Randomized Placebo-Controlled Trial of 60-Day Percutaneous Peripheral Nerve Stimulation Treatment Indicates Relief of Persistent Postoperative Pain, and Improved Function After Knee Replacement.

OBJECTIVES: Total knee arthroplasty (TKA) is an effective surgery for end-stage knee osteoarthritis, but chronic postoperative pain and reduced function affect up to 20% of patients who undergo such surgery. There are limited treatment options, but percutaneous peripheral nerve stimulation (PNS) is a promising nonopioid treatment option for chronic, persistent postoperative pain. The objective of the present study was to evaluate the effect of a 60-day percutaneous PNS treatment in a multicenter, randomized, double-blind, placebo-controlled trial for treating persistent postoperative pain after TKA. MATERIALS AND METHODS: Patients with postoperative pain after knee replacement were screened for this postmarket, institutional review board-approved, prospectively registered (NCT04341948) trial. Subjects were randomized to receive either active PNS or placebo (sham) stimulation. Subjects and a designated evaluator were blinded to group assignments. Subjects in both groups underwent ultrasound-guided placement of percutaneous fine-wire coiled leads targeting the femoral and sciatic nerves on the leg with postoperative pain. Leads were indwelling for eight weeks, and the primary efficacy outcome compared the proportion of subjects in each group reporting ≥50% reduction in average pain relative to baseline during weeks five to eight. Functional outcomes (6-minute walk test; 6MWT and Western Ontario and McMaster Universities Osteoarthritis Index) and quality of life (Patient Global Impression of Change) also were evaluated at end of treatment (EOT). RESULTS: A greater proportion of subjects in the PNS groups (60%; 12/20) than in the placebo (sham) group (24%; 5/21) responded with ≥50% pain relief relative to baseline (p = 0.028) during the primary endpoint (weeks 5-8). Subjects in the PNS group also walked a significantly greater distance at EOT than did those in the placebo (sham) group (6MWT; +47% vs -9% change from baseline; p = 0.048, n = 18 vs n = 20 completed the test, respectively). Prospective follow-up to 12 months is ongoing. CONCLUSIONS: This study provides evidence that percutaneous PNS decreases persistent pain, which leads to improved functional outcomes after TKA at EOT.

Acanthosis nigricans - a potentially useful clue to the presence of significant occult disease at autopsy.

A 19-year-old male was found dead in his apartment. At autopsy he was morbidly obese (Body mass index; BMI - 40.5) with multiple areas of velvety pigmented thickening of the skin in folds around the neck, in the axillae, in the inframammary regions, over the anterior waistline and groin regions and over the dorsal aspects of the feet. These had the typical appearance of acanthosis nigricans. Internal examination revealed aspiration of gastric contents into the airways. Vitreous humour biochemistry showed markedly elevated levels of both glucose (62.9 mmol/L) and ß-hydroxybutyrate (13.54 mmol/L). Death was, therefore, due to aspiration pneumonia complicating diabetic ketoacidosis on a background of morbid obesity. The initial indicator of underlying diabetes, in conjunction with obesity had been acanthosis nigricans.

The applicability of interprofessional education for collaborative people-centered practice and care to health plans and workforce issues: A thematic global case review.

Background: This article focuses on a growing, global recognition of the importance of the field of interprofessional education for person-centered collaborative practice (IPECP) expressed through high-level policy and accreditation decisions/actions taking place in 5 countries. Policy decisions are used to motivate strategies related to IPECP that align with national health plans, and workforce issues. Methods: Using a collective of representative stories from around the globe, a grouping of case studies were developed to illustrate different approaches and challenges to IPECP implementation. Results: Institutions from countries of various income levels face many similar challenges in the execution, delivery, and sustainability of IPECP. All programs face issues of financing, of preparing faculty, of developing and organizing curricula, and of bridging between campus and community. Discussion: Policies are being developed that promote a global approach to the inclusion of IPECP in the accreditation and regulation of postsecondary institutions and health service organizations, in keeping with WHO National Health Workforce Accounts. Policies developed promote and demonstrate the benefits of IPECP through remote emergency learning methods. The policies also build national systems for IPECP as an integral part of continuing professional development and lifelong learning. The organization of interprofessional research programs and the increasing publication of their results of such programs will lead to a clearer understanding of the efficacy of the field of IPECP. To ensure sustainability, stakeholders and policymakers should continue to foster policies that facilitate IPECP.

Network model of nociceptive processing in the superficial spinal dorsal horn reveals mechanisms of hyperalgesia, allodynia, and spinal cord stimulation.

The spinal dorsal horn (DH) processes sensory information and plays a key role in transmitting nociception to supraspinal centers. Loss of DH inhibition during neuropathic pain unmasks a pathway from nonnociceptive Aß-afferent inputs to superficial dorsal horn (SDH) nociceptive-specific (NS) projection neurons, and this change may contribute to hyperalgesia and allodynia. We developed and validated a computational model of SDH neuronal circuitry that links nonnociceptive Aß-afferent inputs in lamina II/III to a NS projection neuron in lamina I via a network of excitatory interneurons. The excitatory pathway and the NS projection neuron were in turn gated by inhibitory interneurons with connections based on prior patch-clamp recordings. Changing synaptic weights in the computational model to replicate neuropathic pain states unmasked a low-threshold excitatory pathway to NS neurons similar to experimental recordings. Spinal cord stimulation (SCS) is an effective therapy for neuropathic pain, and accumulating experimental evidence indicates that NS neurons in the SDH also respond to SCS. Accounting for these responses may inform therapeutic improvements, and we quantified responses to SCS in the SDH network model and examined the role of different modes of inhibitory control in modulating NS neuron responses to SCS. We combined the SDH network model with a previously published model of the deep dorsal horn (DDH) and identified optimal stimulation frequencies across different neuropathic pain conditions. Finally, we found that SCS-generated inhibition did not completely suppress model NS activity during simulated pinch inputs, providing an explanation of why SCS does not eliminate acute pain.NEW & NOTEWORTHY Chronic pain is a severe public health problem that reduces the quality of life for those affected and exacts an enormous socio-economic burden worldwide. Spinal cord stimulation (SCS) is an effective treatment for chronic pain, but SCS efficacy has not significantly improved over time, in part because the mechanisms of action remain unclear. Most preclinical studies investigating pain and SCS mechanisms have focused on the responses of deep dorsal horn (DDH) neurons, but neural networks in the superficial dorsal horn (SDH) are also important for processing nociceptive information. This work synthesizes heterogeneous experimental recordings from the SDH into a computational model that replicates experimental responses and that can be used to quantify neuronal responses to SCS under neuropathic pain conditions.

The development of interprofessional education and collaborative practice in Latin America and the Caribbean: preliminary observations.

The Pan-American Health Organization (PAHO) and World Health Organization have encouraged countries across Latin America and the Caribbean (LAC) to incorporate interprofessional education and collaborative practice (IPECP) into policies on the health workforce, and support policymakers in expanding its use. PAHO recommend countries to promote the development of interprofessional teams in integrated health services networks using IPECP. The creation of the Regional Network for Interprofessional Education in the Americas, the mobilization of a series of IPECP regional meetings, and the development of national IPECP action plans are the most promising results achieved thus far. This report describes the process of implementing IPECP in LAC countries as an innovative initiative in interprofessional health policy.

Laryngeal oncocytic cystadenoma and sudden death.

An 86-year-old woman with Alzheimer disease collapsed in her nursing home and was not able to be resuscitated. At autopsy, the major findings were in the larynx where a pedunculated oncocytic cystadenoma had occluded the glottis. Oncocytic cysts or cystadenomas of the larynx are rare histologically benign lesions that account for only 0.1-1% of laryngeal lesions. While the usual presentation is of a sensation of a mass in the throat, hoarseness, or stridor, very occasionally, there may be acute airway compromise and sudden death. Oncocytic cystadenoma should, therefore, be included in the differential diagnosis of potentially lethal obstructive laryngeal lesions.

Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement.

Low-frequency (<200 Hz), subperception spinal cord stimulation (SCS) is a novel modality demonstrating therapeutic efficacy for treating chronic neuropathic pain. When stimulation parameters were carefully titrated, patients experienced rapid onset (seconds-minutes) pain relief without paresthesia, but the mechanisms of action are unknown. Using an integrated computational model and in vivo measurements in urethane-anesthetized rats, we quantified how stimulation parameters (placement, pulse width, frequency, and amplitude) influenced dorsal column (DC) axon activation and neural responses in the dorsal horn (DH). Both modeled and recorded DC axons responded with irregular spiking patterns in response to low-amplitude SCS. Maximum inhibition of DH neurons occurred at ∼80% of the predicted sensory threshold in both modeled and recorded neurons, and responses were strongly dependent on spatially targeting of stimulation, i.e., the complement of DC axons activated, and on stimulation parameters. Intrathecal administration of bicuculline shifted neural responses to low-amplitude stimulation in both the model and experiment, suggesting that analgesia is dependent on segmental GABAergic mechanisms. Our results support the hypothesis that low-frequency subperception SCS generates rapid analgesia by activating a small number of DC axons which inhibit DH neuron activity via surround inhibition.

Evaluating optimized temporal patterns of spinal cord stimulation (SCS).

BACKGROUND: Temporal patterns of stimulation represent a novel dimension for improving the efficacy of spinal cord stimulation to treat chronic neuropathic pain. OBJECTIVE: We hypothesized that nonregular temporal patterns of stimulation designed using a computational model would be superior to conventional stimulation at constant frequencies or completely random patterns of stimulation. METHODS: Using a computational model of the dorsal horn network and an optimization algorithm based on biological evolution, we designed an optimized pattern of spinal cord stimulation with comparable efficacy and increased efficiency relative to constant frequency (CF) stimulation. We evaluated the effect of different temporal patterns on individual neurons recorded in the dorsal horn of urethane-anesthetized rats. RESULTS: The optimized pattern and 50 Hz CF stimulation produced greater inhibition of spontaneously firing neurons recorded in vivo than random 50 Hz stimulation or a pattern designed intentionally with poor fitness. Spinal Cord Stimulation (SCS) led to significant changes in the firing patterns of recorded units, and stimulation patterns that generated significant inhibition also tended to reduce entropy and regularize the firing patterns of units, suggesting that patterns of dorsal horn neuron activity may be important for pain perception in addition to the firing rate. CONCLUSIONS: These results demonstrate that the computational model can be used as a tool for optimizing stimulation parameters and suggest that optimized temporal patterns may increase the efficacy of spinal cord stimulation.

Accreditation as a driver of interprofessional education: the Canadian experience.

BACKGROUND: The purpose of this study was to (1) explore evidence provided by Canadian health and social care (HASC) academic programs in meeting their profession-specific interprofessional education (IPE)-relevant accreditation standards; (2) share successes, exemplars, and challenges experienced by HASC academic programs in meeting their IPE-relevant accreditation standards; and (3) articulate the impacts of IPE-relevant accreditation standards on enabling interprofessional learning to the global HASC academic community. METHODS: Profession-specific (bilingual, if requested) surveys were developed and emailed to the Deans/Academic Program Directors of eligible academic programs with a request to forward to the individual who oversees IPE accreditation. Responses were collated collectively and by profession. Open-ended responses associated with our first objective were deductively categorized to align with the five Accreditation of Interprofessional Health Education (AIPHE) standards domains. Responses to our additional questions associated with our second and third objectives were inductively categorized into themes. RESULTS/DISCUSSION: Of the 270 HASC academic programs surveyed, 30% (n = 24) partially or completely responded to our questions. Of the 106 IPE-relevant standards where evidence was provided, 62% (n = 66) focused on the Educational Program, 88% of which (n = 58) were either met or partially met, and 47% (n = 31) of which focused on practice-based IPE. Respondents cited various exemplars and challenges in meeting IPE-relevant standards. CONCLUSIONS: The overall sentiment was that IPE accreditation was a significant driver of the IPE curriculum and its continuous improvement. The array of exemplars described in this paper may be of relevance in advancing IPE implementation and accreditation across Canada and perhaps, more importantly, in countries where these processes are yet emerging.

Patterned lividity - the 'underwear sign'.

Lividity or livor mortis occurs when blood settles in dependent areas after death due to gravitational effects. Patterned lividity may result from a body lying against a variety of surfaces. Two case are presented where lividity was prevented by tight fitting elastic underwear except in areas where letters from the manufacturers' names had elevated the material, thus permitting capillaries in the underlying skin to fill. This type of patterned lividity may act as a useful record of the type of clothing being worn at the time of death and in the hours following.

Factors Causing Variation in World Health Organization Surgical Safety Checklist Effectiveness-A Rapid Scoping Review.

INTRODUCTION: This review was conducted to determine what factors might be responsible for prejudicing the outcomes after the implementation of a World Health Organization Surgical Safety Checklist (WHO SSC), grouping them appropriately and proposing strategies that enable the SSC a more helpful and productive tool in the operating room. METHODS: It was a rapid scoping review conducted as per Preferred Reporting Items for Systematic Review and Meta-analyses extension guidelines for scoping reviews (PRISMA-Scr). Comprehensive search on MEDLINE and Embase was carried out, to include all relevant studies published during last 5 years. Twenty-seven studies were included in analysis. The barriers to SSC implementation were classified into 5 main groups, with further subdivisions in each. RESULTS: The results of review revealed that there are 5 major barriers to SSC at the following levels: organizational, checklist, individual, technical, and implementation. Each of these major barriers, on further evaluation, was found to have more than one contributing factors. All these factors were analyzed individually. CONCLUSIONS: This rapid scoping review has consolidated data, which may pave the way for experts to further examine steps that might be taken locally or globally in order that the WHO SSC to successfully achieve all its desired goals.

Cavitating Lung Disease Associated With Sudden Death.

CASE PRESENTATION: A 16-year-old boy presented with 6 days of left iliac fossa pain. He had a medical history of right subtalar dislocation and appendicitis requiring laparotomy 3 years earlier, complicated by wound dehiscence. His family history was significant for his brother's sudden death 3 weeks prior after a 12-month illness with intermittent epigastric pain, weight loss, and hemoptysis. Travel history was significant for travel to the Philippines 3 years prior, in which he spent time in the hospital for appendicitis.

Machine learning for emerging infectious disease field responses.

Emerging infectious diseases (EIDs), including the latest COVID-19 pandemic, have emerged and raised global public health crises in recent decades. Without existing protective immunity, an EID may spread rapidly and cause mass casualties in a very short time. Therefore, it is imperative to identify cases with risk of disease progression for the optimized allocation of medical resources in case medical facilities are overwhelmed with a flood of patients. This study has aimed to cope with this challenge from the aspect of preventive medicine by exploiting machine learning technologies. The study has been based on 83,227 hospital admissions with influenza-like illness and we analysed the risk effects of 19 comorbidities along with age and gender for severe illness or mortality risk. The experimental results revealed that the decision rules derived from the machine learning based prediction models can provide valuable guidelines for the healthcare policy makers to develop an effective vaccination strategy. Furthermore, in case the healthcare facilities are overwhelmed by patients with EID, which frequently occurred in the recent COVID-19 pandemic, the frontline physicians can incorporate the proposed prediction models to triage patients suffering minor symptoms without laboratory tests, which may become scarce during an EID disaster. In conclusion, our study has demonstrated an effective approach to exploit machine learning technologies to cope with the challenges faced during the outbreak of an EID.

Interprofessional educators' competencies, assessment, and training - IPEcat: protocol of a global consensus study.

Contemporary practice in interprofessional education (IPE) has evolved predominantly focusing on the competencies for interprofessional collaboration (IPC) that learners must acquire. Competencies that educators need to successfully deliver IPC have been overlooked. This lack of attention is further confounded by a field replete with inconsistent terminology and standards and no global consensus on the core competencies needed for IPE facilitation. There are no globally accepted tools to assess interprofessional educators' competencies nor are there established training programmes that might be used as the basis for a collective global approach to these issues. The International Working Group for Interprofessional Educators Competencies, Assessment, and Training (IWG_IPEcat) seeks to address this gap using a sequential mixed-method approach, to deliver globally developed, empirically derived tools to foster IPE educator competencies. This article presents the protocol of the research project.

Lethal giant basal cell carcinoma.

Basal cell carcinomas are the most common malignancy in Caucasian populations with a very low predisposition to metastatic disease and an excellent prognosis if appropriately treated. Given the rarity of a lethal outcome two cases are reported. Case 1: A 61-year-old reclusive man who had an untreated facial basal cell carcinoma for 10 years died of hypothermia and sepsis complicating the extensively ulcerated and infected tumour. He also had underlying cardiomegaly, ischaemic heart disease and chronic obstructive pulmonary disease. Case 2: A 60-year-old man who had an untreated lower lumbar basal cell carcinoma for 14 years died of sepsis, inanition and pulmonary thromboembolism (due to a right-sided deep venous thrombosis) complicating the deeply ulcerated tumour. Untreated giant basal cell carcinoma may uncommonly present for medicolegal assessment with complex pathophysiological lethal mechanisms. The possibility of Diogenes syndrome should be considered.

Macroscopic identification of visceral titanium pigment in an intravenous drug user.

Autopsy findings in intravenous drug addicts are quite variable and may involve a number of organ systems. Reports of the macroscopic identification at autopsy of components of tablets that have been crushed and injected are, however, exceedingly rare. The case of 34-year-old man who died of zolpidem toxicity on a background of pulmonary hypertension attributed to intravenous injections of crushed tablets is described. A very unusual finding was very fine white stippling on the cut surfaces of both the liver and spleen which was shown on energy-dispersive x-ray spectroscopy (EDS) to be titanium dioxide most likely from the coating of the zolpidem tablets. This case is significant in demonstrating titanium dioxide accumulation within organs at both macroscopic and microscopic levels, with confirmation of exposure by EDS analysis. The clinical significance of exposure to such high levels of titanium dioxide is unclear.