Custom-made 3D printed masks for children using non-invasive ventilation: a feasibility study of production method and testing of outcomes in adult volunteers

Abstract

Non-invasive ventilation (NIV) is assisted mechanical ventilation delivered via a facemask for people with chronic conditions that affect breathing. NIV is most commonly delivered via an interface (mask) covering the nose (nasal mask) or the nose and mouth (oronasal mask). The number of children in the UK requiring NIV is currently estimated to be around 5000. Mass-produced masks are available for both the adult and paediatric markets but masks that fit well are difficult to find for children who are small or have asymmetrical facial features. A good conforming fit between the mask and the patient’s face to minimise unintentional air leakage is essential to deliver the treatment effectively; most ventilators will trigger an alarm requiring action if such leakage is detected. We present an innovative use of 3D scanning and manufacturing technologies to deliver novel mask-face interfaces to optimise mask fit to the needs of individual patients. Ahead of planned user trials with paediatric patients, the project team trialled the feasibility of the process of creating and printing bespoke masks from 3D scan data and carried out testing of the masks in adult volunteers to select the strongest design concept for the paediatric trial. The evaluation of the process of designing a bespoke mask from scan data, arranging for its manufacture and carrying out user testing has been invaluable in gaining knowledge and discovering the pitfalls and timing bottlenecks in the processes. This allowed the team to iteratively refine the techniques and methods involved, informing user trials later on in the project. It has also provided indicative cost estimates for 3D printed mask prototype components which are useful in project decision making and trial planning. The value of the process extends to considerations for future implementation of the process within a clinical pathway.     

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long‐term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then consider the efficacy of bone marrow–derived mesenchymal stem/stromal cell (BM‐MSC) transplantation as a therapy for these injuries. Finally, we examine recent laboratory and clinical studies utilizing transplanted BM‐MSCs as antiinflammatory and neurorestorative treatments for stroke and TBI. Clinical trials of BM‐MSC transplants for stroke and TBI support their promising protective and regenerative properties. Future research is needed to allow for better comparison among trials and to elaborate on the emerging area of cell‐based combination treatments.     

Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management

Interindividual variability in analgesic effects of nonsteroidal anti‐inflammatory drugs prescribed for sickle cell disease (SCD) pain is attributed to polymorphisms in the CYP2C8 and CYP2C9 enzymes. We described CYP2C8 and CYP2C9 genotype/phenotype profiles and frequency of emergency department (ED) visits for pain management in an African American SCD patient cohort. DNA from 165 unrelated patients was genotyped for seven CYP2C8 and 15 CYP2C9 alleles using the iPLEX ADME PGx multiplexed panel. CYP2C8*1 (0.806),*2 (0.164), *3 (0.018), and *4 (0.012) alleles were identified. Genotype frequencies were distributed as homozygous wild type (66.7%), heterozygous (27.8%), and homozygous variant/compound heterozygous (5.4%), respectively. CYP2C9*1 (0.824), *2 (0.027), *3 (0.012), *5 (0.009), *6 (0.009), *8 (0.042), *9 (0.061), and *11(0.015) were observed with extensive (68.5%), intermediate (18.1%) and poor predicted metabolizers (0.6%), respectively. Fifty‐two and 55 subjects, respectively had at least one variant CYP2C8 or CYP2C9 allele. Although the distribution of the CYP2C9 (p = 0.0515) phenotypes was marginally significantly in high and low ED users; some CYP2C8 and CYP2C9 allelic combinations observed in 15.2% (25) of the cohort are associated with higher risks for analgesic failure. CYP2C8 and CYP2C9 preemptive genotyping could potentially enable clinicians to identify patients with impaired metabolic phenotypes.     

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

Advancing primary and community care for persons with spinal cord injury: Key findings from a Canadian summit

Context: Persons with spinal cord injury (SCI) experience significant challenges when they access primary care and community services.

Design: A provincial summit was held to direct research, education, and innovation for primary and community care for SCI.

Setting: Toronto, Ontario, Canada.

Participants: Key stakeholders (N?=?95) including persons with SCI and caregivers, clinicians from primary care, rehabilitation, and specialized care, researchers, advocacy groups, and policy makers.

Methods: A one-day facilitated meeting that included guest speakers, panel discussions and small group discussions was held to generate potential solutions to current issues related to SCI care and to foster collaborative relationships to advance care for SCI. Perspectives on SCI management were shared by primary care, neurosurgery, rehabilitation, and members of the SCI community

Outcome Measures: Discussions were focused on five domains: knowledge translation and dissemination, application of best practices, communication, research, and patient service accessibility.

Results: Summit participants identified issues and prioritized solutions to improve primary and community care including the creation of a network of key stakeholders to enable knowledge creation and dissemination; an online repository of SCI resources, integrated health records, and a clinical network for SCI care; development and implementation of strategies to improve care transitions across sectors; implementation of effective care models and improved access to services; and utilization of empowerment frameworks to support self-management.

Conclusions: This summit identified priorities for further collaborative efforts to advance SCI primary and community care and will inform the development of a provincial SCI strategy aimed at improving the system of care for SCI.