Risk of serious bacterial infection associated with tumour necrosis factor-alpha inhibitors in children with juvenile idiopathic arthritis.

OBJECTIVES: TNF-α inhibitors (TNFIs) have a black box warning for increased risk of serious infection that was based on evidence from studies of adults. Evidence of the association is lacking for children. We aimed to examine the risk of infection posed by TNFIs compared with DMARDs in children with JIA. METHODS: We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims and Encounters database. Children <16 years old with JIA who initiated monotherapy with TNFIs or DMARDs were identified and followed for occurrence of serious bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios for infection associated with TNFIs compared with DMARDs, adjusting for potential confounders with high-dimensional propensity scores and time-varying CS use. RESULTS: We identified 2013 DMARD initiators and 482 TNFI initiators with a mean follow-up of 255 and 307 days, respectively. We identified 18 and 11 patients with a serious infection in the DMARD and TNFI groups, resulting in crude rates of 1.28 (95% CI 0.76-2.02) and 2.72 (95%CI 1.36-4.86) per 100 person-years, respectively. In adjusted models, TNFIs were associated with an increased risk of serious bacterial infection compared with DMARDs (adjusted hazard ratio 2.72, 95% CI: 1.08, 6.86). CONCLUSION: Use of TNFIs poses a higher risk of serious infection compared with DMARDs in children with JIA. Our analysis confirms the US Food and Drug Administration warning about TNFI-associated infection in children with JIA.

Encouraging pharmacist intervention and standardization of labeling and dispensing of oral liquid medications.

OBJECTIVES: To initiate a call to action for community pharmacists and key-pharmacy stakeholders in the standardization of oral-liquid dosage forms. DATA SOURCES: Not applicable. SUMMARY: Unintentional overdose of medication due to administration error results in thousands of pediatric hospitalizations yearly. A lack of prescription and dosage device standardization pertaining to oral-liquid medications continue to be a public health hazard. Multiple professional organizations have publicly endorsed the standardization of oral liquid dosage forms. Universal adoption will not be achieved until key-pharmacy stakeholders encourage their pharmacists to use best practices when verifying and preparing prescription medication. Specifically, these practices should include immediate conversion of prescriptions containing non-metric volumes into metric volumes, providing appropriate sized oral dosing syringes for all oral liquid prescriptions, writing dosing directions in the safest format, and counseling patients and caretakers of proper medication administration. CONCLUSION: Community pharmacists are uniquely positioned to lead the universal adoption of these best practices to ensure proper oral-liquid dosing administration for all patients.

Evaluation of Outpatient Antibiotic Prescribing for Urinary Tract Infection in Pediatric Patients Ages 2 Months to 18 Years.

OBJECTIVE: To characterize the diagnosis and management of urinary tract infection (UTI) in pediatric patients at the University of Illinois Hospital and Health Sciences System (UIH), with an emphasis on antibiotic prescribing; in addition, to characterize pediatric uropathogen patterns to help guide future empiric therapy choices. METHODS: We used a retrospective, descriptive study of pediatric patients ages 2 months to ≤18 years seen at the UIH emergency department or clinic from January 1, 2014, to August 31, 2018, with ICD-9 or ICD-10 discharge diagnosis of UTI. Data collected included presenting symptoms, urinalysis, details of antibiotic regimens, urine culture, and susceptibility results. RESULTS: Of the 207 patients included, the median age was 5.7 years (IQR, 3.2-9.4), and 183 patients (88.4%) were female. Common symptoms included dysuria (57%) and fever (37%). Empiric antibiotics were p-rescribed in 96.1% of cases, most commonly cefdinir (42%), cephalexin (22%), and sulfamethoxazole-trimethoprim (14%). Urine cultures were collected in 161 patients (77.8%), with 81 growing >50,000 colony-forming units bacteria. Escherichia coli was the most commonly isolated organism (82.1%), showing susceptibility to third-generation cephalosporins (97%), nitrofurantoin (95%), and sulfamethoxazole-trimethoprim (84%). Although 25 urine cultures showed no growth, antibiotics were discontinued in only 4 cases. CONCLUSIONS: Pediatric patients with UTI symptoms were often empirically prescribed cefdinir, possibly an unnecessarily broad choice because many E coli isolates were susceptible to narrower agents. Both urinalysis and urine cultures should be obtained during the diagnostic evaluation of UTI, with better follow-up of negative cultures to potentially discontinue antibiotics. This study highlights areas for improvement in the diagnosis, treatment, and antimicrobial stewardship in pediatric UTI.

Closer look at autism and the measles-mumps-rubella vaccine.

OBJECTIVE: To educate pharmacists regarding the hypothesis that the measles-mumps-rubella (MMR) vaccine is linked to the development of autism. DATA SOURCES: Articles published from 1998 to 2009 were identified through electronic searches of Medline. STUDY SELECTION: Articles were included if they evaluated or reviewed a possible link between the MMR vaccine and autism or discussed MMR epidemiology, legal proceedings involving the MMR vaccine and autism, or health professionals' impact on immunization decisions. DATA SYNTHESIS: A total of 27 articles were identified. Of the articles, 74% (20 of 27) were included in the review because of their relevance to the study topic. CONCLUSION: The evidence presented does not show a causal relationship between the MMR vaccine and autism. Myths presented to potentially support any relationship between the MMR vaccine and autism have not been proven. Expert testimony refuting initial scientific theories has led to Supreme Court decisions that do not support a link between the MMR vaccine and autism. Pharmacists and all health care providers are responsible for informing and educating parents and families regarding this information so that they can make informed decisions about immunizations.

Identification of Errors in Pediatric Prescriptions and Interventions to Prevent Errors: A Survey of Community Pharmacists.

OBJECTIVES: Assess the competency of community pharmacists in identifying errors in pediatric prescriptions and to determine how often pharmacists perform interventions known to mitigate the likelihood of error. The study sought to recognize factors that may impact the pharmacist's ability to identify and mediate these errors, and to detect barriers that limit the role of the pharmacist pediatric patient care. METHODS: A survey was distributed through the University of Illinois at Chicago College of Pharmacy Alumni Network and the Illinois Pharmacists Association email listservs. Pharmacists practicing in a retail setting within the last 5 years were included. Three prescription scenarios for commonly used pediatric medications with corresponding questions were created to assess a pharmacist's ability to identify errors. Demographics pertaining to the pharmacist and the practice site, as well as information about dispensing practices, were collected. Logistic regression was used to identify factors that might impact the pharmacists' ability to identify errors. RESULTS: One hundred sixty-one respondents began the survey and 138 met inclusion criteria. In 15% to 59% of scenario-based questions, pharmacists did not appropriately identify errors or interventions that would decrease the likelihood of error. Correct identification of doses was associated with total prescription volume in one scenario and with pediatric prescription volume in another scenario. Pharmacists did not consistently label prescriptions for oral liquids in milliliters or dispense oral syringes. Barriers to pharmacist involvement included availability and interest of the caregiver, ability to contact prescriber, and pharmacy staffing. CONCLUSION: Community pharmacists did not consistently identify medication errors or use interventions known to mitigate error risk.

Considerations for Providing Ambulatory Pharmacy Services for Pediatric Patients.

Pediatric clinical pharmacists are an integral part of the health care team. By practicing in an ambulatory care clinic, they can reduce the risk of medication errors, improve health outcomes, and enhance patient care. Unfortunately, because of limited data, misconceptions surrounding the role of pharmacists, and reimbursement challenges, there may be difficulty in establishing or expanding pediatric clinical pharmacy services to an ambulatory care setting. The purpose of this paper is to provide an overview of considerations for establishing or expanding pharmacy services in a pediatric ambulatory care clinic. The primer will discuss general and pediatric-specific pharmacy practice information, as well as potential barriers, and recommendations for identifying a practice site, creating a business plan, and integrating these services into a clinic setting.

Risk of Serious Bacterial Infection Associated With Tumor Necrosis Factor-Alpha Inhibitors in Children and Young Adults With Inflammatory Bowel Disease.

Background: Prior studies evaluating the relationship between tumor necrosis factor-alpha inhibitors (TNFI) and infection were conducted in adults and had conflicting findings. We sought to examine the risk of serious infection associated with TNFIs compared with nonbiologic immunomodulators in children and young adults with inflammatory bowel disease (IBD) and to compare the risk among individual TNFIs. Methods: We conducted a cohort study using the Truven MarketScan Commercial Claims and Encounters database of patients age <30 years with a diagnosis of IBD who initiated treatment with a TNFI or immunomodulator (thiopurines or methotrexate) between 2009 and 2013. The outcome of interest was serious infection, defined as a nongastrointestinal bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for serious infection associated with TNFIs compared with immunomodulators. Results: We identified 10,838 children and young adults with IBD; 236 and 192 cases of serious infection were observed in 4502 TNFI initiators (5.25/100 person-years) and 6336 immunomodulator initiators (3.59/100 person-years), respectively. Compared with immunomodulators, TNFIs were associated with a higher risk of serious infection (HR, 1.36; 95% CI, 1.08-1.72). Among TNFI users, certolizumab showed a 3.38-fold (95% CI, 2.25-5.09) increased risk vs infliximab, and subcutaneously administered TNFIs also exhibited a higher risk (HR, 1.34; 95% CI, 1.18-1.53) than intravenous TNFIs. Conclusions: TNFIs pose a higher risk of serious infection compared with immunomodulators in children and young adults with IBD, and this risk differs among individual TNFIs and routes of administration.

A Review of Pharmacological Management of Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common psychological diagnosis in children. This disorder impacts children and adolescents in all areas of life, including academic performance, extracurricular activities, and social interactions. ADHD can continue into adulthood where unemployment and substance abuse has been described. Although behavioral therapy is recommended for all patients with ADHD, medication management typically is initiated soon after diagnosis. Psychostimulants remain the primary medication of choice. This review focuses on the clinical use of psychostimulant medication in children and adolescents. The pharmacodynamic and pharmacokinetic differences between the newest long-acting formulations as well as commonly encountered adverse drug reactions, with suggested management strategies, will be highlighted. Non-stimulant therapy with atomoxetine or alpha2-adrenergic agonists is also reviewed. These agents may be warranted for patients who cannot tolerate psychostimulant therapy or have a comorbid condition. Finally, the 8-year multimodal treatment study results are also discussed.

Use of Tumor Necrosis Factor-Alpha Inhibitors in Children and Young Adults With Juvenile Idiopathic Arthritis or Rheumatoid Arthritis.

OBJECTIVE: To characterize the use of tumor necrosis factor-α inhibitors (TNFIs) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA). METHODS: Patients with incident JIA or RA were identified by using the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. The incident diagnosis was defined as no prior claims with a JIA/RA code and no JIA/RA medications recorded during the previous 6 months. TNFI use patterns were examined, including switching among TNFIs, adherence, persistence, and time from diagnosis to TNFI use. Earlier TNFI treatment without prior use of traditional disease-modifying antirheumatic drugs (DMARDs) and use of specific TNFIs were analyzed by age group. RESULTS: Of 6929 children and young adults with new diagnoses of JIA/RA, 18.6% were treated with TNFIs. In these TNFI users, 39.1% received earlier TNFI therapy without prior use of DMARDs. The use of TNFIs was higher in patients diagnosed between 2012 and 2013 than that in patients diagnosed between 2009 and 2011 (hazard ratio 1.13, 95% confidence interval 1.00-1.28). Etanercept was the most commonly used, especially by children aged < 12 (75.5%) and adolescents aged 12 to 17 (62.5%) years. Adherence measured as mean proportion of days covered ranged from 70.4% to 93.2% for individual TNFI agents. Only about 60% of patients continuously took TNFIs for 12 months. When switching occurred, switching from etanercept to adalimumab was the most common pattern. CONCLUSION: Earlier TNFI therapy was observed in 39.1% of children and young adults taking TNFIs. In addition, the time to the first TNFI prescription became shorter over the study period. Future research should evaluate the long-term effectiveness and safety of this more aggressive TNFI therapy.

Top-down Versus Step-up Prescribing Strategies for Tumor Necrosis Factor Alpha Inhibitors in Children and Young Adults with Inflammatory Bowel Disease.

BACKGROUND: Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described. METHODS: We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies. RESULTS: A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%). CONCLUSIONS: Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination.

Approach to the pediatric prescription in a community pharmacy.

Pediatric patients are more susceptible to medication errors for a variety of reasons including physical and social differences and the necessity for patient-specific dosing. As such, community pharmacists may feel uncomfortable in verifying or dispensing a prescription for a pediatric patient. However, the use of a systematic approach to the pediatric prescription can provide confidence to pharmacists and minimize the possibility of a medication error. The objective of this article is to provide the community pharmacist with an overview of the potential areas of medication errors in a prescription for a pediatric patient. Additionally, the article guides the community pharmacist through a pediatric prescription, highlighting common areas of medication errors.

The Latest Update on Over-the-Counter Cough and Cold Product Use in Children.

The use of over-the-counter (OTC) cough and cold products in children has become a hot topic in the news in the past year due to the potential risk associated with using these products in children. The most recent recommendations were announced in October 2008 from The Consumer Healthcare Products Association (CHPA) which stated that OTC cough and cold medications should not be used in children less than 4 years old.(1) Because of this, parents and healthcare professionals have many questions and concerns. This article will review the current data supporting the recent recommendations and provide strategies and suggestions for educating parents and caregivers when a child has complaints of cough and cold symptoms.

Identification of medication non-adherence factors in adolescent transplant patients: the patient's viewpoint.

Studies report a clear association between medication non-adherence and an unfavorable transplant outcome. The adolescent population, in particular, has difficulty adhering to post-transplant medication regimens. The purpose of this study is to identify, categorize and understand the opinions of adolescent transplant patients regarding why they may not take their medications as prescribed. From January to August 2005, nine adolescent kidney transplant patients at an urban medical center were surveyed and asked to rank-order 33 statements regarding their opinions on why adolescents may not take their medications as prescribed. Q-methodology, a powerful tool in subjective study, was used to identify and categorize the viewpoints of adolescents on this subject. Three factors emerged and were labeled to reflect their distinct viewpoints: (1) Medication Issues (e.g. taste, size, frequency, schedule), (2) Troubled Adolescent (e.g. poor home life, depression, overwhelming situation), and (3) Deliberate Non-Adherer (e.g. attention-seeker, infallible attitude). By understanding these different viewpoints and the factors that contribute to them, it may be easier to identify which management approach to non-adherence works best in specific subgroups of patients.

Early discontinuation of steroids is safe and effective in pediatric kidney transplant recipients.

In pediatric kidney transplantation, steroid induced growth retardation and cushingoid features are of particular concern. In children, gradual steroid withdrawal late after kidney transplantation increases the risk of rejection. In this pilot study, we investigated the outcome of pediatric renal transplantation with an early steroid withdrawal protocol. This is a retrospective case-control study of pediatric renal transplants with age-matched historical control. Groups were comparable in terms of HLA matching, donor type and graft ischemia time. In the steroid withdrawal group (SWG, n = 13), induction therapy included mycophenolate mofetil (MMF) and a 5-day course of steroids with Thymoglobulin in 11 and basiliximab in two other patients. In the steroid group (SG, n = 13), in addition to steroids, four patients were given basiliximab, eight were given Thymoglobulin, and one OKT3. Maintenance therapy included tacrolimus (SWG n = 11, SG n = 3) or cyclosporine (SWG n = 2, SG n = 10). Azathioprine was given to all the patients in the SG, except the last two patients of this series who were prescribed MMF. MMF was given to all in the SWG. Patient and graft survival rates were 100% in both groups. In the SWG, no acute rejection episode was detected. In the steroid group, three patients (25%) presented with an acute rejection episode. All but one patient in either group showed immediate graft function. Patients in the steroid-withdrawal group exhibited a significantly higher creatinine clearance at 6 and 12 months post-transplant (95.8 +/- 23.3 vs. 71.3 +/- 21.9, p = 0.03; and 91.3 +/- 21.6 vs. 69.6 +/- 28.6, p = 0.04). In the SWG delta BMI was significantly lower and delta height Z score was significantly higher, and we observed significantly less hyperlipidemia, body disfigurement, and need for anti-hypertensive medication. Early steroid withdrawal in pediatric renal transplant recipients is efficacious and safe and does not increase risk of rejection, preserving optimal growth and renal function, and reducing cardiovascular risk factors.