Category: Statistics

Zhongguo Fei Ai Za Zhi. 2021 Aug 30. doi: 10.3779/j.issn.1009-3419.2021.102.26. Online ahead of print.

ABSTRACT

BACKGROUND: Programmed cell death 1 or programmed cell death-ligand 1 inhibitor (PD-1/PD-L1 inhibitor) and docetaxel, as the standard second-line treatments of advanced non-small cell lung cancer (NSCLC) patients, have limited effects. There are few studies on whether docetaxel combined with PD-1/PD-L1 inhibitor can increase the efficacy and make patients better benefit. The aim of this study is to evaluate the efficacy and safety of docetaxel combined with PD-1/PD-L1 inhibitor for the second-line treatment of stage IV NSCLC patients.

METHODS: Stage IV NSCLC patients (n=118) who received treatment at Shandong Cancer Hospital between October 1, 2018, and December 31, 2020, were retrospectively analyzed. They were divided into observation group (n=69) and control group (n=49) according to different treatment plan. Observation group was given docetaxel plus PD-1/PD-L1 inhibitor, while control group was given PD-1/PD-L1 inhibitor. The clinical curative effect and the incidence of adverse reactions of grade 3 and above were compared between the two groups.

RESULTS: The disease control rate (DCR) was higher in the observation group (89.9%) than that in the control group (73.5%) (P=0.019), and the objective response rate (ORR) showed no significant difference between observation group (24.6%) and control group (16.3%) (P=0.276). Till June 22, 2021, the 1-year PFS rate showed no difference between observation group (16.5%) and control group (7.7%) (P=0.205). During the treatment period, the adverse reactions of the two groups were mostly grade 1 to 2, and could be tolerated. The incidence of bone marrow suppression in observation group was higher than that in the control group (P<0.05), and the remaining adverse reactions were not statistically different from control group. Cox regression analysis showed that performance status (PS) (P=0.020) and age (P=0.049) were independent prognostic factors for the effect of docetaxel combined with PD-1/PD-L1 inhibitor.

CONCLUSIONS: The second-line treatment with docetaxel plus PD-1/PD-L1 inhibitor in patients with stage IV NSCLC can improve the DCR and prolong the PFS, and the adverse reactions are tolerable.

PMID:34455735 | DOI:10.3779/j.issn.1009-3419.2021.102.26

J Thromb Haemost. 2021 Aug 29. doi: 10.1111/jth.15516. Online ahead of print.

ABSTRACT

BACKGROUND: In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients OBJECTIVES: To evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban.

PATIENTS/METHODS: In this nested case-control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4-week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type.

RESULTS: 24 cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01-12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5-16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1-1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5-3.5).

CONCLUSION: Advanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power.

PMID:34455706 | DOI:10.1111/jth.15516

J Complement Integr Med. 2021 Aug 30. doi: 10.1515/jcim-2021-0181. Online ahead of print.

ABSTRACT

OBJECTIVES: Insomnia and sleep disorders are common and can be severe amongst patients with cancer, especially during chemotherapy. The aim of this study was to evaluate the efficacy of lettuce seed syrup in breast cancer patients who suffer from insomnia or disordered sleep.

METHODS: This pilot study was a double-blinded randomized controlled clinical trial conducted in Shoha–e-Tajrish Hospital (Tehran, Iran) from September 2018 to June 2019. 50 adult patients with breast cancer with insomnia or sleep disorders were enrolled. Participants were randomly allocated to lettuce seed syrup (5 mL twice daily), or placebo syrup at the same dose for four weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality before and after the intervention.

RESULTS: Compared to placebo, the mean of the total PSQI score decreased significantly in participants who received lettuce seed syrup (p=0.014). In addition, there were statistically significant reductions in the mean scores of subject quality sleep (p=0.002), sleep duration (p=0.038), habitual sleep efficacy (p=0.029) and sleep disturbance (p=0.032) in patients who received lettuce seed syrup.

CONCLUSIONS: Lettuce seed syrup may improve self-reported sleep quality in participants with breast cancer. Larger trials are indicated in diverse samples of participants with caner to learn if these finds are generalizable.

PMID:34455726 | DOI:10.1515/jcim-2021-0181

Oral Dis. 2021 Aug 29. doi: 10.1111/odi.14013. Online ahead of print.

ABSTRACT

OBJECTIVE: The objectives of this study were to estimate the prognostic value of the tumour-stroma ratio (TSR) and tumour budding (TB) in oral tongue squamous cell carcinoma (OTSCC) and to establish a reliable model to predict the outcome of OTSCC patients.

METHODS: A total of 103 patients surgically treated at our hospital were enrolled in this study. Chi-square tests, Kaplan-Meier analyses, and Cox proportional hazards regression models were performed for statistical analysis.

RESULTS: Fifty-six patients were categorized as stroma-rich, and forty-seven patients were categorized as stroma-poor. Only pathological grade was associated with the TSR (P=0.017). Kaplan-Meier analysis showed that stroma-rich, high-intensity budding and high risk groups were associated with worse prognosis. The Cox regression model showed that the TSR was an independent risk factor for OTSCC patients prognosis, and the high risk group was also related to poor prognosis (P<0.05). TB was significantly associated with poor prognosis but was not an independent risk factor.

CONCLUSIONS: We found that patients in the stroma-rich group had a worse long-term prognosis. The TSR is an independent risk factor for OTSCC patients outcome. In addition, a risk model that combined the TSR and TB proved to be valuable for predicting OTSCC patients outcome.

PMID:34455659 | DOI:10.1111/odi.14013

Int J Clin Pract. 2021 Aug 29:e14763. doi: 10.1111/ijcp.14763. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to investigate the effect on the occurrence of emergence delirium of propofol and ketofol with intranasal dexmedetomidine and midazolam applied as premedication to paediatric patients during magnetic resonance imaging (MRI).

METHODS: The study included children aged 2-10 years who received sedation for MRI, separated into four groups. Group MP (midazolam-propofol) received intranasal midazolam (0.2mg/kg) for premedication and intravenous (IV) propofol (1mg/kg) as the anaesthetic agent. Group MK (midazolam-ketofol) received intranasal midazolam (0.2mg/kg) for premedication and IV ketofol (1mg/kg) as the anaesthetic agent. Group DP (dexmedetomidine-propofol) received intranasal dexmedetomidine (1mcg/kg) for premedication and IV propofol (1mg/kg) as the anaesthetic agent. Group DK (dexmedetomidine-ketofol) received intranasal dexmedetomidine (1mcg/kg) for premedication and IV ketofol (1mg/kg) as the anaesthetic agent. The Paediatric Anaesthesia Emergence Delirium (PAED) scale was used to evaluate delirium. A PAED score ≥ 10 was accepted as delirium.

RESULTS: Statistical analysis was made of 140 paediatric patients. Delirium developed in 1.42% of all the patients, and in 5.7% of Group MP. The mean Aldrete and PAED scores were lower and the length of stay in the recovery room was shorter in Group DP than in the other groups. The need for additional anaesthetic was highest in Group DP at 94.3% and lowest in Group DK at 14.3%. The groups administered ketofol were observed to have a lower requirement for additional anaesthetic.

CONCLUSION: Delirium was seen at a very low rate only in the Group MP and it is difficult to say the best combination in terms of delirium frequency. However, intranasal dexmedetomidine and IV ketofol seem to be better and safer than the other groups in terms of the need for additional doses and the number of side effects. The addition of ketamine to propofol reduces the need for additional doses with a synergistic effect.

PMID:34455665 | DOI:10.1111/ijcp.14763

Int J Clin Pract. 2021 Aug 29:e14760. doi: 10.1111/ijcp.14760. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to determine the predictive risk factors for development of severe bronchiolitis in patients with acute bronchiolitis with no previous chronic disease.

METHODS: Four hundred forty children aged 1-24 months hospitalized with acute bronchiolitis, were examined between February 2018 and February 2019 in this prospective study.

RESULTS: Eighty-five cases were regarded as severe bronchiolitis and 355 as mild-moderate bronchiolitis. Statistically significant differences were observed between the severe and mild-moderate bronchiolitis groups in terms of weight-for-age z-scores, history of bronchiolitis, hemoglobin levels, and time elapsed between onset of symptoms and admission. Weight-for-age z-scores, the mean time interval between onset of symptoms and admission, and mean hemoglobin values were lower in the severe bronchiolitis group while the mean number of bronchiolitis attacks was higher than in the mild-moderate bronchiolitis group. Logistic regression analysis determined that a low weight-for-age z-score increased the risk of severe bronchiolitis development 0.56-fold (CI: 0.409 – 0.760), a short duration between the onset of symptoms and admission increased the risk 0.62-fold (CI: 0.519 – 0.735), a frequent history of bronchiolitis increased the risk 1.81-fold (CI: 1.135 – 2.968) and low hemoglobin levels increased the risk 0.72-fold (CI: 0.537 – 0.969).

CONCLUSION: Low weight-for-age z-scores, a short duration between the onset of symptoms and admission, a high number of previous attacks, and low hemoglobin levels were identified as independent parameters of severe bronchiolitis development.

PMID:34455690 | DOI:10.1111/ijcp.14760

J Card Surg. 2021 Aug 29. doi: 10.1111/jocs.15952. Online ahead of print.

ABSTRACT

INTRODUCTION: To assess the efficacy of C-reactive protein (CRP) and procalcitonin (PCT) at identifying infection in children after congenital heart surgery (CHS) with cardiopulmonary bypass (CPB).

MATERIALS AND METHODS: Systematic review of the literature was conducted to identify studies with data regarding CRP and/or PCT after CHS with CPB. The primary variables identified to be characterized were CRP and PCT at different timepoints. The main inclusion criteria were children who underwent CHS with CPB. Subset analyses for those with and without documented infection were conducted in similar fashion. A p value of less than .05 was considered statistically significant.

RESULTS: A total of 21 studies were included for CRP with 1655 patients and a total of 9 studies were included for PCT with 882 patients. CRP peaked on postoperative Day 2. A significant difference was noted in those with infection only on postoperative Day 4 with a level of 53.60 mg/L in those with documented infection versus 29.68 mg/L in those without. PCT peaked on postoperative Day 2. A significant difference was noted in those with infection on postoperative Days 1, 2, and 3 with a level of 12.9 ng/ml in those with documented infection versus 5.6 ng/ml in those without.

CONCLUSIONS: Both CRP and PCT increase after CHS with CPB and peak on postoperative day 2. PCT has a greater statistically significant difference in those with documented infection when compared to CRP and a PCT of greater than 5.6 ng/ml should raise suspicion for infection.

PMID:34455653 | DOI:10.1111/jocs.15952

Int Endod J. 2021 Aug 29. doi: 10.1111/iej.13620. Online ahead of print.

ABSTRACT

AIM: To investigate whether TGF-β/BMP signaling participates in Jagged1-induced osteogenic differentiation in human dental pulp cells (hDPs).

METHODOLOGY: Bioinformatic analysis of publicly available RNA sequencing data of Jagged1 treated hDPs was performed using NetworkAnalyst. The mRNA expression was validated using real-time polymerase chain reaction. hDPs were seeded on Jagged1 immobilized surface in the presence or absence of TGF-β or BMP inhibitor. Osteogenic differentiation was evaluated using alkaline phosphatase staining, osteogenic marker gene expression, and mineralization assay. Statistical analyses were performed using a Kruskal Wallis test, followed by a pairwise comparison for more than three group comparison. Mann Whitney U test was employed for two group comparison. The statistical significance was considered at p< 0.05.

RESULTS: Jagged1 treatment in growth medium significantly promoted TGFB1, TGFB2, and TGFB3 while significantly inhibited BMP2, BMP4, and BMP6 mRNA expression (p<0.05). In osteogenic induction medium, Jagged1 significantly upregulated TGFB1, TGFB2, and TGFB3 at day 1 and 3 (p<0.05). Pretreatment with TGF-β1, TGF-β2, or TGF-β3 prior to osteogenic induction resulted in the significant increase of osteogenic marker gene expression, collagen type 1 protein expression, alkaline phosphatase enzymatic activity, and mineral deposition (p<0.05). However, TGF-β signaling inhibition with SB431542 (4 μM) or SB505124 (47 and 129 nM) failed to attenuate the effect of Jagged1-induced osteogenic differentiation in hDPs. Dorsomorphin (4 and 8 μM) treatment significantly abolished the effect of Jagged1 on mineralization by hDPs (p<0.05).

CONCLUSION: Notch signaling activation by Jagged1 modulated TGF-β and BMP ligand expression. Dorsomorphin, but not TGF-β receptor inhibitor, attenuated Jagged1-induced osteogenic differentiation in hDPs.

PMID:34455605 | DOI:10.1111/iej.13620

Zoo Biol. 2021 Aug 29. doi: 10.1002/zoo.21648. Online ahead of print.

ABSTRACT

Many amphibian species are threatened with extinction. Understanding their vitamin A (retinol), E (alpha-tocopherol), and carotenoid requirements is vital, as normal levels of these nutrients have a known connection to breeding success with abnormal levels leading to disease. This research examined vitamins A, E, and carotenoids (apocarotenoid, beta-carotene; beta-cryptoxanthin, lutein, zeaxanthin, and esters) concentration kinetics in the liver and plasma of 65 (57.8) cane toads (Rhinella marina) over 4 months supplemented with commercially available invertebrates in human care. Cane toads were opportunistically collected as part of a population control program for use as an amphibian model species. Toads were randomly assigned to one of two diets: treatment 1 was brown house crickets (Acheta domesticus) consuming Mazuri® Hi Calcium Gut Loading Diet without vitamin A or E supplement, plus fresh raw vegetables (carrot/sweet potato); Treatment 2 was the same diet except no vegetables. Ten toads were euthanized on Day 0 to analyze baseline free-ranging liver and plasma metabolites. Six toads consuming each treatment were euthanized on Days 22, 50, and 81, and n = 7 on Day 119 for analysis. Regardless of dietary treatment, most liver and blood metabolites were substantially higher at time 0 than all time points thereafter (p < .05); Ex: liver vitamin A at time 0 was 87.7 ± 16.12 µg/g while Day 119 for treatments 1 and 2 were 11.6 ± 1.19 and 8.2 ± 0.74, respectively. Few statistically significant differences between diets at the same time point were noted (p < .05). The results from this study indicate that additional or alternative diet supplementation may be needed for cane toads (and potentially other amphibians) to mimic their free-ranging diets.

PMID:34455629 | DOI:10.1002/zoo.21648

Adv Ther. 2021 Aug 29. doi: 10.1007/s12325-021-01897-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Migraine is a debilitating neurological condition, affecting up to 15% of Americans. Recent estimates from a long-term safety study of rimegepant showed evidence of decreased monthly migraine days (MMD) in people with episodic migraine treated with rimegepant 75 mg. The objective of this study was to characterize migraine-specific quality of life version 2.1 (MSQv2) scores and corresponding mapped EuroQol-5 Dimensions-3 Level (EQ-5D-3L) utility values.

METHODS: Study participants were randomized into two treatment regimens: individuals with 2-14 MMD received rimegepant 75 mg as needed (PRN), and those with 4-14 MMD at baseline who received rimegepant on a fixed every-other-day schedule plus an as needed dose on days they did not treat (QOD + PRN). MSQv2 was mapped to EQ-5D-3L utilities using a validated algorithm. Outcomes were assessed for the PRN arm at baseline weeks 12, 24, 36, and 52 and for the QOD + PRN arm at baseline and week 12.

RESULTS: At baseline, MSQv2 data were available for 1,800 patients: 1,033 with 2-8 MMD in the PRN group, 481 with 9-14 MMD in the PRN group, and 286 with 4-14 MMD in the QOD + PRN group. For all MSQv2 domains as well as mapped utility values, outcomes improved over each study visit. At baseline, EQ-5D-3L utilities were 0.66, 0.63, and 0.65 for the 2-8 MMD PRN, 9-14 MMD PRN, and 4-14 MMD QOD + PRN groups, respectively. At end-of-study, utilities had increased by + 0.09, + 0.10, and + 0.12 for the three groups, respectively (p < 0.001 for all comparisons with baseline). Similar trends in improvement were observed across MSQv2 subdomains; all differences were statistically significant.

CONCLUSIONS: Rimegepant 75 mg, which has been shown to be associated with reduced MMD, is associated with improvement in MSQv2 domains over time, leading to estimated improvement in EQ-5D-3L utilities. While this improvement was observed in all patient-groups, it was most pronounced in those with higher MMD and those taking rimegepant QOD + PRN.

TRIAL REGISTRATION: Clinical Trials NCT03266588.

PMID:34455556 | DOI:10.1007/s12325-021-01897-2