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Nevin Manimala Statistics

Differential variability analysis of single-cell gene expression data

Brief Bioinform. 2023 Aug 20:bbad294. doi: 10.1093/bib/bbad294. Online ahead of print.

ABSTRACT

The advent of single-cell RNA sequencing (scRNA-seq) technologies has enabled gene expression profiling at the single-cell resolution, thereby enabling the quantification and comparison of transcriptional variability among individual cells. Although alterations in transcriptional variability have been observed in various biological states, statistical methods for quantifying and testing differential variability between groups of cells are still lacking. To identify the best practices in differential variability analysis of single-cell gene expression data, we propose and compare 12 statistical pipelines using different combinations of methods for normalization, feature selection, dimensionality reduction and variability calculation. Using high-quality synthetic scRNA-seq datasets, we benchmarked the proposed pipelines and found that the most powerful and accurate pipeline performs simple library size normalization, retains all genes in analysis and uses denSNE-based distances to cluster medoids as the variability measure. By applying this pipeline to scRNA-seq datasets of COVID-19 and autism patients, we have identified cellular variability changes between patients with different severity status or between patients and healthy controls.

PMID:37598422 | DOI:10.1093/bib/bbad294

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Nevin Manimala Statistics

Development and validation of 18F-FDG PET/CT radiomics-based nomogram to predict visceral pleural invasion in solid lung adenocarcinoma

Ann Nucl Med. 2023 Aug 20. doi: 10.1007/s12149-023-01861-w. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to establish a radiomics model based on 18F-FDG PET/CT images to predict visceral pleural invasion (VPI) of solid lung adenocarcinoma preoperatively.

METHODS: We retrospectively enrolled 165 solid lung adenocarcinoma patients confirmed by histopathology with 18F-FDG PET/CT images. Patients were divided into training and validation at a ratio of 0.7. To find significant VPI predictors, we collected clinicopathological information and metabolic parameters measured from PET/CT images. Three-dimensional (3D) radiomics features were extracted from each PET and CT volume of interest (VOI). Receiver operating characteristic (ROC) curve was performed to determine the performance of the model. Accuracy, sensitivity, specificity and area under curve (AUC) were calculated. Finally, their performance was evaluated by concordance index (C-index) and decision curve analysis (DCA) in training and validation cohorts.

RESULTS: 165 patients were divided into training cohort (n = 116) and validation cohort (n = 49). Multivariate analysis showed that histology grade, maximum standardized uptake value (SUVmax), distance from the lesion to the pleura (DLP) and the radiomics features had statistically significant differences between patients with and without VPI (P < 0.05). A nomogram was developed based on the logistic regression method. The accuracy of ROC curve analysis of this model was 75.86% in the training cohort (AUC: 0.867; C-index: 0.867; sensitivity: 0.694; specificity: 0.889) and the accuracy rate in validation cohort was 71.55% (AUC: 0.889; C-index: 0.819; sensitivity: 0.654; specificity: 0.739).

CONCLUSIONS: A PET/CT-based radiomics model was developed with SUVmax, histology grade, DLP, and radiomics features. It can be easily used for individualized VPI prediction.

PMID:37598412 | DOI:10.1007/s12149-023-01861-w

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Nevin Manimala Statistics

Impact of family networks on uptake of health interventions: evidence from a community-randomized control trial aimed at increasing HIV testing in South Africa

J Int AIDS Soc. 2023 Aug;26(8):e26142. doi: 10.1002/jia2.26142.

ABSTRACT

INTRODUCTION: While it is widely acknowledged that family relationships can influence health outcomes, their impact on the uptake of individual health interventions is unclear. In this study, we quantified how the efficacy of a randomized health intervention is shaped by its pattern of distribution in the family network.

METHODS: The “Home-Based Intervention to Test and Start” (HITS) was a 2×2 factorial community-randomized controlled trial in Umkhanyakude, KwaZulu-Natal, South Africa, embedded in the Africa Health Research Institute’s population-based demographic and HIV surveillance platform (ClinicalTrials.gov # NCT03757104). The study investigated the impact of two interventions: a financial micro-incentive and a male-targeted HIV-specific decision support programme. The surveillance area was divided into 45 community clusters. Individuals aged ≥15 years in 16 randomly selected communities were offered a micro-incentive (R50 [$3] food voucher) for rapid HIV testing (intervention arm). Those living in the remaining 29 communities were offered testing only (control arm). Study data were collected between February and November 2018. Using routinely collected data on parents, conjugal partners, and co-residents, a socio-centric family network was constructed among HITS-eligible individuals. Nodes in this network represent individuals and ties represent family relationships. We estimated the effect of offering the incentive to people with and without family members who also received the offer on the uptake of HIV testing. We fitted a linear probability model with robust standard errors, accounting for clustering at the community level.

RESULTS: Overall, 15,675 people participated in the HITS trial. Among those with no family members who received the offer, the incentive’s efficacy was a 6.5 percentage point increase (95% CI: 5.3-7.7). The efficacy was higher among those with at least one family member who received the offer (21.1 percentage point increase (95% CI: 19.9-22.3). The difference in efficacy was statistically significant (21.1-6.5 = 14.6%; 95% CI: 9.3-19.9).

CONCLUSIONS: Micro-incentives appear to have synergistic effects when distributed within family networks. These effects support family network-based approaches for the design of health interventions.

PMID:37598389 | DOI:10.1002/jia2.26142

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Nevin Manimala Statistics

Cerebral venous sinus thrombosis cases detected in on-call CT venographies in Sweden, 2019-2022

J Thromb Thrombolysis. 2023 Aug 20. doi: 10.1007/s11239-023-02883-x. Online ahead of print.

ABSTRACT

No well-established criteria exist for assessing the risk of cerebral venous sinus thrombosis (CVST). Here, we sought to gain an understanding of CVST cases and associated risk factors, based on the rates of emergency CT venographies (CTVs) performed after hours. Furthermore, we aimed to assess possible correlations between CVST rates and COVID-19, including at the start of the COVID-19 vaccination campaign. We collected reports of emergency CTVs performed after hours at 56 Swedish hospitals between 1/1/2019 and 12/31/2022, and divided them into five groups: (I) from 1/1/2019 to 1/31/2020, before the emergence of COVID-19 cases in Sweden; (II) from 2/1/2020 to 12/26/2020, after the emergence of COVID-19 but before vaccination rollout; (III) from 12/27/2020 to 7/28/2021, from the start of the COVID-19 vaccination campaign until 50% of the adult population in Sweden had been vaccinated; (IV) from 7/29/2021 to 2/1/2022, from when 50% of the adult population was vaccinated until restrictions were lifted; and (V) from 2/2/2022 to 12/31/2022, after restriction measures were suspended. For all included patients, we collected information on demographics and clinical history, including pregnancy, recent partum, and use of oral contraceptives or post-menopausal hormone replacement therapy. In total, we collected 430 reports (92% female, 8% male). The CVST positivity rate was 22.2% in men vs. 2.3% in women. None of the pregnant (n = 49) or postpartum (n = 12) women had CVST positivity. The frequency of CTV examinations was lowest in group 2; during this period, the average time between patients being imaged was 7 days. The frequency of CTV examinations was highest in group IV; during this period, a patient underwent this type of scan every 1.5 days, on average. The frequency of CVST-positive scans was lowest in group II; during this period, a positive case was found every 66 days, on average. The frequency of CVST-positive scans was highest in group IV; during this period, a positive case was found every 62 days, on average, and no statistical difference with respect to group II was observed. Pregnancy and recent partum were not significant risk factors for CVST. The elevated CVST positivity rate observed during the height of the COVID-19 pandemic suggested that patients with less likelihood for positive CVST had fewer emergency visits. The positivity rate did not increase with the start of the COVID-19 pandemic or the rollout of COVID-19 vaccination.

PMID:37598388 | DOI:10.1007/s11239-023-02883-x

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Evaluation of postoperative outcomes of minimally invasive distal pancreatectomy for left-sided pancreatic tumors based on the modified frailty index: A retrospective cohort study

Int J Surg. 2023 Aug 18. doi: 10.1097/JS9.0000000000000670. Online ahead of print.

ABSTRACT

BACKGROUND: This study compared the postoperative outcomes of minimally invasive distal pancreatectomy (MIDP) for left-sided pancreatic tumors based on the modified frailty index (mFI).

MATERIALS AND METHODS: This retrospective study included 2,212 patients who underwent MIDP for left-sided pancreatic tumors between 2005 and 2019. Postoperative outcomes, including complications (morbidity and mortality), were analyzed using mFI, and the participants were divided into two groups: frail (n=79) and nonfrail (n=2,133). A subanalysis of 495 MIDPs for pancreatic ductal adenocarcinoma was conducted to compare oncological outcomes.

RESULTS: Clinically relevant postoperative pancreatic fistula was significantly higher in the frail group than in the nonfrail group. A significant between-group difference was observed in overall complications with Clavien-Dindo classification grade ≥III. Furthermore, the proportion of all complications before readmission was higher in the frail group than in the nonfrail group. Among all readmitted patients, the frail group had a higher number of grade ≥IV patients requiring intensive care unit treatment. The frail group’s 90-day mortality was 1.3%; the difference was statistically significant (nonfrail: 0.3%, P=0.021). In the univariate and multivariate logistic regression analyses, mFI ≥0.27 (odds ratio 3.231, 95% confidence interval 1.889-5.523, P<0.001), extended pancreatectomy, body mass index ≥30 kg/m2, male sex, and malignancy were risk factors for Clavien-Dindo classification grade ≥III.

CONCLUSION: mFI is a potential preoperative tool for predicting severe postoperative complications, including mortality, in patients who have undergone MIDP for left-sided tumors.

PMID:37598358 | DOI:10.1097/JS9.0000000000000670

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Nevin Manimala Statistics

Factors associated with CD4 cell count recovery among males and females with advanced HIV disease

AIDS. 2023 Aug 18. doi: 10.1097/QAD.0000000000003695. Online ahead of print.

ABSTRACT

OBJECTIVE: HIV/AIDS mortality remains significantly high in Sub-Saharan Africa, mostly driven by opportunistic infections and advanced HIV disease (AHD). This study aimed to assess CD4 cell count recovery following ART initiation and factors associated with immune reconstitution.

METHODS: We conducted a prospective cohort study between 2015-2016. HIV-infected adults (≥18 years) with AHD (CD4 cell count ≤100 cells/mm3) receiving care at 20 outpatient HIV treatment facilities in Harare, Zimbabwe were enrolled. CD4 cell count recovery (CD4 cell count >200 cells/mm3) was assessed following 12-month ART initiation and factors associated with immune reconstitution were investigated using Logistic regression analysis. All statistical analyses were performed on SPSS v23.

RESULTS: 1320 participants were enrolled and 56.4% were males. The median (IQR) age was 37 (32-43) years. Tuberculosis was seen in 16.0%. Of the 739 participants that had CD4 cell count at 12 months, CD4 cell count recovery above 200 cells/mm3 was observed in 163 (22.1%) participants. Median (IQR) CD4 cell count at 12-months increased to 127 (75-190) cells/mm3 from 31 (14 – 55) at baseline. Factors associated with CD4 cell count recovery were younger age at baseline (OR≥40/<40 = 0.58, 95%CI: 0.40-0.85, P = 0.005), sex (ORfemale/male = 2.07, 95%CI:1.44-2.99,P < 0.0001) and baseline CD4 cell count (OR≥50/<50 = 1.60, 95%CI:1.10-2.33,P = 0.013).

CONCLUSION: A significant proportion (77.9%) of patients seeking care with AHD in a resource limited setting failed to recover a CD4 cell count >200 cells/mm3. Male sex, older age and low CD4 cell count at ART initiation were factors associated with poor immune reconstitution. Better differentiated care deliveries targeting this vulnerable population are critical for improving clinical outcomes and quality of life of the patients.

PMID:37598355 | DOI:10.1097/QAD.0000000000003695

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Nevin Manimala Statistics

Anticoagulation prescription among atrial fibrillation patients managed with and without an anticoagulant initiation pathway: a cohort study

Eur J Emerg Med. 2023 Aug 18. doi: 10.1097/MEJ.0000000000001072. Online ahead of print.

ABSTRACT

BACKGROUND AND IMPORTANCE: The Canadian Association of Emergency Physicians atrial fibrillation (AF) checklist advises that emergency physicians initiate anticoagulation therapy for patients with AF or flutter who are CHADS65 positive.

OBJECTIVES: The aim was to compare anticoagulation initiation rates between patients treated with and without an anticoagulation assessment pathway (the SAFE pathway).

DESIGN: This was a retrospective cohort study.

SETTINGS AND PARTICIPANTS: All emergency department patients were discharged home with a diagnosis of AF between June 2018 and May 2020 at two Canadian emergency departments.

INTERVENTION: The SAFE pathway is a hard copy form which allows emergency physicians to document contraindications to anticoagulation, the positive components of the CHADS65 score, and details how to prescribe anticoagulation.

OUTCOME MEASURES AND ANALYSIS: Trained researchers abstracted data on the use of the SAFE pathway by the presence or absence of the completed, scanned pathway in the electronic medical chart. The exposure of interest was use of this pathway. Patients were followed forward in time for 90 days by electronic medical record review to document stroke, transient ischemic attack, arterial embolism and major bleeding events. All events were independently adjudicated. Adjusted odds ratios were calculated to compare outcomes between those managed with and without the SAFE pathway.

RESULTS: In total, 766 patients were included, of whom 264 were already taking anticoagulation, 166 were CHADS65 negative and 65 had a contraindication to anticoagulation, leaving 271 patients eligible for anticoagulation prescription. Among the 271 eligible patients, 137/166 managed with the SAFE pathway were initiated on anticoagulation and 24/105 managed without the SAFE pathway started anticoagulation (adjusted odds ratio 25.9; 13.1-51.2). There was no statistically significant difference in the 90-day rate of stroke or bleeding.

CONCLUSION: Use of the SAFE pathway was associated with a higher rate of anticoagulation prescription.

PMID:37598348 | DOI:10.1097/MEJ.0000000000001072

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Nevin Manimala Statistics

Virtual biopsies: Proof of concept for a novel quantitative approach to liver biopsy adequacy and pathology education

Am J Clin Pathol. 2023 Aug 20:aqad104. doi: 10.1093/ajcp/aqad104. Online ahead of print.

ABSTRACT

OBJECTIVES: To quantitatively measure liver biopsy adequacy requirements and the effect of a teaching intervention that uses a virtual biopsy platform.

METHODS: A library of virtual liver biopsies was created using digital whole-slide, trichrome-stained tissue sections from liver resection material and QuPath image analysis software. Blinded participants staged fibrosis on the virtual biopsies before and after a teaching intervention.

RESULTS: This platform both modeled adequacy requirements for cirrhosis diagnosis on biopsy material and measured the effect of a teaching intervention on participant performance. Using this platform, diagnostic accuracy for cirrhosis could be modeled according to the function y = λ(1 ‒ e‒x/γ). The platform demonstrated that the relationship between biopsy size and diagnostic accuracy was statistically significant and that biopsies smaller than 6 mm long and 0.8 mm wide were insufficient to diagnosis cirrhosis. The platform also measured improvement in fibrosis staging accuracy among participants following a teaching intervention.

CONCLUSIONS: These results provide proof of concept for a virtual biopsy method by which outstanding questions in anatomic pathology can be addressed quantitatively using open source software. Future work is needed to validate these findings in clinical practice.

PMID:37598345 | DOI:10.1093/ajcp/aqad104

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Nevin Manimala Statistics

Development and validation of nomograms for predicting the risk of central lymph node metastasis of solitary papillary thyroid carcinoma of the isthmus

J Cancer Res Clin Oncol. 2023 Aug 20. doi: 10.1007/s00432-023-05146-7. Online ahead of print.

ABSTRACT

BACKGROUND: This study was conducted to develop nomograms and validate them by assessing risk factors for the development of central lymph node metastasis (CLNM) in patients with solitary papillary thyroid carcinoma of the isthmus (PTCI) for predicting the probability of CLNM.

METHODS: Demographic and clinicopathological variables of patients with solitary papillary thyroid carcinoma (PTC) from May 2018 to May 2023 at the First Hospital of Shanxi Medical University were retrospectively analyzed, and the lobar group and the isthmus group were divided according to tumor location. Patients with the same sex, age difference of less than 3 years, and equal gross tumor diameter were selected from the lobar group and compared with the paraisthmic tumor group. Independent risk factors were determined using univariate and multivariate logistic regression analysis. On this basis, clinical predictive nomograms were developed and validated.

RESULTS: Clinical data from 326 patients with solitary PTCI and 660 cases of solitary lobar PTC were used for analysis in our study. The incidence of solitary tumors CLNM located in the median isthmus, paracentral isthmus, and lobes was 69.8%, 40.9%, and 33.6%, respectively. Statistical analysis revealed that gender, age, isthmus location, maximum nodal diameter, the presence of possible CLNM in advance on preoperative ultrasound, chronic lymphocytic thyroiditis, and the lymphocyte/monocyte ratio were independent risk factors for preoperative CLNM in patients with solitary PTCI. Age, isthmus location, chronic lymphocytic thyroiditis, gross tumor diameter, presence of intraoperative extrathyroidal extension, and presence of metastasis in the Delphian lymph node on frozen section were independent risk factors for intraoperative CLNM. The concordance indices of nomograms for preoperative and intraoperative are 0.871 and 0.894 in the training set and 0.796 and 0.851 in the validation set, calibration curve and decision curve analysis also demonstrated the strong reliability and clinical applicability of this clinical prediction model.

CONCLUSION: In this study, we concluded that solitary PTCI is more aggressive compared to solitary lobar PTC, and we constructed nomograms and risk stratification to accurately identify patients with solitary PTCI who are at high risk of developing CLNM, which will help clinicians in personalized decision making.

PMID:37598343 | DOI:10.1007/s00432-023-05146-7

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Worldwide prevalence of natal and neonatal teeth: Systematic review and meta-analysis

J Am Dent Assoc. 2023 Aug 19:S0002-8177(23)00403-8. doi: 10.1016/j.adaj.2023.06.017. Online ahead of print.

ABSTRACT

BACKGROUND: Identifying the presence of teeth in newborns is important as it may require immediate care. This study aimed to determine the worldwide prevalence of natal and neonatal teeth.

TYPE OF STUDIES REVIEWED: Six electronic databases and the gray literature were searched on February 23, 2023 to identify observational studies reporting the prevalence of natal or neonatal teeth. Studies assuming natal and neonatal teeth as identical terms or not reporting prevalence indicators were excluded. The methodological quality of the studies was assessed using the Joanna Briggs Institute checklist for studies reporting prevalence data. The worldwide prevalence of natal and neonatal teeth was estimated via proportion meta-analysis using a β-binomial model. Heterogeneity across studies was explored via subgroup analyses and meta-regression.

RESULTS: None of the 23 included studies fulfilled all items of the methodological quality checklist. The worldwide prevalence of natal teeth was 34.55 (95% CI, 20.12 to 59.26) per 10,000, and the prevalence of neonatal teeth was 4.52 (95% CI, 2.59 to 17.91) per 10,000. Subgroup analysis by continent showed that the prevalence of natal teeth ranged from 11.26 (95% CI, 7.58 to 16.61) per 10,000 in Asia through 75.32 (95% CI, 51.11 to 99.86) per 10,000 in North America, and the prevalence of neonatal teeth ranged from 3.52 (95% CI, 1.73 to 7.06) per 10,000 in Europe through 6.01 (95% CI, 2.25 to 16.60) per 10,000 in South America. Meta-regression did not find a statistically significant association between prevalence rates and year of publication or sample size.

PRACTICAL IMPLICATIONS: Approximately 1 in 289 newborns had natal teeth and 1 in 2,212 had neonatal teeth. Although this is not a high prevalence, professionals must be alert to identify these conditions, which often require immediate care.

PMID:37598330 | DOI:10.1016/j.adaj.2023.06.017