Nevin Manimala

Eur J Cancer. 2021 Nov 13;159:237-246. doi: 10.1016/j.ejca.2021.10.015. Online ahead of print.

ABSTRACT

BACKGROUND: Enzalutamide combined with androgen deprivation therapy (ADT) significantly prolonged metastasis-free survival and overall survival (OS) versus ADT alone in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with rapidly rising prostate-specific antigen (PSA). The objective of this post hoc analysis of the PROSPER trial is to evaluate OS benefit and safety of enzalutamide in patients across age and regional subgroups.

PATIENTS AND METHODS: Eligible men with nmCRPC, PSA doubling time ≤10 months and PSA ≥2 ng/mL with continued ADT use were randomised 2:1 to enzalutamide 160 mg or placebo. OS and safety were examined by age (<70 vs ≥70 years) and region (North America, Europe, Asia or the rest of the world). The impact of prior and subsequent therapy was also examined.

RESULTS: In total, 1401 men were enrolled (median age, 74 years). Enzalutamide plus ADT reduced the risk of death, independent of age or region. Multivariate analyses identified Eastern Cooperative Oncology Group (ECOG) status (P < 0.0001), log (PSA; P = 0.0002) and subsequent therapy (P < 0.0001) as statistically significant factors impacting OS. Safety was consistent across age and regional subgroups. Any grade treatment-emergent adverse events were similar across age groups, were more common in the placebo group and had regional variation.

CONCLUSIONS: In men with nmCRPC and rapidly rising PSA, the benefit and safety of enzalutamide were consistent across age and regional subgroups. Variables impacting OS included ECOG status, log (PSA) and subsequent therapy. CLINICALTRIALS.

GOV IDENTIFIER: NCT02003924.

PMID:34784577 | DOI:10.1016/j.ejca.2021.10.015

Midwifery. 2021 Oct 28;104:103185. doi: 10.1016/j.midw.2021.103185. Online ahead of print.

ABSTRACT

OBJECTIVE: Adherence to iron and folic acid supplementation represents a significant factor contributing to the prevention and treatment of anaemia in pregnancy. However, limited studies have systematically investigated iron and folic acid supplementation adherence among pregnant mothers using a global perspective. We aimed to systematically identify iron and folic acid supplementation adherence and associated factors among pregnant women.

DESIGN: For this systematic review and meta-analysis, we did a systematic search of Academic Search Complete, CINAHL, MEDLINE, PubMed, and Web of Science from inception to October 20, 2020. We included all cohort, case-control, and cross-sectional studies and used the Joanna Briggs Institute tool to assess study quality. A meta-analysis was performed to synthesise the pooled odds ratio for iron and folic acid supplementation adherence using a random-effects model. Heterogeneity was measured using the I² statistic, and Egger’s test was used to assess publication bias.

MEASUREMENTS AND FINDINGS: Eighteen studies were included in systematic review and meta-analysis, including a total of 5,537 pregnant women. The pooled odds ratio for iron and folic acid supplementation adherence in primipara vs multipara, anaemia vs non-anaemia, knowledgeable vs limited knowledge of anaemia, and knowledgeable vs limited knowledge of iron and folic acid supplementation were 3.91 (95% confidence interval: 1.75-8.75), 1.09 (95% confidence interval: 0.67-1.77), 0.32 (95% confidence interval: 0.15-0.69), and 2.48 (95% confidence interval: 1.13-5.47), respectively.

KEY CONCLUSIONS: This review yielded evidence that having one pregnancy, having anaemia, and having satisfactory knowledge of both anaemia and iron and folic acid supplementation were positively associated with iron and folic acid supplementation adherence.

PMID:34784576 | DOI:10.1016/j.midw.2021.103185

Poult Sci. 2021 Oct 13;101(1):101536. doi: 10.1016/j.psj.2021.101536. Online ahead of print.

ABSTRACT

Florfenicol is a broad-spectrum antibacterial drug used in the treatment of farm animals, including poultry. This drug is poorly soluble in water, therefore, administration in drinking water may lead to high variability of concentrations in treated individuals. The use of injection preparations, however, requires individual administration and may have a negative effect on the quality of the carcass. In addition, the renal portal system in birds may reduce the bioavailability of the drug administered in the caudofemoral region of the body. The aim of this study was to compare the pharmacokinetics of florfenicol in turkeys after a single intravenous, intramuscular, and subcutaneous administration at a dose of 15 mg/kg body weight. Additionally, to evaluate the effect of renal portal system on drug kinetics, the intramuscular administration was divided into pectoral and caudofemoral administration. The study showed that the area under the concentration-time curve (AUC) was similar regardless of the route of administration. The mean values for clearance and volume of distribution were 0.33 L/kg/h and 0.92 L/kg, respectively. The mean residence time (MRT) was 2.87 h for an intravenous bolus, while for the extravascular administrations it was approx. 5.5 h. The elimination half-life was approx. 4 h regardless of the route of administration. The maximum plasma concentration did not differ statistically between intramuscular (approx. 6.8 mg/L) and subcutaneous (8.2 mg/L) administrations, while the time to appear for this concentration was the longest for caudofemoral administration (1.5 h). The bioavailability was 88.64% for subcutaneous administration, 77.95% for pectoral administration and 85.30% for caudofemoral administration. Overall, all 3 routes of extravascular administration allowed for efficient drug absorption. There was no evidence of an influence of the renal portal system on the kinetic parameters of the drug administered to the lower extremities of the body.

PMID:34784513 | DOI:10.1016/j.psj.2021.101536

Oral Oncol. 2021 Nov 13;123:105629. doi: 10.1016/j.oraloncology.2021.105629. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to evaluate the clinical value of an entire-circumferential intraoperative frozen section analysis (e-IFSA) for the complete resection of superficial squamous cell carcinoma (SCC) of the tongue.

MATERIALS AND METHODS: A total 276 specimens from 51 patients with pT1-2, N0, mucosal or submucosal invasion SCC were analyzed to evaluate the diagnostic accuracy of the e-IFSA and the added value of the e-IFSA to iodine staining. The e-IFSA results were compared with the final histologic results obtained using permanent sections. All specimens for the e-IFSA were taken over the entire circumference 5 mm outside from the iodine unstained areas. The outline of the main resected specimen after taking these outer mucosal specimens were defined as the surgical margins determined by iodine staining alone.

RESULTS: The e-IFSA results were in excellent agreement with final histological results (Cohen’s kappa value: 0.85) and the e-IFSA showed high sensitivity (100%) and high negative predictive value (100%). The actual complete resection rate with an e-IFSA was 100% (51/51), and no patient required additional resection after surgery. In contrast, 10/51 patients (20%) patients showed residual atypical mucosal epithelium at or beyond the margin determined by iodine staining alone; this difference was statistically significant (P = 0.002). The 5-year local control rate and 5-year overall survival rate after this procedure were both 100%.

CONCLUSION: An e-IFSA has additional value when performed in conjunction with iodine staining. An e-IFSA would be useful for achieving complete resection of superficial SCC of the tongue.

PMID:34784507 | DOI:10.1016/j.oraloncology.2021.105629

Neuron. 2021 Nov 9:S0896-6273(21)00845-X. doi: 10.1016/j.neuron.2021.10.030. Online ahead of print.

ABSTRACT

In basic neuroscience research, data are often clustered or collected with repeated measures, hence correlated. The most widely used methods such as t test and ANOVA do not take data dependence into account and thus are often misused. This Primer introduces linear and generalized mixed-effects models that consider data dependence and provides clear instruction on how to recognize when they are needed and how to apply them. The appropriate use of mixed-effects models will help researchers improve their experimental design and will lead to data analyses with greater validity and higher reproducibility of the experimental findings.

PMID:34784504 | DOI:10.1016/j.neuron.2021.10.030

Public Health. 2021 Oct 18;201:55-60. doi: 10.1016/j.puhe.2021.10.003. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a critical appraisal tool for non-computational-specialist public health professionals to assess the quality and relevance of modelling studies about Test and Trace (and Protect – TTP) programmes’ impact on COVID-19 transmission.

STUDY DESIGN: Decision-making tool development.

METHODS: Using Tugwell et al.’s 1985 Health Care Effectiveness equation as a conceptual framework, combined with a purposive search of the relevant early modeling literature, we developed six critical appraisal questions for the rapid assessment of modeling studies related to the evaluation of TTP programmes’ effectiveness.

RESULTS: By applying the critical appraisal tool to selected recent COVID-19 modeling studies, we demonstrate how models can be evaluated using the six questions to evaluate internal and external validity and relevance.

CONCLUSIONS: These six critical appraisal questions are able to discriminate between modeling studies of higher and lower quality and relevance to evaluating TTP programmes’ impact. However, these questions require independent validation in a larger and systematic sample of relevant modeling studies which have appeared in later stages of the pandemic.

PMID:34784502 | DOI:10.1016/j.puhe.2021.10.003

Leg Med (Tokyo). 2021 Nov 11;54:101991. doi: 10.1016/j.legalmed.2021.101991. Online ahead of print.

ABSTRACT

Age estimation is a mandatory procedure when the chronological age is unknown or uncertain. Dental development is the preferred characteristic for estimating a child’s age. There are many methods for dental age estimation, but their reliability can differ between populations. This study compared the accuracy of three of these methods-the London Atlas (LA), Haavikko’s method (HM), and Cameriere’s European formula (CF)-in Turkish children living in northwestern Turkey. Panoramic radiographs of 980 children from northwestern Turkey aged between 6.00 and 14.99 years were examined for the whole study group and separately for different ages and sexes by all three methods. Statistical differences between chronological age and dental age were tested using the paired sample t-test and the Wilcoxon signed-rank test. The LA, HM, and CF accuracies were determined based on the mean absolute error. Spearman’s rank correlation coefficient showed that the correlation between chronological age and dental age for both sexes was linear for all methods. The LA overestimated the chronological age by 0.09 years, while HM and CF underestimated it by 0.49 and 0.11 years, respectively. The difference between dental age and chronological age was significant in all samples, for all methods, except for the LA in boys. When boys, girls, and the total sample were evaluated, values with the lowest mean absolute error were obtained by HM and were statistically significant in all three groups. Therefore, HM is more accurate than the LA and CF for dental age estimation in Turkish children living in northwestern Turkey.

PMID:34784498 | DOI:10.1016/j.legalmed.2021.101991

ACS Appl Mater Interfaces. 2021 Nov 16. doi: 10.1021/acsami.1c15727. Online ahead of print.

ABSTRACT

We investigated the effect of the Si/graphite weight ratio in half-cells on the solid electrolyte interphase (SEI) layer’s chemistry. The nominal concentrations of active materials were (wt % Si/wt % Gr) 15/73, 30/58, 60/28, and 80/0. The electrolyte in the cells consisted of either 1.2 M LiPF₆ in ethylene carbonate/ethyl methyl carbonate (3:7 by wt) or 1.2 M LiPF₆ in ethylene carbonate:ethyl methyl carbonate (3:7 by wt) + 10 wt % fluoroethylene carbonate. These coin cells were cycled five times at the C/10 rate. As expected, the addition of silicon to the electrode significantly increased the measured capacity. Examination of the aged composite material showed that the electrolyte influenced the concentration of chemical environments on the surface. Depth profiling revealed that these concentrations of surface environments changed with sputtering time. A statistics-of-mixtures model was used to deconvolute how silicon and graphite interacted during the formation of these species and how the interaction changed with depth.

PMID:34784472 | DOI:10.1021/acsami.1c15727

BJU Int. 2021 Nov 16. doi: 10.1111/bju.15647. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the prognostic utility of reporting neuroendocrine staining at prostate cancer diagnosis, we performed a systematic review and meta-analysis. Specifically, we aimed to understand the variability in reporting of neuroendocrine staining, and determine whether different reporting approaches impact the correlation between staining and patient outcome.

METHODS: Medical databases were searched to identify studies where adenocarcinoma specimens were stained with any of four neuroendocrine markers: Chromogranin A (CgA), Neuron Specific Enolase (NSE), synaptophysin and CD56. Prevalence of neuroendocrine staining and correlation to patient outcomes were analysed using a random-effects model. All statistical tests were two-sided.

RESULTS: Sixty-two studies spanning 7,616 patients were analysed. The pooled prevalence for the most common marker, CgA (41%), was similar to NSE (39%) and higher than synaptophysin (31%). Prevalence of CgA staining was significantly influenced by reporting criteria, where objective thresholds reduced the variation in prevalence to 26%. No correlation was found between CgA prevalence and tumour grade. Patients positive for CgA staining using objective criteria had more rapid biochemical progression (hazard ratio 1.98 (95% CI = 1.49 to 2.65)) and poorer prostate cancer-specific survival (hazard ratio: 7.03 (95% CI = 2.55 to 19.39)) compared to negative patients, even among those with low risk cancers.

CONCLUSION: Discrepancies in the reported prevalence of neuroendocrine cells in adenocarcinoma are driven by the inconsistent scoring criteria. This study unequivocally demonstrates that when neuroendocrine cell staining is assessed with objective criteria it identifies patients with poor clinical outcomes. Future studies need to determine the exact quantifiable thresholds to report neuroendocrine cell staining, to identify patients at higher risk of progression.

PMID:34784097 | DOI:10.1111/bju.15647

Transfusion. 2021 Nov 16. doi: 10.1111/trf.16739. Online ahead of print.

ABSTRACT

BACKGROUND: The demand and supply of blood are highly variable over time. Blood inventory management that relies heavily on experience-based decisions may not be adaptive to real demand, leading to high operational costs, wastage, and shortages.

METHODS: We combined statistical modeling, machine learning, and optimization methods to develop a data-driven demand forecasting and inventory management strategy for red blood cells (RBCs). We then used the strategy to inform daily blood orders. A secondary semi-weekly (twice per week) ordering strategy was developed to handle the last-mile split delivery problem for blood suppliers, characterized by multi-deliveries to the same location multiple times during a short period of time. Both strategies were evaluated using the TRUST database including all patient data across four hospitals in Hamilton, Ontario.

RESULTS: We identified 227,944 RBC transfusions for 40,787 patients in Hamilton, Ontario from 2012 to 2018. The predicted daily demand from the hybrid demand forecasting model was not significantly different from the actual daily demand (paired t-test p-value = 0.163); however, the proposed daily ordering quantity from the model was significantly lower than the actual ordering quantity (p-value <0.001). The proposed daily ordering strategy reduced inventory levels by 38.4% without risk of shortages, leading to an overall cost reduction of 43.0% (95% confidence interval [CI]: 42.3%, 43.7%) compared with the actual cost. The semi-weekly ordering strategy reduced ordering frequency by 62.6% (95% CI: 61.5%, 63.7%).

CONCLUSION: The proposed data-driven ordering strategy combining demand forecasting and inventory optimization can achieve significant cost savings for healthcare systems and blood suppliers.

PMID:34784053 | DOI:10.1111/trf.16739