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Purpose: A systematic review to identify treatment approaches for the management of pain following peripheral nerve injury. Methods: A published literature search was performed for the concepts of peripheral nerve injury and pain management with related synonyms. The strategies were created using a combination of controlled vocabulary terms and keywords and were executed in Embase.com, Ovid-Medline All, and Scopus from database inception. Database searches were completed on August 22, 2023. Results: The initial search resulted in a total of 1,793 citations. In total, 724 duplicates were removed, leaving 1,069 unique citations remaining for analysis. This review excluded all papers that were not specific to pain following peripheral nerve injury. Case and cohort studies (n < 5) were also excluded. Thirty-two articles on pain management strategies after peripheral nerve injury remained, with years of publication ranging from 1981 to 2023. An additional four articles were identified by manual search. Of the 36 articles reviewed, 15 articles reported on the approach to the treatment of pain after a peripheral nerve injury, and the other 22 articles consisted of cohort and case series studies. Conclusions: There is a lack of literature describing efficacy of various treatment strategies for pain following peripheral nerve injuries. Few studies provide clear, stepwise clinical guidance for practicing physicians and other health care providers on the treatment of these complicated patients.

Introduction Communication failings may compromise the diagnostic process and pose a risk to quality of care and patient safety. With a focus on emergency care settings, this project aims to examine the critical role and impact of communication in the diagnostic process, including in diagnosis-related health and research policy, and diagnostic patient–clinician interactions in emergency departments (EDs).Methods and analysis This project uses a qualitatively driven multimethod design integrating findings from two research studies to gain a comprehensive understanding of the impact of context and communication on diagnostic excellence from diverse perspectives. Study 1 will map the diagnostic policy and practice landscape in Australia, New Zealand and the USA through qualitative expert interviews and policy analysis. Study 2 will investigate the communication of uncertainty in diagnostic interactions through a qualitative ethnography of two metropolitan Australian ED sites incorporating observations, field notes, video-recorded interactions, semistructured interviews and written medical documentation, including linguistic analysis of recorded diagnostic interactions and written documentation. This study will also feature a description of clinician, patient and carer perspectives on, and involvement in, interpersonal diagnostic interactions and will provide crucial new insights into the impact of communicating diagnostic uncertainty for these groups. Project-spanning patient and stakeholder involvement strategies will build research capacity among healthcare consumers via educational workshops, engage with community stakeholders in analysis and build consensus among stakeholders.Ethics and dissemination The project has received ethical approvals from the Human Research Ethics Committee at ACT Health, Northern Sydney Local Health District and the Australian National University. Findings will be disseminated to academic peers, clinicians and healthcare consumers, health policy-makers and the general public, using local and international academic and consumer channels (journals, evidence briefs and conferences) and outreach activities (workshops and seminars).

Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by neurodevelopmental delays, hyperphagia, difficulties with social communication and challenging behaviours. Individuals require intensive supervision from caregivers which may negatively affect caregiver quality of life. This study used data collected in the Australasian PWS Registry (n = 50, mean age 11.2 years) to evaluate associations between child behaviours and caregiver mental well-being. Symptoms of sleep-related breathing disorder, child depression and social difficulties were associated with poorer caregiver mental and physical well-being. Growth hormone therapy use was associated with better caregiver mental and physical well-being. Optimising management of problematic behaviours and sleep disturbances have the potential to support caregivers who are the most vital network of support for individuals affected by PWS.

Shifting baselines can skew species harvest guidelines and lead to potentially inaccurate assessments of population status and range. The North American Fur Trade (~1600–1900 CE) profoundly impacted the continent’s socio-ecological systems, but its legacies are often not incorporated in management discussions. We apply a conservation paleobiology lens to address shifting baselines of nine species of fur-bearing mammals in Vermont, including seven mesocarnivores and two semi-aquatic rodents. Using a database maintained by the Vermont Division for Historic Preservation, we identified 25 existing radiocarbon dates of fur-bearer associated features from 16 archaeological localities spanning the Early-Late Holocene. We also generated 7 new radiocarbon dates on beaver and muskrat bones from the Ewing (VT-CH-005), Bohannon (VT-GI-026), and Chimney Point (VT-AD-329) localities. Our new radiocarbon dates cluster within the Late Holocene, immediately prior to and throughout the European contact period, and overlap with The Beaver Wars. We recover a ~8,000 year record of beaver harvest, affirming the millennial scale importance of beavers, a species that is often the focus of human-wildlife conflict research. Comparison of zooarchaeological occurrences with digitized natural history specimens and community science observations reveals geographic range continuity for most species except for the American marten, which was historically extirpated, and confirms the native status of the red fox. While taphonomic constraints make our dataset a conservative assessment, our case studies demonstrate how wildlife managers can employ zooarchaeological data to better understand long-term properties of coupled socio-ecological systems and highlight the cultural importance of these species to Indigenous trade networks prior to the Fur Trade in Vermont.

Emergency Department (ED) care is provided for a diverse range of patients, clinical acuity and conditions. This diversity often calls for different vital signs monitoring requirements. Requirements often change depending on the circumstances that patients experience during episodes of ED care. To describe expert consensus on vital signs monitoring during ED care in the Australasian setting to inform the content of a joint Australasian College for Emergency Medicine (ACEM) and College of Emergency Nursing Australasia (CENA) position statement on vital signs monitoring in the ED. A 4-hour online nominal group technique workshop with follow up surveys. Twelve expert ED nurses and doctors from adult, paediatric and mixed metropolitan and regional ED and research facilities spanning four Australian states participated in the workshop and follow up surveys. Consensus building generated 14 statements about vital signs monitoring in ED. Good consensus was reached on whether vital signs should be assessed for 15 of 19 circumstances that patients may experience. This study informed the creation of a joint position statement on vital signs monitoring in the Australasian ED setting, endorsed by CENA and ACEM. Empirical evidence is needed for optimal, safe and achievable policy on this fundamental practice. [ABSTRACT FROM AUTHOR]

Abstract. Introduction:. There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored. Objectives:. The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain. Methods:. In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram before and 30 minutes after the nerve block procedure. To determine the specific cortical electrophysiological correlates of relief from chronic pain, 12 healthy participants undergoing cold-pressor test to induce experimental acute pain were used as a control group. The data were analyzed to characterize power spectral density patterns of pain relief and identify their source generators at cortical level. Results:. Chronic pain relief was associated with significant delta, theta, and alpha power increase at the frontal area. However, only midfrontal theta power increase showed significant positive correlation with magnitude of reduction in pain intensity. The sources of theta power rebound were located in the left dorsolateral prefrontal cortex (DLPFC) and midline frontal cortex. Furthermore, theta power increase in the midline frontal cortex was significantly higher with chronic vs acute pain relief. Conclusion:. These findings may provide basis for targeting chronic pain relief via modulation of the midline frontal theta oscillations.

In this paper, we study the flow of signals through linear paths with the nonlinear condition that a node emits a signal when it receives external stimuli or when two incoming signals from other nodes arrive coincidentally with a combined amplitude above a fixed threshold. Sets of such nodes form a polychrony group and can sometimes lead to cascades. In the context of this work, cascades are polychrony groups in which the number of nodes activated as a consequence of other nodes is greater than the number of externally activated nodes. The difference between these two numbers is the so-called profit. Given the initial conditions, we predict the conditions for a vertex to activate at a prescribed time and provide an algorithm to efficiently reconstruct a cascade. We develop a dictionary between polychrony groups and graph theory. We call the graph corresponding to a cascade a chinampa. This link leads to a topological classification of chinampas. We enumerate the chinampas of profits zero and one and the description of a family of chinampas isomorphic to a family of partially ordered sets, which implies that the enumeration problem of this family is equivalent to computing the Stanley-order polynomials of those partially ordered sets.

Aims. We have shown that growth hormone (GH) treatment poststroke increases neuroplasticity in peri-infarct areas and the hippocampus, improving motor and cognitive outcomes. We aimed to explore the mechanisms of GH treatment by investigating how GH modulates pathways known to induce neuroplasticity, focusing on association between brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the peri-infarct area, hippocampus, and thalamus. Methods. Recombinant human growth hormone (r-hGH) or saline was delivered (0.25 μl/hr, 0.04 mg/day) to mice for 28 days, commencing 48 hours after photothrombotic stroke. Protein levels of pro-BDNF, total-mTOR, phosphorylated-mTOR, total-p70S6K, and phosporylated-p70S6K within the peri-infarct area, hippocampus, and thalamus were evaluated by western blotting at 30 days poststroke. Results. r-hGH treatment significantly increased pro-BDNF in peri-infarct area, hippocampus, and thalamus (p

Complex regional pain syndrome (CRPS) is a debilitating neuroinflammatory condition of unknown etiology. Symptoms include excruciating pain and trophic changes in the limbs as defined by the Budapest criteria. The severity and functional recovery of CRPS, unlike most pain conditions, is quantifiable using a variation of the Budapest criteria known as the CRPS severity score. Like many chronic pain conditions, CRPS is difficult to treat once pain has been present for more than 12 months. However, previous work has demonstrated that a subset of patients with new-onset CRPS (~50%) improve if treated within one year, while the rest have minimal to no symptom improvement. Unfortunately, this leads to permanent disability and often requires invasive and costly treatments such as spinal cord stimulation or long-term opioid therapy. Because the etiology is unknown, treatment is multimodal, and often supportive. Biomarkers that predict severity or resolution of symptoms would significantly change treatment but have not yet been identified. Interestingly, there are case reports of remission or resolution of CRPS symptoms with the use of antibiotics known to affect the gut flora. Mouse studies have demonstrated that modulation of the gut microbiome is anti-nociceptive in visceral, inflammatory and neuropathic pain models. We hypothesize that the variable clinical potential for recovery and response to therapy in CRPS may be secondary to or reflected in changes in the gut microbiota. We suggest that the microbiota may mediate or reflect clinical status via the metabolome, activation of the immune system and/or microglial activation. We hypothesize that the gut microbiome is a potential mediator in development and persistence of CRPS symptoms and propose that the clinical condition of CRPS could provide a unique opportunity to identify biomarkers of the microbiota and potential therapies to prevent pain chronification.

This article discusses the importance of finding the right balance in the use of diagnostic tests in healthcare. Failure to order tests when necessary or misinterpreting their results can lead to diagnostic errors and adverse outcomes, while overuse of tests can result in false positives, unnecessary labeling of diseases, and further unnecessary testing and treatment. The appropriateness of diagnostic investigations varies depending on the clinical setting, test choice, and study methodology. The article proposes strategies for achieving the "sweet spot" in using diagnostic tests, including questioning the role of testing, considering patient preferences and treatment options, understanding pre-test probability and test performance, avoiding misinterpretation of test results, using diagnostic decision support tools, ordering and sequencing tests appropriately, responding to diagnostic uncertainty, and applying system-level strategies for optimizing test use. [Extracted from the article]

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.

Intracellular Ca2+ dynamics in astrocytes can be triggered by neuronal activity and in turn regulate a variety of downstream processes that modulate neuronal function. In this fashion, astrocytic Ca2+ signaling is regarded as a processor of neural network activity by means of complex spatial and temporal Ca2+ dynamics. Accordingly, a key step is to understand how different patterns of neural activity translate into spatiotemporal dynamics of intracellular Ca2+ in astrocytes. Here, we introduce a minimal compartmental model for astrocytes that can qualitatively reproduce essential hierarchical features of spatiotemporal Ca2+ dynamics in astrocytes. We find that the rate of neuronal firing determines the rate of Ca2+ spikes in single individual processes as well as in the soma of the cell, while correlations of incoming neuronal activity are important in determining the rate of “global” Ca2+ spikes that can engulf soma and the majority of processes. Significantly, our model predicts that whether the endoplasmic reticulum is shared between soma and processes or not determines the relationship between the firing rate of somatic Ca2+ events and the rate of neural network activity. Together these results provide intuition about how neural activity in combination with inherent cellular properties shapes spatiotemporal astrocytic Ca2+ dynamics, and provide experimentally testable predictions.

The level of minimal residual disease (MRD) in marrow predicts outcome and guides treatment in childhood acute lymphoblastic leukemia (ALL) but accurate prediction depends on accurate measurement.Forty-one children with ALL were studied at the end of induction. Two samples were obtained from each iliac spine and each sample was assayed twice. Assay, sample and side-to-side variation were quantified by analysis of variance and presumptively incorrect decisions related to high-risk disease were determined using the result from each MRD assay, the mean MRD in the patient as the measure of the true value, and each of 3 different MRD cut-off levels which have been used for making decisions on treatment.Variation between assays, samples and sides each differed significantly from zero and the overall standard deviation for a single MRD estimation was 0.60 logs. Multifocal residual disease seemed to be at least partly responsible for the variation between samples. Decision errors occurred at a frequency of 13-14% when the mean patient MRD was between 10-2 and 10-5. Decision errors were observed only for an MRD result within 1 log of the cut-off value used for assessing high risk. Depending on the cut-off used, 31-40% of MRD results were within 1 log of the cut-off value and 21-16% of such results would have resulted in a decision error.When the result obtained for the level of MRD is within 1 log of the cut-off value used for making decisions, variation in the assay and/or sampling may result in a misleading assessment of the true level of marrow MRD. This may lead to an incorrect decision on treatment.

Introduction Fournier’s gangrene is a poly-microbial necrotizing fasciitis that involves the perineum and/or external genitalia. Urgent surgical debridement is well recognized as essential acute treatment yet unique challenges arise for plastic surgical reconstruction to obtain a complete functional recovery. This case describes a successful delayed pedicle flap repair based upon the anterior abdominal wall. Case description A 24 year old man was admitted to ICU ten days after elective circumcision with Fournier’s gangrene. He underwent a number of surgical debridements, and was referred for plastic surgical management. He had penile reconstruction using a random pattern abdominal flap, which was performed as a three stage procedure including flap vascular delay technique. Discussion Perineal and penile skin loss can be significant and is difficult to repair. Various techniques have been used to reconstruct lost tissue: skin grafts, transposition of the testes and spermatic cords to the thigh, flaps, and other types of pediculated myocutaneous flaps. Muscle flap reconstruction provides an environment that allows for complete regeneration of the urethral epithelium but is bulky and unsightly. Skin grafts contract and may produce painful and dysfunctional reconstructions. This novel technique produces a functional, and aesthetic reconstruction. Conclusion Penile skin recovery following Fournier’s gangrene recovery is problematic. This case demonstrates the functionality of a delayed flap repair using the anterior abdominal wall.

The Convention on the Rights of Persons with Disabilities (CRPD) creates duties for States Parties and UN agencies to ensure that individuals under their protection have equal enjoyment of the full range of human rights. This includes the Article 25 right to enjoy ‘the highest attainable standard of health without discrimination on the basis of disability.’ However, refugees, who are forced to seek protection outside their state, face particular obstacles to maintaining an adequate level of wellbeing and accessing services to meet their health needs. Among this group, those who have a disability may confront multiple intersecting challenges. This paper draws on the findings of research across countries that play host to significant refugee populations. It explores the contribution of the CRPD to the international human rights framework for refugees, with particular attention to the right to health. Incorporating evidence from the field, it discusses the implementation of these rights and related duties in humanitarian responses across the world. This article discusses common barriers to health services for refugees with disabilities in six host countries. Based on the broad conceptualization of health and wellbeing established in the international legal framework, it also examines the relationship between the fulfilment of Article 25 and other basic socioeconomic rights. It provides examples of good practice and identifies strategies to better ensure the rights set out in Article 25 of the CRPD.

52-year-old patient presented with palpitation and well tolerated monomorphic ventricular tachycardia. He had normal echocardiogram and coronary angiogram 3 months prior to presentation. Surface EKG revealed regular wide-complex tachycardia with right bundle branch block morphology and right inferior axis. In conjunction with recent negative cardiac evaluation, this suggested idiopathic focal ventricular tachycardia from anterolateral basal left ventricle. CARTO based activation mapping confirmed the presence of VT focus in that area. Radiofrequency ablation at the site of perfect pacemap resulted in a partial suppression of the focus. Echocardiogram was subsequently performed because of progressive dyspnea. It revealed asymmetrical thickening of posterolateral left ventricle, with delayed enhancement on contrast magnetic resonance imaging. Fine needle aspiration of abdominal fat stained with Congo red confirmed the diagnosis of systemic AL amyloidosis due to IgG λ-light chain deposition. Consequently, the patient underwent placement of implantable defibrillator and hematopoetic stem cell transplantation. He remains in excellent functional status 18 months after presentation.

The authors sought to determine the attitudes of public health service board members and senior executives toward patient experience and to describe the governance activities of the boards in this area. The study was based on an online survey of 322 board members from 85 public health services and semi-structured interviews with 35 board members and senior executives from 13 public health services in Victoria, Australia. The results showed that while some health service boards had high aspirations and clear plans for improving patient experience, others remained sluggish or even cynically resistant to changing their existing models of care. Interviewees associated with highly active boards described initiatives to improve patient experience at multiple levels in the organisation - from boardroom to bedside. Among less active boards, efforts to improve patient experience tended to be more ad hoc and there was greater uncertainty about how to scale up or systematise. The authors conclude that addressing the gap between the responsibility of boards to address patient experience, and the reality of their governance activities, requires a nuanced understanding of the attitudes and activities of board members. The approaches taken by “positive attitude, high activity” boards could be showcased as exemplars for others.

IntroductionWhile Dupuytren's disease can cause disabling contractures requiring open surgery, a less-invasive option using Clostridium Histolyticum collagenase (CHC) via percutaneous injection was recently reported. A recent prospective, randomized trial demonstrated few complications during 90 days follow-up, however did not assess any longer term follow-up for these patients. Long-term outcomes in this setting have not been adequately reported, and the current manuscript aims to identify late complications from the clinical use of percutaneous CHC.MethodsThe current manuscript reports an extended 12-month follow-up for a cohort of twelve of patients enrolled in the original prospective, randomized trial, treated at a single institution. An analysis of complications requiring surgical intervention was undertaken.ResultsTwo of twelve patients reported debilitating pain and triggering requiring surgical intervention. Extensive deep-tissue scarring and adhesions were identified, providing the first visual and qualitative analysis of the pathologic effects of CHC.ConclusionLate complications from CHC use can and have occurred, outside the follow-up period of the initial phase III trials. Longer term follow-up of such patients is thus essential, and further investigation and characterization of the late effects of CHC use is warranted.

The nature of higher education institutions is changing, primarily as a result of reduced government financial support for the sector. Fiscal restraint towards education funding has been observed in Australia, New Zealand, the United States, Canada, the UK and much of Europe. There has been steady growth in demand for higher education but reduced capacity by governments to fund it. Increasingly, students are required to contribute to the cost of their own education. Although these trends are problematic for higher education institutions that have been reliant previously upon government funding, it has also created an opportunity for those that are able to fill the gap between supply and demand for higher education services.