Background The efficacy of olanzapine as an antiemetic agent in cancer chemotherapy has been demonstrated. However, few high-quality reports are available on the evaluation of olanzapine's efficacy ...and safety at a low dose of 5 mg among patients treated with carboplatin regimens. Therefore, in this study, we investigated the efficacy and safety of 5 mg olanzapine for managing nausea and vomiting in cancer patients receiving carboplatin regimens and identified patient-related risk factors for carboplatin regimen-induced nausea and vomiting treated with 5 mg olanzapine. Methods Data were pooled for 140 patients from three multicenter, prospective, single-arm, open-label phase II studies evaluating the efficacy and safety of olanzapine for managing nausea and vomiting induced by carboplatin-based chemotherapy. Multivariable logistic regression analyses were performed to determine the patient-related risk factors. Results Regarding the endpoints of carboplatin regimen-induced nausea and vomiting control, the complete response, complete control, and total control rates during the overall study period were 87.9, 86.4, and 72.9%, respectively. No treatment-related adverse events of grade 3 or higher were observed. The multivariable logistic regression models revealed that only younger age was significantly associated with an increased risk of non-total control. Surprisingly, there was no significant difference in CINV control between the patients treated with or without neurokinin-1 receptor antagonist. Conclusions The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy. Keywords: Antiemetics, Carboplatin, Nausea, Olanzapine, Vomiting
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC).
Chemotherapy-naïve ...patients with advanced NSCLC were eligible. In the phase I dose-escalation cohort (3 + 3 design), patients received nab-paclitaxel (80 or 100 mg/m
given intravenously on days 1, 8 and 15) plus cisplatin (60 or 75 mg/m
given intravenously on day 1) every 4 weeks. The maximum tolerated dose was not reached. Nab-paclitaxel (100 mg/m
given intravenously on days 1, 8 and 15) plus cisplatin (75 mg/m
given intravenously on day 1) every 4 weeks was selected for the phase II cohort. The primary endpoint was the objective response rate (ORR).
Twenty-three patients (phase I, n = 6; phase II, n = 17) were enrolled, and 22 patients were eligible. The median age was 67.5 years (range 37-75), 90.9% were males, 45.5% had adenocarcinoma and 81.8% had stage IV disease. The ORR was 59.1% (90% confidence interval (CI); 41.8-74.4), and the disease control rate was 86.4% (95% CI; 66.7-95.3). The median progression-free survival was 5.1 months (95% CI; 4.0-6.7), and the median overall survival was 24.2 months (95% CI; 8.4 months to not estimable). The common grade ≥ 3 adverse events were neutropenia (31.8%), leukopenia (27.3%), lung infection (18.2%) and hyponatremia (18.2%). There was one instance of grade 2 interstitial pneumonia and no treatment-related death.
Nab-paclitaxel plus cisplatin was well tolerated and associated with encouraging response outcomes in chemotherapy-naïve patients with advanced NSCLC. Further investigation is warranted.
UMIN Clinical Trials Registry: UMIN000011776; Date of registration: 17 September 2013; Date of enrolment of the first participant to the trial: 23 January 2014.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Comorbidity is known to be associated with the severity and mortality of pneumonia. The severity of each underlying disease varies, and performance status, which is known to be a prognostic ...factor of malignant diseases, reflects the overall patient condition as affected by his/her comorbidity and underlying diseases of various severity. We investigated whether premorbid patients' performance status is associated with the severity and mortality of pneumococcal pneumonia. This retrospective study assessed these factors in hospitalized patients suffering from pneumococcal pneumonia from 2002 to 2015. We included 424 patients aged 68.9 ± 14.1 years in the study, of which 68.9% were men. A multivariate analysis found that advanced age (≥65 years), diabetes mellitus, and poor performance status were independent factors associated with severity, whereas old pulmonary tuberculosis, poor performance status, pneumococcal bacteremia, and severe pneumonia were independent factors that were associated with non-survival. Poor performance status was associated with the severity and mortality of pneumococcal pneumonia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective The long-term clinical course and prognosis of patients with chronic eosinophilic pneumonia (CEP) including factors predictive of the relapse of CEP have not been fully investigated. The ...aim of the present study was to investigate these issues. Methods We retrospectively investigated the rate of relapse and prognosis in 73 patients diagnosed as having CEP. Results Systemic corticosteroid therapy was administered at a prednisolone dose of 29.4±7.6 mg/day. During a median follow-up period of 1,939 days, 27 patients suffered from relapse of CEP. Two patients developed steroid-induced diabetes mellitus, and 1 patient developed pulmonary nontuberculous mycobacteriosis. Five patients died; however, none died of CEP. A history of smoking was the only independent negative risk factor for relapse of CEP hazard ratio, 0.37 (0.14-0.98). Conclusion Patients with CEP frequently relapse. During the follow-up, metabolic and infectious complications under prolonged corticosteroid therapy are problematic. A history of smoking was a negative factor for predicting the risk of CEP relapse.
The Mann–Whitney effect is a measure for comparing survival distributions between two groups. The Mann–Whitney effect is interpreted as the probability that a randomly selected subject in a group ...survives longer than a randomly selected subject in the other group. Under the independence assumption of two groups, the Mann–Whitney effect can be expressed as the traditional integral formula of survival functions. However, when the survival times in two groups are not independent of each other, the traditional formula of the Mann–Whitney effect has to be modified. In this article, we propose a copula-based approach to compute the Mann–Whitney effect with parametric survival models under dependence of two groups, which may arise in the potential outcome framework. In addition, we develop a Shiny web app that can implement the proposed method via simple commands. Through a simulation study, we show the correctness of the proposed calculator. We apply the proposed methods to two real datasets.
Planar cell polarity (PCP) coordinates the patterning and orientation of cells and their structures along tissue planes, and although its acquisition during the formation of airway epithelium has ...been described, the mechanisms for its maintenance and reconstruction are poorly understood. We aimed to clarify whether ambient environment change by orthotropic autologous transplantation affected PCP at the cellular level.
We performed orthotropic autologous transplantation by inverting tracheal segments in rats, and then performed morphological evaluation by microscopy. The PCP of the tracheal epithelium was assessed over time by analyzing the directions of mucociliary transport and ciliary beat, the positional relationship between the basal body and basal foot, and the bias of Vang-like protein 1 (Vangl1) at 2, 4, and 6 months postoperatively.
After 2 months, the directions of mucociliary transport and ciliary beat were preserved toward the lung in the inverted tracheal segments. The positional relationship between the basal body and the basal foot, and the bias of Vangl1, also indicated preservation of PCP in the inverted tracheal segments. Similar results were obtained at 6 months.
The PCP of ciliated epithelium was preserved in reversed trachea, even after long-term observation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective Presently, the predominant subtypes of influenza viruses in the world, except for those in local epidemics, include influenza pandemic H1N1 2009 (pH1N1), H3N2, and B viruses. There are few ...reports on the differences in the clinical features, radiographic findings, treatment, and outcomes of influenza virus-associated pneumonia among these three viral subtypes. The purpose of this study was to investigate whether the clinical features, radiographic findings, treatment, and outcomes differ among the viral subtypes. Methods We retrospectively analyzed 96 patients with influenza virus-associated pneumonia whose viral subtypes were clarified. Results Patients with pH1N1 virus-associated pneumonia tended to be young. The frequency of primary viral pneumonia differed among the virus-associated pneumonia subtypes (pH1N1, 80%; H3N2, 26.5%; and B, 31%). Patients with pH1N1 virus-associated pneumonia more frequently showed bilateral ground-glass opacities (GGOs), which affected more lobes than in patients with H3N2 and B virus-associated pneumonia. However, patients with H3N2 virus-associated pneumonia showed a higher frequency of consolidation and diffuse bronchial wall thickening than did the patients with pH1N1 virus-associated pneumonia. The severity and mortality did not differ among the three pneumonia subtypes. Conclusion In the patients who developed influenza virus-associated pneumonia, those with pH1N1 virus-associated pneumonia frequently developed primary viral pneumonia resulting in bilateral and broad areas of GGOs on imaging, whereas patients with H3N2 virus-associated pneumonia frequently showed consolidation and diffuse bronchial wall thickening on pulmonary imaging.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by localized and generalized bone loss. The risk of fractures is doubled in patients with RA. Denosumab, an anti-RANKL ...monoclonal antibody, is used for those with osteoporosis at high risk fracture and it has inhibitory effect of progressive bone erosion in patients with RA. While the increase in bone mineral density by denosumab has been reported in patients with RA, preventive effect of fracture by denosumab remains unknown. This study aimed to evaluate the efficacy of denosumab in treating clinical fracture risk in patients with RA.
Patients with RA who received denosumab treatment between 2013 and 2019 were retrospectively evaluated using the ANSWER (Kansai Consortium for the Well-Being of Rheumatic Disease Patients) cohort data. Fracture rates were evaluated between 0 and 6 months (reference period) versus > 6 months (post-reference period) of denosumab use.
A total of 873 patients with RA received denosumab, and their characteristics were as follows: 88% females, mean age 68 years, and average disease duration 14.5 years. The hazard rates of all clinical fractures were 0.69 (per 100 person-years) in the reference period and 0.35 in the post-reference period, indicating a 49.2% decrease (p = 0.03).
Denosumab suppresses the risk of clinical fractures in patients with RA.
Background
The standard treatment for unresectable advanced/recurrent esophageal cancer in Japan is 5-fluorouracil plus platinum-containing drugs as first-line chemotherapy and taxanes as second-line ...chemotherapy. However, the standard regimen after patients become refractory to these treatments remains to be established. Therefore, we investigated the efficacy of trifluridine/tipiracil (FTD/TPI) in patients with esophageal cancer who are refractory or intolerant to 5-fluorouracil, platinum-containing drugs, and taxanes.
Methods
This single-arm phase II trial was conducted in seven hospitals in Japan. Eligible patients were those with unresectable advanced/recurrent esophageal cancer that was refractory or intolerant to 5-fluorouracil, platinum-containing drugs, and taxanes. The primary endpoint was the 3-month progression-free survival rate, and the secondary endpoints were the 6-month progression-free survival rate, progression-free survival, overall survival, response rate, disease control rate, and toxicity.
Results
Forty-two patients were enrolled between October 2015 and June 2016. All tumors were squamous cell carcinomas. The progression-free survival rates at 3 and 6 months were 15.4% (90% confidence interval 7.4–26.0%) and 7.7% (90% confidence interval 2.6–16.6%), respectively. The median progression-free survival and median overall survival were 1.3 (95% confidence interval 1.0–1.8) months and 4.5 (95% confidence interval 3.6–5.7) months, respectively. The response rate was 0%, and the disease control rate was 23.8% (95% confidence interval 13.5–38.5%). The major grade 3/4 toxicities were neutropenia (47.6%), leukocytopenia (35.7%), and anemia (21.4%). No treatment-related deaths occurred. Exploratory subgroup analyses showed better progression-free survival in the subgroup without distant metastasis at diagnosis.
Conclusions
Trifluridine/tipiracil monotherapy is feasible and shows modest activity in patients with refractory esophageal squamous cell carcinoma.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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