Phage display antibody libraries are a rich resource for discovery of potential therapeutic antibodies. Single-chain variable fragment (scFv) libraries are the most common format due to the efficient display of scFv by phage particles and the ease by which soluble scFv antibodies can be expressed for high-throughput screening. Typically, a cascade of screening and triaging activities are performed, beginning with the assessment of large numbers of E. coli-expressed scFv, and progressing through additional assays with individual reformatting of the most promising scFv to full-length IgG. However, use of high-throughput screening of scFv for the discovery of full-length IgG is not ideal because of the differences between these molecules. Furthermore, the reformatting step represents a bottle neck in the process because each antibody has to be handled individually to preserve the unique VH and VL pairing. These problems could be resolved if populations of scFv could be reformatted to full-length IgG before screening without disrupting the variable region pairing. Here, we describe a novel strategy that allows the reformatting of diverse populations of scFv from phage selections to full-length IgG in a batch format. The reformatting process maintains the diversity and variable region pairing with high fidelity, and the resulted IgG pool enables high-throughput expression of IgG in mammalian cells and cell-based functional screening. The improved process led to the discovery of potent candidates that are comparable or better than those obtained by traditional methods. This strategy should also be readily applicable to Fab-based phage libraries. Our approach, Screening in Product Format (SiPF), represents a substantial improvement in the field of antibody discovery using phage display.
Introduction: Incontinence and/or pelvic organ prolapse symptoms are prevalent in women in Australia and the estimated healthcare cost is considerable. Internationally accepted best practice evidence supports a trial of conservative Physiotherapy treatment with a Physiotherapist trained in the management of pelvic floor dysfunction before surgical options should be considered. Existing referral pathways in the tertiary healthcare system to access conservative Physiotherapy treatment require direct referral from Gynaecology staff. Objective: To identify the pathway to conservative pelvic floor physiotherapy for women referred to a tertiary hospital in Australia with incontinence and/or pelvic organ prolapse symptoms following existing referral pathways. Results: Attendance data for the period January to June 2015 identified 63 women as being primarily referred for incontinence and/or pelvic organ prolapse by their local healthcare provider. Half of these 63 women (n = 31) were referred on to Physiotherapy for conservative management; the other half were not. The time between local healthcare provider referral to specialist Gynaecology appointment ranged from 49 days to 351 days (average 169.6 days). Of the 31 women referred to Physiotherapy, the majority (n = 22, 70.9%) were referred on the day of their initial Gynaecology consultation, the 9 remaining women waited between 2 to 126 days for Physiotherapy referral. The shortest pathway from local healthcare provider referral to Physiotherapy consultation was 64 days; the longest pathway was 402 days. Of the 31 women who were not referred to Physiotherapy, 18 (58%) proceeded directly to surgery. Conclusion: This audit demonstrates that existing referral pathways for women referred with incontinence and/or pelvic organ prolapse create lengthy delays between local healthcare provider referral and access to Physiotherapy services. Only half of those women who would be appropriate for a trial of conservative therapy are being referred to Physiotherapy which is in direct contrast to the widely accepted best practice guidelines for the management of pelvic floor dysfunction mandating conservative therapy as a first line approach for these conditions. The opportunity to implement an advanced scope model of care that promotes more timely access and earlier commencement of conservative Physiotherapy for these women would significantly improve the clinical care pathway for this cohort of patients in the tertiary healthcare setting.
Background: Pregnancy and childbirth have a profound and lasting effect on the female body. Reduced length of postnatal hospital stay has impacted the ability of physiotherapy staff to provide early intervention and education on postnatal recovery and rehabilitation. A novel method of providing physiotherapy education to postnatal women was implemented in an attempt to meet consumer needs in the changing hospital environment. A digital health resource was developed and evaluated to determine consumer satisfaction and access. Methods: Postnatal women admitted to the postnatal ward were invited to participate in a survey of the digital health resource during a 17-day recruitment period. A participant information sheet was provided to the patient and a signed consent form collected from those willing to participate. Online surveys were emailed to women at approximately 2 weeks postnatal and a thematic analysis of the responses was completed. Results: A total of 88 women were recruited to the study during a 17-day recruitment period with a 30% response rate (n=27) to an online survey sent at approximately 2 weeks postpartum. Of the 27 respondents, 33% had watched the digital health resource and were able to provide feedback on resource content, format and length, as well as enablers and barriers to access and viewing habits. Survey responses indicated the resource was viewed only after discharge from hospital and most commonly on a mobile device. Most women engaged with the resource to learn more about their own recovery, and all women found the advice on pelvic floor exercise useful. Lack of time was the most commonly reported barrier to viewing the digital health resource. Conclusions: This quality assurance project demonstrated the existing digital health resource provides useful information to women following discharge from the postnatal ward but strategies to improve awareness of the resource should be investigated further.
Introduction: Incontinence and pelvic organ prolapse (POP) commonly affect many people for whom physiotherapy may be an important, front-line management strategy. However, traditional referral pathways in the tertiary health care system limit or delay access to this management option resulting in poor outcomes. Objective: The aim of this pilot study was to determine the impact of an advanced scope of practice physiotherapy model of care for women referred with incontinence and/or POP symptoms compared to traditional referral pathways in a tertiary hospital in Australia. Methods: A prospective audit was conducted with consecutive sampling of those triaged into the physiotherapy-led clinic during the trial period. A database was created to record patient demographic information, key dates in the patient pathway, and the clinical outcome measures obtained. Results: Forty-one women were assessed in the physiotherapy-led clinic during the trial period October 2015-March 2016. The results indicate improved access to care (time between referral to first consult during the trial was 27.3 days, compared with 169.6 days first consult using the traditional referral pathway), improved adherence to conservative management (96% attending their individual consultation compared to 55%) and positive patient satisfaction. Conclusion: This pilot study demonstrated that an advanced scope physiotherapy-led model of care such as the Gynecology Physiotherapy Assessment Service can result in improved access to care while positively impacting experiences of women with incontinence and/or POP symptoms.
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