Tag: nevin manimala

Clin Drug Investig. 2022 Jul 16. doi: 10.1007/s40261-022-01179-x. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients with extensive-stage small-cell lung cancer. Trilaciclib is a substrate and time-dependent inhibitor of cytochrome P450 3A4 and an inhibitor of multidrug and toxin extrusion 1, multidrug and toxin extrusion 2-K, organic cation transporter 1, and organic cation transporter 2. Here, we investigate the pharmacokinetic drug-drug interaction potential of trilaciclib.

METHODS: Two phase I studies were conducted as prospective, open-label, fixed-sequence drug-drug interaction studies in healthy subjects (n = 57, n = 20) to investigate potential interactions between intravenously administered trilaciclib (200 or 240 mg/m²) and orally administered midazolam (5 mg), metformin (1000 mg), itraconazole (200 mg), and rifampin (600 mg). A population pharmacokinetic model was fit to phase Ib/IIa data in patients with extensive-stage small-cell lung cancer (n = 114) to assess the impact of trilaciclib dose and exposure (area under the plasma concentration-time curve) on topotecan clearance.

RESULTS: Coadministration with trilaciclib had minimal effects on the exposure (area under the plasma concentration-time curve from time 0 to infinity) of midazolam (geometric least-square mean ratio [GMR] vs midazolam alone 1.065; 90% confidence interval [CI] 0.984-1.154) but statistically significantly increased plasma exposure (GMR 1.654; 90% CI 1.472-1.858) and decreased renal clearance (GMR 0.633; 90% CI 0.572-0.701) of metformin. Coadministration of trilaciclib with rifampin or itraconazole decreased trilaciclib area under the plasma concentration-time curve from time 0 to infinity by 17.3% (GMR 0.827; 90% CI 0.785-0.871) and 14.0% (GMR 0.860; 0.820-0.902), respectively, vs trilaciclib alone. Population pharmacokinetic modeling showed no significant effect of trilaciclib on topotecan clearance.

CONCLUSIONS: Overall, the drug-drug interaction and safety profiles of trilaciclib in these studies support its continued use in patients with extensive-stage small-cell lung cancer.

CLINICAL TRIAL REGISTRATION: Study 106: EudraCT number: 2019-002303-18; Study 114: not applicable; Study 03: Clinicaltrials.org: NCT02514447; August 2015.

PMID:35842567 | DOI:10.1007/s40261-022-01179-x

Cancer Epidemiol. 2022 Jul 13;80:102216. doi: 10.1016/j.canep.2022.102216. Online ahead of print.

ABSTRACT

BACKGROUND: Georgia is an upper middle-income country, which has lower cancer survival rates than most of the countries in the World Health Organization European region, as well as compared to many other post-Soviet states and upper middle-income countries. The purpose of our study was to analyse the cancer stage distribution data of Georgia as a first step towards identifying the areas of early cancer detection in the country that might need improvement or require further research.

METHODS: Descriptive analysis of the population-based cancer registry of Georgia was performed using the data for the period of 01.01.2018-31.12.2019.

RESULTS: Around 57 % of cancers in males and 56 % of cancers in females were amenable to early detection. At least 35.7 % of these cancers in males and 44.2 % in females were detected early. 15.2 % (n = 964) of male and 35.3 % (n = 3179) of female cancer patients met the age criteria for the respective cancer screening programmes. Breast, colorectal, cervical and stomach cancers contributed to 58.7 % of all late-stage cancers in females. Lung, prostate, colorectal, laryngeal and stomach cancers made up 72.4 % of all late-stage cancer cases among males. At least 83.8 % (n = 1438) of thyroid cancers in females and 84.2 % (n = 246) of thyroid cancers in males were diagnosed at stage I. Moreover, stage I thyroid cancer cases made up 50.7 % of all stage I cancer cases detected in women and 25.6 % of all stage I cancers in men. At least 42.4 % of stage I thyroid cancers in females and 37.4 % of stage I thyroid cancers in males were papillary microcarcinomas.

CONCLUSION: The potential of early cancer detection is underutilised in Georgia and there is a need to strengthen screening and especially early diagnosis in the country. The possibility of thyroid cancer overdiagnosis requires further investigation.

PMID:35841760 | DOI:10.1016/j.canep.2022.102216

Complement Ther Clin Pract. 2022 Jul 9;49:101639. doi: 10.1016/j.ctcp.2022.101639. Online ahead of print.

ABSTRACT

BACKGROUND: Mindfulness interventions can improve psychological distress and quality of life (QoL) in cancer survivors. Few mindfulness programs for cancer recovery exist in Southeastern U.S. The primary objective of this study was to assess the feasibility of a modified mindfulness-based stress reduction (MBSR) program for breast cancer patients in Birmingham, Alabama. The secondary objective was to explore potential program effects on mindfulness skills and QoL.

METHODS: This study was a prospective, quasi-experimental feasibility study conducted over 10 months at a university hospital. Feasibility was achieved if 80% of eligible patients screened enrolled in the study and 70% of enrolled patients attended all 8 program sessions. Effectiveness was estimated by changes in mindfulness and QoL indicators measured with validated scales administered at 3 time points and assessed with a non-parametric Friedman test. Sessions included meditation, yoga, and an attention practice called body scan. There were 3 groups of 2-5 patients.

RESULTS: The sample totaled 12 patients. Forty-four percent (12/27) of eligible patients enrolled in the study, and two out of 12 enrolled patients completed 8 program sessions, resulting in 16.7% (2/12) retention. However, more than half (66.7%) of participants completed at least 7 sessions. Between baseline and 8-week follow-up, patients demonstrated statistically significant improvements in distress, general wellbeing, and fatigue-related QoL.

CONCLUSIONS: Feasibility objectives were not achieved. However, a majority of participants (66.7%) completed 7 of 8 program sessions. Program effects were promising for distress, fatigue, and wellbeing. Results warrant further research on MBSR-like programs for breast cancer patients in Alabama.

PMID:35841719 | DOI:10.1016/j.ctcp.2022.101639

Oral Oncol. 2022 Jul 13;132:106019. doi: 10.1016/j.oraloncology.2022.106019. Online ahead of print.

ABSTRACT

BACKGROUND: Fibular (FFF) and scapular free flaps (SFF) are versatile tissue transfers for head and neck reconstruction. However, their relative morbidity has been sparsely studied. The primary goal of this study was to evaluate the morbidity and patient-reported outcome measures of these two reconstructive options.

MATERIALS AND METHODS: Case series of patients from 2017 to 2020 who underwent a FFF or SFF for head and neck ablation. Demographic and surgical outcome measures, such as Charlson Comorbidity Index (CCI), anesthetic time, donor site morbidity, and perioperative morbidity score (POMs) were extracted. Patients were contacted to complete the Decision Regret Scale (DRS), University of Washington Quality of Life (UW-QoL), Oral Health Impact-14, and limb specific functional outcome measures. Statistical analyses included a linear regression.

RESULTS: In total, 97 FFF (mean age 58.5, 62.9% male) and 55 SFF (mean age 64.8, 63.6% male) were included. Total surgical time was higher in the SFF group (p < 0.05) and they had more comorbidities (p < 0.01). SFF patients had lower POM scores on post-operative day three (p < 0.05) while FFF patients scored better on the UW-QoL Physical Domain (p < 0.01). The DRS for both groups (FFF mean DRS 22.7, SFF mean DRS 19.2) was similar. When adjusted for patient morbidity, however, the SFF group had less decisional regret (p < 0.05).

CONCLUSION: This is the largest comprehensive evaluation of patient-reported outcome measures for FFF and SFFs. SFFs required longer surgical times but had less early morbidity than FFFs. Patients who underwent either reconstructions reported mild decisional regret, proving these are generally well tolerated procedures.

PMID:35841704 | DOI:10.1016/j.oraloncology.2022.106019

Talanta. 2022 Jul 6;250:123721. doi: 10.1016/j.talanta.2022.123721. Online ahead of print.

ABSTRACT

Geopolymers, synthesized starting from aluminosilicate precursors activated with alkaline solutions, constitute a class of materials of high interest as potential substitutes of traditional, cementitious, binders. Infrared spectroscopy is one of the routine analytical techniques employed to study these materials and to verify the occurrence of geopolymerization; on the other hand, its portable version working in diffuse reflection is not enough exploited for their characterization. The aim of this work is therefore to assess the potentiality of Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) in the study of geopolymers. The combination of this technique with Principal Components Analysis (PCA) statistical treatment was used to search for criteria able to discriminate the successful products from those which require a correction in their formulation. Mainly, two groups of geopolymers were studied, based respectively on clay sediments and ceramic waste precursors, in the latter case with the possible addition of metakaolin. These samples were studied both after maturation, comprising several variables in their mix-design and curing, and during the first hours of solidification of the slurry. The results allowed to identify the best formulations within the analyzed groups. Besides, the extension of this study to a wider selection of geopolymers, such as the pumice-, volcanic paleo-soil- and/or metakaolin-based ones, already studied with other techniques, further confirmed the efficacy of DRIFT spectroscopy in the identification of the geopolymerization reaction.

PMID:35841660 | DOI:10.1016/j.talanta.2022.123721

Poult Sci. 2022 Jun 10;101(9):101997. doi: 10.1016/j.psj.2022.101997. Online ahead of print.

ABSTRACT

To seek viable alternatives to antibiotics, we determined the combinatorial effects of Lactobacillus and a quorum quenching enzyme (QQE) on broiler growth performance, antioxidant capacity, immune responses, and cecal microbial populations. In total, 360 one-day-old male broilers (Ross 308) were randomly allotted to 3 dietary treatments, with 12 replicate pens/treatment and 10 birds/replicate pen. Dietary treatments lasted 42 d and comprised: corn-soybean meal basal diet (control group, CON); control plus antibiotic growth promoter supplement group (AGP); and control plus Lactobacillus and QQE supplement group (LQ). Dietary LQ supplementation significantly increased final body weight (BW) and average daily gain (ADG) when compared with CON and AGP groups between 22 and 42 d and 1 to 42 d (P < 0.05). No significant differences were observed for serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels between treatments (P > 0.05). A higher concentration of total antioxidant capacity (T-AOC) was observed on d 42 in the LQ group (P = 0.06). Feeding LQ significantly increased serum immunoglobulins (IgA and IgG) levels when compared with other treatments (P < 0.05). A statistical trend was also observed for increased cecal butyrate levels (P = 0.06) in the LQ group. Bacterial α-diversity was unaffected by dietary treatments (P > 0.05). However, from principal component analysis (PCoA), the microbial community structure was different between the LQ and AGP groups. Diet supplemented with LQ significantly (P < 0.05) decreased the relative abundance of Synergistota and Proteobacteria and significantly (P < 0.05) increased the proportion of Ruminococcaceae and Faecalibacterium. Thus, supplemental LQ improved growth performance, immune status, and modulated intestinal microbial communities in broilers. We provide a new perceptive on antibiotic substitutes in the poultry industry.

PMID:35841646 | DOI:10.1016/j.psj.2022.101997

Vet Rec. 2022 Jul 16:e1971. doi: 10.1002/vetr.1971. Online ahead of print.

ABSTRACT

BACKGROUND: Liver lobe torsion (LLT) in rabbits can be under-recognised and potentially fatal. The clinical features of cases presented to an exotic animal veterinary service in Australia were retrospectively reviewed.

METHOD: Medical records of confirmed rabbit LLT cases between 2016 and 2021 were reviewed for signalment, clinical signs and findings, diagnostic imaging results, management strategies and outcomes. Variables of interest were analysed for statistical association with outcome.

RESULTS: A total of 40 rabbits were included. The mean presenting age was 56.2 months (SD 30.5). Neutered males (23/40, 57.5%) were over-represented. Common clinical signs and findings included reduced appetite (40/40, 100%), lethargy (32/40, 80.0%), reduced faecal production (16/40, 40.0%), a doughy distended stomach (20/40, 50.0%), pale mucous membranes (19/40, 47.5%) and hypothermia (17/40, 42.5%). Anaemia and elevated plasma alanine aminotransferase and blood urea nitrogen were common clinicopathologic findings. Computed tomography (CT) was performed in 34 of 40 rabbits, confirming the presence and position of LLT (34/34, 100%), stenosis of the caudal vena cava or portal system (28/34, 82.4%) and increased free peritoneal fluid (29/34, 85.3%). Fifteen (15/40, 37.5%) rabbits were medically managed, and surgical intervention was performed in 23 of 40 (57.5%) rabbits. Overall, 30 of 40 (75.0%) rabbits survived. Surgical intervention did not confer a significant difference in outcome compared to medical management (odds ratio 0.77, 95% confidence interval 0.15-4.10, p = 0.761).

CONCLUSION: CT can be an invaluable diagnostic modality for rabbit LLT. Favourable outcomes can be achieved in selected cases with medical management alone.

PMID:35841624 | DOI:10.1002/vetr.1971

Indian J Gastroenterol. 2022 Jul 16. doi: 10.1007/s12664-021-01228-x. Online ahead of print.

ABSTRACT

BACKGROUND: Successful completion of colonoscopy depends largely on the quality of bowel preparation. Polyethylene glycol (PEG) is a commonly used preparation for colonoscopy. The timing of bowel preparation has evolved from previous day evening to the currently recommended split-dose regimen. It was observed that consumption of entire or a portion of PEG on the previous day can interfere with work and sleep. Hence, we designed this single-blinded randomized controlled trial (RCT) to evaluate the efficacy, tolerability, and acceptability of the same-day PEG as compared with lowvolume split-dose PEG in patients undergoing late morning colonoscopy.

METHODS: A total of 384 patients were randomized to same-day (SD group; n = 192) and split-dose (SPL group; n = 192) bowel preparation. The patients in both the groups received bisacodyl 10 mg at bedtime on the day prior to colonoscopy. The patients in the SD group took 2 L of PEG between 5:00 AM and 7:00 AM on the day of colonoscopy. The SPL group took 1 L of PEG between 6:00 PM and 7:00 PM on the preceding day and another liter between 6:00 AM and 7:00 AM on the day of colonoscopy. The adequacy of bowel preparation was assessed using the Boston Bowel Preparation Scale (BBPS). Tolerability was scored by recording symptoms such as nausea, vomiting, bloating, and abdominal pain. Acceptability was based on the overall satisfaction, willingness to repeat the same preparation, and interference with sleep on the preceding night.

RESULTS: The median (interquartile range, [IQR]) BBPS in the SD group was 8 (6-9) while that in the SPL group was 6 (5-8) and this difference was statistically significant (p < 0.001). Similarly, a significantly higher proportion of patients in the SD group (86%) achieved adequate bowel preparation (BBPS score ≥ 6) when compared to those in the SPL group (73.4%) (p = 0.002). Tolerability as assessed by nausea, vomiting, bloating, and abdominal pain was similar in both the groups. There was also no significant difference with respect to overall satisfaction of taking bowel preparation (p = 0.33) or willingness to repeat the same regimen (p = 0.37) between the two groups. Patients in the SPL group had more interference with sleep on the preceding night (54% vs. 14.5%, p < 0.001).

CONCLUSION: Same-day morning PEG regimen can be considered an effective, well-tolerated, and acceptable bowel preparation for colonoscopy.

PMID:35841521 | DOI:10.1007/s12664-021-01228-x

Environ Sci Pollut Res Int. 2022 Jul 16. doi: 10.1007/s11356-022-21921-4. Online ahead of print.

ABSTRACT

The Cumulative Ordinary Kriging (COK) interpolation method has been proposed for the spatial prediction of atmospheric radioactive fallout in any given region. COK is built on the Ordinary Kriging and Cumulative Semivariogram methods and combines all their advantages to achieve statistically significant results. It is verified in this paper the reliability of the results from COK with other well-known Modified Shepard’s Method (MSM), Inverse Distance Square (INDSQ), Polynomial Regression (PR), Natural Neighbour (NN), Radial Basis (RB), and Kriging Method interpolation methods. The model is tested in detail and in every possible way in two and three dimensions and applied to real-time Cs-134 and Cs-137 radioactive fallout data from the Chernobyl and Fukushima reactor accidents by combining both experimental and theoretical results. The results obtained from the applications for all interpolation methods are included in the supplementary materials section at the end of the article for the benefit of the readers. COK can also be used for spatial modelling of any particle at micro or macro scale. It can contribute significantly to environmental quality, ecological, and human health.

PMID:35841508 | DOI:10.1007/s11356-022-21921-4

Environ Sci Pollut Res Int. 2022 Jul 16. doi: 10.1007/s11356-022-21944-x. Online ahead of print.

ABSTRACT

Aurelia aurita (AA), a legally registered harmful marine organism in South Korea, is damaging marine human leisure activities, local residents’ tourism income, fisheries, and cooling water intake at power plants. The government is therefore seeking to eradicate AA by removing AA-attached larvae (polyps). This article looks into the public willingness to pay (WTP) for the eradication, utilizing a contingent valuation. For the sake of eliciting the WTP response, the one-and-one-half-bounded (OB) model was adopted. For comparison, the single-bounded (SB) model, which uses only the response to the first question in the OB model, was also applied. A spike model with a considerable plausibility that could explicitly deal with zero WTP responses was employed. Consequently, the estimation results of the SB model were used for further policy analysis. The household average WTP was estimated as KRW 3,911 (USD 3.49) per year, securing statistical significance. The national value was KRW 80.46 billion (USD 71.71 million) per annum. This figure can be interpreted as public value of the AA eradication project and used as essential basic data to evaluate the economic feasibility of implementing the project. Some factors such as income and education level significantly positively affected the intention of paying a suggested bid.

PMID:35841502 | DOI:10.1007/s11356-022-21944-x