Real-world experience with calcitonin gene-related peptide-targeted antibodies for migraine prevention: a retrospective observational cohort study at two Japanese headache centers.

BACKGROUND: Although randomized controlled trials (RCTs) have shown that calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (CGRP mAbs) are an efficacious and safe therapeutic modality for migraine prevention, their clinical benefits have not been well validated in Japanese patients in the real-world setting. The present study aimed to evaluate the real-world efficacy and safety of galcanezumab, fremanezumab, and erenumab in Japanese patients with migraine. METHODS: This observational retrospective cohort study was conducted at two headache centers in Japan. Patients with migraine who had experienced treatment failure with at least one traditional oral migraine preventive agent were treated with a CGRP mAb de novo. The primary efficacy endpoints were the changes from baseline in monthly migraine days (MMDs) and Headache Impact Test-6 (HIT-6) score after 3 dosing intervals (V3). We explored whether demographic and clinical characteristics predicted therapeutic outcomes at V3. RESULTS: Sixty-eight patients who completed three doses of a CGRP mAb (85.3% female [58/68], mean age: 46.2 ± 13.1 years) were included in the analysis. There were 19 patients with chronic migraine. The baseline MMDs were 13.4 ± 6.0. After 3 doses, the MMDs significantly decreased to 7.4 ± 5.5 (p < 0.0001), and the 50% response rate was 50.0%. HIT-6 score was significantly reduced from 66.7 ± 5.4 to 56.2 ± 8.7 after 3 doses (P = 0.0001). There was a positive correlation between the changes in MMDs and HIT-6 score from baseline after 2 doses (p = 0.0189). Those who achieved a ≥ 50% therapeutic response after the first and second doses were significantly more likely to do so at V3 (crude odds ratio: 3.474 [95% CI: 1.037 to 10.4], p = 0.0467). The most frequent adverse event was constipation (7.4%). None of the adverse events were serious, and there was no need for treatment discontinuation. CONCLUSIONS: This real-world study demonstrated that CGRP mAbs conferred Japanese patients with efficacious and safe migraine prevention, and an initial positive therapeutic response was predictive of subsequent favorable outcomes. Concomitant measurement of MMDs and HIT-6 score was useful in evaluating the efficacy of CGRP mAbs in migraine prevention.

Comparison of four value sets derived using different TTO and DCE approaches: application to the new region-specific PBM, AP-7D.

BACKGROUND: AP-7D is a newly developed preference-based measure (PBM) in East and Southeast Asia. However, no value set has been established yet. Comparison of the characteristics of value sets obtained by different methods is necessary to consider the most appropriate methodology for valuation survey of AP-7D. METHOD: We surveyed the general population's preference of AP-7D health states by four valuation methods (a) composite time trade-off (cTTO); (b) simple discrete choice experiment (DCE); (c) DCE with duration; and (d) ternary DCE. In Japan, we collected approximately 1,000 samples for cTTO tasks through a face-to-face survey and 2,500 samples for each of the three DCE tasks. Respondents were selected through quota sampling based on the sex and age. The cTTO data were analyzed using a linear mixed and tobit model; the DCE data were analyzed using a simple and panel conditional logit model. Where the results of the analysis showed inconsistencies, a constrained model was used. RESULTS: Since all the unconstrained models, except simple DCE, showed one or more inconsistencies, the constrained model was used for the analyses. The minimum values for the models were as follows: TTO model, -0.101; simple DCE model, -0.106; DCE with duration model, -0.706; ternary DCE model, -0.306. The score for the DCE with the duration model was much lower than that for the other models. Although the value sets for AP-7D differed among the four valuation methods, the ternary DCE model showed intermediate characteristics between those of the cTTO and DCE with duration models. As compared with to EQ-5D-5L, the distributions of all the scores on the Japanese AP-7D moved to the left. Although "Energy" was one of the domains with the least influence on the AP-7D score in all four models, "Burden to others" had the largest impact on the preferences. CONCLUSION: We constructed four value sets using different TTO and DCE methods. Our findings are expected not only to contribute to the development of AP-7D, but also other preference-based measures.

Health-related quality of life and caregiver burden of pediatric patients with inborn errors of metabolism in Japan using EQ-5D-Y, PedsQL, and J-ZBI.

PURPOSE: Inborn errors of metabolism (IEM) are known with poor long-term health concerns; however, the health-related quality of life (HRQoL) and the burden placed on families remain unclear. This study investigated the self- and proxy-reported HRQoL of pediatric patients with IEM with or without developmental disabilities and the burden placed on their caregivers. METHODS: Patients with IEM aged 8-15 years and their caregivers were asked to respond to the Pediatric Quality of Life Inventory (PedsQL), EuroQoL five-dimension questionnaire for younger populations (EQ-5D-Y), and Japanese version of the Zarit Caregiver Burden Interview (J-ZBI). We compared EQ-5D-Y scores with matched EQ-5D-Y population norms. Intraclass correlation coefficients (ICC) for self and proxy HRQoL scores of those without developmental disabilities were calculated. Correlation coefficients of HRQoL proxy responses with J-ZBI score were estimated. RESULTS: We included 66 patients with IEM (mean age, 11.5 years; males, 41.2%) in the study. The mean (± standard deviation) EQ-5D-Y scores without and with developmental disabilities were 0.957 (± 0.071) and 0.821 (± 0.175), respectively. The EQ-5D-Y scores significantly increased compared with the reference values (p < 0.01, effect size = 0.337). The ICC values were 0.331 and 0.477 for the EQ-5D-Y and PedsQL scores, respectively. HRQoL proxy scores had strong negative correlations with J-ZBI scores. CONCLUSION: The HRQoL of patients with IEM without developmental disabilities in our study was similar to that of the general Japanese population. The HRQoL of patients with IEM with developmental disabilities was low and associated with a tendency towards an increased burden of care.

Nutritional therapy for reducing disability and improving activities of daily living in people after stroke.

BACKGROUND: Stroke patients often face disabilities that significantly interfere with their daily lives. Poor nutritional status is a common issue amongst these patients, and malnutrition can severely impact their functional recovery post-stroke. Therefore, nutritional therapy is crucial in managing stroke outcomes. However, its effects on disability, activities of daily living (ADL), and other critical outcomes have not been fully explored. OBJECTIVES: To evaluate the effects of nutritional therapy on reducing disability and improving ADL in patients after stroke. SEARCH METHODS: We searched the trial registers of the Cochrane Stroke Group, CENTRAL, MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), and AMED (from 1985) to 19 February 2024. We also searched trials and research registries (ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform) and reference lists of articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared nutritional therapy with placebo, usual care, or one type of nutritional therapy in people after stroke. Nutritional therapy was defined as the administration of supplemental nutrients, including energy, protein, amino acids, fatty acids, vitamins, and minerals, through oral, enteral, or parenteral methods. As a comparator, one type of nutritional therapy refers to all forms of nutritional therapies, excluding the specific nutritional therapy defined for use in the intervention group. DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to assess the initial search results. Two review authors independently screened references that met the inclusion criteria, extracted data, and assessed the risk of bias and the certainty of the evidence using the GRADE approach. We calculated the mean difference (MD) or standardised mean difference (SMD) for continuous data and the odds ratio (OR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. The primary outcomes were disability and ADL. We also assessed gait, nutritional status, all-cause mortality, quality of life, hand and leg muscle strength, cognitive function, physical performance, stroke recurrence, swallowing function, neurological impairment, and the development of complications (adverse events) as secondary outcomes. MAIN RESULTS: We identified 52 eligible RCTs involving 11,926 participants. Thirty-six studies were conducted in the acute phase, 10 in the subacute phase, three in the acute and subacute phases, and three in the chronic phase. Twenty-three studies included patients with ischaemic stroke, three included patients with haemorrhagic stroke, three included patients with subarachnoid haemorrhage (SAH), and 23 included patients with ischaemic or haemorrhagic stroke including SAH. There were 25 types of nutritional supplements used as an intervention. The number of studies that assessed disability and ADL as outcomes were nine and 17, respectively. For the intervention using oral energy and protein supplements, which was a primary intervention in this review, six studies were included. The results for the seven outcomes focused on (disability, ADL, body weight change, all-cause mortality, gait speed, quality of life, and incidence of complications (adverse events)) were as follows: There was no evidence of a difference in reducing disability when 'good status' was defined as an mRS score of 0 to 2 (for 'good status': OR 0.97, 95% CI 0.86 to 1.10; 1 RCT, 4023 participants; low-certainty evidence). Oral energy and protein supplements may improve ADL as indicated by an increase in the FIM motor score, but the evidence is very uncertain (MD 8.74, 95% CI 5.93 to 11.54; 2 RCTs, 165 participants; very low-certainty evidence). Oral energy and protein supplements may increase body weight, but the evidence is very uncertain (MD 0.90, 95% CI 0.23 to 1.58; 3 RCTs, 205 participants; very low-certainty evidence). There was no evidence of a difference in reducing all-cause mortality (OR 0.57, 95% CI 0.14 to 2.28; 2 RCTs, 4065 participants; low-certainty evidence). For gait speed and quality of life, no study was identified. With regard to incidence of complications (adverse events), there was no evidence of a difference in the incidence of infections, including pneumonia, urinary tract infections, and septicaemia (OR 0.68, 95% CI 0.20 to 2.30; 1 RCT, 42 participants; very low-certainty evidence). The intervention was associated with an increased incidence of diarrhoea compared to usual care (OR 4.29, 95% CI 1.98 to 9.28; 1 RCT, 4023 participants; low-certainty evidence) and the occurrence of hyperglycaemia or hypoglycaemia (OR 15.6, 95% CI 4.84 to 50.23; 1 RCT, 4023 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain about the effect of nutritional therapy, including oral energy and protein supplements and other supplements identified in this review, on reducing disability and improving ADL in people after stroke. Various nutritional interventions were assessed for the outcomes in the included studies, and almost all studies had small sample sizes. This led to challenges in conducting meta-analyses and reduced the precision of the evidence. Moreover, most of the studies had issues with the risk of bias, especially in terms of the absence of blinding and unclear information. Regarding adverse events, the intervention with oral energy and protein supplements was associated with a higher number of adverse events, such as diarrhoea, hyperglycaemia, and hypoglycaemia, compared to usual care. However, the quality of the evidence was low. Given the low certainty of most of the evidence in our review, further research is needed. Future research should focus on targeted nutritional interventions to reduce disability and improve ADL based on a theoretical rationale in people after stroke and there is a need for improved methodology and reporting.

How to select and understand guidelines for patient-reported outcomes: a scoping review of existing guidance.

BACKGROUND: Over the past few decades, patient-reported outcomes (PROs) have been used to understand patient health conditions better. Therefore, numerous PRO measures (questionnaires) and guidelines or guidance have been developed. However, it is challenging to select target guidance from among the many available guidance and to understand the chosen guidance. This study comprehensively collected the existing PRO guidance for clinical trials or studies and practices to support novice PRO users in academia, industry, clinical practice, and regulatory and reimbursement decision-making. METHODS: For the scoping review, we searched the MEDLINE, Embase, Google Books, WorldCat, and the National Library of Medicine (NLM) Bookshelf databases from 2009 to 2023. The eligibility criteria were PRO guidance for clinical trials, clinical practice, or application such as health technology assessment. Those guidance cover aspects such as quality of life (QOL), PRO, health-related QOL, health state utilities, psychometric requirements, implementation methods, analysis and interpretation, or clinical practice applications. After the systematic search, three researchers individually reviewed the collected data, and the reviewed articles and books were scrutinized using the same criteria. RESULTS: We collected the PRO guidance published in articles and books between 2009 and 2023. From the database searches, 1,455 articles and 387 books were identified, of which one book and 33 articles were finally selected. The collected PRO guidance was categorized into the adoption of PRO measures, design and reporting of trials or studies using PROs, implementation of PRO evaluation in clinical trials or studies or clinical practice, analysis and interpretation of PROs, and application of PRO evaluation. Based on this categorization, we suggest the following for novices: When selecting guidance, novices should clarify the "place" and "purpose" where the guidance will be used. Additionally, they should know that the terminology related to PRO and the scope and expectations of PROs vary by "places" and "purposes". CONCLUSIONS: From this scoping review of existing PRO guidance, we provided summaries and caveats to assist novices in selecting guidance that fits their purpose and understanding it.

Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.

OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting. STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty. RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening. CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.

Age at surgery and native liver survival in biliary atresia: a systematic review and meta-analysis.

Biliary atresia (BA) is a childhood rare disease of the liver and bile ducts that requires prompt surgical intervention. Age at surgery is an important prognostic factor; however, controversy exists with regard to the benefit of early Kasai procedure (KP). We aimed to conduct a systematic review and meta-analysis to examine the relationship between the age at KP and native liver survival (NLS) of BA patients. We performed the electronic database search using Pubmed, EMBASE, Cochrane, and Ichushi Web and included all relevant studies published from 1968 up to May 3, 2022. Studies that examined the timing of KP at ages 30, 45, 60, 75, 90, 120, and/or 150 days were included. The outcome measures of interest were NLS rates at 5, 10, 15, 20, and 30 years post-KP and the hazard ratio or risk ratio for NLS. The quality assessment was used using the ROBINS-I tool. Among 1653 potentially eligible studies, nine articles met the inclusion criteria for the meta-analysis. Meta-analysis for hazard ratios revealed that there was a significantly faster time to liver transplantation in the group of patients who had KP at later timing as compared with earlier KP (HR = 2.12, 95% CI 1.51-2.97). The risk ratio comparing KP ≤ 30 days and KP ≥ 31 days on native liver survival was 1.22 (95% CI 1.13-1.31). The sensitivity analysis showed that comparing KP ≤ 30 days and KP 31-60 days, the risk ratio was 1.13, 95% CI 1.04-1.22.  Conclusion: Our meta-analysis showed the importance of early diagnosis and surgical interventions ideally before 30 days of life in infants with BA on native liver survival on 5, 10, and 20 years. Therefore, effective newborn screening of BA targeting KP ≤ 30 days is needed to ensure prompt diagnosis of affected infants. What is Known: • Age at surgery is an important prognostic factor. What is New: • Our study performed an updated systematic review and meta-analysis to examine the relationship between age at Kasai procedure and native liver survival in patients with BA.

Strategies for cost-effectiveness analysis of rehabilitation for older patients with acute heart failure.

The prevalence of heart failure (HF) is increasing in the ageing world population, and its burden on the medical and health economic fields is enormous. Rehabilitation is an essential component of the nonpharmacological treatment of patients with HF; however, its efficacy and cost-effectiveness for patients with acute HF remain unclear. A trial assessed the cost-effectiveness of acute cardiac rehabilitation among older adults. Herein, we discussed strategies for the cost-effectiveness analysis of acute cardiac rehabilitation using the rehabilitation therapy in older acute heart failure patients trial.

Direct health care cost of treatment and medication of biliary atresia patients using the National Database of Health Insurance Claims and Specific Health Checkups.

BACKGROUND: Treatment of biliary atresia (BA), which typically requires an initial surgical intervention called the Kasai procedure (KP) and possible liver transplant (LT) afterwards, is quite resource-intensive and would affect patients and families for a lifetime; yet a comprehensive view of the economic burden has not been reported. We estimated direct health care costs from the public payer perspective using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. METHODS: Children newly diagnosed at ages 0 days to 4 years between April 2010 and September 2019 were identified. Costs of treatment were estimated for six phases of care: prediagnosis, KP and inpatient hospitalization, follow-up after KP, pre-transplant checkup, LT and inpatient hospitalization, and follow-up after LT. RESULTS: Mean total prediagnosis medical cost was $6847 (USD) and KP and inpatient hospitalization was $42,157 per year. Follow-up after KP was $15,499, and pre-transplant checkup after KP was $36,015 per year. Mean cost for LT and inpatient hospitalization was $105,334, and follow-up after liver transplant was $25,459 per year. CONCLUSIONS: Treatment of BA requires extensive medical resource consumption. The use of the comprehensive national database allowed us to estimate the costs which will be useful for health service planning and cost-effectiveness analysis.

A Cost Projection of Scheduled Physician Home-Visit Services in Japan: 2014 to 2064.

This study predicts the volume and spending on scheduled physician home-visit (SPHV) services over five decades. This model-based evaluation study considered the following scenarios in Japan: (1) change in services-delivery; (2) technology-assisted services; (3) a combination of (1) and (2). The model predicted that the volume and spending on SPHV will increase as the population and working-age population decline. Scenario analysis indicated that a combined strategy could reduce the relative rate of spending to less than 2.00 in 2064, indicating that home health-care service reforms through changes in services-delivery and cost-reduction through technology-assisted services are promising in countries facing aging population.

Variation in somatic symptoms by patient health questionnaire-9 depression scores in a representative Japanese sample.

BACKGROUND: This study aims to evaluate variation in somatic symptoms by age using patient health questionnaire-9 (PHQ) depression scores, which may be helpful in identifying depression. METHODS: The study evaluated a nationally representative cross-sectional sample of community-dwelling adults in Japan in 2013. We utilized the PHQ to identify risk for depression, with PHQ ≥ 10 defining at least moderate depression. Bivariate and factor analyses were used to capture underlying patterns in self-reported symptoms over a 30 day period; aged-stratified multivariate logistic regression was performed to further explore associations between age, symptoms, and depression. RESULTS: Of 3753 respondents, 296 (8, 95% CI 7.0-8.8) reported a PHQ ≥ 10; 42% of these were male and mean age was 51.7 years old (SD = 18.6). Multivariate analysis showed that presence of fatigue and malaise (OR = 1.7, 95% CI 1.3-2.4) was significantly associated with PHQ ≥ 10. After stratification by age, PHQ ≥ 10 was associated with gastrointestinal complaints among 18-39 year olds (OR = 1.7, 95% CI 1.0-2.9); fatigue and malaise (OR = 1.8, 95% CI 1.1-3.1) among 40-64 year olds; and fatigue and malaise (OR = 1.8, 95% CI 1.1-3.0) as well as extremity pain (OR = 1.7, 95% CI 1.0-2.8) in over 65 year olds. CONCLUSION: Age-related somatic symptom correlates of PHQ ≥ 10 differ across the lifespan. Predominantly gastrointestinal symptoms in younger patients, and generalized fatigue, malaise, and musculoskeletal pain in older groups were observed. In order for screening physicians to proactively identify depression, awareness of age-related somatic symptoms is warranted.

Reassessing the Ecology of Medical Care in Japan.

Studies on ecology of medical care can provide valuable information on how people seek healthcare in a specific geographic area. The objective of this study was to update a 2003 report on the ecology of medical care in Japan, identifying relevant changes in healthcare patterns. We collected information based on a prospective health diary recorded for a month in 2013 (n = 4548; 3787 adults and 797 children) using a population-weighted random sample from a nationally representative panel. We compared our overall and stratified findings with a similar study conducted in 2003. During a one-month period, per 1000 adults and children living in Japan, we estimated that 794 report at least one symptom, 447 use an over-the-counter (OTC) drug, 265 visit a physician's office, 117 seek help from a professional provider of complementary or alternative medicine (CAM), 70 visit a hospital outpatient clinic (60 community-based and 10 university-based), 6 are hospitalized, and 4 visit a hospital emergency department. After adjusting for demographic variables, we found that healthcare seeking behaviors were influenced by age, gender and area of living. Compared with the 2003 study, participants in this study had fewer symptoms, fewer physician and emergency room visits, and less OTC use, but reported higher frequency of CAM use (p < .01 for all). Compared with 2003, reported symptoms, physician visits and OTC use has decreased, while CAM use has increased. Our findings may be useful to policymakers in Japan in a context where healthcare expenditure and a rapidly aging population are two challenging issues.

An iPhone application using a novel stool color detection algorithm for biliary atresia screening.

BACKGROUND: The stool color card has been the primary tool for identifying acholic stools in infants with biliary atresia (BA), in several countries. However, BA stools are not always acholic, as obliteration of the bile duct occurs gradually. This study aims to introduce Baby Poop (Baby unchi in Japanese), a free iPhone application, employing a detection algorithm to capture subtle differences in colors, even with non-acholic BA stools. METHODS: The application is designed for use by caregivers of infants aged approximately 2 weeks-1 month. Baseline analysis to determine optimal color parameters predicting BA stools was performed using logistic regression (n = 50). Pattern recognition and machine learning processes were performed using 30 BA and 34 non-BA images. Additional 5 BA and 35 non-BA pictures were used to test accuracy. RESULTS: Hue, saturation, and value (HSV) were the preferred parameter for BA stool identification. A sensitivity and specificity were 100% (95% confidence interval 0.48-1.00 and 0.90-1.00, respectively) even among a collection of visually non-acholic, i.e., pigmented BA stools and relatively pale-colored non-BA stools. CONCLUSIONS: Results suggest that an iPhone mobile application integrated with a detection algorithm is an effective and convenient modality for early detection of BA, and potentially for other related diseases.

Application of High-Pressure Treatment to Enhancement of Functional Components in Agricultural Products and Development of Sterilized Foods.

In 1988, the late Prof. Rikimaru Hayashi had first proposed "Use of High Pressure in Food", introducing his views, i.e., "heat and pressure are independently capable of transforming the state of a substance, and such state transforming factors are only heat and pressure in nature." Sc. D. Masaru Nakahara stated in his note that he had been impressed by the unique starting point of Prof. Hayashi's idea. Prof. Hayashi had explored some good method for food processing without using heat, so he alternatively thought of high-pressure treatment (Hayashi R (1989) Use of high pressure to food processing and preservation. In: Hayashi R (ed) Use of high pressure in food. San-Ei Publishing Co, Kyoto, pp 1-30; Nakahara M (1990) Water and ions at high pressure: their fundamental properties relevant to the pressure treatment to food. In: Hayashi R (ed) Pressure-processed food--research and development. San-Ei Publishing Co, Kyoto, pp 3-21). Since the start-up of Japanese research group of high pressure in biological field (the present "Japanese Research Group of High Pressure Bioscience and Biotechnology (JHPBB)") and "International Association of High Pressure Bioscience and Biotechnology (IAHPBB)", we have continued to research into the industrial use of high-pressure treatment over a period of 25 years to realize our dream, that is, the same as Prof. Hayashi's dream. Although heat and pressure were found to be independent factors capable of transforming the state of a substance, use of heat has been overwhelmingly more frequent in food processing up to now. However, the pressure treatment has the advantages of instantaneous transmission, uniform distribution in vessels, and ability of inducing uniform change in quality. The high-pressure treatment does not cause cleavage of the covalent bond in the substance, thereby lessening the decomposition of nutrients, the generation of offensive smell, and the production of abnormal materials when compared with the heat application. In addition, energy consumption in the high-pressure treatment is less than that in the heat treatment. For the reasons mentioned above, the high-pressure treatment has thus been regarded as suitable for future food processing, and much attention has been paid to the researches of high-pressure treatment again. Then, we reviewed the previous researches in which little interest had been taken because of imperfectness of non-heat sterilization. Surprisingly, we discovered some novel findings about the effect of high-pressure treatment, that is, pressure history on the subsequent event. Then, we decided to present two theses on the themes, "Application of High-pressure Treatment to Enhancement of Functional Components in Agricultural Products" and "Application of High-pressure Treatment to Development of Sterilized Foods".

An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation.

We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked-in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation-dependent transactivation response DNA-binding protein of 43 kDa (pTDP-43)-positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin- and p62-positive inclusions was markedly lower than that of pTDP-43-positive inclusions. NCIs and many fine dot-like pTDP-43-positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti-pTDP-43 antibody was slightly different from previous TDP-43 pathological subtypes.

Donepezil can improve ischemic muscle atrophy by activating angiomyogenic properties of satellite cells.

BACKGROUND: Saving more limbs of patients with peripheral arterial disease (PAD) from amputation by accelerating angiogenesis in affected limbs has been anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil (DPZ), can activate angiomyogenic properties of satellite cells, myogenic progenitors, and thus be an additional pharmacological therapy against PAD. METHODS AND RESULTS: In a murine hindlimb ischemia model, we investigated the angiogenic effects of a clinical dose of DPZ (0.2 mg·kg(-1)·day(-1)) and its combination with cilostazol, a platelet aggregation inhibitor and a conventional therapeutic drug against PAD. The combination therapy most effectively improved skin coldness and most effectively upregulated vascular endothelial growth factor (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super-restoration in affected hindlimbs. The in vitro study with human aortic endothelial cells showed that DPZ or its combination with cilostazol effectively upregulated the expression of pAkt, hypoxia inducible factor-1α, and VEGF protein. Likewise, in primary cultured satellite cells, DPZ, alone or in combination, upregulated the expression of VEGF, interleukin-1ß, and fibroblast growth factor 2 protein. CONCLUSIONS: The present results suggest that a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both endothelial and satellite cells. Therefore, DPZ is a potential additional choice for conventional drug therapy against PAD.

Loop-mediated isothermal amplification method for diagnosing Pneumocystis pneumonia in HIV-uninfected immunocompromised patients with pulmonary infiltrates.

Loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We retrospectively evaluated 78 consecutive HIV-uninfected patients who underwent LAMP method for diagnosing Pneumocystis pneumonia (PCP). Diagnosis of PCP was made by the detection of Pneumocystis jirovecii (P. jirovecii) with positive LAMP or conventional staining (CS) (Grocott methenamine silver staining or Diff-Quick™) on the basis of compatible clinical symptoms and radiologic findings. Additionally, we reviewed HIV-uninfected immunocompromised patients who underwent subcontract PCR as a historical control. LAMP was positive in 10 (90.9%) of 11 positive-CS patients. Among 13 negative-CS patients with positive LAMP, 11 (84.6%) had PCP, and the remaining 2 were categorized as having P. jirovecii colonization. LDH levels in negative-CS PCP were higher than in positive-CS PCP (p = 0.026). (1 → 3)-ß-D-glucan levels in negative-CS PCP were lower than in positive-CS PCP (p = 0.011). The interval from symptom onset to diagnosis as PCP in LAMP group (3.45 ± 1.77 days; n = 22) was shorter than in subcontract PCR group (6.90 ± 2.28 days; n = 10; p < 0.001). As for patients without PCP, duration of unnecessary PCP treatment in LAMP group (2; 2-3 days; n = 10) was shorter than in subcontract PCR group (7; 7-12.25 days; n = 6; p = 0.003). LAMP showed higher sensitivity (95.4%) and positive predictive value (91.3%) than subcontract PCR did. Pneumocystis LAMP method is a sensitive and cost-effective diagnostic method and is easy to administer in general hospitals. In-house LAMP method would realize early diagnosis of PCP, resulting in improving PCP prognosis and reducing unnecessary PCP-specific treatment.

A large benign struma ovarii with atypical imaging findings.

Struma ovarii is a mature ovarian teratoma characterized by the predominant presence of thyroid-tissue components. Typically, struma ovarii presents as relatively small masses (<10 cm) that often appear as multilocular cystic tumors with solid components. Herein, we report the unique case of a 44-year-old female with a large tumor including a solid mass. The solid components of the tumor comprised typical thyroid tissues with multiple small cystic structures containing colloid-like material. Given the rarity of struma ovarii, atypical imaging features can sometimes be misleading. This article highlights the unusual magnetic resonance imaging characteristics of a large struma ovarii, with a specific focus on the presence of solid components.

Association of oral hypofunction with aspiration pneumonia, fractures, and mortality in older Japanese adults.

AIM: In Japan's public health system, dentists can assess and intervene in oral hypofunction cases. However, the associations between oral hypofunction and health outcomes and costs remain unclear. This study aimed to identify these associations. METHODS: This retrospective cohort study using a Japanese health insurance claims database included 45 916 individuals aged ≥65 years who underwent dental examinations for oral hypofunction. The primary outcomes were incidence rates of aspiration pneumonia, femoral or vertebral fractures and all-cause mortality. Secondary outcomes were annual medical and dental costs. We used competing risk regression and Cox models to estimate primary outcomes, and gamma regression models for secondary outcomes. RESULTS: The adjusted hazard ratios were 0.84 (95% CI 0.74-0.96) for the incidence of aspiration pneumonia, 1.11 (1.02-1.21) for the incidence of femoral or vertebral fractures and 1.27 (1.07-1.50) for all-cause mortality in individuals with oral hypofunction compared with those without. The adjusted relative risk was 1.05 (1.01-1.10) for annual medical costs and 0.94 (0.81-1.09) for annual dental costs in individuals with oral hypofunction compared with those without. CONCLUSIONS: Individuals with oral hypofunction were at increased risk of femoral or vertebral fractures and all-cause mortality, and they incurred significantly higher annual medical costs, compared with those without this condition. Notably, they showed a lower risk of aspiration pneumonia, suggesting potential benefits of dental intervention. Integrating dental care into medical strategies might be necessary to improve health outcomes and reduce healthcare costs for those with oral hypofunction. Geriatr Gerontol Int 2024; 24: 1053-1059.