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INTRODUCTION: Severe obesity predisposes youth to a higher risk of venous thromboembolism (VTE). This study evaluates a BMI-stratified prophylactic dosing regimen of enoxaparin in adolescents with severe obesity undergoing surgery. METHODS: Adolescents aged 12-20 years received prophylactic enoxaparin at 40 mg SC (for a BMI < 50 kg/m(2)) and 60 mg SC (for a BMI ≥ 50 kg/m(2)) every 12 hours until discharge. Blood samples were drawn at pre-dose, 1, 2, 4, 6, and 12 hrs. Plasma Anti-Factor Xa (Anti-FXa) activity was used as a surrogate marker for enoxaparin pharmacokinetics. RESULTS: Ten female and two male obese adolescents (age range 14-19 years) had a mean BMI of 49.9 kg/m(2) (38.4-58 kg/m(2)). Four patients had a BMI of less than 50 kg/m(2) and received 40 mg enoxaparin, resulting in a mean dosage of 0.352 ± 0.070 mg/kg body weight. Eight patients were dosed with 60 mg enoxaparin every 12 hours, resulting in a mean dosage of 0.395 ± 0.028 mg/kg. Peak plasma anti-FXa activity (C(max)) ranged from 0.14 to 0.30 IU/mL, median C(max) was 0.205 IU/mL. Median T(max) was 5.67 hours (range 3.78 to 7.52 hours). Median AUC(i) was 1.00 h*IU/mL (range 0.42 to 1.67 h*IU/mL). 10 out of 12 patients (83%) reached the primary endpoint with anti-FXa activity in the range for VTE prevention (0.1-0.3 IU/mL). CONCLUSIONS: Our dosing scheme of 40 mg vs 60 mg enoxaparin stratified according to BMI proved to be effective in reaching prophylactic anti-FXa activity in 83% of adolescent patients.

Adolescents seeking bariatric surgery may present with pre-existing psychiatric diagnoses for which they use chronic medications. To heighten awareness concerning perioperative polypharmacy in adolescents with extreme obesity, we conducted a retrospective review of patients undergoing laparoscopic sleeve gastrectomy between February 2010 and May 2017 at Children's National Health System (CNHS). A total of 167 adolescent patients had pre-existing psychiatric diagnoses which included depression (50%), anxiety (23%), ADHD (23%), and binge eating disorder (11%). Medications prescribed to treat these diagnoses included selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Additionally, all patients were given fentanyl, ondansetron, morphine, and acetaminophen perioperatively. Although no life threatening symptoms of drug-drug interactions (DDIs) were appreciated, the combined use of many different potent drugs in these patients warrants attention.

Aim and objectives To describe the lived experience of young adults with perinatally acquired HIV (PaHIV). Background With the advancement of the highly active antiretroviral treatment, PaHIV infection has transformed into a chronic lifelong illness that is faced by young adults who grew up with HIV. The known challenges that are associated with HIV are poverty, stigma and social and emotional isolation. Design This was a qualitative single-interview study of a convenience sample of PaHIV-infected young adults receiving care at a large metropolitan pediatric hospital. Methods The participants had individual face-to-face interviews which were audio-taped and transcribed verbatim. Themes were developed to describe their living space, and Max Van Manen's lifeworld guide was used to describe their lived experience. Findings Seventeen participants (eight males/nine females) were enrolled. Four major themes emerged: (i) limited social capital, especially when orphaned participants reflected on a life void of parental guidance; (ii) incomplete education and unemployment, participants described an idle existence; (iii) a harsh life, described as participants facing difficulties meeting their life's milestones; (iv) unanticipated adult issues, where participants described their limited ability to care for themselves and their children. Van Manen lifeworld themes also described the space they occupied, their memories growing up with PaHIV, their health care and relationships. Conclusion Our study provides a valuable insight into the social and emotional difficulties faced by youth with PaHIV. The findings underscore the importance of extensive support and coordination of services between adult and pediatric providers to optimize long-term outcomes among young adults with PaHIV. Relevance to clinical practice The young adults with PaHIV require close attention and support from the healthcare providers, who can offer them a safe space to discuss lived experiences and support their ability to achieve full lives.

The number of obese pediatric patients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there are no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity. An institutional review board-approved exploratory pilot study was conducted in six adolescents aged 14–19 years undergoing bariatric surgery. Mean total body weight (TBW) and mean BMI were 137.4 ± 14.3 kg and 49.6 ± 6.4 kg/m2 (99.5th BMI percentile), respectively. Fentanyl was administered intravenously for intraoperative analgesia based on ideal body weight per standard of care. PK blood samples were drawn over a 24-h post-dose period. Fentanyl PK parameters were calculated by non-compartmental analysis. Mean fentanyl AUC0–∞ was 1.5 ± 0.5 h·ng/mL. Systemic clearance of fentanyl was 1522 ± 310 mL/min and 11.2 ± 2.6 mL/min·kg TBW. Volume of distribution was 635 ± 282 L and 4.7 ± 2.1 L/kg TBW. While absolute clearance was increased, absolute volume of distribution was comparable to previously established adult values. These results suggest that fentanyl clearance is enhanced in adolescents with clinically severe obesity while volume of distribution is comparable to previously published studies. NCT01955993 (clinicaltrials.gov).

AIM: To examine the impact of pre-existing psychiatric/psychological diagnoses on perioperative analgesic requirements in adolescents with morbid obesity undergoing bariatric surgery. METHODS: A retrospective cohort study of adolescents with morbid obesity undergoing bariatric surgery. Primary and secondary outcomes included perioperative analgesic intake and pain scores [(Numerical Rating Scale (0-10) NRS] throughout the hospital stay. RESULTS: From our Bariatric Surgery Research Registry, we identified 17 adolescents with psychiatric/psychological diagnoses prior to undergoing bariatric surgery. Fifteen patients from the same registry and without such diagnosis undergoing bariatric surgery during the same time time interval served as controls. In both groups there was a predominance of female patients. During the perioperative period, in both groups, oral morphine equivalent, ketorolac and acetaminophen intake were similar. Notably, the perioperative median pain scores at the times examined were below 5 for all patients. The median pain scores in the PACU, day of surgery and first post-operative day were similar. Conversely, on postoperative day 2, pain scores were higher in patients with diagnoses of psychiatric/psychological disorders (p=0.004) compared to those without. CONCLUSION: In this cohort of morbidly obese adolescents undergoing bariatric surgery, patients with and without pre-existing psychiatric/psychological diagnoses had similar analgesic requirements during the perioperative period. This finding appears contrary to those suggesting that preexisting depression and/or anxiety might be associated with increased analgesic requirements during the perioperative period.

This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CLformation) of oxidative pathway metabolites. Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (

BackgroundSevere obesity predisposes adults and youth to a higher risk of venous thromboembolism (VTE). Enoxaparin is frequently used for their VTE management. This study evaluates a BMI-stratified prophylactic dosing regimen of enoxaparin in severely obese adolescents undergoing bariatric surgery.MethodsThis prospective study enrolled severely obese adolescents aged 12–20 years undergoing laparoscopic sleeve gastrectomy. Prophylactic enoxaparin was dosed at 40 mg SC (for a BMI less than 50 kg/m2) and 60 mg SC (for a BMI equal to or greater than or 50 kg/m2). Blood samples were drawn until 12 hrs post-dose. Plasma Anti-Factor Xa (Anti-FXa) activity was used as a surrogate marker for enoxaparin plasma concentration and pharmacokinetics were assessed using non-compartmental PK analysis. The primary efficacy outcome was the anti-FXa activity 4–6 hours after dosing, and the primary endpoint was the proportion of patients who reached prophylactic anti-FXa activity of 0.1–0.3 U/mL between 4–6 hours after dosing.ResultsTen female and two male obese adolescents (age range 14–19 years) had a mean body weight of 140.8 kg (93.7–174 kg) and a mean BMI of 49.9 kg/m2 (38.4–58 kg/m2). Four patients received 40 mg enoxaparin, 8 patients were dosed with 60 mg enoxaparin. No VTE or major bleeding occurred. Peak plasma anti-FXa activity (Cmax) ranged from 0.14–0.30 IU/mL (median Cmax 0.205 IU/mL). Median Tmax was 5.67 hours (range 3.78–7.52 hours). Median AUCi was 1.00 h*IU/mL (range 0.42–1.67 h*IU/mL). 10 out of 12 patients (83%) reached the primary endpoint with anti-FXa activity in the range for VTE prevention (0.1–0.3 IU/mL).ConclusionsIn this single center cohort study, the dosing scheme of 40 mg vs 60 mg enoxaparin stratified according to BMI proved to be effective in reaching prophylactic anti-FXa activity in 83% of adolescent patients. This dosing scheme is in accordance with current practice in adults.Disclosure(s)J. Vaughns and J. van den Anker are supported by the Eunice Kennedy Shriver National Institute of Child Health and Development (5T32HD087969).

Lopinavir/ritonavir (Kaletra) is first-line therapy for pediatric HIV infection. In clinical practice, Kaletra tablets are occasionally crushed for pediatric administration. This study compared lopinavir/ritonavir exposure between whole and crushed tablets in HIV-infected children.This was a randomized, open-label, cross-over study of pediatric patients taking lopinavir/ritonavir as part of their antiretroviral regimen. Each subject had 2 separate (within 30 days) steady-state 12-hour pharmacokinetic (PK) studies with crushed and whole 200/50 mg lopinavir/ritonavir tablets.PK blood samples were drawn at 0 (predose), 1, 2, 4, 6, 8, and 12 hours postdose. Lopinavir and ritonavir plasma concentrations measured by high-performance liquid chromatography were used to calculate non-compartmental area under the concentration versus time curve (AUC) and clearance. Wilcoxon signed-rank tests compared PK values between crushed and whole tablets.Twelve children, median age of 13 years (10-16 years), took 550/138 mg·m(-2) per day lopinavir/ritonavir divided every 12 hours. The median lopinavir AUC after crushed and whole tablets were 92 mg·hr·L(-1) and 144 mg·hr·L(-1), respectively, with an AUC ratio of 0.55 (P = 0.003). Median ritonavir AUC of crushed and whole tablets were 7 mg·hr·L(-1) and 13.3 mg·hr·L(-1), respectively, with an AUC ratio of 0.53 (P = 0.006).Administration of crushed 200/50 mg lopinavir/ritonavir tablets to children significantly reduced lopinavir and ritonavir exposure with a decrease in AUC by 45% and 47%, respectively. The administration of crushed tablets would require higher doses and therapeutic drug monitoring to ensure adequate lopinavir exposure in patients requiring this practice. The use of crushed lopinavir/ritonavir tablets should be avoided, if possible.