Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study).

AIM: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. METHODS: This was a decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive-behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem-solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire-9 (PHQ-9) total score between baseline and week 8. Secondary outcomes included anxiety. RESULTS: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ-9 total score was significantly reduced from baseline for all participants by -1.41 points (95% confidence interval [CI] -1.89, -0.92), but between-group differences in change scores were not significant (BA: -0.04, 95% CI -0.75, 0.67; AT: -0.16, 95% CI -0.87, 0.55; PS: -0.19, 95% CI -0.90, 0.52). CONCLUSION: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence-based recommendations regarding the use of specific smartphone psychotherapy.

An Estimation Formula for Resonance Frequency Using Sex and Height for Healthy Individuals and Patients with Incurable Cancers.

Resonance frequency breathing is a technique that involves breathing that maximizes heart rate variability. It is specific to individuals and is determined through a procedure taking approximately 30 min, using a procedure that is often best carried out at specialized medical institutions. This is a physical and time-consuming burden because of hospital visits and measurements, particularly for patients with cancer. Therefore it would be beneficial if a procedure can be found to determine resonance frequency from the patient's physical characteristics, without the need for special assessment procedures. This exploratory cross-sectional study examined the correlation between individual characteristics and resonance frequency in healthy volunteers. Multiple regression analysis was performed with the measured resonance frequency as the target variable and individual characteristic parameters as explanatory variables. The study aims to build an estimation formula for resonance frequency with some of these parameters and assess its validity. In addition, the validity of the formula's applicability to patients with incurable cancers is assessed. A total of 122 healthy volunteers and 32 patients with incurable cancers were recruited as participants. The median resonance frequency of 154 participants was six breaths per min. Sex and height were selected as explanatory variables associated with the measured resonance frequency in the volunteers. The estimation formula for resonance frequency using individual characteristics was 17.90-0.07 × height for men and 15.88-0.06 × height for women. Adjusted R-squared values were 0.55 for men and 0.47 for women. When the measured resonance frequency in patients with incurable cancers was six breaths per minute or less, the resonance frequency estimated by this formula was slightly larger than the measured ones. Information on individual characteristics, such as sex and height, which can be easily obtained, was useful to construct an estimation formula for resonance frequency.

Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

OBJECTIVES: There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. METHODS: This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. RESULTS: Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. SIGNIFICANCE OF RESULTS: This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

Morphine Versus Oxycodone for Cancer Pain Using a Catechol-O-methyltransferase Genotype Biomarker: A Multicenter, Randomized, Open-Label, Phase III Clinical Trial (RELIEF Study).

BACKGROUND: We hypothesized that the high-dose opioid requirement in patients carrying the rs4680-GG variant in the COMT gene encoding catechol-O-methyltransferase would be greater for patients taking morphine than for those taking oxycodone, thus providing a much-needed biomarker to inform opioid selection for cancer pain. METHODS: A randomized, multicenter, open-label trial was conducted at a Japanese hospital's palliative care service. Patients with cancer pain treated with regular doses of nonsteroidal anti-inflammatory drugs or acetaminophen were enrolled and randomized (1:1) into morphine (group M) and oxycodone (group O) groups. The minimum standard dose of immediate-release (IR) oral opioids was repeatedly administered by palliative care physicians to achieve pain-reduction goals (Pain reduction ≥ 33% from baseline and up to ≤ 3 on a numerical rating scale). The primary endpoint was the proportion of subjects requiring high-dose opioids on day 0 with the GG genotype. RESULTS: Of 140 participants who developed cancer-related pain among 378 subjects registered and pre-screened for the genotype, 139 were evaluated in the current study. Among patients carrying a COMT rs4680-GG genotype, 48.3% required high-dose opioids in group M, compared with the 20.0% in group O (95% CI, 3.7%-50.8%; P = .029). Of those with the non-GG genotype, 41.5% treated with morphine and 23.1% with oxycodone required high-dose opioids (95% CI, 3.3%-38.3%; P = 0.098). CONCLUSION: Using the COMT rs4680 genotype alone is not recommended for selecting between morphine and oxycodone for pain relief.

A multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of ramelteon for the prevention of postoperative delirium in elderly cancer patients: a study protocol for JORTC-PON2/J-SUPPORT2103/NCCH2103.

Postoperative delirium is an important issue in cancer patients, affecting surgical outcomes and the quality of life. Ramelteon is a melatonin receptor agonist with high affinity for MT1 and MT2 receptors. Clinical trials and observational studies in Japan, including in surgical cancer patients, have shown efficacy of ramelteon in delirium prevention, with no serious safety concerns. However, clinical trials from the USA have reported conflicting results. A Japanese phase II study investigated the efficacy and safety of ramelteon for delirium prevention following gastrectomy in patients aged ≥75 years, with findings suggesting the feasibility of a phase III trial. The aim of this multi-centre, double-blind, randomized placebo-controlled phase III trial is to evaluate the effectiveness and safety of oral ramelteon for postoperative delirium prevention in cancer patients aged ≥65 years as advanced medical care. The trial protocol is described here.

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.

Clinical practice guidelines for the care of psychologically distressed bereaved families who have lost members to physical illness including cancer.

The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer developed evidence-based clinical practice guidelines for the care of psychologically distressed bereaved families who have lost members to physical illness including cancer. The guideline development group formulated two clinical questions. A systematic literature review was conducted. The level of evidence and the strength of the recommendations were graded and recommendation statements validated using the modified Delphi method. The recommendations were as follows: non-pharmacological interventions were indicated for serious psychological distress (depression and grief); antidepressants were indicated for depression; however, psychotropic medications including antidepressants were not recommended for 'complicated' grief. These guidelines will facilitate the provision of appropriate care to distressed bereaved family members and highlight areas where further research is needed.

Prevalence of Myofascial Pain Syndrome and Efficacy of Trigger Point Injection in Patients with Incurable Cancer: A Multicenter, Prospective Observational Study (MyCar Study).

OBJECTIVE: Myofascial pain syndrome (MPS) is caused by overload or disuse of skeletal muscles. Patients with cancer are often forced to restrict their movement or posture for several reasons. The study was conducted to investigate the prevalence and risks of MPS in patients with incurable cancer. The efficacy of trigger point injection (TPI) was also explored. METHODS: This was a multicenter, prospective observational study. Patients with incurable cancer who started receiving specialist palliative care were enrolled. We investigated the MPS in this population and accompanying risk factors for restricting body movement. Pre- and post-TPI pain was also evaluated using a Numerical Rating Scale (NRS) in patients who received TPI. The primary outcome was the prevalence of MPS. RESULTS: A total of 101 patients were enrolled from five institutions in Japan. Most of the patients (n = 94, 93.1%) had distant metastases, and half of the patients (50, 49.5%) received anticancer treatment. Thirty-nine (38.6%) patients had MPS lesions at 83 sites. Multivariate analysis revealed that the significant risk factor for MPS was poor Performance Status (PS) (odds ratio 3.26; 95% confidence interval [CI] 1.18-9.02, P = .023). We performed TPI for 40 out of 83 MPS lesions. Mean NRS for MPS before TPI was 7.95, which improved to 4.30 after TPI (P < .001). CONCLUSIONS: MPS was common in patients with incurable cancer and the risk factor identified in this study was poor performance status. TPI could be a treatment option.

The current clinical use of adjuvant analgesics for refractory cancer pain in Japan: a nationwide cross-sectional survey.

BACKGROUND: Although adjuvant analgesics are used to treat opioid-refractory cancer pain, there is insufficient evidence to support this practice and limited data to guide the choice depending on cancer pain pathophysiology, dose titration and starting dose. This survey aimed to clarify the current use of adjuvant analgesics for treating opioid-refractory cancer pain. METHODS: In this cross-sectional study, we sent an online survey questionnaire to 208 certified palliative care specialists. Primary outcomes were (i) effective pathophysiological mechanism of cancer pain and (ii) initiating doses and time period to the first response to each adjuvant analgesic therapy. RESULTS: In total, 87 (42%) palliative care specialists responded. Of all patients with cancer pain, 40% of patients (median) with refractory cancer pain were prescribed adjuvant analgesics. Additionally, 94.3, 93.1 and 86.2% of palliative care specialists found dexamethasone/betamethasone effective for neuropathic pain caused by tumor-related spinal cord compression, pregabalin effective for malignant painful radiculopathy and dexamethasone/betamethasone effective for brain tumor or leptomeningeal metastases-related headache, respectively. The median starting dose of pregabalin, dexamethasone/betamethasone, lidocaine and ketamine were 75, 4, 200, and 50 mg/day, respectively, and the median time to the first response of those medications were 5, 3, 2 and 3 days, respectively. CONCLUSIONS: Many palliative care specialists select adjuvant analgesics depending on the pathophysiological mechanism of cancer pain in each case. They used such adjuvant analgesics in low doses for cancer pain with short first-response periods.

Predictors of duloxetine response in patients with neuropathic cancer pain: a secondary analysis of a randomized controlled trial-JORTC-PAL08 (DIRECT) study.

PURPOSE: Duloxetine has some effect against cancer neuropathic pain (CNP); however, predictors of duloxetine response are unclear. This study sought to identify predictors of duloxetine response in patients with CNP. METHODS: Patients (N = 70) with CNP unresponsive to or intolerant of opioid-pregabalin combination therapy, with a brief pain inventory-short form (BPI-SF) Item 5 score (average pain) ≥ 4, and with a total hospital anxiety and depression scale score < 20, were randomized to a duloxetine or a placebo group. Multiple linear regression analysis was conducted to identify predictors of duloxetine response as a secondary analysis with the change in the average pain score on day 10 from day 0 as the dependent variable, and the following five covariates; baseline (day 0) average pain score, baseline opioid dose, continuation/discontinuation of pregabalin, and items 20 and 21 score of the short-form McGill pain questionnaire 2 (SF-MPQ-2) as independent variables. RESULTS: Of the four domains (continuous pain, intermittent pain, neuropathic pain, and affective descriptors) score of SF-MPQ-2 on day 0, significant differences were observed in the neuropathic pain domain (p = 0.040) in change on the average pain between day 10 and day 0 in the duloxetine group. Multiple linear regression analysis revealed that patients with a high score for SF-MPQ-2 Item 21 (tingling pain) on day 0 had a significantly greater change in average pain between day 10 and day 0 (p = 0.046). CONCLUSION: Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.

Attitude of Japanese palliative care specialists towards adjuvant analgesics cancer-related neuropathic pain refractory to opioid therapy: a nationwide cross-sectional survey.

Cancer-related neuropathic pain (CNP) requires therapy involving multiple pharmaceuticals, including anticonvulsants and antidepressants; however, strong evidence to support this practice is limited. This study is a cross-sectional questionnaire-based survey. As the standard dose of adjuvant analgesics for CNP refractory to opioid therapy is not clear, the purpose of this study is to clarify the opinions of specialists about the usage of duloxetine and pregabalin for patients with CNP refractory to opioid therapy. Two hundred and eight certified palliative care specialists were surveyed and a total of 87 (42%) responses were analyzed. Twenty-five percent of specialists had considered increasing duloxetine doses up to 60 mg/day and 58% had considered increasing pregabalin doses up to 300 mg/day for CNP refractory to opioid therapy. However, 23% of the specialists succeeded in increasing duloxetine doses up to 60 mg/day and 17% in increasing pregabalin doses up to 300 mg/day, respectively.

Efficacy of immediate-release oxycodone for dyspnoea in cancer patient: cancer dyspnoea relief (CDR) trial.

BACKGROUND: Guidelines recommend morphine as the first-line pharmacological treatment for cancer dyspnoea. However, trials with other opioids have not been performed. Our aim was to demonstrate the non-inferiority of oxycodone to morphine for relieving dyspnoea in cancer patients. METHODS: We conducted a multicentre, open-label, parallel-group, randomized control trial. We randomly and equally assigned cancer patients on regular oxycodone who developed dyspnoea to get a single dose of oral immediate-release oxycodone or morphine. We evaluated the change in dyspnoea intensity (numeric rating scale: 0-10) and adverse events after the medication administration. RESULTS: This study was preconfidence interval -maturely terminated. All 17 enroled patients (8 using oxycodone, 9 using morphine) completed evaluations. In the oxycodone group, dyspnoea intensity decreased 1.75 points [95% confidence interval, 0.72-2.78] at 60 min and 1.50 points (95% confidence interval, -0.11 to 3.11) at 120 min. In the morphine group, dyspnoea decreased 1.33 points (95% confidence interval, 0.41-2.25) at 60 min and 1.00 point (95% confidence interval, -0.08 to 2.08) at 120 min. The differences did not fulfil the non-inferiority requirement. Although two and four patients in morphine group developed drowsiness at 60 and 120 min, no patient in oxycodone group developed significant adverse events. CONCLUSIONS: Although we did not show the non-inferiority of oxycodone, oxycodone may have some effectiveness for cancer dyspnoea without significant safety concern. CLINICAL TRIAL REGISTRATION: UMIN-CTR: UMIN 000005760.

Side effects of corticosteroids in patients with advanced cancer: a systematic review.

PURPOSE: Corticosteroids are commonly used in palliative care settings, but are associated with several side effects. Although adverse events (AEs) are highly distressing for patients, few data are available from prospective studies to look at incidence or predictors of such harms. The aim of this study is to identify AE reporting among studies of patients with advanced cancer receiving corticosteroids for any reason. METHODS: A systematic review was conducted using the following data sources: PubMed, Medline, SCOPUS, Cochrane reviews, and CINAHL. Randomized controlled trials (RCTs) with patients with advanced cancer assessing the effect of corticosteroids were included. Consecutive cohort observational studies of corticosteroid toxicities in cancer patients were also included. RESULTS: Twenty-seven RCTs and 12 consecutive cohort observational studies were identified. The most frequently reported primary outcome of RCTs was nausea and vomiting (8/27). Dexamethasone was prescribed in almost half of RCTs (13/27). In consecutive cohort studies, the primary outcomes were a wide variety of symptoms. Dexamethasone was also the most common glucocorticoid used (7/12). In terms of quality of AE reporting, two RCTs and one consecutive cohort study used a validated AE assessment tool in their studies. CONCLUSIONS: Side effects of corticosteroids in advanced cancer patients were poorly reported with few data using validated tools. Researchers should be aware of the guideline of AE reporting to provide the best evidence of risk-benefit balance. Developing specific consensus guidelines about AE reporting in studies of glucocorticoids in studies of people with advanced cancer would be useful.

Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study).

BACKGROUND: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group. A biomarker for selection of opioids for cancer pain relief would be particularly useful clinically, and therefore we have planned a randomized comparative study of morphine and oxycodone, using the COMT rs4680 SNP as a biomarker. This study is aimed at verifying the assumption that patients in the GG group require an increased morphine dose for pain relief. METHODS: The RELIEF study is a randomized, multi-institutional, open-label trial with a primary endpoint of the proportion of subjects requiring high-dose opioids, as calculated from the dose of a rescue preparation administered on day 0. Secondary endpoints include the Hospital Anxiety and Depression Scale, Short form McGill Pain Questionnaire-2, European Organization for Research and Treatment of Cancer QLQ-C15-PAL, Pain Catastrophizing Scale, and adverse events, Eligibility criteria are patients with advanced carcinoma with non-daily use of opioids in initial screening for registration; and cancer pain targeted for daily opioid treatment, NSAIDs or acetaminophen, NRS ≥3(average over 24 h), opioid-treatment naive within 30 h, no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and written informed consent at the time of second registration. Between November 2014 and June 2017, an estimated 110 patients from two sites in Japan were randomized (1:1) to morphine or oxycodone in GG and non-GG groups. DISCUSSION: A method for selection of appropriate opioids in cancer patients is a high unmet medical need. This study was designed to evaluate the efficacy of different opioids in patients with cancer based on gene polymorphism, as the first potential multi-institutional registration trial to be conducted in cancer patients with pain. TRIAL REGISTRATION: UMIN000015579 Date of registration: 4 November 2014. It is updated once every six months, the latest update is 30 June 2017. Trial status. The enrollment started in November 2014. At the time of manuscript submission (July 2017), Three-quarters of patients have participated. We thus expect to complete the recruitment by March 2018.

Expectation of a Decrease in Pain Affects the Prognosis of Pain in Cancer Patients: a Prospective Cohort Study of Response to Morphine.

PURPOSE: Cancer pain is a multidimensional experience that includes physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Few prospective studies have examined the relationship between a patient's expectation of pain improvement and the pain prognosis. The aim of this prospective study was to investigate whether patients' expectation to pain reduction was associated with pain intensity after morphine treatment in opioid treatment-naïve patients with various types of cancer. METHODS: The subjects were patients scheduled for cancer pain treatment with morphine who were taking nonsteroidal anti-inflammatory drugs daily. Morphine treatment was performed according to the standard method, including titration (NCCN Guidelines™, Adult Cancer Pain). Simple regression analysis was performed between pain intensity numerical rating scale (NRS) (day 8) as the dependent variable, expectation of pain decrease NRS (day 1), tumor types, and the following covariates as independent variables: patients' characteristics such as age, gender, PS (day 1), genotype of catechol-O-methyltransferase, total scores of Hospital Anxiety and Depression Scale (day 1), and pain intensity NRS (day 1). Multiple regression analysis was performed using forced entry methods with pain intensity NRS (day 8) as the dependent variable, and expectation of pain decrease NRS (day 1) and the covariates as independent variables that had a p value <0.05 in the simple regression models. RESULTS: A total of 100 patients with baseline data were included, and 97 patients (51% female) met the inclusion criteria. Patients with a high expectation of pain decrease NRS had a significantly lower pain intensity NRS (day 8) (p = 0.001). CONCLUSION: Non-pharmacological factors such as expectations for pain treatment could also be important factors to treat cancer pain, which might be associated with communication skills in physicians.

Chemotherapeutic drugs that penetrate the blood-brain barrier affect the development of hyperactive delirium in cancer patients.

OBJECTIVE: Delirium is a frequently encountered psychiatric disease in terminal cancer patients. However, the mechanism of delirium is unclear. The aim of our study was to investigate the relationship between administration of chemotherapy drugs that penetrate the blood-brain barrier (BBB) and the development of delirium in cancer patients. METHOD: We retrospectively analyzed 166 cancer patients (97 males, 69 females) continuously who died between September of 2007 and January of 2010 using a review of medical charts. Multiple logistic regression analysis was employed to investigate the effects of antineoplastic drugs penetrating the BBB on development of delirium in cancer patients with control for other risk factors. RESULTS: In multivariate analysis, antineoplastic drugs that penetrated the BBB were significantly associated with development of delirium (OR = 18.92, CI 95 = 1.08-333.04, p < 0.001). SIGNIFICANCE OF RESULTS: The use of chemotherapy drugs that penetrate the BBB may be a risk factor for delirium. This information may allow palliative care doctors and medical oncologists to predict which patients are at increased risk for delirium.

Severe behavioral and psychological symptoms of dementia successfully treated at home with a blonanserin transdermal patch: A case report.

AIM: Behavioral psychological symptoms of dementia (BPSD) are sometimes difficult to treat due to severe psychiatric symptoms such as delusions of poisoning and violent behavior. Moreover, in cases of parental neglect, the management of these psychiatric symptoms becomes more difficult. Therefore, home-visiting doctors sometimes have to manage patients with BPSD and severe psychiatric symptoms, and a new approach is needed. In this case report, the effect of blonanserin transdermal patch on these patients is to be highlighted. METHODS: The patient is a 91-year-old woman diagnosed with Alzheimer's disease. She had severe BPSD such as delusion of robbery and violent behavior, and refused oral medications including memantine and yokukansan. Then she was treated with blonanserin transdermal patch (20 mg/day). The severity of psychiatric symptoms of BPSD was assessed over time using the Neuropsychiatric Inventory (NPI) score. Moreover, the patient's cognitive function was also assessed over time by Mini-Mental State Examination (MMSE). RESULTS: After the introduction of blonanserin patch, the patient's psychiatric symptoms were stabilized markedly, and both NPI and MMSE scores improved. The patient was able to stay at home calmly and was mentally well stabilized to the extent that she did not require hospitalization. No apparent side effects were admitted. CONCLUSIONS: The blonanserin transdermal patch may be able to manage BPSD at home and is effective in patients who refuse oral medications. Home-visiting doctors may consider the use of blonanserin patches at home for patients with severe BPSD, manifesting as delusions of poisoning and refusing oral drugs.

Relationship between dyspnoea and related factors in patients with cancer: a cross-sectional study.

OBJECTIVES: Dyspnoea is a common and distressing symptom in patients with cancer. We aimed to analyse the association between dyspnoea and related factors and to estimate their causal relationship. METHODS: A cross-sectional study was conducted. Patients with cancer with dyspnoea and a mean Numerical Rating Scale (NRS) of ≥3 over 24 hours were enrolled at 10 institutions in Japan from December 2019 to February 2021. The outcomes included dyspnoea, cough and pain NRS over 24 hours, Eastern Cooperative Oncology Group Performance Status, Hospital Anxiety and Depression Scale, Somatosensory Amplification Scale, opioids for dyspnoea and respiratory failure. Path analyses were conducted to estimate the direct and indirect paths with reference to dyspnoea and related factors. RESULTS: A total of 209 patients were enrolled and 208 patients were included in the analysis. Cough worsened dyspnoea (ß=0.136), dyspnoea increased emotional distress (ß=1.104), emotional distress increased somatosensory amplification (ß=0.249) and somatosensory amplification worsened cough (ß=0.053) according to path analysis. CONCLUSION: There may be a vicious circle among dyspnoea and related factors: cough worsened dyspnoea, dyspnoea increased emotional distress, emotional distress increased somatosensory amplification and somatosensory amplification worsened cough. When treating dyspnoea in patients with cancer, managing these factors aimed at interrupting this vicious circle may be useful. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000038820).

Early palliative intervention for patients with advanced cancer.

BACKGROUND: Early palliative intervention in advanced cancer patients with metastatic non-small-cell-lung cancer has been shown to improve survival time. Possibly, palliative intervention at the time of outpatient care further improves patient survival time. OBJECTIVE: We performed a comparative study of late and early referrals of patients with advanced cancer to clarify the appropriate time for palliative intervention and the improvement in survival time. METHODS: Two hundred and one cancer patients, all since deceased, who were treated in our department over a period of 4 years were divided into two groups: patients who experienced outpatient services for <7 days (late referral group, 64 patients) and those who experienced outpatient services for ≥7 days (early referral group, 137 patients). Survival time, duration of chemotherapy and post-progression survival were retrospectively analyzed through examination of medical records. RESULTS: Survival time of the early referral group was longer than that of the late referral group in all the cases (19.0 vs. 6.5 months, P < 0.001). Survival time in advanced non-small-cell lung cancer was 3.5 and 14.0 months (P = 0.010) and 16.5 and 20.9 months (P = 0.039) in advanced colorectal cancer, respectively. There was no significant difference in gastric cancer (P = 0.310). Post-progression survival in each group was 0.7 and 2.7 months (P = 0.018) in non-small-cell lung cancer. CONCLUSIONS: The results of this study suggested that early outpatient referral and palliative intervention leads to improvement of the outcome in patients with advanced non-small-cell lung cancer and colorectal cancer. A prospective comparative study is warranted.

[Psycho-Oncology: An Overview of Clinical Practice Guidelines for the Care of Psychologically Distressed Bereaved Families Who Have Lost a Family Member to Physical Illness, Including Cancer].

Psycho-oncology is an interdisciplinary field encompassing physical, psychological, social, and behavioral aspects of the cancer experience for both patients and caregivers. The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer developed evidence-based clinical practice guidelines for the care of psychologically distressed bereaved families who have lost members to physical illness including cancer. Because of the wide variation in international attitudes toward bereavement care, we have enhanced the descriptions in the general comment section. Two clinical questions were set and a systematic literature review was conducted by the guideline development group. The level of evidence and the strength of the recommendations were graded, and the modified Delphi method was used to validate the recommendation statements. Recommendations were as follows: nonpharmacologic interventions were indicated for severe psychological distress (depression and grief), and antidepressants were indicated for depression; however, psychotropic medications, including antidepressants, were not recommended for "complicated" grief. These guidelines facilitate the provision of appropriate care for distressed bereaved families and identify areas in need of further research.