Tag: nevin manimala

Discov Oncol. 2022 Sep 22;13(1):90. doi: 10.1007/s12672-022-00558-2.

ABSTRACT

BACKGROUND: Nectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens.

PATIENTS AND METHODS: Specimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC).

RESULTS: In total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042).

CONCLUSION: Nectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape.

PMID:36136143 | DOI:10.1007/s12672-022-00558-2

Ann Hematol. 2022 Sep 22. doi: 10.1007/s00277-022-04984-8. Online ahead of print.

ABSTRACT

Despite widespread concern about energy imbalance due to tumor and chemotherapy-related side effects, little is known about detailed variations in energy input, metabolic rate, and physical activity. This study explored changes in energy balance components and serum biomarkers of patients with hematologic malignancies undergoing chemotherapy. Our prospective study included 40 patients with hematologic malignancies hospitalized for chemotherapy. We measured energy balance components, physical function, and serum biomarkers at baseline and weekly after chemotherapy for 3 weeks. Significant weight loss, representing negative energy balance, occurred at 2 (p = 0.002) and 3 weeks (p < 0.001) post-chemotherapy. Statistically reduced oral intake was observed at 3 weeks post-chemotherapy (p = 0.040), and resting energy expenditure statistically decreased according to Harris-Benedict equation, but not to Penn State University equation. Physical function according to DEMMI score decreased significantly at 3 weeks post-chemotherapy (p = 0.002). Serum biomarker analysis demonstrated significant changes in albumin, total protein, CXCL13, and GDF15, with exception of leptin. Although conventional serum biomarkers (total protein and albumin) did not reach pathological states despite their statistical differences, subgroup analysis showed CXCL13 in weight loss group and GDF15 in reduced oral intake group were significantly changed. Over half of patients (65.0%, n = 26) suffered from energy imbalance associated with weight loss and reduced oral intake during chemotherapy. Serial laboratory results suggested that novel biomarkers (CXCL13, GDF15) could be correlated with cachexic state and reduced food intake. Monitoring clinical and serum biomarkers associated with energy balance together can help identify needs for nutritional support in patients with hematologic malignancies undergoing chemotherapy.

PMID:36136099 | DOI:10.1007/s00277-022-04984-8

Biom J. 2022 Sep 22. doi: 10.1002/bimj.202200035. Online ahead of print.

ABSTRACT

Web surveys have replaced Face-to-Face and computer assisted telephone interviewing (CATI) as the main mode of data collection in most countries. This trend was reinforced as a consequence of COVID-19 pandemic-related restrictions. However, this mode still faces significant limitations in obtaining probability-based samples of the general population. For this reason, most web surveys rely on nonprobability survey designs. Whereas probability-based designs continue to be the gold standard in survey sampling, nonprobability web surveys may still prove useful in some situations. For instance, when small subpopulations are the group under study and probability sampling is unlikely to meet sample size requirements, complementing a small probability sample with a larger nonprobability one may improve the efficiency of the estimates. Nonprobability samples may also be designed as a mean for compensating for known biases in probability-based web survey samples by purposely targeting respondent profiles that tend to be underrepresented in these surveys. This is the case in the Survey on the impact of the COVID-19 pandemic in Spain (ESPACOV) that motivates this paper. In this paper, we propose a methodology for combining probability and nonprobability web-based survey samples with the help of machine-learning techniques. We then assess the efficiency of the resulting estimates by comparing them with other strategies that have been used before. Our simulation study and the application of the proposed estimation method to the second wave of the ESPACOV Survey allow us to conclude that this is the best option for reducing the biases observed in our data.

PMID:36136044 | DOI:10.1002/bimj.202200035

Mol Pharm. 2022 Sep 22. doi: 10.1021/acs.molpharmaceut.2c00573. Online ahead of print.

ABSTRACT

A pair of popular thermodynamic models for pharmaceutical applications, namely, the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and the conductor-like screening model for real solvents (COSMO-RS) are thoroughly benchmarked for their performance in predicting the solubility of active pharmaceutical ingredients (APIs) in pure solvents. The ultimate goal is to provide an illustration of what to expect from these progressive frameworks when applied to the thermodynamic solubility of APIs based on activity coefficients in a purely predictive regime without specific experimental solubility data (the fusion properties of pure APIs were taken from experiments). While this kind of prediction represents the typical modus operandi of the first-principles-aided COSMO-RS, PC-SAFT is a relatively highly parametrized model that relies on experimental data, against which its pure-substance and binary interaction parameters (k_ij) are fitted. Therefore, to make this benchmark as fair as possible, we omitted any binary parameters of PC-SAFT (i.e., k_ij = 0 in all cases) and preferred pure-substance parameter sets for APIs not trained to experimental solubility data. This computational approach, together with a detailed assessment of the obtained solubility predictions against a large experimental data set, revealed that COSMO-RS convincingly outperformed PC-SAFT both qualitatively (i.e., COSMO-RS was better in solvent ranking) and quantitatively, even though the former is independent of both substance- and mixture-specific experimental data. Regarding quantitative comparison, COSMO-RS outperformed PC-SAFT for 9 of the 10 APIs and for 63% of the API-solvent systems, with root-mean-square deviations of the predicted data from the entire experimental data set being 0.82 and 1.44 log units, respectively. The results were further analyzed to expand the picture of the performance of both models with respect to the individual APIs and solvents. Interestingly, in many cases, both models were found to qualitatively incorrectly predict the direction of deviations from ideality. Furthermore, we examined how the solubility predictions from both models are sensitive to different API parametrizations.

PMID:36136040 | DOI:10.1021/acs.molpharmaceut.2c00573

Milbank Q. 2022 Sep 22. doi: 10.1111/1468-0009.12582. Online ahead of print.

ABSTRACT

Policy Points Social determinants of health are an important predictor of future health care costs. Medicaid must partner with other sectors to address the underlying causes of its beneficiaries’ poor health and high health care spending.

CONTEXT: Social determinants of health are an important predictor of future health care costs but little is known about their impact on Medicaid spending. This study analyzes the role of social determinants of health (SDH) in predicting future health care costs for adult Medicaid beneficiaries with similar past morbidity burdens and past costs.

METHODS: We enrolled into a prospective cohort study 8,892 adult Medicaid beneficiaries who presented for treatment at an emergency department or clinic affiliated with two hospitals in Washington, DC, between September 2017 and December 31, 2018. We used SDH information measured at enrollment to categorize our participants into four social risk classes of increasing severity. We used Medicaid claims for a 2-year period; 12 months pre- and post-study enrollment to measure past and future morbidity burden according to the Adjusted Clinical Groups system. We also used the Medicaid claims data to characterize total annual Medicaid costs one year prior to and one year after study enrollment.

RESULTS: The 8,892 participants were primarily female (66%) and Black (91%). For persons with similar past morbidity burdens and past costs (p < 0.01), the future morbidity burden was significantly higher in the upper two social risk classes (1.15 and 2.04, respectively) compared with the lowest one. Mean future health care spending was significantly higher in the upper social risk classes compared with the lowest one ($2,713, $11,010, and $17,710, respectively) and remained significantly higher for the two highest social risk classes ($1,426 and $3,581, respectively), given past morbidity burden and past costs (p < 0.01). When we controlled for future morbidity burden (measured concurrently with future costs), social risk class was no longer a significant predictor of future health care costs.

CONCLUSIONS: SDH are statistically significant predictors of future morbidity burden and future costs controlling for past morbidity burden and past costs. Further research is needed to determine whether current payment systems adequately account for differences in the care needs of highly medically and socially complex patients.

PMID:36134645 | DOI:10.1111/1468-0009.12582

Integr Environ Assess Manag. 2022 Sep 22. doi: 10.1002/ieam.4688. Online ahead of print.

ABSTRACT

Pesticide surface water monitoring data have rarely been used as the only quantitative measure of exposure because the available monitoring data for most pesticides has not been considered robust enough for direct use in pesticide exposure assessments due to infrequent sampling. The cost of daily sample collection and analysis prohibits high sampling frequency for most monitoring programs. In this context, a common question raised in assessments is how likely peak concentrations (i.e., annual maximums) may be missed if sampling intervals are greater than daily. The US Geological Survey developed the statistical model ‘seasonal wave with streamflow adjustment and extended capability’ (SEAWAVE-QEX) to address the need to estimate infrequently occurring pesticide concentrations, such as annual maximum daily concentrations, for sites with non-daily monitoring data. This study compares the results of two post-processing methods and evaluates the capability of SEAWAVE-QEX to estimate annual maximum concentrations of three commonly used herbicides and one metabolite in a catchment in Belgium. The study concludes that the appropriateness of using SEAWAVE-QEX to estimate annual maximum concentrations is dependent on pesticide characteristics and usage and that the model can be particularly sensitive to non-flow correlated exposure events (e.g., point source contributions or drift). This article is protected by copyright. All rights reserved. © 2022 SETAC.

PMID:36134644 | DOI:10.1002/ieam.4688

Nutr Hosp. 2022 Sep 20. doi: 10.20960/nh.04074. Online ahead of print.

ABSTRACT

INTRODUCTION: several studies have questioned body mass index (BMI) as an accurate diagnostic tool for obesity and therefore a predictor of cardiovascular risk. But BMI is widely used currently.

OBJECTIVE: we analyzed the sensitivity and specificity of BMI and compared cardiovascular risk factors in middle-income urban participants in Guanajuato, Mexico, at different ages.

DESIGN: an analytical and cross-sectional study was carried out in 385 apparently healthy subjects, stratified by age ranges (20 to 59 years old). A high global CVD risk was obtained with the Framingham risk score (Framingham Risk Score > 20 %). The odds ratio was used to assess the association between high global CVD risk and the dietetic and anthropometric variables. Sensitivity, specificity, and correlation statistical analyses were carried out between BMI and other anthropometric variables with high cardiovascular risk, and this was integrated to derive recommendations to improve risk factor detection (p < 0.05 and power of 80 %).

RESULTS: a high global CVD risk was found in 4 % of the sample. BMI ≥ 30 kg/m2 had a sensitivity of 77 % for the detection of high cardiovascular risk; waist circumference ≥ 90 cm (men) or ≥ 80 cm (women) and body fat percentage ≥ 2 5% (men) or ≥ 35 % (women) had a sensitivity of 100 %. BMI showed a significant association with high global CVD risk (OR = 6.1; 95 % CI, 1.6-22.6, p < 0.01), but was not able to predict high global CVD risk in at least 30 % of the cases. There was not significative difference by age group for waist circumference, body fat percentage, total cholesterol, and low-density lipoprotein. Regarding the comparison of dietary intake of the stratified population by age group, intake of cholesterol, added sugars, fiber, sodium were highest in the 20 years group.

CONCLUSIONS: a higher intake of cholesterol, simple sugars, and sodium was observed in the 20-year-old age group. The use of BMI with waist circumference and percentage of body fat used together allow a better assessment of cardiovascular risk. We need to integrate this new recommendation to increase early detection of main risk factors for cardiovascular disease.

PMID:36134593 | DOI:10.20960/nh.04074

Nutr Hosp. 2022 Sep 21. doi: 10.20960/nh.04076. Online ahead of print.

ABSTRACT

BACKGROUND: maternal obesity is associated with an increase of both maternal and fetal complications as macrosomia.

AIM: to assess the quality of diet in a cohort of pregnant women in terms of Mediterranean diet (MD) adherence and to examine the association between diet quality, obesity, weight gain and fetal growth and perinatal complications.

METHODS: Mediterranean Diet Adherence Screener (MEDAS) was applied to assess diet quality in 542 pregnant women. Fetal biometric measurements at third-trimester ultrasound were collected and perinatal outcomes were recorded.

RESULTS: only 35 % of pregnant women presented a good quality of diet, in terms of adherence to MD. Diet quality significantly increased with lower values of body mass index (BMI) and higher maternal age. Higher BMI was significantly associated with a higher abdominal circumference and estimated fetal weight at the third trimester, a higher risk of hypertension disorder, induction of labor and a higher birthweight. A statistically significant association between diet quality and ultranosographic measures or perinatal outcome was not found. However, a higher weight gain across gestation was significantly associated with a higher risk of gestational diabetes, a higher gestational age at delivery and a higher birthweight.

CONCLUSION: most of our pregnant women did not showed a great diet quality, but there was no evidence that diet quality affected pregnancy complications. On the contrary, pre-pregnancy BMI was related to fetal and neonatal growth and obstetric outcomes, similarly to weight gain across gestation.

PMID:36134591 | DOI:10.20960/nh.04076

Nutr Hosp. 2022 Sep 19. doi: 10.20960/nh.03969. Online ahead of print.

ABSTRACT

BACKGROUND: type 2 diabetes (T2D) is a risk factor for nonalcoholic fatty liver disease (NAFLD).

OBJECTIVE: to evaluate the prevalence of NAFLD in a cohort of patients with T2D.

METHODS: an observational, descriptive study performed between May 2018 and December 2019 at the Endocrinology and Nutrition Unit. The χ² test was performed for qualitative variables and a non-parametric test for the comparison of medians of quantitative variables. Steatosis degree was defined by the coefficient attenuated parameter (CAP): (S0: < 248 dB/m; S1: 248-268 dB/m; S2: 268-288 dB/m; S3: > 288 dB/m) or stiffness: F0-F1: < 8 kPa; F2: 8-10 kPa; F3: 10-15 kPa; F4: > 15 kPa, using transient elastography (TE) (FibroScan®). A univariate analysis was performed and subsequently a multivariate analysis with statistically significant variables used to study the predictive factors of intense steatosis and advanced fibrosis.

RESULTS: n = 104 patients with T2D; 84 (80.7 %) were obese. TE demonstrated advanced fibrosis in 20 % and intense steatosis (S3) in more than 50 %. Lower total bilirubin (OR: 0.028; 95 % CI: (0.002-0.337); p = 0.005) was found to be an independent factor for S3 steatosis in the multivariate analysis. BMI ((OR: 1.497; 95 % CI: (1.102-2.034); p = 0.01)) was a predictive factor for advanced fibrosis in a multivariate analysis.

CONCLUSIONS: NAFLD-associated intense steatosis and NAFLD-associated fibrosis were commonly found in patients with T2DM and obesity. Diabetic patients should be screened for liver disease as one more target organ.

PMID:36134588 | DOI:10.20960/nh.03969

J Clin Pharm Ther. 2022 Sep 22. doi: 10.1111/jcpt.13779. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar.

METHODS: This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher’s exact test was used to compare reaction rates.

RESULTS AND DISCUSSION: A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p = 0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p = 0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p = 0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients).

WHAT IS NEW AND CONCLUSIONS: Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice.

PMID:36134561 | DOI:10.1111/jcpt.13779