Background: Caffeine is commonly consumed during pregnancy, crosses the placenta, with fetal serum concentrations similar to the mother's, but studies of birth outcome show

Background: Ovarian, peritoneal, and fallopian tube cancer are deadly diseases with similar pathological and clinical features. Despite initial therapy with cytoreductive surgery and platinum-based therapy, many patients experience disease relapse either during (refractory) or within 6 months after (resistant) first-line platinum-based therapy. In these patients, various chemotherapies offer clinical activity but none is universally preferred. WEE1 tyrosine kinase is a critical component of G2/M cell cycle checkpoint control and mediates cell cycle arrest by regulating the phosphorylation of cyclin-dependent kinase 1 (CDK1). Inhibition of WEE1 leads to premature mitotic entry, DNA damage and apoptosis induction, and cell death. ZN-c3 is a novel, selective, and orally bioavailable WEE1 inhibitor that has demonstrated significant antitumor activity in nonclinical in vitro and in vivo models. A first-in-human study identified the maximum tolerated dose (MTD) of ZN-c3 when given as monotherapy.Combining ZN-c3 with chemotherapy may inhibit repair of chemotherapy-induced DNA damage and provide therapeutic benefit in this population.Trial design: This phase 1b, open-label, multicenter study is evaluating the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of ZN-c3 in combination with pegylated liposomal doxorubicin, carboplatin, paclitaxel, or gemcitabine. The primary objectives are to determine MTDs and recommended phase 2 doses for each combination by a modified Bayesian continual reassessment method. Subjects are adult women with high-grade serous epithelial ovarian, peritoneal, or fallopian tube carcinoma who have received 1 or 2 prior chemotherapy regimens including platinum-based therapy and are refractory or resistant to platinum-based therapy. Study drug therapy is given in repeated 21-or 28-day cycles until disease progression or unacceptable toxicity. ZN-c3 is taken orally once daily. Chemotherapy is administered per protocol. Pharmacodynamic effects of therapy in tumor tissue and hair follicle samples will be explored. Subject recruitment is ongoing.

AimsPATCH is a pilot acute community children’s nurse led service delivering assessment and treatment for children at home who are moderately unwell and might otherwise be admitted to hospital or attend Paediatric Emergency Department (PED). Children are referred by PED or GP and followed up via telephone support and home visits depending on clinical need for duration of acute illness.MethodsPilot year funded by Imperial Charity. Using evaluation to build business case for sustained commissioned service. Phase 1 Sept 2016 – May 2017 : reduced short stay admissions and re-attendances to PED for common mild-moderate respiratory conditions e.g., viral wheeze, bronchiolitis. Phase 2 from May 2017 : piloting direct GP referrals to PATCH team to evaluate impact in reducing attendances to PED for children needing further assessment or support beyond GP consultation, and enabling families to manage common acute conditions at home.Using QI methodology, Model for Improvement we developed a driver diagram and used real-time PDSA cycles to capture our learning and inform small iterative changes of service development. Process mapping and world cafe style events were held with local community nurses, health visitor leads, GPs and commissioners to co-design referral pathways and explore more widely how PATCH fits into the whole urgent care system.Figure 1Parental feedback evaluated via semi structured interviews.ResultsActivity – Appendix 1Phase 1 – Concentrated on respiratory conditions from PED.Total 188 referrals in first 7 months. Bronchiolitis 45%; viral wheeze 37.5%; asthma 7%; lower respiratory tract infections 5.4%.Figure 250% of patients received home visits and telephone consultations; 50% only telephone support.Successes: Cost effective – Appendix 273 acute admissions avoided, costing c£400 per/night97 PED re-attendances prevented at £117 per attendance.Projected cost avoidance within acute care provider £3 27 640 pa.Estimated cost of service £2 84 000 pa.Positive feedback and reported health seeking behaviour change – Appendix 3ChallengesInformation governance, cross organisational working, complex commissioning arrangements.Figure 3DiscussionWithin first 7 months PATCH has had a significant impact on avoiding admissions and re-attendances, thus improving flow and performance in PED. The projected financial impact is that it is cost effective.We are using this data to pursue a business case internally and with local CCGs. We are optimistic of succeeding and using phase 2 to build on partnerships garnered across the whole system to expand PATCH’s impact further by reducing PED attendances and continuing to improve our local urgent care pathway for children.

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