Secondary immunodeficiencies and infectious considerations of biologic immunomodulatory therapies.

Biologic immunomodulatory medications have rapidly expanded in the previous decades, providing new treatment options for individuals with a spectrum of oncologic, allergic, rheumatologic, and neurologic conditions. Biologic therapies alter immune function and can impair key host defense mechanisms, resulting in secondary immunodeficiency and increased infectious risks. Biologic medications can increase general risk for upper respiratory tract infections but can also be associated with unique infectious risks owing to distinct mechanisms of action. With the widespread use of these medications, providers in every area of medicine will likely care for individuals receiving biologic therapies and understanding their potential infectious complications can help mitigate these risks. This practical review discusses the infectious implications of biologics by class of medication and provides recommendations regarding the examination and screening both before therapy initiation and while the patient is receiving the medication. With this knowledge and background, providers can reduce risk whereas patients receive the treatment benefits of these biologic medications.

Integrating education for clinical practice change.

BACKGROUND: Children with chronic medical conditions and their families have significant emotional health concerns, yet paediatricians are often ill-equipped to address these needs. The American Board of Pediatrics launched the Roadmap Project to better support emotional health as part of routine care. We present pilot work in paediatric training programmes to test educational approaches and explore lessons learned. APPROACH: Four institutions implemented Roadmap tools into their paediatric training programmes, either incorporating them into existing educational structures or embedding them into the clinical workplace. One programme utilised an existing longitudinal curriculum, and another incorporated into a block rotation. Two programmes embedded training for residents into a larger programme for the healthcare team within the clinical space, one in outpatient clinics and one in an inpatient service. EVALUATION: Evaluation strategies at each site matched the intended outcomes. Sites working within education programmes evaluated learners, demonstrating increases in resident skills and confidence on pre-/post-self-assessments. Sites embedding tools into the practice context measured changes in the clinical practice of the healthcare team. Despite variability in implementation, all approaches improved trainee skills; sites embedding education into a clinical setting saw greater changes in clinical practice. IMPLICATIONS: Our pilot provided structure yet allowed for flexibility, and all sites improved trainee skills. Engaging the entire healthcare team within practice settings appears advantageous, thus embedding education into clinical practice may be preferable to a separate education programme. Similar to outcomes found in interprofessional education (IPE), educating clinical teams together may be more impactful for cultural shifts needed for changing clinical practice.

Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

Improving Vitamin D Screening in a Pediatric Rheumatology Clinic Using Structured Quality Improvement Process.

Introduction: Monitoring levels of 25-hydroxyvitamin D (25-OHD) is an integral part of bone health assessment in the general pediatric population, especially in at-risk populations such as children with juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (c-SLE), and juvenile dermatomyositis (JDM). However, only 38% of the patients with JIA, c-SLE, and JDM receiving care at Nationwide Children's Hospital Rheumatology clinic in 2016 had a 25-OHD level ordered in the preceding year. The objective of this project was to increase the percentage of 25-OHD levels ordered in patients with JIA, c-SLE, and JDM from 38% to 80% in 11 months and sustain it for 6 months. Methods: A multidisciplinary team initiated a continuous improvement project utilizing the Lean Six Sigma methodology. The team diagrammed the clinical process and identified steps that needed improvement. In addition, the team completed a root cause analysis of the process and brainstormed subsequent countermeasures. Results: The team did not meet the 80% target but did order a 25-OHD level on 61% of patients by the end of the study period compared to 38% at the start of the study (P value 0.001). The level was sustained after the study period, with 68% of these children having a 25-OHD level ordered. Conclusion: The team successfully improved the screening processes for vitamin D deficiency in a busy subspecialty clinic setting using Lean Six Sigma methodology.

Alternatively activated macrophages in intestinal helminth infection: effects on concurrent bacterial colitis.

The distribution of several pathogenic helminth infections coincides geographically with many devastating microbial diseases, including enteric bacterial infections. To dissect the mechanisms by which helminths modulate the host's response to enteric bacteria and bacteria-mediated intestinal inflammation, we have recently established a coinfection model and shown that coinfection with the helminth Heligmosomoides polygyrus exacerbates colitis induced by infection with the gram-negative bacterial pathogen Citrobacter rodentium. The disease severity of the coinfected mice was correlated with high Citrobacter loads in the gut, translocation of the bacteria into mucosal and systemic immune compartments, delayed bacterial clearance, and a significantly enhanced colonic TNF-alpha response. In the present study, using our in vivo coinfection model as well as in vitro approaches, we test the hypothesis that the phenotypic and functional alterations in macrophages induced by the helminth-driven T cell response may contribute to the observed alterations in the response to C. rodentium. We show that via a STAT6-dependent mechanism H. polygyrus coinfection results in a marked infiltration into the colonic lamina propria of F4/80+ cells that have the phenotype of alternatively activated macrophages. Functional analysis of these macrophages further shows that they are impaired in their killing of internalized bacteria. Yet, these cells produce an enhanced amount of TNF-alpha in response to C. rodentium infection. These results demonstrate that helminth infection can impair host protection against concurrent enteric bacterial infection and promote bacteria-induced intestinal injury through a mechanism that involves the induction of alternatively activated macrophages.