest that concentrations of Mn in drinking water frequently exceed current guidelines and occur at concentrations shown to be associated with adverse health outcomes, especially for vulnerable and susceptible subpopulations like children. Future studies that comprehensively examine exposure to Mn in drinking water and its associations with children’s health are needed to protect public health.

PMID:37301899 | DOI:10.1038/s41370-023-00563-9