Opioid-induced respiratory depression suspected of drug interaction in a prostate cancer patient: a case report.

BACKGROUND: Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant. CASE DESCRIPTION: The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems. CONCLUSIONS: The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.

Venue of catheter insertion does not significantly impact the event of central line-associated bloodstream infection in patients with haematological diseases.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is a serious complication of central venous catheter (CVC) placement in patients with haematological diseases associated with neutropenia and immunosuppression. However, whether the venues where CVC are inserted influence CLABSI development remains unclear. METHODS: We investigated whether CVC insertion at venues with different standards of cleanliness altered the occurrence of CLABSI. We evaluated data from 279 patients (545 CVC insertions) with haematological diseases including age, sex, underlying disease, reason for insertion, insertion site, number of lumens, venue, dates of insertion and removal, complete blood counts, percentage of neutrophils and serum albumin concentrations at the time of CVC insertion. FINDINGS: Overall, 55 CLABSI events occurred during a period of 23,434 catheter days (2.35 per 1,000 catheter days). In total, 153 and 190 patients underwent 226 and 305 CVC insertions, respectively in a ward and in an operating room, respectively. Univariate analysis identified the operating room (P = 0.017), allogeneic haematopoietic stem cell transplantation (P < 0.001), triple lumen catheter (P = 0.002), haemoglobin (P = 0.019), white blood cell count (P = 0.012) and percentage of neutrophils (P = 0.012) as significant factors for the development of CLABSI. However, multivariate analysis adjusted for age, reason for insertion, insertion site, number of lumens, haemoglobin, percentage of neutrophils and platelet counts found no significant differences between the venue where CVC were inserted and CLABSI development (P = 0.158). CONCLUSION: The venue of CVC insertion is unlikely to influence CLABSI development in patients with haematological diseases.

[Quantitative Bayesian diagnosis developed for lower respiratory tract infections due to methicillin-resistant Staphylococcus aureus].

Using quantitative Bayesian analysis as a clinical epidemiological approach, we developed a diagnosis for lower respiratory tract infection (LRTI) due to Methicillin-resistant Staphylococcus aureus (MRSA). We retrospectively reviewed the charts of 181 subjects--a derivation cohort-with MRSA retrieved from lower respiratory specimens June 2006 to March 2008. Dividing them into infection or colonization (no infection) groups, we compared them for the presence or absence of clinical parameters, including fever > 38 degrees C, MRSA >106 CFU (colony-forming units)/mL, phagocytosis on Gram staining, serum albumin < 3.0 g/dL, and peripheral WBC count > 15,000/mL. We them determined positive and negative likelihood ratios (LR +, LR -) for these parameters to quantify MRSA-LRTI diagnostic probability based on combined likelihood ratios (Bayesian analysis). We then determined Bayesian MRSA-LRTI diagnostic probabilities (BDPs) in 40 subjects with respiratory MRSA--a validation cohort-from May 2008 to October 2008 clinically judged with either infection (n = 14) or colonization (n = 26) by infection control personnel (ICP) blinded to the test (parameter LR+ and LR -). BDPs (mean +/- SD) quantified by combining the four parameters-fever, MRSA CFU, phagocytosis, and serum albumin-were 62.3 +/- 25.4% for 14 judged with infection, and 40.2% +/- 20.4% for 26 patients judged with colonization (p = 0.005). Using a diagnostic probability of 51% as the cut off, we compared positive and negative predictive Bayesian diagnoses ICP judgment, i.c., 77% vs. 85%. The Bayesian approach proved useful in quantitatively diagnosing infectious disease such as MRSA-LRTI that lack established diagnostic, and may aid physicians in deciding the need for specific antimicrobial therapy.

A new route to diverse 1-azasugars from N-Boc-5-hydroxy-3-piperidene as a common building block.

A new general method for the synthesis of a variety of 1-azasugars with a nitrogen atom at the anomeric position is described. The readily available chiral N-Boc-5-hydroxy-3-piperidene 3 is transformed to isofagomine (2), homoisofagomine (13), and 5'-deoxyisofagomine (14) via stereoselective epoxidation and regioselective ring-cleavage in a highly stereocontrolled manner. In addition, the synthesis of all four stereoisomers of 3,4,5-trihydroxypiperidines (18-21) classified as 1-azasugar-type glycosidase inhibitors was stereoselectively achieved from the (chiral) piperidene 3.