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.

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.

Preliminary External Validation Results of the Artificial Intelligence-Based Headache Diagnostic Model: A Multicenter Prospective Observational Study.

The misdiagnosis of headache disorders is a serious issue, and AI-based headache model diagnoses with external validation are scarce. We previously developed an artificial intelligence (AI)-based headache diagnosis model using a database of 4000 patients' questionnaires in a headache-specializing clinic and herein performed external validation prospectively. The validation cohort of 59 headache patients was prospectively collected from August 2023 to February 2024 at our or collaborating multicenter institutions. The ground truth was specialists' diagnoses based on the initial questionnaire and at least a one-month headache diary after the initial consultation. The diagnostic performance of the AI model was evaluated. The mean age was 42.55 ± 12.74 years, and 51/59 (86.67%) of the patients were female. No missing values were reported. Of the 59 patients, 56 (89.83%) had migraines or medication-overuse headaches, and 3 (5.08%) had tension-type headaches. No one had trigeminal autonomic cephalalgias or other headaches. The models' overall accuracy and kappa for the ground truth were 94.92% and 0.65 (95%CI 0.21-1.00), respectively. The sensitivity, specificity, precision, and F values for migraines were 98.21%, 66.67%, 98.21%, and 98.21%, respectively. There was disagreement between the AI diagnosis and the ground truth by headache specialists in two patients. This is the first external validation of the AI headache diagnosis model. Further data collection and external validation are required to strengthen and improve its performance in real-world settings.

Reliability and validity of the Japanese version of the Chemotherapy-induced Alopecia Distress Scale.

BACKGROUND: The Chemotherapy-induced Alopecia Distress Scale (CADS) is a patient-reported outcome measure for assessing distress associated with Chemotherapy-induced alopecia (CIA). This study aimed to confirm the psychometric validity of the Japanese version of the CADS (CADS-J). METHODS: A total of 132 patients with breast cancer who developed CIA were asked to complete the CADS-J twice at 2 week intervals to confirm test-retest reliability. The body image domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) breast cancer-specific module, the self-esteem scale from the Rosenberg Self-Esteem Scale, and the emotional domain of the EORTC QLQ Core 30 were used to confirm the convergent validity of the CADS-J. The overall quality of life and physical domains of the EORTC QLQ Core 30 were used to confirm the discriminant validity of the CADS-J. RESULTS: In total, 125 participants provided valid responses. The mean age was 52.2 years. The overall Cronbach's alpha for the CADS-J was 0.903. The intraclass correlation coefficients of the first and second responses were r = 0.874, r = 0.952, r = 0.911, and r = 0.959 for the physical domain, emotional domain, activity domain, and relationship domain, respectively. In terms of convergent validity, the total CADS-J score was moderately correlated with body image (r = - 0.63), self-esteem (r = - 0.48), and the emotional domain (r = - 0.61). Regarding discriminant validity, the total CADS-J score was weakly correlated with the overall quality of life (r = - 0.34) and physical domain (r = - 0.24). CONCLUSIONS: The CADS-J is psychometrically reliable and valid for evaluating the distress caused by CIA. It is expected to be used in daily practice and as an endpoint in various studies.

Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease.

BACKGROUND: Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD. METHODS: A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204). RESULTS: Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = -0.275) and Hb (P < 0.005, r = -0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = -0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = -0.148). CONCLUSION: Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.

Development of a Model for Quantitative Assessment of Newborn Screening in Japan Using the Analytic Hierarchy Process.

Whether or not conditions should be included in publicly funded newborn screening (NBS) programs should be discussed according to objective and transparent criteria. Certain criteria have been developed for the introduction of NBS programs in the context of individual countries; however, there are no standard selection criteria for NBS programs in Japan. This study aimed to develop a quantitative scoring model to assess newborn screening that incorporates the views of a variety of stakeholders in Japan. The five recommended eligibility criteria for NBS were stratified based on previous studies and expert opinions, using the analytic hierarchy process. We conducted a cross-sectional, web-based questionnaire targeting a wide range of people involved in NBS to investigate pairwise comparisons of the evaluation items between February and April of 2022. There were 143 respondents. Most of our respondents (44.1%) were physicians. Fifty-eight respondents (40.6%) had been engaged in NBS-related research or work for more than 10 years. The distribution of allocation points was the highest for 'intervention', 'screening test', 'follow-up setting', 'economic evaluation', and 'disease/condition', in that order. The algorithm in this study will guide decision makers in collecting and evaluating objective data, thus enabling transparent discussions to occur.