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.     

Functionally navigated transcranial magnetic stimulation to evoke lingual pressure in stroke survivors with dysphagia and healthy adults: a proof of concept trial

ABSTRACT

Background

Post-stroke dysphagia is characterized by reduced corticolingual excitability and lingual pressure; however, it remains unknown if transcranial magnetic stimulation (TMS) directly facilitates lingual pressure generation.     

Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

Deciphering the role of Rhodnius prolixus CYP4G genes in straight and methyl‐branched hydrocarbon formation and in desiccation tolerance

Insect cuticle hydrocarbons are involved primarily in waterproofing the cuticle, but also participate in chemical communication and regulate the penetration of insecticides and microorganisms. The last step in insect hydrocarbon biosynthesis is carried out by an insect‐specific cytochrome P450 of the 4G subfamily (CYP4G). Two genes (CYP4G106 and CYP4G107) have been reported in the triatomines Rhodnius prolixus and Triatoma infestans. In this work, their molecular and functional characterization is carried out in R. prolixus, and their relevance to insect survival is assessed. Both genes are expressed almost exclusively in the integument and have an expression pattern dependent on the developmental stage and feeding status. CYP4G106 silencing diminished significantly the straight‐chain hydrocarbon production while a significant reduction – mostly of methyl‐branched chain hydrocarbons – was observed after CYP4G107 silencing. Molecular docking analyses using different aldehydes as hydrocarbon precursors predicted a better fit of straight‐chain aldehydes with CYP4G106 and methyl‐branched aldehydes with CYP4G107. Survival bioassays exposing the silenced insects to desiccation stress showed that CYP4G107 is determinant for the waterproofing properties of the R. prolixus cuticle. This is the first report on the in vivo specificity of two CYP4Gs to make mostly straight or methyl‐branched hydrocarbons, and also on their differential contribution to insect desiccation.     

Start-up propulsion biomechanics changes with fatiguing activity in persons with spinal cord injury

Objective: Shoulder pathology is a common condition in wheelchair users that can considerably impact quality of life. Shoulder muscles are prone to fatigue, but it is unclear how fatigue affects start-up propulsion biomechanics. This study determines acute changes in start-up wheelchair propulsion biomechanics at the end of a fatiguing propulsion protocol.

Design: Quasi-experimental one-group pretest-postest design.

Setting: Biomechanics laboratory. Participants: Twenty-six wheelchair users with spinal cord injury (age: 35.5?±?9.8 years, sex: 73% males and 73% with a paraplegia).

Interventions: Protocol of 15 min including maximum voluntary propulsion, right- and left turns, full stops, start-up propulsion, and rests.

Outcome measures: Maximum resultant force, maximum rate of rise of applied force, mean velocity, mean fraction of effective force, and mean contact time at the beginning and end of the protocol during start-up propulsion.

Results: There was a significant reduction in maximum resultant force (P?<?0.001) and mean velocity (P?<?0.001) at the end of the protocol. Also, contact time was reduced in the first stroke of start-up propulsion (P?<?0.001). Finally, propelling with a shorter contact time was associated with a greater reduction in performance (maximum velocity) at the end of the protocol.

Conclusion: There are clear changes in overground propulsion biomechanics at the end of a fatiguing propulsion protocol. While reduced forces could protect the shoulder, these reduced forces come with shorter contact times and lower velocity. Investigating changes in start-up propulsion biomechanics with fatigue could provide insight into injury risk.