BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

Opioid therapy is the cornerstone of treatment for acute procedural and postoperative pain and is regularly prescribed for severe and debilitating chronic pain conditions. Although beneficial for many patients, opioid therapy may have side effects, limited efficacy, and potential negative outcomes. Multidisciplinary pain management treatments incorporating pharmacological and integrative non-pharmacological therapies have been shown to be effective in acute and chronic pain management for pediatric populations. A multidisciplinary approach can also benefit psychological functioning and quality of life, and may have the potential to reduce reliance on opioids. The aims of this paper are to: (1) provide a brief overview of a multidisciplinary pain management approach for pediatric patients with acute and chronic pain, (2) highlight the mechanisms of action and evidence base of commonly utilized integrative non-pharmacological therapies in pediatric multidisciplinary pain management, and (3) explore the opioid sparing effects of multidisciplinary treatment for pediatric pain.

As awareness increases about the side effects of opioids and risks of misuse, opioid use and appropriate weaning of opioid therapies have become topics of significant clinical relevance among pediatric populations. Critically ill hospitalized neonates, children, and adolescents routinely receive opioids for analgesia and sedation as part of their hospitalization, for both acute and chronic illnesses. Opioids are frequently administered to manage pain symptoms, reduce anxiety and agitation, and diminish physiological stress responses. Opioids are also regularly prescribed to youth with chronic pain. These medications may be prescribed during the initial phase of a diagnostic workup, during an emergency room visit; as an inpatient, or on an outpatient basis. Following treatment for underlying pain conditions, it can be challenging to appropriately wean and discontinue opioid therapies. Weaning opioid therapy requires special expertise and care to avoid symptoms of increased pain, withdrawal, and agitation. To address this challenge, there have been enhanced efforts to implement opioid-reduction during pharmacological therapies for pediatric pain management. Effective pain management therapies and their outcomes in pediatrics are outside the scope of this paper. The aims of this paper were to: (1) Review the current practice of opioid-reduction during pharmacological therapies; and (2) highlight concrete opioid weaning strategies and management of opioid withdrawal.

In 2018, 29 states allow the use of medicinal marijuana. In these states, minors, with parental permission, are granted access. Use has increased in some states, although there remains a paucity of clear evidence regarding usefulness and dosing. There are 2 Food and Drug Administration–approved synthetic derivatives. One purified compound was just approved by the Food and Drug Administration, and another is undergoing Food and Drug Administration review. This article will review the literature regarding the use of each of these compounds in the literature, with particular attention to data in children. The history, known pharmacology, data from nonmedicinal use, current evidence, and anesthetic considerations will be described.