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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.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

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.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.

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.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.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.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.

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.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.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%.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.

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.

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.

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.

Background: Bortezomib is used as first-line therapy for multiple myeloma. Observational studies based on the FDA Adverse Event Reporting System database analysis and systematic reviews indicate that the incidence of peripheral neuropathy (PN) and tumor lysis syndrome (TLS) tends to be higher with bortezomib than that of other drugs. In a comprehensive analysis assessing drugs that cause PN in Japanese patients, the incidence of bortezomib-induced adverse events (AEs) was reportedly high. However, a comprehensive assessment of bortezomib is lacking. Objectives: The purpose of this study was to determine the frequency of bortezomib AEs in Japanese patients and to determine the incidence, time to onset, and post hoc outcomes of unique AEs using the Japanese Adverse Drug Event Report database. Method: To investigate the association between bortezomib and AEs, we analyzed the Japanese Adverse Drug Event Report database, which contains spontaneous AE reports submitted to the Pharmaceuticals and Medical Devices Agency from April 2004 to December 2020. Criteria indicating the presence of an AE signal were met when the following requirements were fulfilled: proportional reporting ratios ≥2 and χ2 ≥ 4. Time to onset and post-event outcomes were analyzed for characteristic AEs. Results: Among 26 extracted AEs, 13 presented AE signals. The post-exposure outcomes of 12 AEs showed fatal outcomes at rates exceeding 10%, including cardiac failure (30%), lung disorder (24%), pneumonia (18%), and TLS (10%). Furthermore, a histogram of time to onset revealed that the 12 AEs were concentrated from the beginning to approximately 1 month after bortezomib administration. The median onset times for cardiac failure, lung disorder, pneumonia, and TLS were 28, 13, 42, and 5 days, respectively. Conclusions: Cardiac failure, lung disorder, pneumonia, and TLS had a higher rate of fatal clinical outcomes after onset than other AEs. These AEs exhibited a greater onset tendency in the early post-dose period. This study suggests that there is a need to monitor signs of cardiac failure, lung disorder, pneumonia, and TLS, potentially resulting in serious outcomes.

This article presents a continuous-time (CT) multistage noise-shaping (MASH) delta–sigma ( $\Delta \Sigma$ ) analog-to-digital converter (ADC) with enhanced tolerance to temperature and operating-frequency variations through on-chip multi-rate (MR) background calibration based on the least-mean-square (LMS) algorithm. The proposed digital calibration, which combines MR operation, post-conditioners, and pseudorandom-noise injection at the quantizer input, efficiently and accurately matches digital transfer functions to the corresponding analog ones for cancellation of quantization error. The first modulator in the proposed MASH ADC considers sufficient quantizer delay and reduces input-signal leakage into the second modulator to enable successful quantization-error transmission while minimizing distortion in the second stage, which cannot be tolerated in the case of calibrated digital noise-cancellation filter. A CT 2–2 MASH $\Delta \Sigma $ ADC prototype fabricated in 40-nm CMOS achieves the dynamic range (DR) of 79 dB and the signal-to-noise and distortion ratio (SNDR) of 78.5 dB over an 8-MHz bandwidth with 7.3-mW analog power and 16-mW digital power, reaching Schreier figure of merit (FoMs) of 168.9 dB, and demonstrates conversion-accuracy robustness within 1-dB SNDR fluctuation for temperature variations from −40° to 125° and within 2-dB SNDR degradation for frequency variations of 20% range.

It is necessary to assess functional impairment when treating schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) has been adopted as a measure of functional disability in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This study was a secondary analysis from a cross-sectional study of health-related behaviors among patients with schizophrenia. We examined the validity and reliability of the Japanese version of the 12-item WHODAS 2.0 when self-administered by such patients. Participants were 350 outpatients with schizophrenia from a psychiatric hospital. The standard six-factor structure of the WHODAS 2.0 showed a good fit for these participants. The Cronbach's alpha coefficient was 0.858, showing good internal consistency. The WHODAS 2.0 showed moderate correlations with the modified Global Assessment of Functioning and Kessler 6 scales (r=-0.434 and 0.555, respectively). The results of this study show that the Japanese version of the 12-item self-administered WHODAS 2.0 has good internal consistency and convergent validity among patients with schizophrenia. Further exploration of the usefulness of WHODAS 2.0 in clinical settings is needed.

This letter presents a continuous-time (CT) multi-stage noise-shaping (MASH) delta–sigma ADC with enhanced tolerance to temperature and operating frequency variations through multi-rate background calibration based on the least-mean-square (LMS) algorithm. A first stage modulator of the proposed ADC, which considers sufficient quantizer delay and reduces input signal leakage into second stage modulator, enables undisturbed quantization error cancellation with digital noise-cancellation filter (DNCF) calibration. A CT 2-2 MASH delta–sigma ADC prototype fabricated in 40-nm CMOS achieves DR of 79 dB, SNDR of 78.5 dB over an 8-MHz bandwidth, Schreier figure of merit (FoMs) of 168.9 dB and demonstrates conversion accuracy robustness within 1-dB SNDR fluctuation for temperature variations from −40 to 125 degrees, and within 2-dB SNDR degradation for frequency variation of 20% range.

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.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.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.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.

Background We performed a follow up study about willingness and behaviors to quit smoking among smokers with schizophrenia in Japan. Methods Participants were outpatients with schizophrenia aged 20–69 years who had been visiting the hospital for ≥1 year as of April 1, 2016, and had visited the hospital more than once in the previous 6 months. A baseline survey on smoking behaviors including current smoking status and smoking cessation stage, was administered in 420 participants that were randomly extracted from a patient pool (n = 680) in 2016, and a follow-up survey was administered in 2017. We calculated the distribution and change in smoking cessation stage, number of smokers and nonsmokers after 1 year, and quitting rate from a naturalistic 1-year smoking-cessation follow up. Results The number of baseline respondents was 350; 113 current smokers and 68 former smokers. Among the 113 current smokers, 104 (92.0%) were followed for 1 year, 79 (70.0%) were interested in smoking cessation, and only 7 had received smoking cessation treatments at baseline. Among the tracked 104 participants, only 6 (5.8%) stopped smoking after 1 year. Among the 25 participants who had intentions to quit smoking within 6 months at baseline, 6 (24.0%) maintained their intention to quit smoking for 1 year, and 16 (64.0%) did not maintain their intention to quit smoking. Conclusions Our findings showed that many smokers with schizophrenia were interested in quitting smoking, but few patients received treatment and actually quit smoking. Timely intervention, including the option to receive smoking cessation treatment, is necessary for those patients with schizophrenia who smoke. Trial registration UMIN Clinical Trials Registry (UMIN000023874, registered on August 31, 2016).

OBJECTIVE We examined the efficacy of a case management approach to improve participation in colorectal cancer screening among people with schizophrenia. METHODS This was a randomized, parallel group trial. We recruited outpatients with schizophrenia aged 40 years or over from two psychiatric hospitals in Japan. Participants were randomly assigned (1:1) to treatment as usual or case management intervention plus treatment as usual using a web-based system. Attending clinicians and participants were unmasked to the allocation. Case management included education and patient navigation for colorectal cancer screening using a fecal occult blood test. Treatment as usual included direct mail government recommendations. The primary endpoint was participation in colorectal cancer screening assessed using municipal records. We also assessed the secondary endpoint of participation in other cancer screenings (lung, gastric, breast, and cervical). RESULTS Between 3 June and 9 September 2019, 172 eligible participants were randomly assigned to the case management plus treatment as usual group (n = 86) or treatment as usual group (n = 86). One participant was ineligible and another withdrew consent; both were excluded from analysis. A significantly higher proportion of participants received colorectal cancer screening in the case management plus treatment as usual group than in the treatment as usual group (40 [47.1%] of 85 participants vs. 10 [11.8%] of 85 participants, p

ObjectivesWe 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 settingThis 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.ParticipantsOf 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 analysisUsing 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.ResultsForty-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.ConclusionsThis study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers.Trial registration numberUMIN000036017.

Ischemia–reperfusion injury impairs the efficacy of reperfusion therapy after ischemic stroke. Cyclophilin D (CypD)-mediated openings of mitochondrial permeability transition pore (mPTP) and subsequent monocyte-mediated inflammation are considered as major mechanisms of reperfusion injury. However, no medical therapies are currently available. Therefore, we have tested a hypothesis that simultaneous targeting of mPTP and inflammation confers substantial neuroprotection after cerebral ischemia–reperfusion. To address this point, we prepared CypD knockout mice, C–C chemokine receptor 2 (CCR2) knockout mice and CypD/CCR2 double knockout mice. These mice were subjected to 60 min transient cerebral ischemia by occluding middle cerebral arteries. Neurological deficits evaluated 3 days after reperfusion were significantly attenuated in CypD/CCR2 double knockout mice as compared to wild-type mice and other single knockout mice. Then, we have prepared polymeric nanoparticles containing cyclosporine A (CsA-NPs) and pitavastatin (Pitava-NPs), targeting mPTP opening and inflammation, respectively. Simultaneous administration of CsA-NP and Pitava-NP at the time of reperfusion also decreased infarct size and attenuated neurological deficits as compared to control nanoparticles and single administration of CsA-NPs or Pitava-NPs. These results indicate that simultaneous targeting of the mPTP opening and monocyte-mediated inflammation could be a novel strategy for better neurological outcomes in patients with ischemic stroke.

The mm-wave radar is an indispensable component for autonomous driving. A continuous-time (CT) $\Delta\Sigma$ ADC is expected to be suitable for this application due to its high precision and wide bandwidth as well as inherent anti-aliasing effect. However, the stable performance of the ADC against excessive input and PVT variations is a primary issue for real products which has so far not been addressed sufficiently. Since a high OSR for a wide-band CT $\Delta\Sigma$ ADC requires a prohibitively high sampling rate, the higher-order noise shaping [1] needs to be applied instead. In addition, the MASH structure [2-3] is preferred due to its robustness against the instability caused by excessive input. However, since the analog transfer function of a CT MASH $\Delta\Sigma$ ADC is vulnerable to PVT variations, significant quantization-noise leakage occurs due to mismatch of the transfer function between analog and digital domains. Although the sturdy-MASH (SMASH) structure [4] can obviate the transfer-function matching on the first stage, it requires a zero-order second stage for sufficient matching on this stage, which needs to be compensated by a 4b quantizer and noise coupling [5]. Such design complication makes the PVT-robust operation of SMASH a critical issue.

Background Smoking behavior among people with serious psychological distress (SPD) has not been fully investigated in Asia, although smoking has become a public health concern worldwide. Many Western population-based studies indicate that people with psychological distress are more likely to smoke. Methods This study used a national representative data set from the 2010 Comprehensive Survey of Living Conditions of Japan. SPD was defined as scores ≥13 or greater on the Kessler Psychological Distress Scale (K6). Multivariate logistic regression analyses were conducted to analyze the association between SPD and current smoking in Japanese adults. Results In both men (n = 27,937) and women (n = 30,786), SPD was significantly associated with current smoking (adjusted odds ratios [95% confidence intervals]: 1.169 [1.030–1.328] for men and 1.677 [1.457–1.931] for women). Among men, SPD was significantly associated with current smoking only in people aged ≥50 years (1.519 [1.232–1.874]) and married (1.456 [1.228–1.728]). SPD was significantly associated with current smoking in women of all ages. SPD had a greater impact on current smoking for women aged 20–49 years than for those aged ≥50 years (1.832 [1.552–2.162] and 1.445 [1.099–1.900], respectively). Limitations The cross-sectional design precludes assumptions about the direction of causality. In addition, smoking status was self-reported. Conclusions SPD was significantly associated with current smoking in Japan and the association was much stronger for younger women. Clinical strategies are needed to reduce the prevalence of smoking among people with SPD to reduce excess mortality in this population.

The syntheses of fluorinated cyclopentanone derivatives, which have pharmaceutical and agrochemical importance are reported. The catalytic reaction of copper(I) and nickel(II) difluorocarbenes with silyl dienol ethers afforded 4,4-difluoro- and 5,5-difluorocyclopent-1-en-1-yl silyl ethers, respectively. The fluorine-directed and -activated Nazarov cyclization of 1-fluorovinyl vinyl ketones, which were prepared from silyl dienol ethers and free difluorocarbene, proceeded efficiently to afford 2-fluorocyclopent-2-en-1-ones. Moreover, fluorine-­directed Nazarov cyclizations of 2,2-difluorovinyl vinyl ketones and 1-(trifluoromethyl)vinyl vinyl ketones afforded 3-fluorocyclopent-2-en-1-ones and 5-(trifluoromethyl)cyclopent-2-en-1-ones, respectively. In addition, derivatization of ring-difluorinated products also provided 3-fluorocyclopent-2-en-1-ones.

BACKGROUND It is unclear whether individuals who have serious psychological distress (SPD) are less likely to participate in screening tests for gastric cancer, lung cancer, and other types of cancer. Of the few studies that have examined the association between SPD and participation in cancer screening, none have reported modifying effects of educational, marital, or employment status. METHODS The authors analyzed a national representative data set from the 2010 Comprehensive Survey of Living Conditions of Japan., including individuals aged

Aim The influence of schizophrenic patients’ functional disability on cancer screening participation worldwide is unclear. There are few findings on the disparities in schizophrenic patients’ participation in cancer screening programs in Asia. The aim of this study was to investigate the screening rate and the associations between screening and symptom severity/functional disability in patients with schizophrenia. Methods This cross-sectional study was conducted in a psychiatric hospital outpatient clinic in Japan. We recruited schizophrenic patients meeting the national program criteria for cancer screening for colorectal, gastric, lung, breast, and cervical cancer (n = 224, 223, 224, 110, and 175, respectively). Receipt of cancer screenings was assessed using a self-report questionnaire. Scores on the modified Global Assessment of Functioning (mGAF) were evaluated by participants’ primary psychiatrists. Results Rates of cancer screenings were as follows: 24.1% for colorectal, 21.5% for gastric, 30.8% for lung, 25.5% for breast, and 19.4% for cervical cancer. A multivariable logistic analysis showed that a 1-point increase in severity/disability (100 minus mGAF score) was associated with significantly lower odds ratios (OR) for receipt of cancer screenings, except for breast cancer (OR, 0.95, 95% confidence interval [CI], 0.93–0.98 for colorectal; OR, 0.96, 95%CI, 0.93–0.98 for gastric; OR, 0.95, 95%CI, 0.93–0.97 for lung; OR, 0.97, 95%CI, 0.94–1.00 for breast; and OR, 0.95, 95%CI, 0.92–0.98 for cervical cancer). Conclusion The findings demonstrated low rates of cancer screenings in schizophrenic patients in Japan. Our study suggests the need to encourage attendance at cancer screenings, especially in schizophrenic patients with severe symptoms/functional disability.

IntroductionOne of the reasons for the high mortality rate from cancer in people with schizophrenia is delay in diagnosis. Many studies have shown lower cancer screening rates in people with schizophrenia; however, there are no interventions for people with schizophrenia to increase cancer screening. Therefore, we developed a case management (CM) intervention to encourage participation in cancer screening. The purpose of this study was to examine the efficacy of CM to encourage participation in cancer screening for people with schizophrenia, with particular focus on colorectal cancer screening by faecal occult blood testing, compared with usual intervention (UI), namely, municipal public education.Methods and analysisThis is an individually randomised, parallel group trial with blinded outcome assessments. The participants will be randomly allocated to either the CM plus UI group or UI alone group in a 1:1 ratio using a web-based program at a data management centre. The primary end point of the study is participation in colorectal cancer screening in the year of intervention, which will be assessed based on municipal records.Ethics and disseminationThis study is performed in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan’s Ministry of Education, Science, and Technology and the Ministry of Health, Labour, and Welfare and the modified Act on the Protection of Personal Information as well as the Declaration of Helsinki. This study was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital on 23 April 2019 (approval number: RIN1904-003). The findings of this trial will be submitted to an international peer-reviewed journal.Trial registration numberUMIN000036017.

Internet addiction (IA) has been reported as prevalent in adolescents with autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD). However, the course of IA in this population has not been elucidated. The authors performed a 2-year follow-up study including 89 out of 132 adolescents with ASD and/or ADHD in a psychiatric clinical setting who participated in the original cross-sectional study assessing IA prevalence. Within this sample of participants from both the original and the follow-up study, results showed a 2-year IA remission and incidence rate of 60% and 5%, respectively. Our findings imply that the course of IA in psychiatric populations with ASD and/or ADHD might be similar to reports from previous studies with general adolescent populations.