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.     

Current Understanding in Pathogenesis of Atopic Dermatitis

There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process.     

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.     

Association of sociocultural factors with initiation of the kidney transplant evaluation process

Although research shows that minorities exhibit higher levels of medical mistrust, perceived racism, and discrimination in healthcare settings, the degree to which these underlying sociocultural factors preclude end‐stage renal disease (ESRD) patients from initiating kidney transplant evaluation is unknown. We telephone surveyed 528 adult ESRD patients of black or white race referred for evaluation to a Georgia transplant center (N = 3) in 2014‐2016. We used multivariable logistic regression to examine associations between sociocultural factors and evaluation initiation, adjusting for demographic, clinical, and socioeconomic characteristics. Despite blacks (n = 407) reporting higher levels of medical mistrust (40.0% vs 26.4%, P < .01), perceived racism (55.5% vs 18.2%, P < .01), and experienced discrimination (29.0% vs 15.7%, P < .01) than whites (n = 121), blacks were only slightly less likely than whites to initiate evaluation (49.6% vs 57.9%, P = .11). However, after adjustment, medical mistrust (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.39, 0.91), experienced discrimination (OR: 0.62, 95% CI: 0.41, 0.95), and perceived racism (OR: 0.61; 95% CI: 0.40, 0.92) were associated with lower evaluation initiation. Results suggest that sociocultural disparities exist in early kidney transplant access and occur despite the absence of a significant racial disparity in evaluation initiation. Interventions to reduce disparities in transplantation access should target underlying sociocultural factors, not just race.     

Community-acquired pneumonia in the emergency department: a practical approach to diagnosis and management

Pneumonia is one of the most common conditions for which patients seek emergency care. It is a challenging infection in that the spectrum of illness ranges from the nontoxic patient appropriate for outpatient antibiotics to the critically ill patient requiring intensive care hospitalization. Current data and diagnostic technology provide the emergency physician with the tools for an appropriately rapid evaluation and consideration of the differential diagnosis. Key critical thinking and application of published findings allow for intelligent empirical antibiotic treatment and risk stratification for the best disposition. Although antibiotic-resistant organisms increasingly are being identified, patients continue to benefit from early institution of standard ED treatment. Coverage for atypical organisms improves patient response and outcome. Finally, identification and treatment of the complications of pneumonia and accompanying sepsis must be considered by the ED physician when evaluating critically ill patients.     

Extended phase I study of human beta-interferon in human cancer

Ten patients with advanced cancer were treated with weekly intravenous escalating doses of human beta-interferon (HuIFN beta) 4 days each week. The starting dose of HuIFN beta was 3.0 X 10(6) units/m2 and the dose was doubled each week until dose-limiting toxicity was observed. Subjective toxicity included mild fevers and chills, malaise and flu-like symptoms. The lowest dose which caused suppression of the platelet and/or white cell count was 64 X 10(6) units daily, and the maximum dose given was 320 X 10(6) units daily. Both subjective and objective toxicity were not dose-related, easily managed and reversible. Serum interferon levels and the duration of measurable interferon activity on natural killer cells was in general dose-dependent. Two patients had an objective partial response, and two others showed stable disease while receiving HuIFN beta.