Pediatric Extrapolation Approach for U.S. Food and Drug Administration Approval of Brexpiprazole in Patients Aged 13 to 17 Years with Schizophrenia.

A pharmacokinetic (PK) bridging approach was successfully employed to support the dosing regimen and approval of brexpiprazole in pediatric patients aged 13-17 years with schizophrenia. Brexpiprazole was approved in 2015 for the treatment of schizophrenia and the adjunctive treatment of major depressive disorder in adults based on efficacy and safety data from clinical trials. On January 13, 2020, the US Food and Drug Administration issued a general advice letter to sponsors highlighting the acceptance of efficacy extrapolation of certain atypical antipsychotics from adult patients to pediatric patients considering the similarity in disease and exposure-response relationships. Brexpiprazole is the first atypical antipsychotic approved in pediatrics using this approach. The PK data available from pediatric patients aged 13-17 years have shown high variability due to the limited number of PK evaluable subjects, which limits a robust estimation of differences between adult and pediatric patients. The PK model-based approach was thus utilized to evaluate the appropriateness of the dosing regimen by comparing PK exposures in pediatric patients aged 13-17 years with exposures achieved in adults at the approved doses. In addition to exposure matching, safety data from a long-term open-label clinical study in pediatric patients informed the safety profile in pediatric patients. This report illustrates the potential of leveraging previously collected efficacy, safety, and PK data in adult patients to make a regulatory decision in pediatric patients for the indication of schizophrenia.

Racial and Ethnic Differences in Encounters Related to Suicidal Behavior Among Children and Adolescents With Medicaid Coverage During the COVID-19 Pandemic.

This cohort study evaluates rates of encounters for suicidal behavior by race and ethnicity among children with Medicaid coverage during vs before the COVID-10 pandemic.

Suicides Among American Indian or Alaska Native Persons - National Violent Death Reporting System, United States, 2015-2020.

Compared with the general U.S. population, American Indian or Alaska Native (AI/AN) persons, particularly those who are not Hispanic or Latino (Hispanic) AI/AN, are disproportionately affected by suicide; rates among this group consistently surpass those among all other racial and ethnic groups (1). Suicide rates among non-Hispanic AI/AN persons increased nearly 20% from 2015 (20.0 per 100,000) to 2020 (23.9), compared with a <1% increase among the overall U.S. population (13.3 and 13.5, respectively) (1). Understanding characteristics of suicide among AI/AN persons is critical to developing and implementing effective prevention strategies. A 2018 report described suicides in 18 states among non-Hispanic AI/AN persons only (2). The current study used 2015-2020 National Violent Death Reporting System (NVDRS) data among 49 states, Puerto Rico, and the District of Columbia to examine differences in suicide characteristics and contributing circumstances among Hispanic and non-Hispanic AI/AN populations, including multiracial AI/AN. Results indicated higher odds across a range of circumstances, including 10 of 14 relationship problems (adjusted odds ratio [aOR] range = 1.2-3.8; 95% CI range = 1.0-5.3) and six of seven substance use problems (aOR range = 1.2-2.3; 95% CI range = 1.1-2.5), compared with non-AI/AN persons. Conversely, AI/AN decedents had reduced odds of having any current known mental health condition, any history of mental health or substance use treatment, and other common risk factors (aOR range = 0.6-0.8; 95% CI = 0.2-0.9). Suicide is preventable. Communities can implement a comprehensive public health approach to suicide prevention that addresses long-standing inequities affecting AI/AN populations (3).

Prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014.

PURPOSE: To estimate prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014. METHODS: We conducted a cohort study of singleton live birth deliveries. Maternal characteristics were ascertained from health plan and/or birth certificate data and opioids dispensed during pregnancy from health plan pharmacy records. Prevalence of prescription opioid use during pregnancy was calculated for any use, cumulative days of use, and number of dispensings. RESULTS: We examined prevalence of prescription opioid use during pregnancy in each health plan. Tennessee Medicaid had appreciably greater prevalence of use compared to the seven other health plans. Thus, results for the two groups were reported separately. In the seven health plans (n = 587 093 deliveries), prevalence of use during pregnancy was relatively stable at 9%-11% throughout 2001-2014. In Tennessee Medicaid (n = 256 724 deliveries), prevalence increased from 29% in 2001 to a peak of 36%-37% in 2004-2010, and then declined to 28% in 2014. Use for ≥30 days during pregnancy was stable at 1% in the seven health plans and increased from 2% to 7% in Tennessee Medicaid during 2001-2014. Receipt of ≥5 opioid dispensings during pregnancy increased in the seven health plans (0.3%-0.6%) and Tennessee Medicaid (3%-5%) during 2001-2014. CONCLUSION: During 2001-2014, prescription opioid use during pregnancy was more common in Tennessee Medicaid (peak prevalence in late 2000s) compared to the seven health plans (relatively stable prevalence). Although a small percentage of women had opioid use during pregnancy for ≥30 days or ≥ 5 dispensings, they represent thousands of women during 2001-2014.

Postoperative Spica Cast Care: RN Comfort-Level Survey Score Improvement After a 30-Minute Educational Video.

Spica casts are utilized to immobilize young patients who have sustained femur fractures or who have undergone hip procedures/surgery. These casts typically need to stay in place for 4-6 weeks. Improper postoperative care can lead to unplanned, increased morbidity and sequelae. We show that with appropriate education using a video module teaching method, learners who are less familiar with the specific care of these patients and casts will gain an improved comfort level and increased knowledge base. This will translate to better patient care and more complete caregiver education for home.

A Rare Cause of Postoperative Abdominal Pain in a Spinal Fusion Patient.

We present the case of a 12-year-old girl who underwent an uncomplicated posterior spinal fusion with instrumentation for scoliosis and who later developed nausea, emesis, and abdominal pain. We discuss the epidemiology, prevalence, anatomic findings, symptoms, diagnostic tests, and clinical management, including nonsurgical and surgical therapies, of superior mesenteric artery syndrome (SMAS), a rare condition. Over a 2-week period, the patient developed an uncommon type of bowel obstruction likely related to her initial thin body habitus, correction of her deformity, and weight loss after surgery. The patient returned to the operating room for placement of a Stamm gastrostomy feeding tube with insertion of a transgastric-jejunal (G-J) feeding tube. The patient had the G-J feeding tube in place for approximately 6 weeks to augment her enteral nutrition. As she gained weight, her duodenal emptying improved, and she gradually transitioned to normal oral intake. She has done well since the G-J feeding tube was removed. Posterior spinal fusion for adolescent idiopathic scoliosis is a relatively common procedure, and SMAS is a rare condition. However, in the case of an asthenic adolescent with postoperative weight loss, intestinal obstruction can develop. When planning operative spinal correction in scoliosis patients who have a low body mass index at the time of surgery and who have increased thoracic stiffness, be alert for signs and symptoms of SMAS. This rare complication can develop, and timely diagnosis and medical management will decrease morbidity and shorten the length of time needed for nutritional rehabilitation.

Orthopaedic clinical care model in a pediatric orthopaedic setting: outcomes of a 1: 1 model--orthopaedic surgeon and nurse practitioner.

Over the last 10 years, nurse practitioners have become an essential part of the multidisciplinary orthopaedic team within a Level 1 pediatric trauma hospital. This overview will outline the process used and noted results during the development of a new model of care for pediatric orthopaedic patients, in both the hospital setting and outpatient clinics. Data from a 12-month period was reviewed in an effort to show the benefits of establishing a 1:1 model utilizing an orthopaedic surgeon and nurse practitioner. The advantages of this team concept include increased access to care, fiscal improvement, and positive patient outcomes due to standardized protocols and patient continuity.

Proximal humerus fractures.

Proximal humerus fractures are among the most common fractures associated with osteoporosis. With an aging population, incidence of these fractures will only increase. The proximal humerus not only forms the lateral portion of the shoulder articulation but also has significant associations with musculoskeletal and neurovascular structures. As a result, fractures of the proximal humerus can significantly impact not only the function of the shoulder joint, but the health and function of the entire upper extremity as well. Understanding of these fractures, the management options, and associated nursing care, can help reduce morbidity rate and improve functional outcomes.

A retrospective quality improvement study of ketorolac use following spinal fusion in pediatric patients.

BACKGROUND: There are studies and literature that support the claim that ketorolac use after spinal fusion in the adult population can increase the risk of pseudarthrosis, instrumentation failure, and/or nonunion. There is limited research when using ketorolac in the pediatric population, especially short-term use. METHODS: Chart review of 46 pediatric patients who had prior spinal fusions for scoliosis between July 2003 and August 2005. Twenty-five of the patients received ketorolac and 21 did not. The lengths of stay, incidence of curve progression, and/or incidence of nonunion or instrumentation failure were compared in the 2 groups. RESULTS: At the 1-year follow-up, 95% of the patients returned and at the 3-year follow-up, 52% of the patients returned and there was no clinical or radiographic evidence of curve progression, nonunion, or instrumentation failure. LEVEL OF EVIDENCE: This is a retrospective study looking at results of 2 patient groups. This is a level III study.

Transdermal selegiline in patients receiving electroconvulsive therapy.

BACKGROUND: Concurrent use of monoamine oxidase inhibitors (MAOIs) during a course of electroconvulsive therapy (ECT) is controversial. OBJECTIVE: In this report, the authors present outcomes of this concurrent treatment approach. METHOD: The authors present two cases of patients taking the newest MAOI approved for depression, namely, transdermal selegiline, while receiving ECT. RESULTS: The authors conclude that there is no evidence of complications or adverse events associated with concurrent use of ECT and low-dose transdermally administered selegiline. CONCLUSION: The authors further conclude that beginning a low dose of transdermal selegiline before finishing a course of ECT is a viable option for relapse prevention in the treatment of depression.

Anxiety disorders as a risk factor for subsequent depression.

Abstract Introduction. Patients with comorbid depression and anxiety disorders have a higher suicide risk, increased social and vocational dysfunction and more severe and refractory illness. Methods. This paper reviews the studies examining the temporal relationship between onset of anxiety disorders and depression. Results. The highest rates of subsequent depression have been found in generalized anxiety disorder, followed by panic disorder and social anxiety disorder. The largest numbers of studies have been done on social anxiety disorder. Panic attacks, separation anxiety disorder and specific phobia also have an association with higher rates of subsequent depression in a limited number of studies. Conclusion. Further studies are needed to investigate whether treatment and treatment outcomes in anxiety disorders has an effect on the risk for developing subsequent depression.

Lawn mower injuries in pediatric patients.

Lawn mower injuries are painful, devastating, and life-altering. Pediatric patients who sustain these injuries suffer various forms of physical trauma. Some are minor, but many others are disfiguring or even fatal. The psychological and social impact is far-reaching as well. These injuries have high rates of morbidity, include many days lost from school, and can cause financial loss for the parents due to the hospitalization and missed work. The primary objective with regards to lawn mower injuries is prevention that is accomplished by education. However, once the patient has been injured and admitted to the hospital, then immediate treatment with timely discharge is the main objective. Excellent wound care, acceptable cosmetic appearance, and infection prevention are the ultimate goals. Use of the Vacuum Assisted Closure (VAC) device has helped facilitate the end results. Psychological adjustment with regards to this traumatic event is also addressed immediately for both the patient and the caregivers. Inpatient and outpatient counseling and follow-up all play a role in this stressful time.

Concurrent use of methotrexate and acitretin revisited.

BACKGROUND: According to Food and Drug Administration (FDA)-approved prescribing information, combination therapy with acitretin and methotrexate (MTX) is contraindicated. This is based on company data suggesting increased hepatotoxicity in patients who received concomitant methotrexate and etretinate, the prodrug of acitretin. METHODS: We reviewed the clinical data of 18 patients with psoriasis who received methotrexate and acitretin concurrently. Patients received 25 mg of acitretin once daily or alternating days and 7.5-25 mg methotrexate weekly. Baseline metabolic panels, including lipids, and complete blood counts (CBC) were drawn prior to therapy and every 4-12 weeks while on therapy. RESULTS: The average length of treatment was 9 months. Two patients discontinued treatment after refusal to abstain from alcohol. Seven patients discontinued treatment due to a lack of response. Two patients discontinued treatment after clearing. One patient discontinued treatment secondary to hair loss. Six patients are currently continuing therapy. CONCLUSIONS: In this series of patients, combination therapy with acitretin and methotrexate was well tolerated and often effective. There were no new or unusual adverse events noted, including significant hepatotoxicity. In patients who would benefit from the use of acitretin, the concomitant use of methotrexate is not an absolute contraindication.

Use of wound V.A.C. therapy in pediatric patients with infected spinal wounds: a retrospective review.

BACKGROUND: Deep wound infection in patients that have had a posterior spinal fusion for scoliosis is a major complication in pediatric spine surgery. PURPOSE: To explore characteristics of pediatric patients who had a posterior spinal fusion with segmental spinal instrumentation and bone graft and subsequently developed deep spinal wound infections that were treated with wound vacuum-assisted closure (V.A.C.) therapy METHOD: Retrospective Chart Review. Characteristics of patients' age, gender, comorbid illnesses, identified bacteria, antibiotics, time on V.A.C. device, infection recurrence, any instrumentation removal, and additional surgical intervention was collected. FINDINGS: There were 249 patients who had spinal fusions from December 2002 through January 2006, and 11 developed an infection after their spinal fusion and had the use of the V.A.C. device. Those who developed infection within 1 year of their fusion had instrument retention. Wound closure occurred in all cases that used V.A.C. therapy.