A B S T R A C THealth information technology (HIT) has great potential for increasing patient engagement. Pediatric hematopoietic cell transplantation (HCT) is a setting ripe for using HIT but in which little research exists. "BMT Roadmap" is a web-based application that integrates patient-specific information and includes several domains: laboratory results, medications, clinical trial details, photos of the healthcare team, trajectory of transplant process, and discharge checklist. BMT Roadmap was provided to 10 caregivers of patients undergoing firsttime HCT. Research assistants performed weekly qualitative interviews throughout the patient's hospitalization and at discharge and day 100 to assess the impact of BMT Roadmap. Rigorous thematic analysis revealed 5 recurrent themes: emotional impact of the HCT process itself; critical importance of communication among patients, caregivers, and healthcare providers; ways in which BMT Roadmap was helpful during inpatient setting; suggestions for improving BMT Roadmap; and other strategies for organization and management of complex healthcare needs that could be incorporated into BMT Roadmap. Caregivers found the tool useful and easy to use, leading them to want even greater access to information. BMT Roadmap was feasible, with no disruption to inpatient care. Although this initial study is limited by the small sample size and singleinstitution experience, these initial findings are encouraging and support further investigation.
Objective The Periodic fever syndromes (PFS) are a group of disorders of the innate immune system. We investigated patients diagnosed with PFS at the Dartmouth Hitchcock Pediatric Rheumatology Clinic. Methods Case acquisition was performed by reviewing ICD 9/10 coded records for familial Mediterranean fever (ICD 9 277.31), laboratory test records for PFS genetic screening, and clinic records between 1/1/2011 and 12/31/2017. Results Twenty-seven cases had clinical evaluations including PFS genetic screening. Clinical diagnoses included familial Mediterranean fever (FMF) (10 cases), Muckle-Wells (2 cases), tumor necrosis factor receptor associated periodic syndrome (TRAPS) (4 cases), hyper IgD syndrome (HIDS) (1 case), Crohn’s Disease (1 case), systemic onset juvenile idiopathic arthritis (SoJIA) (1 case), fever of unknown origin (FUO) (1 case), periodic fever adenitis pharyngitis aphthous ulcer (PFAPA) (6 cases), and cold-induced urticaria (1 case). Fifteen cases were associated with a genetic cause. Seven of the 10 FMF cases were confirmed genetically and were either heterozygous or compound heterozygotes. Both cases of Muckle-Wells had either a compound heterozygote for CIAS 1 or a NOD gene mutation. Both TRAPS cases presented atypically with patients developing systemic lupus erythematosus (SLE) or being asymptomatic. Two patients had novel syndromes. One FMF patient had a TRNT1 gene mutation who responded to intravenous immunoglobulin (IVIg) and colchicine after failing multiple treatments. The other had SoJIA with a LPIN 2 gene mutation but responded to colchicine. Only one of the 15 genetically proven cases had classical presentation and genetics (HIDS secondary to a mevalonate kinase (MVK) gene mutation). Conclusion PFS screening was helpful in over half of the cases to develop therapeutic treatment plans. Given the atypical clinical presentations seen with genetically determined PFS, extensive genetic testing is indicated for all patients presenting with a PFS, excluding classical PFAPA syndrome.
Background: High concentration oxygen therapy in hypercapnic chronic obstructive pulmonary disease (COPD) is associated with increased mortality. In ward-based patients with acute exacerbation of COPD and hypercapnia, this study examines oxygen prescription and the association between high concentration oxygen therapy and adverse outcome. Aims:To investigate the association between over-oxygenation and in-hospital adverse events.Methods: Inpatients with acute exacerbation of hypercapnic COPD at a tertiary Australian hospital over a 1-year period were retrospectively identified. Oxygen prescription and therapy was determined based on chart review. Over-oxygenation was defined as ≥10% of nursing chart observations recording oxygen delivery with oxygen saturation above 92%. A composite adverse outcome was defined as medical emergency team response, recommencement of non-invasive ventilation or death. The association between over-oxygenation and adverse outcome was assessed using survival analysis and conditional logistic regression modelling. Results:The study cohort comprised 106 unique patients and 157 admissions. Oxygen prescription was recorded in 132 (84%) and over-oxygenation occurred in 97 (62%) admissions. Over-oxygenation was higher in non-respiratory ward admissions (76% vs 57%, P = 0.03) and those without any form of oxygen prescription (84% vs 58%, P = 0.01). During follow up, 23 (22%) patients experienced an adverse event. Cox proportional hazards modelling found weak evidence for increased risk of an adverse event in over-oxygenated patients (hazard ratio 2.5; 95% confidence interval 0.8-7.3, P = 0.10). Conditional logistic regression, after matching on age, Charlson comorbidity category and length of follow up, found a similar estimate of association (hazard ratio 2.6; 95% confidence interval 0.8-8.7, P = 0.12).Conclusions: Over-oxygenation to hypercapnic COPD inpatients is common and rates of oxygen prescription are suboptimal. We found weak evidence of association between over-oxygenation and adverse events, likely due to low statistical power. Larger prospective studies are needed.
To facilitate high-quality inpatient care for stroke patients, we built a system within our electronic health record (EHR) to identify stroke patients while they are in the hospital; capture necessary data in the EHR to minimize the burden of manual abstraction for stroke performance measures, decreasing daily time requirement from 2 hours to 15 minutes; generate reports using an automated process; and electronically transmit data to third parties. Provider champions and support from the EHR development team ensured that we balanced the needs of the hospital with those of frontline providers. This work summarizes the development and implementation of our stroke quality system.
Inhibition of the DNA damage response (DDR) pathway is an attractive approach to target cancers cells. Unlike normal cells which relay on two cell cycle checkpoints to repair DNA damage, most tumor cells only depend on the G2 checkpoint because their G1 checkpoint is defective. Wee1 regulates the G2/M checkpoint and abrogating the G2 checkpoint by inhibiting Wee-1 in cancer cells with DNA damage can preferentially sensitize cancer cells to undergo mitotic catastrophe. We have developed and characterized ZN-c3, a potent and selective Wee-1 inhibitor with a differentiated kinase selectivity and pharmacokinetics profile. ZN-c3 was evaluated in ER-positive, triple negative, triple negative PARP inhibitor resistant, and Her-2 positive trastuzumab resistant breast cancers. In the ER-positive MCF-7 efficacy model, ZN-c3 demonstrated anti-tumor activity as a single agent as well as in combinations with a CDK4/6 inhibitor (Palbociclib) or ZN-c5, a selective estrogen receptor degrader (SERD). In the MDA-MB-436, a triple negative breast cancer tumor xenograft model, ZN-c3 demonstrated efficacy as a single agent and in combination with the PARP inhibitors Olaparib or Niraparib. We extended these combination studies by evaluating the efficacy of Niraparib in combination with ZN-c3 in patient-derived xenograft (PDX) triple negative breast tumors. ZN-c3 was efficacious as a single agent and the efficacy was enhanced in the combination with Niraparib. PARP inhibitors are effective and have been approved for treatment of some cancer types. However, most patients develop resistance to these agents. We sought to investigate whether ZN-c3 can overcome the acquired resistance to PARP inhibitors (Olaparib and Niraparib). We generated PARP inhibitor resistant breast tumor xenograft models. A significant tumor growth inhibition was observed in these resistant tumor xenograft models when treated with ZN-c3. These data suggest that ZN-c3 as a single agent can overcome the acquired PARP inhibitor resistance. Finally, we also evaluated ZN-c3 activity in a HER-2 positive trastuzumab resistant breast tumor xenograft model (JIMT-1) and ZN-c3 showed anti-tumor activity alone and in combination with trastuzumab. In summary, these results demonstrate that ZN-c3 is effective as a single agent and in combination with other targeted therapies in breast cancer models. Moreover, ZN-c3 can overcome the acquired resistance to PARP inhibitors and trastuzumab. ZN-c3 is currently in clinical trials for several indications and has demonstrated promising clinical activity and good tolerability. Citation Format: Jiali Li, Jianhui Ma, Petrus R. de Jong, Hooman Izadi, Tiffany Hoang, Noah Ibrahim, Brant Boren, Sayee Hegde Hegde, Fernando Doñate, Ahmed A. Samatar. ZN-c3, a potent and selective Wee-1 inhibitor demonstrates anti-tumor activities in combination with other targeted therapies and overcomes PARP inhibitor resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2606.
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