Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain

INTRODUCTION: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches. METHODS AND ANALYSIS: Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function. ETHICS AND DISSEMINATION: The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories. TRIAL REGISTRATION NUMBER: NCT04285112

Mechanisms of urethral continence and their clinical application

Controversy about the basic nature of urethral function does not preclude accurate clinical assessment of disorders of function. While the precise method of treatment of urethral continence dysfunction varies from institution to institution, the basic techniques are quite similar. It is the application of a treatment method to a particular case which causes difficulty. It is important, therefore, to have some understanding of the functional elements in the urethral continence mechanism to be able to determine which element does not function. Most cases of intractable incontinence are associated with poor function of the involuntary part of the sphincter. In general, peak urethral closing pressures are unrelated to continence function unless there is no pressure at all.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47059/1/345_2004_Article_BF00326702.pd

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Mitochondrial Disease and Anesthesia

It is increasingly common for children with mitochondrial disease to undergo surgery and anesthesia. Although many different anesthetics have been used successfully for these patients, serious, unexpected complications have occurred during and following anesthetic exposure. This has led to the widespread opinion among anesthesiologists that mitochondrial patients are at increased risk from the stress of surgery and anesthesia. Defects in function of the mitochondrial electron transport chain can lead to striking hypersensitivity to volatile anesthetics in children. Despite this striking finding, the connection between mitochondrial function and response to anesthetics is unknown. We review here the anesthetic considerations for patients with mitochondrial defects. In addition, we present an approach to anesthetic care of these patients at our institutions

Opioids for chronic non-cancer pain in children and adolescents

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children\u27s persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children\u27s pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children\u27s pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Opioids are used worldwide for the treatment of pain. They bind to opioid receptors in the central nervous system (mu, kappa, delta, and sigma) and can be agonists, antagonists, mixed agonist-antagonists, or partial agonists. Opioids are generally available in healthcare settings across most high-income countries, but access may be restricted in low- and middle-income countries. For example, opioids currently available in the UK include: buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol. Opioids are used in varying doses (generally based on body weight for paediatric patients) by means of parenteral, transmucosal, transdermal, or oral administration (immediate release or modified release). To achieve adequate pain relief in children using opioids, with an acceptable grade of adverse effects, the recommended method is a lower dose gradually titrated to effect in the child. OBJECTIVES: To assess the analgesic efficacy and adverse events of opioids used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing opioids with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat, using standard methods. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a \u27Summary of findings\u27 table. MAIN RESULTS: No studies were eligible for inclusion in this review. We rated the quality of the evidence as very low. We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome. AUTHORS\u27 CONCLUSIONS: There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronicnon-cancer pain in children and adolescents. We are unable to comment about efficacy or harm from the use of opioids to treat chronic non-cancer pain in children and adolescents.We know from adult randomised controlled trials that some opioids, such as morphine and codeine, can be effective in certain chronic pain conditions.This means that no conclusions could be made about efficacy or harm in the use of opioidsto treat chronic non-cancer pain in children and adolescents

Evaluating Telehealth Implementation in the Context of Pediatric Chronic Pain Treatment during COVID-19

Telehealth has emerged as a promising healthcare delivery modality due to its ability to ameliorate traditional access-level barriers to treatment. In response to the onset of the novel coronavirus (COVID-19) pandemic, multidisciplinary pain clinics either rapidly built telehealth infrastructure from the ground up or ramped up existing services. As the use of telehealth increases, it is critical to develop data collection frameworks that guide implementation. This applied review provides a theoretically-based approach to capitalize on existing data sources and collect novel data to inform virtually delivered care in the context of pediatric pain care. Reviewed multisource data are (1) healthcare administrative data; (2) electronic chart review; (3) clinical health registries; and (4) stakeholder feedback. Preliminary telehealth data from an interdisciplinary pediatric chronic pain management clinic (PPMC) serving youth ages 8–17 years are presented to illustrate how relevant implementation outcomes can be extracted from multisource data. Multiple implementation outcomes were assessed, including telehealth adoption rates, patient clinical symptoms, and mixed-method patient-report telehealth satisfaction. This manuscript provides an applied roadmap to leverage existing data sources and incorporate stakeholder feedback to guide the implementation of telehealth in pediatric chronic pain settings through and beyond COVID-19. Strengths and limitations of the modeled data collection approach are discussed within the broader context of implementation science