Feasibility and efficacy of a multicomponent exercise medicine programme in patients with pancreatic cancer undergoing neoadjuvant therapy (the EXPAN trial): Study protocol of a dual-centre, two-armed phase I randomised controlled trial

Introduction Exercise is emerging as a therapy in oncology for its physical and psychosocial benefits and potential effects on chemotherapy tolerability and efficacy. However, evidence from randomised controlled trials (RCTs) supporting exercise in patients with borderline resectable or locally advanced pancreatic cancer (PanCa) undergoing neoadjuvant therapy (NAT) are lacking. Methods and analysis The EXPAN trial is a dual-centre, two-armed, phase I RCT. Forty patients with borderline resectable or locally advanced PanCa undergoing NAT will be randomised equally to an exercise intervention group (individualised exercise+standard NAT) or a usual care control group (standard NAT). The exercise intervention will be supervised and consist of moderate to vigorous intensity resistance and aerobic-based training undertaken two times a week for 45-60 min per session for a maximum period of 6 months. The primary outcome is feasibility. Secondary outcomes are patient-related and treatment-related endpoints, objectively measured physical function, body composition, psychological health and quality of life. Assessments will be conducted at baseline, prior to potential alteration of treatment (∼4 months postbaseline), at completion of the intervention (maximum 6 months postbaseline) and 3-month and 6-month postintervention (maximum 9 and 12 months postbaseline). Ethics and dissemination The EXPAN trial has been approved by Edith Cowan University (reference no.: 2020-02011-LUO), Sir Charles Gairdner Hospital (reference no.: RGS 03956) and St John of God Subiaco Hospital (reference no.: 1726). The study results will be presented at national/international conferences and submitted for publications in peer-reviewed journals. Trial registration number ACTRN12620001081909

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

Background: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. Methods: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. Findings: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28–0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. Interpretation: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The Bristol shared care glaucoma study: outcome at follow up at 2 years

AIM—To examine the outcome of care for patients with glaucoma followed up by the hospital eye service compared with those followed up by community optometrists.
METHODS—A randomised study with patients allocated to follow up by the hospital eye service or community optometrists was carried out in the former county of Avon in south west England. 403 patients with established or suspected primary open angle glaucoma attending Bristol Eye Hospital and meeting defined inclusion and exclusion criteria were studied. The mean number of missed points on visual field testing in the better eye (using a "better/worse" eye analysis) in each group were measured. The visual field was measured using the Henson semiautomated central field analyser (CFA 3000). Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. The mean number of missed points on visual field testing in the worse eye, mean intraocular pressure (mm Hg), and cup disc ratio using a "better/worse" eye analysis in each group at 2 years were also measured. Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. An analysis of covariance comparing method of follow up taking into account baseline measurements of outcome variables was carried out. Additional control was considered for age, sex, diagnostic group (glaucoma suspect/established primary open angle glaucoma), and treatment (any/none).
RESULTS—From examination of patient notes, 2780 patients with established or suspected glaucoma were identified. Of these, 752 (27.1%) fulfilled the entry criteria. For hospital and community follow up group respectively, mean number of missed points on visual field testing at 2 year follow up for better eye was 7.9 points and 6.8 points; for the worse eye 20.2 points and 18.4 points. Similarly, intraocular pressure was 19.3 mm Hg and 19.3 mm Hg (better eye), and 19.1 mm Hg and 19.0 mm Hg (worse eye); cup disc ratio at 2 year follow up was 0.72 and 0.72 (better eye), and 0.74 and 0.74 for hospital and community follow up group respectively. No significant differences in any of the key visual variables were found between the two groups before or after adjusting for baseline values and age, sex, treatment, and type of glaucoma.
CONCLUSIONS—It is feasible to set and run shared care schemes for a proportion of patients with suspected and established glaucoma using community optometrists. After 2 years (a relatively short time in the life of a patient with glaucoma), there were no marked or statistically significant differences in outcome between patients followed up in the hospital eye service or by community optometrists. Decisions to implement such schemes need to be based on careful consideration of the costs of such schemes and local circumstances, including geographical access and the current organisation of glaucoma care within the hospital eye service.


Exercise as medicine in the management of pancreatic cancer: A case study

This study aimed to determine the safety and efficacy of a 6-month supervised exercise program in a pancreatic cancer patient undergoing adjuvant treatment

Feasibility and efficacy of a multicomponent exercise medicine programme in patients with pancreatic cancer undergoing neoadjuvant therapy (the EXPAN trial): study protocol of a dual-centre, two-armed phase I randomised controlled trial

Introduction Exercise is emerging as a therapy in oncology for its physical and psychosocial benefits and potential effects on chemotherapy tolerability and efficacy. However, evidence from randomised controlled trials (RCTs) supporting exercise in patients with borderline resectable or locally advanced pancreatic cancer (PanCa) undergoing neoadjuvant therapy (NAT) are lacking.Methods and analysis The EXPAN trial is a dual-centre, two-armed, phase I RCT. Forty patients with borderline resectable or locally advanced PanCa undergoing NAT will be randomised equally to an exercise intervention group (individualised exercise+standard NAT) or a usual care control group (standard NAT). The exercise intervention will be supervised and consist of moderate to vigorous intensity resistance and aerobic-based training undertaken two times a week for 45–60 min per session for a maximum period of 6 months. The primary outcome is feasibility. Secondary outcomes are patient-related and treatment-related endpoints, objectively measured physical function, body composition, psychological health and quality of life. Assessments will be conducted at baseline, prior to potential alteration of treatment (~4 months postbaseline), at completion of the intervention (maximum 6 months postbaseline) and 3-month and 6-month postintervention (maximum 9 and 12 months postbaseline).Ethics and dissemination The EXPAN trial has been approved by Edith Cowan University (reference no.: 2020-02011-LUO), Sir Charles Gairdner Hospital (reference no.: RGS 03956) and St John of God Subiaco Hospital (reference no.: 1726). The study results will be presented at national/international conferences and submitted for publications in peer-reviewed journals.Trial registration number ACTRN12620001081909

Advancing prostate cancer survivorship research in Australia

Prostate cancer is the most common cancer affecting Australian men, with 1 in 7 males diagnosed before the age of 75 years and most now surviving long-term in the absence of adequate and accessible supportive care for their wellbeing. A substantive proportion of men with prostate cancer experience heightened psychological distress and ongoing unmet needs for supportive care in the domains of sexuality and psychosocial care. This perspective focuses on: men’s psychosocial and psychosexual needs; the role of exercise in survivorship care; health economics; and geographic and sociodemographic disparities in outcomes. It is proposed that prostate cancer survivorship research, translation and education needs to articulate with key factors that influence the acceptability and uptake of services. Stepped care approaches are also needed to meet the challenges of increasing prostate cancer prevalence taking into account constraints in health care resources and unique barriers to care such as geographic location, health literacy, and other aspects of social disadvantage. Finally, close linkage to to community with the patient and family placed at the centre of the care model will be crucial