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The PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) Collaboration

Optimizing risk predictive strategies in febrile neutropenic episodes in children and young people undergoing treatment for malignant disease

Children and young people with cancer are treated with drugs which successfully cure their cancer in about four out of every five treated, but also suppress their immune system making them open to life-threatening infections. This situation is known as ‘febrile neutropenia’ (FN), and is usually treated with a blanket approach of admission to hospital and delivery of intravenous antibiotics. In the past, many groups have attempted to devise simple systems to work out which children are least likely to develop severe infections and then allow these children to leave hospital more quickly or be treated less aggressively.

The PICNICC Collaboration was formed to evaluate the existing research, and to collect and quantitatively synthesise this to develop a new risk prediction model. This was accomplished by the groups sharing individual participant data (IPD) from their original studies. The multivariable predictive model was then tested, alongside others from an Australian group, and developed a new simple rule that altered how we managed patients in the COVID19 pandemic and beyond.

The research group has also developed the methods of undertaking such studies, including advice on what aspects to include and ways of conducting the analyses, and have run international symposia. We are also assessing the benefits of additional blood tests at Leeds Children’s Hospital. One study used a two-minute YouTube video to assist explaining the study to children (and their parents):

https://youtu.be/Z1AXzJqatds

The results are explained in this mini-documentary:

 

Further projects look at other approaches to managing infection, along with developments in the methods of research and communication of similar research findings.

This programme of research has both immediate and longer term possibilities to improve the management of paediatric FN across the world by reducing unnecessary antibiotic usage and increasing intensity of support for those who are likely to become the most seriously unwell.

Should you wish to find out more to consider becoming involved, please contact Dr Bob Phillips at: bob.phillips@york.ac.uk twitter on @drbobphillips or phone (01904) 321099.

Publications

Risk stratification in febrile neutropenic episodes in adolescent/young adult patients with cancer

Predicting microbiologically defined infection in febrile neutropenic episodes in children: global individual participant data multivariable meta-analysis

Systematic review of reduced therapy regimens for children with low risk febrile neutropenia

Core outcomes and definitions for pediatric fever and neutropenia research: A consensus statement from an international panel

Protocol for a systematic review of reductions in therapy for children with low risk febrile neutropenia

"Cross hairs" plots for diagnostic meta-analysis.

Challenges in the management of febrile neutropenia.

Clinical decision rules: how to build them.

Clinical decision rules: how to use them.

Ethical and regulatory considerations in the use of individual participant data for studies of disease prediction.

Fluoroquinolones in pediatric fever and neutropenia – a systematic review of prospective trials.

Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. 

Predicting infectious complications in neutropenic children and young people with cancer (IPD Protocol).

The reporting of outcomes in studies of fever and neutropenia in children with cancer: Time for consensus.

Systematic review and meta-analysis of discriminatory performance of risk prediction rules in febrile neutropenic episodes in children and young people. 

Systematic review and meta-analysis of the value of clinical features to exclude radiographic pneumonia in febrile neutropenic episodes in children and young people. 

Time for paediatric febrile neutropenia guidelines - children are not little adults.

Updated systematic review and meta-analysis of the performance of risk prediction rules in children and young people with febrile neutropenia.

The value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer: a systematic review and meta-analysis