Community pharmacists' measurement of health-related quality of life in outpatients taking high-risk drugs.

Patients experiencing severe side effects when taking high-risk drugs may have a significantly reduced health-related quality of life (QOL); therefore, it is important to identify changes in the health-related QOL in these patients. This study aimed to determine the health-related QOL in community pharmacy outpatients taking high-risk drugs. This prospective observational study was conducted in 29 community pharmacies with 71 pharmacists in 12 regions and cities in Japan from October to December 2020 and 760 patients were enrolled. Using descriptive questionnaires of EuroQOL-5-dimensions-5-levels (EQ-5D-5L), community pharmacists obtained health-related QOL data from outpatients taking high-risk drugs. The mean health-related QOL of all outpatients was 0.869. The health-related QOL decreased with increasing age. The outpatient health-related QOL was 0.700, 0.763, 0.785, and 0.817 when taking antiepileptic, antidepressant, digitalis, and antiarrhythmic drugs, respectively, which was lower than the average health-related QOL of all outpatients. Mobility and pain/ discomfort accounted for a large proportion of the decline in the health-related QOL with increasing age. There were no significant differences in personal care with increasing age; however, the number of outpatients with mobility, normal activity, and pain challenges decreased with age. In contrast, outpatients aged <65 years with anxiety/depression showed a lower than overall average health-related QOL. To the best of our knowledge, this is the first study in Japan to report an investigation by community pharmacists regarding health-related QOL assessment in outpatients taking high-risk drugs.

Cholesterol 25-hydroxylase is a metabolic switch to constrain T cell-mediated inflammation in the skin.

Interleukin-27 (IL-27) is an immunoregulatory cytokine whose essential function is to limit immune responses. We found that the gene encoding cholesterol 25-hydroxylase (Ch25h) was induced in CD4+ T cells by IL-27, enhanced by transforming growth factor­ß (TGF-ß), and antagonized by T-bet. Ch25h catalyzes cholesterol to generate 25-hydroxycholesterol (25OHC), which was subsequently released to the cellular milieu, functioning as a modulator of T cell response. Extracellular 25OHC suppressed cholesterol biosynthesis in T cells, inhibited cell growth, and induced nutrient deprivation cell death without releasing high-mobility group box 1 (HMGB1). This growth inhibitory effect was specific to actively proliferating cells with high cholesterol demand and was reversed when extracellular cholesterol was replenished. Ch25h-expressing CD4+ T cells that received IL-27 and TGF-ß signals became refractory to 25OHC-mediated growth inhibition in vitro. Nonetheless, IL-27­treated T cells negatively affected viability of bystander cells in a paracrine manner, but only if the bystander cells were in the early phases of activation. In mouse models of skin inflammation due to autoreactive T cells or chemically induced hypersensitivity, genetic deletion of Ch25h or Il27ra led to worse outcomes. Thus, Ch25h is an immunoregulatory metabolic switch induced by IL-27 and dampens excess bystander T effector expansion in tissues through its metabolite derivative, 25OHC. This study reveals regulation of cholesterol metabolism as a modality for controlling tissue inflammation and thus represents a mechanism underlying T cell immunoregulatory functions.

Cost-effectiveness of primary prophylaxis of febrile neutropenia with pegfilgrastim in docetaxel, cisplatin and 5-fluorouracil therapy for esophageal cancer.

Objective: The efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy in treating esophageal cancer has been reported. However, febrile neutropenia (FN) is a potentially serious adverse event of DCF therapy with an incidence of 10 to 40%. Pegfilgrastim, a granulocyte colony-stimulating factor (G-CSF), has been shown to have a primary prophylactic role in FN. However, it has been suggested that excessive use of expensive G-CSF should be avoided. Therefore, we performed a cost-utility analysis of primary prophylaxis with pegfilgrastim. Design: Cost-effectiveness analysis using decision tree modelling. Methods: We used a decision tree analysis model based on the report of primary prophylaxis with pegfilgrastim. Based on a previous study, the FN incidence rate was set at 40.0% (95% confidence interval (CI): 11.9-68.1) for the pegfilgrastim group and 43.5% (95%CI: 21.6-65.4) for the no pegfilgrastim group. The FN treatment cost was US$726.63, and the duration of FN was 3.65±1.20 days. The utility value of patients who received DCF therapy was 0.643, and the change in utility value at FN onset was -0.15. Expected cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) were calculated, and cost-utility analysis was performed. Results: The ICER of pegfilgrastim was 184,976.75 USD/QALY. As a result of sensitivity analysis, the utility of FN had the greatest impact on the cost-effectiveness analysis, followed by the drug cost of pegfilgrastim. Conclusion: Primary prophylaxis of FN with pegfilgrastim might not be cost-effectiveness. In determining whether to administer pegfilgrastim it is necessary to consider patient factors, not just the incidence of FN.

Wire-loop lesion is associated with serological immune abnormality, but not renal prognosis, in lupus nephritis.

BACKGROUND: Wire-loop lesion (WL) is one of the active lesions of lupus nephritis (LN). However, few reports have focused on the clinicopathological relationships of WL to serological immune abnormality and renal prognosis. METHODS: We enrolled 126 Japanese LN patients subjected to renal biopsy in 11 hospitals from 2000 to 2018. In patients with class III or IV of the International Society of Nephrology/Renal Pathology Society classification, we retrospectively compared clinicopathological findings between those with WL (WL+ group) and without WL (WL- group) to detect factors associated with WL. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2 for more than three months. We also compared these findings between those with CKD (CKD+ group) and without CKD (CKD- group) at the last visit to investigate factors associated with renal prognosis. RESULTS: Of 126 patients, 100 (79.4%) were classified as class III or IV. WL was found in 36 (36.0%) of them. Although the renal function did not differ, the WL+ group had a higher titre of serum anti-dsDNA antibodies and lower serum complement 3 levels than the WL- group. Linear regression analysis revealed a significant association only between anti-dsDNA antibodies and WL (ß = 0.27, 95% confidence interval (CI) 0.001-0.100, p = 0.01). Of these patients, 69 were tracked for 59.6 ± 55.1 months. Kaplan-Meier analysis showed no difference in renal prognosis between these groups. Next, the CKD+ group included 15 (22.1%) patients. They were older and had higher frequencies of hypertension and hyperuricaemia, serum creatinine (Cr) level, glomerulosclerosis, interstitial inflammation, interstitial fibrosis and tubular atrophy than the CKD- group at the time of renal biopsy. The frequency of WL was not significantly different. Cox regression analysis revealed significant associations of CKD with hypertension, hyperuricaemia, serum Cr level at the time of renal biopsy clinically and with tubular atrophy histologically. CONCLUSIONS: WL was associated with serum anti-dsDNA antibodies but not with renal prognosis, suggesting that WL reflects immune abnormality but is not an independent factor predictive of renal prognosis in LN.

Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment.

BACKGROUND: With the development of direct-acting anti-virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR). AIM: To evaluate the short-term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC. METHODS: This large-scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon-free sofosbuvir-based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan-Meier method and Cox proportional hazard analysis were used to calculate the cumulative HCC incidence and related factors of HCC. RESULTS: During the follow-up period (median: 17 months), 46 (2.7%) patients developed HCC. The 1-year cumulative rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P < 0.001). For cirrhotic patients, serum α-fetoprotein level at the end of treatment (EOT-AFP) was the strongest predictor of de novo HCC. The 1-year cumulative de novo HCC rates were 1.4% and 13.1% in the EOT-AFP < 9.0 ng/mL and ≥ 9.0 ng/mL groups (cut-off value) respectively (log-rank test: P < 0.001). The 1-year cumulative rates of HCC recurrence were 6.5% and 23.1% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P = 0.023). For cirrhotic patients, previous HCC characteristics were significantly associated with HCC recurrence. In contrast, sex, age and metabolic features did not influence de novo HCC or recurrence. CONCLUSIONS: For cirrhotic patients after elimination of HCV, serum EOT-AFP level and previous HCC characteristics would be useful markers for predicting de novo HCC or recurrence.

Helminth community structure of 13 species of anurans from Atlantic rainforest remnants, Brazil.

This study aimed to evaluate the community composition and structure of the helminths found in 13 anuran species, and to evaluate whether this parasite community is determined by anuran characteristics. We found that the helminth fauna of the amphibians from five anuran families consisted of 13 taxa and that Cosmocercidae gen. sp. was the most prevalent taxon, followed by Oswaldocruzia subauricularis. Host body size was a determining factor of the composition and structure of the parasitic fauna. Helminth abundance and richness were positively correlated with host body size. The host Leptodactylus latrans had the highest helminth richness (n = 8). The frog Hypsiboas faber had the greatest helminth diversity (H' = 0.711). The mean helminth species richness and diversity differed significantly between host species (P < 0.05). Taken together, our data indicate that, in sympatric species of amphibians, the morphological and behavioural characteristics of the hosts are important for structuring the helminth parasite communities.

Immune responses against norovirus GII.4 virus-like particles in mice.

Norovirus (NoV) is a causative agent of gastroenteritis in children and adults worldwide. To evaluate the safety and effectiveness of a NoV vaccine candidate, 100 µg of GII.4 NoV-like particles (VLPs) was challenged orally (oral and intrabuccal administration) and by subcutaneous injection without adjuvant in mice. The subcutaneous injection induced IgG in sera, but not IgA in feces. The oral delivery method induced IgA in both sera and feces, but not IgG in sera. However, challenging by the intrabuccal administration induced IgG in sera and IgA in both sera and feces, especially by 2-dose immunization. The peak of specific immune responses by the intrabuccal administration was detected later than that of the oral delivery method. Heterologous immune responses against other genotypes were also recognized. NoV-specific IFN-γ was detected after the intrabuccal administration. These findings indicated that the administration of NoV VLPs by intrabuccal administration could induce the best immune responses against NoV in mice.

Risk Factors for the Discontinuation of Home Medical Care among Low-functioning Older Patients.

OBJECTIVES: Older patients receiving home medical care often have declining functional status and multiple disease conditions. It is important to identify the risk factors for care transition events in this population in order to avoid preventable transitions. In the present study, therefore, we investigated the factors associated with discontinuation of home medical care as a potentially preventable care transition event in older patients. METHODS: Baseline data for participants in the Observational study of Nagoya Elderly with HOme MEdical (ONEHOME) study and data on the mortality, institutionalization, or hospitalisation of the study participants during a 2-year follow-up period were used. Discontinuation of home care was defined as admission to a hospital for any reason, institutionalization, or death. Univariate and multivariate Cox hazard models were used to assess the association of each of the factors with the discontinuation of home care during the observational period. The covariates included in the multivariate analysis were those significantly associated with the discontinuation of home care at the level of P<0.05 in the univariate analysis. RESULTS: The univariate Cox hazard model revealed that a low hemoglobin level (< 11g/dL), low serum albumin level (< 3g/dL), higher Charlson Comorbidity Index score, and low Mini Nutritional Assessment Short Form score (< 7) were significantly associated with the discontinuation of home care. A multivariate Cox hazard model including these four factors demonstrated that all four were independently associated with home-care discontinuation. CONCLUSIONS: The present results demonstrated that anemia, hypoalbuminemia, malnourishment, and the presence of serious comorbidities were associated with the discontinuation of home medical care among low-functioning older patients.

Pathological factors associated with omental metastases in endometrial cancer.

PURPOSE OF INVESTIGATION: This study aimed to assess the role of omentectomy in the surgical therapy of endometrial cancer. MATERI- ALS AND METHODS: A retrospective study was performed in 98 patients who were pathologically diagnosed with endometrial cancer and had initially undergone surgical therapy at the present institution. This study analyzed the relationship between omental metastasis and clinicopathological factors. RESULTS: Omental metastasis was detected in nine patients (9%). On univariate analysis, significant number of omental metastatic lesions were detected in few cases by positive peritoneal cytology, adnexal metastasis, gross dissemination, and lymphovascular space involvement. On multivariate analysis, adnexal metastasis were a significant risk factor. The sensitivity of the spe- cial histological type and the specificity of the macroscopic peritoneal dissemination and adnexal metastasis were all high. CONCLUSION: Omentectomy plays a significant role in determining the exact surgical staging in cases with non-endometrioid cancer, adnexal metas- tasis, and macroscopic peritoneal dissemination.

Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients.

OBJECTIVE: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third- line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. MATERIALS AND METHODS: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. RESULTS: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥ 3 months than for TFI 0-3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256; p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. CONCLUSIONS: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure.

Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG-IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study was carried out to evaluate the effectiveness of simeprevir-based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir-based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG-IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve [3/4 (75.0%)] or with prior relapse [1/1 (100%)] or partial response [5/6 (83.3%)] to PEG-IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct-acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG-IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir-based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG-IFNα and ribavirin. For patients with prior null response to PEG-IFNα and ribavirin, retreatment with simeprevir-based triple therapy is not a useful option.

A patient with elderly-onset atypical hydroa vacciniforme with an indolent clinical course.

Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun-exposed areas without systemic symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T-cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly-onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV-associated LPD including atypical HV. Here we describe a case of elderly-onset atypical HV accompanied by T-cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly-onset atypical HV manifesting a favourable course, and that T-cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly-onset atypical HV.

Anisotropic multi-step etching for large-area fabrication of surface microstructures on stainless steel to control thermal radiation.

Controlling the thermal radiation spectra of materials is one of the promising ways to advance energy system efficiency. It is well known that the thermal radiation spectrum can be controlled through the introduction of periodic surface microstructures. Herein, a method for the large-area fabrication of periodic microstructures based on multi-step wet etching is described. The method consists of three main steps, i.e., resist mask fabrication via photolithography, electrochemical wet etching, and side wall protection. Using this method, high-aspect micro-holes (0.82 aspect ratio) arrayed with hexagonal symmetry were fabricated on a stainless steel substrate. The conventional wet etching process method typically provides an aspect ratio of 0.3. The optical absorption peak attributed to the fabricated micro-hole array appeared at 0.8 µm, and the peak absorbance exceeded 0.8 for the micro-holes with a 0.82 aspect ratio. While argon plasma etching in a vacuum chamber was used in the present study for the formation of the protective layer, atmospheric plasma etching should be possible and will expand the applicability of this new method for the large-area fabrication of high-aspect materials.

Importance of platinum-free interval in second-line chemotherapy for advanced or recurrent endometrial cancer.

PURPOSE: To investigate the effectiveness of platinum-based combination chemotherapy as second-line chemotherapy for patients with advanced or recurrent endometrial cancer treated initially by platinum-based combination chemotherapy. MATERIALS AND METHODS: Subjects were patients who had received platinum-based combination chemotherapy as second-line chemotherapy: 56 patients with recurrent disease who had previously received postoperative adjuvant platinum-based combination chemotherapy (Category 1) and 21 patients who had received first-line chemotherapy but not adjuvant chemotherapy for advanced or recurrent disease (Category 2). Patients' records were searched for the response to second-line chemotherapy and survival, particularly in relation to the platinum-free interval (PFI). RESULTS: APFI over 12 months was a predictor of response (64.7%) and overall survival time (23 months) in Category 1 patients. A PFI of less than three months was a negative predictor of response (0%) and overall survival (nine months) in Category 2 patients. CONCLUSION: Platinum-based combination chemotherapy appears to be effective as second-line chemotherapy for endometrial cancer if the PFI is sufficiently long.