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Nevin Manimala Statistics

Delayed Urological Cancer Care during the COVID-19 Pandemic: Urologists’ Experience

Urol Pract. 2021 May;8(3):367-372. doi: 10.1097/UPJ.0000000000000210. Epub 2021 Mar 26.

ABSTRACT

INTRODUCTION: The arrival of coronavirus disrupted health care systems and forced delays in cancer treatment. We explored the experience of urologists who had to delay their patients’ cancer care.

METHODS: Urologists who treat prostate, bladder, and renal cancers, selected through purposive sampling, responded to a survey about cancer treatment delay. They were asked about their practice setting, decision making and interactions with patients, and they were asked to reflect on their personal experience. A 0 to 10 point scale, modeled on the National Comprehensive Cancer Network’ Distress Thermometer (NCCN-DT), validated for cancer patients with cancer, was used to estimate physician distress. We used descriptive statistics to analyze survey results.

RESULTS: Of the 64 participating urologists, 98% delayed surgical treatment; fewer delayed cases of advanced cancers (42% for ≥T3/T4 or Gleason ≥8 prostate cancers, 58% for muscle invasive bladder cancer, 61% for ≥T2 renal cancers). They reported feeling anxious (44%) and helpless (29%), and their median distress score was 5 (range 0-10). They relied on their own risk assessments (67%) and consulted colleagues (56%) and national guidelines (53%) when making treatment deferral decisions. They identified a number of concerns as they resumed surgeries.

CONCLUSIONS: Based on a comparison to the NCCN-DT clinical cutoff distress level of 4, urologists experienced moderately high levels of distress as they delayed cancer care during the COVID-19 pandemic and expressed concerns going forward. While the focus on patient care is paramount in a pandemic, it is important to recognize physician distress and develop practical and psychological strategies for distress mitigation.

PMID:37145655 | DOI:10.1097/UPJ.0000000000000210

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Nevin Manimala Statistics

Impact of Urology Trainee Debt Levels on Future Practice Choices and Expectations

Urol Pract. 2021 Mar;8(2):303-308. doi: 10.1097/UPJ.0000000000000205. Epub 2020 Oct 28.

ABSTRACT

INTRODUCTION: Excessive trainee debt continues to be a problem. Little is known about how debt influences future practice decisions. We sought to examine the correlation between educational debt and anticipated practice choices and career expectations to better understand the impact of debt on urology trainees to inform urology workforce policy.

METHODS: Data were collected from urology trainees who completed the AUA Annual Census between 2016 and 2018. We examined level of debt among urology trainees against their anticipated practice choices compensation expectation and various debt relief variables.

RESULTS: Among 705 U.S. urology trainees who completed the survey, 22% had no debt, 23% had <$150,000 debt, 27% had $150,000 to $250,000 of debt, and the remaining 27% had >$250,000. Debt level did not appear to significantly affect anticipated future practice setting or the decision to pursue fellowship. Concerning how loan forgiveness influenced practice opportunity, 31% of trainees reported no effect, 42% some effect and 27% great effect. Those trainees with higher level of debt appeared to be more likely to accept a practice opportunity if loan forgiveness was offered (p ≤0.001). Those trainees with higher level of debt were more likely to anticipate higher annual compensation as compared to those with less debt (p=0.001).

CONCLUSIONS: Nearly 70% of those trainees with debt had $150,000 of debt or higher. Our study showed carrying educational debt is statistically associated with trainees’ choice of anticipated practice for better compensation and tuition forgiveness. Workforce policy should consider addressing the financial burden of urology trainees.

PMID:37145622 | DOI:10.1097/UPJ.0000000000000205

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Nevin Manimala Statistics

Estimation of median survival time and its 95% confidence interval using SAS PROC LIFETEST

J Biopharm Stat. 2023 May 5:1-13. doi: 10.1080/10543406.2023.2206481. Online ahead of print.

ABSTRACT

Estimation of median survival and its 95% confidence interval depends on the choice of the survival function, standard error, and a method for constructing the confidence interval. This paper outlines several available possibilities in SAS® (version 9.4) PROC LIFETEST and compares them on theoretical grounds and using simulated data, with criteria: ability to estimate the 95% CI, coverage probability, interval width, and appropriateness for practical use. Data are generated with varying hazard patterns, N, % censoring, and censoring patterns (early, uniform, late, last visit). LIFETEST was run using the Kaplan-Meier and Nelson-Aalen estimators and the transformations available (linear, log, logit, complementary log-log, and arcsine square root). Using the Kaplan-Meier estimator with the logarithmic transformation as well as with the logit leads to a high frequency of LIFETEST not being able to estimate the 95% CI. The combination of Kaplan-Meier with the linear transformation is associated with poor coverage achieved. For small samples, late/last visit censoring has a negative effect on being able to estimate the 95% CI. Heavy early censoring can lead to low coverage of the 95% CI of median survival for sample sizes up to and including N = 40. The two combinations that are optimal for being able to estimate the 95% CI and having adequate coverage are the Kaplan-Meier estimator with complementary log-log transformation, and the Nelson-Aalen estimator with linear transformation. The former fares best on the third criterion (smaller width) and is also the SAS® default and validates the choice of default.

PMID:37144552 | DOI:10.1080/10543406.2023.2206481

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Nevin Manimala Statistics

Robust time selection for interim analysis in the Bayesian phase 2 exploratory clinical trial

J Biopharm Stat. 2023 May 5:1-11. doi: 10.1080/10543406.2023.2208665. Online ahead of print.

ABSTRACT

In phase 2 clinical trials, we expect to make a right Go or No-Go decision during the interim analysis (IA) and make this decision at the right time. The optimal time for IA is usually determined based on a utility function. In most previous research, utility functions aim to minimize the expected sample size or total cost in confirmatory trials. However, the selected time can vary depending on different alternative hypotheses. This paper proposes a new utility function for Bayesian phase 2 exploratory clinical trials. It evaluates the predictability and robustness of the Go and No-Go decision made during the IA. We can make a robust time selection for the IA based on the function regardless of the treatment effect assumptions.

PMID:37144549 | DOI:10.1080/10543406.2023.2208665

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Nevin Manimala Statistics

Water consumption by rinse-off cosmetic products: the case of the shower

Int J Cosmet Sci. 2023 May 5. doi: 10.1111/ics.12866. Online ahead of print.

ABSTRACT

OBJECTIVE: This article measures and discusses the effects of different shower gels on the consumption of water used during a shower.

METHODS: A sensory panel was created for quantifying water consumption associated with the use of shower gels. 15 French panellists were recruited (Age: 59 ± 7, Height: 163 cm ± 9 and Weight: 68 kg ± 20) and trained to assess rinsed skin in a standardized way. Effective panellists were then asked to assess 25 shower gels covering the variety of existing products on the market.

RESULTS: Results showed that the average volume was 4.77 L for heating the water and wetting the body and 4.15 L for rinsing the shower gel off the full body. We observed a significant shower gel effect (p < .0001) with the water volume needed to rinse the 25 shower gels ranging 3.21 L to 5.65 L.

CONCLUSION: This paper demonstrates the impact of shower gel formulation on water consumption during a shower. It thus demonstrates the importance of formulating shower gels to reduce the total amount of water needed to shower. It also introduces the distinction between ‘useful water’ which refers strictly to the volume of water objectively needed to rinse off a product and the ‘used water’ which refers to the total shower volume of water. This distinction helps to better strategize actions in order to reduce water consumption from rinse-off cosmetic products used during showers.

PMID:37144490 | DOI:10.1111/ics.12866

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Nevin Manimala Statistics

Inferring ligand-receptor cellular networks from bulk and spatial transcriptomic datasets with BulkSignalR

Nucleic Acids Res. 2023 May 5:gkad352. doi: 10.1093/nar/gkad352. Online ahead of print.

ABSTRACT

The study of cellular networks mediated by ligand-receptor interactions has attracted much attention recently owing to single-cell omics. However, rich collections of bulk data accompanied with clinical information exists and continue to be generated with no equivalent in single-cell so far. In parallel, spatial transcriptomic (ST) analyses represent a revolutionary tool in biology. A large number of ST projects rely on multicellular resolution, for instance the Visium™ platform, where several cells are analyzed at each location, thus producing localized bulk data. Here, we describe BulkSignalR, a R package to infer ligand-receptor networks from bulk data. BulkSignalR integrates ligand-receptor interactions with downstream pathways to estimate statistical significance. A range of visualization methods complement the statistics, including functions dedicated to spatial data. We demonstrate BulkSignalR relevance using different datasets, including new Visium liver metastasis ST data, with experimental validation of protein colocalization. A comparison with other ST packages shows the significantly higher quality of BulkSignalR inferences. BulkSignalR can be applied to any species thanks to its built-in generic ortholog mapping functionality.

PMID:37144485 | DOI:10.1093/nar/gkad352

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Nevin Manimala Statistics

An Analysis of the Timing for Closure of a Diverting Loop Ileostomy

Am Surg. 2023 May 5:31348231173971. doi: 10.1177/00031348231173971. Online ahead of print.

ABSTRACT

A diverting loop ileostomy (DLI) is used to protect a distal gastrointestinal anastomosis at risk of leakage. While patients typically prefer early DLI closure, surgeons vary in opinion regarding optimal timing. This study evaluated whether the timing of DLI closure impacts outcomes.A retrospective review was performed on patients who underwent DLI creation within one health care system between 2012 and 2020. Patient characteristics and postoperative outcomes were compared across ileostomies closed in ≤2 months, 2-4 months, and >4 months. Outcomes examined included anastomotic leak, other complications, reintervention, and death within 30 days.A total of 500 DLIs were analyzed for the study, 455 of which were closed. The three closure groups were similar in patient characteristics and comorbidities. None of the outcome variables analyzed in this study demonstrated a statistically significant difference between groups, suggesting that in patients otherwise fit for surgery, DLI closure can be safely performed within 2 months of creation.

PMID:37144471 | DOI:10.1177/00031348231173971

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Nevin Manimala Statistics

Analysis of Biomechanical Response After Corneal Crosslinking with Different Fluence Levels in Porcine Corneas

Curr Eye Res. 2023 May 5:1-5. doi: 10.1080/02713683.2023.2205612. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate corneal stiffening of porcine corneas induced by corneal crosslinking (CXL) with constant irradiance as a function of total fluence.

METHODS: Ninety corneas from freshly enucleated porcine eyes were divided into five groups of 18 eyes. Groups 1-4 underwent epi-off CXL using a dextran-based riboflavin solution and an irradiance of 18 mW/cm2, group 5 served as the control group. Groups 1 to 4 were treated with a total fluence of 20, 15, 10.8, and 5.4 J/cm2, respectively. Thereafter, biomechanical measurements were performed on 5 mm wide and 6 mm long strips using an uniaxial material tester. Pachymetry measurements were performed on each cornea.

RESULTS: At 10% strain, the stress was 76, 56, 52, and 31% higher in groups 1-4, respectively compared to the control group. The Young’s modulus was 2.85 MPa for group 1, 2.53 MPa for group 2, 2.46 MPa for group 3, 2.12 MPa for group 4, and 1.62 MPa for the control group. The difference between groups 1 to 4 and the control group 5 were statistically significant (p = <0.001; p = <0.001; p = <0.001; p = 0.021). In addition, group 1 showed significantly more stiffening than group 4 (p = <0.001), no other significant differences were found. Pachymetry measurements revealed no statistically significant differences among the five groups.

CONCLUSION: Additional mechanical stiffening can be achieved by increasing the fluence of the CXL. There was no threshold detected up to 20 J/cm2. A higher fluence could compensate the weaker effect of accelerated or epi-on CXL procedures.

PMID:37144469 | DOI:10.1080/02713683.2023.2205612

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Nevin Manimala Statistics

g:Profiler-interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)

Nucleic Acids Res. 2023 May 5:gkad347. doi: 10.1093/nar/gkad347. Online ahead of print.

ABSTRACT

g:Profiler is a reliable and up-to-date functional enrichment analysis tool that supports various evidence types, identifier types and organisms. The toolset integrates many databases, including Gene Ontology, KEGG and TRANSFAC, to provide a comprehensive and in-depth analysis of gene lists. It also provides interactive and intuitive user interfaces and supports ordered queries and custom statistical backgrounds, among other settings. g:Profiler provides multiple programmatic interfaces to access its functionality. These can be easily integrated into custom workflows and external tools, making them valuable resources for researchers who want to develop their own solutions. g:Profiler has been available since 2007 and is used to analyse millions of queries. Research reproducibility and transparency are achieved by maintaining working versions of all past database releases since 2015. g:Profiler supports 849 species, including vertebrates, plants, fungi, insects and parasites, and can analyse any organism through user-uploaded custom annotation files. In this update article, we introduce a novel filtering method highlighting Gene Ontology driver terms, accompanied by new graph visualizations providing a broader context for significant Gene Ontology terms. As a leading enrichment analysis and gene list interoperability service, g:Profiler offers a valuable resource for genetics, biology and medical researchers. It is freely accessible at https://biit.cs.ut.ee/gprofiler.

PMID:37144459 | DOI:10.1093/nar/gkad347

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Nevin Manimala Statistics

Role of Dickkopf-3 in Blood Pressure Regulation in Mice and Hypertensive Rats

Circ Res. 2023 May 5. doi: 10.1161/CIRCRESAHA.122.321744. Online ahead of print.

ABSTRACT

BACKGROUND: Dkk3 (Dickkopf-3) is a secreted glycoprotein known for its proapoptotic and angiogenic activity. The role of Dkk3 in cardiovascular homeostasis is largely unknown. Remarkably, the Dkk3 gene maps within a chromosome segment linked to the hypertensive phenotype in spontaneously hypertensive rats (SHR).

METHODS: We used Dkk3-/- mice or stroke-resistant (sr) and stroke-prone (sp) SHR to examine the role of Dkk3 in the central and peripheral regulation of blood pressure (BP). We used lentiviral expression vector to rescue Dkk3 in knockout mice or to induce Dkk3 overexpression or silencing in SHR.

RESULTS: Genetic deletion of Dkk3 in mice enhanced BP and impaired endothelium-dependent acetylcholine-induced relaxation of resistance arteries. These alterations were rescued by restoring Dkk3 expression either in the periphery or in the CNS. Dkk3 was required for the constitutive expression of VEGF (vascular endothelium growth factor), and the action of Dkk3 on BP and endothelium-dependent vasorelaxation was mediated by VEGF-stimulated phosphatidylinositol-3-kinase pathway, leading to eNOS (endothelial NO synthase) activation both in resistance arteries and the CNS. The regulatory function of Dkk3 on BP was confirmed in SHR stroke-resistant and SHR stroke-prone in which was blunted in both resistance arteries and brainstem. In SHR stroke-resistant, lentiviral expression vector-induced Dkk3 expression in the CNS largely reduced BP, whereas Dkk3 knock-down further enhanced BP. In SHR stroke-prone challenged with a hypersodic diet, lentiviral expression vector-induced Dkk3 expression in the CNS displayed a substantial antihypertensive effect and delayed the occurrence of stroke.

CONCLUSIONS: These findings demonstrate that Dkk3 acts as peripheral and central regulator of BP by promoting VEGF expression and activating a VEGF/Akt/eNOS hypotensive axis.

PMID:37144413 | DOI:10.1161/CIRCRESAHA.122.321744