Leveraging real-world Data from administrative claims and medical records to inform safety and effectiveness of piperacillin-tazobactam in the Management of Pediatric Hospital Acquired Pneumonia.

Pediatric-specific safety data are required during development of pharmaceutical agents. Retrospective studies can leverage real-world data to assess safety and effectiveness in children where prospective, controlled studies are not feasible. A retrospective cohort study combined data from Pediatric Health Information Systems (PHIS) and medical records to evaluate the safety and effectiveness of piperacillin/tazobactam (P/T) in pediatric patients with hospital-acquired pneumonia (HAP). After identifying 407 patients diagnosed with HAP receiving P/T (n=140) or Comparator (n=267) HAP-appropriate antibiotics between 2003-2016 across seven pediatric institutions, we evaluated comparative risk of a serious adverse event (SAE). Clinical improvement 14 days after therapy initiation was studied as a secondary outcome. Incidence rate ratios (IRRs) were calculated to compare between exposure groups using inverse probability-weighted Poisson regression models. The unadjusted and adjusted IRRs with 95% CIs for SAEs were 1.26(0.66-2.39) and 1.24(0.65-2.35). The unadjusted and adjusted ORs with 95% CIs for clinical improvement were 1.14(0.56-2.34) and 1.50(0.67-3.38). Point estimates from this retrospective analysis suggest similar safety and clinical effectiveness of P/T and comparator antibiotics for treating HAP. However, due to wide CIs, actual between-group differences cannot be excluded. Existing real-world data can be utilized to inform pediatric-specific safety and effectiveness of medications used in off-label settings.

An Usual Presentation of Pneumocystis jirovecii Pneumonia in a Woman Treated With Immune Checkpoint Inhibitor.

We describe a case of Pneumocystis jirovecii pneumonia in an 18-year-old female individual with refractory primary mediastinal B-cell lymphoma treated with the immune checkpoint inhibitor pembrolizumab. She received 11 doses of pembrolizumab without immune-related adverse events (irAEs) before the diagnosis of P. jirovecii pneumonia. However, prophylactic trimethoprim/sulfamethoxazole was discontinued 6 months of postautologous stem cell transplant per standard guidelines. This case report highlights the importance of judicious infectious disease evaluation while on immune checkpoint inhibitor therapy as symptoms can often mimic irAEs. Furthermore, the benefits of immunosuppressive therapy for the treatment of presumptive irAEs must be weighed against the possible increased risk for opportunistic infections.

Ecological Dynamics: Integrating Empirical, Statistical, and Analytical Methods.

Understanding ecological processes and predicting long-term dynamics are ongoing challenges in ecology. To address these challenges, we suggest an approach combining mathematical analyses and Bayesian hierarchical statistical modeling with diverse data sources. Novel mathematical analysis of ecological dynamics permits a process-based understanding of conditions under which systems approach equilibrium, experience large oscillations, or persist in transient states. This understanding is improved by combining ecological models with empirical observations from a variety of sources. Bayesian hierarchical models explicitly couple process-based models and data, yielding probabilistic quantification of model parameters, system characteristics, and associated uncertainties. We outline relevant tools from dynamical analysis and hierarchical modeling and argue for their integration, demonstrating the value of this synthetic approach through a simple predator-prey example.

Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.

PURPOSE: The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. METHODS: An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. RESULTS: The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. CONCLUSION: We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.

Kyphoplasty--minimally invasive vertebral compression fracture repair.

OSTEOPOROSIS is a skeletal disorder that compromises bone strength, predisposing a person to an increased risk of fracture. An estimated 700,000 spinal fragility fractures, such as vertebral compression fractures, directly related to osteoporosis occur annually. KYPHOPLASTY, a minimally invasive fracture reduction procedure, has become a treatment option for osteoporotic fractures. A balloon is used in place of the conventional bone tamp to reduce the fracture and create a void in cancellous spinal bone. Polymethylmethacrylate, a cement-like material, is injected into the void to stabilize the fracture. EARLY DIAGNOSIS AND TREATMENT of vertebral compression fractures with kyphoplasty allows normal anatomy to be restored, ultimately decreasing the risk of patient morbidity.