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Nevin Manimala Statistics

Evaluation of Optimal Assessment Schedules for Surveillance After Definitive Locoregional Treatment of Locally Advanced Head and Neck Cancer: A Retrospective Cohort Study With Parametric Modeling of Event-Free Survival

JAMA Otolaryngol Head Neck Surg. 2022 Sep 29. doi: 10.1001/jamaoto.2022.2561. Online ahead of print.

ABSTRACT

IMPORTANCE: In clinical practice, assessment schedules are often arbitrarily determined after definitive treatment of head and neck cancer (HNC), producing heterogeneous and inconsistent surveillance plans.

OBJECTIVE: To establish an optimal assessment schedule for patients with definitively treated locally advanced HNC, stratified by the primary subsite and HPV status, using a parametric model of standardized event-free survival curves.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study including 2 tertiary referral hospitals and a total of 673 patients with definitive locoregional treatment of locally advanced HNC (227 patients with nasopharyngeal cancer [NPC]; 237 patients with human papillomavirus-positive oropharyngeal cancer [HPV+ OPC]; 47 patients with HPV-negative [HPV-] OPC; 65 patients with hypopharyngeal cancer [HPC]; and 97 patients with laryngeal cancer [LC]). Patients had received primary treatment in 2008 through 2019. The median (range) follow-up duration was 57.8 (6.4-158.1) months. Data analyses were performed from April to October 2021.

MAIN OUTCOMES AND MEASURES: Tumor recurrence and secondary malignant neoplasms. Event-free survival was defined as the period from the end of treatment to occurrence of any event. Event-free survival curves were estimated using a piecewise exponential model and divided into 3 phases of regular follow-up. A 5% event rate criterion determined optimal follow-up time point and interval.

RESULTS: The median (range) age of the 673 patients at HNC diagnosis was 58 (15-83) years; 555 (82.5%) were men; race and ethnicity were not considered. The event rates of NPC, HPV+ OPC, HPV- OPC, HPC, and LC were 18.9% (43 of 227), 14.8% (35 of 237), 36.2% (17 of 47), 44.6% (29 of 65), and 30.9% (30 of 97), respectively. Parametric modeling demonstrated optimal follow-up intervals for HPC, LC, and NPC, respectively, every 2.1, 3.2, and 6.1 months; 3.7, 5.6, and 10.8 months; and 9.1, 13.8, and 26.5 months until 16.5, 16.5 to 25.0, and 25.0 to 99.0 months posttreatment (open follow-up thereafter). For HPV- OPC, assessment was recommended every 2.7, 4.8, and 11.8 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. In contrast, HPV+ OPC optimal intervals were every 7.7, 13.7, and 33.7 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. Five, 4, 12, 15, and 10 follow-up visits were recommended for NPC, HPV+ OPC, HPV- OPC, HPC, and LC, respectively.

CONCLUSIONS AND RELEVANCE: This retrospective cohort study using parametric modeling suggests that the HNC assessment schedules should be patient tailored and evidence based to consider primary subsites and HPV status. Given limited health care resources and rising detection rates and costs of HNC, the guidelines offered by these findings could benefit patients and health systems and aid in developing future consensus guidelines.

PMID:36173618 | DOI:10.1001/jamaoto.2022.2561

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Nevin Manimala Statistics

Reducing the biases in false correlations between discrete characters

Syst Biol. 2022 Sep 29:syac066. doi: 10.1093/sysbio/syac066. Online ahead of print.

ABSTRACT

The correlation between two characters is often interpreted as evidence that there exists a significant and biologically important relationship between them. However, Maddison and FitzJohn (2015) recently pointed out that evidence of correlated evolution between two categorical characters is often spurious, particularly, when the dependent relationship stems from a single replicate deep in time. Here we will show that there may, in fact, be a statistical solution to the problem posed by Maddison and FitzJohn (2015) naturally embedded within the expanded model space afforded by the hidden Markov model (HMM) framework. We demonstrate that the problem of single unreplicated evolutionary events manifests itself as rate heterogeneity within our models and that this is the source of the false correlation. Therefore, we argue that this problem is better understood as model misspecification rather than a failure of comparative methods to account for phylogenetic pseudoreplication. We utilize HMMs to develop a multi-rate independent model which, when implemented, drastically reduces support for correlation. The problem itself extends beyond categorical character evolution, but we believe that the practical solution presented here may lend itself to future extensions in other areas of comparative biology.

PMID:36173613 | DOI:10.1093/sysbio/syac066

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Nevin Manimala Statistics

FRAGILE-COLCOVID19: A Clinical Trial Based on Early Administration of an Oral Combination of Colchicine and Prednisone in Elderly Patients with COVID-19 in Geriatric Facilities

Clin Drug Investig. 2022 Sep 29. doi: 10.1007/s40261-022-01201-2. Online ahead of print.

ABSTRACT

BACKGROUND: Unprotected and fragile elderly people in nursing homes experienced the highest mortality rates during the initial coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: Our aim was to study the role of two oral anti-inflammatory drugs, colchicine and prednisone, in elderly patients with COVID-19 in geriatric centers.

METHODS: A phase II/III, randomized, controlled, multicenter clinical trial was performed in a geriatric population comparing the efficacy and safety of an oral combination of prednisone (60 mg/day for 3 days) and colchicine (at loading doses of 1-1.5 mg/day for 3 days, followed by 0.5 mg/day for 11 days) with the standard treatment, based on intravenous dexamethasone. Primary endpoints assessed the efficacy in reducing death or the modified endpoint death/therapeutic failure to the study drugs over a 28-day period, while secondary endpoints included safety, laboratory changes, and additional therapies used.

RESULTS: Fifty-four patients (35 female/19 male) were enrolled, 25 (46.3%) of whom were allocated to the experimental arm and 29 (53.7%) to the control arm. At day 28, no differences in deaths were observed. The combination of mortality or therapeutic failure occurred in 12 (45.13%) patients receiving dexamethasone and 6 (28.13%) patients receiving colchicine/prednisone, resulting in a reduction of risk difference (RD) of – 17% (p = 0.17), with an average reduction of 39% (risk ratio [RR] 0.61) in patients receiving colchicine/prednisone (p = 0.25). Control patients received higher amounts of additional glucocorticoids (p = 0.0095) over a longer time frame (p = 0.0003). Colchicine/prednisone significantly reduced ferritin levels at day 14, as well as D-dimer and lactate dehydrogenase (LDH) levels at day 28. Adverse events were similar in both groups.

CONCLUSIONS: The combination colchicine/prednisone compared with intravenous dexamethasone has shown a remarkable trend to increase disease survival over a 28-day period in elderly patients requiring oxygen therapy in geriatric centers, without safety issues.

CLINICAL TRIAL REGISTRY: Clinical Trials Registration Number: NCT04492358.

PMID:36173596 | DOI:10.1007/s40261-022-01201-2

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Evaluation of a Sunscreen Product Compared with Reference Standards P3, P5 and P8 in Outdoor Conditions: a Randomized, Double-Blinded, Intra-individual Study in Healthy Subjects

Dermatol Ther (Heidelb). 2022 Sep 29. doi: 10.1007/s13555-022-00815-w. Online ahead of print.

ABSTRACT

INTRODUCTION: The shortcomings of standardized sunscreen testing have been discussed in recent years, noting differences between how sunscreens perform in indoor clinical (in vivo) laboratory testing compared with real-life conditions. We previously developed an outdoor clinical method for ranking sunscreens by performance level. We used this method to test the performance of a new broad-spectrum sunscreen against International Organization for Standardization (ISO) reference products P3, P5 and P8.

METHODS: Sixty-five healthy volunteers with individual typology angle (ITA) ≥ 28° (light to intermediate skin colour) participated in an outdoor study in Mauritius. Test areas were marked on their backs, which were treated with the different products: one commercially available broad-spectrum sun protection factor (SPF) 50 sunscreen [investigational product (IP)] and the three reference products P3 (SPF 15), P5 (SPF 30) and P8 (SPF 50+) from ISO norm 24444:2019 for SPF testing. The test areas were exposed for 2-3 h, depending on the baseline skin colour. They were also compared with an unprotected positive control area and a non-exposed negative control area. Clinical and colorimetry assessment of erythema and pigmentation were performed at 24 h and 8 days, respectively.

RESULTS: Overall, according to this outdoor clinical testing method, the sunscreens’ efficacy was ranked in an appropriate order given their established SPF levels, with higher SPFs giving greater protection against erythema and pigmentation. Between the different levels of SPF, the differences were statistically significant, for both clinical and colorimetry assessments. The new broad-spectrum SPF 50 IP performed similarly to the SPF 50+ (P8) reference product. Even the highest SPF products, SPF 50 and SPF 50+, had some instances of photoprotection failure.

CONCLUSION: These findings confirm the feasibility of this outdoor clinical testing method in ranking sunscreens and provide further evidence, in addition to standardized SPF and UVA protection factor (UVAPF) testing, on how this new broad-spectrum SPF 50 sunscreen performs in extreme outdoor solar exposure: in line with reference product P8 (SPF 50+).

TRIAL REGISTRATION NO: ISRCTN95394014.

PMID:36173595 | DOI:10.1007/s13555-022-00815-w

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Dietary leucine supplementation improves growth performance, metabolic responses of liver via GCN2/ATF4, and insulin signaling pathways in largemouth bass (Micropterus salmoides)

Fish Physiol Biochem. 2022 Sep 29. doi: 10.1007/s10695-022-01126-9. Online ahead of print.

ABSTRACT

An 8-week growth experiment was conducted to investigate the effects of dietary leucine on growth performance, body composition, and gene expression of hepatic nutrient metabolism in the largemouth bass (Micropterus salmoides). Six isonitrogenous (49.87%) diets with graded leucine levels (2.62, 3.07, 3.60, 3.87, 4.20, 4.71% of dry diet) were fed to triplicate groups with 20 juvenile fish (20.00 ± 0.13 g). The results revealed that the specific growth rate (SGR) and weight gain (WG) increased significantly with increasing dietary leucine levels, reached their maximal value in the Leu-4.20% groups, and then decreased slightly. Although the feed conversion ratio (FCR) showed decreasing trends, no significant difference was detected. Leucine supplementation significantly improved the content of body protein and total plasma protein (TP). Additionally, a higher expression level of target of rapamycin (TOR) and ribosomal protein S6 (S6) mRNA was observed in the Leu-3.87% and Leu-4.20% diets, whereas the GCN2 (general control nonderepressible2 kinase) and AFT4 (activating transcription factor 4) mRNA expression levels were suppressed. The lipid content of the body was not influenced by leucine levels, whereas the content of total triglyceride (TG) first decreased significantly with increasing dietary leucine levels from 2.62 to 3.87% and then increased with increasing leucine levels (4.20% to 4.71%). The total cholesterol (TC) and low-density lipoproteins (LDL) trended in a similar direction but did not achieve statistical significance (P > 0.05). The expression of insulin receptor substrate 1 (IRS-1) was significantly elevated by dietary leucine levels, while protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K) expression was inconsistently upregulated. Furthermore, leucine supplementation decreased plasma glucose and hepatic glycogen contents, and the expression levels of glucokinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6pase) were significantly inhibited at 4.20% and 4.71% leucine diets. Analyses of the change in SGR and FCR using the quadratic regression model estimated that the optimum dietary leucine requirement of juvenile largemouth bass was 4.42% and 4.63% of the dry diet (8.86% and 9.28% of dietary protein), respectively.

PMID:36173585 | DOI:10.1007/s10695-022-01126-9

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Procollagen C-proteinase enhancer-1 and renal failure in multiple myeloma

Int Urol Nephrol. 2022 Sep 29. doi: 10.1007/s11255-022-03378-z. Online ahead of print.

ABSTRACT

BACKGROUND: Renal involvement is present in approximately 50% of multiple myeloma (MM) cases and is associated with a poor prognosis. Procollagen C-Proteinase Enhancer 1 (PCPE-1) is an extracellular matrix glycoprotein that has been shown to increase collagen production by enhancing the activity of Procollagen C-Proteinase (PCP) involved in collagen fibrillogenesis and contribute to the fibrotic process. This study investigates the relationship between PCPE-1 and renal function in myeloma patients.

METHODS: Eighty-one adults, consisting of 61 patients diagnosed with MM and 20 healthy controls, were included in this cross-sectional study. The MM patients with renal injury (RI) were classified as “MM-RI( +)” and those with no RI as “MM-RI(-)”.

RESULTS: The median serum PCPE-1 level was 10.7 (5.0-39.4) ng/mL for the entire study population, 9.9 (5.0-13.6) ng/mL for the control group, 10.0 (6.4-22.5) ng/mL for the MM-RI(-) group, and 11.4 (8.1-39.4) ng/mL for the MM-RI( +) group. The difference between the control group and MM-RI( +) group was statistically significant (p < 0.013). PCPE-1 levels negatively correlated with estimated glomerular filtration rate (eGFR), serum albumin, and hemoglobin levels but positively correlated with serum creatinine and CRP levels in the entire study population. Among MM patients, only serum phosphorus and beta-2-microglobulin (β2M) were positively correlated with PCPE-1. PCPE-1 levels was not affected by other parameters in the entire study population and in the MM group.

CONCLUSIONS: Although serum PCPE-1 was higher in the MM-RI( +) group, it was thought to be associated with low GFR reflecting non-specific kidney injury rather than myeloma-related kidney injury.

PMID:36173536 | DOI:10.1007/s11255-022-03378-z

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Meta-analysis of overall survival and postoperative neurologic deficits after resection or biopsy of butterfly glioblastoma

Neurosurg Rev. 2022 Sep 29. doi: 10.1007/s10143-022-01864-7. Online ahead of print.

ABSTRACT

Butterfly glioblastoma (bGBM) is a grade 4 glioma with a poor prognosis. Surgical treatment of these cancers has been reviewed in the literature with some recent studies supporting resection as a safe and effective treatment instead of biopsy and adjuvant therapy. This meta-analysis was designed to determine whether there are significant differences in overall survival (OS) and postoperative neurologic deficits (motor, speech, and cranial nerve) following intervention in patients who underwent tumor resection as part of their treatment, compared to patients who underwent biopsy without surgical resection. A literature search was conducted using PubMed (National Library of Medicine) and Embase (Elsevier) to identify articles from each database’s earliest records to May 25, 2021, that directly compared the outcomes of biopsy and resection in bGBM patients and met predetermined inclusion criteria. A meta-analysis was conducted to compare the effects of the two management strategies on OS and postoperative neurologic deficits. Six articles met our study inclusion criteria. OS was found to be significantly longer for the resection group at 6 months (odds ratio [OR] 2.94, 95% confidence interval [CI] 1.23-7.05) and 12 months (OR 3.75, 95% CI 1.10-12.76) than for the biopsy group. No statistically significant differences were found in OS at 18 and 24 months. Resection was associated with an increased rate of postoperative neurologic deficit (OR 2.05, 95% CI 1.02-4.09). Resection offers greater OS up to 1 year postintervention than biopsy alone; however, this comes at the cost of higher rates of postoperative neurologic deficits.

PMID:36173528 | DOI:10.1007/s10143-022-01864-7

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Does the US regional greenhouse gas initiative affect green innovation?

Environ Sci Pollut Res Int. 2022 Sep 29. doi: 10.1007/s11356-022-23189-0. Online ahead of print.

ABSTRACT

This study measures the impact of the implementation of the Regional Greenhouse Gas Initiative (RGGI) on firms’ green innovation initiatives. We used 20 years of panel data from the Fortune 500 list of the US largest companies. Based on DID, a benchmark regression, the RGGI has a significant adverse effect on the green innovation of Fortune 500 companies, and we verified these findings with multiple robustness tests. As we investigate how energy-intensive industries were affected by RGGI, we found that it slowed down green innovation, but it was not statistically significant. This study provides a novel perspective on how the RGGI influences green innovation in firms and how different types of sectors respond to the policy. The findings indicate that the “weak” Porter Hypothesis has not been confirmed in the present carbon trading market (particularly the RGGI) for Fortune 500 firms in the USA. In terms of policy, we believe that a well-covered and differentiated legislation that fosters green innovation while being realistic about the policy’s goal and the firm’s environmental attitude, like emissions reduction through green innovation, is essential.

PMID:36173521 | DOI:10.1007/s11356-022-23189-0

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Highlighting the adsorption mechanism of dyes onto activated carbon derived from sludge by theoretical physical analysis

Environ Sci Pollut Res Int. 2022 Sep 29. doi: 10.1007/s11356-022-23287-z. Online ahead of print.

ABSTRACT

An activated carbon (AC) deriving from sludge is used in this research for the adsorption of two water pollutants, namely Reactive Black 5 (RB5) and Green Alizarin (GA) dyes, at different temperatures. The adsorption capacities varied from 277.2 to 312.69 mg/g for GA and from 225.82 to 256.02 mg/g for RB5. Comparatively, this adsorbent presents good performances in removing these dyes from wastewater. The application of physical models to adsorption experiments is advantageous to provide new insights into the dyes’ adsorption mechanism. A dedicated physical adsorption model suggests that RB5 and GA dyes are adsorbed in a monolayer. Moreover, the orientation of RB5 and GA dyes on AC resulted in an angled position, determining a multi-molecular process. In addition, both dyes are adsorbed by the occurrence of an aggregation process, forming a dimer. The impact of temperature can be also interpreted, allowing concluding that it plays a relevant role in removing these dyes. The calculation and interpretation of adsorption energies show that the dyes are removed via an endothermic process, and physical forces are involved.

PMID:36173520 | DOI:10.1007/s11356-022-23287-z

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Epidemiology of Newcastle disease in chickens of Ethiopia: a systematic review and meta-analysis

Trop Anim Health Prod. 2022 Sep 29;54(5):328. doi: 10.1007/s11250-022-03330-4.

ABSTRACT

The objective of this systematic review was to estimate the overall pooled prevalence of Newcastle disease in chickens in Ethiopia and identify the sources of heterogeneity among and within studies. The seroprevalence of Newcastle disease was estimated using a single-group meta-analysis. Attempts were also made to identify study-level variables that could explain the heterogeneity in the apparent seroprevalence of the Newcastle disease. The findings were based on 16 published articles and 33 district-level reports and were limited to studies performed during 2005-2017. Due to the presence of heterogeneity, pooled analysis from different districts was conducted using random-effects meta-analysis. The single-group summary of Newcastle disease seroprevalence in chickens was estimated to be 21.47% (19.54-23.4%) with a 95% confidence interval. Our results indicated high inter-study variability (Cochran’s Q statistic = 196.2, true variance (τ2) = 0.36, inverse variance index (I2) = 90.0%, p < 0.001). Of all variables analysed, diagnostic techniques and regions were the most significant predictors (p ˂ 0.05) of heterogeneity. According to the diagnostic technique-based meta-analysis of random pooled prevalence, the haemagglutination inhibition test had the highest prevalence, followed by the enzyme-linked immunosorbent assay. In conclusion, the high-pooled prevalence estimates of the disease, combined with the scarcity of published data for the entire country of Ethiopia, indicate a significant data gap on the distribution of Newcastle disease in the country. While the high pooled prevalence tells the need for intervention to control the disease, there is also a need to assess the disease prevalence in all other parts of the country.

PMID:36173467 | DOI:10.1007/s11250-022-03330-4