A feasibility study of provider-level implementation strategies to improve access to colorectal cancer screening for patients with schizophrenia: ACCESS2 (N-EQUITY 2104) trial.

BACKGROUND: People with schizophrenia have a lower colorectal screening rate than the general population. A previous study reported an intervention using case management to encourage colorectal cancer screening for patients with schizophrenia in psychiatric outpatient settings. In this feasibility study, we developed provider-level implementation strategies and evaluated the feasibility of conducting a definitive trial in terms of the penetration of the intervention assessed at the patient level. Additionally, we examined the fidelity of strategies to implement the intervention at the provider level in a routine clinical psychiatric setting. METHODS: This was a multicenter, single-arm feasibility study with medical staff at psychiatric hospitals in Japan. The provider-level implementation strategies developed in this study included three key elements (organizing an implementation team appointed by the facility director, interactive assistance using a clear guide that outlines who in the hospital should do what, and developing accessible educational materials) to overcome major barriers to implementation of the intervention and four additional elements (progress monitoring, joint meetings and information sharing among participating sites, adaptation of encouragement methods to specific contexts, and education of on-site staff), with reference to the elements identified in the Expert Recommendations for Implementing Change (ERIC). The feasibility of the strategies was evaluated by the proportion of patients who were eligible for encouragement (patients with schizophrenia aged 40, 50, or 60) who received encouragement. We set the goal of providing encouragement to at least 40% of eligible patients at each site. RESULTS: Two public and four private psychiatric hospitals in Okayama and Shimane prefectures participated in this study. Regarding fidelity, all elements of the strategies were conducted as planned. Following the procedures in the guide, each team prepared and provided encouragement according to their own facility and region. Penetration, defined as the proportion of eligible patients who received encouragement, ranged from 33.3 to 100%; five of the six facilities achieved the target proportion. CONCLUSIONS: The provider-level implementation strategies to implement encouragement were feasible in terms of penetration of the intervention assessed at the patient level. The results support the feasibility of proceeding with a future definitive trial of these strategies. TRIAL REGISTRATION: jRCT, jRCT1060220026 . Registered on 06/04/2022.

Adverse Event Profile of Azacitidine: Analysis by Route of Administration Using Japanese Pharmacovigilance Database.

INTRODUCTION: Azacitidine is a useful drug for myelodysplastic syndromes and acute myeloid leukemia. In clinical trials, hematologic toxicity and infection have been observed as adverse events (AEs) of this drug. However, information on the time to onset of high risk AEs and subsequent outcomes, as well as differences in the frequency of AEs due to the route of administration is lacking. In this study, we investigated azacitidine-induced AEs comprehensively using the Japanese Adverse Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency, with disproportionate analysis of AE incidence trends, time to onset, and subsequent outcomes. In addition, we analyzed the differences in AEs by route of administration and the number of days until the occurrence of AEs and generated hypotheses. METHODS: The study used JADER data reported from April 2004 to June 2022. Risk estimation was conducted using reported odds ratio. A signal was detected when the lower limit of the 95% confidence interval of the calculated ROR was ≥1. RESULTS: A total of 34 signals were detected as AEs due to azacitidine. Among them, 15 were hematologic toxicities and 10 were infections, which demonstrated a particularly high rate of death. Signals of AEs such as tumor lysis syndrome (TLS) and cardiac failure, which have been described in case reports, were also detected, and the rate of death after onset was high. In addition, more AEs generally occurred within the first month of treatment. CONCLUSION: The results of this study suggest that more attention should be paid to cardiac failure, hematologic toxicity, infection, and TLS. Because many patients in clinical trials have discontinued treatment due to serious AEs before the therapeutic effect became apparent, appropriate supportive care, dose reduction, and drug withdrawal are important for the continuation of treatment.

Epicardial connection(s) inside the pulmonary vein antrum isolation lines contribute to subsequent atrial fibrillation: a case report.

Aims: Recent reports have demonstrated that ∼10% of patients with atrial fibrillation (AF) have epicardial connections (ECs) inside the pulmonary vein (PV) antrum isolation (AI) (PVAI) lines, which could be a possible mechanism of failure to achieve a complete PVAI, thus contributing to AF recurrence. Case summary: We present an 80-year-old female case with consistently continuing AF associated with ECs. Epicardial connections involving the PVs were detected in the left and right superior PVs after the completion of the PVAI. The AF steadily terminated after the ablation of those ECs. She has remained well without any AF or symptoms for 2 years post-ablation. Discussion: Those ECs might have played a possible important role in initiating and maintaining the AF. The mechanism(s) of the ECs may be a cornerstone of the failure to achieve a complete PVAI contributing to AF recurrence. Ablation of the EC(s) in addition to the PVAI may be better able to achieve the completion of the PVAI. Thus, physicians should be aware of the possibility of the presence of EC(s) when performing ablation of AF, even though complete PVAI lines have been achieved.

Venous Thromboembolism in Eating Disorders: A Retrospective Observational Study.

Eating disorders (EDs) are associated with a high mortality rate. Patients with EDs often experience severe dehydration due to food restriction and/or vomiting. Severely underweight patients are often prescribed bed rest during inpatient care to reduce their energy consumption, and they may thus develop multiple risk factors for venous thromboembolism (VTE). We compared the clinical features of ED inpatients with VTE to those of ED inpatients without VTE. Seventy-one inpatients with ED were treated at Okayama University Hospital's psychiatric ward in 2016-2020; five were experienced a VTE. Compared to the non-VTE group, the VTE group's median age and disease duration were greater and the median body mass index (BMI) was lower. The VTE group's D-dimer peak values were > 5 mg/L. Physical restraint and central venous catheter use were associated with VTE. Longer ED duration and lower BMI might be risk factors for VTE. To make inpatient treatment for ED safer, it is important to avoid the use of physical restraints and central venous catheters. Continuous D-dimer monitoring is necessary for the early detection of VTE in ED patients at high risk of VTE.

Perceptions toward issues in cancer care for people with mental illness among psychiatric care providers: A questionnaire study.

OBJECTIVES: To reduce cancer care disparities in people with mental illness, this study aimed to quantify psychiatric care providers' perceptions regarding issues that are insufficiently addressed or difficult to address. METHODS: Psychiatric care providers at 23 psychiatric hospitals in Japan were surveyed using mail questionnaires. Respondents were asked to rate 15 items with four categories related to insufficiencies/difficulties in cancer care for patients with mental illness on a five-point Likert scale. We analyzed the proportion of respondents who answered "insufficient/difficult" for each item. RESULTS: A total of 255 (76.3%) psychiatric care providers responded. For questions related to the skills and attitudes of psychiatric professionals, 48.3%-58.4% of respondents perceived that efforts for supporting cancer screening and treatment were insufficient. For the questions related to collaborations between cancer and psychiatric care providers, 75.3% of respondents perceived that inpatient visits between psychiatric and cancer hospitals were insufficient. For the questions related to in-psychiatric-hospital medical systems, 50.2%-87.2% of respondents perceived that support for screening, diagnosis/treatment, and palliative care for psychiatric inpatients were insufficient/difficult. 41.9%-57.4% of respondents perceived that social services in the community were insufficient. CONCLUSIONS: This study clarified the level of insufficiency/difficulty perceived by psychiatric care providers regarding issues related to cancer care for people with mental illness. Psychiatric care providers are required to have knowledge and skills in cancer screening and treatment. To improve access to cancer prevention, treatment, and palliative care, it may be helpful to establish systems to promote coordination between cancer hospitals and psychiatric hospitals.

Cardiac Adverse Events Associated with Multiple Myeloma Patients Treated with Proteasome Inhibitors.

BACKGROUND: Proteasome inhibitors (PIs) are standard treatments for multiple myeloma (MM). The risk of cardiac adverse events (CAEs) with PIs has been documented with bortezomib and carfilzomib; however, only a few studies have been reported on ixazomib. Furthermore, the effects of concomitant medications including dexamethasone and lenalidomide remain unclear. OBJECTIVES: This study aimed to determine the safety signals of adverse events related to CAEs, the effect of concomitant medications, the time to the occurrence of CAEs, and the incidence of fatal clinical outcomes after the occurrence of CAEs for three PIs using the US Pharmacovigilance database. METHODS: We examined 1,567,240 cases of 231 drugs registered as anticancer drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1997 to March 2021. We compared the odds of developing CAEs between patients who received PIs and those who received non-PI anticancer drugs. RESULTS: Bortezomib treatment resulted in significantly higher reporting odds ratios (RORs) for cardiac failure, cardiac failure congestive, and atrial fibrillation. Carfilzomib treatment resulted in significantly higher RORs for cardiac failure, congestive cardiac failure, atrial fibrillation, and QT prolonged. However, no adverse event CAE signals were observed with ixazomib treatment. A signal was detected for the safety of cardiac failure with bortezomib or carfilzomib, regardless of the presence or absence of concomitant medications. Safety signals for cardiac failure congestive with bortezomib and for cardiac failure congestive, atrial fibrillation, and QT prolonged with carfilzomib were observed only with dexamethasone combination therapy. Co-administration of lenalidomide and its derivatives did not affect the safety of bortezomib and carfilzomib. CONCLUSION: We identified CAE safety signals for bortezomib and carfilzomib exposure when compared with 231 other anticancer agents. The safety signal for developing cardiac failure for both the drugs did not differ between patients with and without concomitantly administered medications.

The Influence of the Rapid Increase in the Number of Adverse Event Reports for COVID-19 Vaccine on the Disproportionality Analysis Using JADER.

BACKGROUND/AIM: The COVID-19 prophylactic vaccine for the prevention of coronavirus infection was approved in Japan on February 14, 2021. Adverse event reports for the vaccine were collected from the Japan Adverse Drug Event Relief (JADER) database, similar to those for drugs. Reported odds ratios (RORs) and proportional reporting ratios (PRRs) are commonly used in disproportionality analysis to detect safety signals. Therefore, adverse event reports from the vaccinated population may affect the detection of safety signals for the registered drugs. This study determined the impact of adverse event reports on the detection of safety signals for a COVID-19 prophylactic vaccine by analyzing the JADER database using disproportionality analysis. PATIENTS AND METHODS: We extracted data from the JADER dataset, in which the COVID-19 vaccine was reported as a suspected drug, and selected the top 10 adverse events in terms of the number of reports. We then extracted the top 30 drugs by the amount of information in the selected 10 adverse events and compared the changes in the number of signal detections with and without the COVID-19 vaccine report data. RESULTS: The total number of adverse events reported in the JADER database during the study period was 2,002,564. Of the total number of reports, 85,489 (4.3%) reported adverse events related to the COVID-19 vaccine. Of the top 30 drugs reported in the 10 selected adverse events, the ROR and PRR were found to be lower with the inclusion of COVID-19 vaccine data than without. Detection by ROR excluded 23 out of 245 drugs, and detection by PRR excluded 34 out of 204 drugs. CONCLUSION: The rapid increase in the number of adverse event reports for the COVID-19 vaccine in JADER may affect the detection of safety signals by disproportionality analysis.

Comprehensive Analysis of Adverse Events Induced by PARP Inhibitors Using JADER and Time to Onset.

Poly (ADP-ribose) polymerase (PARP) inhibitors are effective against breast cancer susceptibility gene (BRCA) mutations. Clinical trials have reported hematologic toxicity and gastrointestinal symptoms as class effects of PARP inhibitors. However, information on adverse events (AEs) in a Japanese clinical cohort is currently lacking. In this study, we conducted a comprehensive survey of the AEs of two PARP inhibitors, olaparib and niraparib, using the Japanese Adverse Reaction Reporting (JADER) database provided by the Pharmaceuticals and Medical Devices Agency (PMDA). Moreover, we also analyzed the course and time to the onset of AEs. Signals were detected for 15 and 11 AEs for olaparib and niraparib, respectively. Most occurred within the first month of treatment with either agent. These results may indicate the importance of early response and monitoring after beginning PARP inhibitor therapy. The results of this study may be useful for managing side effects and suggesting supportive care for patients using PARP inhibitors in the future.

Epicardial Connections After a Conventional Pulmonary Vein Antrum Isolation in Patients With Atrial Fibrillation.

BACKGROUND: The existence of epicardial connection(s) (ECs) between the pulmonary veins (PVs) and atrium may hinder establishing a complete PV antrum isolation (AI) (PVAI) in patients with atrial fibrillation (AF). Thus, the purpose of this study was to determine the prevalence and location of ECs inside the conventional PVAI lines.Methods and Results: Three-hundred consecutive patients with non-valvular AF were evaluated. This study revealed that: (1) the prevalence of patients with ECs and the number of ECs per patient between the PVs and atrium became significantly greater, respectively, in accordance with the progression of paroxysmal to long-lasting AF and left atrial enlargement; (2) some ECs were located at sites far distal to the PVAI lines; (3) 25% of ECs could be detected only by high-density mapping catheters, but not by conventional circular mapping catheters; (4) a B-type natriuretic peptide (BNP) level of 176.6pg/mL and left atrial volume (LAV) of 129.0 mL may be important predictors of the presence of ECs; and (5) the rate of conduction of ECs from the right PVs was dominantly to the atrium and His-bundle, and that from the left PVs to the coronary sinus was most dominant. CONCLUSIONS: The PVAI may not be completed by using only a conventional PVAI method, and additional EC ablation inside the PVAI lines detected using high-density mapping may be able to achieve a more complete PVAI.

Patients' acceptability and implementation outcomes of a case management approach to encourage participation in colorectal cancer screening for people with schizophrenia: a qualitative secondary analysis of a mixed-method randomised clinical trial.

OBJECTIVES: We examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients' acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers. STUDY DESIGN AND SETTING: This study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention. PARTICIPANTS: Of the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included. DATA COLLECTION AND ANALYSIS: Using a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised. RESULTS: Forty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources. CONCLUSIONS: This study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers. TRIAL REGISTRATION NUMBER: UMIN000036017.

Issues of cancer care in people with mental disorders as perceived by cancer care providers: A quantitative questionnaire survey.

OBJECTIVES: To reduce cancer care disparities, this study aimed to clarify the difficulties in cancer care for people with mental disorders as perceived by cancer care providers. METHODS: Cancer care providers at 17 designated cancer hospitals in Japan were surveyed using mail questionnaires. Respondents were asked to rate 29 items related to difficulties or insufficiencies in cancer care for patients with mental disorders on a five-point Likert scale. We analyzed the proportion of respondents who answered "difficult/insufficient" in each item. We also calculated the proportions of responders stratified according to the presence of psychiatric support systems within their hospitals. RESULTS: A total of 388 (58.4%) cancer care providers responded. Among the issues related to "difficulties in diagnosing and treating cancer," support for decision-making, assessment of treatment adherence, and assessment of physical symptoms were perceived as most difficult (73.5%-81.5% of respondents). Among the issues related to 'difficulties or insufficiencies in collaboration among multidisciplinary health care providers,' the issue of advance consultation and sharing information with the patient's primary psychiatric care provider was perceived as most difficult (52.2%). Among the issues related to "insufficiencies of in-hospital and community medical systems," education to provide reasonable accommodation was perceived as most insufficient (47.4%). The perceived difficulties of over half of the issues varied significantly between hospitals depending on the level of psychiatric support systems. CONCLUSIONS: This study clarified the difficulties of cancer care in patients with mental disorders as perceived by cancer care providers. Some issues may be resolved by psychiatric liaison teams.

Comprehensive Analysis of Ixazomib-Induced Adverse Events Using the Japanese Pharmacovigilance Database.

BACKGROUND: Ixazomib is an orally available proteasome inhibitor for multiple myeloma with adverse effects such as gastrointestinal symptoms, skin rashes, and thrombocytopenia reported in clinical trials and post-marketing surveillance, resulting in treatment discontinuation. However, comprehensive adverse event (AE) assessments for ixazomib are lacking. OBJECTIVES: Herein, we aimed to determine the frequency and risk of AEs associated with ixazomib in Japanese patients using the Japanese Adverse Event Reporting Database (JADER). Additionally, the time to onset and post hoc outcomes of unique AEs were clarified. METHODS: To investigate the association between ixazomib and AEs, we analyzed the JADER database, comprising voluntary AE reports submitted to the Pharmaceuticals and Medical Devices Agency, between April 2004 and June 2021. AEs with ≥10 reports were included in the analysis, and criteria for the presence of AE signals were defined as meeting the requirements of proportional report ratio ≥2 and χ2 ≥ 4. Characteristic AEs were analyzed considering time to onset and onset outcomes. RESULTS: Of 34 extracted AEs, 18 presented AE signals. The 12 post hoc outcomes with fatality rates ≥10% included septic shock (50.0%), infection (41.2%), heart failure (16.7%), pneumonia (14.2%), and tumor necrosis syndrome (13.3%). A median of the time to onset showed that 11 of the 18 AEs occurred from ixazomib initiation to approximately 1 month later. CONCLUSION: Our results suggest that ixazomib may increase the incidence of 18 AEs, 11 of which occurred within the first month of treatment. Furthermore, 8 AEs were found to have potentially fatal outcomes at a rate of ≥10%. Therefore, monitoring AEs during the first month of treatment appears necessary.

Comprehensive analysis of everolimus-induced adverse events using the Japanese real-world database.

WHAT IS KNOWN AND OBJECTIVES: As for adverse events (AEs) caused by everolimus, findings from clinical trials and post-marketing surveillance have reported interstitial lung disease, hyperglycaemia, cardiovascular disease, etc. However, these reports are limited to incidence, and detailed studies on the risk of occurrence, time to onset and post-event clinical outcomes are only related to hyperglycaemia. The purpose of this study was to perform a comprehensive analysis of adverse events during everolimus therapy in patients with renal cell carcinoma (RCC) using the Japanese Adverse Event Report database. METHODS: Data reported between April 2004 and June 2021 in the Japanese Adverse Drug Event Report database were extracted for use. The reported odds ratio, time to onset and post-event course were analysed for the top 30 adverse events reported. RESULTS AND DISCUSSION: Among the top 30 adverse events, 23 adverse event signals were detected and classified into seven categories: lung-related AEs, haematological-related AEs, cancer progression, blood glucose-related AEs, hepatic-related AEs, renal-related AEs and others. The lung-related adverse events category was the most common, and the proportion of fatal outcomes after the occurrence of two adverse events related to infectious pneumonia was more than 10%. WHAT IS NEW AND CONCLUSION: A comprehensive survey of adverse events associated with everolimus administration using the pharmacovigilance database revealed that pulmonary and haematological AEs are frequently reported. The results suggest that attention should be paid to the occurrence of lung disorders because they may lead to fatal outcomes.

Association between depression in chronic phase and future clinical outcome of patients with schizophrenia.

RATIONALE: Depression in schizophrenia is an important symptom. We investigated whether depression and suicidal symptoms in the chronic phase are related to remote future clinical outcomes in patients with schizophrenia and whether psychotropics improved clinical outcomes. OBJECTIVES: The subjects included 462 outpatients of working age (15 to 64 years old) with schizophrenia treated at Okayama University Hospital from January 2010 to December 2011. We investigated the relationship between the Clinical Global Impression-Severity score at the last visit (average 19.2 years) and the existence of previous depression, suicidal ideas, and suicide attempts. We adjusted by several possible confounders including medical history using multiple regression analysis or logistic regression analysis. RESULTS: Of 462 patients, 168 (36.4%) presented with depression 2 years after schizophrenia onset. A history of suicidal ideas and attempts was related to worse clinical outcome. In males, a history of depression was related to worse clinical outcome, but not in females. Lithium carbonate was related to better clinical outcome in all schizophrenia patients with depression, especially in males. Treatment with antidepressants was related to better clinical outcome only in males. CONCLUSIONS: A history of depression or suicidal symptoms in the chronic phase predicted the future worse clinical outcome in patients with schizophrenia. The administration of lithium carbonate or antidepressants might be recommended, especially to male schizophrenia patients with depression.