Prevention of delirium with agitation by yokukansan in older adults after cancer surgery.

OBJECTIVE: Preventing postoperative delirium with agitation is vital in the older population. We examined the preventive effect of yokukansan on postoperative delirium with agitation in older adult patients undergoing highly invasive cancer resection. METHODS: We performed a secondary per-protocol analysis of 149 patients' data from a previous clinical trial. Patients underwent scheduled yokukansan or placebo intervention 4-8 days presurgery and delirium assessment postoperatively. Delirium with agitation in patients aged ≥75 years was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the Japanese version of the Delirium Rating Scale-Revised-98. We assessed odds ratios for yokukansan (TJ-54) compared with placebo for the manifestation of postoperative delirium with agitation across patients of all ages (n = 149) and those aged ≥65 years (n = 82) and ≥ 75 years (n = 21) using logistic regression. RESULTS: Delirium with agitation manifested in 3/14 and 5/7 patients in the TJ-54 and placebo groups, respectively, among those aged ≥75 years. The odds ratio for yokukansan vs. placebo was 0.11 (95% confidence interval: 0.01-0.87). An age and TJ-54 interaction effect was detected in patients with delirium with agitation. No intergroup differences were observed in patients aged ≥65 years or across all ages for delirium with agitation. CONCLUSIONS: This is the first study investigating the preventive effect of yokukansan on postoperative delirium with agitation in older adults. Yokukansan may alleviate workforce burdens in older adults caused by postoperative delirium with agitation following highly invasive cancer resection.

Yokukansan for Treatment of Preoperative Anxiety and Prevention of Postoperative Delirium in Cancer Patients Undergoing Highly Invasive Surgery. J-SUPPORT 1605 (ProD Study): A Randomized, Double-Blind, Placebo-Controlled Trial.

CONTEXT: No standard preventive or therapeutic methods have been established for preoperative anxiety and postoperative delirium in patients with cancer. OBJECTIVES: To clarify the therapeutic effect of yokukansan for perioperative psychiatric symptoms in patients with cancer as well as to confirm its safety profile. METHODS: This is a randomized, double-blind, and placebo-controlled trial conducted at a single center in Tokyo, Japan. About 195 patients with cancer scheduled to undergo tumor resection took one packet of the study drug, which was administered orally. Coprimary outcomes were change in preoperative anxiety assessed with the Hospital Anxiety and Depression Scale-Anxiety and incidence of postoperative delirium assessed with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Interim analysis was performed with one-third (n = 74) of the target number of registered patients. RESULTS: Because this trial was canceled based on the results of the interim analysis and the protocol treatment was discontinued in patients who were already registered, conclusions were based on the full analysis set of 160 participants. There were no significant differences between groups in the change of mean Hospital Anxiety and Depression Scale-Anxiety score (intervention group [SD] 0.4 [3.0] vs. placebo group 0.5 [3.0]; P = 0.796) or the incidence of postoperative delirium (32% vs. 30%; P = 0.798). There were no serious adverse events in either group. CONCLUSION: In patients with cancer undergoing highly invasive surgeries, yokukansan demonstrated no significant efficacy for the treatment of preoperative anxiety or the prevention of postoperative delirium. Yokukansan is already used in daily practice in Japan, but we should be careful with its future use.

Yokukansan for perioperative psychiatric symptoms in cancer patients undergoing high invasive surgery. J-SUPPORT 1605 (ProD Study): study protocol for a randomized controlled trial.

BACKGROUND: Preoperative anxiety and postoperative delirium affect both short- and long-term prognoses in patients with cancer; therefore, these conditions require early prevention and treatment. However, no standard preventive or therapeutic methods have been established for them. Yokukansan, a Japanese herbal medicine for the treatment of insomnia and anxiety, causes relatively few adverse drug reactions and effectively improves the behavioral and psychological symptoms of dementia. Thus, it is expected to be useful for treating and/or preventing perioperative psychiatric symptoms in patients with cancer. The objective of this study is to clarify the therapeutic effect of Yokukansan for preoperative anxiety and its preventive effect on postoperative delirium in cancer patients, as well as to confirm its safety profile. METHODS: This study is a randomized, double-blind, placebo-controlled study in cancer patients scheduled to undergo tumor resection. Patients who provide consent are randomly allocated to receive oral administration of Yokukansan or placebo, and study drug administration is continued for 4 days or longer prior to surgery. We defined two primary endpoints, change in preoperative anxiety and incidence of postoperative delirium. Secondary endpoints are severity score of postoperative delirium, duration of postoperative delirium, amount of benzodiazepines used prior to surgery, amount of antipsychotic agents used after surgery, and number of postoperative hospitalization days. We plan to complete the analysis on March 31, 2021. The target number of registered patients is 110 per group, or 220 in total. DISCUSSION: This study is the first randomized, double-blind, placebo-controlled study intended to clarify the effects of a Japanese herbal medicine, Yokukansan, in the prevention and treatment of perioperative psychiatric symptoms in patients with cancer. The trial was initiated on August 14, 2017, with 195 subjects randomized by October 5, 2018. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000027561 . Registered on 31 May 2017.

Yokukansan for the treatment of preoperative anxiety and postoperative delirium in colorectal cancer patients: a retrospective study.

BACKGROUND: Yokukansan (YKS), a Japanese traditional herbal medicine for neurosis and insomnia, is speculated to be useful for perioperative psychiatric symptoms in cancer patients, but there exists little empirical evidence. This study provides preliminary data about the efficacy, feasibility, and side effects of YKS for the treatment of preoperative anxiety and postoperative delirium in cancer patients. METHODS: We retrospectively reviewed the medical records of colorectal cancer patients who took YKS for preoperative anxiety, evaluating the following: (1) patient characteristics, (2) feasibility of taking YKS, (3) changes in preoperative anxiety based on the Clinical Global Impression (CGI) scale and Edmonton Symptom Assessment System-revised (ESAS-r-anxiety), (4) incidence of postoperative delirium and (5) YKS-related side effects. RESULTS: We reviewed 19 medical records. There was a significant difference between ESAS-r-anxiety scores (P = 0.028) before and after taking YKS, but no difference between CGI scores (P = 0.056). The incidence of postoperative delirium was 5.2% (95% CI = 0.0-14.5). One patient could not complete the course of YKS during the perioperative administration period, but there were no side effects of Grade 2 or worse according to the Common Terminology Criteria for Adverse Events v4. CONCLUSIONS: Cancer patients could safely take YKS before surgery. There was a significant improvement in preoperative anxiety after taking YKS, and the incident rate of postoperative delirium was lower than in previous studies. These results suggest that YKS may be useful for perioperative psychiatric symptoms in cancer patients. Further well-designed studies are needed to substantiate our results.

General and selective C-3 alkylation of indoles with primary alcohols by a reusable Pt nanocluster catalyst.

The platinum rule: Heterogeneous, additive-free C-3 selective alkylation of indoles by aliphatic and aromatic alcohols proceeded under transfer hydrogenation conditions with the reusable Pt/θ-Al2 O3 catalyst (see scheme; TON=turnover number).

Formal synthesis of (+)-madindoline A, a potent IL-6 inhibitor, utilizing enzymatic discrimination of quaternary carbon.

A formal synthesis of (+)-madindoline A was achieved. The Sunazuka's key intermediate, (4R,5S)-(-)-3-butyl-4-(tert-butyldimethylsiloxy)-5-methoxycarbonyl-2,5-dimethyl-2-cyclopentenone, was synthesized from easily available (2S,3S)-3-acetoxy-2-ethenyl-2-methylcyclopentanone. The starting material was reliably supplied by a chemo-enzymatic procedure in enantiomerically pure form. The synthesis was performed by straightforward transformations involving enone formation and regioselective introduction of the two alkyl side chains.

Effects of integrated psychosocial care for distress in cancer patients.

BACKGROUND: Despite some clinical guidelines for incorporating integrated psychosocial care (combining psychological screening and psychological intervention, including adequate collaboration with mental health specialists) into routine oncology practice, definitive empirical evidence regarding the effectiveness of such care remains unavailable. Here the findings of recent experimental studies are reviewed to provide guidance regarding this issue. METHODS: Comparative studies examining integrated psychosocial care were reviewed. RESULTS: Studies examining interventions that include both screening and psychological care have produced contradictory results regarding effectiveness, but all the studies that have examined the effect of psychological care after the identification of distress using systematic screening have shown positive results. CONCLUSIONS: Integrated psychosocial care may affect patients with significant distress, but the adequacy of introducing such care into routine oncology practice remains debatable.

Availability of psychiatric consultation-liaison services as an integral component of palliative care programs at Japanese cancer hospitals.

OBJECTIVE: Collaboration between psychiatry and palliative medicine has the potential to enhance the quality of medical practice. The integration between palliative care and psychiatry has been attempted only in discrete medical settings and is not yet firmly established as an institution. Our objective was to determine the availability and degree of integration between psychiatric consultation-liaison services and palliative care in Japan. METHODS: A survey questionnaire was mailed to consultation-liaison psychiatrists at 375 government-designated cancer hospitals regarding their consultation-liaison services. RESULTS: A total of 375 survey questionnaires were sent to consultation-liaison psychiatrists, with a response rate of 64.8%. Designated cancer hospitals with approved palliative care teams were significantly more likely to have a consultation-liaison psychiatrist in the palliative care team than those in non-approved palliative care teams [80/80 (100%) versus 110/153 (73%); P= 0.008]. Approved palliative care teams had double the number of referrals, conducted rounds more frequently and held conferences more frequently. Psychiatrists of the approved palliative care teams spent more of their time on palliative care consultations, adhered more closely to consultation processes and contributed more actively to the integration of developmental perspectives in treatment plans. CONCLUSIONS: In Japan, most designated cancer hospitals with approved palliative care teams were more likely to integrate psychiatric consultation-liaison services into their palliative care programs. Systematic strategies for integration between palliative care and consultation-liaison psychiatry would contribute to the provision of appropriate psychosocial care for cancer patients and families at all stages.

Involvement of a psychiatric consultation service in a palliative care team at the Japanese cancer center hospital.

OBJECTIVE: Close collaboration between the cancer care team service and the psychiatric consultation service is recommended to provide adequate comprehensive care to cancer patients. In Japan, specialized palliative care teams work in conjunction with consultation-liaison psychiatrists as an essential members. There are, however, few studies reporting on these services. METHODS: We obtained the characteristics, physical and psychiatric symptoms and outcomes of cancer patients by analyzing the database of patients referred to the palliative care team at the National Cancer Center Hospital East, Japan. RESULTS: Among consecutive 2000 referrals, most patients referred to the palliative care team present both physical and psychiatric symptoms. Psychiatric diagnoses were provided for ∼70% of these patients. Consultation-liaison psychiatrists provided medical care to 80% of all the referrals. The main symptoms for psychiatric consultation were delirium (28%), adjustment disorder (18%), major depression (7.6%) and dementia (6.6%). CONCLUSIONS: Psychiatric problems are common in cancer patients of the palliative care team. The palliative care team should assess the psychiatric problems in cancer patients, and the involvement of the consultation-liaison psychiatrists in the palliative care teams may be one of the strategies to establish the psychosocial support for cancer patients in the acute hospital settings.

Conformationally imprinted receptors: atropisomers with "write", "save", and "erase" recognition properties.

[reaction: see text] An atropisomeric receptor with "write", "save", and "erase" recognition properties is presented. The receptor adopts a complementary conformation when heating in the presence of an ethyl adenine-9-acetate guest molecule. This complementary hydrogen bonding conformation is "saved" upon cooling to room temperature due to the reestablishment of restricted rotation and is stable even upon removal of the guest. Finally, the atropisomeric receptor can be "erased" by heating in the absence of the guest.