Cellular and humoral immune responses to COVID-19 booster vaccination in Japanese dialysis patients.

BACKGROUND: Dialysis patients are susceptible to developing severe coronavirus disease 2019 (COVID-19) due to hypoimmunity. Antibody titers against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) after the primary vaccinations are lower in hemodialysis (HD) patients than in healthy individuals. This study aimed to evaluate the effect of a SARS-CoV-2 booster vaccination in HD and peritoneal dialysis (PD) patients based on antibody titers and cellular and humoral immunity. METHODS: Participants of the control, HD, and PD groups were recruited from 12 facilities. SARS-CoV-2 antigen-specific cytokine and IgG-antibody levels were measured. Regulatory T cells and memory B cells were counted using flow cytometry at 6 months after primary vaccination with BNT162b2 and 3 weeks after the booster vaccination in HD and PD patients and compared with those of a control group. RESULTS: Booster vaccination significantly enhanced the levels of antibodies, cytokines, and memory B cells in three groups. The HD group showed significantly higher levels of IgG-antibodies, IL-1ß, IL-2, IL-4, IL-17, and memory B cells than those in the control group at 3 weeks after the booster dose. The PD group tended to show similar trends to HD patients but had similar levels of IgG-antibodies, cytokines, and memory B cells to the control group. CONCLUSIONS: HD patients had significantly stronger cellular and humoral immune responses than the control 3 weeks after the booster dose. Our findings will help in developing better COVID-19 vaccination strategies for HD and PD patients.

The utility of smartphone-based quantitative analysis of SARS-CoV-2-specific antibody lateral flow assays.

OBJECTIVES: Although antibody measurements using lateral flow assay (LFA) kits are convenient, they usually require a specialized reader for quantification. However, a smartphone-based quantification application can be used as a reader for LFA kits. We investigated the quantification ability of the application for SARS-CoV-2-specific antibodies. METHODS: Eight hundred frozen serum samples from 100 healthcare professionals who received a COVID-19 vaccine were analyzed. Images of assayed LFA kits were obtained using a smartphone camera. We determined whether the ratio of color density of the test and control lines of spike protein IgG correlated with chemiluminescent immunoassay-measured titers. RESULTS: Spike protein IgG correlated well with the quantification results of the LFA kits using the application installed on a smartphone (r = 0.886). CONCLUSION: Our results suggest that smartphone-based quantitative analysis of LFA kits enables the quantification of anti-SARS-CoV-2 IgG without special devices, enabling point-of-care assessment of acquired humoral immunity in various settings.

App-based interventions for the prevention of postpartum depression: a systematic review and meta-analysis.

BACKGROUND: This study explored whether psychosocial intervention applications (apps) are effective in preventing postpartum depression. METHODS: We conducted an initial article search on 26 March 2020, and the updated search on 17 March 2023 on the electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Scopus, PsycINFO, CINAHL, and ProQuest Dissertations & Theses A&I. Furthermore, we searched the International Clinical Trials Platform Search Portal (ICTRP), and Clinical Trials. RESULTS: We identified 2515 references, and sixteen studies were ultimately included in this review. We conducted a meta-analysis of two studies on the onset of postpartum depression. There were no significant differences between the intervention and control groups (RR 0.80; 95% CI 0.62 to 1.04; P = 0.570). We performed a meta-analysis of the Edinburgh Postnatal Depression Scale (EPDS). The intervention group had significantly lower EPDS scores than the control group (mean difference -0.96; 95% CI -1.44 to -0.48; P < 0.001, I2 = 82%, Chi2 = 62.75, P < 0.001; high heterogeneity). CONCLUSION: This study presents the results of current RCTs on interventions with apps, including an app with an automated psychosocial component for preventing postpartum depression that has been conducted. These apps improved the EPDS score; furthermore, they may prevent postpartum depression.

Humoral and cellular immune response dynamics in Japanese healthcare workers up to six months after receiving a third dose of BNT162b2 monovalent vaccine.

Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose. UMIN Clinical Trials Registry ID: UMIN000043340.

The impact of system and diagnostic errors for medical litigation outcomes in orthopedic surgery.

BACKGROUND: Medical litigation resulting from medical errors has a negative impact on health economics for both patients and medical practitioners. In medical litigation involving orthopedic surgeons, we aimed to identify factors contributing to plaintiff victory (orthopedic surgeon loss) through a comprehensive assessment. METHODS: This retrospective study included 166 litigation claims against orthopedic surgeons using a litigation database in Japan. We evaluated the sex and age of the patient (plaintiff), initial diagnosis, diagnostic error, system error, the time and place of each claim that led to malpractice litigation, the institution's size, and clinical outcomes. The main outcome was the litigation outcome (acceptance or rejection) in the final judgment. Acceptance meant that the orthopedic surgeon lost the malpractice lawsuit. We conducted multivariable logistic regression analyses to examine the association of factors with an accepted claim. RESULTS: The median age of the patients was 42 years, and 65.7% were male. The litigation outcome of 85 (51.2%) claims was acceptance. The adjusted median indemnity paid was $151,818. The multivariable analysis showed that diagnostic error, system error, sequelae, inadequate medical procedure, and follow-up observation were significantly associated with the orthopedic surgeon losing the lawsuit. In particular, claims involving diagnostic errors were more likely to be acceptance claims, in which the orthopedic surgeon lost (adjusted odds ratio 16.7, 95% confidence intervals: 4.7 to 58.0, p < 0.001). All of the claims in which the orthopedic surgeon lost were associated with a diagnostic or system error, with the most common one being system error. CONCLUSIONS: System errors and diagnostic errors were significantly associated with acceptance claims (orthopedic surgeon losses). Since these are modifiable factors, it is necessary to take measures not only for individual physicians but also for the overall medical management system to enhance patient safety and reduce the litigation risk of orthopedic surgeons.

The impact and prevention of systemic and diagnostic errors in surgical malpractice claims in Japan: a retrospective cohort study.

The Surgical Patient Safety System (SURPASS) has been proven to improve patient outcomes. However, few studies have evaluated the details of litigation and its prevention in terms of systemic and diagnostic errors as potentially preventable problems. The present study explored factors associated with accepted claims (surgeon-loss). We retrospectively searched the national Japanese malpractice claims database between 1961 and 2017. Using multivariable logistic regression models, we assessed the association between medical malpractice variables (systemic and diagnostic errors, facility size, time, place, and clinical outcomes) and litigation outcomes (acceptance). We evaluated whether or not the factors associated with litigation could have been prevented with the SURPASS checklist. We identified 339 malpractice claims made against general surgeons. There were 159 (56.3%) accepted claims, and the median compensation paid was 164,381 USD. In multivariable analyses, system (odds ratio, 27.2 95% confidence interval 13.8-53.5) and diagnostic errors (odds ratio 5.3, 95% confidence interval 2.7-10.5) had a significant statistical association with accepted claims. The SURPASS checklist may have prevented 7% and 10% of the accepted claims and systemic errors, respectively. It is unclear what proportion of accepted claims indicated that general surgeon loses should be prevented from performing surgery if the SURPASS checklist were used. In conclusion, systemic and diagnostic errors were associated with accepted claims. Surgical teams should adhere to the SURPASS checklist to enhance patient safety and reduce surgeon risk.

Assessing anti-SARS-CoV-2 cellular immunity in 571 vaccines by using an IFN-γ release assay.

Memory T cell responses have been analyzed only in small cohorts of COVID-19 vaccines. Herein, we aimed to assess anti-SARS-CoV-2 cellular immunity in a large cohort using QuantiFERON assays, which are IFN-γ release assays (IGRAs) based on short-term whole blood culture. The study included 571 individuals receiving the viral spike (S) protein-expressing BNT162b2 mRNA vaccine. QuantiFERON assays revealed antigen-specific IFN-γ production in most individuals 8 weeks after the second dose. Simultaneous flow cytometric assays to detect T cells expressing activation-induced markers (AIMs) performed for 28 randomly selected individuals provided data correlating with the QuantiFERON data. Simultaneous IFN-γ enzyme-linked immunospot and AIM assays for another subset of 31 individuals, based on short-term peripheral blood mononuclear cell culture, also indicated a correlation between IFN-γ production and AIM positivity. These observations indicated the acquisition of T cell memory responses and supported the usability of IGRAs to assess cellular immunity. The QuantiFERON results were weakly correlated with serum IgG titers against the receptor-binding domain of the S protein and were associated with pre-vaccination infection and adverse reactions after the second dose. The present study revealed cellular immunity after COVID-19 vaccination, providing insights into the effects and adverse reactions of vaccination.

Dynamics of antibody titers and cellular immunity among Japanese healthcare workers during the 6 months after receiving two doses of BNT162b2 mRNA vaccine.

BACKGROUND: The antibody titer is known to wane within months after receiving two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine. However, knowledge of the cellular immune response dynamics following vaccination is limited. This study to aimed to determine antibody and cellular immune responses following vaccination, and the incidence and determinants of breakthrough infection. METHODS: This prospective cohort study a 6-month follow-up period was conducted among Japanese healthcare workers. All participants received two doses of BNT162b2 vaccine. Anti-SARS-CoV-2 antibody titers and T-cell immune responses were measured in serum samples collected at several timepoints before and after vaccination. RESULTS: A total of 608 participants were included in the analysis. Antibody titers were elevated 3 weeks after vaccination and waned over the remainder of the study period. T-cell immune responses showed similar dynamics. Six participants without predisposing medical conditions seroconverted from negative to positive on the IgG assay for nucleocapsid proteins, indicating breakthrough SARS-CoV-2 infection. Five of the six breakthrough infections were asymptomatic. CONCLUSIONS: Both humoral and cellular immunity waned within 6 months after BNT162b2 vaccination. The incidence of asymptomatic breakthrough infection within 6 months after vaccination was approximately one percent. UMIN CLINICAL TRIALS REGISTRY ID: UMIN000043340.

Point-of-care ultrasound for abdominal pain in obstetrics and gynecological diseases.

Ultrasound is a minimally invasive technique recommended for the evaluation of abdominal pain in young, premenopausal women and pregnant women. Ectopic pregnancy, ovarian cyst torsion, ovarian hemorrhage, myoma degeneration, and pyometra can be detected with point-of-care ultrasound (POCUS) in the case of acute abdominal pain. This article describes the utility of POCUS in females with abdominal pain in obstetrics and gynecological diseases.

Young age, female sex, and presence of systemic adverse reactions are associated with high post-vaccination antibody titer after two doses of BNT162b2 mRNA SARS-CoV-2 vaccination: An observational study of 646 Japanese healthcare workers and university staff.

BACKGROUND: SARS-CoV-2 vaccination has started worldwide, including Japan. Although high rates of vaccine response and adverse reactions of BNT162b2 vaccine have been reported, knowledge about the relationship between sex differences and antibody response is limited. Furthermore, it is uncertain whether adverse reactions are associated with the vaccine response. METHODS: This prospective observational study included 673 Japanese participants working in a medical school and its affiliated hospital in Tokyo, Japan (UMIN000043340). Serum samples were collected before the first dose and three weeks after the second dose of BNT162b2 vaccine, and antibody titers against the receptor-binding domain of the spike protein of SARS-CoV-2 were measured. Answers to questionnaires about background characteristics and adverse reactions were obtained at the time of sample collection, and the relationship between antibody titers was analyzed. RESULTS: After excluding participants who did not complete receiving two doses of vaccination or two series of serum sample collection, 646 participants were analyzed. Although all participants became sero-positive after vaccination, antibody titers were highly variable among individuals (260.9-57,399.7A U/mL), with a median titer of 13478.0AU/mL. Mean titer was higher in females than in males and higher in young (≤45 years old) participants than in aged (>45 years old) participants. Participants who experienced adverse reactions demonstrated a higher antibody titer after vaccination than those without adverse reactions. Multivariable analysis demonstrated that young age, female sex, and adverse reactions after the second dose were independently related to higher antibody titers after the second dose. DISCUSSION: A favorable antibody response was observed after two doses of BNT162b2 vaccination among mostly healthy Japanese participants, especially among female and young participants. Although further investigation is essential, our results imply that the systemic adverse reactions (i.e., fever and general fatigue) are associated with a higher antibody response that indicates the acquisition of humoral immunity.

Attitudes toward overtime work and self-training: A survey on obstetricians and gynecologists in Japan.

AIM: The Ministry of Health, Labour, and Welfare of Japan proposed a regulation of overtime work as a reform in work style. However, the regulation may deteriorate the quality of medical services due to the reduction in training time. Thus, the study aimed to reveal perceptions in terms of generation gaps in views on self-training and overtime work, among members of the Japan Society of Obstetrics and Gynecology (JSOG). METHODS: A web-based, self-administered questionnaire survey was conducted among members of the JSOG. In total, 1256 respondents were included in the analysis. Data were collected on age, sex, experience as a medical doctor, location of workplace, work style, the type of main workplace, and number of full-time doctors in the main workplace. The study examined the attitudes of the respondents toward overtime work and self-training. The respondents were categorized based on experience as a medical doctor. RESULTS: According to years of experience, 112 (8.9%), 226 (18.0%), 383 (30.5%), 535 (42.6%) doctors have been working for ≤5, 6-10, 11-19, and ≥ 20 years, respectively. Although 54.5% of doctors with ≤5 years of experience expected the regulation on working hours to improve the quality of medical services, those with ≥20 years of experience expressed potential deterioration. After adjusting for covariates, more years of experience were significantly related with the expectation of deterioration in the quality of medical services. CONCLUSIONS: The study revealed a generation gap in the views about self-training and overtime work among obstetricians and gynecologists in Japan.

Preparation for Quarantine on the Cruise Ship Diamond Princess in Japan due to COVID-19.

BACKGROUND: Japan implemented a large-scale quarantine on the Diamond Princess cruise ship in an attempt to control the spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in February 2020. OBJECTIVE: We aim to describe the medical activities initiated and difficulties in implementing quarantine on a cruise ship. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 were performed for all 3711 people (2666 passengers and 1045 crew) on board. RESULTS: Of those tested, 696 (18.8%) tested positive for coronavirus disease (COVID-19), of which 410 (58.9%) were asymptomatic. We also confirmed that 54% of the asymptomatic patients with a positive RT-PCR result had lung opacities on chest computed tomography. There were many difficulties in implementing quarantine, such as creating a dividing traffic line between infectious and noninfectious passengers, finding hospitals and transportation providers willing to accept these patients, transporting individuals, language barriers, and supporting daily life. As of March 8, 2020, 31 patients (4.5% of patients with positive RT-PCR results) were hospitalized and required ventilator support or intensive care, and 7 patients (1.0% of patients with positive RT-PCR results) had died. CONCLUSIONS: There were several difficulties in implementing large-scale quarantine and obtaining medical support on the cruise ship. In the future, we need to prepare for patients' transfer and the admitting hospitals when disembarking the passengers. We recommend treating the crew the same way as the passengers to control the infection. We must also draw a plan for the future, to protect travelers and passengers from emerging infectious diseases on cruise ships.

Letters to the editor; a possible spurious correlation between human papillomavirus vaccination introduction and birth rate change in the United States.

A possible spurious correlation was found between human papillomavirus (HPV) vaccination introduction and birth rate change in the United States. Thus, the effects of HPV vaccination needed to be followed carefully at an international level. The birth rate change in the US might be representative of the trend of the introduction of new contraception methods and advancing maternal age.

Challenges in providing maternity care in remote areas and islands for primary care physicians in Japan: a qualitative study.

BACKGROUND: Maintaining a maternity care system is one of the biggest issues in Japan due to the decreasing number of obstetricians, especially in remote areas and islands. The aim of this qualitative study was to explore the challenges in women's health and maternity care in remote areas and islands for primary care physicians and obstetricians in order to provide an insight necessary to develop a better health care system. METHODS: We conducted semi-structured interviews with 13 primary care physicians and 4 obstetricians practicing maternity care at clinics/hospitals in remote areas and islands across Japan. Interview data were analyzed, using the modified Grounded Theory Approach, to elucidate the challenges primary care physicians faced in their practice. RESULTS: Primary care physicians who engaged in maternity care recognized the following challenges: low awareness of primary care, lack of training opportunities, unclear goal of the training, lack of certification system, lack of consultation system, and lack of obstetricians to offer support. These six challenges along with the specialty's factors such as sudden changes of patients' condition were considered to result to the provider's hesitation and anxiety to engage in the practice. CONCLUSIONS: This study found six environmental/systemic factors and three specialty's factors as the main challenges for primary care physicians in providing maternity care in remote areas and islands for primary care physicians in Japan. Increasing the awareness of primary care and developing a maternity care training program to certify primary care physicians may enable more primary care physicians to engage in and provide women's health and maternity care in remote areas and islands.

[The Present State of Inter-Laboratory Differences in Setting and Practicing Critical Values -Results of a Questionnaire Survey Performed to the Laboratories of Keio University-Associated Hospitals].

Presently we, Keio Endocrine and Metabolite Survey (KEMS) study group conducted a questionnaire sur- vey with respect to panic values in the laboratories belonging to Keio University-associated hospitals. As to the initial setting, most of the laboratories answered to play a leading role in preparing the necessary matters to implementation of panic values and revise them corresponding to physician's request on each occasion. In almost all laboratories, they did not verify whether the notification procedure does work to exert appropriate clinical action. The numbers of critical values answered by the 18 laboratories distributed widely in the test items (8-39) and their critical limits (10-68). As to the critical limits, the lower limits of serum K and blood glucose converged among the laboratories, however, the limits of other test items diverged. The results of the present survey regarding to critical values, although being in small scale, may submit the im- portant issue to be solved in near future. [Short Communication].