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Background: Many patients report a wearing-off phenomenon with monoclonal antibody treatment for multiple sclerosis in which perceived benefits wear off before the next dose is due. Objectives: To determine prevalence of the wearing-off effect, symptoms experienced, impact on treatment satisfaction, and associated patient characteristics. Methods: Patients receiving natalizumab, ocrelizumab, ofatumumab, or rituximab at a tertiary multiple sclerosis center were invited to take an online survey interrogating their monoclonal antibody experience. Additional history and patient characteristic data were collected. Logistic regression was used to determine if patient characteristics predicted the wearing-off effect and linear regression to evaluate the impact of the wearing-off effect on treatment satisfaction. The models were adjusted for age, disease duration, race, sex, body mass index, education, and depression as measured by the Patient Health Questionnaire-9. Results: We received 258 qualifying responses and 141 (54.7%) patients reported the wearing-off phenomenon. The most common symptom was fatigue (47.7%). Higher Patient Health Questionnaire-9 scores were significantly associated with the wearing-off phenomenon (OR = 1.02, p = 0.005). The wearing-off effect (ß = -0.52, p = 0.04) and higher Patient Health Questionnaire-9 (ß = -0.09, p < 0.01) scores were associated with significantly reduced treatment satisfaction. Conclusion: The wearing-off phenomenon is common, associated with depression, and reduces treatment satisfaction. Research addressing mitigation strategies is needed.

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BACKGROUND: Autism spectrum disorder (ASD) is a neurocognitive disorder characterized by impairments in communication and socialization. There are little data comparing the differences in perioperative outcomes in children with and without ASD. We hypothesized that children with ASD would have higher postoperative pain scores than those without ASD. METHODS: Pediatric patients undergoing ambulatory tonsillectomy/adenoidectomy, ophthalmological surgery, general surgery, and urologic procedures between 2016 and 2021 were included in this retrospective cohort study. ASD patients, defined by International Classification of Diseases-9/10 codes, were compared to controls utilizing inverse probability of treatment weighting based on surgical category/duration, age, sex, race and ethnicity, anesthetizing location, American Society of Anesthesiology physical status, intraoperative opioid dose, and intraoperative dexmedetomidine dose. The primary outcome was the maximum postanesthesia care unit (PACU) pain score, and secondary outcomes included premedication administration, behavior at induction, PACU opioid administration, postoperative vomiting, emergence delirium, and PACU length of stay. RESULTS: Three hundred thirty-five children with ASD and 11,551 non-ASD controls were included. Maximum PACU pain scores in the ASD group were not significantly higher than controls (median, 5; interquartile range [IQR], 0-8; ASD versus median, 5; IQR, 0-8 controls; median difference [95% confidence interval {CI}] of 0 [-1.1 to 1.1]; P = .66). There was no significant difference in the use of premedication (96% ASD versus 95% controls; odds ratio [OR], 1.5; [95% CI, 0.9-2.7]; P = .12), but the ASD cohort had significantly higher odds of receiving an intranasal premedication (4.2% ASD versus 1.2% controls; OR, 3.5 [95% CI, 1.8-6.8]; P < .001) and received ketamine significantly more frequently (0.3% ASD versus <0.1% controls; P < .001). Children with ASD were more likely to have parental (4.9% ASD versus 1.0% controls; OR, 5 [95% CI, 2.1-12]; P < .001) and child life specialist (1.3% ASD versus 0.1% controls; OR, 9.9 [95% CI, 2.3-43]; P < .001) presence at induction, but were more likely to have a difficult induction (11% ASD versus 3.4% controls; OR, 3.42 [95% CI, 1.7-6.7]; P < .001). There were no significant differences in postoperative opioid administration, emergence delirium, vomiting, or PACU length of stay between cohorts. CONCLUSIONS: We found no difference in maximum PACU pain scores in children with ASD compared to a similarly weighted cohort without ASD. Children with ASD had higher odds of a difficult induction despite similar rates of premedication administration, and significantly higher parental and child life specialist presence at induction. These findings highlight the need for future research to develop evidence-based interventions to optimize the perioperative care of this population.

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There are several benefits to clinical registries as an information repository tool, ultimately lending itself to the acquisition of new knowledge. Registries have the unique advantage of garnering much data quickly and are, therefore, especially helpful for niche populations or low-prevalence diseases. They can be used to inform on the ideal structure, process, or outcome involving an identified population. The data can be used in many ways, for example, as an observational tool to reveal associations or as a basis for framing future research studies or quality improvement projects.

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Pulmonary arteriolar thickening in sudden infant death syndrome has been repeatedly reported but this finding has been challenged. We report a case of a previously healthy 23-day-old infant girl who was witnessed by her parents to die suddenly and unexpectedly. During a routine bottle-feeding, she suddenly began to cry loudly and her face became deep-red and then pale. She became limp and began to gasp. Resuscitation efforts were to no avail. The post-mortem examination, including toxicological studies, screening for inborn errors of metabolism and genetic studies for prolonged Qt syndrome, failed to reveal the cause of death. A more focused study of the lungs showed extensive pulmonary arteriolar thickening. The events in the sudden death of this infant are remarkably similar to deaths in infants with various disorders associated with pulmonary arteriolar thickening. We suggest that this vascular abnormality and associated pulmonary hypertension played a critical role in this infant's death.

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OBJECTIVE: Several studies have found that back- or side-sleeping infants who are inexperienced in prone sleeping are at much higher risk for sudden infant death syndrome (SIDS) when they turn to prone or are placed prone for sleep compared with infants who normally sleep prone. Moreover, such inexperienced infants are more likely to be found in the face-down position at death after being placed prone compared with SIDS infants who are experienced in prone sleeping. We hypothesized that lack of experience in prone sleeping is associated with increased difficulty in changing head position to avoid an asphyxiating sleep environment. METHODS: We studied 38 healthy infants while they slept prone. Half of these were experienced and half were inexperienced in prone sleeping. To create a mildly asphyxiating microenvironment, we placed infants to sleep prone with their faces covered by soft bedding. We recorded inspired CO2 (CO2I), electrocardiogram, and respiration, and we videotaped head movements. Also, we assessed gross motor development (Denver Development Scale). RESULTS: When sleeping prone, with their faces covered by bedding, all infants experienced mild asphyxia as a result of rebreathing. All aroused and attempted escape from this environment. Infants used 3 stereotyped head-repositioning strategies. The least effective was nuzzling into the bedding with occasional brief head lifts. More effective were head lifts combined with a head turn. Some infants, however, could turn only to 1 side, right or left. Infants who were inexperienced in prone sleeping had less effective protective behaviors than experienced infants. Infant age did not correlate with efficacy of protective behaviors. Infants who were experienced in prone sleep had advanced gross motor development compared with inexperienced infants. CONCLUSION: Infants who are inexperienced in prone sleeping have decreased ability to escape from asphyxiating sleep environments when placed prone. These observations potentially explain the increased risk associated with prone sleep in infants who are inexperienced. The increased occurrence of the face-down position in such infants is also potentially explained. These findings suggest that airway protective behaviors may be acquired through the mechanism of operant conditioning (learning).

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OBJECTIVE: Infants who sleep prone and face down on soft bedding are particularly vulnerable for sudden infant death syndrome. It has been suggested that 1 mechanism of death in this situation involves rebreathing of expired air. Many infants tolerate rebreathing while lying prone face down for long periods with stable saturations. Others occasionally have rapid desaturations and may require intervention to terminate rebreathing. The present study had 3 objectives: 1) to determine the frequency of rapid desaturations in a large group of healthy infants, 2) to elucidate the mechanism of these desaturations, and 3) to determine the timing of these events during periods of rebreathing. METHODS: We studied respiratory tracings and videotapes of 56 healthy 1- to 6-month-old infants who were sleeping face down and rebreathing on soft bedding in our laboratory. We compared the frequency of desaturations during rebreathing and nonrebreathing periods. We measured respiratory frequency and apnea occurrence before desaturation and nonrebreathing control episodes. We also measured minute ventilation during steady state before desaturation and just before desaturation. RESULTS: There were 25 desaturation episodes in infants while rebreathing, occurring in 11 (19.6%) of the 56 infants. Episodes were significantly more frequent during rebreathing than during nonrebreathing periods. Three desaturation episodes reached <85%; 2 required intervention to terminate rebreathing. The respiratory frequency was not different between nonrebreathing control and desaturation episodes. Brief apneas were significantly more frequent preceding desaturation than control episodes (44% vs 4%). Just before episodes, there was a transient decrease in minute volume despite increasing inspired carbon dioxide in 3 episodes. There was evidence of partial or complete pharyngeal airway obstruction in 3 episodes. Thirty-six percent of all episodes were immediately preceded by behavioral arousal. CONCLUSIONS: Rebreathing in prone sleeping infants is associated with an increased frequency of episodic desaturations. Desaturation may result from respiratory pattern changes such as brief apneas often associated with evidence of behavioral arousal or failure to increase ventilation in the face of rising inspired carbon dioxide, also associated with behavioral arousal.

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UNLABELLED: Recommended preoperative fasting intervals for infant formula vary from 4 to 8 h. We conducted a prospective, randomized, observer-blinded trial of 97 ASA physical status I and II infants scheduled for elective surgery to determine whether average gastric fluid volume (GFV) recovered from infants formula-fasted for 4 h (liberalized fast, Group L) differed from that recovered from infants allowed clear liquids up until 2 h, but fasted 8 h for formula and solids (traditional fast, Group T). In Group L, 31 of 39 subjects followed protocol and ingested formula 4-6 h before surgery. In Group T, 36 of 58 subjects followed protocol, taking clear liquids 2-5 h before the induction of anesthesia. Thirty subjects had prolonged fasts and were included only in a secondary intent-to-treat analysis. Respective mean age (5.7 +/- 2.3 versus 6.4 +/- 2.4 mo; range, 0.7-10.5 mo), weight (7.5 +/- 1.8 versus 7.5 +/- 1.1 kg), and volume of last feed (4.9 +/- 2.2 versus 4.0 +/- 2.3 oz.) did not vary between Groups L and T. GFV (L: 0.19 +/- 0.38 versus T: 0.16 +/- 0.30 mL/kg) and gastric fluid pH (L: 2.5 +/- 0.5 versus T: 2.9 +/- 1.3) did not vary. For all subjects, GFV (mL/kg) increased with age (Spearman correlation coefficient = +0.23, P = 0.03). Infant irritability and hunger and parent satisfaction were similar between groups. We conclude that average GFV after either a 4- to 6-h fast for infant formula or 2-h fast after clear liquids is small and not significantly different between groups. On the basis of these findings, clinicians may consider liberalizing formula feedings to 4 h before surgery in selected infants. IMPLICATIONS: Healthy infants aged < or =10.5 mo may drink formula up to 4 h before surgery without increasing gastric fluid volume compared with infants allowed clear liquids up to 2 h and formula 8 h before surgery.

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OBJECTIVE: Supine sleep is recommended for infants to decrease the risk of sudden infant death syndrome, but many parents report that their infants seem uncomfortable supine. Many cultures swaddle infants for sleep in the supine position. Swaddled infants are said to "sleep better"; presumably they sleep longer or with fewer arousals. However, there have been no studies of the effect of swaddling on spontaneous arousals during sleep. Arousal is initiated in brainstem centers and manifests as a sequence of reflexes: from sighs to startles and then to thrashing movements. Such "brainstem arousals" may progress to full arousal, but most do not. METHODS: Twenty-six healthy infants, aged 80 +/- 7 days, were studied during normal nap times. Swaddled (cotton spandex swaddle) and unswaddled trials were alternated for each infant. Sleep state (rapid eye movement [REM] or quiet sleep [QS]) was determined by behavioral criteria (breathing pattern, eye movements) and electroencephalogram/electrooculogram (10 infants). Respitrace, submental and biceps electromyogram, and video recording were used to detect startles and sighs (augmented breaths). Full arousals were classified by eye opening and/or crying. Frequencies of sighs, startles, and full arousals per hour were calculated. Progression of events was calculated as percentages in each sleep state, as was duration of sleep state. RESULTS: Swaddling decreased startles in QS and REM, full arousal in QS, and progression of startle to arousal in QS. It resulted in shorter arousal duration during REM sleep and more REM sleep. CONCLUSIONS: Swaddling has a significant inhibitory effect on progression of arousals from brainstem to full arousals involving the cortex in QS. Swaddling decreases spontaneous arousals in QS and increases the duration of REM sleep, perhaps by helping infants return to sleep spontaneously, which may limit parental intervention. For these reasons, a safe form of swaddling that allows hip flexion/abduction and chest wall excursion may help parents keep their infants in the supine sleep position and thereby prevent the sudden infant death syndrome risks associated with the prone sleep position.

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OBJECTIVE: The calming effects of swaddling may help infants accept back sleeping and so reduce the risk of sudden infant death syndrome. We hypothesized that swaddling, with minimal leg restraint, would be accepted by postneonatal infants with minimal respiratory effects. STUDY DESIGN: Postneonatal infants (n = 37)were studied for the introduction of swaddling. Four infants were studied by using traditional swaddling techniques. Swaddle tightness was increased in 13 infants, simulating traditional swaddles. Respiratory variables-respiratory rate, tidal volume, oxygen saturation, heart rate, sigh rate, and "grunting"-were measured. RESULTS: Hips were flexed and abducted in the swaddle. The majority of infants accepted swaddling while supine, including 78% of infants who slept prone at home. Acceptance decreased with increasing age. With increased swaddle pressure, respiratory rate increased during quiet sleep (P <.05). In rapid eye movement sleep, a slight effect on heart rate was observed (P <.05). Other variables did not change. CONCLUSIONS: Older infants including usual prone sleepers generally accept a form of swaddling that has minimal respiratory effects. The reintroduction of swaddling, without restricting hip movement or chest wall excursion, combined with supine sleeping, may promote further sudden infant death syndrome reduction.

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UNLABELLED: The peripherally acting prokinetic drug cisapride can overcome opioid-induced gastrointestinal paresis and may thereby eliminate a stimulus for postoperative vomiting. We conducted a prospective, randomized, double-blinded, controlled trial of 96 children undergoing inguinal surgery to determine whether cisapride would reduce the incidence of postoperative vomiting after general anesthesia supplemented with morphine. Group C1 patients (n = 38) received cisapride 0.3 mg/kg orally 1 h before surgery and placebo 6 h later, Group C2 (n = 28) received cisapride both before and after surgery, and Group P (n = 30) received placebo. Mean age (5.0 +/- 2.7 yr) and weight (21.0 +/- 8.6 kg), median pain scores and parent satisfaction scores, and incidence of rescue analgesic administration were similar across groups. Contrary to our hypothesis, incidences of postoperative vomiting in the hospital (32% vs 20%, P = 0.33) and at home (53% vs 46%, P = 0.33) did not vary by treatment group (with [C1 and C2] and without [P] cisapride, respectively). There was a trend toward more severe postoperative vomiting (three or more episodes) in children who received cisapride versus those who did not, both in hospital (6% vs 0%, P = 0.3) and at home (22% vs 8%) (P = 0.13). We conclude that cisapride does not prevent postoperative vomiting in this patient population and speculate that factors other than reduced gastrointestinal motility associated with general anesthesia and opioids are more important determinants of postoperative vomiting. IMPLICATIONS: Cisapride does not prevent postoperative vomiting in children and may increase its severity.

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