Factors associated with COVID-19 booster vaccine hesitancy: a nationwide, cross-sectional survey in Japan.

OBJECTIVES: COVID-19 vaccine hesitancy/fatigue is increasing as the pandemic enters the endemic phase. The present study aimed to explore current perceptions about COVID-19 booster vaccination among the Japanese public. STUDY DESIGN: This was a cross-sectional study. METHODS: This cross-sectional study used data from the Japan COVID-19 and Society Internet Survey conducted in September 2021 and September 2022. The public's perceptions of COVID-19 vaccination and factors associated with COVID-19 booster vaccine hesitancy were analyzed. RESULTS: In total, 56,735 respondents were included. In the Japan COVID-19 and Society Internet Survey 2021, 75.1% of the participants (21,126/28,118) had completed the primary vaccination series. In the 2022 survey, 74.1% of the respondents (21,216/28,617) completed the primary series of vaccination with booster doses. The proportion of fear toward COVID-19 and obtaining information about COVID-19 has decreased from 2021 to 2022. Factors independently associated with booster vaccine hesitancy were young age (range: 18-29 years; adjusted odds ratio [aOR]: 6.56), history of COVID-19 (aOR: 1.82), distrust of the Japanese government's COVID-19 prevention measures (aOR: 1.55), lack of confidence in COVID-19 vaccine efficacy (aOR: 1.30), lack of confidence in COVID-19 vaccine safety (aOR: 1.62), low reliance on the COVID-19 vaccine (aOR: 1.92), and belief in COVID-19 conspiracy theories (aOR: 1.77). CONCLUSIONS: Providing clear and trustworthy information is critically important, especially targeted and tailored messages for the young generation, to promoting COVID-19 booster vaccination. Policymakers should therefore develop consistent and transparent communication strategies and the ability to respond promptly and flexibly to mitigate the negative impact of COVID-19 on the public while preparing for the next pandemic.

De-Training Effects Following Leucine-Enriched Whey Protein Supplementation and Resistance Training in Older Adults with Sarcopenia: A Randomized Controlled Trial with 24 Weeks of Follow-Up.

OBJECTIVES: This study aimed to evaluate the effectiveness of de-training after a combined intervention of leucine-enriched whey protein supplementation and resistance training on skeletal muscle mass and strength in older adults with sarcopenia. DESIGN: A randomized controlled trial. SETTING: A community in Hyogo, Japan. PARTICIPANTS: The study included older adults aged ≥ 65 years who were screened for sarcopenia at the Care Center from, a community in Hyogo, Japan. The participants were randomly allocated to one of three groups: whey protein supplementation after resistance training (RT + PRO; n = 27), resistance training only (RT; n = 27), and whey protein supplementation only (PRO; n = 27). INTERVENTIONS: An intervention program was conducted over a period of 24 weeks. The program included RT and/or PRO supplementation twice a week for 24 weeks, followed by a de-training period for another 24 weeks. PRO supplementation included 11.0 g of protein and 2,300 mg of leucine. The total energy and protein intake amounts for the participants in all groups were controlled to achieve at least 30 kcal/kg ideal body weight (IBW)/day and 1.2 g/kg IBW/day, respectively, during the intervention and de-training periods. MEASUREMENTS: The primary outcomes, such as mean change of appendicular skeletal muscle mass index (ΔASMI), and secondary outcomes, such as handgrip strength (ΔHGS), were measured at baseline, the end of intervention, and at 12 and 24 weeks of de-training. RESULTS: Compared to baseline, ASMI and HGS increased significantly at the end of the intervention period in the RT+PRO group (ASMI and HGS, p < 0.01); however, there were no significant differences in ΔASMI and ΔHGS between each group. At 24 weeks of the de-training period, ΔASMI and ΔHGS were higher in the RT + PRO group than in the RT group (p < 0.05 and p < 0.01, respectively). CONCLUSION: We demonstrated that combined intervention of RT and PRO showed long-term maintenance in treating sarcopenia than RT only at 24 weeks after de-training. Therefore, PRO intake after RT may be useful in the treatment of sarcopenia in older adults.

Relationships between dysphagia and tongue pressure during swallowing in Parkinson's disease patients.

Although dysphagia is a life-threatening problem in patients with Parkinson's disease (PD), the pathophysiology of oropharyngeal dysphagia is yet to be understood. This study investigated the tongue motor function during swallowing in relation to dysphagia and the severity of PD. Thirty patients with PD (14 males and 16 females; average age, 69.4 years), Hoehn and Yahr stage II-IV, in Osaka University Hospital are participated in this study. During swallowing 5 ml of water, tongue pressure on the hard palate was measured using a sensor sheet with 5 measuring points. The maximal tongue pressure at each measuring point during swallowing was compared between patients with PD and healthy controls. Subjective assessment of oropharyngeal dysphagia was performed using Swallowing Disturbance Questionnaire-Japanese. The maximal tongue pressure at each measuring point was significantly lower in patients with PD than in healthy controls (8 males and 12 females; average age, 71.6 years). Furthermore, the maximal tongue pressure was significantly lower in dysphagic PD patients than non-dysphagic PD patients. Loss of tongue pressure production at the anterior part of the hard palate was strongly related to dysphagia in the oral phase as well as in the pharyngeal phase. An abnormal pattern of tongue pressure production was more frequently observed in dysphagic PD patients than in non-dysphagic PD patients. The results suggest that tongue pressure measurement might be useful for early and quantitative detection of tongue motor disability during swallowing in patients with PD.

Multi-frequency force-detected electron spin resonance in the millimeter-wave region up to 150 GHz.

In this article, a novel technique is developed for multi-frequency force-detected electron spin resonance (ESR) in the millimeter-wave region. We constructed a compact ESR probehead, in which the cantilever bending is sensitively detected by a fiber-optic Fabry-Perot interferometer. With this setup, ESR absorption of diphenyl-picrylhydrazyl radical (<1 µg) was clearly observed at multiple frequencies of up to 150 GHz. We also observed the hyperfine splitting of low-concentration Mn(2+) impurities(∼0.2%) in MgO.

Professionalism of physicians at a major teaching hospital during the Fukushima nuclear disaster.

It poses a serious problem if physicians leave a hospital without having a replacement or without permission. A huge earthquake followed by a devastating tsunami seriously damaged the Fukushima-Daiichi nuclear power plant. This disaster overwhelmed a major teaching hospital in the local area and many hospital employees, including some resident physicians, left the premises. Since the threat of severe radiation exposure poses a potentially greater lifetime risk to younger individuals, letting the young resident physicians leave the hospital was not only allowed, it was actually recommended by many attending physicians and hospital administrators. The hospital administrator was required to make the difficult decision of whether to make all efforts to provide the highest level of medical care, including keeping all of the physicians on the premises, or to evacuate the resident physicians in order to preserve their health and their potential future contributions to healthcare. Consideration and compassion needed to be provided to all people, regardless of the reason they wanted to leave. From an ethical perspective, the roles of performance under these complex circumstances should be understood and embraced by us as individuals, professionals, supervisors and society as a whole.

Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21,755 patients from the Japanese breast cancer registry.

BACKGROUND: We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data. PATIENTS AND METHODS: Records of more than 300,000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21,755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization. RESULTS: pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10,973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward. CONCLUSION: We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.

Analysis of gene alterations of mitochondrial DNA D-loop regions to determine breast cancer clonality.

BACKGROUND: It has been a challenge to determine breast cancer clonality accurately. The aim of the present study was to assess methods using formalin-fixed paraffin-embedded (FFPE) tissue to differentiate new primary tumours from true recurrences that are associated with poorer prognoses and often require more aggressive treatment. METHODS: We investigated the novel method of analysing gene alterations of mitochondrial DNA D-loop region (GAMDDL) and compared it with the conventional method of analysing the X-chromosome-linked human androgen receptor (HUMARA). The FFPE sections of primary and secondary breast cancers, the non-neoplastic mammary gland, and lymph nodes were examined. RESULTS: Informative rates for HUMARA, GAMDDL, and combined analyses were 42.1%, 76.9%, and 89.5%, respectively. All of the 10 contralateral breast cancers were determined to be non-clonal. In contrast, 3 out of 8 (37.5%) of the ipsilateral secondary tumours shared a clonal origin with the primary tumour and were classified as true recurrences, whereas 4 out of 8 (50%) were classified as new primary tumours. CONCLUSION: GAMDDL analysis represents a novel and useful molecular method for examining the precise cell lineages of primary and secondary tumours, and was more accurate than HUMARA in determining clonality.

Quantitative analyses of oxidation states for cubic SrMnO(3) and orthorhombic SrMnO(2.5) with electron energy loss spectroscopy.

The oxidation state of Mn in cubic SrMnO(3) and orthorhombic SrMnO(2.5) was investigated by electron energy loss (EEL) spectroscopy. Change in the oxidation state of Mn produced some spectral changes in the O-K edge as well as in the Mn-L(2,3) edge EEL spectra. This study demonstrated that the oxidation state of Mn and the amount of oxygen vacancies in cubic SrMnO(3) and orthorhombic SrMnO(2.5) could be quantified by analyzing the features of the O-K edge spectrum and the Mn L(3)∕L(2) ratio in the Mn-L(2,3) edge spectrum. Our quantitative analysis showed that the spectral changes in the Mn-L(2,3) edge were mainly caused by the oxidation state of Mn, whereas those in the O-K edge could be sensitive to both the oxidation state of Mn and to lattice distortions.

Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies.

BACKGROUND: HER2-positive metastatic breast cancer (MBC) relapsing after trastuzumab-based therapy may require continued HER2 receptor inhibition to control the disease and preserve the patients' quality-of-life. Efficacy and safety of lapatinib monotherapy was evaluated in Japanese breast cancer patients after trastuzumab-based therapies. METHODS: In studies, EGF100642 and EGF104911 evaluated the efficacy and safety of oral lapatinib given 1500 mg once daily in patients with advanced or MBC. All patients progressed on anthracyclines and taxanes; HER2-positive patients had also progressed on trastuzumab. RESULTS: For HER2-positive tumours (n=100), objective response rate was 19.0% (95% confidence interval (CI): 11.8-28.1) and clinical benefit rate (CBR) was 25.0% (95% CI: 16.9-34.7). One out of 22 HER2-negative tumour was documented as complete response (n=22). The median time-to-progression (TTP) in the HER2-positive and HER2-negative groups was 13.0 and 8.0 weeks (P=0.007); median overall survival was 58.3 and 40.0 weeks, respectively. The most frequent adverse event was diarrhoea. TTP and CBR were significantly associated with HER2 expression. Patients with tumours harbouring an H1047R PIK3CA mutation or low expression of PTEN derived clinical benefit from lapatinib. CONCLUSION: Lapatinib monotherapy had shown anti-tumour activity in Japanese patients with HER2-positive MBC that relapsed after trastuzumab-based therapy, including those with brain metastases. Patients benefiting from lapatinib may have biomarker profiles differing from that reported for trastuzumab.

A phase II dose-ranging study of palonosetron in Japanese patients receiving moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide-based chemotherapy.

BACKGROUND: The 5-HT(3) receptor antagonists (RAs) help maintain the standard of care, in various combinations with other agents, for prevention of chemotherapy-induced nausea and vomiting (CINV). Palonosetron is a new generation 5-HT(3) RA with indication not only acute but also delayed nausea and vomiting induced by moderately emetogenic chemotherapy (MEC). This study was carried out to determine the optimal dosage of palonosetron in combination with dexamethasone in patients in Japan. PATIENTS AND METHODS: This study evaluated the efficacy and safety of palonosetron in patients receiving MEC combined with dexamethasone. Patients received single doses of 0.075, 0.25, or 0.75 mg of palonosetron before MEC. Dexamethasone was infused before palonosetron, at 20 mg for the patients receiving paclitaxel (Taxol) and 8 mg for the patients not receiving paclitaxel. The primary end point was complete response (CR: no emetic episodes and no rescue medication) in the acute phase (0-24 h). RESULTS: In total, 204 patients (88 men, 116 women; 96 with paclitaxel, 108 without paclitaxel) were assessable for efficacy. No dose-response relationship was observed regarding the CR rate in the acute phase. CR rates increased dose dependently for delayed (24-120 h) and overall (0-120 h) phases in patients receiving anthracyclines and cyclophosphamide combination (AC/EC, n = 80); however, the difference in CR rates among doses was not statistically significant. The most commonly reported adverse events related to palonosetron were constipation and headache, confirming the class safety profile. CONCLUSION: This study indicates a statistically nonsignificant trend for the dose-response relationship for antiemetic protection in the delayed and overall phases in AC/EC patients (the regimen currently considered to be more emetogenic than MEC).

PDA usage by Japanese resident physicians is low: a cross-sectional survey.

OBJECTIVES: Personal digital assistants (PDAs) are in widespread use by resident physicians in many countries, reaching as high as 95% in some reports. Uses are varied and include clinical decision support and support of evidence-based practice. Utilization by resident doctors in Japan has not been characterized. This study was conducted to determine practice patterns of PDA use by Japanese resident physicians. METHODS: A nationwide cohort survey study was distributed to all 1070 residency teaching programs in Japan. The survey included questions pertaining to use of PDAs in clinical practice. RESULTS: 1124 surveys were returned (response rate of approximately 75%). 297 (30.7%) respondents reported currently using PDAs, while 971 (86.4%) reported having used a PDA in the past. PDA users were more likely to be male (p <0.05), but no other significant differences were found when examining the following variables: age, training site (university hospital versus community teaching hospital), satisfaction with existing information technology access. CONCLUSIONS: Use of PDAs among Japanese resident physicians is much lower than their counterparts in other countries. In light of this, further research on patient outcomes in Japan and the impact of PDA usage on patient outcomes is urgently needed. If demonstrated to improve outcomes, barriers to adoption need to be identified and overcome.

Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome.

The purpose of the present study is to identify genes that contribute to cell proliferation or differentiation of breast cancers independent of signalling through the oestrogen receptor (ER) or human epidermal growth factor receptor 2 (HER2). An oligonucleotide microarray assayed 40 tumour samples from ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) breast cancer tissues. Quantitative reverse transcriptase PCR detected overexpression of a cell cycle-related transcription factor, E2F-5, in ER-negative breast cancers, and fluorescence in situ hybridisation detected gene amplification of E2F-5 in 5 out of 57 (8.8%) breast cancer samples. No point mutations were found in the DNA-binding or DNA-dimerisation domain of E2F-5. Immunohistochemically, E2F-5-positive cancers correlated with a higher Ki-67 labelling index (59.5%, P=0.001) and higher histological grades (P=0.049). E2F-5-positive cancers were found more frequently in ER(-)/progesterone receptor (PgR)(-)/HER2(-) cancer samples (51.9%, P=0.0049) and in breast cancer samples exhibiting a basal phenotype (56.0%, P=0.0012). Disease-free survival in node-negative patients with E2F-5-positive cancers was shorter than for patients with E2F-5-negative cancers. In conclusion, we identify, for the first time, a population of breast cancer cells that overexpress the cell cycle-related transcription factor, E2F-5. This E2F-5-positive breast cancer subtype was associated with an ER(-)/PgR(-)/HER2(-) status, a basal phenotype, and a worse clinical outcome.

Phasic characteristics of inspiratory crackles of bacterial and atypical pneumonia.

BACKGROUND: No known physical findings are available to differentiate between bacterial pneumonia (BP) and atypical pneumonia (AP) in patients with community-acquired pneumonia (CAP). OBJECTIVE: To evaluate the possible differences in phasic characteristics of inspiratory crackles between BP and AP in patients with CAP. METHODS: Retrospective chart reviews were conducted to obtain phasic characteristics of inspiratory crackles (early, early-to-mid, late and pan-inspiratory crackles) in AP and BP groups in a community teaching hospital in Japan (n = 183). RESULTS: 100 patients with BP and 83 patients with AP were evaluated. Patients with BP were significantly more likely to present with pan-inspiratory crackles (49 (49.0) vs 5 (6.0); p<0.0001), whereas patients with AP were more likely to present with late inspiratory crackles (28 (33.7) vs 9 (9.0); p<0.0001) (mean (SD)). Among pneumonia patients with audible crackles, the sensitivity and specificity of pan-inspiratory crackles for BP were 83.1% and 85.7%, respectively, and the sensitivity and specificity of late inspiratory crackles for AP were 80.0% and 84.7%, respectively. DISCUSSION: In patients with CAP and audible crackles, phasic characteristics of inspiratory crackles may be used to distinguish AP from BP. Prospective studies are needed to confirm these findings.