Categories
Nevin Manimala Statistics

A Robust Phenotype-driven Likelihood Ratio Analysis Approach Assisting Interpretable Clinical Diagnosis of Rare Diseases

J Biomed Inform. 2023 Apr 25:104372. doi: 10.1016/j.jbi.2023.104372. Online ahead of print.

ABSTRACT

Phenotype-based prioritization of candidate genes and diseases has become a well-established approach for multi-omics diagnostics of rare diseases. Most current algorithms exploit semantic analysis and probabilistic statistics based on Human Phenotype Ontology and are commonly superior to naive search methods. However, these algorithms are mostly less interpretable and do not perform well in real clinical scenarios due to noise and imprecision of query terms, and the fact that individuals may not display all phenotypes of the disease they belong to. We present a Phenotype-driven Likelihood Ratio analysis approach (PheLR) assisting interpretable clinical diagnosis of rare diseases. With a likelihood ratio paradigm, PheLR estimates the posterior probability of candidate diseases and how much a phenotypic feature contributes to the prioritization result. Benchmarked using simulated and realistic patients, PheLR shows significant advantages over current approaches and is robust to noise and inaccuracy. To facilitate clinical practice and visualized differential diagnosis, PheLR is implemented as an online web tool (http://phelr.nbscn.org).

PMID:37105510 | DOI:10.1016/j.jbi.2023.104372

Categories
Nevin Manimala Statistics

Meta-analysis informed machine learning: Supporting cytokine storm detection during CAR-T cell Therapy

J Biomed Inform. 2023 Apr 25:104367. doi: 10.1016/j.jbi.2023.104367. Online ahead of print.

ABSTRACT

Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown otherwise promising results in cancer treatment. When emerging, CRS could be identified by the analysis of specific cytokine and chemokine profiles that tend to exhibit similarities across patients. In this paper, we exploit these similarities using machine learning algorithms and set out to pioneer a meta-review informed method for the identification of CRS based on specific cytokine peak concentrations and evidence from previous clinical studies. To this end we also address a widespread challenge of the applicability of machine learning in general: reduced training data availability. We do so by augmenting available (but often insufficient) patient cytokine concentrations with statistical knowledge extracted from domain literature. We argue that such methods could support clinicians in analyzing suspect cytokine profiles by matching them against the said CRS knowledge from past clinical studies, with the ultimate aim of swift CRS diagnosis. We evaluate our proposed methods under several design choices, achieving performance of more than 90% in terms of CRS identification accuracy, and showing that many of our choices outperform a purely data-driven alternative. During evaluation with real-world CRS clinical data, we emphasize the potential of our proposed method of producing interpretable results, in addition to being effective in identifying the onset of cytokine storm.

PMID:37105509 | DOI:10.1016/j.jbi.2023.104367

Categories
Nevin Manimala Statistics

Comparison of dentinal tubular penetration of Intra-canal heated and Pre-heated sodium hypochlorite through different agitation techniques

J Endod. 2023 Apr 25:S0099-2399(23)00235-2. doi: 10.1016/j.joen.2023.04.007. Online ahead of print.

ABSTRACT

INTRODUCTION: The efficacy of sodium hypochlorite (NaOCl) as an intracanal irrigant is widely debated in endodontic therapy. This study aimed to analyze and compare the penetration abilities of different modes of NaOCl application and assess the impact of various agitation strategies on promoting root canal cleanliness.

MATERIALS AND METHODS: This study included 168 single-rooted mandibular premolars that were randomly divided into eight groups. The two modes of application of 5% NaOCl evaluated were intracanal heating and preheating, and the agitation strategies included ultrasonic, sonic, and manual dynamic agitations (MDAs). The samples were sectioned and observed at a magnification of 1000× under a scanning electron microscope.

RESULTS: The analysis of variance test showed a statistically significant difference among the various groups of agitation (P < 0.05). The post hoc Tukey test confirmed that preheated NaOCl with ultrasonic agitation, intracanal-heated NaOCl with sonic agitation, and MDA had significantly higher debris scores of 1, 4, and 5, respectively, in the apical third of the canal.

CONCLUSION: The results indicated that the combination of intracanal-heated NaOCl and ultrasonic agitation is an effective method for reducing debris in the root canal system. These findings highlight the importance of considering both the mode of application and the agitation strategies when optimizing the use of NaOCl as an intracanal irrigant in endodontic therapy.

PMID:37105500 | DOI:10.1016/j.joen.2023.04.007

Categories
Nevin Manimala Statistics

Evaluation of the lower face enlargement following mandibular osteotomy: Bilateral Sagittal Split Osteotomy (BSSO) vs Supra basilar sagittal Split Osteotomy (SBSSO)

J Stomatol Oral Maxillofac Surg. 2023 Apr 25:101488. doi: 10.1016/j.jormas.2023.101488. Online ahead of print.

ABSTRACT

INTRODUCTION: The current most common technique for mandibular split is the sagittal split osteotomy described by Obwegeser and modified by Dalpont and Epker. Several studies have shown a lower face enlargement while employing these techniques. The supra-basilar sagittal split osteotomy described in 2017 seems to be an interesting alternative as mandibular angles remain in continuity with the internal valve. The aim of this study was to evaluate lower face enlargement by comparing two techniques: sagittal split osteotomy and supra-basilar sagittal split.

MATERIALS AND METHODS: Cephalograms were analyzed before and after surgery. Bigonial distances (BGD) were measured in frontal cephalograms, ramus length and distances between upper and lower incisors on lateral cephalogram. Control of those measures was also performed by measuring the Nasion-Anterior Clinoid distance and intercanthal distance to assess the comparability and error rate. Finally, a comparison of cephalograms before and after surgery to assess bigonial enlargement, ramus elongation and advancement was performed.

RESULTS: Out of the 69 patients, 18 had a Bilateral Sagittal Split (BSSO) and 52 had a Supra-Basilar Sagittal Split (SBSSO). The error rate and patients’ characteristics were the same in the two groups. A statistically significant widening of the bigonial distance with the BSSO in comparison with the SBSSO was found (BGD difference: 5.82 mm (BSSO) vs – 1.47 mm (SBSSO), p < 0,001). A greater ramus elongation with the SBSSO was found (ramus elongation: 1.12 mm (BSSO) vs 5.1 mm (SBSSO)). This study has shown that the supra-basilar sagittal split is an interesting way to avoid the widening of the mandibular angles.

PMID:37105491 | DOI:10.1016/j.jormas.2023.101488

Categories
Nevin Manimala Statistics

Quantifying the contribution of external loadings and internal hydrodynamic processes to the water quality of Lake Okeechobee

Sci Total Environ. 2023 Apr 25:163713. doi: 10.1016/j.scitotenv.2023.163713. Online ahead of print.

ABSTRACT

The water quality of a waterbody is determined by internal hydrodynamic processes as well as external loadings. Understanding the interaction between the external loading and internal process of a waterbody is essential for efficient water management and water quality improvement. Studies and efforts have focused on water and nutrient loading from drainage watersheds, but the contribution of the waterbody’s internal process to water quality is often ignored and not well documented. This study investigated how the water quality of Lake Okeechobee is controlled by external and internal factors using statistical and numerical modeling approaches. Water quantity and quality observed at the outlets of the Lake Okeechobee drainage basins and 19 monitoring sites located within the lake were statistically analyzed using multilinear regression. A three-dimensional numerical model, namely Environmental Fluid Dynamics Code (EFDC), was calibrated to the observations to mathematically represent the lake’s internal hydrodynamic process. The multilinear regression found that the water quality was the most sensitive to air temperature, the total phosphorus (TP) concentration of inflow entering the lake from the Kissimmee River basins, and the amount of outflow discharged from the lake among external factors. However, the regression models and their explanatory power were substantially varied by the monitoring stations. The model parameter sensitivity analysis of the calibrated EFDC model showed that model parameters related to the lake’s internal algal processes including algal growth, predation, and basal metabolism rates had greater impacts on algal biomass than other model parameters controlling nutrient-related processes such as nutrient half-saturation and hydrolysis rates. The EFDC input data sensitivity analysis found that wind (speed) is the major driving force for the internal hydrodynamic processes; its impact on algal biomass was greater than those of the external loadings. In addition, the algal biomass was found to have an inverse relationship with wind-induced horizontal currents. The results demonstrate the dynamic contribution of the internal and external drivers to the water quality of Lake Okeechobee, suggesting the need to consider both internal hydrodynamic and external loading processes for efficient water quality improvement of the lake.

PMID:37105475 | DOI:10.1016/j.scitotenv.2023.163713

Categories
Nevin Manimala Statistics

Transcriptome comparative analysis of amygdala-hippocampus in depression: A rat model induced by chronic unpredictable mild stress (CUMS)

J Affect Disord. 2023 Apr 25:S0165-0327(23)00534-7. doi: 10.1016/j.jad.2023.04.074. Online ahead of print.

ABSTRACT

BACKGROUND: Depression is a common and complex mental disease, and its pathogenesis involves several brain regions. Abnormalities in the amygdala-hippocampal neural circuits have been shown to be involved in depression. However, the underlying molecular mechanisms remain unclear.

METHODS: A rat model was used to determine the transcriptome changes in the amygdala-hippocampal neural network under chronic unpredictable mild stress (CUMS). Depression-related modules in this neural network were identified using weighted gene co-expression network analysis (WGCNA). Difference and enrichment analyses were used to determine differential gene expression in the two brain regions.

RESULTS: The modules in the amygdala and hippocampus associated with depression-like behavior contained 363 and 225 genes, respectively. Forty-two differentially expressed genes were identified in the amygdala candidate module and 37 in the hippocampus. Enrichment analysis showed that candidate genes in the amygdala were associated with neuronal myelination and candidate genes in the hippocampus were associated with synaptic transmission. Finally, based on module hub gene statistics, differential gene expression, and protein-protein interaction networks, 11 central genes were found in the amygdala candidate module, and one central gene was found in the hippocampal module.

LIMITATIONS: Our study was based on a rat CUMS model. Further evidence is needed to prove that our results are applicable to patients with depression.

CONCLUSION: This study identified critical modules and central genes involved in the amygdala-hippocampal circuit in the context of depression, and may provide further understanding of the pathogenesis of depression and help identify potential targets for antidepressant therapy.

PMID:37105469 | DOI:10.1016/j.jad.2023.04.074

Categories
Nevin Manimala Statistics

A Comparison of Graduate Program Outcomes Based on Entry Requirements

J Acad Nutr Diet. 2023 Apr 25:S2212-2672(23)00220-4. doi: 10.1016/j.jand.2023.04.007. Online ahead of print.

NO ABSTRACT

PMID:37105445 | DOI:10.1016/j.jand.2023.04.007

Categories
Nevin Manimala Statistics

Perioperative Chemotherapy Could Not Improve the Prognosis of Gastric Cancer Patients With Mismatch Repair Deficiency: A Multicenter, Real-World Study

Oncologist. 2023 Apr 27:oyad108. doi: 10.1093/oncolo/oyad108. Online ahead of print.

ABSTRACT

INTRODUCTION: To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer.

MATERIALS AND METHODS: Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival.

RESULTS: In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively).

CONCLUSION: In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.

PMID:37104872 | DOI:10.1093/oncolo/oyad108

Categories
Nevin Manimala Statistics

COVID-19 vaccination telephone outreach: an analysis of the medical student experience

Med Educ Online. 2023 Dec;28(1):2207249. doi: 10.1080/10872981.2023.2207249.

ABSTRACT

INTRODUCTION: The COVID-19 pandemic diminished opportunities for medical students to gain clinical confidence and the ability to contribute to patient care. Our study sought out to understand the value of telephone outreach to schedule COVID-19 vaccines on medical student education.

MATERIALS AND METHODS: Forty students engaged in telephone outreach targeting patients aged 65+ without active patient portals to schedule COVID-19 vaccines. Data consisted of a single administration retrospective pre/post survey inquiring about what students learned, expectations, other health-care processes that would benefit from outreach, and interest in a population health elective. Likert items were analyzed and open response analysis involved inductive coding and generation of thematic summaries by condensing codes into broader themes. Demographic data of patients called and subsequently received the vaccine were also collected.

RESULTS: There were 33 survery respondents. There was a statistically significant increase in net comfortability for pre-clerkship students for documenting in Epic, providing telehealth care, counseling on common health-care myths, having challenging conversations, cold-calling patients, and developing an initial trusting relationship with patients. The majority called and who received the vaccine were non-Hispanic Black, within the high SVI category, and had Medicare and/or Medicaid. Qualitative data showed that students emphasized communication, the role of trusted messengers, the need to be open minded, and meeting patients where they are.

DISCUSSION: Engaging students in telephone outreach early in the COVID-19 pandemic provided students the opportunity to develop their skills as physicians-in-training, contribute to combating the ongoing pandemic, and add value to the primary care team. This experience allowed students to practice patience, empathy, and vulnerability to understand why patients had not received the COVID-19 vaccine; this was an invaluable experience that helped students develop the skills to become empathetic and caring physicians, and supports the continued role of telehealth in future medical school curriculum.

PMID:37104856 | DOI:10.1080/10872981.2023.2207249

Categories
Nevin Manimala Statistics

Experience incentivizing reduction of racial and ethnic disparities in a Medicaid hospital quality incentive program

Am J Manag Care. 2023 Apr 1;29(4):e124-e128. doi: 10.37765/ajmc.2023.89353.

ABSTRACT

OBJECTIVES: We aimed to describe the experience of a state Medicaid agency incentivizing reduction of racial and ethnic disparities in a hospital quality incentive program (QIP).

STUDY DESIGN: Retrospective review of a decade of experience implementing a hospital health disparity (HD) composite measure.

METHODS: Observational analysis of programwide trends in missed opportunity rates and between-group variance (BGV) for the HD composite from 2011 to 2020 and subanalysis of 16 metrics included in the HD composite for at least 4 years over the decade.

RESULTS: Programwide missed opportunity rates and BGV fluctuated widely from 2011 to 2020, likely due to variation in measures included in the HD composite. When the 16 measures that were included in the HD composite for at least 4 years were collapsed into a hypothetical 4-year period, missed opportunity rates decreased across the 4 consecutive years, from 47% in year 1 to 20% in year 4. Differences among racial and ethnic subgroups also decreased across the 4-year period, as reflected in the BGV decrease from 7.85 × 10-4 in year 1 to 5.10 × 10-4 in year 4.

CONCLUSIONS: Construction of a composite measure, use of a summary disparity statistic, and measure selection are key considerations in the design and interpretation of equity-focused payment programs. This analysis revealed improved aggregate quality performance and a modest reduction in racial and ethnic disparities for measures included in the HD composite for at least 4 years. Further research is needed to evaluate the association between equity-oriented incentives and health disparities.

PMID:37104839 | DOI:10.37765/ajmc.2023.89353