Tapentadol Safety and Patient Characteristics Associated with Treatment Discontinuation in Cancer Therapy: A Retrospective Multicentre Study in Japan.

INTRODUCTION: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events. METHODS: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events. RESULTS: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events. CONCLUSIONS: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings. TRIAL REGISTRATION NUMBER: UMIN 000044282 (University Hospital Medical Information Network).

Evaluation of the performance, operability, and safety of Plasauto µ, a new type of machine for cell-free and concentrated ascites reinfusion therapy, in a postmarketing clinical study.

Cell-free and concentrated ascites reinfusion therapy (CART) is performed by collecting the ascites from the patient, followed by filtration and concentration. Thereafter, concentrated cell-free ascites is reinfused into the patient intravenously. The new type of machine, Plasauto µ, for managing the process of CART was launched onto the market. We have evaluated the machine through postmarketing clinical study in 17 patients with malignant ascites. The amounts of original and concentrated ascites were 3673 ± 1920 g and 439 ± 228 g, respectively. Recovery rates were acceptable regarding values of total protein, albumin, and IgG that were 55.6% ± 17.3%, 60.2% ± 20.8%, and 58.2% ± 20.5%, respectively. Recovery rates were positively associated with amounts of original ascites and negatively associated with total protein concentration. No adverse events related to the machine were observed. The new type of machine showed preferable performance in processing malignant ascites.

Efficacy and safety of reinfusion of concentrated ascitic fluid for malignant ascites: a concept-proof study.

PURPOSE: Malignant ascites is one of the symptoms causing discomfort in advanced cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is one treatment modality, but controlled trials are limited. The primary aim of this study was to explore the efficacy and safety of CART, as well as their predictors, to obtain data for planning a further controlled trial. METHODS: This was a single center retrospective cohort study in patients with refractory malignant ascites. Consecutive adult patients who underwent CART were enrolled. The primary endpoints were the time to next paracentesis and seven patient-reported symptoms (e.g., abdominal pain and distension). The secondary endpoints were adverse events, laboratory findings, and physical findings. RESULTS: A total of 104 CART procedures for 51 patients were analyzed. The median time to next paracentesis was 27 days (95% CI, 21-35). Intensities of all seven symptoms were significantly improved after CART (p < 0.0001 for all symptoms). Grade 3 hypotension occurred during one procedure, and mild fever occurred in 5%. Total protein, albumin, and estimated glomerular filtration rate were significantly increased. Hemorrhagic ascites, ascites white blood cell count, serum total protein, and lymphocyte percentages were the independent predictors of the time to next paracentesis. CONCLUSION: The effects of reinfusion of concentrated ascitic fluid may be maintained for 1 month, being potentially longer than that of total paracentesis alone. This study had no comparison groups and examined the short-term effect. A randomized controlled study to compare the long-term effects of total paracentesis alone vs. CART is necessary.

Hydrogen Production from a Methanol-Water Solution Catalyzed by an Anionic Iridium Complex Bearing a Functional Bipyridonate Ligand under Weakly Basic Conditions.

An efficient catalytic system for the production of hydrogen from a methanol-water solution has been developed using a new anionic iridium complex bearing a functional bipyridonate ligand as a catalyst. This system can be operated under mild conditions [weakly basic solution (0.046 mol L(-1) NaOH) below 100 °C] without the use of an additional organic solvent. Long-term continuous hydrogen production from a methanol-water solution catalyzed by the anionic iridium complex was also achieved.

The analgesic efficacy of ultrasound-guided transversus abdominis plane block with mid-axillary approach after gynecologic laparoscopic surgery: A randomized controlled trial.

BACKGROUND AND AIMS: The transversus abdominis plane (TAP) block is widely used in clinical practice as a part of the multimodal analgesic regimen after abdominal surgery. The analgesic efficacy of ultrasound (US)-guided TAP block with the mid-axillary approach was investigated in patients undergoing laparoscopic gynecologic surgery in a randomized controlled clinical trial. MATERIALS AND METHODS: Adult patients (n = 119) undergoing laparoscopic gynecologic surgery were randomized to undergo either TAP block with ropivacaine (Group A, n = 60) or that with saline (Group B, n = 59), in a blinded manner. Following general anesthesia, TAP block was performed bilaterally by infusion of either 20-mL 0.375% ropivacaine/one side in Group A or 20-mL saline/one side in Group B, under US guidance with a mid-axillary approach. Patient-controlled analgesia (PCA) was performed postoperatively with tramadol. The analgesic effect was postoperatively evaluated using a four-grade pain score and the prince Henry pain scale (PHS) at 0, 6, 12, and 24 h. Postoperative tramadol PCA consumption and vomiting/nausea were recorded. Statistical analyses were performed using the Mann-Whitney U-test or Fisher's exact probability test. A P < 0.05 was considered significant. RESULTS: There was no statistically significant difference in background characteristics. The dose of remifentanil was significantly higher in Group B (P = 0.01). The pain score (P = 0.02) and PHS (P = 0.01) were significantly lower in Group A at 0 h. Tramadol PCA consumption in the period of 0-6 h (P = 0.01) and postoperative nausea (P = 0.04) were significantly less in Group A. CONCLUSION: Postoperative pain/nausea and PCA consumption were significantly lower in patients with TAP block in the early postoperative stage. TAP block with a mid-axillary approach holds considerable promise as a part of a balanced postoperative analgesic regimen following laparoscopic gynecologic surgery.

Dehydrogenative oxidation of alcohols in aqueous media using water-soluble and reusable Cp*Ir catalysts bearing a functional bipyridine ligand.

A new catalytic system for the dehydrogenative oxidation of alcohols using a water-soluble Cp*Ir complex bearing a bipyridine-based functional ligand as catalyst has been developed. With this catalytic system, a variety of primary and secondary alcohols have been efficiently converted to aldehydes and ketones, respectively, in aqueous media without using any oxidant. Reuse of the catalyst by a very simple procedure has been also accomplished.

Multialkylation of aqueous ammonia with alcohols catalyzed by water-soluble Cp*Ir-ammine complexes.

Novel water-soluble Cp*Ir-ammine complexes have been synthesized, and a new and highly atom-economical system for the synthesis of organic amines using aqueous ammonia as a nitrogen source has been developed. With a water-soluble and air-stable Cp*Ir-ammine catalyst, [Cp*Ir(NH(3))(3)][I](2), a variety of tertiary and secondary amines were synthesized by the multialkylation of aqueous ammonia with theoretical equivalents of primary and secondary alcohols. The catalyst could be recycled by a facile procedure maintaining high activity. A one-flask synthesis of quinolizidine starting with 1,5,9-nonanetriol was also demonstrated. This new catalytic system would provide a practical and environmentally benign methodology for the synthesis of various organic amines.

[Influence of general anesthesia in pregnant patients for gynecologic surgery].

BACKGROUND: Surgery during pregnancy is suspected to have various harmful influences to pregnant patients and fetuses. Although laparoscopic surgery has been recently reported to have some advantages over open surgery in this condition, it often requires general anesthesia. METHODS: The influence of general anesthesia was retrospectively investigated in 12 patients having undergone gynecologic surgery during pregnancy in comparison with 18 with surgery under lumbar and epidural anesthesia. RESULTS: Patients receiving general anesthesia required less pain relief compared with those receiving lumbar and epidural anesthesia. Pregnancy was adequately maintained after surgery in all patients. No abortions or preterm deliveries occurred. There was no significant difference in influence on mother and babies between these two patient groups. CONCLUSIONS: General anesthesia during pregnancy is not necessarily associated with harmful influences on mother and babies compared with lumbar and epidural anesthesia if selected appropriately.

[Comparative study of anesthesia with remifentanil VS fentanyl in terms of postoperative pain and shivering].

BACKGROUND: Remifentanil is reported to be cleared rapidly more than other any opioids. It is considered that this characteristic may lead to an increase in postoperative pain and shivering after general anesthesia with remifentanil. This study was aimed to examine the influence of remifentanil to these adverse symptoms in comparison with fentanyl. METHODS: The subjects consisted of 41 female patients having undergone a total intravenous anesthesia with remifentanil or/and fentanyl for gynecological laparoscopic surgery. RESULTS: There was no significant difference in the occurrence of postoperative pain. Shivering occurred significantly more frequently in patients who had received remifentanil anesthesia, associated with a significant lower body temperature after general anesthesia. CONCLUSIONS: Careful management of intraoperative body temperature is important to prevent the occurrence of shivering after total intravenous general anesthesia with remifentanil.

[Effects of rikkunshito on the postoperative nausea and vomiting (PONV) after laparoscopic gynecological surgery].

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of unignorable complications after general anesthesia. The aim of this study was to examine prophylactic effects of TSUMURA rikkunshito (TJ-43), a herbal medicine consisting of eight herbs, on PONV after laparoscopic surgery. METHODS: One hundred and forty-two female patients undergoing gynecological laparoscopic surgery (ASA-PS1-2) were randomly allocated to one of two groups receiving rikkunshito (n = 91) and control (n = 51). The oral administration of 2.5 g of TJ-43 was commenced the night before surgery and was continued for 3 days after surgery. The suppository form containing 1.5 g of TJ-43 was used during surgery. RESULTS: There were no significant differences of the incidence of PONV between the two groups. The patterns of change in the degree of PONV were similar between the two groups, although TJ-43 group showed slightly earlier reduction in symptom scores. The patients with TJ-43 showed earlier postoperative recovery of oral meal intake. CONCLUSIONS: Perioperative administration of TJ-43 showed a possible effectiveness to reduce the severity of PONV and to promote earlier recovery of oral meal intake after gynecological laparoscopic surgery.

[Actigraphic assessment of the effects of hypnotics on the night before surgery in relation with the severity of surgery].

BACKGROUND: Hypnotics have been used to provide adequate sleep on the night before surgery, but these effects have rarely been investigated. We investigated whether the preoperative hypnotic effects are related with the severity of surgery with quantitative evaluation using actigraph. METHODS: Sleep time on the night before surgery was evaluated after the administration of brotizolam 0.25 mg in 40 patients awaiting surgery; 20 patients for cardiovascular surgeries (Group I) and 20 patients for general surgeries (Group II). Sleep and awake state were identified by wrist activity measured with a motion-logger actigraph. Sleep time was assessed in total period from 22:00 to 6:00 and its 4 subdivided 2-hour periods (22:00-24:00, 24:00-2:00, 2:00-4:00, 4:00-6:00). RESULTS: The total sleep time in Group II (448 +/- 22 min) was significantly longer than that in Group I (409 +/- 44 min). Group I showed a significant reduction in sleep time in the period of 4:00-6:00 compared with other periods, whereas Group II did not show any difference among 4 periods. Group I showed significant shorter sleep time in the period of 4:00-6:00 compared with Group II. CONCLUSIONS: An actigraphic assessment of sleep time has demonstrated the possible influence of the severity of surgery on the sleep time on the night before surgery.

[The obstruction of a port catheter during the induction of anesthesia].

A 44-year-old woman receiving home hyperalimetation with an implanted port catheter, was scheduled to undergo resection of ovarian cyst and adhesiotomy. For the induction of anesthesia, fentanyl 0.05 mg, thiopental sodium 200 mg, saline 5 ml and vecuronium 10 mg were given through the port catheter. Although she fell asleep, she kept breathing spontaneouly. It was not possible to give any further drugs through this port catheter, suggesting obstruction of the catheter. The endotracheal intubation was assisted with sevoflurane 5% and suxamethonium 80 mg chloride given through the peripheral vein. Five ml of saline used to flash out thiopental sodium before the administration of vecuronium blomide was not considered to be adequate. An experiment was conducted to investigate how much saline is necessary to wash out completely the drug given previously. The results suggest that more than 10 ml of saline should be given through the port catheter. Various types of central venous catheters are being used. Precise knowledge of each catheter is necessary to use this indispensable central vein route, especially at the crucial timing, such as the induction of anesthesia.