Telemedicine visits requiring follow-up in-person visits at an urban academic family medicine centre.

BACKGROUND: With the onset of the COVID-19 pandemic, telemedicine was rapidly implemented in care settings globally. To understand what factors affect the successful completion of telemedicine visits in our urban, academic family medicine clinic setting, we analysed telemedicine visits carried out during the pandemic. METHODS: We conducted a retrospective chart review of telemedicine visits from 2 clinical units within a family medicine centre. To investigate the association between incomplete visits and various factors (age, gender, presenting complaints, physician level of training [resident or staff] and patient-physician relational continuity), we performed a multivariable logistic regression on data from August 2020, February 2021, and May 2021. An incomplete visit is one that requires a follow-up in-person visit with a physician within 3 days. RESULTS: Of the 2,138 telemedicine patient visits we investigated, 9.6% were incomplete. Patients presenting with lumps and bumps (OR: 3.84, 95% CI: 1.44, 10.5), as well as those seen by resident physicians (OR: 1.77, 95% CI: 1.22, 2.56) had increased odds of incomplete visits. Telemedicine visits at the family medicine clinic (Site A) with registered patients had lower odds of incomplete visits (OR: 0.24, 95% CI: 0.15, 0.39) than those at the community clinic (Site B), which provides urgent/episodic care with no associated relational continuity between patients and physicians. CONCLUSION: In our urban clinical setting, only a small minority of telemedicine visits required an in-person follow-up visit. This information may be useful in guiding approaches to triaging patients to telemedicine or standard in-person care.

With the onset of the COVID-19 pandemic, telemedicine was rapidly implemented in care settings globally. To understand what factors affect the successful completion of telemedicine visits in our urban, academic family medicine clinic, we analysed telemedicine visits carried out during the pandemic. On the basis of patient charts, we investigated the association between incomplete visits (telemedicine visits requiring in-person follow-up within 3 days) and various factors (age, gender, presenting complaints, whether the treating physician was a resident or staff doctor, and whether the patient and physician had a prior clinical relationship). Patients presenting with lumps and bumps and those seen by resident physicians had higher odds of being asked to come in-person for further evaluation. Overall, though, these required in-person follow-ups were uncommon: less than 10% of telemedicine visits resulted in the patient physically coming to the clinic within 3 days. The findings of our study could help guide patients to appropriate care services.

Screening for prostate cancer: protocol for updating multiple systematic reviews to inform a Canadian Task Force on Preventive Health Care guideline update.

PURPOSE: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews. METHODS: Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome. DISCUSSION: The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k).

Treatment of complex regional pain syndrome: an updated systematic review and narrative synthesis.

PURPOSE: Although multiple treatments have been advocated for complex regional pain syndrome (CRPS), the levels of supportive evidence are variable and sometimes limited. The purpose of this updated review is to provide a critical analysis of the evidence pertaining to the treatment of CRPS derived from recent randomized-controlled trials (RCTs). SOURCE: The MEDLINE, EMBASE, Psychinfo, and CINAHL databases were searched to identify relevant RCTs conducted on human subjects and published in English between 1 May 2009 and 24 August 2017. PRINCIPAL FINDINGS: The search yielded 35 RCTs of variable quality pertaining to the treatment of CRPS. Published trials continue to support the use of bisphosphonates and short courses of oral steroids in the setting of CRPS. Although emerging evidence suggests a therapeutic role for ketamine, memantine, intravenous immunoglobulin, epidural clonidine, intrathecal clonidine/baclofen/adenosine, aerobic exercise, mirror therapy, virtual body swapping, and dorsal root ganglion stimulation, further confirmatory RCTs are warranted. Similarly, trials also suggest an expanding role for peripheral sympathetic blockade (i.e., lumbar/thoracic sympathetic, stellate ganglion, and brachial plexus blocks). CONCLUSIONS: Since our prior systematic review article (published in 2010), 35 RCTs related to CRPS have been reported. Nevertheless, the quality of trials remains variable. Therefore, further research is required to continue investigating possible treatments for CRPS.

Establishment of motor neuron-V3 interneuron progenitor domain boundary in ventral spinal cord requires Groucho-mediated transcriptional corepression.

BACKGROUND: Dorsoventral patterning of the developing spinal cord is important for the correct generation of spinal neuronal types. This process relies in part on cross-repressive interactions between specific transcription factors whose expression is regulated by Sonic hedgehog. Groucho/transducin-like Enhancer of split (TLE) proteins are transcriptional corepressors suggested to be recruited by at least certain Sonic hedgehog-controlled transcription factors to mediate the formation of spatially distinct progenitor domains within the ventral spinal cord. The aim of this study was to characterize the involvement of TLE in mechanisms regulating the establishment of the boundary between the most ventral spinal cord progenitor domains, termed pMN and p3. Because the pMN domain gives rise to somatic motor neurons while the p3 domain generates V3 interneurons, we also examined the involvement of TLE in the acquisition of these neuronal fates. METHODOLOGY AND PRINCIPAL FINDINGS: A combination of in vivo loss- and gain-of-function studies in the developing chick spinal cord was performed to characterize the role of TLE in ventral progenitor domain formation. It is shown here that TLE overexpression causes increased numbers of p3 progenitors and promotes the V3 interneuron fate while suppressing the motor neuron fate. Conversely, dominant-inhibition of TLE increases the numbers of pMN progenitors and postmitotic motor neurons. CONCLUSION: Based on these results, we propose that TLE is important to promote the formation of the p3 domain and subsequent generation of V3 interneurons.

Perisynaptic glia discriminate patterns of motor nerve activity and influence plasticity at the neuromuscular junction.

In the nervous system, the induction of plasticity is coded by patterns of synaptic activity. Glial cells are now recognized as dynamic partners in a wide variety of brain functions, including the induction and modulation of various forms of synaptic plasticity. However, it appears that glial cells are usually activated by stereotyped, sustained neuronal activity, and little attention has been given to more subtle changes in the patterns of synaptic activation. To this end, we used the mouse neuromuscular junction as a simple and useful model to study glial modulation of synaptic plasticity. We used two patterns of motor nerve stimulation that mimic endogenous motor-neuronal activity. A continuous stimulation induced a post-tetanic potentiation and a phasic Ca(2+) response in perisynaptic Schwann cells (PSCs), glial cells at this synapse. A bursting pattern of activity induced a post-tetanic depression and oscillatory Ca(2+) responses in PSCs. The different Ca(2+) responses in PSCs indicate that they decode the pattern of synaptic activity. Furthermore, the chelation of glial Ca(2+) impaired the production of the sustained plasticity events indicating that PSCs govern the outcome of synaptic plasticity. The mechanisms involved were studied using direct photo-activation of PSCs with caged Ca(2+) that mimicked endogenous plasticity. Using specific pharmacology and transgenic knock-out animals for adenosine receptors, we showed that the sustained depression was mediated by A1 receptors while the sustained potentiation is mediated by A(2A) receptors. These results demonstrate that glial cells decode the pattern of synaptic activity and subsequently provide bidirectional feedback to synapses.

Neurotrophins modulate neuron-glia interactions at a vertebrate synapse.

Neurotrophins are important modulators of synaptic function at both developing and mature synapses in the CNS and PNS. At the neuromuscular junction (NMJ), neurotrophins, as well as perisynaptic Schwann cells (PSCs) are critical for the long-term maintenance and stability of the synapse. Considering this correlation and the acute interactions that occur at the synapse between PSCs and the nerve terminal, we wondered if neurotrophins could also be involved in neuron-glia signalling. To test if neurotrophins were able to signal to PSCs we used brief applications of neurotrophin-3 (NT-3), brain-derived neurotophic factor (BDNF) or nerve growth factor (NGF; 100 ng/mL). Soleus muscles of mice were incubated with the Ca(2+) indicator Fluo-4AM and Ca(2+) responses in PSCs were elicited through nerve stimulation (50 Hz, 30 s). Our results indicate that acute application of both NT-3 and BDNF, but not NGF, increased PSC Ca(2+) responses. Investigation of the mechanisms involved in these increases revealed distinct pathways for BDNF and NT-3. BDNF increased PSC responsiveness through potentiation of ATP responses while NT-3 modulated muscarinic acetylcholine receptor signalling. Using local applications of the neurotrophins, we found that both neurotrophins were able to elicit Ca(2+) responses in PSCs where BDNF used a phospholipase C-inositol 1,4,5-triphosphate (PLC-IP(3)) mechanism, while NT-3 required extracellular Ca(2+). Our results demonstrate a neurotrophin-dependent modulation of neuron-glia signalling through differential mechanisms employed by NT-3 and BDNF. Hence, neurotrophins precisely and differentially regulate PSC functions through modulation of either purinergic or cholinergic signalling pathways.

Neuron-glia interactions at the neuromuscular synapse.

The contribution of glial cells in the regulation of the transfer of information in CNS and PNS is now increasingly recognized. Perisynaptic Schwann cells (PSCs), glial cells at the neuromuscular junction (NMJ), have proven to be an exceptionally important model for studying these roles. PSCs surround nerve terminals at the NMJ and are activated by transmitter release in a frequency-dependent manner. All of these receptors, except one type, are coupled to G proteins and can be regrouped into two categories: activators and modulators of PSCs. In the former category are muscarinic (unknown subtype) and purinergic receptors (P2X and P2Y). In the latter category are adenosine (A1), Substance P (NK-1) and CGRP receptors. All receptors coupled to G proteins induce the release of Ca2+ from internal stores. In return for this activation, PSCs modulate synaptic activity and short-term plasticity. In this review, we will focus on the role of purines in the induction of glial cell activity and their possible involvement in the modulation of synaptic transmission as a result of the synaptic-induced glial activity.

Purinergic modulation of synaptic signalling at the neuromuscular junction.

Purines have physiologically important functions throughout the nervous system. In both the central (CNS) and peripheral nervous systems (PNS), purines in the form of adenosine triphosphate and adenosine can play a number of roles in neuronal activation and inhibition. In addition, purines are known to be important for glial cell signaling in both the CNS and PNS. In the PNS, the neuromuscular junction (NMJ) is an excellent model for studying simple synaptic interactions. It is well suited to investigations of neuron-glia interactions because synaptic properties are well defined and perisynaptic Schwann cells (PSCs), glial cells at the NMJ, dynamically interact with the pre- and postsynaptic elements. At the NMJ, purines are critical for presynaptic modulation but also for neuron-glia interactions. Purines signal to PSCs through metabotropic and ionotropic receptors and activation of these receptors can have both modulatory and activating functions. This review will discuss recent developments in our understanding of purinergic modulation of the NMJ with an emphasis on the involvement of purines in neuron-glia interactions at this synapse.

Glial cells in synaptic plasticity.

Plasticity of synaptic transmission is believed to be the cellular basis for learning and memory, and depends upon different pre- and post-synaptic neuronal mechanisms. Recently, however, an increasing number of studies have implicated a third element in plasticity; the perisynaptic glial cell. Originally glial cells were thought to be important for metabolic maintenance and support of the nervous system. However, work in the past decade has clearly demonstrated active involvement of glia in stability and overall nervous system function as well as synaptic plasticity. Through specific modulation of glial cell function, a wide variety of roles for glia in synaptic plasticity have been uncovered. Furthermore, interesting circumstantial evidence suggests a glial involvement in multiple other types of plasticity. We will discuss recent advances in neuron-glial interactions that take place during synaptic plasticity and explore different plasticity phenomena in which glial cells may be involved.

Activation of ionotropic glutamate receptors on peripheral axons of primary motoneurons mediates transmitter release at the zebrafish NMJ.

The development and function of the vertebrate neuromuscular junction (NMJ) is continually being redefined. Previous studies have indicated that glutamate may play a role in the development or function of the NMJ by associating with presynaptic receptors. We have used larval zebrafish (Danio rerio) to investigate the presence of presynaptic ionotropic glutamate receptors (iGluRs) at the NMJ in vivo. In whole-mount zebrafish larvae, antibody staining directed to NR2A subunits colocalized with specific staining of motoneuron axon tracts. Whole cell voltage-clamp recordings of miniature endplate currents (mEPCs) from axial white muscle were performed during application of iGluR agonists and antagonists. Local perfusion of the NMJ with iGluR agonists resulted in significant increases in the frequency of spontaneous acetylcholine (ACh) release. These increases were blocked by the N-methyl-d-aspartate (NMDA) receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (50 microM) and by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (50 microM). Further pharmacological investigation revealed no effect of the kainate receptor-specific antagonist (2S,4R)-4-methylglutamate (10 microM) on kainate-induced rises in the frequency of spontaneous ACh release. However, these were blocked with the AMPA receptor-specific antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (50 microM). Application of glutamate (1 mM) in the presence of the glutamate uptake inhibitor d-threo-beta-benzyloxyaspartate(200 microM) resulted in a significant increase in the frequency of mEPCs. These results suggest the presence of AMPA and NMDA receptors in association with motoneuron axons of larval zebrafish.