Timing of sedentary behaviour and access to sedentary activities in the bedroom and their association with sleep quality and duration in children and youth: a systematic review. / Revue systématique des liens entre, d'une part, l'horaire des comportements sédentaires et l'accès à des activités sédentaires dans la chambre et, d'autre part, la qualité et la durée du sommeil chez les enfants et les adolescents.

BACKGROUND: The purpose of this study was to systematically review the relationship between the timing of sedentary behaviours and access to sedentary activities in the bedroom with sleep duration and quality in children and youth. A secondary purpose was to examine whether these relationships differ when comparing screen-based and non-screen-based sedentary activities. METHODS: We searched four databases for peer-reviewed studies published between 1 January 2010 and 19 January 2021. Risk of bias assessment for each study and certainty of evidence were assessed using the GRADE framework. RESULTS: We identified 44 eligible papers reporting data from 42 separate datasets and including 239 267 participants. Evening participation in screen-based sedentary behaviours and access to screen-based devices in the bedroom were associated with reduced sleep duration and quality. Daytime screen use was also associated with reduced sleep duration, although this was examined in relatively few studies. Whether performed during the day or night, non-screen-based sedentary behaviours were not consistently associated with sleep duration or quality. The quality of evidence was rated as low to very low for all outcomes. CONCLUSION: In order to maximize sleep duration and quality, children and youth should be encouraged to minimize screen time in the evening and remove screens from bedrooms. (PROSPERO registration no.: CRD42020189082).

CYP2C19 drug-drug and drug-gene interactions in ED patients.

BACKGROUND: CYP450 polymorphisms result in variable rates of drug metabolism. CYP drug-drug interactions can contribute to altered drug effectiveness and safety. STUDY OBJECTIVES: The primary objective was to determine the percentage of emergency department (ED) patients with cytochrome 2C19 (CYP2C19) drug-drug interactions. The secondary objective was to determine the prevalence of CYP2C19 polymorphisms in a US ED population. METHODS: We conducted a prospective observational study in an urban academic ED with 72,000 annual visits. Drug ingestion histories for the 48 hours preceding ED visit were obtained; each drug was coded as CYP2C19 substrate, inhibitor, inducer, or not CYP2C19 dependent. Ten percent of patients were randomized to undergo CYP2C19 genotyping using the Roche Amplichip. RESULTS: A total of 502 patients were included; 61% were female, 65% were white, and median age was 39 years (interquartile range, 22-53). One hundred thirty-one (26.1%) patients had taken at least 1 CYP2C19-dependent home drug. Eighteen (13.7%) patients who were already taking a CYP2C19-dependent drug were given or prescribed a CYP2C19-dependent drug while in the ED. Among the 53 patients genotyped, 52 (98%) were extensive metabolizers and 1 was a poor metabolizer. CONCLUSIONS: In a population of ED patients, more than a quarter had taken a CYP2C19-dependent drug in the preceding 48 hours, but few were given or prescribed another CYP2C19-dependent drug in the ED. On genotyping analysis, CYP2C19 polymorphisms were uncommon in our cohort. We conclude that changing prescribing practice due to CYP2C19 drug-drug interaction or genotype is unlikely to be useful in most US ED populations.

The effect of CYP2D6 drug-drug interactions on hydrocodone effectiveness.

OBJECTIVES: The hepatic cytochrome 2D6 (CYP2D6) is a saturable enzyme responsible for metabolism of approximately 25% of known pharmaceuticals. CYP interactions can alter the efficacy of prescribed medications. Hydrocodone is largely dependent on CYP2D6 metabolism for analgesia, ondansetron is inactivated by CYP2D6, and oxycodone analgesia is largely independent of CYP2D6. The objective was to determine if CYP2D6 medication coingestion decreases the effectiveness of hydrocodone. METHODS: This was a prospective observational study conducted in an academic U.S. emergency department (ED). Subjects were included if they had self-reported pain or nausea and were excluded if they were unable to speak English, were less than 18 years of age, had liver or renal failure, or carried diagnoses of chronic pain or cyclic vomiting. Detailed drug ingestion histories for the preceding 48 hours prior to the ED visit were obtained. The patient's pain and nausea were quantified using a 100-mm visual analog scale (VAS) at baseline prior to drug administration and following doses of hydrocodone, oxycodone, or ondansetron. We used a mixed model with random subject effect to determine the interaction between CYP2D6 drug ingestion and study drug effectiveness. Odds ratios (ORs) were calculated to compare clinically significant VAS changes between CYP2D6 users and nonusers. RESULTS: A total of 250 (49.8%) of the 502 subjects enrolled had taken at least one CYP2D6 substrate, inhibitor, or inducing pharmaceutical, supplement, or illicit drug in the 48 hours prior to ED presentation. CYP2D6 drug users were one-third as likely to respond to hydrocodone (OR = 0.33, 95% confidence interval [CI] = 0.1 to 0.8) and more than three times as likely as nonusers to respond to ondansetron (OR = 3.4, 95% CI = 1.3 to 9.1). There was no significant difference in oxycodone effectiveness between CYP2D6 users and nonusers (OR = 0.53, 95% CI = 0.3 to 1.1). CONCLUSIONS: CYP2D6 drug-drug interactions appear to change effectiveness of commonly prescribed drugs in the ED. Drug-drug interaction should be considered prior to prescribing CYP2D6 drugs.

Phase II trial of cetuximab plus cisplatin and irinotecan in patients with cisplatin and irinotecan-refractory metastatic esophagogastric cancer.

INTRODUCTION: Cetuximab in combination with irinotecan has shown clinically significant activity in patients with irinotecan-refractory colon cancer. We evaluated the efficacy of cetuximab in combination with cisplatin and irinotecan in patients with metastatic esophagogastric cancer refractory to cisplatin and irinotecan. PATIENTS AND METHODS: Patients with disease progression within 3 months of treatment with prior cisplatin and irinotecan received weekly cetuximab and cisplatin/irinotecan for 2 weeks, followed by a 1-week rest period. The primary endpoint was objective response rate. Secondary endpoints included progression-free and overall survival. RESULTS: Sixteen patients were enrolled (87% with adenocarcinoma). The median prior exposure to cisplatin/irinotecan was 3.6 months. The addition of cetuximab to cisplatin and irinotecan was well tolerated and there were no unexpected toxicities. One of 16 patients treated on study experienced durable RECIST partial response lasting 10 months. The median progression-free survival was 1.4 months (range, 0.5 to 10 mo). CONCLUSIONS: The addition of cetuximab did not overcome irinotecan resistance in patients with metastatic esophagogastric cancer. Further investigation of this strategy in esophagogastric cancer is not justified. The limited activity observed for cetuximab is consistent with other studies evaluating single-agent cetuximab.

Vasopressors in cardiac arrest: a systematic review.

OBJECTIVES: To review the literature addressing whether the use of vasopressors improves outcomes in patients who suffer cardiac arrest. METHODS: Databases were searched using the terms: "(adrenaline or noradrenaline or vasopressor) and (heart arrest or cardiac arrest) and therapy". Inclusion criteria were human studies, controlled trials, meta-analysis or case series. Exclusion criteria were articles with no abstract, abstract-only citations without accompanying article, non-English abstracts, vasopressor studies without human clinical trials, case reports, reviews, and articles addressing traumatic arrest. RESULTS: 1603 papers were identified of which 53 articles were included for review. The literature addressed 5 main therapeutic questions. (1) Outcomes comparing any vasopressor to placebo. (2) Outcomes comparing vasopressin (alone or in combination with epinephrine) to epinephrine. (3) Outcomes comparing high dose epinephrine to standard dose epinephrine. (4) Outcomes comparing any alternative vasopressor to epinephrine. (5) Outcomes examining vasopressor use in pediatric cardiac arrest. CONCLUSION: There are few studies that compare vasopressors to placebo in resuscitation from cardiac arrest. Epinephrine is associated with improvement in short term survival outcomes as compared to placebo, but no long-term survival benefit has been demonstrated. Vasopressin is equivalent for use as an initial vasopressor when compared to epinephrine during resuscitation from cardiac arrest. There is a short-term, but no long-term, survival benefit when using high dose vs. standard dose epinephrine during resuscitation from cardiac arrest. There are no alternative vasopressors that provide a long-term survival benefit when compared to epinephrine. There is limited data on the use of vasopressors in the pediatric population.

Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer.

BACKGROUND: Preoperative chemoradiation improves survival in esophageal and gastroesophageal junction (GEJ) cancer. We evaluated irinotecan and cisplatin as induction chemotherapy followed by concurrent chemoradiation in esophageal cancer. METHODS: Patients with uT1N1M0 or uT2-4NanyM0 resectable squamous cancer or adenocarcinoma of the esophagus or GEJ received irinotecan 65 mg/m(2) and cisplatin 30 mg/m(2) for 4 treatments in weeks 1 through 5, followed by 4 treatments in weeks 7 through 11 with 50.4 Gy in daily fractions, followed by surgery. The primary endpoint was pathologic complete response (pCR). Positron emission tomography (PET) scan was performed prior to chemotherapy and as restaging prior to radiotherapy. RESULTS: Fifty-five patients were evaluable, 75% of whom had adenocarcinoma and 65% of whom had uT3N1 disease. Thirty-eight patients underwent R0 resection (69%). The incidence of pCR was 16% (95% confidence interval, 8%-29%). Median overall survival was 31.7 months. An exploratory analysis of PET response to induction chemotherapy indicated a correlation with pCR (32% vs 4%), R0 resection (84% vs 57%), progression-free survival (24.1 vs 7.7 months), and overall survival (40.2 vs 25.5 months). CONCLUSIONS: Weekly treatment with irinotecan, cisplatin, and radiation achieved results no better and potentially inferior to other phase 2 chemoradiotherapy trials with a low rate of pCR. The use of PET scan after induction chemotherapy to direct chemotherapy during subsequent radiotherapy merits further study.

Intraosseous infusion of ice cold saline is less efficacious than intravenous infusion for induction of mild therapeutic hypothermia in a swine model of cardiac arrest.

BACKGROUND: Intravenous (IV) infusion of ice cold saline is an effective method to initiate induction of mild therapeutic hypothermia (MTH) following resuscitation from out-of-hospital cardiac arrest (OOHCA). Intraosseous (IO) infusion of cold saline may be an alternative method to induce MTH. OBJECTIVE: The goal of this study was to determine if IO infusion of cold saline is a comparable alternative to IV infusion for inducing MTH in a laboratory swine model of cardiac arrest. METHODS: Ten mixed breed swine were resuscitated from cardiac arrest and randomized post-resuscitation to infusion with ice cold saline using either IO (n = 5) or IV (n = 5) access. The study endpoints were either a goal esophageal temperature of 34 °C or the elapse of a 30 min time period, simulating a long prehospital transport. RESULTS: Four of five pigs in the IV infusion group achieved goal temperature within 30 min compared to 0/5 in the IO infusion group (p = 0.048). The mean esophageal temperature change was significantly higher in the IV group when compared to the IO group (p < 0.001). Post-arrest hemodynamic parameters were similar between the two groups. CONCLUSIONS: IV infusion of ice cold saline is an efficacious method to achieve MTH in this swine model of cardiac arrest. Furthermore, IO infusion of cold saline is not sufficient to induce MTH in the time routinely available in the prehospital setting following OOHCA.

Postnatal hepatic fatty acid oxidative capacity of preterm pigs receiving TPN does not differ from that of term pigs and is not affected by supplemental arachidonic and docosahexaenoic acids.

To improve pediatric care of preterm infants, a better understanding of the metabolic processes associated with immaturity is needed. To this end, preterm and term pigs were delivered and administered either a control, a low-PUFA [0.3 and 0.6% of total lipids as docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively], or a high-PUFA (5 and 11% of total lipids as DHA and AA, respectively) parenteral solution. Hepatic oxidative capacity and carnitine palmitoyltransferase (CPT) mRNA and activity in the presence or absence of malonyl-CoA were determined after 6 d. Oxidation of [1-(14)C]-palmitate or [1-(14)C]-glucose was similar in liver homogenates isolated from preterm and term pigs receiving the control solution. Oxidative capacity for either substrate did not differ with parenteral solution in preterm pigs, whereas in term pigs, glucose oxidation was 64% greater when the high-PUFA solution was administered relative to the control (P < 0.05). In preterm pigs, CPT I mRNA determined after 6 d of parenteral feeding were 1.5-fold greater (P < 0.05) than newborn estimates irrespective of solution administered, whereas CPT I mRNA were only greater for term pigs receiving the low- and high-PUFA solutions (66 and 115%, respectively; P < 0.05) relative to newborn estimates. Malonyl-CoA-sensitive CPT activity did not differ between preterm and term pigs or parenteral solution. Postnatal adaptations demonstrated by parenterally fed term neonates are present following preterm birth and are not improved by the provision of DHA and AA to parenteral solutions.

Allergic fungal sinusitis in children.

BACKGROUND: Allergic fungal sinusitis (AFS) has been characterized in adults presenting with chronic sinusitis. Rare reports allude to a similar disease in children. OBJECTIVE: To characterize the features of AFS in children. METHODS: Children referred to otolaryngology clinics at Arkansas and LeBonheur Children's Hospitals for chronic sinusitis during a 12-year period were studied. This retrospective analysis reviews the following: clinical presentation, laboratory evaluations, radiographic and pathologic findings, and surgical intervention. Twenty patients (age range, 7-18 years; mean age, 12.5 years; median age, 16 years) met previously published criteria for AFS. Thirteen patients were male and 7 were female. Thirteen were African American and 7 were white. RESULTS: Presentation at diagnosis included the following: atopy (n = 20), nasal symptoms (n = 20), recurrent sinusitis (n = 18), nasal polyps (n = 18), recurrent headaches (n = 12), asthma (n = 11), proptosis (n = 10), and ocular symptoms (n = 10). All had radiographic evidence of sinusitis and allergy to fungal organisms. IgE levels were elevated in 8 of 9 patients, and 10 of 15 patients had eosinophilia. Surgical specimens demonstrated allergic mucin (n = 11), Charcot-Leyden crystals (n = 2), hyphae or fungal debris (n = 9), and fungal growth (n = 17). All patients underwent endoscopic sinus surgery, with 11 requiring multiple surgical procedures. Postoperatively, 19 patients received intranasal and oral steroids, and all had nasal saline washes. Eleven patients (9 who had undergone multiple surgical procedures) were treated with immunotherapy. Relapse was seen in 55% of patients at 1 year of follow-up. CONCLUSION: AFS presents with a higher incidence of proptosis in children when compared with adults. Typically, AFS occurs in atopic children with refractory sinus disease, requiring a high index of suspicion for evaluation and aggressive treatment.