Assessment of antibody dynamics and neutralizing activity using serological assay after SARS-CoV-2 infection and vaccination.

The COVID-19 antibody test was developed to investigate the humoral immune response to SARS-CoV-2 infection. In this study, we examined whether S antibody titers measured using the anti-SARS-CoV-2 IgG II Quant assay (S-IgG), a high-throughput test method, reflects the neutralizing capacity acquired after SARS-CoV-2 infection or vaccination. To assess the antibody dynamics and neutralizing potency, we utilized a total of 457 serum samples from 253 individuals: 325 samples from 128 COVID-19 patients including 136 samples from 29 severe/critical cases (Group S), 155 samples from 71 mild/moderate cases (Group M), and 132 samples from 132 health care workers (HCWs) who have received 2 doses of the BNT162b2 vaccinations. The authentic virus neutralization assay, the surrogate virus neutralizing antibody test (sVNT), and the Anti-N SARS-CoV-2 IgG assay (N-IgG) have been performed along with the S-IgG. The S-IgG correlated well with the neutralizing activity detected by the authentic virus neutralization assay (0.8904. of Spearman's rho value, p < 0.0001) and sVNT (0.9206. of Spearman's rho value, p < 0.0001). However, 4 samples (2.3%) of S-IgG and 8 samples (4.5%) of sVNT were inconsistent with negative results for neutralizing activity of the authentic virus neutralization assay. The kinetics of the SARS-CoV-2 neutralizing antibodies and anti-S IgG in severe cases were faster than the mild cases. All the HCWs elicited anti-S IgG titer after the second vaccination. However, the HCWs with history of COVID-19 or positive N-IgG elicited higher anti-S IgG titers than those who did not have it previously. Furthermore, it is difficult to predict the risk of breakthrough infection from anti-S IgG or sVNT antibody titers in HCWs after the second vaccination. Our data shows that the use of anti-S IgG titers as direct quantitative markers of neutralizing capacity is limited. Thus, antibody tests should be carefully interpreted when used as serological markers for diagnosis, treatment, and prophylaxis of COVID-19.

Assessment of pulmonary artery size at birth as a prognostic factor in congenital diaphragmatic hernia: results of a multicenter study in Japan.

OBJECTIVE: To assess the reliability of pulmonary artery (PA) parameters as a prognostic marker in neonates with isolated left-sided congenital diaphragmatic hernia (IL-CDH). STUDY DESIGN: A retrospective cohort study conducted by the Japanese CDH Study Group (JCDHSG). RESULTS: 323 IL-CDH patients registered with the JCDHSG were included. 272 patients survived to 90 days of age. Right PA (RPA) and left PA (LPA) diameters and pulmonary artery index (PAIndex) at birth were significantly larger in survivors. The cutoff values of RPA and LPA diameters and PAIndex for survival up to 90 days were 3.2 mm, 2.8 mm and 83.7, respectively, and logistic regression analysis showed that these were significantly related to survival. Multiple logistic regression analysis showed that both the PA parameters and liver herniation were significantly related to survival. CONCLUSIONS: The three PA parameters at birth can predict clinical outcomes and are considered as independent risk factors of liver herniation.

Performance evaluation of the Ortho VITROS SARS-CoV-2 Spike-Specific Quantitative IgG test by comparison with the surrogate virus neutralizing antibody test and clinical assessment.

BACKGROUND: Despite the worldwide campaigns of COVID-19 vaccinations, the pandemic is still a major medical and social problem. The Ortho VITROS SARS-CoV-2 spike-specific quantitative IgG (VITROS S-IgG) assay has been developed to assess neutralizing antibody (NT antibody) against SARS-CoV-2 spike (S) antibodies. However, it has not been evaluated in Japan, where the total cases and death toll are lower than the rest of the world. METHODS: The clinical performance of VITROS S-IgG was evaluated by comparing with the NT antibody levels measured by the surrogate virus neutralizing antibody test (sVNT). A total of 332 serum samples from 188 individuals were used. Of these, 219 samples were from 75 COVID-19 patients: 96 samples from 20 severe/critical cases (Group S), and 123 samples from 55 mild/moderate cases (Group M). The remaining 113 samples were from 113 healthcare workers who had received 2 doses of the BNT162b2 vaccine. RESULTS: VITROS S-IgG showed good correlation with the cPass sVNT assay (Spearman rho = 0.91). Both VITROS S-IgG and cPass sVNT showed significantly higher plateau levels of antibodies in Group S compared to Group M. Regarding the humoral immune responses after BNT162b2 vaccination, individuals who were negative for SARS-CoV-2 nucleocapsid (N)-specific antibodies had statistically lower titers of both S-IgG and sVNT compared to individuals with a history of COVID-19 and individuals who were positive for N-specific antibodies without history of COVID-19. In individuals who were positive for N-specific antibodies, S-IgG and sVNT titers were similar to individuals with a history of COVID-19. CONCLUSIONS: Although the automated quantitative immunoassay VITROS S-IgG showed a reasonable correlation with sVNT antibodies, there is some discrepancy between Vitros S-IgG and cPass sVNT in milder cases. Thus, VITROS S-IgG can be a useful diagnostic tool in assessing the immune responses to vaccination and herd immunity. However, careful analysis is necessary to interpret the results.

Projected numbers of knee and hip arthroplasties up to the year 2030 in Japan.

BACKGROUND: The aging population is a risk factor for an increase in osteoarthritis, leading to a potential increase in the number of arthroplasties worldwide. This study aimed to calculate the projected numbers of knee and hip arthroplasties in Japan until 2030 using national health insurance claim data. METHODS: Data on the numbers of knee and hip arthroplasties performed in Japan between 2014 and 2018 were obtained from the National Database of Health Insurance Claims and Specific Health Checkups of Open Data Japan. Demographic data were obtained from the National Institute of Population and Social Security Research. Collected data were categorized into three age subgroups (40-64, 65-74, and ≥75 years) for each sex. Projections were based on the Poisson regression model. RESULTS: The number of knee arthroplasties in Japan in 2030 was projected to be 4052 for men aged 40-64 years, 6942 for men aged 65-74 years, 14,986 for men aged ≥75 years, 7092 for women aged 40-64 years, 22,957 for women aged 65-74 years, and 58,340 for women aged ≥75 years. The number of hip arthroplasties in Japan in 2030 was predicted to be 8936 for men aged 40-64 years, 9005 for men aged 65-74 years, 5972 for men aged ≥75 years, 27,327 for women aged 40-64 years, 36,416 for women aged 65-74 years, and 37,011 for women aged ≥75 years. CONCLUSION: The numbers of knee and hip arthroplasties are expected to continue to increase over the next 10 years in Japan in most age groups. These findings are useful for future healthcare resource planning to meet the demand for knee and hip arthroplasties.

COVID-19 pandemic and the international classification of functioning in multiple system atrophy: a cross-sectional, nationwide survey in Japan.

The present study aimed to determine the magnitude of and risk factors for the effects of the COVID-19 pandemic on the international classification of functioning, disability and health (ICF) in patients with multiple system atrophy (PwMSA). The study was part of a cross-sectional, nationwide, multipurpose mail survey for Japanese PwMSA from October to December, 2020. The primary outcome was the impact of the early COVID-19 pandemic on ICF functioning, consisting of body function, activity, and participation. Age, sex, disease type, disease duration, and dwelling place were asked as participants' characteristics, and the multiple system impairment questionnaire (MSIQ), patient health questionnaire-2, modified rankin scale, barthel index, life-space assessment (LSA), and EuroQoL were examined. Multivariate logistic regression analyses were performed to identify independent risk factors for a worse function score due to the COVID-19 pandemic for each ICF functioning domain. A total of 155 patients (mean age 65.6 [SD 8.1] years; 43.9% women; mean disease duration 8.0 [SD 6.2] years; 65% MSA with cerebellar ataxia, 13% MSA with parkinsonism, 9% MSA with predominant autonomic features) were analyzed. Of the ICF functioning domains, the respondents reported that the early COVID-19 pandemic affected body function in 17.4%, activity in 17.6%, and participation in 46.0%. The adjusted multivariate model identified MSIQ and LSA as the two variables that independently contributed to all domains. The COVID-19 pandemic affected ICF functioning of PwMSA in Japan, and the severity of disease-related impairments and a large daily living space were common risk factors. These results help support the focus on patient characteristics for medical and social welfare support.

Comparing the Japanese Version of the Ocular Surface Disease Index and Dry Eye-Related Quality-of-Life Score for Dry Eye Symptom Assessment.

The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) between the Japanese version of the Ocular Surface Disease Index (J-OSDI) and the Dry Eye-Related Quality-of-Life Score (DEQS). A total of 169 participants were enrolled between September 2017 and May 2018. Patients were administered the J-OSDI and DEQS questionnaires at their first (baseline) and follow-up visits to evaluate DED-related symptoms. The correlations between the J-OSDI total score and DEQS (Frequency and Degree) scores were evaluated using Pearson's correlation coefficient, and their clinical differences were assessed using the Bland-Altman analysis. At the baseline visit, the J-OSDI score and DEQS (Frequency and Degree) were significantly correlated (r = 0.855, r = 0.897, respectively). Moreover, a significant correlation was found between the J-OSDI score and DEQS (Frequency and Degree) at the follow-up visit (r = 0.852, r = 0.888, respectively). The Bland-Altman analysis revealed a difference (bias) of 4.18 units at the baseline and 4.08 units at the follow-up between the scores of the two questionnaires. The J-OSDI and DEQS were significantly correlated with negligible score differences, suggesting that the J-OSDI can be reliably used for Japanese patients, allowing for cross-country comparisons.

Comorbidity status in hospitalized elderly in Japan: Analysis from National Database of Health Insurance Claims and Specific Health Checkups.

The detailed comorbidity status of hospitalized elderly patients throughout Japan has remained largely unknown; therefore, our goal was to rigorously explore this situation and its implications as of the 2015 fiscal year (from April 2015 to March 2016). This study was based on a health insurance claims database, covering all insured policy holders in Japan aged ≥60 years (male: n = 2,135,049, female: 1,969,019) as of the 2015 fiscal year. Comorbidity status was identified by applying principal factor analysis to the database. The factors identified in male patients were [1] myocardial infarction, hypertension, dyslipidemia, and diabetes mellitus; [2] congestive heart failure (CHF), cardiac arrhythmia, and renal failure; [3] Parkinson's disease, dementia, cerebrovascular disease, and pneumonia; [4] cancer and digestive disorders; and [5] rheumatoid arthritis and hip fracture. However, in female patients, the results obtained for the quaternary and quinary factors were the opposite of those obtained in male patients. In superelderly patients, dementia, cerebrovascular disease, and pneumonia appeared as the tertiary factor, and hip fracture and osteoporosis appeared as the quaternary factor. The comorbidities in the elderly patients suggest the importance of coronary heart disease and its related metabolic disorders; in superelderly patients, fracture and osteoporosis appeared as factors, in addition to dementia and pneumonia.

Importance of Quality Assessment in Clinical Research in Japan.

Background: The number of papers published by an institution is acknowledged as an easy-to-understand research outcome. However, the quantity as well as the quality of research papers needs to be assessed. Methods: To determine the relation between the number of published papers and paper quality, a survey was conducted to assess publications focusing on interventional clinical trials reported by 11 core clinical research hospitals. A score was calculated for each paper using Système d'interrogation, de gestionet d'analyse des publications scientifiques scoring system, allowing for a clinical paper quality assessment independent of the field. Paper quality was defined as the relative Journal impact factor (IF) total score/number of papers. Results: We surveyed 580 clinical trial papers. For each of the 11 medical institutions (a-k), respectively, the following was found: number of published papers: a:66, b:64, c:61, d:56, e:54, f:51, g:46, h:46, i:46, j:45, k:45 (median: 51, maximum: 66, minimum: 45); total Journal IF: a:204, b:252, c:207, d:225, e:257, f:164, g:216, h:190, i:156, j:179, k:219 (median: 207, maximum: 257, minimum: 156); relative Journal IF total score: a:244, b:272, c:260, d:299, e:268, f:215, g:225, h:208, i:189, j:223, k:218 (median: 225, maximum: 299, minimum: 189); and paper quality (relative Journal IF total score/number of papers): a:3.70, b:4.25, c:4.26, d:5.34, e:4.96, f:4.22, g:4.89, h:4.52, i:4.11, j:4.96, k:4.84 (median: 4.52, maximum: 5.34, minimum: 3.70). Additionally, no significant relation was found between the number of published papers and paper quality (correlation coefficient, -0.33, P = 0.32). Conclusions: The number of published papers does not correspond to paper quality. When assessing an institution's ability to perform clinical research, an assessment of paper quality should be included along with the number of published papers.

National burden of the pharmaceutical cost of wet compresses and its cost predictors: nationwide cross-sectional study in Japan.

BACKGROUND: Although a high number of wet compresses are prescribed daily in medical institutions in Japan, our understanding of the national burden of the cost of wet compresses and the details regarding their prescription is far from complete. We investigated the national burden of the annual pharmaceutical cost of wet compresses prescribed in Japan and estimated the predictors of this cost using nationwide health insurance claims data. METHODS: We extracted the records on wet compress products from summary table files obtained from the second version of the "NDB Open Data Japan" website and calculated the annual pharmaceutical cost of wet compresses by patients' 5-year age group, sex, and prefecture. We also conducted an ecological study treating each prefecture as an individual unit and multiple linear regression analyses using the age-standardized cost of wet compresses per resident as a dependent variable. RESULTS: The annual pharmaceutical cost of wet compresses prescribed in Japan in fiscal year 2015 was 149.0 billion Japanese yen (1.18 billion euros; 1.33 billion USD). Multiple linear regression analyses showed that the number of orthopedists and rehabilitation physicians per 100,000 residents were significantly positively associated with the annual pharmaceutical cost of wet compresses per resident (P = 0.042 and P = 0.008, respectively). CONCLUSIONS: The annual pharmaceutical cost of wet compresses prescribed in Japan has a considerable impact on the nation's limited healthcare resources. The number of orthopedists and rehabilitation physicians per 100,000 residents may be independent predictors of the wet compress cost in Japan.