Plerixafor stem cell mobilization in Japanese children: A post-marketing study.

BACKGROUND: Plerixafor is approved in Japan for hematopoietic stem cell mobilization prior to autologous transplant, but limited data are available on the use in children. This study evaluates the safety and effectiveness of plerixafor in Japanese children aged <15 years. METHODS: A multicenter, post-marketing surveillance study was conducted in Japan to evaluate the safety and effectiveness of plerixafor in routine clinical practice. This subgroup analysis examined the safety and effectiveness of plerixafor administered as a once-daily, subcutaneous injection in children aged <15 years. The primary effectiveness outcome was the proportion of patients with 2 × 106 cells CD34+ cells/kg collected via apheresis within 4 days. RESULTS: Eighteen patients with solid tumors were included in this analysis; (median age 6.0 years, range, 1-13 years). In addition to granulocyte colony-stimulating factor, all patients had received chemotherapy immediately prior to plerixafor administration. The mean (SD) daily dose of plerixafor was 0.24 (0.01) mg/kg. Seven of the 18 patients (38.9%) developed adverse drug reactions (ADRs), all occurring in patients aged ≥6 years and weighing ≥16 kg. The most common ADRs were pyrexia (n = 4), vomiting (n = 3), nausea (n = 2), and abdominal pain (n = 2). Twelve patients (66.7%) achieved a CD34+ cell count ≥2 × 106 cells/kg within 4 days after the start of plerixafor administration. CONCLUSIONS: The results provide an encouraging sign that plerixafor 0.24 mg/kg may be safe and effective in pediatric patients in routine clinical practice in Japan, but further research in larger studies is needed.

Web-Based Search Volume for HIV Tests and HIV-Testing Preferences During the COVID-19 Pandemic in Japan: Infodemiology Study.

BACKGROUND: Research has found a COVID-19 pandemic-related impact on HIV medical services, including clinic visits, testing, and antiviral therapy initiation in countries including Japan. However, the change in trend for HIV/AIDS testing during the COVID-19 pandemic has not been explored extensively in the Japanese population. OBJECTIVE: This infodemiology study examines the web-based search interest for two types of HIV tests, self-test kits and facility-based tests, before and during the COVID-19 pandemic in Japan. METHODS: The monthly search volume of queried search terms was obtained from Yahoo! JAPAN. Search volumes for the following terms were collected from November 2017 to October 2018: "HIV test," "HIV test kit," and "HIV test health center." The search term "Corona PCR" and the number of new COVID-19 cases by month were used as a control for the search trends. The number of new HIV cases in the corresponding study period was obtained from the AIDS Trend Committee Quarterly Report from the AIDS Prevention Foundation. RESULTS: Compared to the search volume of "corona-PCR," which roughly fluctuated corresponding to the number of new COVID-19 cases in Japan, the search volume of "HIV test" was relatively stable from 2019 to 2022. When we further stratified by the type of HIV test, the respective web-based search interest in HIV self-testing and facility-based testing showed distinct patterns from 2018 to 2022. While the search volume of "HIV test kit" remained stable, that of "HIV test health center" displayed a decreasing trend starting in 2018 and has remained low since the beginning of the COVID-19 pandemic. Around 66%-71% of the search volume of "HIV test kits" was attributable to searches made by male internet users from 2018 to 2022, and the top three contributing age groups were those aged 30-39 (27%-32%), 20-29 (19%-32%), and 40-49 (19%-25%) years. On the other hand, the search volume of "HIV test health centers" by male users decreased from more than 500 from 2018 to 2019 to fewer than 300 from 2020 to 2022. CONCLUSIONS: Our study found a notable decrease in the search volume of "HIV test health center" during the pandemic, while the search volume for HIV self-testing kits remained stable before and during the COVID-19 crisis in Japan. This suggests that the previously reported COVID-19-related decrease in the number of HIV tests mostly likely referred to facility-based testing. This sheds light on the change in HIV-testing preferences in Japan, calling for a more comprehensive application and regulatory acceptance of HIV self-instructed tests.

Mortality Prediction of COVID-19 in Hospitalized Patients Using the 2020 Diagnosis Procedure Combination Administrative Database of Japan.

Objectives Numerous people have died from coronavirus disease 2019 (COVID-19) infection. Identifying crucial predictive biomarkers of disease mortality is critical to support decision-making and logistic planning in healthcare systems. This study investigated the association between mortality and medical factors and prescription records in 2020 in Japan, where COVID-19 prevalence and mortality remain relatively low. Methods This retrospective cohort study analyzed anonymous administrative data from the Diagnosis Procedure Combination (DPC) database in Japan. Results A total of 22,795 patients were treated in DPC hospitals in 2020 in Japan, and of these, 5,980 patients over 50 years old were hospitalized, with 299 (5.0%) dying. There were 2,399 severe patients among 11,440 total hospitalized patients (all ages). The results of a logistic model analysis revealed that an older age, male sex, Parkinson's disease, cerebrovascular diseases, and chronic kidney diseases were risk factors for mortality. A machine learning analysis identified an older age, male sex (mortality), pneumonia, drugs for acid-related disorders, analgesics, anesthesia, upper respiratory tract disease, drugs for functional gastrointestinal disorders, drugs for obstructive airway diseases, topical products for joint and muscular pain, diabetes, lipid-modifying agents, calcium channel blockers, drugs for diabetes, and agents acting on the renin-angiotensin system as risk factors for a severe status. Conclusions This COVID-19 mortality risk tool is a well-calibrated and accurate model for predicting mortality risk among hospitalized patients with COVID-19 in Japan, which is characterized by a relatively low COVID-19 prevalence, aging society, and high population density. This COVID-19 mortality prediction model can assist in resource utilization and patient and caregiver education and be useful as a risk stratification instrument for future research trials.

Increased SARS-CoV-2 seroprevalence and spread of infection without awareness among healthcare workers through 2020-2022 in a Japanese medical center.

Despite Japan's high vaccination coverage, daily numbers of new COVID-19 cases have been high. However, studies on the seroprevalence among Japanese people and the causative factors for rapid spread have remained limited. In this study, we aimed to examine the seroprevalence and associated factors in healthcare workers (HCWs) of a medical center in Tokyo using blood samples drawn at annual check-ups from 2020 to 2022. We found that of the 3,788 HCWs in 2022 (by mid-June), 669 were seropositive for N-specific antibodies (tested by Roche Elecsys Anti-SARS-CoV-2 assay); the seroprevalence surged from 0.3% in 2020 and 1.6% in 2021 to 17.7% in 2022. Notably, our study found 325 (48.6%; 325/669) cases were infected without awareness. Among those with a previously PCR-confirmed SARS-CoV-2 infection during the past three years, 79.0% (282/357) were found after January 2022, after the Omicron variant was first detected in Tokyo at the end of 2021. This study indicates the fast spread of the SARS-CoV-2 among HCWs during the Omicron surge in Japan. The high percentage of infection without awareness may be a key driving factor causing rapid person-to-person transmission, as shown in this medical center with high vaccination coverage and strict infection control measures.

Changes in social environment due to the state of emergency and Go To campaign during the COVID-19 pandemic in Japan: An ecological study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic in Japan, the state of emergency, as a public health measure to control the spread of COVID-19, and the Go To campaign, which included the Go To Travel and Go To Eat campaigns and was purposed to stimulate economic activities, were implemented. This study investigated the impact of these government policies on COVID-19 spread. METHODS: This ecological study included all 47 prefectures in Japan as samples between February 3 and December 27, 2020. We used COVID-19 cases and mobility as variables. Additionally, places where social contacts could accrue, defined as restaurants, companies, transportation, and tourist spots; mean temperature and humidity; the number of inhabitants in their twenties to fifties; and the number of COVID-19 cases in the previous period, which were factors or covariates in the graphical modeling analysis, were divided into five periods according to the timing of the implementation of the state of emergency and Go To campaign. RESULTS: Graphical changes occurred throughout all five periods of COVID-19. During the state of emergency (period 2), a correlation between COVID-19 cases and those before the state of emergency (period 1) was observed, although this correlation was not significant in the period after the state of emergency was lifted (period 3). During the implementation of Go To Travel and the Go To Eat campaigns (period 5), the number of places where social contacts could accrue was correlated with COVID-19 cases, with complex associations and mobility. CONCLUSIONS: This study confirms that the state of emergency affected the control of COVID-19 spread and that the Go To campaign led to increased COVID-19 cases due to increased mobility by changing behavior in the social environment where social contacts potentially accrue.

Safety and Effectiveness of Plerixafor for Peripheral Blood Stem Cell Mobilization in Autologous Stem Cell Transplantation: Results of a Post-Marketing Surveillance Study.

BACKGROUND: Plerixafor was approved in Japan in 2016 for peripheral blood stem cell (PBSC) mobilization in autologous stem cell transplantation (A-SCT). OBJECTIVE: Our objective was to evaluate the safety and effectiveness of plerixafor in Japanese patients undergoing A-SCT for various indications in real-world practice. PATIENTS AND METHODS: This post-marketing surveillance study included Japanese patients initiating PBSC mobilization with plerixafor for A-SCT. Safety assessments included the incidence of adverse events (AEs) including serious AEs, adverse drug reactions (ADRs), and laboratory variables. Effectiveness assessments were the proportion of patients with the target CD34+ cell yield (≥2 × 106 cells/kg) ≤4 days after plerixafor administration and the number of days required to reach the target CD34+ cell yield. RESULTS: In total, 785 patients were registered, and the safety and effectiveness analysis sets comprised 764 and 717 patients, respectively. ADRs occurred in 12.2% of patients, with gastrointestinal disorders (5.5%), laboratory investigations (4.5%), and blood and lymphatic system disorders (3.0%) being the most common. A total of 71.1% of patients had the target CD34+ cell yield within ≤4 days of treatment, with a mean (standard deviation) of 1.3 (0.7) days to reach the target CD34+ cell yield. Over 80% of patients with a baseline CD34+ cell count >2 cells/µL had a target CD34+ cell yield within ≤4 days of treatment. CONCLUSIONS: This large post-marketing surveillance study provided real-world evidence detailing the safety and effectiveness of plerixafor for PBSC mobilization in Japanese patients undergoing A-SCT. Importantly, no new safety concerns were identified, and the safety profile of plerixafor was consistent with the established profile of this drug.

MEdical Database AnaLysIS of Japanese multiple myeloma patienTs with apheresis #2 (MEDALIST-2): the impact of plerixafor use on costs and healthcare resources during mobilization and stem cell transplantation.

Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.

Long-Term Safety and Effectiveness of Thyrotropin Alfa in Japanese Patients: A Post-Marketing Surveillance Study.

INTRODUCTION: Real-world evidence of the safety and effectiveness of recombinant human thyroid-stimulating hormone (rhTSH; thyrotropin alfa) in Japanese patients is lacking. METHODS: This was a post-marketing surveillance study that included all Japanese patients who received thyrotropin alfa, either as a supporting diagnostic from January 2009 to December 2016, or as adjunctive treatment for ablation from May 2012 to October 2018. Information was collected on patient demographics, thyroid cancer characteristics, adverse drug reactions (ADRs), scintigraphy, serum thyroglobulin (Tg) testing, and hypothyroidism symptoms. RESULTS: A total of 9268 patients were included in the safety analysis and 9031 in the effectiveness analysis. In the safety analysis set, 3444 patients received thyrotropin alfa as a diagnostic and 5822 received it as treatment. ADRs occurred in 7.1% (n = 660) of patients, including 9.4% (n = 324) of patients who received thyrotropin alfa as a diagnostic and 5.8% (n = 336) of patients who received it as treatment. Nausea was the most common ADR (4.0% of overall safety population). Among patients who received thyrotropin alfa as a diagnostic (n = 1835), the Tg test was positive in 53.6% after the second dose. The scintigram was rated as "readable" in 3023 of the 3054 patients included in this analysis (99.0%). Of the 765 patients who were included in the assessment of response to ablation at 6 months to 1 year after the procedure, 621 (81.2%) were considered to have had "treatment success". There were no significant differences in the proportions of patients who had hypothyroidism symptoms before the first and after the second dose of thyrotropin alfa. CONCLUSION: In this large post-marketing surveillance study, thyrotropin alfa was well tolerated and showed effectiveness that was comparable to that observed in randomised, controlled trials.

[Case of latex allergy manifested during cesarean section].

A 26-year-old G1P0 woman with past history of bronchial asthma underwent emergency cesarean section for non-reassuring fetal status under spinal anesthesia. She had not had surgery before. Thirteen minites after the start of the procedure, she started complaining of flushing and itching of her hands and mouth. We suspected anaphylactic reaction due to cefazolin, but after a thorough work up, it turned out that the symptom was manifestation of latex allergy. She had worked as a dental assistant and, had experienced mouth swelling by touching latex gloves. But she had not recognized it as a symptom of latex allergy. After the discharge from the hospital, she experienced food allergy. It is known that several antigens which cause latex allergy share common structures with defense related proteins of plants. It is to be noticed that, patients sensitized by those defense related proteins by plants intake, may develop latex allergy even though they are not considered to be high risk group from relevant occupational exposure and, co-morbid conditions. We should consider latex allergy as one of the causes of shock during intraoperative period even when the possibility of latex allergy seems scant.

Postoperative management with dexmedetomidine in a pregnant patient who underwent AVM nidus removal: a case report.

BACKGROUND: Following cerebral arteriovenous malformation (AVM) surgery, severe brain edema and hemorrhage may be caused by postoperative normal perfusion pressure breakthrough (NPPB). Sedation is necessary for this population. It is a challenge for the anesthesiologist to maintain hemodynamic stability without interfering with the neurological assessment. In Japan, propofol is contraindicated for pregnant patients. Dexmedetomidine is a versatile drug in anesthesia practice and may be useful for this situation. There is no report using dexmedetomidine for the purpose of NPPB control in pregnant patients. We describe the postoperative management with dexmedetomidine for a pregnant patient who underwent cerebral AVM nidus removal. CASE PRESENTATION: A 32-year-old patient presented with headache at the 16th week of gestation. Neuroimaging revealed an intraventricular hemorrhage and an AVM at the right anterior horn of the lateral ventricle which caused bleeding. A multidisciplinary team discussion was done, and then a craniotomy for AVM nidus removal was performed under general anesthesia. Preanesthetic aspiration prophylaxis and rapid sequence induction were added to our conventional anesthetic management. Hypotension occurred after anesthetic induction but the patient recovered by volume resuscitation and vasopressors. Anesthesia was maintained with 50% O2 in air and sevoflurane. The AVM was completely removed, and no perioperative complications occurred. Postoperative sedation with dexmedetomidine was used to prevent breakthrough hyperperfusion and cerebral edema. CONCLUSIONS: Dexmedetomidine infusion was used for postoperative sedation without causing any side effects, and it can be an alternative for sedation, especially when propofol is contraindicated.