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Nevin Manimala Statistics

Survival Analysis Using the Covid-death Mean-imputation (CoDMI) Algorithm: A First Clinical Application in Radiation Oncology

In Vivo. 2022 Nov-Dec;36(6):2986-2992. doi: 10.21873/invivo.13043.

ABSTRACT

BACKGROUND/AIM: To report long-term survival results after trimodal approach for locally advanced rectal cancer (LARC) in the Covid-19 era. We herein illustrate a clinical application of Covid-death mean-imputation (CoDMI) algorithm in LARC patients with Covid-19 infection.

PATIENTS AND METHODS: We analyzed 94 patients treated for primary LARC. Overall survival was calculated in months from diagnosis to first event (last follow-up/death). Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events, the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using the CoDMI algorithm. Patients who died of Covid-19 (DoC) are mean-imputed by the Kaplan-Meier estimator. Under this approach, the observed lifetime of each DoC patient is considered as an “incomplete data” and is extended by an additional expected lifetime computed using the classical Kaplan-Meier model.

RESULTS: Sixteen patients were dead of disease (DoD), 1 patient was DoC and 77 cases were censored (Cen). The DoC patient died of Covid-19 52 months after diagnosis. The CoDMI algorithm computed the expected future lifetime provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, the CoDMI algorithm estimated that this patient would have died after 79.5 months of follow-up.

CONCLUSION: The CoDMI algorithm leads to “unbiased” probability of overall survival in LARC patients with Covid-19 infection, compared to that provided by a naïve application of Kaplan-Meier approach. This allows for a proper interpretation/use of Covid-19 events in survival analysis. A user-friendly version of CoDMI is freely available at https://github.com/alef-innovation/codmi.

PMID:36309383 | DOI:10.21873/invivo.13043

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Prognostic Impact of Quality and Distribution of Adipose Tissue in Patients With Primary Central Nervous System Lymphoma

In Vivo. 2022 Nov-Dec;36(6):2828-2834. doi: 10.21873/invivo.13021.

ABSTRACT

BACKGROUND/AIM: Body composition assessment has shown promising results as a prognostic biomarker as depicted by cross-sectional imaging of several tumor entities including lymphomas. The present study sought to elucidate the prognostic relevance of subcutaneous and visceral fat tissue (SAT and VAT) in patients with primary central nervous system lymphoma (PCNSL).

PATIENTS AND METHODS: Overall, 74 patients (36 female patients, 46.7%) with a mean age of 64.2±12.8 years (range=23-81 years) were identified in the database with sufficient clinical and imaging data and included into this retrospective study. Fat area assessment was performed on one axial slide on L3-height derived from staging computed tomography (CT) images. Subcutaneous, visceral, and intramuscular adipose tissues (SAT, VAT, IMAT) were estimated. Also, density of SAT, VAT, and IMAT were estimated. Finally, the ratio VAT/SAT (VSR) was calculated. Overall and progression-free survival (OS and PFS) were used as study end points.

RESULTS: In the observation period, overall, 47 patients (63.5%) died. Mean OS was 33.8±45.4 months and mean PFS was 26.6±42.7 months. The mean VAT value was 162±99.5 cm2, the mean SAT was 202.4±103.3 cm2, the mean VSR was 0.92±0.69. The hazard ratios (HRs) for overall survival were 0.87 for high VAT, 1.52 for SAT, and 0.73 for VSR in univariable analysis. For PFS it was 0.24 for VAT, 1.11 for SAT, and 1.07 for VSR. No values achieved statistical significance. Similar results were shown in Kaplan-Meier analysis for OS and PFS, respectively.

CONCLUSION: Parameters of adipose tissue are not associated with OS and PFS in patients with PCNSL.

PMID:36309379 | DOI:10.21873/invivo.13021

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Validation of the Rat Model of Prostate Cancer: Correlating Seminal Vesicle Lesions With Dorsolateral Prostate Lesions

In Vivo. 2022 Nov-Dec;36(6):2662-2668. doi: 10.21873/invivo.13001.

ABSTRACT

BACKGROUND/AIM: Lesions in the seminal vesicle are described in the most used protocols for prostate cancer (PCa) induction. This study aimed to characterize the lesions of seminal vesicles associated with a protocol of PCa induction in rats to contribute to better characterization of this model.

MATERIALS AND METHODS: Forty-five male Wistar Unilever rats were randomly divided into two control groups: CONT1 (n=10) and CONT2 (n=10); and two PCa-induced groups: IND1 (n=10) and IND2 (n=15), sacrificed at 35 and 61 weeks, respectively. Animals from the induced groups were exposed to a multistep protocol for PCa induction. Animals, seminal vesicles and dorsolateral prostate were weighed. Seminal vesicles and dorsolateral prostate were submitted to histopathological and immunohistochemical analysis.

RESULTS: Animals in which PCa was induced had a lower mean body weight when compared with the control animals (p<0.05). The relative mean seminal vesicle weight was higher in groups with PCa when compared with control groups (p<0.05). Although the differences were not statistically significant, animals from the IND2 group developed more lesions than animals from the IND1 and CONT2 groups. It is worth noting that the animals from group IND2 developed papillary adenomas and carcinomas in situ, which were not observed in any other group. Similar to observations in seminal vesicles, animals from group IND2 developed more dorsolateral prostate lesions than animals from the IND1 group (p<0.05).

CONCLUSION: We observed that the longer the exposure to testosterone was, the greater was the incidence of preneoplastic and neoplastic lesions in both the seminal vesicle and the prostate, suggesting that testosterone exposure affects the spectrum of developed lesions.

PMID:36309374 | DOI:10.21873/invivo.13001

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Safety and Efficacy of Direct-acting Antiviral Therapies for Chronic HCV Infection in Hemodialysis Patients

In Vivo. 2022 Nov-Dec;36(6):2918-2922. doi: 10.21873/invivo.13033.

ABSTRACT

BACKGROUND/AIM: The aim of this study was to determine the safety and efficacy of a direct-acting antiviral treatment, ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, in a real-life setting.

PATIENTS AND METHODS: We performed a prospective observational study including 108 patients undergoing hemodialysis for end-stage kidney disease, referred to our clinic for antiviral therapy for chronic hepatitis C virus infection. Patients received treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, for 12 weeks. Sustained virologic response (SVR) was defined as undetectable viremia at 12 weeks after the end of therapy. For safety analysis, we monitored serum levels of hemoglobin, albumin, total bilirubin, alanine-aminotransferase and aspartate- aminotransferase at the beginning and end of therapy, as well as at SVR. Verbal Numeric Rating Scale was used to assess the presence of nausea, headaches and fatigue.

RESULTS: We noted a high prevalence of diabetic and hypertensive nephropathy as the underlying cause of chronic kidney disease. Most of the patients had F2 and F3 liver fibrosis (32.40% and 34.25%, respectively). The SVR rate was 96.2% (103/107 patients). We recorded an unrelated death after the completion of antiviral therapy. We found increased levels of nausea, headaches and fatigue at the end of therapy compared to at initiation, The presence and degree of symptoms did not correlate with the underlying cause of renal disease (p=0.72) nor with the degree of fibrosis (p=0.08). Minimal increases in transaminases and bilirubin were recorded at the end of treatment, with no statistical significance.

CONCLUSION: Oral antiviral therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir can be safely used in hemodialysis patients, with similar response rates compared to the general population.

PMID:36309363 | DOI:10.21873/invivo.13033

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Nevin Manimala Statistics

The Incidence and Effect of COVID-19 Vaccine Adverse Events on Breakthrough Infections: Decentralized Observational Study that Includes Underrepresented Groups

JMIR Form Res. 2022 Oct 29. doi: 10.2196/41914. Online ahead of print.

ABSTRACT

BACKGROUND: Despite continuing efforts to improve inclusion of underserved groups in clinical research, gaps in diversity remain. Participation of special populations is especially important when facing problems of unprecedented complexity such as COVID-19. A better understanding of factors associated with immune response in diverse populations would advance future preventive and curative approaches.

OBJECTIVE: The objective of this study was to investigate the factors potentially responsible for adverse events following the COVID-19 immunization. The population of the study included adults from rural areas, developing countries, and those with medically understudied conditions, across a broad age range.

METHODS: The study evolved from peer-support networks developed during the COVID-19 pandemic. Participants were recruited digitally through online neighborhood and health communities. Some of the participants volunteered as study investigators assisting with off-line recruitment and safety monitoring. Individuals who consented to participate were asked to share their vaccination experiences either using constantly-evolving online surveys or via one-to-one communication. Inferential statistics to estimate differences between study groups was performed using parametric and non-parametric tests.

RESULTS: Of 1430 participants who shared their vaccination experiences, 648 had outcome measures at their 1.5-year follow-up. Statistically significant differences were found between age groups, types of vaccine adverse events (VAEs), incidences of breakthrough infections and health conditions linked to the microbiome. Pairwise comparisons showed that VAEs interfering with daily activities were significantly higher in both younger (18-59) and older groups (80-100, P < .001) when compared to the 60-79 age bracket. Short term VAEs were associated with lower incidence of breakthrough COVID-19 relative to those who reported either minimal or long-term adverse events (P < .001). A genetic origin was suggested for some adverse reactions.

CONCLUSIONS: The findings of this study demonstrate that vaccine adverse reactions in the elderly are being overlooked and the incidence of VAEs impairing immunity may be higher than previously thought. Better preventive measures are needed for all those at risk for life-threatening and long-term adverse events of vaccination. Supportive community-based studies focusing on these populations could add important data to the body of knowledge. Further and more comprehensive studies should follow.

CLINICALTRIAL: ClinicalTrials.gov NCT04832932; https://clinicaltrials.gov/ct2/show/NCT04832932.

INTERNATIONAL REGISTERED REPORT: RR2-10.1101/2021.06.28.21256779.

PMID:36309347 | DOI:10.2196/41914

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Nevin Manimala Statistics

Failure of internal cerebrospinal fluid shunt: a systematic review and meta-analysis of the overall prevalence in adult

World Neurosurg. 2022 Oct 26:S1878-8750(22)01490-5. doi: 10.1016/j.wneu.2022.10.073. Online ahead of print.

ABSTRACT

OBJECTIVE: Reported rates of failures varies greatly from below 5% up to over 50% and, no meta-analysis to assess the overall prevalence has ever been performed. Herein, the authors estimated the failure rate after internal CSF shunt (ICSFS) insertion and searched for associated factors.

METHODS: Six databases were searched from January 1990 to February 2022. Only original articles reporting the rate of adult shunt failure were included. Random-effects meta-analysis with generalised linear mixed model method and logit transformation was used to compute the overall failure prevalence. Subgroup analysis and meta-regression were implemented to search for associated factors.

RESULTS: Of 1,763 identified articles, 46 were selected, 70,859 ICSFS implantations and for 13,603 shunt failure, suggesting an accumulated incidence of 19.2%. However, the calculated pooled prevalence value and its 95% confidence interval (CI) were 22.7% 95%CI[19.8-5.8]. The CI of the different estimates did not overlap, indicating a strong heterogeneity confirmed by a high I2 of 97.5%, 95%CI[97.1-97.8], p<0.001 with a τ2=0.3. Ninety-five percent prediction interval of shunt failure prevalence ranged from 8.75% up to 47.36%. A meta-regression of prevalence by year of publication found a barely significant decreasing failure rate of about two percent per year (-2.11, 95%CI[-4.02- -0.2], p-value=0.031).

CONCLUSION: Despite being a quite simple neurosurgical procedure, ICSFS insertion has one of the highest risk of complications with failure prevalence involving more than 1 patient out of 5. Nonetheless, all the efforts to lower these frustrating high level of shunt failure seem to be effective.

TRIAL REGISTRATION: This meta-analysis is registered in https://www.crd.york.ac.uk/PROSPERO/, PROSPERO ID: CRD42022339954.

PMID:36309337 | DOI:10.1016/j.wneu.2022.10.073

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The Influence of Roussouly Type on the Prevalence, Subtype and Distribution Characteristics of Modic Changes in Patients with Lumbar Degenerative Disc Disease

World Neurosurg. 2022 Oct 26:S1878-8750(22)01487-5. doi: 10.1016/j.wneu.2022.10.070. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between Roussouly type and Modic changes (MCs) is unknown. Thus, the aim of our study was to investigate the influence of Roussouly type on the characteristics of MCs in patients with lumbar degenerative disc disease (LDD).

METHODS: This cross-sectional observational study included 270 patients with LDD from Huashan Hospital. All the subjects were divided into four groups according to the Roussouly classification. The prevalence, subtype and distribution characteristics of MCs from L1-L2U to L5-S1L were compared between four Roussouly types.

RESULT: A total of 270 patients were included in our study, 65 cases (24.1%) of Roussouly type Ⅰ, 115 cases (42.6%) of Roussouly type Ⅱ, 55 cases (20.4%) of Roussouly type Ⅲ, and 35 cases (13.0%) of Roussouly type Ⅳ. MCs were present in 45.9% (n=270) subjects, 12.7% (n=2700) endplates and 11.8% (n=1350) intervertebral discs. The prevalence rate of MCs by subtype and intervertebral disc among four Roussouly types was statically different (P<0.05) and the prevalence rate of MCs by intervertebral disc in Roussouly type Ⅰ was statistically higher than other three Roussouly types. In Roussouly type Ⅰ and Ⅳ, the prevalence rate of MCs at L4-L5 level showed no significant differences compared with those at upper lumbar levels while in Roussouly type Ⅱ and Ⅲ, the prevalence rate of MCs at L4-L5 level was significantly higher than those at upper lumbar levels.

CONCLUSION: We concluded that Roussouly types can influence the prevalence, subtype and distribution characteristics of MCs in patients with LDD.

PMID:36309336 | DOI:10.1016/j.wneu.2022.10.070

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Nevin Manimala Statistics

Spatially-enhanced clusterwise inference for testing and localizing intermodal correspondence

Neuroimage. 2022 Oct 26:119712. doi: 10.1016/j.neuroimage.2022.119712. Online ahead of print.

ABSTRACT

With the increasing availability of neuroimaging data from multiple modalities-each providing a different lens through which to study brain structure or function-new techniques for comparing, integrating, and interpreting information within and across modalities have emerged. Recent developments include hypothesis tests of associations between neuroimaging modalities, which can be used to determine the statistical significance of intermodal associations either throughout the entire brain or within anatomical subregions or functional networks. While these methods provide a crucial foundation for inference on intermodal relationships, they cannot be used to answer questions about where in the brain these associations are most pronounced. In this paper, we introduce a new method, called CLEAN-R, that can be used both to test intermodal correspondence throughout the brain and also to localize this correspondence. Our method involves first adjusting for the underlying spatial autocorrelation structure within each modality before aggregating information within small clusters to construct a map of enhanced test statistics. Using structural and functional magnetic resonance imaging data from a subsample of children and adolescents from the Philadelphia Neurodevelopmental Cohort, we conduct simulations and data analyses where we illustrate the high statistical power and nominal type I error levels of our method. By constructing an interpretable map of group-level correspondence using spatially-enhanced test statistics, our method offers insights beyond those provided by earlier methods.

PMID:36309332 | DOI:10.1016/j.neuroimage.2022.119712

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Nevin Manimala Statistics

Gestational exposure to perfluoroalkyl substances is associated with placental DNA methylation and birth size

Sci Total Environ. 2022 Oct 26:159747. doi: 10.1016/j.scitotenv.2022.159747. Online ahead of print.

ABSTRACT

DNA methylation is one potential mechanism for the effects of gestational exposure to perfluoroalkyl substances (PFASs) on fetal growth. We investigated 180 pregnant women who participated in a cohort study conducted in Tangshan City, Northern China, and determined the concentrations of 11 PFASs and the methylation of two genes related to fetal growth [insulin-like growth factor 2 (IGF2) and nuclear receptor subfamily 3 group C member 1 (NR3C1)] and one surrogate marker for global methylation [long interspersed nuclear element-1 (LINE-1)] in placenta tissue. Multiple linear regression analysis was performed to examine the associations of log transformed PFASs with the DNA methylation and birth size. Weighted quantile sum regression was used to determine the mixture effect of PFASs. After adjusting for potential confounders, perfluorooctane sulfonate (PFOS) was negatively associated with the overall methylation of LINE-1. PFASs mixture was negatively associated with the methylation of all CpG loci of LINE-1 and overall methylation of NR3C1. Perfluorootanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and the PFASs mixture showed negative associations with head circumference. After stratified by newborns’ sex, PFOA, PFNA and the PFASs mixture was negatively associated with overall methylation of LINE-1 only in the male subgroup and the methylation of all CpG loci of LINE-1 was negatively associated with ponderal index only in the female subgroup. The interaction of newborns’ sex with PFOS and PFOA on overall methylation of IGF2 was statistically significant and so was the interaction of sex with PFOS on overall methylation of LINE-1. These findings suggested that intrauterine exposure to PFASs affected placental DNA methylation and reduced fetal growth, which might be modified by sex.

PMID:36309289 | DOI:10.1016/j.scitotenv.2022.159747

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Assessment of natural and anthropogenic contamination sources in a Mediterranean aquifer by combining hydrochemical and stable isotope techniques

Sci Total Environ. 2022 Oct 26:159763. doi: 10.1016/j.scitotenv.2022.159763. Online ahead of print.

ABSTRACT

The Atalanti basin is an intensively cultivated area in central Greece, facing groundwater quality deterioration threats due to natural and anthropogenic-related contamination sources. A combination of statistical and hydrogeochemical techniques, and stable isotope compositions (δ2H-H2O and δ18Ο-Η2Ο, δ15Ν-ΝΟ3 and δ18Ο-ΝΟ3, δ34S-SO42- and δ18O-SO42-) were applied to elucidate the origin of salinity and nitrate contamination, and shed light on the potential associations between geogenic Cr(VI) and NO3 sources and transformations. Nitrate and Cr(VI) concentrations reached up to 337 mg L-1 and 76.1 μg L-1, respectively, exceeding WHO threshold values in places. The cluster of samples with the high salinity was mostly influenced by irrigation return flow and marine aerosols, and less by seawater intrusion, as evidenced by the ionic ratios (e.g., Na+/Cl) and the stable isotopes of oxygen and hydrogen in water, and sulphur and oxygen in sulphates. The δ15Ν-ΝΟ3 and δ18O-NO3 values ranged from +2.0 ‰ to +14.5 ‰ and + 0.3 ‰ to +11.0 ‰, respectively. We found that the dominant sources of NO3 in groundwater were fertilizers in the central part of the area and sewage waste in the northern part around the residential area of Livanates. The occurrence of denitrification was evident in the northern part of the basin, where the DO levels were lowest (≤ 2.2 mg L-1), whereas nitrification of NH4+-fertilizers prevailed in the central part. High Cr(VI) values (≥ 20 μg/l) were associated with the lowest deviation of the measured from the theoretical nitrification δ18Ο-NO3 values, whereas the lowest Cr(VI) values were observed in the denitrified water samples. Our isotope findings revealed the strong influence of redox conditions on the biogeochemical transformations of N species and the mobilization of Cr(VI) that will help improve the understanding of the fate of these contaminants from the unsaturated zone to the groundwater in areas of agricultural and urban land use.

PMID:36309271 | DOI:10.1016/j.scitotenv.2022.159763