Afatinib versus gefitinib or erlotinib in first-line setting for Malaysia patients with EGFR mutant advanced lung adenocarcinoma

Abstract Background Afatinib is an irreversible second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) while gefitinib or erlotinib are reversible first-generation EGFR-TKIs. Methods A retrospective analysis of patients with EGFR mutant advanced lung adenocarcinoma receiving first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 113 patients, 24 (21.2%) received afatinib, 63 (55.8%) received gefitinib and 26 (23.0%) received erlotinib in first-line setting. Their demographic and clinical characteristics are shown in the table. Afatinib was used significantly more frequently in patients with rare or complex EGFR mutations (p = 0.005), and more often in patients with symptomatic brain metastases. The median progression-free survival (mPFS) of patients treated with afatinib (13.1 months) was longer than that of patients treated with gefitinib (10.9 months) or erlotinib (7.8 months) (p = 0.479). Patients receiving afatinib had consistently longer PFS than patients receiving gefitinib for the first 17 months and erlotinib for the first 20 months. The overall response rate was higher in patients on afatinib (75.0%) than those on gefitinib (63.5%) or erlotinib (53.8%). There was no difference in the disease control rate. Three patients (2.7%) had severe side-effects while on EGFR-TKI. Of two patients on afatinib, one had grade-3 diarrhea while another had grade 3 stomatitis, rash and paronychia. One patient had grade 3 rash on gefitinib. Conclusions Patients receiving first-line afatinib demonstrated longer mPFS than those on first-line gefitinib or erlotinib. The lack of statistical significance in this study is because of the small number of patients treated with afatinib, more frequent rare or complex EGFR mutations and more symptomatic brain metastases among afatinib treated patients

Health literacy and long-term health outcomes following myocardial infarction: protocol for a multicentre, prospective cohort study (ENHEARTEN study)

Introduction: Low health literacy is common in people with cardiovascular disease and may be one factor that affects an individual’s ability to maintain secondary prevention health behaviours following myocardial infarction (MI). However, little is known about the association between health literacy and longer-term health outcomes in people with MI. The ENhancing HEAlth literacy in secondary pRevenTion of cardiac evENts (ENHEARTEN) study aims to examine the relationship between health literacy and a number of health outcomes (including healthcare costs) in a cohort of patients following their first MI. Findings may provide evidence for the significance of health literacy as a predictor of long-term cardiac outcomes. Methods and analysis: ENHEARTEN is a multicentre, prospective observational study in a convenience sample of adults (aged >18 years) with their first MI. A total of 450 patients will be recruited over 2 years across two metropolitan health services and one rural/regional health service in Victoria, Australia. The primary outcome of this study will be all-cause, unplanned hospital admissions within 6 months of index admission. Secondary outcomes include cardiac-related hospital admissions up to 24 months post-MI, emergency department presentations, health-related quality of life, mortality, cardiac rehabilitation attendance and healthcare costs. Health literacy will be observed as a predictor variable and will be determined using the 12-item version of the European Health Literacy Survey (HLS-Q12). Ethics and dissemination: Ethics approval for this study has been received from the relevant human research ethics committee (HREC) at each of the participating health services (lead site Monash Health HREC; approval number: RES-21- 0000- 242A) and Services Australia HREC (reference number: RMS1672). Informed written consent will be sought from all participants. Study results will be published in peer-reviewed journals and collated in reports for participating health services and participants. Trial registration number: ACTRN12621001224819.Alison Beauchamp, Jason Talevski, Stephen J Nicholls, Anna Wong Shee, Catherine Martin, William Van Gaal, Ernesto Oqueli, Jaithri Ananthapavan, Laveena Sharma, Adrienne O, Neil, Sharon Lee Brennan-Olsen, Rebecca Leigh Jessu

Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib

Abstract Background Patients receiving first-line afatinib, gefitinib or erlotinib for epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer develop progression of disease (PD) after an average of 9-13 months. Methods A retrospective analysis of PD pattern and prevalence of acquired T790M mutation among patients failing first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 87 patients who developed PD while on first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, 19 (21.8%) were on afatinib, 49 (56.3%) were on gefitinib, and 19 (21.8%) were on erlotinib. The median progression-free survival (mPFS) of these patients is as shown in the table. Of 20 patients (23.0%) who developed new symptomatic brain metastases, one (5.0%) had new leptomeningeal metastases, three (15.0%) had both new leptomeningeal metastases and solid brain metastases, and the remaining 16 (80.0%) had new solid brain metastases only. New leptomeningeal metastases occurred in one patient treated with afatinib and three patients treated with gefitinib. Forty-nine patients (56.3%) were investigated for acquired T790M mutation either by plasma biopsy or tissue biopsy or both. The prevalence of acquired T790M mutation was 61.2%. There was no difference in the pattern of PD or prevalence of acquired T790M mutation among patients treated with afatinib, gefitinib or erlotinib. Conclusions New leptomeningeal metastases were uncommon in patients receiving first-line EGFR-TKI. The choice of first-line first- or second generation EGFR-TKI did not influence the pattern of PD and prevalence of acquired T790M mutation. However, patients receiving afatinib appeared to have longer mPFS than those on gefitinib or erlotinib

Acceptability of the 6-PACK falls prevention program: A pre-implementation study in hospitals participating in a cluster randomized controlled trial

There is limited evidence to support the effectiveness of falls prevention interventions in the acute hospital setting. The 6-PACK falls prevention program includes a fall-risk tool; 'falls alert' signs; supervision of patients in the bathroom; ensuring patients' walking AIDS are within reach; toileting regimes; low-low beds; and bed/chair alarms. This study explored the acceptability of the 6-PACK program from the perspective of nurses and senior staff prior to its implementation in a randomised controlled trial. A mixed-methods approach was applied involving 24 acute wards from six Australian hospitals. Participants were nurses working on participating wards and senior hospital staff including: Nurse Unit Managers; senior physicians; Directors of Nursing; and senior personnel involved in quality and safety or falls prevention. Information on program acceptability (suitability, practicality and benefits) was obtained by surveys, focus groups and interviews. Survey data were analysed descriptively, and focus group and interview data thematically. The survey response rate was 60%. Twelve focus groups (n = 96 nurses) and 24 interviews with senior staff were conducted. Falls were identified as a priority patient safety issue and nurses as key players in falls prevention. The 6-PACK program was perceived to offer practical benefits compared to current practice. Nurses agreed fall-risk tools, low-low beds and alert signs were useful for preventing falls (>70%). Views were mixed regarding positioning patients' walking aid within reach. Practical issues raised included access to equipment; and risk of staff injury with low-low bed use. Bathroom supervision was seen to be beneficial, however not always practical. Views on the program appropriateness and benefits were consistent across nurses and senior staff. Staff perceived the 6-PACK program as suitable, practical and beneficial, and were open to adopting the program. Some practical concerns were raised highlighting issues to be addressed by the implementation plan

How Effective Are Non-Operative Intra-Articular Treatments for Bone Marrow Lesions in Knee Osteoarthritis in Adults? A Systematic Review of Controlled Clinical Trials

Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review assessed the efficacy and safety of intra-articular therapies for improving OA-BMLs and reducing pain in adults with KOA. The study was conducted following registered review protocol (PROSPERO CRD42020189461) and six bibliographic databases, and two clinical trial registries were searched. We included eight randomised clinical trials involving 1294 participants, reported in 12 publications from 2016 to 2021. Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up. Two studies with corticosteroids reported mixed findings with no beneficial effect beyond 14 weeks of follow-up. One study assessing platelet-rich plasma found no significant improvement in OA-BMLs at 12 months follow-up. Knee pain was improved in two studies evaluating TissueGene-C and one study assessing APS; the remaining studies found no improvement in knee pain. Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA

Implementing an intervention to promote normal labour and birth: a study of clinicians’ perceptions

Background: Confronted with an increasing caesarean section rate, a regional Victorian hospital has introduced an intervention to support safe, normal labour and birth for low risk primigravidas, consisting of a change in protocol and practice, supported by education. Prior to implementation of the Normal Labour and Birth Bundle (NLBB), this study aimed to identify any clinician factors that may have influenced the uptake, acceptance and of use of the intervention. Method: The Theory of Planned Behaviour (TPB) provided the framework for the conduct and analysis of the staff survey and focus groups. Descriptive and inferential statistics where used to anlayse the survey and findings from the focus groups were derived from thematic analysis. Results: Seventy-six clinicians (88.8%) responded to the survey. Mean scores for TPB constructs were well above the mid-scale score of 4, indicating strong positive attitudes, high levels of self-efficacy and positive social pressure to use the (NLBB) and strong intentions to use it in the future. Self-efficacy was the strongest independent predictor (β =0.48, p<.05) of intention to use the NLBB. The themes identified from the two focus groups were philosophy of care, effective collaboration, clinical decision making during labour and the regional health environment. Conclusions: Understanding staff perceptions allowed for specific strategies to be employed to implement and sustain the intervention

Engaging with pregnancy care providers: an interview study of teenage women

Background: Teenage pregnancy is associated with a large societal and personal burden, worldwide. The rate of teenage pregnancy at Ballarat Health Services (14.2/1000 births) was higher than the Victorian average of 10/1000 births. Attendance for pregnancy care is associated with improved outcomes. The aim of this study was to explore the barriers and facilitators to engagement with pregnancy care providers experienced by teenage women. Method: Between Feb-Jun 2017 semi structured interviews were conducted with women from Ballarat, Ararat and Maryborough health services who were pregnant aged ≤ 19 yrs. Interviews were audio taped and professionally transcribed. Thematic analysis was undertaken. Results: Transcripts of 16 women were analysed and four themes emerged: Valuing pregnancy care, Access, Individualised care and Resilience, Young women were motivated to attend to ensure the wellbeing of their baby and lack of engagement occurred when the importance of care was not understood. Flexibility of appointments and a central location was important; most participants were highly reliant on others for transport. Continuity of carer was valued and the interpersonal skills of staff was keenly noted. Many women had fractured families and pregnancy led to a contraction of their social world yet there was a sense of purpose in their lives. Conclusions: These findings have informed the development of best practice for teenage pregnancy care

Research translation mentoring for emerging clinician researchers in rural and regional health settings: a qualitative study

Abstract Background Building clinician and organisation-level research translation capacity and capability is fundamental for increasing the implementation of research into health practice and policy and improving health outcomes. Research translation capacity and capability building is particularly crucial in rural and regional settings to address complex problems impacting these socially and economically disadvantaged communities. Programs to build clinicians’ research translation capability typically involve training and mentoring. Little is known about the features of and influences on mentorships in the context of training for emerging clinician-researchers working in rural and regional healthcare settings. Research translation mentorships were established as part of the Supporting Translation Research in Rural and Regional settings (STaRR) program developed and delivered in Victoria, Australia from 2020 to 2021. The study sought to address the following research questions: 1) What context-specific types of support do research translation mentors provide to emerging researchers?. 2) How does the mentoring element of a rural research translational training program influence research translation capacity and capability development in rural emerging researchers and mentors, if at all?. 3) How does the mentoring element of the program influence translation capacity and capability at the organisational and regional level, if at all? Methods We conducted a qualitative descriptive study. Interviews with individuals involved in the STaRR program took place approximately 12 months after the program and explored participants’ experiences of the mentored training. Interviews were undertaken via telephone, audio-recorded, and transcribed. Data were analysed using a team-based five-stage framework approach. Results Participants included emerging researchers (n = 9), mentors (n = 5), and managers (n = 4), from five health services and two universities. We identified four themes in the interview data: (1) Mentors play an educative role; (2) Mentoring enhanced by a collaborative environment; (3) Organisational challenges can influence mentorships, and (4) Mentorships help develop research networks and collective research and translation capacity. Conclusions Mentorships contributed to the development of research translation capabilities. The capabilities were developed through mentors’ deepened understanding of the rural and regional healthcare contexts in which their emerging researchers worked, the broadening and strengthening of rural and regional research networks, and building and sharing research translation knowledge and skills