Wait times and patient throughput after the implementation of a novel model of virtual care in an outpatient neurology clinic: A retrospective analysis.

INTRODUCTION: Neurology wait times - from referral to consultation - continue to grow, leading to various adverse effects on patient outcomes. Key elements of virtual care can be leveraged to improve efficiency. This study examines the implementation of a novel virtual care model - Virtual Rapid Access Clinics - at the Neurology Centre of Toronto. The model employs a patient-centred care workflow, involving multidisciplinary staff and online administrative tools that are synthesized to expedite care and maintain quality. METHODS: Virtual Rapid Access Clinic efficacy was studied by determining average wait times and patient throughput, calculated from anonymous data that was extracted from the clinic patient database (n = 1542). Comparative analysis focused on new patient consultations during the 12-month periods prior to (pre-Virtual Rapid Access Clinic, n = 456) and following (post-Virtual Rapid Access Clinic, n = 1086) Virtual Rapid Access Clinic implementation. RESULTS: After Virtual Rapid Access Clinic implementation, there was a mean 15-day wait time reduction, and a monthly average 52-patient increase in patient throughput. Wait time reductions and increased patient throughput were observed in all three Virtual Rapid Access Clinic sub-clinics - epilepsy, headache and concussion. Respectively, average wait times reduced significantly by 26.4 and 18.9 days and insignificantly by 1.1 days; monthly average patient throughputs increased by 235%, 95% and 161%. DISCUSSION: These findings demonstrated that the Virtual Rapid Access Clinic model of care is effective at reducing patient wait times and increasing patient throughput. While the Virtual Rapid Access Clinic presents a feasible model both during and after pandemic restrictions, further research exploring its scalability in other care contexts, potential changes in care quality and efficiency outside of pandemic restrictions must be performed.

Potential Benefit of Add-on Δ9-Tetrahydrocannabinol in Pediatric Drug-Resistant Epilepsy: A Case Series.

We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other cannabinoids) in the treatment of pediatric DRE. Based on our experiences and reports in the literature, we propose that, in patients who fail management with an initial trial of high-dose CBD-focused therapy, there may be a role for add-on THC-focused formulations.

Evaluation of Patient Reported Safety and Efficacy of Cannabis From a Survey of Medical Cannabis Patients in Canada.

With the medical use of cannabis permitted in Canada since 2001, patients seek to use this botanical drug to treat a range of medical conditions. However, many healthcare practitioners express the need for further scientific evidence around the use of medical cannabis. This real-world evidence study aimed to address the paucity of scientific data by surveying newly registered medical cannabis patients, before beginning medical cannabis treatment, and at one follow up 6 weeks after beginning medical cannabis treatment. The goal was to collect data on efficacy, safety and cannabis product type information to capture the potential impact medical cannabis had on patient-reported quality of life (QOL) and several medical conditions over a 6-week period using validated questionnaires. The 214 participants were mainly male (58%) and 57% of the population was older than 50. The most frequently reported medical conditions were recurrent pain, post-traumatic stress disorder (PTSD), anxiety, sleep disorders [including restless leg syndrome (RLS)], and arthritis and other rheumatic disorders. Here we report that over 60% of our medical cannabis cohort self-reported improvements in their medical conditions. With the use of validated surveys, we found significant improvements in recurrent pain, PTSD, and sleep disorders after 6 weeks of medical cannabis treatment. Our findings from patients who reported arthritis and other rheumatic disorders are complex, showing improvements in pain and global activity sub-scores, but not overall changes in validated survey scores. We also report that patients who stated anxiety as their main medical condition did not experience significant changes in their anxiety after 6 weeks of cannabis treatment, though there were QOL improvements. While these results show that patients find cannabis treatment effective for a broad range of medical conditions, cannabis was not a remedy for all the conditions investigated. Thus, there is a need for future clinical research to support the findings we have reported. Additionally, while real-world evidence has not historically been utilized by regulatory bodies, we suggest changes in public policy surrounding cannabis should occur to reflect patient reported efficacy of cannabis from real-world studies due to the uniqueness of medical cannabis's path to legalization.

Healing of a Chronic Pressure Injury in a Patient Treated With Medical Cannabis for Pain and Sleep Improvement: A Case Report.

BACKGROUND: A small body of evidence suggests medical cannabis may facilitate wound healing, but the exact mechanism of this effect is unclear. PURPOSE: This case report describes a patient with a pressure injury (PI) who received cannabis oil treatment for pain management and sleep improvement. METHODS: A 37-year-old woman with multiminicore disease, scoliosis, short-chain acyl-CoA dehydrogenase deficiency, and epilepsy presented to the Neurology Centre of Toronto with chronic pain and sleep disturbance, including difficulty initiating and maintaining sleep. She also had a 5-year history of a PI between her right iliac crest and right rib cage that had progressively worsened. The patient received a medical cannabis oil protocol that used a combination of cannabidiol and tetrahydrocannabinol. RESULTS: Cannabis oil was effective in treating pain and sleep difficulties. Unexpectedly, during the first 2 weeks of treatment, the PI started to heal and was almost completely closed at the 2-month follow-up. CONCLUSION: Although it is unknown if the observed healing of this refractory PI was indirectly or directly related to the cannabidiol and tetrahydrocannabinol treatment, the potential relationships among pain, sleep disturbance, cannabis treatment, and healing should be explored.

Pain descriptors of taxane acute pain syndrome (TAPS) in breast cancer patients-a prospective clinical study.

BACKGROUND: Taxane acute pain syndrome (TAPS) is a clinically significant side-effect of taxane chemotherapy, often described as arthralgia and myalgia that occurs 2-3 days after infusion. The aim of this study was to assess pain descriptors used by patients during their experience of TAPS. METHODS: A clinical prospective cohort study was conducted on breast cancer patients who had not received prior chemotherapy and were asked to complete diaries on three consecutive docetaxel treatment cycles on days 1-7, 14, and 21 (acute phase). Questionnaires to assess pain severity, descriptors of pain, and the interference in activities due to pain were adapted from the Brief Pain Inventory and the McGill Pain Questionnaire. Telephone questionnaire follow-up was done at 1, 3, 6, 9, and 12 months following docetaxel (delayed phase). RESULTS: The most commonly used descriptor for acute and chronic pain was "aching" (90-96%). However, in the delayed phase of the study, "burning" (32-50%), "radiating" (39-48%), and "sharp" (40-69%) were used more often. In both acute and chronic pain phases, most patients experienced moderate/severe pain regardless of the location. Pain in cycle 1 was predictive of pain in subsequent taxane cycles (p < 0.0001). Pain in cycle 3 was predictive of chronic pain (p < 0.002). CONCLUSIONS: The descriptors used by patients experiencing chemotherapy-induced pain (ChIP) may be reflective of the underlying mechanisms. It is suspected that TAPS initiates as an acute inflammatory pain, which over time develops into neuropathic pain, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the subjective pain experience varies from patient to patient.

Human Pharmacokinetic Parameters of Orally Administered Δ9-Tetrahydrocannabinol Capsules Are Altered by Fed Versus Fasted Conditions and Sex Differences.

Background: There is variability in the reported Δ9-tetrahydrocannabinol (THC) and 11-hydroxy-tetrahydrocannabinol (11-OH-THC) pharmacokinetic (PK) and pharmacodynamic (PD) parameters between studies and there is limited investigation into how the presence of food or sex affect these parameters. In this study, we examined the PK and PD parameters of an encapsulated THC extract and its major active metabolite, 11-OH-THC, under different fed states. Methods: The study was a single-dose, randomized, double-blinded, four-way crossover investigation. THC capsules (1 or 2×5 mg) were administered to 28 healthy adults (13 females: 15 males) under a fasted condition or after a high-fat meal. Blood samples were collected and PK parameters were determined through noncompartmental analysis. Adverse events (AEs), cognitive function (through completion of digit symbol substitution tests), blood pressure, and heart rate were also recorded. Results: The presence of high-fat food significantly enhanced time to peak plasma concentration (T max) and area under the curve (AUC0-24) for both THC and 11-OH-THC and reduced THC's apparent volume of distribution (V z/F) and apparent clearance (Cl/F). Females had a significantly greater peak plasma concentration (C max) compared with males after 5 mg THC in a fasted state. No cardiovascular or cognitive effects and only mild AEs (somnolence, fatigue, and euphoric mood) were reported. Conclusion: These findings may help to inform the guidelines provided by governing health bodies on the effects of cannabis, such as time to onset and duration of action, and aid health care practitioners in their prescribing practices. Furthermore, the doses used in this study are safe to consider for future interventional studies in disease conditions where THC has been shown to have therapeutic efficacy.

Predictive biomarkers of chemotherapy-induced peripheral neuropathy: a review.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxane treatment during chemotherapy. Identifying predictive biomarkers of CIPN would allow physicians to alter treatment given to patients according to a personal risk of developing this condition. The current literature on CIPN biomarkers is reviewed, identifying biomarkers which have been found to be significantly related to CIPN. Three genetic biomarkers are identified (ARHGEF10 rs9657362, CYP2C8 rs11572080/rs10509681 and FGD4 rs10771973) which have been found to act as predictive CIPN biomarkers in multiple studies. Possible mechanisms underlying the relationship between these single nucleotide polymorphisms and CIPN development are explored. The biomarkers identified in this study should be investigated further to generate predictive biomarkers that may be used in a clinical setting.

Symptom clusters using the EORTC QLQ-C15-PAL in palliative radiotherapy.

BACKGROUND: Patients with advanced cancer often experience a multitude of symptoms. Due to the potential interrelation of symptoms, symptom clusters of 2 or more concurrent symptoms have been advocated for use in the palliative setting to provide better management of symptoms. METHODS: The principal component analysis (PCA), exploratory factor analysis (EFA) and hierarchal cluster analysis (HCA) were conducted on responses to items 1-14 in the European Organisation for Research and Treatment of Cancer Quality of Life-C15-Palliative (EORTC QLQ-C15-PAL) at baseline and days 5 and 10 following RT. RESULTS: There was complete data for 109, 90 and 87 patients at baseline, day 5 and day 10 respectively. The average age was 72 years. The most common site of primary was the prostate (36.7%), and almost all patients presented with bone metastases (95.4%). Analyses identified 2-4 clusters at each interval. From baseline to day 10 follow-up, across all analyses, items associated with physical functioning clustered consistently with shortness of breath. Pain and pain interference clustered with nausea at baseline; and with sleep at both follow-up intervals. Cronbach's alpha values for the clusters ranged from 0.53 to 0.90. CONCLUSIONS: Fluctuation of symptom clusters was observed in a short time frame following palliative RT. Although clusters were dynamic, several items tended to cluster together. Further research is required to validate these clusters.

Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies.

Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon. Five recent pre-clinical studies identified from Medline published between 2013 and 2016 were selected for review. All studies evaluated the effect of small-molecule agonists or antagonists on components of the endocannabinoid system in rats or mice, using cisplatin or paclitax-el-induced allodynia as a model of chemotherapy-induced neuropathic pain. Activation of the cannabinoid receptor-2 (CB-2) receptor by AM1710 blocked paclitaxel-induced mechanical and cold allodynia in one study. Four studies investigating the activation of both cannabinoid receptor-1 (CB-1) and CB-2 receptors by dual-agonists (WIN55,21 and CP55,940), or by the introduction of inhibitors of endocannabinoid metabolisers (URB597, URB937, JZL184, and SA-57) showed reduction of chemotherapy-induced al-lodynia. In addition, their results suggest that anti-allodynic effects may also be mediated by additional receptors, including TRPV1 and 5-hydroxytryptamine (5-HT1A). Pre-clinical studies demon-strate that the activation of endocannabinoid CB-1 or CB-2 receptors produces physiological effects in animal models, namely the reduction of chemotherapy-induced allodynia. These studies also provide in-sight into the biological mechanism behind the therapeutic utility of cannabis compounds in managing chemotherapy-induced neuropathic pain, and provide a basis for the conduct of future clinical studies in patients of this population.

Symptomatic palliation with radiotherapy in extensive heterotopic ossifications.

Heterotopic ossification (HTO) is the dystrophic formation of mature lamellar bone outside the confines of normal osseous tissues. It is frequently a complication which occurs following traumatic insult, both iatrogenic and non-iatrogenic, and neurological compromise. While mild degree of disease is often asymptomatic, significant pain and mobility limitations may result in reduced quality of life in advanced cases. Currently, the commonly accepted management for patients experiencing significant symptomatic HTOs is a combination therapy of surgical excision with prophylactic radiotherapy in the immediate perioperative period. In this article, we present a patient who achieved satisfactory pain relief and improvements in overall quality of life with the sole use of external beam radiation to illustrate the possibility of using radiotherapy alone for symptomatic management of HTO.

A selective review of medical cannabis in cancer pain management.

Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.

The role of ants, birds and bats for ecosystem functions and yield in oil palm plantations.

One of the world's most important and rapidly expanding crops, oil palm, is associated with low levels of biodiversity. Changes in predator communities might alter ecosystem services and subsequently sustainable management but these links have received little attention to date. Here, for the first time, we manipulated ant and flying vertebrate (birds and bats) access to oil palms in six smallholder plantations in Sumatra (Indonesia) and measured effects on arthropod communities, related ecosystem functions (herbivory, predation, decomposition and pollination) and crop yield. Arthropod predators increased in response to reductions in ant and bird access, but the overall effect of experimental manipulations on ecosystem functions was minimal. Similarly, effects on yield were not significant. We conclude that ecosystem functions and productivity in oil palm are, under current levels of low pest pressure and large pollinator populations, robust to large reductions of major predators.

Epigenetic control of meiotic recombination in plants.

Meiotic recombination is a deeply conserved process within eukaryotes that has a profound effect on patterns of natural genetic variation. During meiosis homologous chromosomes pair and undergo DNA double strand breaks generated by the Spo11 endonuclease. These breaks can be repaired as crossovers that result in reciprocal exchange between chromosomes. The frequency of recombination along chromosomes is highly variable, for example, crossovers are rarely observed in heterochromatin and the centromeric regions. Recent work in plants has shown that crossover hotspots occur in gene promoters and are associated with specific chromatin modifications, including H2A.Z. Meiotic chromosomes are also organized in loop-base arrays connected to an underlying chromosome axis, which likely interacts with chromatin to organize patterns of recombination. Therefore, epigenetic information exerts a major influence on patterns of meiotic recombination along chromosomes, genetic variation within populations and evolution of plant genomes.

Delayed fluorescence as a universal tool for the measurement of circadian rhythms in higher plants.

The plant circadian clock plays an important role in enhancing performance and increasing vegetative yield. Much of our current understanding of the mechanism and function of the plant clock has come from the development of Arabidopsis thaliana as a model circadian organism. Key to this rapid progress has been the development of robust circadian markers, specifically circadian-regulated luciferase reporter genes. Studies of the clock in crop species and non-model organisms are currently hindered by the absence of a simple high-throughput universal assay for clock function, accuracy and robustness. Delayed fluorescence (DF) is a fundamental process occurring in all photosynthetic organisms. It is luminescence-produced post-illumination due to charge recombination in photosystem II (PSII) leading to excitation of P680 and the subsequent emission of a photon. Here we report that the amount of DF oscillates with an approximately 24-h period and is under the control of the circadian clock in a diverse selection of plants. Thus, DF provides a simple clock output that may allow the clock to be assayed in vivo in any photosynthetic organism. Furthermore, our data provide direct evidence that the nucleus-encoded, three-loop circadian oscillator underlies rhythms of PSII activity in the chloroplast. This simple, high-throughput and non-transgenic assay could be integrated into crop breeding programmes, the assay allows the selection of plants that have robust and accurate clocks, and possibly enhanced performance and vegetative yield. This assay could also be used to characterize rapidly the role and function of any novel Arabidopsis circadian mutant.

Demand outstrips supply of US pediatric dermatologists: results from a national survey.

BACKGROUND: The US pediatric dermatology workforce was last examined in 1986 when limited employment opportunity was found. OBJECTIVE: We sought to re-examine pediatric dermatology workforce issues. METHODS: US dermatology chairpersons and residency program directors were surveyed for: (1) agreement with pediatric dermatology workforce statements; and (2) pediatric dermatology faculty and fellow numbers. RESULTS: Respondents agreed that having a pediatric dermatologist or dermatologists on faculty is important, and that a shortage of pediatric dermatologists exists, but did not agree that increasing pediatric dermatology training requirements will increase this shortage. Almost half of the programs (45/94) employed a full-time pediatric dermatologist, and 24 programs had currently been recruiting a pediatric dermatologist for more than 1 year. Only 6 pediatric dermatology fellows were in training. CONCLUSION: Given that open pediatric dermatology faculty positions greatly exceed the number of fellows in training and that formal training requirements will be increasing, the shortage of pediatric dermatologists will likely continue.