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).

A Facile Method for the Quantification of Urinary Uracil Concentration by a Uracil-Specific Fluorescence Derivatization Reaction.

A facile and reliable fluorescence method for the quantification of urinary uracil concentration is proposed herein. The assay utilizes a specific fluorescence (FL) derivatization reaction for uracil using 3-methylbenzamidoxime as a fluorogenic reagent. Although the presence of urine inhibited the FL reaction, 10 µL of urine was sufficient for the detection of urinary uracil. The uracil derivative was successfully separated from other fluorescent impurities using simple reversed-phase LC with FL detection. Urinary uracil concentrations from 16 people were compared with the concentrations obtained by the traditional column-switching liquid chromatographic analysis with UV detection. The FL derivative of uracil appeared as a single peak in the chromatograms of all samples. However, several samples showed an additional peak overlapping the uracil peak when using the column-switching method because of UV-active impurities. These results indicated that that the present method is not affected by interfering substances in urine and affords a precise determination of urinary uracil. We expect the proposed method to be applicable for diagnosing dihydropyrimidine dehydrogenase deficiency in 5-fluorouracil chemotherapy.

Comparison between patient-reported and clinician-reported outcomes: Validation of the Japanese version of the Integrated Palliative care Outcome Scale for staff.

OBJECTIVES: The goal of palliative and supportive care is to improve patients' quality of life (QoL). Patient-reported outcome measures (PROMs) are the gold standard for the assessment of QoL and symptoms; however, when self-reporting is complicated, PROMs are often substituted with proxy-reported outcome measures, such as clinician-reported outcome measures. The objective of this study was to assess the validity and reliability of the Japanese version of the Integrated Palliative care Outcome Scale (IPOS) for staff (IPOS-Staff). METHODS: This multicenter, cross-sectional observational study was conducted concurrently with the validation of the IPOS for patients (IPOS-Patient). Japanese adult patients with cancer and their staff were recruited. We assessed the characteristics of the patients and staff members, missing values, prevalence, and total IPOS scores. For the analysis of criterion validity, intra-rater, and inter-rater reliability, we calculated intraclass correlations (ICCs). RESULTS: One hundred and forty-three patients completed the IPOS-Patient, and 79 medical staff members completed the IPOS-Staff. The most common missing values from IPOS-Staff were Family Anxiety (3.5%) and Sharing Feelings (3.5%). Over half of the patients scored themselves moderate or worse for Poor Mobility, Anxiety, and Family Anxiety, while staff members scored patients moderate or worse for Weakness, Anxiety, and Family Anxiety. For criterion validity (patient-staff agreement) as well as intra-rater and inter-rater reliability, ICCs ranged from 0.114 (Sharing Feelings) to 0.826 (Nausea), 0.720 (Anxiety) to 0.933 (Nausea), and -0.038 (Practical Problems) to 0.830 (Nausea), respectively. SIGNIFICANCE OF RESULTS: The IPOS-Staff is easy to respond to; it has fair validity and reliability for physical items but poor for psycho-social items. By defining the context and objectives of its use and interpretation, the IPOS-Staff can be a useful tool for measuring outcomes in adult patients with cancer who cannot complete self-evaluations.

Changes in cardiovascular parameters in rats exposed to chronic widespread mechanical allodynia induced by hind limb cast immobilization.

To elucidate the relationship between chronic pain conditions with cast immobilization and autonomic function, we investigated the functional changes of the autonomic nervous system in conscious rats with chronic post-cast pain (CPCP) induced by a two-week cast immobilization of one hind limb. We telemetrically examined the time courses of systolic arterial blood pressure (SBP), heart rate (HR), and the middle-frequency (MF) component obtained from the power spectral analysis of SBP variability as a vasomotor sympathetic index. We also investigated the baroreflex sensitivity to phentolamine, an α-adrenoceptor antagonist, and the SBP and HR responses to a low ambient temperature (LT; 9.0 ± 0.2°C) exposure, a sympathetic stimulant. Rats exposed to cast immobilization exhibited mechanical allodynia lasting for at least 10 weeks after cast removal in the calf area (skin and muscle) of the bilateral hind limbs. Under resting conditions, the SBP, HR, and MF components were significantly increased during cast immobilization (all p < 0.001). Following cast removal, these parameters gradually decreased and within 1 week reached lower than baseline levels, lasting for over 10 weeks. Phentolamine administration (10 mg/kg, intraperitoneally) significantly decreased the SBP before and during cast immobilization (before, p < 0.001; during, p = 0.001) but did not lower the SBP after cast removal. The baroreflex gain after phentolamine administration, calculated as the HR increase divided by the SBP reduction, was significantly increased after cast removal (p = 0.002). The SBP increase on LT exposure was significantly greater after cast removal than that before cast immobilization, suggesting hypersensitivity to sympathetic neurotransmitters. These results revealed that, in the CPCP model, sympathetic activation was augmented during cast immobilization, which then decreased after cast removal and remained below normal levels with persisting pain behaviors. Additionally, the responsiveness of the autonomic nervous system was impaired in the CPCP model.

Gene signature of children with severe respiratory syncytial virus infection.

BACKGROUND: The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection. METHODS: We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes. RESULTS: Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes. CONCLUSIONS: These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV. IMPACT: Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.

Genomic characteristics of listeria monocytogenes causing invasive listeriosis in Japan.

We reviewed 18 listeriosis cases in Japan and performed molecular analysis of causative Listeria monocytogenes (LM) isolates. Strains genetically related to those from other countries caused various types of listeriosis, including vascular listeriosis in immunocompetent elderly people. Our results highlight the importance of integrated clinical and genomic analysis of LM.

How successful are we in relieving terminal dyspnea in cancer patients? A real-world multicenter prospective observational study.

PURPOSE: Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status. METHODS: This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3-4, a dyspnea intensity ≥ 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h. RESULTS: We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0-3.2) at the baseline to 2.1 (95%CI = 1.9-2.2) at 6 h, and remained 1.6-1.8 over 12-48 h. The proportion of patients with dyspnea relief (STAS-J ≤ 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12-48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 ≥ 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h. CONCLUSIONS: Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.

A Multicenter Cohort Study to Explore Differentiating Factors between Tumor Fever and Infection among Advanced Cancer Patients.

Background: Tumor fever and infection are common febrile etiologies among advanced cancer patients. To date, only few studies have been conducted to differentiate between tumor fever and infections. Objective: This study aimed to identify discriminating factors that provide rapid results and are feasible and minimally invasive for discriminating between tumor fever and infection in advanced cancer patients. Methods: This is a retrospective cohort study. Advanced cancer patients with clinically diagnosed tumor fever or infection, who received medical treatment from palliative care specialists in 10 nationwide Japanese hospitals, were consecutively identified during August 2012 and November 2014. The symptoms, physical findings, blood test results at baseline and during fever, imaging findings, and sociodemographic factors of these patients were retrospectively extracted. Results: Thirty-three patients with tumor fever and 72 patients with infection were identified. Their mean age was 68.8 years, 68 (64.8%) were men, and the median palliative performance status (PPS) was 50. Statistically significant factors predicting tumor fever by logistic regression analysis were as follows: deterioration of PPS (odds ratio, 0.078), shaking chills during fever (0.067), and change from baseline data of neutrophil/lymphocyte ratio of ≥5 (0.14). Conclusions: Shaking chills during fever, and changes from baseline of performance status and white blood cell differentiation can be useful to differentiate between tumor fever and infection among advanced cancer patients. Further confirmatory studies are needed.

Multidrug-resistant Gram-negative Bacterial Bloodstream Infections in Children's Hospitals in Japan, 2010-2017.

BACKGROUND: The risk factors of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bloodstream infection (BSI) are not yet known in children. Our aim was to evaluate risk factors and outcomes associated with MDR GNB BSI in children. METHODS: Patients with GNB BSI were enrolled between April 2010 and March 2017 at 8 children's hospitals in Japan. Clinical and microbiologic data were collected retrospectively. The risk factors and outcomes of MDR and non-MDR GNB BSI were compared. RESULTS: In total, 629 GNB BSI episodes met the case definition. The median age and proportion of males were 2 years (interquartile range, 0.3-8.7) and 50.7%, respectively. An underlying disease was found in 94% of patients. The proportion of BSI cases that developed >48 hours after admission was 76.2%. MDR comprised 24.5% of BSI cases. The MDR rate did not change over time (P = 0.540). The effective coverage rate of the initial empiric therapy for the MDR and non-MDR BSI cases was 60.4% and 83.4%, respectively (P < 0.001). The all-cause mortality rate at 28 days for all BSI, MDR-BSI and non-MDR BSI cases was 10.7%, 13.6% and 9.7%, respectively (P = 0.167). MDR BSI was independently associated with cancer chemotherapy within 30 days (odds ratio [OR] 43.90), older age (OR 1.05) and admission to the neonatal ward (OR 0.019). CONCLUSIONS: One-fourth of GNB BSI cases were MDR. Cancer chemotherapy and older age were risk factors for MDR GNB BSI in children's hospitals. MDR did not increase the all-cause mortality rate.

Validation of the Integrated Palliative care Outcome Scale (IPOS) - Japanese Version.

BACKGROUND: To improve palliative care practice, the need for patients-reported outcome measures is increasing globally. The Integrated Palliative care Outcome Scale (IPOS) is a streamlined outcome scale developed to comprehensively evaluate patients' distress. The goal of this study is to assess the reliability and validity of IPOS-Japanese version in cancer patients. METHODS: This is a multicenter, cross-sectional observational study. We assessed the missing values, prevalence, test-retest reliability, criterion validity and known-group validity in Japanese adult cancer patients. Patients provided responses to IPOS, European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and Functional Assessment of Chronic Illness Therapy- Spiritual 12 (FACIT-Sp12). Our medical staff provided responses to Support Team Assessment Schedule (STAS). RESULTS: One hundred forty-two patients were enrolled at six palliative care facilities. Missing values accounted for less than 1% of most items, with a maximum of 2.8%. The prevalence of symptoms was 17.7-88.7%. The intra-class correlation coefficient ranged from 0.522 to 0.951. The range of correlation coefficients with EORTC-QLQ-C30, FACIT-Sp12 and STAS as gold standards was 0.013 to 0.864 (absolute values). Total IPOS scores were positively correlated with Eastern Corporative Oncology Group Performance Status (P < 0.001). CONCLUSION: IPOS-Japanese version is a valid and reliable tool. The scale is useful in assessing physical, psychological, social and spiritual symptoms and in measuring outcomes of adult cancer patients in Japan.

First report on USA300 outbreak in a neonatal intensive care unit detected by polymerase chain reaction-based open reading frame typing in Japan.

Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) in the neonatal intensive care unit (NICU) have been reported worldwide. Some outbreaks were caused by USA300, which is a community-associated MRSA clone. In 2011, polymerase chain reaction-based open reading frame typing (POT) for the initial MRSA isolates from all inpatients was started at the Tokyo Metropolitan Children's Medical Center. From March 2014 to April 2015, a total of 131 MRSA strains were isolated, 104 of which were analyzed as healthcare-associated MRSA. Thirteen stains (12.5%) had a POT number of 106-9-93, which strongly suggested USA300; these included 6 from nasal swabs, 6 from blood cultures and 1 from subcutaneous pus. All the MRSA strains were isolated from patients in the NICU; were typed as sequence type 8, spa type t008, and staphylococcal cassette chromosome type mec IVa; and possessed the lukS-lukF and arginine catabolic mobile element-arcA gene. Pulsed-field gel electrophoresis of all the strains, with USA300-0114 as a reference, showed indistinguishable banding pattern. Based on these results, POT was useful in recognizing this first MRSA outbreak of USA300 in a Japanese NICU and was advantageous in terms of swiftness, less cost and monitoring change of the epidemic MRSA lineage.

Jaw Exercise Therapy and Psychoeducation to Reduce Oral Parafunctional Activities for the Management of Persistent Dentoalveolar Pain.

Objective: To retrospectively analyze the effects of our original combination therapy treatment on patients with nonodontogenic persistent dentoalveolar pain. Methods: Twenty-one patients suffering from persistent dentoalveolar pain (nineteen females and two males; mean age ± standard deviation: 55.7 ± 19.6 years) participated in this study. They were treated with a therapy combination of jaw exercise and psychoeducation to reduce oral parafunctional activities every month. The intensity of pain in these subjects was evaluated using a numerical rating scale (NRS) before and after treatment. Results: The NRSs at the baseline ranged from 5 to 10 (median, 8), from 0 to 10 (median, 2) at one month after treatment, from 0 to 10 (median, 1) at three months after treatment, and from 0 to 10 (median, 0) at the end of treatment. Pain intensity after treatment improved significantly. Conclusion: There was a significant reduction in pain after our combination of therapies as nonpharmacological treatments, and therefore this treatment could be useful in the management of NPDP patients.

The Association Between Constipation or Stool Consistency and Pain Severity in Patients With Chronic Pain.

BACKGROUND: Bacteria can influence a variety of gut functions. Some studies showed that stool consistency and constipation were associated with gut microbiome (GM) composition, and enterotype, dysbiosis. Growing evidence indicates the significant role of GM in the homeostatic function of the host body. The GM may regulate multiple neurochemical and neurometabolic pathways. Chronicity of the pain is actively modulated at the molecular to the network level by means of several neurotransmitters. The GM to some extent can affect pain perception. OBJECTIVES: The current study aimed at investigating the relationship between constipation state or usual stool form and pain severity of patients with chronic pain. METHODS: The current study was conducted on 365 patients with chronic pain. The participants were evaluated on their stool form (the Bristol stool form scale; BSFS), constipation state (the Cleveland clinic constipation score; CCCS), body mass index (BMI), and usual pain severity (numerical rating scale; NRS). In addition, the participants were assigned into five groups according to the pain region (i e, low back and/or lower limb, whole body, neck and/or upper back and/or upper limb, head and/or face, chest and/or abdominal). RESULTS: The CCS showed a significant and positive association with the pain severity of the total patients and patients with low back and/or lower limb pain. Simultaneous multiple linear regression analyses revealed that a predictor of the pain severity was the CCS for the total patients and patients with low back and/or lower limb, whole body pain. CONCLUSIONS: Constipation displayed a significant and positive association with the pain severity of the total patients and patients with low back and/or lower limb pain, whole body.

Validation of the Edmonton Symptom Assessment System: Ascites Modification.

CONTEXT: Few patient-reported outcomes are available to measure the symptoms associated with malignant-related ascites in patient care and clinical research. Although the Edmonton Symptom Assessment System: Ascites Modification (ESAS:AM) is a brief tool to measure symptoms associated with malignant-related ascites, it remains to be fully validated. OBJECTIVES: The objective of the study was to validate the ESAS:AM in Japanese cancer patients. METHODS: We assessed the internal consistency, test-retest reliability, concurrent validity, and construct validity in 292 Japanese adult patients with cancer. They completed Japanese versions of the ESAS:AM, M.D. Anderson Symptom Inventory, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module. RESULTS: Cronbach's alpha coefficient of the ESAS:AM was 0.89. The intraclass correlation coefficient on test-retest examination of its total score was 0.93 (P < 0.001). Pearson correlation coefficients of the total score of the ESAS:AM with the total score of the M.D. Anderson Symptom Inventory and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module ranged from 0.44 to 0.81 (P < 0.001) and those with global health status/quality of life and functional subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 ranged from -0.40 to -0.61 (P < 0.001). The total scores of the ESAS:AM were significantly higher in 20 patients with symptomatic ascites (34 [SD, 26]) than 267 patients without symptomatic ascites (23 [SD, 19]) (P = 0.018). CONCLUSION: The ESAS:AM is a reliable and valid tool for measuring symptoms associated with malignant-related ascites and can be used in daily patient care and future epidemiological studies and clinical trials.

Analysis of follow-up data from an outpatient pain management program for refractory chronic pain.

BACKGROUND: Numerous reports indicate that multifaceted pain management programs based on cognitive-behavioral principles are associated with clinically meaningful long-term improvements in chronic pain. However, this has not yet been investigated in Japan. This study investigated the effects of a multifaceted pain management program in Japanese patients with chronic pain, both immediately after the program and 6 months thereafter. METHODS: A total of 96 patients, 37 male and 59 female (mean age 63.8 years) experiencing treatment difficulties and suffering from intractable pain for more than 6 months were enrolled in the study. The programs were conducted with groups of 5-7 patients who met weekly for 9 weeks. Weekly sessions of approximately 2 h in duration incorporating a combination of lectures and exercise were conducted. Several measures related to pain and physical function were assessed at the start of the program, the end of the program, and 6 months after completion of the program. The resulting data were analyzed via Wilcoxon signed-rank test, and 'r' estimated by effect size was also assessed. RESULTS: Of the 96 initial participants, 11 dropped out during the program and 85 completed it. Thereafter, we evaluated 62 subjects at 6 months after the program, while 23 could not be evaluated at that time-point. Pain intensity upon moving, catastrophizing scores, and pain disability scores showed good improvements at the 6-month follow-up, with large efficacy (r > 0.5). Moving capacity and 6-min walking distance also showed good improvements with large efficacy, both at the end of the program and at the 6-month follow-up (r > 0.5). CONCLUSIONS: A multifaceted pain-management program based on cognitive-behavioral principles was effective in Japanese patients with chronic pain, resulting in improved long-term clinical outcomes.

Uric acid, an important antioxidant contributing to survival in termites.

Reactive oxygen species (ROS) are generated spontaneously in all organisms and cause oxidative damage to biomolecules when present in excess. Accumulated oxidative damage accelerates aging; enhanced antioxidant capacity may be a positive factor for longevity. Recently, numerous studies of aging and longevity have been performed using short-lived animals, however, longevity mechanisms remain unknown. Here we show that a termite Reticulitermes speratus that is thought to be long-lived eusocial insect than other solitary insects uses large quantities of uric acid as an antioxidant against ROS. We demonstrated that the accumulation of uric acid considerably increases the free radical-scavenging activity and resistance against ultraviolet-induced oxidative stress in laboratory-maintained termites. In addition, we found that externally administered uric acid aided termite survival under highly oxidative conditions. The present data demonstrates that in addition to nutritional and metabolic roles, uric acid is an essential antioxidant for survival and contributes significantly to longevity. Uric acid also plays important roles in primates but causes gout when present in excess in humans. Further longevity studies of long-lived organisms may provide important breakthroughs with human health applications.

Predictors of Delirium in Corticosteroid-Treated Patients with Advanced Cancer: An Exploratory, Multicenter, Prospective, Observational Study.

BACKGROUND: Corticosteroids are often used to treat fatigue and anorexia, but occasionally produce delirium. Information on the predictors of delirium in corticosteroid-treated cancer patients remains limited. OBJECTIVE: To identify potential factors predicting the development of delirium in corticosteroid-treated cancer patients. DESIGN: An exploratory, multicenter, prospective, observational study. SETTING/SUBJECTS: Inclusion criteria for this study were patients who had metastatic or locally advanced cancer and a fatigue or anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale. MEASUREMENT: Univariate and multivariable analyses were performed to identify the predictors of delirium diagnosed by the Confusion Assessment Method (CAM) within three days of initiation of corticosteroids. RESULTS: Among 207 patients administered corticosteroids, 35 (17%; 95% confidence interval [CI] 12%-23%) developed at least one episode of delirium diagnosed by the CAM. Factors predictive of the development of delirium were as follows: Palliative Performance Scale ≤20, Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 4, the Support Team Assessment Schedule (STAS) score of drowsiness >1, concurrent opioid use, parenteral hydration volume ≤500 mL, and the absence of lung metastasis. A multivariable analysis identified the independent factors predicting responses as ECOG PS = 4 (odds ratio [OR] 4.0; 95% CI 1.7-9.3), STAS score of drowsiness >1 (OR 3.4; 95% CI 1.4-8.2), and concurrent opioid use (OR 3.7; 95% CI 1.0-13). CONCLUSION: Delirium in corticosteroid-treated advanced cancer patients may be predicted by PS, drowsiness, and concurrent opioid use. Larger prospective studies are needed to confirm these results.

C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative care.

BACKGROUND: The association between C-reactive protein (CRP) level, symptoms, and activities of daily living (ADL) in advanced cancer patients is unclear. METHODS: Secondary data analysis of a multicenter prospective cohort study consisted of 2426 advanced cancer patients referred to palliative care settings was conducted to examine the cross-sectional relationships between CRP level, symptoms, and ADL disabilities. Laboratory data, symptoms, ADL, and manual muscle testing (MMT) results were obtained at baseline. Participants were divided into four groups: low (CRP < 1 mg/dl), moderate (1 = < CRP <5 mg/dl), high (5 = < CRP < 10 mg/dl), and very high CRP (10 mg/dl = < CRP). The proportions of eight symptoms, five ADL disabilities, and three categories of MMT according to the CRP groups were tested by chi-square tests. Multiple-adjusted odd ratios (ORs) were calculated by using ordinal logistic regression after adjustment for age, gender, site of primary cancer, metastatic disease, performance status, chemotherapy, and setting of care. RESULTS: A total of 1702 patients were analysed. Positive rates of symptoms and ADL disabilities increased with increasing CRP level. In the very high-CRP group, rates of positivity for anorexia, fatigue, and weight loss were 89.8%, 81.0%, and 79.2%, respectively, and over 70% of patients received assistance for bathing, dressing, going to the toilet, and transfer. The grade of MMT also deteriorated with increasing CRP level. Adjusted ORs for the accumulated symptoms significantly increased with increasing CRP level in the moderate-CRP, high-CRP, and very high-CRP groups [1.6 (95% confidence interval 1.2-2.0), P < 0.001; 2.5 (1.9-3.2), P < 0.001; 3.5 (2.7-4.6), P < 0.001, respectively]. Adjusted ORs for the accumulated ADL disabilities significantly increased in the very high-CRP groups [2.1 (1.5-2.9), P < 0.001]. CONCLUSIONS: Associations between CRP level, symptoms, and ADL were observed in advanced cancer patients receiving palliative care.

Predictors of responses to corticosteroids for anorexia in advanced cancer patients: a multicenter prospective observational study.

PURPOSE: Although corticosteroids are widely used to relieve anorexia, information regarding the factors predicting responses to corticosteroids remains limited. The purpose of the study is to identify potential factors predicting responses to corticosteroids for anorexia in advanced cancer patients. METHODS: Inclusion criteria for this multicenter prospective observational study were patients who had metastatic or locally advanced cancer and had an anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting ≥2-point reduction in NRS on day 3. RESULTS: Among 180 patients who received corticosteroids, 99 (55 %; 95 % confidence interval [CI], 47-62 %) had a response with ≥2-point reduction. Factors that significantly predicted responses were Palliative Performance Scale (PPS) > 40 and absence of drowsiness. In addition, factors that tended to be associated with ≥2-point reduction in NRS included PS 0-3, absence of diabetes mellitus, absence of peripheral edema, presence of lung metastasis, absence of peritoneal metastasis, baseline anorexia NRS of >6, presence of pain, and presence of constipation. A multivariate analysis showed that the independent factors predicting responses were PPS of >40 (odds ratio = 2.7 [95 % CI = 1.4-5.2]), absence of drowsiness (2.6 [1.3-5.0]), and baseline NRS of >6 (2.4 [1.1-4.8]). CONCLUSIONS: Treatment responses to corticosteroids for anorexia may be predicted by PPS, drowsiness, and baseline symptom intensity. Larger prospective studies are needed to confirm these results.

Predictors of response to corticosteroids for dyspnea in advanced cancer patients: a preliminary multicenter prospective observational study.

PURPOSE: Although corticosteroids can relieve dyspnea in advanced cancer patients, factors predicting the response remain unknown. We aimed to explore potential factors predicting the response to corticosteroids for dyspnea in advanced cancer patients. METHODS: In this preliminary multicenter prospective observational study, we included patients who had metastatic or locally advanced cancer, were receiving specialized palliative care services, and had a dyspnea intensity of ≥3 on a 0-10 Numerical Rating Scale (NRS) (worst during the last 24 h). The primary endpoint was NRS of dyspnea on day 3 after the administration of corticosteroids. Univariate/multivariate analyses were conducted to identify factors predicting ≥1-point reduction in NRS. RESULTS: Of 74 patients who received corticosteroids, 50 (68%) showed ≥1-point reduction in dyspnea NRS. Factors that significantly predicted the response were an age of 70 years or older (82 vs. 53%, p = 0.008), absence of liver metastases (77 vs. 46%, p = 0.001), Palliative Prognostic Index (PPI) ≤ 6 (90 vs. 61%, p = 0.041), presence of pleuritis carcinomatosa with a small collection of pleural effusions (84 vs. 55%, p = 0.011), presence of audible wheezes (94 vs. 60%, p = 0.014), and baseline dyspnea NRS ≥7 (76% vs. 52%, p = 0.041). In a multivariate analysis, factors predicting response included PPI <6 (odds ratio (OR), 36.2; p = 0.021), baseline dyspnea NRS (worst) ≥7 (OR, 6.6; p = 0.036), and absence of liver metastases (OR, 0.19; p = 0.029) or ascites/liver enlargement (OR, 0.13; p = 0.050). CONCLUSIONS: The patient characteristics, etiologies of dyspnea, and clinical manifestations may predict responses to corticosteroids for dyspnea. Larger prospective studies are promising to confirm our findings.