Incidence of Delirium With Different Oral Opioids in Previously Opioid-Naive Patients.

BACKGROUND: Opioids are known to induce delirium, but few studies have closely investigated differences in incidence of delirium among different opioids. OBJECTIVES: To determine whether there is a clinically significant difference in the incidence of delirium between oral opioids in previously opioid-naive patients. METHODS: Subjects were 259 opioid-naive in-patients with cancer who were started on morphine sulfate, oxycodone hydrochloride, or tapentadol hydrochloride extended-release tablets at our hospital between August 1, 2014, and September 30, 2018. The incidence of delirium during the first week of treatment was compared between the drugs. RESULTS: The incidence of delirium was 4.8% (n = 83) for morphine sulfate, 6.9% (n = 131) for oxycodone hydrochloride, and 6.7% (n = 45) for tapentadol hydrochloride. The incidence did not significantly differ between oxycodone hydrochloride (OR = .69, 95% CI = .20-2.30, P [Fisher's exact test] = .77) or tapentadol hydrochloride (OR = .71, 95% CI = .15-3.32, P [Fisher's exact test] = .70) and morphine sulfate (reference group). Moreover, the incidence did not significantly differ between tapentadol hydrochloride (OR = 1.03, 95% CI = .27-3.00, P [Fisher's exact test] = 1.00) and oxycodone hydrochloride (reference group). CONCLUSION: The incidence of delirium in previously opioid-naive patients did not differ significantly among morphine sulfate, oxycodone hydrochloride, and tapentadol hydrochloride extended-release tablets, suggesting similar risk of delirium in opioid-naive patients among these oral opioids.

Influence of genetic variants of opioid-related genes on opioid-induced adverse effects in patients with lung cancer: A STROBE-compliant observational study.

ABSTRACT: Despite the dramatic advancement of cancer chemotherapy and immunotherapy, the insufficient progress has been made in basic or translational research on personalization of opioid therapy. Predicting the effectiveness of opioid analgesic therapy and the risk of adverse effects prior to therapy are expected to enable safer and more appropriate opioid therapy for cancer patients. In this study, we compared the incidence of opioid-induced adverse effects between patients with different variants of the genes related to responsiveness to opioid analgesics.Participants were 88 patients with lung cancer who provided general consent for exome sequencing and were treated with morphine or oxycodone at Shizuoka Cancer Center Hospital between April 2014 and August 2018. Incidence rates for 6 adverse effects of opioid therapy (somnolence, nausea, constipation, delirium, urinary retention, and pruritus) were determined and the influence of single nucleotide polymorphisms in coding regions of the opioid µ receptor 1 (OPRM1) (rs1799971), opioid δ receptor 1 (rs2234918), opioid κ receptor 1 (rs1051660), catechol-O-methyltransferase (COMT) (rs4680), dopamine receptor D2 (rs6275), adenosine triphosphate binding cassette B1 (rs1045642), G-protein regulated inward rectifier potassium channel 2 (rs2070995), and fatty acid amide hydrolase (rs324420) genes on those adverse effects were analyzed.Analysis of OPRM1 gene variant status (Asn133Asp A > G) showed that G/G homozygotes were at significantly lower risk of somnolence compared with A allele carriers (0% vs 28.4%; Fisher exact test, P = .005; OR, 0; 95% CI, 0-0.6), and analysis of COMT gene variant status (Val158Met, G > A) showed that G/G homozygotes were at significantly higher risk of somnolence compared with A allele carriers (35.0% vs 10.4%; Fisher exact test, P = .008; OR, 4.5; 95% CI, 1.4-18.1). No relationship between variant status and adverse effects was found for the other genes.These findings demonstrate that OPRM1 and COMT gene variants influence the risk of somnolence as an adverse effect of opioid analgesic therapy.

Safety profile of prophylactic rescue dosing of immediate-release oral opioids in cancer patients.

BACKGROUND: Appropriate prophylactic rescue dosing of opioids is considered effective for cancer pain relief, but no study has reported the safety of such prophylactic rescue. We compared the safety of prophylactic rescue dosing of immediate-release oral opioids with that of regular rescue dosing. METHODS: The study included 103 cancer patients who used either immediate-release morphine syrup or immediate-release oxycodone powder at Shizuoka Cancer Center between January and December 2016. Patients were divided into those who mostly used (prophylactic group) and those who never used (regular group) prophylactic rescue doses of opioids and compared the incidence of adverse events (AEs). We also investigated whether the prophylactic rescue dose negatively interfered with its objective activity, such as meals. RESULTS: Incidence of each AE in the prophylactic versus regular groups was as follows: somnolence, 20.6% versus 14.3%; nausea, 22.1% versus 17.1%; constipation, 19.1% versus 20.0%; urinary retention, 1.5% versus 2.9%; delirium, 4.4% versus 8.6%; and pruritus, 0% versus 2.9%. No serious AE associated with prophylactic rescue dosing was observed. No significant difference was observed in the incidence of any AE between the two groups (p > 0.05, Fisher's exact test). No AE interfered with the objective activity of the prophylactic rescue dose. CONCLUSION: Incidence of AEs associated with prophylactic rescue dosing is not different from that associated with regular rescue dosing. In addition, the prophylactic rescue dose did not adversely affect its objective activity, suggesting the safety of appropriate prophylactic rescue dosing was similar to that of regular rescue dosing. TRIAL REGISTRATION: The study approval number in the institution; H29-J30-29-1-3. Registered June 5, 2017.

Development of a Standard for Hospital-Based Palliative Care Consultation Teams in Japan Using a Modified Delphi Method.

CONTEXT: Hospital-based palliative care consultation teams (PCCTs) are rapidly being disseminated throughout Japan. The roles of PCCTs have changed during the past decade, particularly with the introduction of a modified national cancer care act to promote early palliative care and integrated oncology and palliative care. OBJECTIVES: This study aimed to develop a consultation team standard for hospital-based palliative care in Japan. METHODS: We developed a provisional standard based on literature review and used a modified questionnaire-based Delphi method. Our Delphi panel comprises 20 experts selected from all relevant disciplines. RESULTS: All experts selected responded to the surveys over all rounds, and 14 of the 20 participated in the panel meeting. In the first round, 79 of 109 statements were judged to be appropriate, and 30 of 109 statements led to disagreements. About 16 of those 30 statements underwent minor revision, 1 was divided into two statements, and 13 remained unchanged. We then added six statements based on a discussion among participants and authors. In addition, based on comments from an external reviewer, we revised the standard, resulting in four statements being combined into two for a new total of 114 statements. In the second round, 108 of 114 statements were judged to be appropriate, and in the third round, none of the six controversial statements were judged to be appropriate. The final version comprises 108 statements. CONCLUSION: We developed a standard for PCCTs in Japanese cancer hospitals. This standard provides a useful guide for clinical activities and a tool to evaluate quality of palliative care.

Community response to a step change in the aircraft noise exposure around Hanoi Noi Bai International Airport.

In December 2014, a new terminal building was opened at the Hanoi Noi Bai International Airport (HNBIA) with two runways, causing a 20%-30% increase in the number of flights. Three socio-acoustic surveys were conducted in August-September 2014, February-March 2015, and August-September 2015, to contribute not only to the environmental impact assessments and aircraft noise policies in Vietnam but also to more global intervention studies. Because of the change of runway use, in addition to the increased number of flights, noise exposure at each site changed considerably among the surveys. Changes in the noise exposure from the first to the second or third survey (ΔLden and ΔLnight) were used as a measure of exposure change. Multiple logistic regression analysis showed that ΔLden has a significant positive effect on annoyance regardless of ΔLden ranges, but the effect of ΔLnight on insomnia was significant only for ΔLnight > 0. Annoyance increase in the overall ΔLden range may be caused by the respondents' recognition of increase in emission in addition to practical increase in exposure. More severe attitudes to airplanes around HNBIA might increase annoyance even if noise exposure decreases. Thus, the change effect clearly occurs in annoyance but partially in insomnia.

Combined Effects of High-Speed Railway Noise and Ground Vibrations on Annoyance.

The Shinkansen super-express railway system in Japan has greatly increased its capacity and has expanded nationwide. However, many inhabitants in areas along the railways have been disturbed by noise and ground vibration from the trains. Additionally, the Shinkansen railway emits a higher level of ground vibration than conventional railways at the same noise level. These findings imply that building vibrations affect living environments as significantly as the associated noise. Therefore, it is imperative to quantify the effects of noise and vibration exposures on each annoyance under simultaneous exposure. We performed a secondary analysis using individual datasets of exposure and community response associated with Shinkansen railway noise and vibration. The data consisted of six socio-acoustic surveys, which were conducted separately over the last 20 years in Japan. Applying a logistic regression analysis to the datasets, we confirmed the combined effects of vibration/noise exposure on noise/vibration annoyance. Moreover, we proposed a representative relationship between noise and vibration exposures, and the prevalence of each annoyance associated with the Shinkansen railway.

Palliative Care for Patients with Gynecologic Cancer in Japan: A Japan Society of Gynecologic Palliative Medicine (JSGPM) Survey

Purpose: To evaluate palliative care for patients with gynecologic cancer in Japan. Materials and Method: A questionnaire asking facility characteristics, systems to coordinate palliative care, current status of end-of-life care, provision of symptom relief, palliative radiation therapy and chemotherapy, and cases of death from gynecological cancer, was mailed to facilities treating gynecologic cancer. Results: A total of 115 facilities (29.3% of the total) responded to the questionnaire. Of these, 33.0 (29.0%) had a palliative care ward. End-of-life care was managed by obstetricians and gynecologists in 72.0% of the facilities. The site where end-of-life care was provided was most often a ward in the department where the respondent worked. The waiting period for transfer to a hospice was 2 weeks or more in 52% of facilities. Before the start of primary treatment, pain control was managed by obstetrians and gynecologists in 98.0% of facilities. Palliative radiation therapy or chemotherapy was administered at 93.9% and 92.0% of facilities, respectively. Of the 115 facilities, 34.0 (29.6%) reported cases of death from gynecological cancer. There were 1,134 cases of death. The median time between the last cycle of chemotherapy and death was 85 days for all gynecological cancers. The proportion of patients receiving chemotherapy in the last 30 and 14 days of life were 17.4% and 7.1%, respectively. Conclusions: This large-scale survey showed characteristics of palliative care given to patients with gynecologic cancer in Japan. Assessment of death cases showed that the median time between the last cycle of chemotherapy and death was relatively short.

A case of trigeminal neuralgia complicated by ipsilateral temporal arteritis.

Trigeminal neuralgia (TN) complicated with temporal arteritis (TA) is not a common disease, but it is a very important syndrome to consider for diagnosing facial pain in individuals older than 50 years. We therefore report on a rare case of TN with TA that occurred simultaneously on the same side with each symptom responding to specific treatment.

Correlation between salivary alpha-amylase activity and pain scale in patients with chronic pain.

BACKGROUND AND OBJECTIVES: The visual analog scale (VAS) is commonly used to assess pain intensity. However, the VAS is of limited value if patients fail to reliably report. Objective assessments are therefore clearly preferable. Previous reports suggest that elevated salivary alpha-amylase may reflect increased physical stress. There is a close association between salivary alpha-amylase and plasma norepinephrine under stressful physical conditions. In this study, we have determined the usefulness of a portable salivary alpha-amylase analyzer as an objective biomarker of stress. METHODS: Thirty patients (male/female = 15/15, age: 60.5 +/- 15.3 years) with chronic low back or leg pain (pain (+) group) and 20 pain-free control patients undergoing elective surgery under general anesthesia with epidural analgesia (pain (-) group) were recruited. Patients received epidural block with 5 to 10 mL 1% lidocaine. VAS, blood pressure, and heart rates were assessed before and 30 and 45 minutes after the epidural block. Salivary alpha-amylase was simultaneously measured using a portable analyzer. The relationship between the VAS and salivary alpha-amylase in chronic pain patients was assessed. RESULTS: After the epidural block both heart rate and systolic blood pressure decreased by approximately 8%. In the pain (+) group, the epidural block markedly decreased the VAS pain scale and salivary alpha-amylase from 56 +/- 22 to 19 +/- 16 mm (P < .01) and from 82 +/- 48 to 45 +/- 28 U/mL (P < .01), respectively, with a significant correlation between the 2 measures (r = 0.561, P < .01). In contrast, salivary alpha-amylase did not change significantly in the pain (-) group. CONCLUSIONS: Because there was a significant correlation between VAS pain scale and salivary alpha-amylase, we suggest that this biomarker may be a good index for the objective assessment of pain intensity. In addition, a simple to use portable analyzer may be useful for such assessment.

The relationship between salivary biomarkers and state-trait anxiety inventory score under mental arithmetic stress: a pilot study.

Measurement of stress hormones is a common objective method for assessment of mental stress. However, the stress of blood sampling alone may also increase stress hormone levels. In the present study, we sampled salivary biomarkers from healthy volunteers under noninvasive conditions and determined their efficacy to assess mental stress. Specifically, we examined the relationship between State Anxiety Inventory score (STAI-s) in subjects exposed to arithmetic stress and salivary chromogranin-A, alpha-amylase, or cortisol. The STAI-s was significantly correlated to salivary alpha-amylase (r = 0.589; P < 0.01) but not to salivary chromogranin-A or cortisol. Therefore, salivary alpha-amylase is a useful indicator of psychosocial stress.

Effect of phenylephrine on histamine-induced bronchoconstriction in dogs.

PURPOSE: Although an α-adrenoceptor has been suggested to be involved in the mechanism of asthma, the effect of α1-agonist on the airway is still unclear. In this study we evaluated the effect of phenylephrine on the airway with a direct visualization method using a superfine fiberoptic bronchoscope (SFB). METHODS: Seven mongrel dogs were anesthetized with pentobarbital (30 mg·kg-1 IV) and paralyzed by pancuronium (0.2mg·kg-1·h-1). The trachea was intubated with an endotracheal tube (ID 7 mm) that has a second lumen for insertion of a SFB (OD 2.2 mm) to monitor the bronchial cross-sectional area (BCA) continuously. The tip of a SFB was placed at the level between the second and third bronchial bifurcation. To assess hemodynamics, the direct arterial blood pressure (ABP) and pulmonary arterial pressure (PAP) were monitored via a femoral arterial catheter and Swan-Granz catheter. Bronchoconstriction was elicited by histamine (10 µg·kg-1+ 500 µg·kg-1·h-1_. At 30 min after the histamine was started, saline or phenylephrine (1, 10, and 100µg·kg-1) was given intravenously. The BCA and hemodynamic variables were assessed before (basal) and 30 min after the histamine was started and 5 min after saline and each phenylephrine dose. RESULTS: Histamine reduced BCA by 40.3±6.3%. Phenylephrine at 10 and 100 µg·kg-1 significantly increased the ABP and PAP; and it significantly decreased the BCA, by 6.5±6.9% and 14.2±7.9%, respectively. Plasma epinephrine and norepinephrine were also significantly reduced following phenylephrine 100 µg·kg-1 IV. CONCLUSION: The dose of phenylephrine that produced vasopressive actions worsened the histamine-induced bronchoconstriction slightly but significantly. Therefore, phenylephrine should be used with caution in asthmatic patients.