Study protocol: a pilot quasi-experimental trial of tele-rehabilitation and tele-drain care post-mastectomy.

BACKGROUND: Breast cancer is the leading cancer affecting women in Singapore. Its survivors commonly experience decline in physical function and quality of life post-mastectomy, due to their upper limb morbidity and wound issues. Rehabilitation can address the aforementioned issues. When rehabilitation is accessible and easy to adhere, it can optimize recovery. Home-based tele-rehabilitation guided by healthcare professionals and self-managed by patients can potentially optimize the patients' adherence to rehabilitation and recovery. With that in mind, a team of breast cancer specialists (oncologists, nurses, and therapists) in Singapore has developed one of the first tele-rehabilitation systems for local women undergoing a unilateral mastectomy. To our knowledge, no such systems have been evaluated or proven effective as a treatment option among local breast cancer patients with acute disabilities. METHODS: This is a pilot quasi-experimental trial that aims to evaluate the feasibility of tele-rehabilitation and tele-drain care compared to usual care. Up to 40 patients (20 per group) will be recruited for this trial. They will be assigned to an intervention group that receives rehabilitation via a tele-rehabilitation system or a control group that receives rehabilitation in person at their clinic. The primary outcome of this trial is rehabilitation participation (i.e., the time spent on rehabilitation). The secondary outcomes are upper extremity functioning, perceived health, and quality of life. DISCUSSION: As part of this pilot trial, patients who opt in for the tele-rehabilitation will be asked to share their experience with and thoughts on the tele-rehabilitation system. With the evidence obtained from the tele-rehabilitation patients of this trial, we will be able to improve the current system for our future trial. Further, our additional data on rehabilitation participation, physical function, and quality of life will help us design a sufficiently powered future main trial. TRIAL REGISTRATION: The trial was approved by the National Healthcare Group's Domain Specific Review Board (#2019/00283) and registered with www.ClinicalTrials.gov (# NCT04269967 ) in February 2020.

Autophagy is deregulated in cancer-associated fibroblasts from oral cancer and is stimulated during the induction of fibroblast senescence by TGF-ß1.

Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-ß1, induced fibroblast activation and senescence: In response to TGF-ß1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-ß1-treated NHOFs enhance OSCC cell migration but only TGF-ß1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-ß1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.

Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2.

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease.

Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.

Role transition: A descriptive exploratory study of assistant nurse clinicians in Singapore.

AIM: To explore the role-transition experiences of assistant nurse clinicians after their first year of appointment. BACKGROUND: The National Nursing Taskforce was set up in Singapore to examine the professional development and recognition of nurses. It created the assistant nurse clinician role as an avenue for the nurses' career development. The role was intended to assist nurse managers to guide the nursing team in the assessment, planning, and delivery of patient care. METHODS: A qualitative descriptive study design was adopted. A purposive sample of 22 registered nurses from six acute care institutions and two polyclinics in Singapore participated in the face-to-face interviews. An inductive content analysis approach was used to analyse the data. RESULTS: Four themes emerged: (a) promotion to assistant nurse clinician is a form of recognition and vindication; (b) there was uncertainty about the expected role of the assistant nurse clinician; (c) experience eases transition; and (d) there was a need for peer support, mentorship, and training. CONCLUSIONS: The job description of the assistant nurse clinician needs to be better defined to provide greater clarity about their clinical and administrative duties and what is expected of their performance. IMPLICATIONS FOR NURSING MANAGEMENT: It is essential for nurse managers to provide successful role-transition strategies to help the newly appointed assistant nurse clinicians to become efficient and effective leaders.

The effects of a video-based education in women with newly diagnosed breast cancer in Singapore.

PURPOSE: The purpose of this study was to evaluate the impact of an educational video among women who were newly diagnosed with breast cancer on knowledge, anxiety, and satisfaction with their surgical decision. METHODS: A pre-post-test design was used to evaluate knowledge, anxiety, and satisfaction levels with decision-making regarding surgery among women with breast cancer. A purposive sampling strategy was implemented to compare outcomes of newly diagnosed breast cancer women who received standard of care that included breast care nurse counseling sessions and written materials to women who received standard of care plus a supplement educational video. Knowledge and anxiety scores were collected at baseline and 2 weeks post-operatively. Satisfaction with decision (SWD) on the nature of surgery was gathered 2 weeks after surgery. RESULTS: Sixty-two subjects were recruited in a Singapore tertiary cancer center with a cohort of 32 women in the non-video group and 30 women in the video group. There was a statistically significant interaction effect of group and time (p = .008), wherein knowledge increased for both groups, although the increase was steeper for the video group. Both groups had significantly lower anxiety at post-implementation compared to pre-implementation (p < .001). There were no differences in SWD scores in both groups. CONCLUSIONS: Use of an additional video-based education significantly increased breast cancer knowledge levels among women in the educational video group. Nurses and healthcare professionals should focus on identifying individual informational needs based on surgical options to provide personalize care and transfer the necessary knowledge in empowering woman's decision-making process on her nature of breast surgery.

Virtual reality for upper extremity rehabilitation in early stroke: a pilot randomized controlled trial.

OBJECTIVES: To investigate the effect of virtual reality (VR) rehabilitation on upper extremity motor performance of patients with early stroke. DESIGN: Pilot randomized controlled trial. SETTING: Rehabilitation wards. PARTICIPANTS: Twenty three adults with stroke (mean age (SD) = 58.35 (13.45) years and mean time since stroke (SD) = 16.30 (7.44) days). INTERVENTIONS: Participants were randomly assigned to VR group (n=11) or control group (n=12). VR group received nine 30 minutes upper extremity VR therapy in standing (five weekdays in two weeks) plus conventional therapy, which included physical and occupational therapy. Control group received only conventional therapy, which was comparable to total training time received by VR group (mean training hours (SD):VR = 17.07 (2.86); control = 15.50 (2.79)). MAIN OUTCOME MEASURES: The main outcome measure was the Fugl-Meyer Assessment (FMA). Secondary outcomes included Action Research Arm Test, Motor Activity Log and Functional Independence Measure. Results were taken at baseline, post intervention and 1-month post intervention. Participants' feedback and adverse effects were recorded. RESULTS: All participants improved in FMA scores (mean change (SD) = 11.65 (8.56), P<.001). These effects were sustained at one month after intervention (mean (SD) change from baseline = 18.67 (13.26), P<.001). All other outcome measures showed similar patterns. There were no significant differences in improvement between both groups. Majority of the participants found VR training useful and enjoyable, with no serious adverse effects reported. CONCLUSION: Although additional VR training was not superior to conventional therapy alone, this study demonstrates the feasibility of VR training in early stroke.

Validation of EORTC QLQ-C30 and QLQ-BR23 questionnaires in the measurement of quality of life of breast cancer patients in Singapore.

OBJECTIVE: To validate EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires and to measure the health-related quality of life (HRQOL) of women with breast cancer in Singapore during their first 4 years of post-diagnosis and treatments. METHODS: A quantitative and cross-descriptive sectional study. All of 170 subjects were recruited in a Singapore tertiary cancer center. The European Organization for Research and Treatment-QOL questionnaire and breast cancer specific module (EORTC QLQ-C30 and QLQ-BR23) were used to measure the HRQOL among women with breast cancer. All statistical tests were performed using SPSS Version 18. The reliability of the EORTC QLQ-C30 and QLQ-BR23 questionnaires was examined using Cronbach's alpha test. EORTC QLQ-C30 was validated against EuroQol Group's 5-domain questionnaires (EQ5D) by examining its concurrent validity using Pearson Product Moment Correlation to calculate the total scores. RESULTS: The Cronbach's alpha coefficient results for EORTC QLQ-C30 and QLQ BR-23 were 0.846 and 0.873 respectively which suggested relatively good internal consistency. The correlation between EORTC QLQ-C30 and EQ5D QOL instruments demonstrated a modest linear relationship (r=0.597; P<0.001) that indicated a moderately strong correlation between the two measures. The study showed that Singaporean women with breast cancer had enjoyed high levels of HRQOL during their first 4 years of survivorship but they had significant concern over the financial impact of breast cancer. One of the key findings was younger women had experienced more physical and psychosocial concerns than older women. CONCLUSION: The EORTC QLQ-C30 and QLQ-BR23 questionnaires are feasible and promising instruments to measure the levels of HRQOL in Singaporean women with breast cancer in future studies.