Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is rapidly expanding in cancer treatment. ICIs have a unique safety profile, characterised by immune-related adverse events (irAEs). The safety profile of ICIs lacks patient experience and perspectives. This study primarily aims to obtain a database for descriptive research on the status of irAEs using the Patient-Reported Outcomes version of the Common Terminology Criteria (PRO-CTCAE) in patients with gastrointestinal cancer, lung cancer and malignant pleural mesothelioma treated with regimens containing ICIs. METHODS AND ANALYSIS: This is an ongoing, multicentre, observational study in Japan. Eligible patients must be at least 20 years old and have been diagnosed with lung cancer, malignant pleural mesothelioma or gastrointestinal cancer and plan to use ICIs. Participants will install the electronic PRO (ePRO) application and report adverse events via ePRO using PRO-CTCAE once weekly for up to 48 weeks. A registry will be established using background information obtained from medical records. The sample size is determined by 1 year projection without using statistical methods. Statistical analyses will include point estimates and 95% CIs for the incidence of each adverse event by cancer type and regimen at each time point. ETHICS AND DISSEMINATION: This research will be conducted per the Declaration of Helsinki, the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects issued by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor and Welfare, and the revised Personal Information Protection Law. The study protocol was approved by the Ethics Committee (approval ID T2021-0180) of Tokyo Medical University Hospital on 15 October 2021. REGISTRATION DETAILS: The study began enrolling patients in December 2021. The target enrolment is 260; as of October 2022, 141 have been enrolled, and the enrolment is scheduled to end on 30 June 2023. TRIAL REGISTRATION NUMBER: UMIN000046418.

Consequences of Different Corticosteroids on Serum Potassium and Prostate-Specific Antigen in Patients Receiving Abiraterone for Castration-Resistant Prostate Cancer: A Retrospective Observational Study.

BACKGROUND: Abiraterone acetate is an androgen synthesis inhibitor approved for the treatment of castration-resistant prostate cancer (CRPC). Although co-administration of either prednisone or prednisolone at 10 mg/d has been recommended to reduce the risk of abiraterone-induced hyperaldosteronism (notably hypokalemia) and to give adjunctive pain relief effects, whether these glucocorticoids can be substituted by dexamethasone remains unknown. METHODS: We performed a retrospective review of medical records of patients who were given abiraterone for the treatment of CRPC with either prednisolone (ABI/PSL) 10 mg/d or dexamethasone (ABI/DEX) 0.5 or 1 mg/d between 2014 and 2017 in Juntendo University Nerima Hospital. Demographic and biochemical data including prostate-specific antigen (PSA) level were retrieved from the electronic medical records. RESULTS: Fifty-three eligible patients (27 in ABI/PSL group and 26 in ABI/DEX group) were extracted from the records. Both groups showed no significant changes in serum potassium level before and after starting treatment. In the ABI/PSL group, 12 patients (46%) showed elevations of PSA and 7 patients (27%) discontinued treatment within 3 months. In contrast, in the ABI/DEX group, only 6 patients (25%) showed elevations of PSA and 3 patients (13%, all were given dexamethasone 1 mg/d) discontinued treatment. CONCLUSIONS: Dexamethasone and prednisolone may be equally effective in preventing abiraterone-induced hypokalemia.

The Japanese version of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE): psychometric validation and discordance between clinician and patient assessments of adverse events.

BACKGROUND: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed by the National Cancer Institute as an adverse event assessment system to evaluate patients' symptoms, which tend to be underestimated in cancer clinical trials. The aim of this study was to assess the psychometric properties of the Japanese version of the PRO-CTCAE and the degree of adverse event assessment discordance between clinicians and patients. METHODS: A total of 187 cancer patients receiving systemic therapy were enrolled. Reproducibility, criterion validity, and responsiveness of the Japanese version of PROCTCAE were assessed. The EORTC QLQ-C30 was used as an external anchor. Discordance of assessment of adverse events between clinician and patients were also assessed using the CTCAE and PRO-CTCAE. RESULTS: A total of 187 participants (187 for criterion validity, 80 for reproducibility, and 100 for responsiveness), were analyzed (Mage = 62.4 years). All patients responded to at least one symptom item (M = 16). The mean (SD) intra-class correlation coefficients of overall reproducibility for the Japanese PRO-CTCAE was 0.63 (0.02). The correlation coefficient for the corresponding items in the EORTC QLQ-C30 and the Japanese PRO-CTCAE was high (Pearson r = 0.56-0.76). The analysis of responsiveness revealed significant dose-response trends (Jonckheere-Terpstra test, ps < 0.001). Depending on the adverse events, a discrepancy was observed in evaluation between the clinician and patient. CONCLUSIONS: These results revealed that there is underestimation in the assessment of adverse events in Japan, and that the Japanese version of the PRO-CTCAE had acceptable reliability and validity for common and clinically important symptoms.

Enhancement of chemical sensing capability in a photonic crystal fiber with a hollow high index ring defect at the center.

A new type of index-guided photonic crystal fiber is proposed to enhance chemical sensing capability by introducing a hollow high index ring defect that consists of the central air hole surrounded by a high index GeO2 doped SiO2 glass ring. Optical properties of the fundamental guided mode were numerically analyzed using the full-vector finite element method varying the design parameters of both the defects in the center and the hexagonal air-silica lattice in the cladding. Enhanced evanescent wave interaction in the holey region and lower confinement loss by an order of magnitude were achieved simultaneously, which shows a high potential in hyper sensitive fiber-optic chemical sensing applications.

Dispersion properties of dual-core photonic-quasicrystal fiber.

We propose a photonic quasi-crystal fiber with a dual-core structure. The circular-like outer core caused by the quasi-periodic arrangement gives rise to an interesting dispersion property that is different from that of a photonic crystal fiber with a dual-core structure. The absolute value of negative dispersion for the dual-core photonic quasi-crystal fiber increases as the distance between the nearest holes increases, while the absolute value of negative dispersion for the dual-core photonic crystal fiber decreases. The dispersion property can be useful in reducing the coupling loss between the compensating dispersion fiber and a conventional single mode fiber.

Modified rectangular lattice photonic crystal fibers with high birefringence and negative dispersion.

We propose a modified rectangular lattice PCF and numerically investigate its birefringence and dispersion. Based on the plane wave expansion method, it is shown that the proposed structure provides high birefringence and negative dispersion. Numerical results show that the birefringence of the modified PCF reaches 10(-2) and the leakage loss is about 1000 times smaller than that of an original rectangular PCF because the modification gives rise to the strong confinement of guided modes. Dispersion and its slope are also negative over the C band.

Dispersion and birefringence of irregularly microstructured fiber with an elliptic core.

We have investigated the dispersion and birefringence of an irregularly microstructured fiber with an elliptic silica core and irregular airholes. The polarization-dependent output power through the fiber reveals two well-defined principal-axis modes despite the irregularity of airholes. The dispersion of the fiber is measured in the range of 680 to 1000 nm using the Mach-Zehnder interferometric technique with sub-10 fs laser pulses, which yield two zero dispersion wavelengths at 683 and 740 nm for the two principal modes, respectively. The birefringence measured using the wavelength scanning method is about 0.0055 at 800 nm. It is also demonstrated that this irregularly microstructured fiber with high birefringence and short zero dispersion wavelength is useful for the one-octave-spanning supercontinuum generation suitable for an f-2f interferometric system.

Novel optical properties of six-fold symmetric photonic quasicrystal fibers.

We have investigated optical properties of an optical fiber having a six-fold symmetric quasiperiodic array of air holes in cladding, a six-fold symmetric photonic quasicrystal fiber. The photonic quasicrystal fiber exhibits larger cutoff ratio for endlessly single mode operation than that of a triangular photonic crystal fiber having six-fold symmetry and almost zero ultra-flattened chromatic dispersion, 0+/-0.05 ps/km/nm, in the range of wavelength from 1490 to 1680 nm. The dispersion value is much less than those of the proposed dispersion flattened PCFs.

Frequency-domain intermodal interferometer for the bandwidth measurement of a multimode fiber.

A new bandwidth measurement technique for a multimode optical fiber (MMF) using a frequency-domain intermodal interferometer is proposed. We have demonstrated that the relative modal delay (RMD) of a MMF can be obtained easily and accurately based on an optical frequency-domain reflectometry (OFDR) technique by using an intermodal interference signal among the excited modes of a MMF. As an example, a photonic crystal fiber with a few modes is prepared and its RMD is measured by using our proposed measurement technique. Measurement results are compared with those from a previously reported frequency-domain method. We have also measured the RMD of a commercial MMF as a practical application and compared our result with the one obtained from a well-known time-domain differential mode delay measurement technique.

Versatile control of geometric birefringence in elliptical hollow optical fiber.

A novel optical fiber fabrication technique was developed by converting the symmetry of the silica substrate into the germanosilicate ring core to efficiently introduce geometric birefringence in an elliptical hollow optical fiber. Due to high ellipticity in the hollow ring core, the fiber provides an extremely high group birefringence of 2.35 x 10(-3) at 1550 nm. Single-mode single-polarization guidance was also experimentally confirmed, with a bandwidth of approximately 35 nm. The generic adiabatic mode conversion capability in the taper also provided a stable fusion splice to conventional single-mode fiber with low loss and high tensile strength.

Defect and lattice structure for air-silica index-guiding holey fibers.

We propose new design parameters for index-guiding holey fiber that can provide flexibility in defect and lattice design and adiabatic mode transformation capability. The new defect consists of a central air hole and a germanosilicate ring surrounding it, which results in a large-area annulus mode profile, low splice losses to standard fiber, 0.7 dB at 1.55 microm, and chromatic dispersion with a low slope, 0.002 ps/km nm2.

Decrease in skin permeation and antibacterial effect of parabens by a polymeric additive, poly(2-methacryloyloxyethyl phosphorylcholine-co-butylmetacrylate).

The inhibitory effect of poly(2-methacryloyloxyethyl phosphorylcholine-co-butylmetacrylate) (PMB) on the in vitro skin permeation of p-hydroxybenzoic acid and its esters (parabens; methylparaben, ethylparaben, n-propylparaben and n-butylparaben) as model compounds was evaluated. Solubility of the parabens in distilled water was increased by addition of PMB, and the increasing ratio was dependent on the concentration of PMB. The increment of the ratio was more marked in lipophilic parabens than hydrophilic ones. Skin permeability of parabens from their aqueous suspensions was decreased by addition of PMB, and the decreasing ratio was dependent on the PMB concentration. Then, antibacterial effect of parabens of their aqueous solutions was determined with and without PMB by measuring minimum inhibitory concentration (MIC) against E. coli and S. aureus. As results, MIC and antibacterial effect were increased and decreased, respectively, by addition of PMB. The contribution of PMB was more marked in butylparaben than methylparaben. These decreases in skin permeation and antibacterial effect of parabens by PMB are probably due to a higher solubility in water and a lower partition to the skin and bacterial membranes of parabens by addition of PMB.

New defect design in index guiding holey fiber for uniform birefringence and negative flat dispersion over a wide spectral range.

A novel silica index guiding holey fiber (IGHF) design is proposed utilizing a new defect structure that is composed of an elliptic high index ring structure and an elliptic air-hole at the center with triangular lattice structure. The proposed IGHF showed unique modal properties such as uniform and high birefringence over a wide spectral range and single polarization single mode (SPSM) guidance along with a flat negative chromatic dispersion. Optical waveguide properties were numerically analyzed using the plane wave expansion method in terms of mode intensity distribution, modal birefringence, chromatic dispersion for the new defect structural parameters.

[Effect of admixture of betamethasone butyrate propionate ointment on preservative efficacy].

Twenty percent of dermatologists have experienced a separation of water or deterioration of topical corticosteroids mixed with commercially available ointments and/or creams. However, few investigations of this deterioration of admixtures have been reported. To assess the effects of preservatives in preventing microbial contamination of these admixtures, we attempted to investigate the concentration of preservative agents in admixtures and the microbial contamination of these admixtures with a topical corticosteroid ointment (Antebate). The concentration of parabens was reduced by half using an admixture of corticosteroid ointment with four types of moisturizing creams, Urepearl, Pastaronsoft, Hirudoid, and Hirudoidsoft. After a further 3 months, no decrease in parabens was seen. No microbial contamination was found in any admixture stored at room temperature for 1 week and touched two times daily with a finger. The concentration and ratio of the parabens in the aqueous phase and oil phase were entirely different in the admixtures before being centrifuged. The aqueous phase of the admixtures of the oil/water (O/W)-type emulsions of Urepearl and Hirudoid was not found to have microbial contamination immediately after being centrifuged. All aqueous phases stored at room temperature or in a refrigerator for 1 week and touched with a finger twice daily exhibited microbial contamination. These experiments demonstrated that O/W-type emulsions, in which the water easily separates from the bases, should be thoroughly mixed to prevent microbial contamination.