Acute Pain Management for a Tibial Plateau Fracture Shortly After a Buprenorphine XR Depot Injection: A Case Report.

Acute pain management of patients on buprenorphine for opioid use disorder remains a challenge. The buprenorphine extended-release depot injection which lasts for 1 month and has a higher plasma concentration of buprenorphine compared to the sublingual formulation is increasingly being used in patients. Acute pain management of patients on buprenorphine depot remains a challenge because waiting for the washout of the medication is not feasible and discontinuation is challenging because it requires surgical excision. We describe here the pharmacokinetics of the buprenorphine depot formulation and the clinical implications of its long duration of action. A 39-year-old woman with a history of alcohol and opioid use disorder, on buprenorphine depot, was admitted to the hospital with a left tibial plateau fracture. Acute pain service managed her pain by utilizing a multimodal analgesia plan including femoral and popliteal nerve catheters, intravenous patient-controlled analgesia and oral opioid and nonopioid medications. The patient had a prolonged length of stay of 11 days but was successfully weaned off nerve catheters and intravenous medications and converted to an oral medication regiment such that she could be discharged from the acute care hospital.

Cost-effectiveness Analysis of Preoperative Screening Strategies for Obstructive Sleep Apnea among Patients Undergoing Elective Inpatient Surgery.

BACKGROUND: Obstructive sleep apnea is underdiagnosed in surgical patients. The cost-effectiveness of obstructive sleep apnea screening is unknown. This study's objective was to evaluate the cost-effectiveness of preoperative obstructive sleep apnea screening (1) perioperatively and (2) including patients' remaining lifespans. METHODS: An individual-level Markov model was constructed to simulate the perioperative period and lifespan of patients undergoing inpatient elective surgery. Costs (2016 Canadian dollars) were calculated from the hospital perspective in a single-payer health system. Remaining model parameters were derived from a structured literature search. Candidate strategies included: (1) no screening; (2) STOP-Bang questionnaire alone; (3) STOP-Bang followed by polysomnography (STOP-Bang + polysomnography); and (4) STOP-Bang followed by portable monitor (STOP-Bang + portable monitor). Screen-positive patients (based on STOP-Bang cutoff of at least 3) received postoperative treatment modifications and expedited definitive testing. Effectiveness was expressed as quality-adjusted life month in the perioperative analyses and quality-adjusted life years in the lifetime analyses. The primary outcome was the incremental cost-effectiveness ratio. RESULTS: In perioperative and lifetime analyses, no screening was least costly and least effective. STOP-Bang + polysomnography was the most effective strategy and was more cost-effective than both STOP-Bang + portable monitor and STOP-Bang alone in both analyses. In perioperative analyses, STOP-Bang + polysomnography was not cost-effective compared to no screening at the $4,167/quality-adjusted life month threshold (incremental cost-effectiveness ratio $52,888/quality-adjusted life month). No screening was favored in more than 90% of iterations in probabilistic sensitivity analyses. In contrast, in lifetime analyses, STOP-Bang + polysomnography was favored compared to no screening at the $50,000/quality-adjusted life year threshold (incremental cost-effectiveness ratio $2,044/quality-adjusted life year). STOP-Bang + polysomnography was favored in most iterations at thresholds above $2,000/quality-adjusted life year in probabilistic sensitivity analyses. CONCLUSIONS: The cost-effectiveness of preoperative obstructive sleep apnea screening differs depending on time horizon. Preoperative screening with STOP-Bang followed by immediate confirmatory testing with polysomnography is cost-effective on the lifetime horizon but not the perioperative horizon. The integration of preoperative screening based on STOP-Bang and polysomnography is a cost-effective means of mitigating the long-term disease burden of obstructive sleep apnea.

Mental illness after admission to an intensive care unit.

PURPOSE: Survivors of critical illness may be at higher risk of developing subsequent mental illness. We sought to determine the risk of new mental illness diagnoses across a large population of intensive care unit (ICU) survivors compared with hospitalized patients. METHODS: Population-based study (2005-2015) conducted in adults hospitalized in Ontario, Canada. The primary exposure was ICU admission for ≥ 48 h; secondary exposures were ICU procedures including mechanical ventilation and duration of ICU. The primary outcome was mental illness diagnosed during the year after hospital discharge. To account for case mix differences between ICU and other hospitalized patients, sensitivity analyses were conducted restricting to six pre-specified diagnoses that can lead to hospitalization with or without ICU. RESULTS: 1,847,462 patients survived hospitalization, of whom 121,101 were admitted to ICU for ≥ 48 h. ICU patients had a higher rate of new mental illness diagnoses in the year after discharge compared to hospitalized patients (17 vs. 15%, adjusted hazard ratio (aHR) 1.08, 95% CI 1.07-1.10). In analyses restricted to pre-specified most responsible diagnoses, the increased risk associated with ICU was only significant for patients with pneumonia. Among ICU survivors, exposure to mechanical ventilation (aHR: 1.08; 95% CI 1.05-1.12) or longer ICU stays (aHR: 1.004 per day; 95% CI 1.003-1.005) increased the risk of new mental illness diagnosis. CONCLUSIONS: ICU was associated with a marginally increased risk of mental illness diagnosis after hospitalization that was often no longer apparent when reason for admission was considered. Patients exposed to mechanical ventilation or longer ICU stays may be at higher risk of subsequent mental illnesses.

A systematic literature analysis of correlative studies in low-dose metronomic chemotherapy trials.

Low-dose metronomic (LDM) chemotherapy is a beneficial and very well-tolerated form of chemotherapy utilization characterized by the frequent and uninterrupted administration of low doses of conventional chemotherapeutic agents over prolonged periods of time. While patients resistant to standard maximum tolerated dose (MTD) chemotherapy may still benefit from LDM chemotherapy, there is a lack of predictive markers of response to LDM chemotherapy. We searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for correlative studies conducted as part of LDM chemotherapy trials in order to identify the most promising biomarker candidates. Given the antiangiogenic properties of LDM chemotherapy, angiogenesis-related biomarkers were most commonly studied. However, significant correlations between angiogenesis-related biomarkers and study end points were rare and variable, even so far as biomarkers correlating positively with an end point in some studies and negatively with the same end point in other studies. Pursuing biomarkers outside the angiogenesis field may be more promising.

In vivo passage of human prostate cancer cells in mice results in stable gene expression changes affecting numerous cancer-associated biological processes.

BACKGROUND: While therapeutic resistance is difficult to model in vitro in its entirety, in vivo passage and re-derivation of treatment resistant prostate cancer cell variants is a strategy to study therapeutic resistance more comprehensively. However, the process of in vivo passage itself may result in gene expression changes that could confound the analysis of such resistant cell variants compared to their parental cell lines. METHODS: We compared the expression profiles of parental PC-3 human prostate cancer cells and PC-3 cells re-derived after in vivo passage in athymic nude mice. Whole transcriptome information was obtained using the SOLiD 4 system (Applied Biosystems). Differentially expressed genes were mapped to genes in the Database for Annotation, Visualization and Integrated Discovery for gene enrichment and functional annotation analysis. The expression of a panel of these genes was validated using quantitative RT-PCR. RESULTS: Altogether, 21,032 distinct transcripts were found in PC-3 and/or NS1.1. Of these, 906 were differentially regulated (≥2-fold) in NS1.1 versus PC-3. 337 transcripts were upregulated, and 569 were downregulated, including genes previously associated with various aspects of prostate carcinogenesis such as TLR4 and IGFBP5, respectively. Gene ontology analysis of the differentially expressed transcripts revealed enrichment for biological processes such as cell adhesion, migration, and angiogenesis. CONCLUSIONS: When using in vivo as opposed to in vitro derived prostate cancer cell variants for comparative genetic studies of complex traits such as therapeutic resistance, one may be better served to use similarly in vivo passaged control cell variants instead of parental cell lines.