How Do Hospital Palliative Care Teams Use the WHO Guidelines to Manage Unrelieved Cancer Pain? A 1-Year, Multicenter Audit in Japan.

It has been reported that pain relief for patients with cancer is suboptimal in Japan. This has been mainly attributed to inadequate dissemination of the World Health Organization (WHO) guidelines for cancer pain management. To better understand this problem, we reviewed how 6 hospital palliative care teams (HPCTs) used the WHO guidelines for unrelieved pain in a 1-year audit that included 534 patients. The HPCT interventions were classified according to the contents of the WHO guidelines. In our study, HPCT interventions involved opioid prescriptions in >80% of referred patients, and "For the Individual" and "Attention to Detail" were the 2 most important principles. Our study indicates which parts of the WHO guidelines should be most heavily emphasized, when disseminating them in Japan.

Involvement of a cyclic adenosine monophosphate-dependent signal in the diet-induced canalicular trafficking of adenosine triphosphate-binding cassette transporter g5/g8.

UNLABELLED: The adenosine triphosphate-binding cassette (ABC) half-transporters Abcg5 and Abcg8 promote the secretion of neutral sterol into bile. Studies have demonstrated the diet-induced gene expression of these transporters, but the regulation of their trafficking when the nutritional status changes in the liver remains to be elucidated. Here, we generated a novel in vivo kinetic analysis that can monitor the intracellular trafficking of Abcg5/Abcg8 in living mouse liver by in vivo transfection of the genes of fluorescent protein-tagged transporters and investigated how hypernutrition affects the canalicular trafficking of these transporters. The kinetic analysis showed that lithogenic diet consumption accelerated the translocation of newly synthesized fluorescent-tagged transporters to intracellular pools in an endosomal compartment and enhanced the recruitment of these pooled gene products into the bile canalicular membrane in mouse liver. Because some ABC transporters are reported to be recruited from intracellular pools to the bile canaliculi by cyclic adenosine monophosphate (cAMP) signaling, we next evaluated the involvement of this machinery in a diet-induced event. Administration of a protein kinase A inhibitor, N-(2-{[3-(4-bromophenyl)-2-propenyl]amino}ethyl)-5-isoquinolinesulfonamide, decreased the canalicular expression of native Abcg5/Abcg8 in lithogenic diet-fed mice, and injection of a cAMP analog, dibutyryl cAMP, transiently increased their levels in standard diet-fed mice, indicating the involvement of cAMP signaling. Indeed, canalicular trafficking of the fluorescent-tagged Abcg5/Abcg8 was enhanced by dibutyryl cAMP administration. CONCLUSION: These observations suggest that diet-induced lipid loading into liver accelerates the trafficking of Abcg5/Abcg8 to the bile canalicular membrane through cAMP signaling machinery.

One-year follow-up of an educational intervention for palliative care consultation teams.

OBJECTIVE: This study explored how an educational intervention affects interdisciplinary palliative care consultation teams. METHODS: A pre-post questionnaire survey conducted before the intervention, as well as immediately, 3, 6 and 12 months later. The outcome measurements were behavior (four domains-17 items) and confidence (one domain-6 items). RESULTS: Of the 252 workshop participants (63 teams), 248 submitted a pre-intervention response, 240 responded immediately after, 198 after 3 months, 197 after 6 months and 184 after 12 months. The behavior domain score significantly increased from pre- to 12 months post-intervention, as follows: 'regional partnership and consultation availability from medical personnel in region', from 15.0 to 17.8 (P < 0.001, effect size = 0.59); 'direct practice or care by member', from 12.8 to 13.4 (P < 0.001, effect size = 0.26); 'provision of information to patient and family', from 11.4 to 12.5 (P < 0.001, effect size = 0.42). The confidence score for palliative care consultation teams activities significantly increased from 18.5 pre-intervention to 20.2 at 12 months later (P < 0.001, effect size = 0.37). By the analysis according to the profession of the team member, the score changes for physicians and psychiatrists were larger than that for nurses and pharmacists. CONCLUSIONS: Participant behavior and confidence scores significantly increased after the educational intervention for the interdisciplinary team. In particular, physicians and psychiatrists showed the largest change. Future studies are needed to confirm the findings.

Diet-induced lipid accumulation in liver enhances ATP-binding cassette transporter g5/g8 expression in bile canaliculi.

The ATP-binding cassette half-transporters Abcg5 and Abcg8 promote the secretion of neutral sterols into bile. Studies have demonstrated the diet-induced expression of these transporters in liver, but precisely where this occurs remains to be elucidated. This study investigated the changes in the expression of these transporters in bile canaliculi in cholesterol-loaded livers. Mice were fed either a standard (SD) diet or a high-fat and high-sucrose (HF/HS) diet for 3 weeks. Bile canaliculi proteins and cryosections were prepared from the liver, and the protein levels and distribution of Abcg5/Abcg8 were determined. The high-calorie diet induced a marked accumulation of lipids in mouse liver. Protein levels of Abcg5 and Abcg8 in bile canaliculi were significantly increased by the HF/HS diet compared to the SD diet. No significant differences in Abca1, Abcb4 (Mdr2), Abcb11 (Bsep), or Abcc2 (Mrp2) levels were observed. Immunohistochemical analyses confirmed that these increases occurred in bile canaliculi. These results suggest that diet-induced lipid loading of the liver causes a significant increase in the expression of Abcg5 and Abcg8 in bile canaliculi.

[A phase II clinical study of once-a-day fentanyl citrate patch in patients with cancer pain--switching from once-every-three-days fentanyl patch to once-a-day fentanyl citrate patch].

We examined the efficacy and safety of a new transdermal fentanyl citrate patch (HFT-290), which was applied once daily in patients with cancer pain who were receiving a stable dose of once-every-three-day application transdermal fentanyl patch [TDF (72 hr)]. After TDF (72 hr) was applied for three days at the same dose used before starting the study, treatment was switched to HFT-290 (once daily) for 9 days. The analgesic effect was judged with a 5-point scale based on each patient's assessment of pain on a 100-mm visual analog scale (VAS). Seventy-eight patients were enrolled. The efficacy rate (95% confidence interval) of the analgesic effect at the time of final removal of HFT-290 (the primary efficacy end-point) was high at 83.9% (71.7-92.4%; 47/56 patients). Furthermore, based on the shift of the VAS, good pain control was achieved after switching. All adverse drug reactions were either mild or moderate, and the main reactions were those commonly observed with opioid analgesics. No respiratory depression was observed. HFT-290 demonstrated good tolerability after switching from TDF (72 hr) and provided stable pain control.

[Validity of recommended minimum dose of prior morphine to initiate transdermal fentanyl patch in prescribing information - multicenter survey of on prescriptions by palliative care specialists in Japan].

For initiating the minimum-size (0.25 microg/hour) transdermal fentanyl patch (TDF), 45 mg a day of oral morphine is the recommended minimum dose (RMD) in Japan according to the prescribing information. However, little is known about the validity of the RMD, and we can presume there are many cases where clinicians are inclined to initiate the minimum-size TDF at the early stage contrary to the RMD due to the high morbidity rate of digestive system cancer in Japan. In order to verify the validity of the RMD, we collected 71 retrospective cases where the minimum-size TDF was initiated against the restriction of RMD. The prior morphine (or equivalent doses of other opioids) was prescribed by palliative care specialists at 5 facilities which belong to Symptom Control Research Group (SCORE-G). Then, the side effects and pain control from the 1st to the 4th day were analyzed. The mean age of subjects was 68, and the main reason for initiating TDF therapy was gastrointestinal symptoms (63.4%). The frequency of side effects such as somnolence, nausea, vomiting and constipation did not show a significant correlation with the prior opioid dose.However,severe dyspnea and respiration depression were documented in two patients, and the above rate was three times higher than the nationwide result of the same side effects (0.9 8%). According to the Numeric Rating Scale (from 0: no pain to 10: the worst pain), the pain intensity decreased from 6.6 on the 1st day to 2.8 on the 2nd day, 3.3 on the 3rd day, and 2.9 (p < 0.001) on the 4th day. We conclude that, although introducing the minimum-size TDF against the RMD served to decrease the pain intensity,it raised the side effects on the respiratory system even when prescribed by palliative care specialists. Therefore,the RMD regulation is valid for general practitioners from a medical safety standpoint.

[Palliative care team at general hospital].

Some three hundred thousand patients die from cancer in a year, most of whom end their lives at a general hospital. Considering this situation, the general hospital has to provide palliative care and make up interdisciplinary Palliative Care Team (PCT). Since April 2002, we established a PCT at Akita City Hospital. Our PCT educated doctors and nurses for palliative care medicine and established a system for palliative care. For example, the assessment sheet of cancer pain is useful for treatment of pain and to equally recognize the patient's condition by each team. The PCT provides support for doctors and nurses in the general unit. We general doctors must learn more about how to provide palliative care medicine for at least cancer pain as well as cancer treatment. A team approach is needed for all cancer patients.

Plasma exchange for hypertriglyceridemic acute necrotizing pancreatitis: report of two cases.

We report two cases of hypertriglyceridemic necrotizing pancreatitis treated by plasma exchange (PE). The outcome of each case was quite different according to the timing of PE. A 36 year old man presented with abdominal pain, and a diagnosis of severe acute pancreatitis was made. His serum triglyceride (TG) level was 6,460 mg/dl. He did not undergo PE at first, however, his condition never improved and PE was performed 20 days after the onset of his illness. Finally, he died of multiple organ failure and sepsis. In contrast, a 52 year old man with acute necrotizing pancreatitis was referred to our department. He received PE quickly after hospital admission. His serum TG level, which was 3,540 mg/dl at hospital admission, dramatically returned to normal limits, and he was discharged from the hospital 62 days after admission. The prognosis of severe necrotizing pancreatitis due to hypertriglyceridemia is extremely poor. PE should be applied for the treatment of hypertriglyceridemic necrotizing pancreatitis immediately after its onset.