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Nevin Manimala Statistics

Cardiac protective techniques in left breast radiotherapy: rapid selection criteria for routine clinical decision making

Eur J Med Res. 2023 Nov 9;28(1):504. doi: 10.1186/s40001-023-01470-3.

ABSTRACT

OBJECTIVE: In left breast radiotherapy (RT) desired heart doses may be achieved without heart-sparing RT techniques in some patients. We aimed to examine the existence of predictive factors and cutoff points to determine which patients are the main candidates for heart-sparing RT techniques.

MATERIAL AND METHOD: Dosimetric data for left breast cancer was examined. RT plans were made at conventional doses to the breast and peripheral lymph nodes. Statistical analyses were performed using SPSS 22.0 (SPSS Inc., IBM Corp., Armonk, NY).

RESULT: 114 cases were evaluated by ROC (Receiver operating characteristic) analysis in the breast-conserving surgery (BCS) and mastectomy groups. While only left lung volume (AUC: 0.74, 95% CI 0.61-0.87, p = 0.002) was significant in BCS cases, in cases with mastectomy, left lung volume (AUC: 0.81, 95% CI 0.69-0.94, p = 0.002) and lung/heart volume ratio (AUC: 0.83, 95% CI 0.70-0.96, p = 0.001) had a significant relationship with the relevance of heart doses. The cutoff point of 1.92 was selected for the lung/heart volume ratio for the mastectomized patients. Moreover, the cutoff point 1154 cc and 1208 cc was determined for the left lung volume for the BCS and mastectomized patients, respectively.

CONCLUSION: Various cutoff points in left breast RT can be used to predict whether RT plans will meet QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) heart dose limits. Evaluating only these few cutoff points before planning makes it possible to eliminate 70% of patients with BCS and 40% of patients with mastectomy from respiratory-controlled methods, which require time and effort. Patients with lung volume and lung/heart volume ratio smaller than the cutoff values can be considered primary candidates for heart-sparing techniques.

PMID:37941070 | DOI:10.1186/s40001-023-01470-3

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Nevin Manimala Statistics

Estimating genome-wide DNA methylation heterogeneity with methylation patterns

Epigenetics Chromatin. 2023 Nov 9;16(1):44. doi: 10.1186/s13072-023-00521-7.

ABSTRACT

BACKGROUND: In a heterogeneous population of cells, individual cells can behave differently and respond variably to the environment. This cellular diversity can be assessed by measuring DNA methylation patterns. The loci with variable methylation patterns are informative of cellular heterogeneity and may serve as biomarkers of diseases and developmental progression. Cell-to-cell methylation heterogeneity can be evaluated through single-cell methylomes or computational techniques for pooled cells. However, the feasibility and performance of these approaches to precisely estimate methylation heterogeneity require further assessment.

RESULTS: Here, we proposed model-based methods adopted from a mathematical framework originally from biodiversity, to estimate genome-wide DNA methylation heterogeneity. We evaluated the performance of our models and the existing methods with feature comparison, and tested on both synthetic datasets and real data. Overall, our methods have demonstrated advantages over others because of their better correlation with the actual heterogeneity. We also demonstrated that methylation heterogeneity offers an additional layer of biological information distinct from the conventional methylation level. In the case studies, we showed that distinct profiles of methylation heterogeneity in CG and non-CG methylation can predict the regulatory roles between genomic elements in Arabidopsis. This opens up a new direction for plant epigenomics. Finally, we demonstrated that our score might be able to identify loci in human cancer samples as putative biomarkers for early cancer detection.

CONCLUSIONS: We adopted the mathematical framework from biodiversity into three model-based methods for analyzing genome-wide DNA methylation heterogeneity to monitor cellular heterogeneity. Our methods, namely MeH, have been implemented, evaluated with existing methods, and are open to the research community.

PMID:37941029 | DOI:10.1186/s13072-023-00521-7

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Nevin Manimala Statistics

A TaqMan-based RT-qPCR assay for serotyping of Southern African territories (SAT) 2 strains of Foot-and-Mouth disease virus (FMDV) in Southern Africa

BMC Res Notes. 2023 Nov 8;16(1):323. doi: 10.1186/s13104-023-06586-7.

ABSTRACT

OBJECTIVE: Determining the serotype of circulating virus strains is important in implementing effective vaccination. In this study, Foot-and-Mouth Disease (FMD) Southern African territory 2 (SAT2) specific primers and TaqMan probe were designed towards rapid SAT2 detection and serotyping. The primers were tested by endpoint reverse transcription (RT) polymerase chain reaction (PCR) and quantitative PCR (RT-qPCR) using the vaccine strain SAT2035. The SAT2 serotype-specific RT-qPCR assay was compared with currently used ELISA and VP1 sequencing using Cohen’s kappa statistics.

RESULTS: The primers yielded amplicons of band size 190 bp during endpoint RT-PCR. When coupled with the probe, the primers reaction efficiency was determined to be 99% with an r2 value of 0.994. The results show that the SAT2 assay has comparable performance to VP1 sequencing (k = 1) and a moderate degree of agreement with ELISA (k = 0.571). The data shows that the newly designed assay could be considered for serotyping of SAT2 strains. However, for this assay to be complete there is a need to design effective SAT1 and SAT3 primers and probes that can be multiplexed to target other serotypes that co-circulate within relevant FMD endemic pools. For future implementation of the assay there is also a need to increase the number of field samples towards validation of the assay.

PMID:37941022 | DOI:10.1186/s13104-023-06586-7

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Nevin Manimala Statistics

Green chromatographic methods for determination of co-formulated lidocaine hydrochloride and miconazole nitrate along with an endocrine disruptor preservative and potential impurity

BMC Chem. 2023 Nov 8;17(1):151. doi: 10.1186/s13065-023-01065-3.

ABSTRACT

Recently, green analytical chemistry (GAC) is a key issue towards the idea of sustainability, the analytical community is focused on developing analytical methods that incorporate green chemistry principles to minimize adverse impacts on the environment and humans. Herein, we present 2 sustainable, selective, and validated chromatographic methods. Initially, lidocaine hydrochloride (LDC) and miconazole nitrate (MIC) with two preservatives; methyl paraben (MTP) and saccharin sodium (SAC) were chromatographed via TLC-densitometric method which employed ethyl acetate: methanol: formic acid (9:1:0.1, by volume) as the mobile phase with UV detection at 220.0 nm, good correlation was obtained in the range of 0.3-3.0 µg/band for MIC and LDC. Following that, RP-HPLC was successfully applied for separating quinary mixture of LDC, MIC, MTP, SAC along with LDC impurity; dimethyl aniline (DMA) using C18 column, and a gradient green mobile phase composed of methanol and phosphate buffer (pH 6.0) in different ratios with a flow rate 1.5 mL/min and UV detection at 210.0 nm, linearity ranges from 1.00 to 100.00 µg/mL for MIC, 2.00-100.00 µg/mL for LDC and 1.00–20.00 µg/mL for MTP and DMA. No records to date regarding the determination of the two drugs, besides MTP and DMA. The proposed methods were validated according to the ICH guidelines and applied successfully to the analysis of the compounds. The methods’ results were statistically compared to those obtained by applying the reported one, indicating no significant difference regarding both accuracy and precision. The methods’ greenness profiles have been assessed and compared with those of the reported method using different assessment tools.

PMID:37941018 | DOI:10.1186/s13065-023-01065-3

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Nevin Manimala Statistics

Roles of gut microbiota in atrial fibrillation: insights from Mendelian randomization analysis and genetic data from over 430,000 cohort study participants

Cardiovasc Diabetol. 2023 Nov 8;22(1):306. doi: 10.1186/s12933-023-02045-6.

ABSTRACT

BACKGROUND: Gut microbiota imbalances have been suggested as a contributing factor to atrial fibrillation (AF), but the causal relationship is not fully understood.

OBJECTIVES: To explore the causal relationships between the gut microbiota and AF using Mendelian randomization (MR) analysis.

METHODS: Summary statistics were from genome-wide association studies (GWAS) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) (the Dutch Microbiome Project) and two large meta-GWASs of AF. The significant results were validated in FinnGen cohort and over 430,000 UK Biobank participants. Mediation MR analyses were conducted for AF risk factors, including type 2 diabetes, coronary artery disease (CAD), body mass index (BMI), blood lipids, blood pressure, and obstructive sleep apnea, to explore the potential mediation effect of these risk factors in between the gut microbiota and AF.

RESULTS: Two microbial taxa causally associated with AF: species Eubacterium ramulus (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.12, P = 0.0001, false discovery rate (FDR) adjusted p-value = 0.023) and genus Holdemania (OR 1.15, 95% CI 1.07-1.25, P = 0.0004, FDR adjusted p-value = 0.042). Genus Holdemania was associated with incident AF risk in the UK Biobank. The proportion of mediation effect of species Eubacterium ramulus via CAD was 8.05% (95% CI 1.73% – 14.95%, P = 0.008), while the proportion of genus Holdemania on AF via BMI was 12.01% (95% CI 5.17% – 19.39%, P = 0.0005).

CONCLUSIONS: This study provided genetic evidence to support a potential causal mechanism between gut microbiota and AF and suggested the mediation role of AF risk factors.

PMID:37940997 | DOI:10.1186/s12933-023-02045-6

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Nevin Manimala Statistics

Effect of knee osteoarthritis on the postoperative outcome of proximal femoral nail anti-rotation in the treatment of intertrochanteric fractures in the elderly: a retrospective analysis

BMC Musculoskelet Disord. 2023 Nov 8;24(1):868. doi: 10.1186/s12891-023-07012-6.

ABSTRACT

BACKGROUND: The proximal femoral nail anti-rotation (PFNA) is a commonly used internal fixation system for intertrochanteric fractures (IFs) in older adults. Knee osteoarthritis (KOA) is a degenerative lower extremity disease that occurs most frequently in the elderly. Some patients have already had KOA before the IFs. However, whether KOA impacts the postoperative outcome of IFs has not been reported.

OBJECTIVE: This study aimed to investigate the effect of KOA on the fracture side on the outcome after PFNA for IFs in the elderly.

METHODS: Between January 2016 and November 2021, 297 elderly patients treated with PFNA for IFs were enrolled in this study. They were divided into two groups according to the American Rheumatism Association KOA clinical and radiographic criteria: the control group and the KOA group. Intraoperative bleeding, operative time, length of hospital stay, postoperative time out of bed, fracture healing time, postoperative complications, postoperative Harris hip function score, and Barthel ability to daily living Score were compared between the two groups. Follow-up was routinely scheduled at 1, 3, 6, and 12 months postoperatively.

RESULTS: Based on the exclusion criteria, 254 patients who met the requirements were left to be included in this study, including the control group (n = 133) and the KOA group (n = 121). Patients were followed up for a mean of 17.5 months (12-24 months). There was no significant difference between the two groups in preoperative demographic data, intraoperative blood loss, operation time, and length of stay in the hospital. The control group was statistically significant compared to the KOA group in terms of postoperative time out of bed (17.8 ± 4.0 days vs. 19.1 ± 5.8 days), fracture healing time (13.7 ± 2.2 weeks vs. 14.6 ± 3.7 weeks), and postoperative complications (12.8 vs. 23.1%). The Harris hip function score and Barthel ability to daily living score were higher in the control group than in the KOA group at 1, 3, 6, and 12 months postoperatively (the control group: 63.8 ± 10.9, 71.8 ± 10.3, 81.5 ± 8.7, and 91.6 ± 6.3 vs. The KOA group 61.0 ± 10.4, 68.6 ± 9.1, 79.0 ± 9.2, and 88.5 ± 5.9).

CONCLUSIONS: In elderly patients with IFs combined with KOA of the fracture side treated with PFNA internal fixation, KOA increases the incidence of postoperative complications of the fracture, prolongs postoperative time out of bed and fracture healing, and reduces postoperative hip function and ability to daily living. Therefore, treating KOA on the fractured side needs to be considered when treating IFs in the elderly.

PMID:37940993 | DOI:10.1186/s12891-023-07012-6

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Nevin Manimala Statistics

Characteristics of hemoglobin distributions in preschool children and non-pregnant women of reproductive age and their implications for establishing quality control criteria for hemoglobin data in field surveys: evidence from 483 surveys conducted in refugee settings worldwide

Popul Health Metr. 2023 Nov 9;21(1):20. doi: 10.1186/s12963-023-00315-9.

ABSTRACT

BACKGROUND: Currently, there is a lack of clear guidance on hemoglobin (Hb) data quality parameters and plausible flagging ranges for population-representative surveys. There is a need to determine which properties of Hb data indicate lower data quality and increased measurement error and which represent intrinsic statistical properties of Hb distributions rather than quality problems.

METHODS: We explored statistical characteristics of Hb distributions and plausible exclusion ranges in population-representative surveys of non-pregnant women of reproductive age (WRA) (15-49 years, n = 401 surveys) and children (6-59 months, n = 461 surveys) conducted in refugee settings by the United Nations High Commissioner for Refugees (UNHCR). Hb distribution characteristics [standard deviation (SD), skewness and kurtosis] were compared to those from Demographic and Health Surveys (DHS).

RESULTS: Overall, 0.08% of child and 0.14% of WRA Hb values were outside of the previously proposed 4.0-18.0 g/dL plausible range. Surveys conducted in Uganda tended to have unusually high SD compared with surveys from other settings, possibly an indication of problematic measurement quality. We therefore used summary results on SD, skewness and kurtosis excluding surveys from Uganda when comparing with DHS results or proposing plausible ranges. Both WRA and child Hb distributions tended to be left-skewed and had excess positive kurtosis. Mean survey-level SD was greater, mean skewness more negative, and mean kurtosis more positive in WRA surveys compared to child surveys. All these findings were broadly similar to those from DHS surveys. Mean SD in DHS surveys was higher than that in our data for both children (1.48 vs. 1.34) and WRA (1.58 vs. 1.43).

CONCLUSIONS: We observed several statistical characteristics of Hb distributions that may not necessarily be indicative of data quality problems and bear strong similarities with the characteristics found in DHS surveys. Hb distributions tended to be negatively skewed and positively kurtotic, and SD in many surveys exceeded 1.5 (previously proposed upper plausible range). Based on our empirical evidence, surveys with skewness above + 0.2 and kurtosis below -0.5 or Hb SD outside the range of 1.1-1.55 g/dL for children (6-59 mo) or 1.1-1.65 g/dL for non-pregnant WRA (15-49 y) may require further quality investigation.

PMID:37940990 | DOI:10.1186/s12963-023-00315-9

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Bayesian methods: a potential path forward for sepsis trials

Crit Care. 2023 Nov 8;27(1):432. doi: 10.1186/s13054-023-04717-x.

ABSTRACT

BACKGROUND: Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods.

METHODS: We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment.

RESULTS: In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored.

CONCLUSIONS: Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

PMID:37940985 | DOI:10.1186/s13054-023-04717-x

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Nevin Manimala Statistics

Triglyceride-glucose index in the prediction of clinical outcomes after successful recanalization for coronary chronic total occlusions

Cardiovasc Diabetol. 2023 Nov 8;22(1):304. doi: 10.1186/s12933-023-02037-6.

ABSTRACT

BACKGROUND: Triglyceride-glucose index (TyG) has been widely used to predict cardiovascular outcomes. However, it remains unclear whether TyG holds prognostic significance for patients with coronary chronic total occlusions (CTO). Thus, our study aimed to evaluate the predictive accuracy and prognostic value of TyG in individuals who underwent successful percutaneous coronary intervention (PCI) for CTO.

METHODS: A total of 331 consecutive patients with ≥ 1 successful CTO-PCI were included. The baseline and angiographic data were acquired. The duration of follow-up ranged from 32 to 79 months, with a median of 44 months and an interquartile range of 39 to 67 months. The primary outcome measured was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), including mortality, target vessel revascularization, recurrent myocardial infarction, and stroke.

RESULTS: After controlling for confounders, multivariate Cox regression analysis revealed that TyG remained statistically significant, regardless of being a continuous or categorical variable. In the partially adjusted regression model, the Hazard ratio (95%CI) for MACCE was 2.54 (1.12-5.79) in tertile 3 and 1.61 (1.22-2.12) per SD increase in the TyG.Kaplan-Meier survival analysis demonstrated significant differences in MACCE-free survival rates across tertiles of the TyG, as indicated by the log-rank test (p = 0.001). ROC analysis was conducted to evaluate the predictive ability of TyG for MACCE, resulting in an AUC of 0.677.

CONCLUSION: The TyG index demonstrates independent predictive capabilities for MACCE in patients who have undergone successful CTO-PCI. These findings suggest that TyG holds the potential as a valuable tool in risk stratification and the identification of patients who may benefit from early intervention in the management of CTO.

PMID:37940976 | DOI:10.1186/s12933-023-02037-6

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Nevin Manimala Statistics

Adverse drug reactions in hospitals: population estimates for Portugal and the ICD-9-CM to ICD-10-CM crosswalk

BMC Health Serv Res. 2023 Nov 8;23(1):1222. doi: 10.1186/s12913-023-10225-z.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADR), both preventable and non-preventable, are frequent and pose a significant burden. This study aimed to produce up-to-date estimates for ADR rates in hospitals, in Portugal, from 2010 to 2018. In addition, it explores possible pitfalls when crosswalking between ICD-9-CM and ICD-10-CM code sets for ADR identification.

METHODS: The Portuguese Hospital Morbidity Database was used to identify hospital episodes (outpatient or inpatient) with at least one ICD code of ADR. Since the study period spanned from 2010 to 2018, both ICD-9-CM and ICD-10-CM codes based on previously published studies were used to define episodes. This was an exploratory study, and descriptive statistics were used to provide ADR rates and summarise episode features for the full period (2010-2018) as well as for the ICD-9-CM (2010-2016) and ICD -10-CM (2017-2018) eras.

RESULTS: Between 2010 and 2018, ADR occurred in 162,985 hospital episodes, corresponding to 1.00% of the total number of episodes during the same period. Higher rates were seen in the oldest age groups. In the same period, the mean annual rate of episodes related to ADR was 174.2/100,000 population. The episode rate (per 100,000 population) was generally higher in males, except in young adults (aged ’15-20′, ’25-30′ and ’30-35′ years), although the overall frequency of ADR in hospital episodes was higher in females.

CONCLUSIONS: Despite the ICD-10-CM transition, administrative health data in Portugal remain a feasible source for producing up-to-date estimates on ADR in hospitals. There is a need for future research to identify target recipients for preventive interventions and improve medication safety practices in Portugal.

PMID:37940971 | DOI:10.1186/s12913-023-10225-z