Updates in the treatment of asthma in pediatrics: A review for pharmacists.

PURPOSE: The purpose of this review is to summarize the management of asthma in children and to highlight different guideline-based approaches. This review also discusses literature regarding the use of corticosteroids, both inhaled and systemic, as well as biologic agents, in asthma management. SUMMARY: Asthma is a common chronic respiratory condition in the pediatric population and has evolved into a highly patient-specific disease. Of the 2 main asthma guidelines, one developed by the National Asthma Education and Prevention Program was recently published as a focused update in 2020. The other, from the Global Initiative for Asthma, focuses on a global strategy for management and prevention, with the most recent update in 2023. Both reports discuss diagnosis, assessment, and treatment of asthma in adults and children. Treatment is designed as a stepwise approach in both reports, although there are key differences. This article focuses on gaps in these guidelines, including the use of bronchodilators and inhaled corticosteroids with single maintenance and reliever therapy and long-acting muscarinic antagonists in children. It also reviews treatment in children under 5 years of age, although recommendations are limited due to a lack of evidence in this age group. Finally, this review discusses considerations for emerging treatments, including biologics, for patients who are difficult to treat. CONCLUSION: New treatment strategies and agents have emerged in the treatment of pediatric asthma. Pharmacists play a key role in providing education about, dispensing, and recommending the newest evidence-based treatment options for children.

Systemic Heparinization After Neuraxial Anesthesia in Vascular Surgery: A Retrospective Analysis.

OBJECTIVES: The American Society of Regional Anesthesia and Pain Medicine's guidelines recommend a 1-hour interval after neuraxial anesthesia (NA) before systemic heparinization to mitigate the risk of spinal hematoma (SH). The study authors aimed to characterize the time interval between NA and systemic heparinization in vascular surgery patients (primary outcome). The secondary outcomes included the historic incidence of SH, and risk estimation of the SH formation based on available data. Heparin dose, length of surgery, difficulty and/or the number of NA attempts, and patient demographics were recorded. DESIGN: A retrospective analysis between April 2012 and April 2022. SETTING: A single (academic) center. PARTICIPANTS: Vascular surgery patients. INTERVENTIONS: Intravenous heparin administration. MEASUREMENTS AND MAIN RESULTS: All (N = 311) vascular patients were reviewed, of whom 127 (5 femoral-femoral bypass, 67 femoral-popliteal bypass, and 55 endovascular aneurysm repairs [EVAR]) received NA and were included in the final analysis. Patients receiving general anesthesia alone (N = 184) were excluded. Neuraxial anesthesia included spinal (N = 119), epidural (N = 4), or combined spinal-epidural (N = 4) blocks. The average time between NA and heparin administration was 42.8 ± 22.1 minutes, with 83.7% of patients receiving heparin within 1 hour of NA. The time between NA and heparin administration was 40.4 ± 22.3, 50.1 ± 23.4, and 31.3 ± 12.5 minutes for femoral-femoral bypass, femoral-popliteal bypass, and EVAR, respectively. Heparin was administered after 1 hour of NA in 20% of femoral-femoral bypass, 27% of femoral-popliteal bypass, and 3.9% of EVAR patients. No SHs were reported during the study period. CONCLUSIONS: The vast majority of vascular surgery patients at the authors' center received heparin within 1 hour of NA. Further studies are required to assess if their findings are consistent in other vascular surgery settings and/or centers.

Just DOAC: Use of direct-acting oral anticoagulants in pediatrics.

PURPOSE: The aim of this article is to provide an overview of the current literature for direct-acting oral anticoagulant (DOAC) use in pediatric patients and summarize ongoing trials. SUMMARY: In treatment of venous thromboembolism (VTE) in pediatric patients, evidence supports use of both dabigatran and rivaroxaban. Dabigatran has been shown to be noninferior to standard of care (SOC) in terms of efficacy, with similar bleeding rates. Similarly, treatment with rivaroxaban in children with acute VTE resulted in a low recurrence risk and reduced thrombotic burden, without increased risk of bleeding, compared to SOC. Treatment of pediatric cerebral venous thrombosis as well as central venous catheter-related VTE with rivaroxaban appeared to be both safe and efficacious and similar to that with SOC. Dabigatran also has a favorable safety profile for prevention of VTE, and rivaroxaban has a favorable safety profile for VTE prevention in children with congenital heart disease. Many studies with several different DOACs are ongoing to evaluate both safety and efficacy in unique patient populations, as well as VTE prevention. CONCLUSION: The literature regarding pediatric VTE treatment and prophylaxis is growing, but the need for evidence-based pediatric guidelines remains. Additional long-term, postauthorization studies are warranted to further elucidate safety and efficacy in clinical scenarios excluded in clinical trials. Additional data on safety, efficacy, and dosing strategies for reversal agents are also necessary, especially as the use of DOACs becomes more common in the pediatric population.

Erector spinae plane block as perioperative analgesia for midline sternotomy in cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Inadequate analgesia following cardiac surgery increases postoperative complications. Opioid-based analgesia is associated with side effects that may compromise postoperative recovery. Regional anesthetic techniques provide an alternative thereby reducing opioid requirements and potentially enhancing postoperative recovery. The erector spinae plane block has been used in multiple surgical procedures including sternotomy for cardiac surgery. We, therefore, aimed to characterize the impact of this block on post-sternotomy pain and recovery in cardiac surgery patients. METHODS: We conducted an electronic search for studies reporting on the use of the erector spinae plane block in adult cardiac surgery via midline sternotomy. Randomized controlled trials, cohort studies, and case-control studies were considered for inclusion. Outcomes of interest included postoperative pain, time-to-extubation, and intensive care unit length of stay. RESULTS: In total, 498 citations were identified and five were included in the meta-analysis. The erector spinae plane block did not significantly reduce self-reported postoperative pain scores at 4 h (-2.04; 95% confidence interval [CI] -8.15 to 4.07; p = .29) or 12 h (-0.27; 95% CI -2.48 to 1.94; p = .65) postextubation, intraoperative opioid requirements (-3.07; 95% CI -6.25 to 0.11; p = .05], time-to-extubation (-1.17; 95% CI -2.81 to 0.46; p = .12), or intensive care unit (ICU) length of stay (-4.51; 95% CI -14.23 to 5.22; p = .24). CONCLUSIONS: Erector spinae plane block was not associated with significant reduction in postoperative pain, intraoperative opioid requirements, time-to-extubation, and ICU length of stay in patients undergoing cardiac surgery. The paucity of large randomized controlled trials and the high heterogeneity among studies suggest that further studies are required to assess its effectiveness in cardiac surgery patients.

Median sternotomy pain after cardiac surgery: To block, or not? A systematic review and meta-analysis.

BACKGROUND: Inadequate pain control after median sternotomy leads to reduced mobilization, increased respiratory complications, and longer hospital stays. Typically, postoperative pain is controlled by opioid analgesics that may have several adverse effects. Parasternal intercostal block (PSB) has emerged as part of a multimodal strategy to control pain after median sternotomy. However, the effectiveness of this intervention on postoperative pain control and analgesic use has not been fully established. METHODS AND RESULTS: We conducted a meta-analysis to assess the effect of PSB on postoperative pain and analgesic use in adult cardiac surgery patients undergoing median sternotomy. PubMed, Embase, Google Scholar, and the Cochrane database were searched with the following search strategy: ([postoperative pain] or [pain relief] OR [analgesics] or [analgesia] or [nerve block] or [regional block] or [local block] or [regional anesthesia] or [local anesthetic] or [parasternal block] and [sternotomy]) and (humans [filter]). Inclusion criteria were: patients who underwent cardiac surgery via median sternotomy, age >18 and parasternal block (continuous and single dose). Exclusion criteria were: noncardiac surgery, nonparasternal nerve blocks, and the use of NSAIDS in parasternal block. Quality assessment was performed by three independent reviewers via the Cochrane risk of bias assessment tool. Of 1165 total citations, 18 were found to be relevant. Of these 18 citations, 7 citations (N = 2223 patients) reported postoperative pain scores in an extractable format and 11 citations (N = 2155 patients) reported postoperative opioid use in an extractable format. For postoperative opioid use, morphine equivalent doses were calculated for all studies and postoperative pain scores were standardized to a 10-point visual analog scale for comparison between studies; both these were reported as total opioid use or cumulative score ranging from 24 to 72 h postoperative. All data analyses were run using a random effects model, using a restricted maximum likelihood estimator, to obtain summary standardized mean differences with 95% confidence interval (CI's). For studies which only reported median and interquatile range (IQR), the median was standard deviation was estimated by IQR/1.35. Following median sternotomy both postoperative pain (SMD [95% CI] -0.49 [-0.92 to -0.06]) and postoperative morphine equivalent use (SMD [95% CI] -1.68 [-3.11 to -0.25]) were significantly less in the PSB group. CONCLUSION: Our meta-analysis suggests that parasternal nerve block significantly reduces postoperative pain and opioid use.

The use of sutureless and rapid-deployment aortic valve prosthesis in patients with bicuspid aortic valve: A focused review.

OBJECTIVE: The objective of this scoping review is to describe the postoperative outcomes and complications of patients with bicuspid aortic valve (BAV) treated with sutureless or rapid-deployment prosthesis. BACKGROUND: The use of sutureless and rapid-deployment prostheses is generally avoided in patients with BAV due to anatomical concerns and the elevated risk of para-prosthetic leaks. Multiple studies have reported the use of these prostheses into patients with BAV with varying degrees of success. The focus of this review is to consolidate the current available evidence on this topic. METHODS: A scoping review was conducted using a comprehensive search strategy in multiple databases (Medline, Embase, Cochrane Central Register of Controlled Clinical Trials) for relevant articles. All abstracts and full texts were screened by two independent reviewers according to predefined inclusion and exclusion criteria. Thirteen articles, including case reports and case series were ultimately included for analysis. RESULTS: Of 1052 total citations, 44 underwent full text review and 13 (4 case reports, 6 retrospective analyses, and 3 prospective analyses) were included in the scoping review. Across all 13 studies, a total of 314 patients with BAV were used for data analysis. In sutureless and rapid-deployment prostheses, the mean postoperative aortic valvular gradients were less than 15 mmHg in all studies with mean postoperative aortic valvular areas all greater than 1.3 cm.2 There were 186 total complications for an overall complication rate of 59%. Individual complications included new onset atrial fibrillation (n = 65), required pacemaker insertion (n = 24), intraprosthetic aortic regurgitation (n = 20), new onset atrioventricular block (n = 18), and new onset paravalvular leakage (n = 10). CONCLUSIONS: The use of sutureless and rapid deployment prostheses in patients with BAV showed comparable intraoperative and implantation success rates to patients without BAV. Postoperative complications from using these prostheses in patients with BAV included new onset atrial fibrillation, intraprosthetic aortic regurgitation, new onset atrioventricular block, and required pacemaker insertion. Various techniques have been described to minimize these complications in patients with BAV receiving sutureless or rapid deployment prostheses.

Galectin-3 as a Predictor of Post Cardiac Surgery Atrial Fibrillation: A Scoping Review.

Galectin-3 is associated with myocardial fibrosis, a known risk factor for developing re-entrant circuits associated with atrial fibrillation (AF). Previous studies have demonstrated increased galectin levels in AF patients. Whether preoperative galectin-3 levels can predict the incidence of postoperative atrial fibrillation (POAF) remains unknown.This scoping review was conducted in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Electronic searches were conducted in Medline, EMBASE, Cochrane, and Google Scholar databases using a predetermined strategy. Methodological variables, demographics and operative data were extracted. Data extraction was performed manually by 3 reviewers.The search yielded 620 citations, of which 74 underwent full text review, and 3 citations with 3 independent samples (n=1812) met full inclusion/exclusion criteria and were included. Of the 3 studies that reported on the association between preoperative galectin-3 levels and POAF, 2 studies compared median galectin levels in patients who developed POAF and those who did not. While Alexandre et al. reported a significant difference (P=0.002), Bening et al did not find a significant difference between POAF and non-POAF groups (P=0.3). A third study reporting on the association between galectin-3 and atrial fibrillation comparing third and first tercile galectin-3 levels found a significant association between preoperative galectin levels and POAF on univariate analysis (OR 1.54; 95% CI 1.14-2.09).Galectin-3 is an emerging biomarker that has been associated with the development of AF. However, there is currently not enough evidence to establish its prognostic role in postcardiac surgery atrial fibrillation.

Key articles and guidelines for the pediatric clinical pharmacist from 2019 and 2020.

PURPOSE: To summarize recently published research reports and practice guidelines deemed to be significantly impactful for pediatric pharmacy practice. SUMMARY: Our author group was composed of 8 board-certified pediatric pharmacists. Eight major themes were identified: critical care, hematology/oncology, medication safety, general pediatrics, infectious diseases, neurology/psychiatry, gastrointestinal/nutrition, and neonatology. The author group was assigned a specific theme(s) based on their practice expertise and were asked to identify articles using MEDLINE and/or searches of relevant journal articles pertaining to each theme that were published from January 2019 through December 2020 that they felt were "significant" for pediatric pharmacy practice. A final list of compiled articles was distributed to the authors, and an article was considered significant if it received a vote from 5 of the 8 authors. Thirty-two articles, including 16 clinical practice guidelines or position statements and 16 review or primary literature articles, were included in this review. For each of these articles, a narrative regarding its implications for pediatric pharmacy practice is provided. CONCLUSION: Given the heterogeneity of pediatric patients, it is difficult for pediatric pharmacists to stay up to date with the most recent literature, especially in practice areas outside their main expertise. Over the last few years, there has been a significant number of publications impacting the practice of pediatric pharmacists. This review of articles that have significantly affected pediatric pharmacy practice may be helpful in staying up to date on key articles in the literature.

Evaluation of initial atypical antipsychotic monitoring parameters in children and adolescents.

INTRODUCTION: Atypical antipsychotics (AAPs) are associated with serious cardiometabolic disturbances, including hyperlipidemia, hyperglycemia, and weight gain. The American Academy of Child and Adolescent Psychiatry Practice parameter for the use of AAPs in children and adolescents encourages that the same monitoring schedule as recommended by the American Diabetes Association be applied to the pediatric population. This study assessed adherence to these monitoring recommendations for AAPs in children and adolescents admitted to a community teaching hospital's inpatient child and adolescent psychiatry unit. METHODS: Patients age <18 years were included if therapy was initiated with an AAP during an inpatient admission to the child and adolescent psychiatry unit. Patients were excluded if prescribed an AAP prior to admission or if the AAP was ordered as needed. The presence of the following was collected upon initiation: body mass index (BMI), fasting blood glucose (FBG), blood pressure (BP), fasting lipids, heart rate (HR), waist circumference, electrocardiogram when indicated, and assessment of efficacy and extrapyramidal symptoms (EPS). Any adverse effects and means of mitigation of those adverse effects were also collected. RESULTS: In the 45 patients included, the following monitoring parameters were collected: 91.1% had BMI, 84.4% had FBG, 46.6% had fasting lipids, and 0% had waist circumference recorded. Additionally, 100% of patients had an assessment of efficacy and EPS and BP and HR documented. DISCUSSION: Although this study included a small number of patients, there is area for improvement in obtaining baseline monitoring parameters in children and adolescents initiated on AAPs during an inpatient admission.

Historical H1N1 Influenza Virus Imprinting Increases Vaccine Protection by Influencing the Activity and Sustained Production of Antibodies Elicited at Vaccination in Ferrets.

Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines.

Preliminary evidence of biased attentional mechanisms and reward processing in adults with obsessive-compulsive disorder.

Individuals with obsessive-compulsive-disorder (OCD) may have difficulties in using feedback from rewarding and punishing experiences to optimally guide future decisions. The current aim was to examine how adults with OCD use associative learning feedback to direct attention toward learned stimuli when the action-outcome contingency for those stimuli has changed. Participants first learned to select high-probability (over low-probability) rewarding stimuli and low-probability (over high-probability) loss stimuli. Participants then saw these stimuli as the second of two targets in a task where available attentional resources were limited. Recognition of learned stimuli during limited attention was driven by previously learned stimulus-response associations instead of an attentional benefit toward the most favorable action-outcome associations (reward-associated stimuli), as demonstrated in prior research with non-OCD adults. The current evidence supports the hypothesis that individuals with OCD have difficulties shifting from learned stimulus-response associations when the response-outcome contingencies change.

Back to the Future for Influenza Preimmunity-Looking Back at Influenza Virus History to Infer the Outcome of Future Infections.

The influenza virus-host interaction is a classic arms race. The recurrent and evolving nature of the influenza virus family allows a single host to be infected several times. Locked in co-evolution, recurrent influenza virus infection elicits continual refinement of the host immune system. Here we give historical context of circulating influenza viruses to understand how the individual immune history is mirrored by the history of influenza virus circulation. Original Antigenic Sin was first proposed as the negative influence of the host's first influenza virus infection on the next and Imprinting modernizes Antigenic Sin incorporating both positive and negative outcomes. Building on imprinting, we refer to preimmunity as the continual refinement of the host immune system with each influenza virus infection. We discuss imprinting and the interplay of influenza virus homology, vaccination, and host age establishing preimmunity. We outline host signatures and outcomes of tandem infection according to the sequence of virus and classify these relationships as monosubtypic homologous, monosubtypic heterologous, heterosubtypic, or heterotypic sequential infections. Finally, the preimmunity knowledge gaps are highlighted for future investigation. Understanding the effects of antigenic variable recurrent influenza virus infection on immune refinement will advance vaccination strategies, as well as pandemic preparedness.

A RANDOMIZED CONTROLLED TRIAL IN COMMUNITY MENTAL HEALTH CENTERS OF COMPUTER-ASSISTED COGNITIVE BEHAVIORAL THERAPY VERSUS TREATMENT AS USUAL FOR CHILDREN WITH ANXIETY.

OBJECTIVE: This study aims to examine the real-world effectiveness of a computer-assisted cognitive behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among anxious children presenting at community mental health centers. METHODS: One hundred children (7-13 years) with clinically significant anxiety were randomized to receive either 12 weekly computer-assisted CBT sessions or TAU for an equivalent duration. Assessments were conducted by independent evaluators at screening/baseline, midtreatment, posttreatment, and 1-month followup (for computer-assisted CBT treatment responders). RESULTS: There were significant between-group effects favoring the computer-assisted CBT condition on primary anxiety outcomes. Thirty of 49 (61.2%) children randomized to computer-assisted CBT responded to treatment, which was superior to TAU (6/51, 11.8%). Relative to TAU, computer-assisted CBT was associated with greater reductions in parent-rated child impairment and internalizing symptoms, but not child-rated impairment and anxiety and depressive symptoms. Treatment satisfaction and therapeutic alliance in those receiving computer-assisted CBT was high. Treatment gains in computer-assisted CBT responders were maintained at 1-month followup. CONCLUSIONS: Within the limitations of this study, computer-assisted CBT is an effective and feasible treatment for anxious children when used in community mental health centers by CBT-naïve clinicians.

Phenomenology and clinical correlates of family accommodation in pediatric anxiety disorders.

Despite evidence documenting high prevalence of family accommodation in pediatric obsessive-compulsive disorder, examination in other pediatric anxiety disorders is limited. Preliminary evidence suggests that family accommodation is common amongst children with anxiety disorders; however, the impact on clinical presentation and functional impairment has not been addressed. This study assessed the nature and clinical correlates of family accommodation in pediatric anxiety, as well as validating a mechanistic model. Participants included 112 anxious youth and their parents who were administered a diagnostic clinical interview and measure of anxiety severity, as well as questionnaires assessing internalizing and externalizing symptoms, family accommodation and functional impairment. Some form of accommodation was present in all families. Family accommodation was associated with increased anxiety severity and externalizing behaviors, having a diagnosis of separation anxiety, and increased functional impairment. Family accommodation partially mediated the relationship between anxiety severity and functional impairment, as well as externalizing behaviors and functional impairment. Family accommodation is common in pediatric anxiety disorders, and is associated with more severe clinical presentations and functional impairment. These findings highlight the importance of parental involvement in treatment and the need to specifically target accommodation practices during interventions to mitigate negative outcomes in anxious youth. Further studies utilizing longitudinal data are needed to validate mechanistic models.

A pilot trial of cognitive-behavioral therapy augmentation of antibiotic treatment in youth with pediatric acute-onset neuropsychiatric syndrome-related obsessive-compulsive disorder.

BACKGROUND: This study reports an open trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD) exhibiting an onset pattern consistent with pediatric acute-onset neuropsychiatric syndrome (PANS). METHODS: Eleven primarily Caucasian youth with PANS-related OCD (range=4-14 years; 6 boys) who were incomplete responders to antibiotic treatment, received family-based CBT delivered either face-to-face or via web camera. RESULTS: All participants completing treatment (8 of 8) were considered improved at posttreatment, and average obsessive-compulsive symptom severity was reduced by 49%. Significant reductions in obsessive-compulsive symptom severity and in clinician- and parent-rated OCD-related impairment were noted. Reductions in parent- and child-rated anxiety, child-rated OCD-related impairment, and comorbid neuropsychiatric symptoms were not statistically significant. CONCLUSIONS: Gains were maintained at follow-up, with 100% (6 of 6) of those assessed remaining improved. Implications for treatment and further research are discussed.