Evaluation of a joint workshop on study design for hospital and community pharmacists: a retrospective cross-sectional survey.

BACKGROUND: Although pharmacists often identify numerous clinical questions, they face several barriers, including the lack of mentors for research activities in clinical settings. Therefore, a workshop for the appropriate selection of a study design, which is a fundamental first step, may be necessary. The purpose of this study was to evaluate the effectiveness of a workshop on study design for hospital and community pharmacists. Moreover, the characteristics of pharmacists with little involvement in research activities were extracted using decision-tree analysis to guide the design of future workshops. METHODS: A workshop was conducted on October 1, 2023. It comprised three parts: lectures, group work, and presentations. Questionnaire-based surveys were conducted with workshop participants regarding their basic information, their background that influenced research activities, their satisfaction, and their knowledge/awareness. For the questions on knowledge/awareness, the same responses were requested before and after the workshop using a five-scale scoring system. Multivariate logistic regression analysis was conducted to identify independent factors influencing research activities. Decision tree analysis was performed to extract low-effort characteristics of the research activities. RESULTS: Of the 40 workshop attendees, the overall satisfaction score for the workshop was 4.38 of 5, and the score for each question was 4 or higher. Significant increases were observed in the scores of knowledge/awareness after the workshop. Moreover, 95% of the pharmacists answered that it would be highly useful to conduct a joint workshop between hospitals and community pharmacists. Although independent influencing factors were not detected in the multivariate logistic regression analysis, the decision tree analysis revealed that pharmacists who were no member of an academic society (85%, 11/13) or members without any certifications or accreditations related to pharmacy practice (80%, 4/5) were the least active in clinical research. In contrast, those belonging to academic societies and holding certifications or accreditations related to pharmacy practice frequently conducted clinical research. CONCLUSION: The present study revealed that a joint workshop on study design may have the potential to change pharmacists' knowledge and awareness of research activities. Moreover, future workshops should be conducted with pharmacists who do not belong to academic societies.

A pregnant woman with long-standing, retained intraabdominal glass shards who gave birth to a live infant with no complications: a case report.

BACKGROUND: Most cases of traumatic injury during pregnancy involve blunt trauma, with penetrating trauma being uncommonly rare. In glass shard injuries, fragments often penetrate deeply, and multiple injuries may occur simultaneously; attention must be paid to the possibility of organ injury from the residual fragments. However, no case of this occurring during pregnancy has been reported yet. CASE PRESENTATION: We present the case of a 34-year-old pregnant Cameroonian woman who retained intraabdominal glass shards following a penetrating injury at 13 weeks gestation and not diagnosed until 22 weeks gestation. Notably, this patient continued the pregnancy without complications and gave birth via cesarean section at 36 weeks gestation. CONCLUSION: In pregnant women sustaining a penetrating glass trauma during pregnancy, careful attention should be paid to the fragments; in that case, computed tomography is a useful modality for accurately visualizing any remaining fragments in the body. Essentially, the foreign bodies in glass shard injuries during pregnancy should be removed immediately, but conservative management for term delivery is an important choice for patients at risk for preterm delivery.

Investigation of an efficient method of oocyte retrieval by dual stimulation for patients with cancer.

Purpose: To examine the optimal timing of second ovarian stimulation using the dual stimulation method for good ovarian responders with cancer undergoing oocyte retrieval for fertility preservation. Methods: A retrospective analysis was conducted using data from 69 patients with cancer who underwent oocyte retrieval for fertility preservation at four Japanese institutions during 2010-2021. Twenty-two patients underwent two oocyte retrievals for fertility preservation. We studied the relationship between the initial number of oocytes retrieved via dual stimulation and risk of ovarian enlargement as well as the appropriate waiting interval between the end of the first ovarian stimulation and beginning of the second ovarian stimulation. Results: The risk of ovarian enlargement was high when the initial number of oocytes retrieved via dual stimulation was ≥5. An 8-day waiting interval may be more effective for performing a second ovarian stimulation oocyte retrieval in these cases, although the difference was not significant. Conclusions: This study provides one policy for effectively managing ovarian enlargement and timing of second ovarian stimulation during oocyte retrieval via the dual stimulation method for patients with cancer undergoing fertility preservation. If more facilities implement this procedure, more oocytes may be obtained in a short period for fertility preservation purposes.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

Text mining in a literature review of abnormal uterine bleeding according to the FIGO classification.

AIM: Abnormal uterine bleeding, as proposed in 2007, is defined as unexpected uterine bleeding in women of reproductive age; the cause of the bleeding is categorized using the PALM-COEIN system. Identifying the diagnostic and treatment modalities for each cause might be intriguing. To summarize the options for abnormal uterine bleeding assessment, we employed text-mining analysis for each of its causes. METHODS: We analyzed abstracts based on PALM-COEIN from PubMed and Web of Science in March 2022. The literature was divided into categories; topics about the disorders were retrieved, and covalent network analysis was conducted to find information for evaluating abnormal uterine bleeding. RESULTS: Diagnostic approaches for PALM included histological and image analysis, including computerized tomography, magnetic resonance imaging, sonography, and hysteroscopy. The therapeutic approaches varied according to the cause. Diagnostic approaches for COEIN were mostly medical history interviews and blood sampling, and the therapeutic approaches for COEIN were ablation, hysteroscopy, and hormonal treatment. The PALM-COEIN classification co-occurrence search revealed each cause's diagnostic procedures, symptoms, and treatment procedures. CONCLUSION: Our text-mining methodology revealed comprehensive insights, important study themes, and clinical trends for abnormal uterine bleeding. A tailored approach to medical realities is required for treating abnormal uterine bleeding properly.

Oncofertility-related psycho-educational therapy for young adult patients with breast cancer and their partners: Randomized controlled trial.

BACKGROUND: A couples' psycho-educational program called Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy was created and its effect when provided before cancer treatment was examined. METHODS: This multicenter randomized controlled trial with nonmasking, parallel two-group comparison enrolled women aged 20 to 39 years with early-stage breast cancer and their partners. They were randomly assigned to receive O!PEACE (37 couples) or usual care (37 couples). Primary end points were cancer-related posttraumatic stress symptoms, symptoms of depression, and anxiety. Secondary end points were stress-coping strategies, resilience, and marital relationship. RESULTS: Women receiving psycho-educational therapy had significantly reduced Impact of Event Scale-revised version for Japanese scores (p = .011, ηp 2  =  = .089). For patients with Impact of Event Scale-revised version for Japanese scores at baseline ≥18.27, O!PEACE therapy improved these scores when compared with usual care (U = 172.80, p = .027, r = 0.258). A >5-point reduction was present in 59.3% and 30% of women in the O!PEACE therapy and usual-care groups, respectively. For partners, O!PEACE therapy significantly improved stress-coping strategies (95% CI, -0.60 to -0.05; p = .018, ηp 2  =  = .074) and escape-avoidance marital communication (95% CI, -0.33 to -0.08; p = .001, ηp 2  = .136). O!PEACE therapy significantly improved the partners' support (95% CI, 0.10-0.50; p = .001, ηp 2  = .127), the rate of receiving fertility preservation consultations, and knowledge levels. CONCLUSIONS: O!PEACE therapy before cancer treatment can improve posttraumatic stress symptoms, stress-coping behavior, and marital relationships. Larger sample sizes and longer term follow-up are required. PLAIN LANGUAGE SUMMARY: A psycho-educational program, the Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy program was developed and evaluated for women diagnosed with breast cancer and their partners. A multicenter randomized controlled trial showed that the O!PEACE psycho-educational therapy, with only two precancer treatment sessions, can reduce cancer-related posttraumatic stress symptoms and improve oncofertility knowledge and marital relationships in young adult patients with breast cancer. The therapy could also improve stress-coping strategies in marital communications with their partners. Couples may use O!PEACE psycho-educational therapy to consider fertility preservation and improve their psychosocial aspects.

Comparative retrospective study on the validity of point-of-care testing device for massive obstetrical hemorrhage: dry hematology vs thromboelastography.

BACKGROUND: Early recognition of hypofibrinogenemia and prompt initiation of transfusion therapy in patients with massive obstetrical hemorrhage can improve prognosis. There are reports on the usefulness of point-of-care testing, which provides quicker test results compared with fibrinogen measurements using the conventional Clauss method. OBJECTIVE: This study aimed to compare and investigate the diagnostic accuracy of dry hematology and thromboelastography in point-of-care testing for the diagnosis of hypofibrinogenemia. STUDY DESIGN: A single-center, retrospective study of 126 massive obstetrical hemorrhage cases with point-of-care testing before treatment was initiated. The correlation of fibrinogen values with the Clauss method and the diagnostic accuracy for hypofibrinogenemia were compared between dry hematology and thromboelastography. RESULTS: Fibrinogen value in dry hematology showed a strong positive correlation with values measured by the Clauss method, and the diagnostic accuracy for hypofibrinogenemia was high, but there were many residuals above 100 mg/dL, and the distribution of these residuals was not uniform. Although thromboelastography cannot be used to directly measure fibrinogen values, maximum amplitude citrated functional fibrinogen, amplitude-10 citrated rapid thromboelastography, and amplitude-10 citrated functional fibrinogen showed a strong positive correlation with fibrinogen values using the Clauss method, and no significant difference in correlation or diagnostic accuracy was observed relative to dry hematology. CONCLUSION: Dry hematology and thromboelastography were equally accurate in diagnosing hypofibrinogenemia, with results correlating well with fibrinogen values measured by the Clauss method.

A Nationwide Survey Aimed at Establishing an Appropriate Long-Term Storage and Management System for Fertility Preserving Specimens in Japan.

Purpose: The demand for fertility preservation continues to grow as cancer treatment outcomes improve. The specimen storage period is longer for fertility preservation than for conventional fertility treatment; therefore, a robust management system for stored specimens is required. We conducted the first national survey in Japan on the management of cryopreserved specimens in fertility preservation facilities. Methods: Questionnaires were mailed to 130 fertility preservation facilities. Primary outcomes included the official position of the storage manager, support system in case of facility closure, disaster countermeasures, management and operating system for liquid nitrogen storage containers, preservation costs, and method to confirm the intention to continue storage. Results: The response rate was 63.8%. The facility director most commonly functioned as the storage manager (59.0%). In case of facility closure, 20.5% had an approved transfer site; 59.0% had not made any decisions. In the management of liquid nitrogen containers, 83.1% regularly replenished the liquid nitrogen, 65.1% regularly checked the amount, and 16.9% had alarm monitoring systems. Regarding disaster countermeasures, 70.9% had taken measures to protect specimens. Conclusion: This survey revealed issues such as disparities among facilities regarding long-term specimen storage systems. Accordingly, management standards for fertility preservation facilities should be established.

National survey of abnormal uterine bleeding according to the FIGO classification in Japan.

AIM: To investigate the status of abnormal uterine bleeding (AUB) in Japan using the International Federation of Gynecology and Obstetrics (FIGO) classification (AUB system 1 and 2; PALM-COEIN) and to clarify the relationship between AUB symptoms and the diseases causing AUB. METHODS: In a nationwide study, we enrolled first-time patients who visited target facilities during two consecutive weeks from December 1, 2019 to January 31, 2020. The FIGO classification was used to investigate patients with symptoms and causative diseases of AUB. Based on the proportion of patients in the nationwide study, 373 cases were included in the detailed survey. Survey items included symptoms of AUB according to AUB system 1, examination details, and causative diseases according to the PALM-COEIN classification. RESULTS: Within the study period, we encountered 61 740 first-time patients, of which 8081 (13.1%) were diagnosed with AUB. Among them, 39.9% had abnormal menstrual cycles and 56.9% had abnormal menstrual bleeding. In the survey, PALM had the highest percentage of AUB-L and COEIN had the highest percentage of AUB-O. Correspondence analysis showed that COEIN was strongly associated with abnormal menstrual cycles and PALM with abnormal menstrual bleeding. CONCLUSION: We conducted the first nationwide survey of AUB in Japan. The FIGO classification was a useful tool for the diagnosis of AUB, with a strong correlation between symptoms of AUB by AUB system 1 and the causative disease of AUB by PALM-COEIN. Conversely, a high percentage of AUB-N and AUB-E suggests that AUB system 1 and PALM-COEIN are ambiguous as diagnostic tools.

Current Status and Issues of the Japan Oncofertility Registry.

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan.

[Oncofertility Care in Japan Update-What We Aim by Public Funding].

Fertility preservation such as sperm and oocyte cryopreservation are not covered by public medical insurance, and the financial burden on patients and their families has been a problem. Various public subsidy programs have been implemented at the local government level, and in April 2021, the Research Promotion of Fertility Preservation for Childhood and AYA Generation Cancer Patients was launched. This project provides uniform national public subsidies for various types of fertility preservation, but it is important to note that it is positioned as a research promotion project to establish evidence for fertility preservation, rather than a subsidy for therapies with established efficacy. Therefore, hospital and clinics that provide fertility preservation must participate in a oncofertility network of each prefecture and obtain institutional accreditation, as well as follow up patients over the long term and keep information on prognosis, pregnancy, and childbearing registered in the Japan Oncofertility Registry(JOFR). For this purpose, the understanding and cooperation of not only facilities that provide fertility preservation, but also cancer treatment facilities, patients, and their families are essential, and the expansion of systems and projects for this purpose is currently under consideration.

The safety and effectiveness of elective laparoscopic surgery for benign ovarian cysts during pregnancy-Comparison with emergency surgery.

AIM: Relatively small benign ovarian cysts are conservatively managed in early pregnancy. However, emergency surgery is required should acute abdomen occur. Our study aimed to examine and compare the outcomes of benign ovarian cysts treated with elective laparoscopic surgery or emergency surgery during pregnancy. METHODS: From 2004 to 2017, we treated 135 pregnant patients (110 elective and 25 emergencies) with benign ovarian cysts at our tertiary perinatal center and compared their surgical and perinatal outcomes. RESULTS: There was no significant difference in cyst diameter (7.6 ± 2.5 vs. 6.8 ± 2.1 cm), but cysts <6 cm were significantly more common in emergency (36%) than in elective (15%) cases. Mature teratomas were significantly more common in elective cases (89% vs. 52%) but corpus luteum cysts were more common in emergency cases (0% vs. 32%). The rates of laparoscopic surgery (98.2% vs. 52.0%) and ovarian conservation (99.1% vs. 80.0%) were significantly higher, and post-surgical hospitalization (4.6 ± 1.3 vs. 9.8 ± 10.5 days) was significantly shorter in elective than in emergency cases. There was no significant difference in the gestational age for delivery (38.9 ± 1.9 vs. 38.4 ± 2.7 weeks), preterm birth rate (12% vs. 20%), or birth weight (2939 ± 469 vs. 3019 ± 510 g). CONCLUSIONS: We cannot state that an emergency surgery during pregnancy is rarely required for small benign ovarian cysts. However, the surgical outcomes were significantly better for elective than for emergency surgery, with no difference in perinatal outcomes. If a benign ovarian cyst is found early in pregnancy, elective laparoscopic surgery may be considered with adequate informed consent.

The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan.

Purpose: In 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016-2019) and compared the results with our previous survey (2011-2015). The authors also surveyed reproductive specialists' awareness of the guidelines and implementation problems. Methods: The authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology. Results: The authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011-2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists' interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources. Conclusions: The practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.

A practical survey of fertility-preservation treatments in the startup phase in Japan.

AIM: The actual status of fertility preservation treatments in the startup phase in Japan was investigated as a basis for discussing future directions. METHODS: This study was conducted as "Research project to promote support of children and parenting 2016" which was supported by Ministry of Health in Japan with the approval of the institutional review board at St. Marianna University. Subjects of the survey were facilities registered with the Japan Society of Obstetrics and Gynecology as fertility preservation facilities, and facilities belonging to the Japan Association of Private Assisted Reproductive Technology Clinics and Laboratories. We provided questionnaires to survey both the medical care system and cases for which fertility preservation was implemented between 2006 and 2016. RESULTS: Responses were obtained from 68 facilities (of the 64, 59 [92.2%] responded to the questionnaire and 9 clinics cooperated). Many facilities limited the cryopreservation of oocytes and ovaries to patients 40-41 years old and the use of eggs to patients 44-45 years old. In the patient survey, 812 cases of oocyte cryopreservation and 201 cases of ovarian tissue cryopreservation were performed during study period. Breast cancer was the most indicated disease, with oocyte cryopreservation in the late 30s and ovarian tissue cryopreservation in the early 30s. Very few babies were born from fertility preservation, and no live birth cases of ovarian tissue cryopreservation were identified. CONCLUSIONS: Even from the early days, fertility preservation was implemented according to certain standards in Japan, but was characterized by a large variety of facilities.

Guidance on the need for contraception related to use of pharmaceuticals: the Japan Agency for Medical Research and Development Study Group for providing information on the proper use of pharmaceuticals in patients with reproductive potential.

BACKGROUND: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have published guidelines on the use of cancer treatments in young people of reproductive potential. However, no such guideline is available in Japan. Therefore, this project aimed to gather relevant data and draft a respective guidance paper. METHODS: From April 2019 to March 2021, the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential at the Japan Agency for Medical Research and Development gathered opinions from experts in reproductive medicine, toxicology, and drug safety measures. The group considered these opinions, the FDA and EMA guidelines, and relevant Japanese guidelines and prepared a guidance paper, which they sent to 19 related organizations for comment. RESULTS: By November 2020, the draft guidance paper was completed and sent to the related organizations, 17 of which provided a total of 156 comments. The study group finalized the guidance paper in March 2021. CONCLUSIONS: The "Guidance on the Need for Contraception Related to Use of Pharmaceuticals" (The report of the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential, Research on Regulatory Science of Pharmaceuticals and Medical Devices, Japan Agency for Medical Research and Development: JP20mk0101139) is expected to help Japanese healthcare professionals provide fertility-related care and advice to adolescents, and young adults with cancer and their families.

Workflow Optimization for Identification of Female Germline or Oogonial Stem Cells in Human Ovarian Cortex Using Single-Cell RNA Sequence Analysis.

In 2004, the identification of female germline or oogonial stem cells (OSCs) that can support post-natal oogenesis in ovaries of adult mice sparked a major paradigm shift in reproductive biology. Although these findings have been independently verified, and further extended to include identification of OSCs in adult ovaries of many species ranging from pigs and cows to non-human primates and humans, a recent study rooted in single-cell RNA sequence analysis (scRNA-seq) of adult human ovarian cortical tissue claimed that OSCs do not exist, and that other groups working with OSCs following isolation by magnetic-assisted or fluorescence-activated cell sorting have mistaken perivascular cells (PVCs) for germ cells. Here we report that rare germ lineage cells with a gene expression profile matched to OSCs but distinct from that of other cells, including oocytes and PVCs, can be identified in adult human ovarian cortical tissue by scRNA-seq after optimization of analytical workflow parameters. Deeper cell-by-cell expression profiling also uncovered evidence of germ cells undergoing meiosis-I in adult human ovaries. Lastly, we show that, if not properly controlled for, PVCs can be inadvertently isolated during flow cytometry protocols designed to sort OSCs because of inherently high cellular autofluorescence. However, human PVCs and human germ cells segregate into distinct clusters following scRNA-seq due to non-overlapping gene expression profiles, which would preclude the mistaken identification and use of PVCs as OSCs during functional characterization studies.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2.

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.