Neurodevelopment of children exposed to prolonged anesthesia in infancy: GABA study interim analysis of resting-state brain networks at 2, 4, and 10-months old.

BACKGROUND: Previous studies have raised concerns regarding neurodevelopmental impacts of early exposures to general anesthesia and surgery. Electroencephalography (EEG) can be used to study ontogeny of brain networks during infancy. As a substudy of an ongoing study, we examined measures of functional connectivity in awake infants with prior early and prolonged anesthetic exposures and in control infants. METHODS: EEG functional connectivity was assessed using debiased weighted phase lag index at source and sensor levels and graph theoretical measures for resting state activity in awake infants in the early anesthesia (n = 26 at 10 month visit, median duration of anesthesia = 4 [2, 7 h]) and control (n = 38 at 10 month visit) groups at ages approximately 2, 4 and 10 months. Theta and low alpha frequency bands were of primary interest. Linear mixed models incorporated impact of age and cumulative hours of general anesthesia exposure. RESULTS: Models showed no significant impact of cumulative hours of general anesthesia exposure on debiased weighted phase lag index, characteristic path length, clustering coefficient or small-worldness (conditional R2 0.05-0.34). An effect of age was apparent in many of these measures. CONCLUSIONS: We could not demonstrate significant impact of general anesthesia in the first months of life on early development of resting state brain networks over the first postnatal year. Future studies will explore these networks as these infants grow older.

Rescue designs in analgesic trials from 0 to 2 years of age: scoping review.

Pediatric analgesic trials are challenging, especially in newborns and infants. Following an FDA-academic consensus meeting, we analyzed pragmatic rescue designs in postoperative trials of local anesthetics, acetaminophen, opioids, and NSAIDs involving children ages 0-2 years and assessed surgical volumes to provide trial design recommendations. Searches of PubMed, Embase, CINAHL, The Cochrane Library, and Web of Science were conducted. A scoping approach identified trends in analgesic trials with an emphasis on randomized controlled trials (RCTs) utilizing immediate rescue designs. Age-specific surgical volumes were estimated from French national databases. Of 3563 studies identified, 23 RCTs used study medication(s) of interest and immediate rescue paradigms in children ages 0-2 years. A total of 270 studies met at least one of these criteria. Add-on and head-to-head designs were common and often used sparing of non-opioid or opioid rescue medication as a primary outcome measure. According to French national data, inguinal and penile surgeries were most frequent in ages 1 month to 2 years; abdominal and thoracic surgeries comprise approximately 75% of newborn surgeries. Analgesic trials with rescue sparing paradigm are currently sparse among children ages 0-2 years. Future trials could consider age-specific surgical procedures and use of add-on or head-to-head designs. IMPACT: Clinical trials of analgesic medications have been challenging in pediatrics, especially in the group from newborns to 2 years of age. Following an FDA-academic workshop, we analyzed features of completed analgesic trials in this age group. Studies using immediate rescue in placebo control, add-on, and head-to-head trial designs are pragmatic approaches that can provide important information regarding clinical effectiveness, side effects, and safety. Using a French national dataset with a granular profile of inpatient, outpatient, and short-stay surgeries, we provide information to future investigators on relative frequencies of different operations in neonates and through the first 2 years of life.

Clinical Characterization of Pediatric Erythromelalgia: A Single-Center Case Series.

Erythromelalgia is a descriptive term for severe burning pain and erythema in the distal extremities relieved by cold and exacerbated by heat. Pediatric case series to date are relatively small. We extracted and analyzed medical record data for 42 pediatric patients to describe clinical characteristics, associated conditions, and responses to treatments. Informed consent was obtained according to an IRB-approved protocol that included gene discovery. Three patients had confirmed Nav1.7 sodium channelopathies, with six additional patients under investigation with novel gene candidates. There was a female predominance (2.5:1), and the median onset age was 12 years (IQR = 3-14). Patients saw a median of three specialists (IQR = 2-3) for a diagnosis. The majority (90%) reported bilateral symptoms. Cooling methods usually provided partial relief, while heat and exercise exacerbated pain. No medication appeared to be consistently effective; commonly prescribed medications included sodium channel blockers (n = 37), topical analgesics (n = 26), gabapentin (n = 22), and aspirin (n = 15). Based on the currently published literature, we believe this cohort is the largest pediatric study of erythromelalgia to date. Many findings are consistent with those of previously published case series. Work is in progress to establish a prospective cohort and multi-center registry.

Late-presenting dural leak following spine fusion in the pediatric population.

PURPOSE: The purpose is to describe how patients with a late-presenting dural leak (LPDL) after posterior spinal fusion (PSF) was diagnosed and treated at a single institution. METHODS: Of the 1991 patients who underwent a PSF between 2010 and 2018, 6 patients were identified with a clinical course consistent with a potential LPDL. RESULTS: Six patients with median age 16.9 years had onset of headache ranging 1-12 weeks postoperatively (median 6.5 weeks). All six patients presented with positional headache, and half (3/6) presented with emesis. 5/6 patients underwent contrast brain MRI, which demonstrated pachymeningeal enhancement. 4/5 patients with dural enhancement went on to have CT myelogram. Five patients had a CT myelogram, which identified a dural leak in all patients and localized the leak in four of five patients. All patients underwent an epidural blood patch, which resolved the pain in five patients. One patient without relief underwent revision surgery with removal of a medially placed screw and fibrin glue placement resolving symptoms. CONCLUSIONS: Postoperative dural leaks associated with PSF may present in a delayed fashion. The majority of leaks were not associated with screw malposition. In diagnosing patients with suspected LPDL, we suggest brain MRI with contrast as a first step. Most patients with pachymeningeal enhancement shown on contrast brain MRI had dural leaks that were identified through CT myelograms. For patients with a dural leak, if there is no disruption from screws, a blood patch appears to be an effective treatment. LEVEL OF EVIDENCE: IV.

A framework for individualized splice-switching oligonucleotide therapy.

Splice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases1, but the systematic identification of such individuals remains a challenge. Here we performed whole-genome sequencing analyses to characterize genetic variation in 235 individuals (from 209 families) with ataxia-telangiectasia, a severely debilitating and life-threatening recessive genetic disorder2,3, yielding a complete molecular diagnosis in almost all individuals. We developed a predictive taxonomy to assess the amenability of each individual to splice-switching ASO intervention; 9% and 6% of the individuals had variants that were 'probably' or 'possibly' amenable to ASO splice modulation, respectively. Most amenable variants were in deep intronic regions that are inaccessible to exon-targeted sequencing. We developed ASOs that successfully rescued mis-splicing and ATM cellular signalling in patient fibroblasts for two recurrent variants. In a pilot clinical study, one of these ASOs was used to treat a child who had been diagnosed with ataxia-telangiectasia soon after birth, and showed good tolerability without serious adverse events for three years. Our study provides a framework for the prospective identification of individuals with genetic diseases who might benefit from a therapeutic approach involving splice-switching ASOs.

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier-White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey-Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population-based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

Electroencephalographic delta and alpha oscillations reveal phase-amplitude coupling in paediatric patients undergoing sevoflurane-based general anaesthesia.

BACKGROUND: Sevoflurane-induced anaesthesia generates frontal alpha oscillations as early as 6 months of age, whereas strong delta oscillations are present at birth. In adults, delta oscillations and alpha oscillations are coupled: the phase of delta waves modulates the amplitude of alpha oscillations in a phenomenon known as phase-amplitude coupling. We hypothesise that delta-alpha phase-amplitude coupling exists in young children and is a feature of sevoflurane-based general anaesthesia distinct from emergence after anaesthesia. METHODS: Electroencephalographic data from 31 paediatric patients aged 10 months to 3 yr undergoing elective surgery with sevoflurane-based anaesthesia were analysed retrospectively. Delta-alpha phase-amplitude coupling was evaluated during maintenance of anaesthesia and during emergence. RESULTS: Delta-alpha phase-amplitude coupling was observed in the study population. Strength of phase-amplitude coupling, represented by the delta-alpha mean amplitude vector, was greater during general anaesthesia than during emergence (Wilcoxon paired signed-rank test, Z=3.107, P=0.002). Frontal alpha amplitude during anaesthesia was not uniformly distributed across all delta phases. During general anaesthesia, alpha power was restricted to the positive phase of the delta wave (omnibus circular uniformity, general anaesthesia: P<0.001, mean phase: 114º; 99% confidence interval: 90º-139º; emergence: P=0.35, mean phase 181º, 99% confidence interval: 110º-253º). CONCLUSIONS: Sevoflurane-based anaesthesia is associated with delta-alpha phase-amplitude coupling in paediatric patients. These findings improve our understanding of cortical dynamics in children undergoing general anaesthesia, which might improve paediatric intraoperative depth of anaesthesia monitoring techniques.

Emerging functional connectivity patterns during sevoflurane anaesthesia in the developing human brain.

BACKGROUND: Spectral-based EEG is used to monitor anaesthetic state during surgical procedures in adults. Spectral EEG features that can resemble the patterns seen in adults emerge in children after the age of 10 months and cannot distinguish wakefulness and anaesthesia in the youngest children. There is a need to explore alternative EEG measures. We hypothesise that functional connectivity is one of the measures that can help distinguish between consciousness states in children. METHODS: An EEG data set of children undergoing sevoflurane general anaesthesia (age 0-3 yr) was reanalysed using debiased weighted phase lag index as a measure of functional connectivity in wakefulness (n=38) and anaesthesia (n=73). Network topology measures were compared between states in 0- to 6-, 6- to 10-, and >10-month-old children. RESULTS: Functional connectivity was reduced in anaesthesia vs wakefulness in delta band (n=cluster of 17 significant connections; P=0.013; 58% connections surviving thresholding in wakefulness and 49% in anaesthesia). Network density and node degree were lower in anaesthesia even in the youngest children (0.57 in wakefulness; 0.48 in anaesthesia; t [9]=3.39; P=0.029; G=0.98; confidence interval [CI] [0.25-1.77]). Modularity was higher in anaesthesia (0-6 months: 0.16 in wakefulness and 0.19 in anaesthesia, t [9]=-2.95, P=0.04, G=-0.85, CI [-1.60 to -0.16]; >10 months: 0.16 vs 0.21, t [13]=-6.45, P<0.001, G=-1.62, CI [-2.49 to -0.85]) and decreased with age (ρ [73]=-0.456; P<0.001). CONCLUSIONS: Anaesthesia modulates functional connectivity. Increased segregation into a more modular structure in anaesthesia decreases with age as adult-like features develop. These findings advance our understanding of the network architecture underlying the effects of anaesthesia on the developing brain.

Ultrasound-guided spinal anesthesia in infants: a narrative review.

BACKGROUND/IMPORTANCE: Infant spinal anesthesia has many potential benefits. However, the delivery of infant spinal anesthesia is technically challenging. The landmark-based technique has not changed for over a century. Advancements in ultrasound technology may provide an opportunity to improve infant spinal procedures. OBJECTIVE: Our primary objective is to conduct a comprehensive review of the current literature on ultrasonography for spinal anesthesia in infants. Given the narrow scope of this topic, our secondary objective is to review the current literature on ultrasonography for lumbar puncture in infants. EVIDENCE REVIEW: We reviewed all papers related to the use of ultrasound for infant spinal anesthesia. Two large databases were searched with key terms. Eligibility criteria were full-text articles in English. For our secondary objective, we searched one large database for key terms relating to ultrasonography and infant lumbar puncture. Eligibility criteria were the same. FINDINGS: Our primary search retrieved six articles. These consisted of four review articles, one case report, and one retrospective observational study. Our secondary search retrieved fourteen articles. These consisted of five randomized control trials, four prospective studies, three retrospective studies, and two review papers. CONCLUSIONS: Ultrasound yields high-quality images of the infant spine. Most literature regarding ultrasound for infant spinal procedures arises from emergency medicine or interventional radiology specialties. The literature on ultrasound for infant spinal anesthesia is extremely limited, but shows promise. Future studies are needed in order to determine whether ultrasound can improve the success rate for delivery of infant spinal anesthesia.

Tactile sensitivity and motor coordination in infancy: Effect of age, prior surgery, anaesthesia & critical illness.

BACKGROUND: Tactile sensitivity in the infant period is poorly characterized, particularly among children with prior surgery, anaesthesia or critical illness. The study aims were to investigate tactile sensitivity of the foot and the associated coordination of lower limb motor movement in typically developing infants with and without prior hospital experience, and to develop feasible bedside sensory testing protocols. MATERIALS AND METHODS: A prospective, longitudinal study in 69 infants at 2 and 4 months-old, with and without prior hospital admission. Mechanical stimuli were applied to the foot at graded innocuous and noxious intensities. Primary outcome measures were tactile and nociceptive threshold (lowest force required to evoke any leg movement, or brisk leg withdrawal, respectively), and specific motor flexion threshold (ankle-, knee-, hip-flexion). Secondary analysis investigated (i) single vs multiple trials reliability, and (ii) the effect of age and prior surgery, anaesthesia, or critical illness on mechanical threshold. RESULTS: Magnitude of evoked motor activity increased with stimulus intensity. Single trials had excellent reliability for knee and hip flexion at age 1-3m and 4-7m (ICC range: 0.8 to 0.98, p >0.05). Nociceptive threshold varied as a function of age. Tactile sensitivity was independent of age, number of surgeries, general anaesthesia and ICU stay. CONCLUSIONS: This brief sensory testing protocol may reliably measure tactile and nociceptive reactivity in human infants. Age predicts nociceptive threshold which likely reflects ongoing maturation of spinal and supraspinal circuits. Prior hospital experience has a negligible global effect on sensory processing demonstrating the resilience of the CNS in adverse environments.

Nusinersen for Patients With Spinal Muscular Atrophy: 1415 Doses via an Interdisciplinary Institutional Approach.

BACKGROUND: Spinal deformity and prior spinal fusion pose technical challenges to lumbar puncture (LP) for nusinersen administration for patients with spinal muscular atrophy (SMA). In this retrospective study over two study phases, we evaluated (1) factors associated with difficult LP or unscheduled requirement for image guidance and (2) effectiveness of a triage pathway for selective use of image guidance and nonstandard techniques, particularly for patients with spinal instrumentation/fusion to the sacrum. METHODS: With institutional review board approval, electronic health records, imaging, and administrative databases were analyzed for patients receiving nusinersen from January 2012 through September 2021. Descriptive statistics and univariate analyses were used. RESULTS: From January 2012 to March 2018 (phase 1), among 82 patients with SMA, 461 of 464 (99.4%) LP attempts were successful. Univariate analyses associated difficulty with prior spinal instrumentation, higher body mass index, and severity of the spinal deformity. Based on this experience, starting in April 2018 (phase 2), 125 patients were triaged selectively for ultrasound, fluoroscopy, or Dyna computed tomography. Patients with spinal instrumentation/fusion to the sacrum were treated primarily via intrathecal ports (137 doses) or transforaminal LP (55 doses). From April 2018 through September 2021, 704 of 709 (99.3%) LPs were successful. In total from January 2012 to September 2021, 1415 doses were administered. Over 50% of LPs were performed by neurology nurse practitioners without image guidance. Safety outcomes were excellent. CONCLUSIONS: A stratified approach resulted in successful intrathecal nusinersen delivery and efficient resource allocation for patients with SMA, with or without complex spinal anatomy.

Transforaminal lumbar puncture for spinal anesthesia or novel drug administration: a technique combining C-arm fluoroscopy and ultrasound.

BACKGROUND: Lumbar puncture (LP) may be challenging for patients with scoliosis and other conditions following previous posterior fusion and instrumentation from thoracic to sacral levels. Interventional radiologists have described CT approaches to transforaminal LP. We hypothesized that combined C-arm fluoroscopy and ultrasound could be a feasible approach to transforaminal LP for interventional pain physicians and regional anesthesiologists. METHODS: With institutional review board approval, we reviewed medical records and imaging of six patients with spinal muscular atrophy and prior spine fusion. Non-cutting needles of 24 or 25 gage were advanced through 20-gage introducers. Prior imaging guided selection of a preferred side and spinal level. Initial procedures were performed in the interventional radiology suite. Subsequent procedures were performed in an operating room (OR). We report on technical success and complications and describe a case using this approach for spinal anesthesia. RESULTS: Six patients underwent a total of 54 transforaminal LPs, including 51 for administration of the antisense oligonucleotide nusinersen, 2 for myelography, and 1 for spinal anesthesia; 45 of these procedures were performed using OR C-arm fluoroscopy and ultrasound. Transient paresthesias and short-term headaches occurred; none required intervention. No other complications were noted. CONCLUSIONS: Transforaminal LP appears technically feasible for patients with full-spine fusions using a straight-needle approach with combined fluoroscopy and ultrasound guidance. Larger case series and prospective studies may better define the success rates, risks, and benefits of this approach relative to alternative approaches to intrathecal access for patients with previous long-segment posterior spine fusions.

Modified Sensory Testing in Non-verbal Patients Receiving Novel Intrathecal Therapies for Neurological Disorders.

Several neurological disorders may be amenable to treatment with gene-targeting therapies such as antisense oligonucleotides (ASOs) or viral vector-based gene therapy. The US FDA has approved several of these treatments; many others are in clinical trials. Preclinical toxicity studies of ASO candidates have identified dose-dependent neurotoxicity patterns. These include degeneration of dorsal root ganglia, the cell bodies of peripheral sensory neurons. Quantitative sensory testing (QST) refers to a series of standardized mechanical and/or thermal measures that complement clinical neurologic examination in detecting sensory dysfunction. QST primarily relies on patient self-report or task performance (i.e., button-pushing). This brief report illustrates individualized pragmatic approaches to QST in non-verbal subjects receiving early phase investigational intrathecal drug therapies as a component of clinical trial safety protocols. Three children with neurodevelopmental disorders that include Neuronal Ceroid Lipofuscinosis Type 7, Ataxia-Telangiectasia, and Epilepsy of Infancy with Migrating Focal Seizures are presented. These case studies discuss individualized testing protocols, accounting for disease presentation, cognitive and motor function. We outline specific considerations for developing assessments for detecting changes in sensory processing in diverse patient groups and safety monitoring trials of early phase investigational intrathecal drug therapies. QST may complement information obtained from the standard neurologic examination, electrophysiologic studies, skin biopsies, and imaging. QST has limitations and challenges, especially in non-verbal subjects, as shown in the three cases discussed in this report. Future directions call for collaborative efforts to generate sensory datasets and share data registries in the pediatric neurology field.

Standardizing Opioid Prescribing in a Pediatric Hospital: A Quality Improvement Effort.

BACKGROUND: Opioids are indicated for moderate-to-severe pain caused by trauma, ischemia, surgery, cancer and sickle cell disease, and vaso-occlusive episodes (SCD-VOC). There is only limited evidence regarding the appropriate number of doses to prescribe for specific indications. Therefore, we developed and implemented an opioid prescribing algorithm with dosing guidelines for specific procedures and conditions. We aimed to reach and sustain 90% compliance within 1 year of implementation. METHODS: We conducted this quality improvement effort at a pediatric academic quaternary care institution. In 2018, a multidisciplinary team identified the need for a standard approach to opioid prescribing. The algorithm guides prescribers to evaluate the medical history, physical examination, red flags, pain type, and to initiate opioid-sparing interventions before prescribing opioids. Opioid prescriptions written between January 2015 and September 2020 were included. Examples from 2 hospital departments will be highlighted. Control charts for compliance with guidelines and variability in the doses prescribed are presented for selected procedures and conditions. RESULTS: Over 5 years, 83 037 opioid prescriptions in 53 804 unique patients were entered electronically. The encounters with ≥1 opioid prescription decreased from 48% to 25% between 2015 and 2019. Compliance with the specific guidelines increased to ∼85% for periacetabular osteotomies and SCD-VOC and close to 100% for anterior-cruciate ligament surgery. In all 3 procedures and conditions, variability in the number of doses prescribed decreased significantly. CONCLUSION: We developed an algorithm, guidelines, and a process for improvement. The number of opioid prescriptions and variability in opioid prescribing decreased. Future evaluation of specific initiatives within departments is needed.

Mendelian etiologies identified with whole exome sequencing in cerebral palsy.

OBJECTIVES: Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single-gene disorders is under-characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP. METHODS: We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non-cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline. RESULTS: We included 50 probands in this analysis (20 females, 30 males). Twenty-four had cryptogenic CP, 20 had non-cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic-ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty-six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST-related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non-cryptogenic CP (n = 3/20) had a Mendelian disorder on WES. INTERPRETATION: WES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors.

The Effectiveness of Cancer Pain Management in a Tertiary Hospital Outpatient Pain Clinic in Thailand: A Prospective Observational Study.

Objectives: The objective was to examine the effectiveness of the updated approach. Methods: With IRB approval, outpatients with cancer were enrolled from January to December 2018. Assessments were recorded at baseline and three consecutive visits (BL, FU1, FU2, and FU3), including Numerical Rating Scale (NRS), the Brief Pain Inventory (BPI), the Edmonton Symptom Assessment System (ESAS), side effects, and analgesic use. The primary outcome was a favorable response, defined as an NRS decrease more than 30% or NRS <4. Secondary outcomes included trends over time in BPI, ESAS, side effects, and analgesic use. Pain response predictors at FU3 were analyzed using logistic regression. Results: Among 150 patients, 72 (48%) completed follow-ups. Of these, 61% achieved a favorable response at FU3. Pain interference diminished at all visits relative to baseline (p < 0.05). Median morphine equivalent daily dosage (MEDD) at BL was 20 mg/day, with a statistically significant, but clinically modest increase to 26.4 mg/day at FU3. Radiation therapy during pain care was a predictor of pain responders. Conclusion: The current Siriraj multidisciplinary approach provided effective relief of pain and stabilization of other cancer-related symptoms. Radiation therapy during pain care can be used to predict pain outcomes. Ongoing improvement domains were identified and considered in the context of cultural, economic, and geographic factors.

Racial and Ethnic Disparities in Pain Management of Children With Limb Fractures or Suspected Appendicitis: A Retrospective Cross-Sectional Study.

Objective: To evaluate whether racial/ethnical differences in analgesia administration existed in two different cohorts of children with painful conditions: children with either limb fracture or suspected appendicitis. Methods: Retrospective cross-sectional analysis of children visiting a pediatric emergency department (Boston Children Hospital) for limb fracture or suspected appendicitis from 2011 to 2015. We computed the proportion of children that received any analgesic treatment and any opioid analgesia. We performed multivariable logistic regressions to investigate race/ethnicity differences in analgesic and opioid administration, after adjusting for pain score, demographics and visit covariates. Results: Among the 8,347 children with a limb fracture and the 4,780 with suspected appendicitis, 65.0 and 60.9% received any analgesic treatment, and 35.9 and 33.4% an opioid analgesia, respectively. Compared to White non-Hispanic Children, Black non-Hispanic children and Hispanic children were less likely to receive opioid analgesia in both the limb fracture cohort [Black: aOR = 0.61 (95% CI, 0.50-0.75); Hispanic aOR = 0.66 (95% CI, 0.55-0.80)] and in the suspected appendicitis cohort [Black: aOR = 0.75 (95% CI, 0.58-0.96); Hispanic aOR = 0.78 (95% CI, 0.63-0.96)]. In the limb fracture cohort, Black non-Hispanic children and Hispanic children were more likely to receive any analgesic treatment (non-opioid or opioid) than White non-Hispanic children [Black: aOR = 1.63 (95% CI, 1.33-2.01); Hispanic aOR = 1.43 (95% CI, 1.19-1.72)]. Conclusion: Racial and ethnic disparities exist in the pain management of two different painful conditions, which suggests true inequities in health care delivery. To provide equitable analgesic care, emergency departments should monitor variation in analgesic management and develop appropriate universal interventions.

Trends in Gabapentin and Pregabalin Prescribing in a Tertiary Pediatric Medical Center.

OBJECTIVES: Analgesic medications are commonly prescribed in pediatrics, with prescribing practices frequently extrapolated from adult trials. Gabapentinoids (gabapentin and pregabalin) are widely used as analgesics but are labeled in pediatrics only for epilepsy. We aim to (1) define trends in pediatric gabapentinoid prescribing (label and off-label) over 7 years, and (2) evaluate use in chronic pain clinic (CPC) patients during 2018. METHODS: Retrospective data from a tertiary-care pediatric hospital were collected between 2013 and 2019. Annual numbers of gabapentinoid prescriptions were stratified by prescriber specialty. Additional information about gabapentinoid prescribing in the CPC was manually collected from initial clinic notes in 2018. RESULTS: There were 15 808 outpatient prescriptions for gabapentinoids among 5172 patients over 7 years. Of these, 93% were gabapentin and 7% were pregabalin. Numbers of patients receiving gabapentin and pregabalin prescriptions increased by 1.4- and 1.3-fold, respectively, between 2013 and 2019. Few prescriptions were done for patients with a previous epilepsy diagnosis (in 2019, 16% for gabapentin and 13% for pregabalin). Approximately 28% of 650 CPC new patients were prescribed gabapentin or pregabalin before referral. Among those, 44% had discontinued the medication because of adverse events (35%), inefficacy (46%), or both (5%). Most side effects reported were mild to moderate. Diagnoses at first visit were diverse, not limited to neuropathic pain conditions, and did not differ between patients receiving or not receiving gabapentinoid prescriptions. CONCLUSIONS: In our hospital, gabapentinoids are commonly prescribed off-label for diverse indications, including chronic pain. Future research is needed to evaluate gabapentinoid efficacy in these indications.