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.

Rotatable sphincterotome as a rescue device for endoscopic retrograde cholangiopancreatography cannulation: a single-center experience.

BACKGROUND/AIMS: Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation. METHODS: We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021. RESULTS: TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups. CONCLUSION: The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Risk factors for recurrent stenosis after balloon dilation for benign hepaticojejunostomy anastomotic stricture.

BACKGROUND/AIMS: Hepaticojejunostomy anastomotic stricture (HJAS) is a feared adverse event associated with hepatopancreatobiliary surgery. Although balloon dilation for benign HJAS during endoscopic retrograde cholangiopancreatography with balloon-assisted enteroscopy has been reported to be useful, the treatment strategy remains controversial. Therefore, we evaluated the outcomes and risk factors of recurrent stenosis after balloon dilation alone for benign HJAS. METHODS: We retrospectively analyzed consecutive patients who underwent balloon-assisted enteroscopy-endoscopic retrograde cholangiopancreatography for benign HJAS at our institution between July 2014 and December 2020. RESULTS: Forty-six patients were included, 16 of whom had recurrent HJAS after balloon dilation. The patency rates at 1 and 2 years after balloon dilation were 76.8% and 64.2%, respectively. Presence of a residual balloon notch during balloon dilation was an independent predictor of recurrence (hazard ratio, 2.80; 95% confidence interval, 1.01-7.78; p=0.048), whereas HJAS within postoperative 1 year tended to be associated with recurrence (hazard ratio, 2.43; 95% confidence interval, 0.85-6.89; p=0.096). The patency rates in patients without a residual balloon notch were 82.1% and 73.1% after 1 and 2 years, respectively. CONCLUSION: Balloon dilation alone may be a viable option for patients with benign HJAS without residual balloon notches on fluoroscopy.

Two-devices-in-one-channel method for fractured pancreatic duct stent retrieval in a case of severe chronic pancreatitis.

When a pancreatic plastic stent for symptomatic chronic pancreatitis breaks during its removal, severe pancreatic duct stenosis may complicate its retrieval. Takuma and colleagues report on the successful retrieval of a fragmented and displaced pancreatic plastic stent by applying the two-device-in-one-channel method using forceps and a snare.

Comparison of the incidence of vancomycin-associated nephrotoxicity following the change from trough-guided dosing to AUC-guided doing using trough-only data.

OBJECTIVES: Although use of AUC-guided vancomycin dosing was recommended in the revised 2020 consensus guideline, collection of multiple vancomycin serum samples to calculate AUC may cause clinical complications. AUC calculated from trough-only data (one-point AUC-guided dosing) has not been sufficiently validated. The aim of the present study was to compare the incidence of nephrotoxicity following the change from trough-guided to one-point AUC-guided dosing. METHODS: We conducted a single-centre, prospective cohort study to compare the incidence of nephrotoxicity between a trough-guided dosing group and one-point AUC-guided dosing group. RESULTS: One-point AUC-guided dosing significantly decreased the incidence of acute kidney injury (AKI) compared with trough-guided dosing (2.8% versus 17.4%, P = 0.002). Further, Kaplan-Meier plots for cumulative incidence of the AKI-free rate indicated that the onset of AKI was significantly longer in the one-point AUC-guided dosing group than in trough-guided dosing (HR, 6.5; 95% CI, 1.5-27.4; P = 0.011). Moreover, multivariate Cox proportional hazard analysis indicated that implementation of one-point AUC-guided dosing was a significant protective factor against the incidence of AKI (age-adjusted HR, 0.164; 95% CI, 0.04-0.69; P = 0.014). CONCLUSIONS: Compared with trough concentration-guided dosing, AUC-guided dosing using one-point sampling markedly reduced the incidence of AKI, without additional serum sampling.

Participation of medical students in the medical team of sports events.

Including medical student volunteers in the medical team for the triathlon strengthens the medical team structure, and encourages medical students to involve in sports medicine. Family physicians who play a role in the medical team for sports events can adopt medical students as a member and can educate them.

Geometrical isomerization of arachidonic acid during lipid peroxidation interferes with ferroptosis.

Geometrical mono-trans isomers of arachidonic acid (mtAA) are endogenous products of free radical-induced cis-trans double bond isomerization occurring to natural fatty acids during cell metabolism, including lipid peroxidation (LPO). Very little is known about the functional roles of mtAA and in general on the effects of mono-trans isomers of polyunsaturated fatty acids (mtPUFA) in various types of programmed cell death, including ferroptosis. Using HT1080 and MEF cell cultures, supplemented with 20 µM PUFA (i.e., AA, EPA or DHA) and their mtPUFA congeners, ferroptosis occurred in the presence of RSL3 (a direct inhibitor of glutathione peroxidase 4) only with the PUFA in their natural cis configuration, whereas mtPUFA showed an anti-ferroptotic effect. By performing the fatty acid-based membrane lipidome analyses, substantial differences emerged in the membrane fatty acid remodeling of the two different cell fates. In particular, during ferroptosis mtPUFA formation and their incorporation, together with the enrichment of SFA, occurred. This opens new perspectives in the role of the membrane composition for a ferroptotic outcome. While pre-treatment with AA promoted cell death for treatment with H2O2 and RSL3, mtAA did not. Cell death by AA supplementation was suppressed also in the presence of either ferroptosis inhibitors, such as the lipophilic antioxidant ferrostatin-1, or NADPH oxidase (NOX) inhibitors, including diphenyleneiodonium chloride and apocynin. Our results confirm a more complex scenario for ferroptosis than actually believed. While LPO processes are active, the importance of environmental lipid levels, balance among SFA, MUFA and PUFA in lipid pools and formation of mtPUFA influence the membrane phospholipid turnover, with crucial effects in the occurrence of cell death by ferroptosis.

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.

Pemafibrate inhibited renal dysfunction and fibrosis in a mouse model of adenine-induced chronic kidney disease.

AIMS: Peroxisome proliferator-activated receptor-alpha (PPARα) levels are markedly lower in the kidneys of chronic kidney disease (CKD) patients. Fibrates (PPARα agonists) are therapeutic agents against hypertriglyceridemia and potentially against CKD. However, conventional fibrates are eliminated by renal excretion, limiting their use in patients with impaired renal function. Here, we aimed to evaluate the renal risks associated with conventional fibrates via clinical database analysis and investigate the renoprotective effects of pemafibrate, a novel selective PPARα modulator mainly excreted into the bile. MAIN METHODS: The risks associated with conventional fibrates (fenofibrate, bezafibrate) to the kidneys were evaluated using the Food and Drug Administration Adverse Event Reporting System. Pemafibrate (1 or 0.3 mg/kg/day) was administered daily using an oral sonde. Its renoprotective effects were examined in unilateral ureteral obstruction (UUO)-induced renal fibrosis model mice (UUO mice) and adenine-induced CKD model mice (CKD mice). KEY FINDINGS: The ratios of glomerular filtration rate decreased and blood creatinine increased were markedly higher after conventional fibrate use. Pemafibrate administration suppressed increased gene expressions of collagen-I, fibronectin, and interleukin 1 beta (IL-1ß) in the kidneys of UUO mice. In CKD mice, it suppressed increased plasma creatinine and blood urea nitrogen levels and decreased red blood cell count, hemoglobin, and hematocrit levels, along with renal fibrosis. Moreover, it inhibited the upregulation of monocyte chemoattractant protein-1, IL-1ß, tumor necrosis factor-alpha, and IL-6 in the kidneys of CKD mice. SIGNIFICANCE: These results demonstrated the renoprotective effects of pemafibrate in CKD mice, confirming its potential as a therapeutic agent for renal disorders.

Identification of bleeding points after bile duct biopsy using red dichromatic imaging during peroral cholangioscopy: A case report.

Red dichromatic imaging is a new image-enhancement technology that clarifies the differences in blood concentrations and improves the visibility of the bleeding point. A 71-year-old man was presented with a common bile duct stone, which was completely removed using electrohydraulic shock wave lithotripsy with peroral cholangioscopy. During peroral cholangioscopy, a nodular lesion was found at the confluence of the cystic duct, and a forceps biopsy was performed. It was difficult to confirm the bleeding point using white-light imaging because of the pooling of blood. After switching to red dichromatic imaging mode 2 and washing the bile duct with saline solution, the bleeding point was observed in darker yellow than the surrounding blood, allowing the identification of the bleeding point. Red dichromatic imaging can be used in the future to maintain hemostasis during peroral cholangioscopy.

Removal of Duckbill-type laser-cut anti-reflux metal stents: Clinical evaluation and in vitro study.

Objectives: Duckbill-type metal stent (DMS) was the first laser-cut biliary metal stent with an anti-reflux valve. Removal of DMS is believed to be difficult and relevant reports are scarce. This study aims to investigate the feasibility of DMS removal. Methods: We retrospectively analyzed patients who underwent DMS removal between June 2019 and March 2022 to evaluate success rates and factors affecting outcomes. In addition, six different methods of DMS removal were reproduced in vitro, varying removal devices, angle of applied force, and grasped location. Extraction resistance, the distance of forceps stroke, and stent length after removal were compared. Results: Forty patients were enrolled, and DMS removal was successful in 31 cases (78%). No adverse events were observed. Tumor ingrowth was evident in 78% (7/9) of failed cases. Patients receiving biliary metal stents for the first time (naïve cases), long indwelling time, longer stent, and stent tearing during removal were associated with unsuccessful stent removal. In the in vitro study, a larger force was required to remove the stent at an extraction angle of 120° than at 0°. Among cases in which force was applied at 120°, the load tended to be lower when rat-tooth forceps were applied horizontally across the stent. Conclusions: Stent removal was possible in a majority of cases. Deployment of additional stents inside DMS may be preferable to forceful removal in the presence of factors associated with difficult stent removals, such as tumor ingrowth, naïve cases, longer stents, long indwelling time, and stent tearing during removal.

A pharmacist check of patients' infection-related condition prior to drug preparation reduces anticancer drug wastage after mixing: a retrospective study.

BACKGROUND: We previously reported that a standardized pharmacist check of medical orders related to the administration criteria of anticancer drugs prior to preparation of injectable anticancer drugs was useful for reducing drug wastage after mixing. To further reduce anticancer drug wastage after preparation, we added a pharmacist check of patients' infection-related condition to the previous protocol and assessed the effectiveness of the modified protocol for reducing injectable anticancer drug wastage. METHODS: In addition to the administration criteria of anticancer drugs, patients' infection-related condition, which was based on a body temperature ≥ 37.5 °C or elevated C-reactive protein (CRP) or white blood cell (WBC) count from baseline, was added to pharmacists' checklist of items used previously to prepare injectable anticancer drugs. We retrospectively compared the number, type and cost of anticancer drugs discarded after preparation and the reasons for discarding these drugs between pre- and post-protocol modification. RESULTS: The rate at which anticancer drugs were discarded after preparation was significantly reduced after introducing the modified protocol compared to the original protocol (0.288% [18/6253] vs. 0.095% [6/6331], P = 0.013). Furthermore, the number of cases for which mixed anticancer agents were discarded because of infection decreased from 11 (fever: n = 8; elevated CRP or WBC: n = 3) to one (elevated CRP: n = 1) a year. CONCLUSIONS: In addition to the standard administration criteria of anticancer drugs, checking patients' infection-related condition, defined by a body temperature ≥ 37.5 °C or elevated CRP or WBC from baseline, before mixing by the pharmacist is useful for reducing anticancer drug wastage after preparation.

The efficacy and safety of a duckbill-type anti-reflux metal stent as the initial metal stent for distal malignant biliary obstruction in unresectable pancreatic cancer.

Background: The usefulness of duckbill-type anti-reflux metal stent (DMS) in self-expandable metal stent-naïve pancreatic cancer (PC) patients has not been well-studied. This study aimed to evaluate the efficacy and safety of DMS in such patients. Methods: We analyzed consecutive patients with unresectable PC who received a covered metal stent (CMS) as the initial self-expandable metal stent at our institution. Technical success, functional success, causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates were compared between DMS and conventional CMS (c-CMS). Results: A total of 69 patients were included (DMS: 28, c-CMS: 41). Technical success, functional success, and AEs were similar between groups. Tumor ingrowth was more common in the DMS group (18% vs. 0%, p = 0.009), while non-occlusion cholangitis tended to be more common in the c-CMS group (0% vs. 15%, p = 0.074). Median time to RBO was similar between groups (276 vs. 273 days, p = 0.915). The anti-reflux valve of DMS was found torn in 56% of patients. Endoscopic reintervention was successful in all cases, despite failed stent removal in 88% of patients in the DMS group. Conclusions: DMS was not associated with longer time to RBO compared to c-CMS in self-expandable metal stent-naïve patients.

Relationship Between Osimertinib Concentration and Clinical Response in Japanese Patients With Non-small Cell Lung Cancer.

BACKGROUND/AIM: Osimertinib is the first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The present study aimed to determine the previously unclarified association of osimertinib plasma trough concentrations with efficacy, adverse events, and genetic polymorphisms in Japanese patients with NSCLC harboring EGFR mutations. PATIENTS AND METHODS: In this prospective study, blood samples of 25 patients who received osimertinib were collected to measure plasma osimertinib concentrations and to genotypically characterize ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2 polymorphisms. Plasma osimertinib concentrations were analyzed using validated multiple reaction monitoring mode-based liquid chromatography-tandem mass spectrometry. Osimertinib concentration necessary to achieve optimal median progression-free survival (PFS) was determined using receiver operating characteristic curve analysis. PFS and overall survival were analyzed using the Kaplan-Meier method, and between-group differences were compared using the log-rank test. Plasma osimertinib concentrations between different patient groups were compared using the Mann-Whitney U-test. RESULTS: Patients were divided into high and low concentration groups based on a plasma osimertinib cut-off concentration of 211 ng/ml. Median PFS was longer in the high trough concentration group than that in the low trough concentration group (46.3 vs. 16.8 months, p=0.029). Plasma osimertinib concentrations adjusted for dose and body weight did not differ between the patients with and without variant polymorphisms. CONCLUSION: Monitoring plasma trough concentrations during maintenance might improve osimertinib treatment efficacy in patients with NSCLC harboring EGFR mutations.

Are Newer Extracorporeal Shock Wave Lithotripsy Models Truly Improving Pancreatolithiasis Lithotripsy Performance? A Japanese Single-Center Study Using Endoscopic Adjunctive Treatment.

Background/Aims: Many Japanese institutions use electromagnetic extracorporeal shock wave lithotripsy (ESWL) systems for treating pancreatic duct stones. However, there are no reports on direct comparisons between recent electromagnetic lithotripters. This study aimed to verify whether the new electromagnetic lithotripter can improve the efficiency of pancreatic stone fragmentation, and to clarify the role of combined endoscopic treatment on the clearance of pancreatic duct stones. Methods: We retrospectively identified 208 patients with pancreatolithiasis who underwent endoscopic adjunctive treatment after pancreatic ESWL at a single Japanese center over a 17-year period. We evaluated the outcome data of this procedure performed with SLX-F2 (last 2 years; group A) and Lithostar/Lithoskop (first 15 years; group B), as well as additional endoscopic treatments for pancreatolithiasis. We also performed logistic regression analysis to detect various factors associated with the procedure. Results: For pancreatic head stones, ESWL disintegration was achieved in 93.7% of group A patients and 69.0% of group B patients (p=0.004), and adjunctive endoscopic treatment removed stones in 96.8% of group A patients and 73.0% of group B patients (p=0.003). Multivariate analysis revealed that lithotripter type (odds ratio, 6.99; 95% confidence interval, 1.56 to 31.33; p<0.01) and main pancreatic duct stricture (odds ratio, 2.87; 95% confidence interval, 1.27 to 6.45; p<0.01) were significant factors for ESWL fragmentation. Conclusions: The SLX F2 showed high performance in fragmenting the pancreatic duct stones. In addition, endoscopic adjunctive treatment improved the overall success rate of the procedure. The improved ESWL lithotripter has many advantages for patients undergoing pancreatic lithotripsy treatment.

Long-term outcomes of duckbill-type anti-reflux metal stents versus conventional covered metal stents in reinterventions after covered biliary metal stent dysfunction in unresectable pancreatic cancer.

BACKGROUND: The use of duckbill-type anti-reflux metal stents (DMS) in reinterventions after covered metal stent (CMS) dysfunction has been reported in patients with distal malignant biliary obstruction (MBO). However, the superiority of DMS over conventional CMS (c-CMS) has not been established. Therefore, we conducted this retrospective study to evaluate the long-term efficacy and safety of DMS as a second stent in comparison with c-CMS. METHODS: We investigated consecutive patients with distal MBO due to unresectable pancreatic cancer who underwent reintervention after dysfunction of initial biliary CMS at our institution. We compared causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates of DMS and c-CMS in this stenting. RESULTS: A total of 76 patients were included (DMS 41 and c-CMS 35). While overall RBO rates were similar between the two groups (46% vs. 63%, p = 0.172), RBO due to non-occlusion cholangitis tended to be less frequent in the DMS group than in the c-CMS group (2% vs. 14%, p = 0.089). Median TRBO was significantly longer in the DMS group (286 days vs. 112 days, p = 0.029). DMS was identified as the only significant risk factor for TRBO (hazard ratio, 0.52; p = 0.044). Overall AE rates were significantly lower in the DMS group (2% vs. 23%, p = 0.010), with non-occlusion cholangitis being the most common AE in the c-CMS group. Endoscopic reintervention was successfully performed in all patients in both groups, despite failed stent removal in 15% of patients in DMS group. CONCLUSIONS: DMS was associated with a significantly longer TRBO and lower rate of AEs compared with c-CMS in reinterventions after initial CMS dysfunction. DMS may be preferable to c-CMS as a second stent after biliary CMS dysfunction.

Focal pancreatic ductal change induced by 10-Fr S-type plastic stent in chronic pancreatitis.

BACKGROUND AND AIM: Stent-induced ductal change (SIDC) is a complication of endoscopic pancreatic stenting (EPS) in patients with chronic pancreatitis (CP). However, the evaluation of SIDC associated with S-type pancreatic plastic stent (PS) and large-caliber PS, such as 10 Fr, is limited. This study aimed to analyze the SIDC of the main pancreatic duct (MPD) associated with 10-Fr S-type PS in patients with CP. METHODS: Between January 2008 and December 2021, 132 patients with CP in whom a 10-Fr S-type PS had been installed by EPS were retrospectively reviewed. The SIDC incidence rate was examined, and the clinical features of patients with and without SIDC were investigated, including the outcomes for detected SIDC. RESULTS: Stent-induced ductal change during EPS was confirmed in 41 patients (31.1%) of 132 patients at a site coincident with the PS tip or distal flap in the MPD. All patients were asymptomatic during the development of SIDC. Morphological changes in the MPD were detected as elevated (75.6%) or bearing stricture changes (24.4%). A total of 90.2% of SIDC developed after the first 10-Fr PS installation. No significant differences were noted between the patients with and without SIDC. The outcomes of continued PS installment for SIDC showed persistence and secondary change. CONCLUSIONS: Stent-induced ductal change-associated 10-Fr PS installation was performed in just under one-third of the patients, indicating a substantial incidence rate and a possible development of SIDC from early stages onwards. More emphasis should be placed on SIDC as the complication.