Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper

Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into question after reports of a disproportionate increase in opioid-induced deaths in recent years. The American Pain Society, College on Problems of Drug Dependence, and the Heart Rhythm Society collaborated to issue guidelines on best practices to maximize methadone safety and efficacy, but guidelines for the end-of-life scenario have not yet been developed. A panel of 15 interprofessional hospice and palliative care experts from the U.S. and Canada convened in February 2015 to evaluate the American Pain Society methadone recommendations for applicability in the hospice and palliative care setting. The goal was to develop guidelines for safe and effective management of methadone therapy in hospice and palliative care. This article represents the consensus opinion of the hospice and palliative care experts for methadone use at end of life, including guidance on appropriate candidates for methadone, detail in dosing, titration, and monitoring of patients' response to methadone therapy.     

In vitro antimicrobial activity of various medication preparations on E. faecalis in root canal dentin

The purpose of this study was to evaluate the antimicrobial activity of several medication preparations in root canal dentin infected with Enterococcus faecalis. Roots of extracted bovine incisors were prepared to standardized cylindrical test specimens, 5 mm in height. The smear layer was removed and the samples were autoclaved and then incubated at 37 degrees C/5% CO2 for 24 h in brain-heart infusion (BHI) broth containing 7.0 x 10(4) colony forming units per ml of E. faecalis. The samples were washed in phosphate buffered saline and mounted to individual culture wells with sticky wax. Test medications were applied to fill the canal lumina; medication groups were: (a) sterile H2O (positive control); (b) a 10% mixture of 1.0 g Ca(OH)2 USP in 10 ml sterile H2O; (c) 10% Ca(OH)2 in 0.12% chlorhexidine gluconate (Peridex); (d) Peridex; and (e) uninoculated BHI (negative control). The samples were incubated at 37 degrees C/5% CO2 for 24 h. Dentin samples for quantitative microbiology were then obtained with consecutive sterile burs (ISO 029, 035, 042). All three experimental groups demonstrated significantly greater antimicrobial activity than the positive control (p < 0.001). Group 2 demonstrated significantly greater antimicrobial activity than Group 3 or Group 4 at all dentin depths (p < 0.05). These results suggest that 10% Ca(OH)2 may be more effective than Peridex or 10% Ca(OH)2 in Peridex for the elimination of E. faecalis from dentin tubules.     

Evaluation of pluronic polyols as carriers for grafting materials: study in rat calvaria defects

BACKGROUND: Pluronic polyols are a family of non-ionic surfactants currently used as drug carriers for antibiotic, anti-inflammatory, and anti-neoplastic agents. Therapeutic administration of non-ionic surface-active agents is known to facilitate early collagen synthesis and microcirculation, thus promoting wound healing. The purpose of this study was to determine the in vivo effects of pluronic polyols combined with either an allograft or an alloplast on the healing of critical-sized calvarial defects. METHODS: One hundred fifty (150) adult (95 to 105 days old) male Sprague-Dawley rats weighing between 375 and 425 g were randomly and evenly assigned to each of 15 separate treatment groups and anesthetized, and 8 mm calvarial critical-sized defects were created. Pluronic F-68 (F-68) or pluronic F-127 (F-127) was administered either topically or systemically and in conjuction with demineralized bone powder (DBP), tricalcium phosphate (TCP), or non-grafted controls. Pluronic polyols are easily mixed with either DBP or TCP to improve handling ease. Calvaria were harvested at 12 weeks postsurgery and evaluated histomorphometrically, by contact radiography with subsequent densitometric analysis, through energy spectrometry utilizing a scanning electron microscope, and by fluorescent microscopy. RESULTS: There was a significant difference in the percentage of bone fill among the control, TCP, and DBP only groups, P <0.05. The only significant difference within any of these groups was between the TCP control and TCP plus systemic F-127, P<0.05. CONCLUSIONS: Although there were isolated differences, the overall trend was that the pluronic polyol and the mode of administration did not result in a significant change in bone wound healing as measured by the percentage of bone fill. Pluronic polyols may be considered as carriers for osseous graft materials.     

Effects of nicotine on the strength of attachment of gingival fibroblasts to glass and non-diseased human root surfaces

BACKGROUND: The aim of this study was to evaluate the effect of nicotine on the strength of attachment of human gingival fibroblast cells to glass and non-diseased human root surfaces. METHODS: Human gingival fibroblast cells (HGF) were trypsinized, suspended in RPMI 1640 medium, and incubated with autoclaved human root and glass sections and nicotine (NIC) concentrations of 0 (control), 25, 50, and 100 ng/ml for 1 week. HGF attached and grew on glass and root surfaces for 4 weeks at all NIC concentrations. HGF cultures were subjected to a rotary shaker machine for 30 minutes to test the strength of attachment of these cells at 100, 150, and 200 rpm. The root and glass sections were examined at 48 hours by light microscopy. RESULTS: Control groups exhibited a monolayer of long, spindle-shaped fibroblasts with a parallel alignment and minimal overlapping. With a concentration of NIC of 50 or 100 ng/ml as well as with increasing "speeds," the number of cells attached to these surfaces decreased dramatically. When 200 rpm was used for both groups at all NIC concentrations, very few HGF remained attached to these surfaces. CONCLUSIONS: This study showed that the nature of cell attachment to either glass or root surfaces is altered by nicotine, and marked detachment was noted when nicotine exposure was coupled with vigorous agitation at different rpm. Marked detachment noted in all specimens at 200 rpm indicates that this speed is excessive for use in subsequent experimentation.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

The Effect of Human-Immunodeficiency Virus Status on Outcomes in Penetrating Abdominal Trauma: An Interim Analysis

Background

The purpose of this study was to determine whether the outcomes of hemodynamically stable patients undergoing exploratory laparotomy for penetrating abdominal trauma differed as a result of their HIV status.

Methods

This was an observational, prospective study from February 2016 to May 2017. All hemodynamically stable patients with penetrating abdominal trauma requiring a laparotomy were included. The mechanism of injury, the HIV status, age, the penetrating abdominal trauma index (PATI), and the revised trauma score (RTS) were entered into a binary logistic regression model. Outcome parameters were in-hospital death, morbidity, admission to intensive care unit (ICU), relaparotomy within 30 days, and length of stay longer than 30 days.

Results

A total of 209 patients, 94% male, with a mean age of 29 ± 10 years were analysed. Twenty-eight patients (13%) were HIV positive. The two groups were comparable. Ten (4.8%) laparotomies were negative. There were two (0.96%) deaths, both in the HIV negative group. The complication rate was 34% (n = 72). Twenty-nine patients (14%) were admitted to the ICU. A higher PATI, older age, and a lower RTS were significant risk factors for ICU admission. After 30 days, 12 patients (5.7%) were still in hospital. Twenty-four patients (11%) underwent a second laparotomy. The PATI score was the single independent predictor for complications, relaparotomy, and hospital stay longer than 30 days.

Conclusions

Preliminary results reveal that HIV status does not influence outcomes in patients with penetrating abdominal trauma.

     

Non‐invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological‐pathological correlation analysis

Objectives

To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis.

Methods

Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification.

Results

A total of 40 elastography scans were carried out (median creatinine 172.5 μmol/L [interquartile range 133.8–281.8 μmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8–25.7 kPa] vs 22.3 kPa [interquartile range 19.0–26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7–18.0 kPa] vs 15.6 kPa [interquartile range 14.4–18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70–0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78–0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61–0.89), 0.85 (95% CI 0.75–0.95) and 0.65 (95% CI 0.53–0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively.

Conclusions

Shear wave elastography can be used as a non‐invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.