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Cells Jun 2024Chronic pain is a pathological state defined as daily pain sensation over three consecutive months. It affects up to 30% of the general population. Although significant... (Review)
Review
Chronic pain is a pathological state defined as daily pain sensation over three consecutive months. It affects up to 30% of the general population. Although significant research efforts have been made in the past 30 years, only a few and relatively low effective molecules have emerged to treat chronic pain, with a considerable translational failure rate. Most preclinical models have focused on sensory neurotransmission, with particular emphasis on the dorsal horn of the spinal cord as the first relay of nociceptive information. Beyond impaired nociceptive transmission, chronic pain is also accompanied by numerous comorbidities, such as anxiety-depressive disorders, anhedonia and motor and cognitive deficits gathered under the term "pain matrix". The emergence of cutting-edge techniques assessing specific neuronal circuits allow in-depth studies of the connections between "pain matrix" circuits and behavioural outputs. Pain behaviours are assessed not only by reflex-induced responses but also by various or more complex behaviours in order to obtain the most complete picture of an animal's pain state. This review summarises the latest findings on pain modulation by brain component of the pain matrix and proposes new opportunities to unravel the mechanisms of chronic pain.
Topics: Animals; Humans; Chronic Pain; Disease Models, Animal; Pain; Nerve Net
PubMed: 38920628
DOI: 10.3390/cells13120997 -
Cancer Management and Research 2024There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials....
PURPOSE
There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials. Similarly, insights from the perspective of trial staff caring for this group of patients are missing. This study aims to investigate patient, relative and trial staff experiences regarding participation in clinical neurooncological trials.
METHODS
Within a qualitative exploratory study, 29 semi-structured interviews with brain tumor patients, relatives and trial staff were conducted and analyzed using reflexive thematic analysis (RTA) by Braun and Clarke. A patient researcher and patient council were involved in data analysis and interpretation.
RESULTS
Four themes were developed reflecting significant aspects of the trial experience: 1. "It all revolves around hope"; 2. "Trial participation: experiencing unique medical care"; 3. "Everyone's roles are changing"; 4. "Communication as a possible area of conflict". Experiencing trial participation and general medical treatment were found to be interconnected to such a degree that they were often not meaningfully distinguished by patients and relatives.
CONCLUSION
In addition to assessing traditional endpoints for patient outcomes, we recommend increased emphasis on investigating the impact of the "soft" components constituting trial participation. Due to the interconnectedness of medical treatment and trial participation, we recommend further investigation in comparison to experiences in regular care. A deeper understanding of trial participation is needed to inform improvements for patient experiences and staff satisfaction alongside medical and scientific progress.
PubMed: 38919873
DOI: 10.2147/CMAR.S447407 -
Frontiers in Psychiatry 2024Augmentative alternative communication (AAC) devices or systems are often prescribed to minimally verbal or nonspeaking autistic individuals and other individuals with...
Augmentative alternative communication (AAC) devices or systems are often prescribed to minimally verbal or nonspeaking autistic individuals and other individuals with complex communication needs to facilitate communication or as an alternative to spoken language. AAC use can result in communication gains and improved quality of life for minimally verbal or nonspeaking individuals. Despite this, AAC abandonment is high, limiting societal participation of the individual on the autism spectrum with complex communication needs. Our study is a novel exploration of the barriers of AAC use from a multi-stakeholder perspective, and a qualitative analysis of similarities and differences between stakeholders. We conducted semi-structured interviews and focus groups with 30 parent-carers, educators and clinicians currently supporting AAC users in Western Australia and analysed the data using reflexive thematic analysis. Barriers from each stakeholder group were coded, resulting in 17 subthemes forming five main themes common to all stakeholders: Stakeholder Knowledge, Stakeholder Attitudes and Stigma, Resources, AAC User Engagement, and Device Fit. Contrasting perspectives included actual and perceived stigma associated with AAC use (parent-carers vs clinicians); different struggles with resources and knowledge (parent-carers vs clinicians and educators); and a lack of clinician communication in the processes that determined AAC-fit for school environments (educators only). Findings are discussed in the context of improving inter-stakeholder collaboration and capacity building in Australian health service and practice to better support minimally verbal or nonspeaking autistic individuals and individuals with complex communication needs. Suggestions are also offered for communication partner training.
PubMed: 38919639
DOI: 10.3389/fpsyt.2024.1385947 -
Journal of Anaesthesiology, Clinical... 2024The objective of the study was to evaluate the performances of qCON and qNOX indices in pediatric populations undergoing surgery under general anesthesia (GA), focusing...
BACKGROUND AND AIMS
The objective of the study was to evaluate the performances of qCON and qNOX indices in pediatric populations undergoing surgery under general anesthesia (GA), focusing on the induction and recovery periods. Both the indices are derived from electroencephalogram (EEG) and implemented in the CONOX monitor (Fresenius Kabi, Germany).
MATERIAL AND METHODS
After approval of the institutional ethics committee, this prospective observational study was conducted in pediatric patients of either sex in the age group of 1-12 years belonging to the American Society of Anesthesiology (ASA) grade I and II undergoing elective surgery under GA. Anesthetic technique was GA with or without regional analgesia (RA). All patients underwent inhalation induction and maintenance using sevoflurane. Patients were monitored with the use of a CONOX monitoring system (Fresenius Kabi, Germany), connected via a set of electrodes placed over the forehead. qCON and qNOX scores were recorded during awake (on operating table premedicated with oral midazolam 0.5 mg/kg), at induction, at loss of eyelash reflex, intubation/laryngeal mask airway (LMA) insertion, before and after regional anesthesia, surgical incision, at cessation of anesthesia, emergence, extubation, and eye-opening. Registered results were also analyzed compared with the minimum alveolar concentration of sevoflurane (MAC).
RESULTS
A total of 46 pediatric patients were enrolled in the study with a mean age of 5.6 years. All the patients were either ASA I or II. There was a simultaneous fall and rise of qCON and qNOX upon induction and recovery, respectively. There was a rise in qNOX with surgical incision irrespective of RA. However, there was a greater rise in qNOX following surgical incision in those who did not receive RA ( = 0.33) Also both qCON ( = 0.06) and qNOX ( = 0.41) were poorly correlated with MAC values of sevoflurane during GA in the pediatric population.
CONCLUSIONS
Both qCON and qNOX values change predictably with changes in the conscious level and with different noxious stimuli. Further studies are required to confirm the findings taking into account the postoperative assessment of delirium and recall of intraoperative events.
PubMed: 38919439
DOI: 10.4103/joacp.joacp_453_22 -
Research Involvement and Engagement Jun 2024Lived experience researchers draw on their lived and living experiences to either lead on or inform research. Their personal experiences are relevant to the research...
BACKGROUND
Lived experience researchers draw on their lived and living experiences to either lead on or inform research. Their personal experiences are relevant to the research topic and so they must manage the interplay of their health and healthcare experiences with the research, population, and data they work with, as well as the more general challenges of being a researcher. Lived experience researchers must navigate these dilemmas in addition to queries over their competency, due to issues relating to intersectionality and epistemic injustice. This justifies a motivation to better understand the experiences of lived experience researchers and develop appropriate and personalised supervision based on their preferences and needs.
METHODS
Q methodology was used to identify a collection of identity-related issues that impact lived experience researchers during PhD research in the context of the UK. These issues were presented in the form of 54 statements to 18 lived experience researchers to prioritise as topics to explore in supervision.
RESULT
It was found that lived experiences researchers could be grouped into three distinct factors following an inverted factor analysis: Factor 1: Strengthening my identity, skills, growth, and empowerment; Factor 2: Exploring the emotional and relational link I have with the research and Factor 3: Navigating my lived and professional experiences practically and emotionally. The findings suggest that there may be three types of lived experience researchers, each with different needs from supervision, suggesting the population is heterogeneous.
CONCLUSION
The research identified a deeper understanding of the needs of lived experience researchers and highlights the importance of personalised supervision according to the individual needs of the researcher and their preferences for supervision. The findings reinforce the importance of integrating a clinical dimension into supervision to support the needs of all lived experience researchers.
PubMed: 38918822
DOI: 10.1186/s40900-024-00596-w -
JMIR Formative Research Jun 2024Measurement-based care in behavioral health uses patient-reported outcome measures (PROMs) to screen for mental health symptoms and substance use and to assess symptom...
BACKGROUND
Measurement-based care in behavioral health uses patient-reported outcome measures (PROMs) to screen for mental health symptoms and substance use and to assess symptom change over time. While PROMs are increasingly being integrated into electronic health record systems and administered electronically, paper-based PROMs continue to be used. It is unclear if it is feasible to administer a PROM on paper when the PROM was initially developed for electronic administration.
OBJECTIVE
This study aimed to examine the feasibility of patient self-administration of a 2-part substance use screener-the Tobacco, Alcohol, Prescription medications, and other Substances (TAPS)-on paper. This screener was originally developed for electronic administration. It begins with a limited number of questions and branches to either skip or reflex to additional questions based on an individual's responses. In this study, the TAPS was adapted for paper use due to barriers to electronic administration within an urgent care behavioral health clinic at an urban health safety net hospital.
METHODS
From August 2021 to March 2022, research staff collected deidentified paper TAPS responses and tracked TAPS completion rates and adherence to questionnaire instructions. A retrospective chart review was subsequently conducted to obtain demographic information for the patients who presented to the clinic between August 2021 and March 2022. Since the initial information collected from TAPS responses was deidentified, demographic information was not linked to the individual TAPS screeners that were tracked by research staff.
RESULTS
A total of 507 new patients were seen in the clinic with a mean age of 38.7 (SD 16.6) years. In all, 258 (50.9%) patients were male. They were predominantly Black (n=212, 41.8%), White (n=152, 30%), and non-Hispanic or non-Latino (n=403, 79.5%). Most of the patients were publicly insured (n=411, 81.1%). Among these 507 patients, 313 (61.7%) completed the TAPS screener. Of these 313 patients, 76 (24.3%) adhered to the instructions and 237 (75.7%) did not follow the instructions correctly. Of the 237 respondents who did not follow the instructions correctly, 166 (70%) answered more questions and 71 (30%) answered fewer questions than required in TAPS part 2. Among the 237 patients who did not adhere to questionnaire instructions, 44 (18.6%) responded in a way that contradicted their response in part 1 of the screener and ultimately affected their overall TAPS score.
CONCLUSIONS
It was challenging for patients to adhere to questionnaire instructions when completing a substance use screener on paper that was originally developed for electronic use. When selecting PROMs for measurement-based care, it is important to consider the structure of the questionnaire and how the PROM will be administered to determine if additional support for PROM self-administration needs to be implemented.
PubMed: 38916950
DOI: 10.2196/52801 -
Cureus May 2024Acute transverse myelitis (ATM) is a syndrome of multiple etiologies, with acute or subacute onset in which inflammation of the spinal cord results in neurological...
Acute transverse myelitis (ATM) is a syndrome of multiple etiologies, with acute or subacute onset in which inflammation of the spinal cord results in neurological deficits, including weakness, sensory loss, and autonomic dysfunction. It is often associated with infectious or autoimmune etiologies but can be considered idiopathic when extensive workup is negative. We present a case of a young African American female who presented with acute onset of bilateral lower extremity weakness, loss of sensation, and autonomic dysfunction. On physical exam, she had absent lower extremity reflexes, 0-1/5 power, and markedly diminished sensation with no pain/temperature discrimination with an abdominal sensory level at T4. There was no upper extremity involvement. She was incidentally found to be COVID-19-positive and denied ever being vaccinated in the past. MRI of the spine revealed diffuse signal abnormality within the cervical and thoracic spine extending to the conus, and an MRI of the brain showed two white matter lesions in the frontal lobes. Lumbar puncture showed lymphocytic pleocytosis and elevated protein; Gram stain did not reveal any pathogen. The patient was treated initially with high doses of steroids with minimal response. She underwent multiple sessions of plasmapheresis with good tolerance and response. Differential diagnoses considered for this case were Guillain Barre syndrome, neuromyelitis optica (NMO), multiple sclerosis, SLE-induced transverse myelitis, or infectious cases. All lab work and workup came back negative for these diseases, leaving us with an interesting culprit: COVID-19 associated. There have been few cases mentioned in the literature of transverse myelitis caused by COVID-19, and this remains a possibility, as all other causes were ruled out.
PubMed: 38916003
DOI: 10.7759/cureus.61066 -
Cureus Jun 2024Bupropion is an antidepressant used in the treatment of major depressive disorder, seasonal affective disorder, nicotine addiction, and weight loss. It primarily...
Bupropion is an antidepressant used in the treatment of major depressive disorder, seasonal affective disorder, nicotine addiction, and weight loss. It primarily functions via norepinephrine and dopamine reuptake inhibition. At toxic doses, bupropion can elicit seizures, as well as precipitate corrected QT interval (QTc) and QRS prolongation. We describe a case of an 18-year-old female who reportedly ingested 28 grams of extended-release bupropion, a dose much higher than in previously reported cases. Toxic ingestion precipitated status epilepticus, prolonged QTc, widened QRS, pulseless ventricular tachycardia (pVT), and subsequent cardiovascular collapse necessitating veno-arterial extracorporeal membrane oxygenation (ECMO) and Impella support. Historically, the cardiotoxic effects of bupropion toxicity have largely been treated with supportive care, sometimes requiring ECMO. This patient's course was complicated by a widening QRS despite aggressive bicarbonate therapy and recurrent pVT, which was ultimately aborted with lidocaine. Neurological prognostication was further complicated by a lack of brainstem reflexes on the exam. With maximal supportive care, the patient was liberated from Impella, ECMO, and the ventilator by hospital day seven. At discharge, she was neurologically intact with full recovery of cardiac function. This case emphasizes the need for early consideration of transfer to an ECMO center in the setting of a bupropion overdose and offers a potentially effective treatment option for bupropion-induced ventricular arrhythmia.
PubMed: 38915842
DOI: 10.7759/cureus.62873 -
BioRxiv : the Preprint Server For... Jun 2024Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring...
Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.
PubMed: 38915687
DOI: 10.1101/2024.06.13.598885 -
BMC Geriatrics Jun 2024Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults...
BACKGROUND
Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD.
METHODS
We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups.
RESULTS
LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes.
CONCLUSIONS
The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.
Topics: Humans; Male; Aged; Female; Blinking; Reflex, Pupillary; Depression; Aged, 80 and over; Middle Aged; Adult; Pupil; Darkness; Young Adult; Light
PubMed: 38914987
DOI: 10.1186/s12877-024-05034-w