Methods to Include Environmental Impacts in Health Economic Evaluations and Health Technology Assessments: A Scoping Review.

OBJECTIVES: The environmental impacts of healthcare are important factors that should be considered during health technology assessments. This study aims to summarize the evidence that exists about methods to include environmental impacts in health economic evaluations and health technology assessments. METHODS: We identified records for screening using an existing scoping review and a systematic search of academic databases and gray literature up to September 2023. We screened the identified records for eligibility and extracted data using a narrative synthesis approach. The review was conducted following the JBI Manual for Evidence Synthesis and reported according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses Extension for Scoping Reviews checklist. RESULTS: We identified 2898 records and assessed the full text of 114, of which 54 were included in this review. Ten methods were identified to include environmental impacts in health economic evaluations and health technology assessments. Methods included converting environmental impacts to dollars or disability-adjusted life years and including them in a cost-effectiveness, cost-utility, or cost-benefit analysis, calculating an incremental carbon footprint effectiveness ratio or incremental carbon footprint cost ratio, incorporating impacts as one criteria of a multi-criteria decision analysis, and freely considering impacts during health technology assessment deliberation processes. CONCLUSIONS: Methods to include environmental impacts in health economic evaluations and health technology assessments exist but have not been tested for widespread use by health technology assessment agencies. Further research and implementation work is needed to determine which method can best aid decision makers to choose low environmental impact healthcare interventions.

Quality-of-life measurement long-term after resection of colorectal liver metastases - is there an optimal assessment tool?

BACKGROUND: There is limited literature on health-related quality-of-life (HRQoL) in patients with colorectal liver metastases (CRLM). Furthermore, there is no consensus on which HRQoL tool is most appropriate. This study assessed the long-term HRQoL in patients who undergo liver resection for CRLM and assessed which HRQoL tool is most useful. METHODS: This was a cross-sectional study of patients who had curative resection for CRLM between 2010 and June 2021. Three validated instruments were used: The European Organisation for Research and Treatment of Cancer (EORTC), which consists of the QLQ-C30 (a generic questionnaire) and QLQ-LMC21 (CRLM specific); the EuroQol-5D (EQ-5D) and the 36-Item Short Form Survey. RESULTS: 121 patients underwent liver resection for CRLM, of which 85 were alive. There was a 61 % response rate (n = 52). The median post-operative time when the survey was completed was 4.0 years. Across all three questionnaires, patients performed exceptionally well in all domains, with median functional scores >90. The EQ-5D-5L VAS and the EROTC QLQ-C30 produced similar results. CONCLUSION: This study demonstrates excellent long-term HRQoL in patients who undergo resection for CRLM. The EQ-5D questionnaire is the preferred questionnaire because it is shorter and simpler to complete than the other tools without compromising accuracy.

The Impact of Surveillance Imaging Frequency on the Detection of Distant Disease for Patients with Resected Stage III Melanoma.

BACKGROUND: It is not known whether there is a survival benefit associated with more frequent surveillance imaging in patients with resected American Joint Committee on Cancer stage III melanoma. OBJECTIVE: The aim of this study was to investigate distant disease-free survival (DDFS), melanoma-specific survival (MSS), post distant recurrence MSS (dMSS), and overall survival for patients with resected stage III melanoma undergoing regular computed tomography (CT) or positron emission tomography (PET)/CT surveillance imaging at different intervals. PATIENTS AND METHODS: A closely followed longitudinal cohort of patients with resected stage IIIA-D disease treated at a tertiary referral center underwent 3- to 4-monthly, 6-monthly, or 12-monthly surveillance imaging between 2000 and 2017. Survival outcomes were estimated using the Kaplan-Meier method, and log-rank tests assessed the significance of survival differences between imaging frequency groups. RESULTS: Of 473 patients (IIIA, 19%; IIIB, 31%; IIIC, 49%; IIID, 1%) 30% underwent 3- to 4-monthly imaging, 10% underwent 6-monthly imaging, and 60% underwent 12-monthly imaging. After a median follow-up of 6.2 years, distant recurrence was recorded in 252 patients (53%), with 40% detected by surveillance CT or PET/CT, 43% detected clinically, and 17% with another imaging modality. Median DDFS was 5.1 years (95% confidence interval 3.9-6.6). Among 139 IIIC patients who developed distant disease, the median dMSS was 4.4 months shorter in those who underwent 3- to 4-monthly imaging than those who underwent 12-monthly imaging. CONCLUSION: Selecting patients at higher risk of distant recurrence for more frequent surveillance imaging yields a higher proportion of imaging-detected distant recurrences but is not associated with improved survival. A randomized comparison of low versus high frequency imaging is needed.

PRehabIlitatiOn with pReoperatIve exercise and educaTion for patients undergoing major abdominal cancer surgerY: protocol for a multicentre randomised controlled TRIAL (PRIORITY TRIAL).

BACKGROUND: Radical surgery is the mainstream treatment for patients presenting with advanced primary or recurrent gastrointestinal cancers; however, the rate of postoperative complications is exceptionally high. The current evidence suggests that improving patients' fitness during the preoperative period may enhance postoperative recovery. Thus, the primary aim of this study is to establish the effectiveness of prehabilitation with a progressive, individualised, preoperative exercise and education program compared to usual care alone in reducing the proportion of patients with postoperative in-hospital complications. The secondary aims are to investigate the effectiveness of the preoperative intervention on reducing the length of intensive care unit and hospital stay, improving quality of life and morbidity, and reducing costs. METHODS: This is a multi-centre, assessor-blinded, pragmatic, comparative, randomised controlled trial. A total of 172 patients undergoing pelvic exenteration, cytoreductive surgery, oesophagectomy, hepatectomy, gastrectomy or pancreatectomy will be recruited. Participants will be randomly allocated to prehabilitation with a preoperative exercise and education program (intervention group), delivered over 4 to 8 weeks before surgery by community physiotherapists/exercise physiologists, or usual care alone (control group). The intervention will comprise 12 to 24 individualised, progressive exercise sessions (including aerobic/anaerobic, resistance, and respiratory exercises), recommendations of home exercises (16 to 32 sessions), and daily incidental physical activity advice. Outcome measures will be collected at baseline, the week prior to surgery, during the hospital stay, and on the day of discharge from hospital, and 1 month and 1 months postoperatively. The primary outcome will be the development of in-hospital complications. Secondary outcomes include the length of intensive care unit and hospital stay, quality of life, postoperative morbidity and costs. DISCUSSION: The successful completion of this trial will provide robust and high-quality evidence on the efficacy of a preoperative community- and home-based exercise and education intervention on important postoperative outcomes of patients undergoing major gastrointestinal cancer surgery. TRIAL REGISTRATION: This trial was registered prospectively with the Australian New Zealand Clinical Trials Registry ( ACTRN12621000617864 ) on 24th May 2021.

Performance of Long-Term CT and PET/CT Surveillance for Detection of Distant Recurrence in Patients with Resected Stage IIIA-D Melanoma.

BACKGROUND: Follow-up for patients with resected stage IIIA-D melanoma may include computed tomography (CT) or positron emission tomography (PET)/CT imaging to identify distant metastases. The aim of this study was to evaluate the test performance over follow-up time, of structured 6- and 12-monthly follow-up imaging schedules in these patients. METHODS: We conducted a retrospective analysis of consecutive resected stage IIIA-D melanoma patients from Melanoma Institute Australia (2000-2017). Patients were followed until a confirmed diagnosis of distant metastasis, end of follow-up schedule, or death. Test accuracy was evaluated by cross-classifying the results of the test against a composite reference standard of histopathology, cytology, radiologic imaging, and/or clinical follow-up, and then quantified longitudinally using logistic regression models with random effects. RESULTS: In total, 1373 imaging tests were performed among 332 patients. Distant metastases were detected in 110 (33%) patients during a median follow-up of 61 months (interquartile range 38-86), and first detected by imaging in 86 (78%) patients. 152 (68%) patients had at least one false-positive result. Sensitivity of the schedule over 5 years was 79% [95% confidence interval (CI) 70-86%] and specificity was 88% (95% CI 86-90%). There was no evidence of a significant difference in test performance over follow-up time or by American Joint Committee on Cancer (AJCC) substage. The positive predictive value ranged between 33 and 48% over follow-up time, reflecting a ratio of 1:2 false-positives per true-positive finding. CONCLUSIONS: Regular 6- or 12-monthly surveillance imaging using CT or PET/CT has reasonable and consistent sensitivity and specificity over 5-year follow-up for resected stage IIIA-D melanoma patients. These data are useful when discussing the risks and benefits of long-term follow-up.

False-Positive Results and Incidental Findings with Annual CT or PET/CT Surveillance in Asymptomatic Patients with Resected Stage III Melanoma.

OBJECTIVE: The aim of this study was to quantify false-positive and incidental findings from annual surveillance imaging in asymptomatic, American Joint Committee on Cancer stage III melanoma patients. METHODS: This was a cohort study of patients treated at Melanoma Institute Australia (2000-2015) with baseline computed tomography (CT) or positron emission tomography (PET)/CT imaging and at least two annual surveillance scans. False-positives were defined as findings suspicious for melanoma recurrence that were not melanoma, confirmed by histopathology, subsequent imaging, or clinical follow-up, while incidental findings were defined as non-melanoma-related findings requiring further action. Outcomes of incidental findings were classified as 'benign' if they resolved spontaneously or were not seriously harmful; 'malignant' if a second malignancy was identified; or 'other' if potentially harmful. RESULTS: Among 154 patients, 1022 scans were performed (154 baseline staging, 868 surveillance) during a median follow-up of 85 months (interquartile range 56-112); 57 patients (37%) developed a recurrence. For baseline and surveillance imaging, 124 false-positive results and incidental findings were identified in 81 patients (53%). The frequency of these findings was 5-14% per year, and an additional 181 tests, procedures, and referrals were initiated to investigate these findings. The diagnosis was benign in 109 findings of 124 findings (88%). Fifteen patients with a benign finding underwent an unnecessary invasive procedure. Surveillance imaging identified distant metastases in 20 patients (13%). CONCLUSION: False-positive results and incidental findings occur in at least half of all patients undergoing annual surveillance imaging, and the additional healthcare use is substantial. These findings persist over time. Clinicians need to be aware of these risks and discuss them with patients, alongside the expected benefits of surveillance imaging.

Use of shared care and routine tests in follow-up after treatment for localised cutaneous melanoma.

BACKGROUND: Patients may decide to undertake shared care with a general practitioner (GP) during follow-up after treatment for localised melanoma. Routine imaging tests for surveillance may be commonly used despite no evidence of clinical utility. This study describes the frequency of shared care and routine tests during follow-up after treatment for localised melanoma. METHODS: We randomly sampled 351 people with localised melanoma [American Joint Cancer Committee (AJCC) substages 0 - II] who had not had recurrent or new primary melanoma diagnosed from a total of 902 people diagnosed and treated for localised melanoma at a specialist centre in 2014. We interviewed participants by telephone about their experience of follow-up in the past year, and documented the proportion of patients who were undertaking shared care follow-up with a GP. We also recorded the frequency and type of investigations during follow-up. We calculated weighted estimates that are representative of the full inception cohort. RESULTS: Of the 351 people who were invited to participate, 230 (66%) people consented to the telephone interview. The majority undertook shared care follow-up with a GP (61%). People who choose to have shared care follow-up with a GP are more likely to be male (p = 0.006), have lower AJCC stage (p for trend = 0.02), reside in more remote areas (p for trend< 0.001), and are less likely to have completed secondary school (p < 0.001). Few people saw a non-doctor health practitioner as part of their follow-up (9%). Many people report undergoing tests for melanoma, much of which may be routine tests for surveillance (37%). CONCLUSIONS: The majority of people treated for a first primary localised melanoma at a specialist centre, without recurrent or new melanoma, choose to undertake shared care follow-up with a GP. Many appear to have routine diagnostic imaging as part of their melanoma surveillance.

Fear of new or recurrent melanoma after treatment for localised melanoma.

OBJECTIVE: To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. METHODS: We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. RESULTS: Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. CONCLUSIONS: There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis.

Psychometric properties of the Fear of Cancer Recurrence Inventory: an item response theory approach.

OBJECTIVE: Classical psychometric methods have been used to demonstrate the validity and reliability of the 42-item Fear of Cancer Recurrence Inventory (FCRI). Our aim was to expand on this evidence with information on the discriminative value of the individual items when administered to people with a personal history of melanoma, using an item response theory (IRT) approach. METHODS: We used a two-parameter IRT model to examine all items of the FCRI, primarily regarding whether people with a personal history of melanoma use the response scale as expected (as indicated by item characteristic curves), and whether the items can discriminate between those low and high on the constructs assessed by the instrument. RESULTS: The sample was comprised of 286 adults with a personal history of melanoma (58% male, mean age: 59.1 years). The established factor structure of the FCRI was generally confirmed. IRT highlighted several items with problematic item characteristic curves, including most items in the Reassurance and Coping Strategies domains. Several other items exhibited poor discrimination. CONCLUSIONS: Based on this IRT analysis, we outline suggestions for refinement of the FCRI and potential development of a short-form, that could reduce respondent burden. Generalisability of these findings beyond melanoma warrants further examination. Copyright © 2015 John Wiley & Sons, Ltd.

Economic evaluations of psychosocial interventions in cancer: a systematic review.

OBJECTIVE: Although the effectiveness of many psychosocial interventions for people with cancer has been established, one barrier to implementation in routine clinical care is a lack of data on cost-effectiveness. We conducted a systematic review to assess the cost-effectiveness of psychosocial interventions for improving psychological adjustment among people with cancer. METHODS: A systematic review of the literature, study appraisal and narrative synthesis. RESULTS: Eight studies involving 1668 patients were identified. Four of these reported outcomes in a cost per quality adjusted life year (QALY) framework. Six studies reported psychosocial interventions to be cost-effective for improving health-related quality of life, mood, pain, distress or fear of cancer progression, compared with usual care. Of the six psychosocial interventions identified as cost-effective, three were cognitive-behavioural therapy-based interventions, one was a nurse-delivered telephone follow-up plus educational group programme, one was a group-based exercise and psychosocial intervention and one was a series of 10 face-to-face or telephone-based individual support sessions delivered by a nurse. The quality of studies assessed according to the Consensus Health Economic Criteria-list criteria was good overall; however, some studies were limited by their choice of outcome measure and omission of important categories of costs. CONCLUSIONS: Several psychosocial interventions, particularly those based on cognitive-behavioural therapy, have been demonstrated to represent good value for money in cancer care. Future research should include a clear definition of the economic question, inclusion of all relevant costs, and consideration of utility-based quality of life measures for QALY estimation. Copyright © 2016 John Wiley & Sons, Ltd.

"Melanoma: Questions and Answers." Development and evaluation of a psycho-educational resource for people with a history of melanoma.

PURPOSE: People with melanoma often report pervasive fears about cancer recurrence, unmet information needs, and difficulties accessing psychological care. Interventions addressing the supportive care needs of people with melanoma are rare, and needs are often overlooked. The study evaluated a newly developed, evidence-based, psycho-educational resource for people with melanoma. METHODS: The evaluation study comprised three groups: adults at high risk of new primary disease due to multiple previous melanomas or one melanoma and dysplastic nevus syndrome (DNS), adults at moderate risk due to one previous melanoma and no DNS, and health professionals involved in melanoma care. Participants evaluated a 68-page psycho-educational booklet, Melanoma: Questions and Answers, developed by a multidisciplinary team in accordance with published evidence, clinical guidelines, and intervention development frameworks. The booklet comprised seven modules featuring information on melanoma diagnosis, treatment, prognosis, and ongoing clinical management; risk factors and the role of genetic counseling services for melanoma; psycho-education on emotional, behavioral, and cognitive responses to melanoma, including psycho-education on fear of cancer recurrence; description of healthy coping responses; a suite of tailored tools to support skin self-examination, doctor-patient communication, and identification of the signs and symptoms of anxiety and depression; a list of community-based services and resources; and tools to support melanoma-related record keeping and monitoring. Resource acceptability, relevance, quality, dissemination preferences, emotional responses, unmet information needs, and demographic characteristics were assessed. RESULTS: Nineteen melanoma survivors (response rate 50 %) and 10 health professionals (response rate 83 %) evaluated the resource. Responses were overwhelmingly positive; the booklet was thoroughly read and highly rated in terms of quality and quantity of information, utility of health education tools, and capacity to address unmet needs. Ninety-five percent of melanoma survivors would recommend the booklet to others. Most preferred a paper-based format, provided by their treating doctor at diagnosis. CONCLUSIONS: Melanoma: Questions and Answers was feasible and acceptable and demonstrated a strong capacity to address the information and psycho-educational needs of people with melanoma at low fiscal cost.

Improving subjective perception of personal cancer risk: systematic review and meta-analysis of educational interventions for people with cancer or at high risk of cancer.

BACKGROUND: Newly diagnosed patients with cancer require education about the disease, the available treatments and potential consequences of treatment. Greater understanding of cancer risk has been found to be associated with greater health-related quality of life, improved psychological adjustment and greater health-related behaviours. The aim of this sytematic review was to assess the effectiveness of educational interventions in improving subjective cancer risk perception and to appraise the quality of the studies. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies. Eligible studies were identified via Medline, PsycINFO, AMED, CINAHL and Embase databases. After screening titles and abstracts, two reviewers independently assessed the eligibility of 206 full-text articles. RESULTS: Forty papers were included in the review; the majority of studies were conducted among breast cancer patients (n = 29) and evaluated the effect of genetic counselling on personal perceived risk (n = 25). Pooled results from RCTs (n = 12) showed that, both in the short and long term, educational interventions did not significantly influence risk perception level (standardised mean difference 0.05, 95% CI -0.24-0.34; p = 0.74) or accuracy (odds ratio = 1.96, 95% CI: 0.61-6.25; p = 0.26). Only one RCT reported a short-term difference in risk ratings (p = 0.01). Of prospective observational studies (n = 28), many did demonstrate changes in the level of perceived risk and improved risk accuracy and risk ratings in both the short and long term. However, only one (of three) observational studies reported a short-term difference in risk ratings (p < = 0.003). CONCLUSION: Further development and investigation of educational interventions using good quality, RCTs are warranted.

What Australian women want and when they want it: cervical screening testing preferences, decision-making styles and information needs.

BACKGROUND: New testing technologies and human papillomavirus (HPV) vaccines have recently brought changes to cervical cancer screening. In 2006, the Australian government also changed the protocol for managing abnormal Pap smears. Australian women's attitudes and preferences to these changes are largely unknown. Quantitative data on information needs and community attitudes to informed decision making in screening in Australia are also limited. OBJECTIVE: This national study measures women's preferences for testing and management of abnormal screening results, preferred decision-making styles and information needs for cervical cancer screening. DESIGN: A randomly selected sample of Australian women aged 18-70 participated in a structured telephone questionnaire, exploring testing preferences, information and decision-making needs. RESULTS: A total of 1279, of 1571 eligible women, participated in the study with an overall response rate of 81.4%. Half of the women (n = 637) preferred having their Pap smears at least annually, and 85% wanted concurrent HPV testing. A large proportion of women preferred to be involved in decision making for both routine Pap smears (87%) and follow-up for abnormal results (89%). The majority of women wanted information on screening risks (70%) and benefits (77%); of these 81 (85%) wanted this information before screening. However, 63% of women only wanted information about follow-up examinations if they had an abnormal Pap test result. CONCLUSION: Australian women want to be involved in decision making for cervical cancer screening and require information on the risks and benefits of Pap testing prior to undergoing any screening.

Lifetime direct healthcare costs of treating colorectal cancer: a systematic review.

Colorectal cancer is a global public health issue and imposes a significant economic burden on populations and healthcare systems. This paper systematically reviews the literature to estimate the direct costs of colorectal cancer incurred during different phases of treatment (initial, continuing and end of life). MEDLINE, EMBASE, Web of science, Evidence-based medicine reviews: National health service economic evaluation database guide, econlit and grey literature from the 1st of January 2000 to the 1st of February 2020. The methodological quality of the included studies was assessed using the Evers' Consensus on health economic criteria checklist. In total, 39,489 records were retrieved, and 17 studies were included. Costs by phase of treatment varied due to heterogeneity. However, studies that examined average costs for each phase of treatment showed a V-shaped distribution where the initial and end of life phases contribute the most and the continuing phase the least. The initial phase ranged from $7,893 to $60,289; the continuing annual phase ranged from $2,323 to $15,744; and the end of life phase ranged from $15,916 to $99,687. Studies that provided the total cost of each phase conversely showed that the continuing phase was the highest contributor to the cost of treating CRC. This study estimates the cost of the contemporary management of colorectal cancer despite the methodological heterogeneity. These costs place a heavy burden on healthcare providers, patients and their families. Identifying these costs can impact health care budgets and guide policymakers in making informed decisions for the future.

Exploring the Integration of Environmental Impacts in the Cost Analysis of the Pilot MEL-SELF Trial of Patient-Led Melanoma Surveillance.

AIMS: Human health is intrinsically linked with planetary health. But planetary resources are currently being degraded and this poses an existential threat to human health and the sustainability of our healthcare systems. The aims of this study were to (1) describe an approach to integrate environmental impacts in a cost analysis; and (2) demonstrate this approach by estimating select environmental impacts alongside traditional health system and other costs using the example of the pilot MEL-SELF randomised controlled trial of patient-led melanoma surveillance. METHODS: Economic costs were calculated alongside a randomised trial using standard cost analysis methodology from a societal perspective. Environmental impacts were calculated using a type of carbon footprinting methodology called process-based life cycle analysis. This method considers three scopes of carbon emissions: Scope 1, which occur directly from the intervention; Scope 2, which occur indirectly from the intervention's energy use; and Scope 3, which occur indirectly because of the value chain of the intervention. In this study we only included emissions from patient transport to attend their melanoma clinic over the study period of 6 months. RESULTS: The environmental impact per participant across allocated groups for patient transport to their melanoma clinic was estimated to be 10 kg carbon dioxide equivalent. Economic costs across the allocated groups indicated substantial health system costs, out-of-pocket costs, and productivity losses associated with melanoma surveillance. The largest cost contributor was health system costs, and the most expensive category of health system cost was hospital admission. CONCLUSION: Calculating environmental impacts is worthwhile and feasible within a cost analysis framework. Further work is needed to address outstanding conceptual and practical issues so that a comprehensive assessment of environmental impacts can be considered alongside economic costs in health technology assessments.

A systematic review with evidence mapping of supportive care interventions for melanoma patients and caregivers.

AIM: We conducted a systematic review and evidence gap mapping to explore the existing supportive care interventions and their impact on well-being outcomes for melanoma patients and caregivers. METHODS: We searched MEDLINE, Embase, Web of Science Index Medicus, CINAHL, Lilacs, CENTRAL (Cochrane Library) and PsycINFO in December 2022, including interventional studies assessing the effectiveness of any supportive care intervention among melanoma patients and/or their caregivers. FINDINGS: Twenty studies were included in this review. These studies consisted of randomised controlled trials (n = 11, 55%), pre-post studies (n = 7, 35%) and quasi-experimental trials (n = 2, 10%). All studies originated from high-income countries and focused primarily on melanoma patients, with no studies identified that focused solely on caregivers. Educational interventions were the most common (n = 7, 35%), followed by psychoeducational interventions (n = 6, 30%) and psychotherapeutic interventions (n = 4, 20%). Nearly all included studies (n = 18, 90%) reported a positive effect of the intervention on the primary outcome of interest; however, most studies (n = 17, 85%) were judged to be at moderate or high risk of bias. Due to heterogeneity of study designs, intervention characteristics and outcome measures, meta-analysis was not conducted. IMPLICATIONS: Supportive care interventions have positive impacts on melanoma patient well-being outcomes, while being acceptable and feasible to conduct. More research is needed regarding supportive care interventions for melanoma caregivers. Future research should focus on eliminating sources of bias through rigorous methodology, with the development of standardised outcome measures for psychosocial outcomes to facilitate future meta-analyses.

Study protocol of the WashT Trial: transfusion with washed versus unwashed red blood cells to reduce morbidity and mortality in infants born less than 28 weeks' gestation - a multicentre, blinded, parallel group, randomised controlled trial.

INTRODUCTION: Many extremely preterm newborns develop anaemia requiring a transfusion, with most receiving three to five transfusions during their admission. While transfusions save lives, the potential for transfusion-related adverse outcomes is an area of growing concern. Transfusion is an independent predictor of death and is associated with increased morbidity, length of hospital stay, risk of infection and immune modulation. The underlying mechanisms include adverse pro-inflammatory and immunosuppressive responses. Evidence supports an association between transfusion of washed red cells and fewer post-transfusion complications potentially through removal of chemokines, lipids, microaggregates and other biological response modifiers. However, the clinical and cost-effectiveness of washed cells have not been determined. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded trial of washed versus unwashed red cells. Infants <28 weeks' gestation requiring a transfusion will be enrolled. Transfusion approaches will be standardised within each study centre and will occur as soon as possible with a recommended fixed transfusion volume of 15 mL/kg whenever the haemoglobin is equal to or falls below a predefined restrictive threshold, or when clinically indicated. The primary outcome is a composite of mortality and/or major morbidity to first discharge home, defined as one or more of the following: physiologically defined bronchopulmonary dysplasia; unilateral or bilateral retinopathy of prematurity grade >2, and; necrotising enterocolitis stage ≥2. To detect a 10% absolute reduction in the composite outcome from 69% with unwashed red blood cell (RBCs) to 59% with washed RBCs with 90% power, requires a sample size of 1124 infants (562 per group). Analyses will be performed on an intention-to-treat basis with a prespecified statistical analysis plan. A cost-effectiveness analysis will also be undertaken. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Women's and Children's Health Network Human Research Ethics Committee (HREC/12/WCHN/55). The study findings will be disseminated through peer-reviewed articles and conferences. TRIAL REGISTRATION NUMBER: ACTRN12613000237785 Australian New Zealand Clinical Trials Registry.

Cost of colorectal cancer by treatment type from different health economic perspectives: A systematic review.

Advancements in colorectal cancer treatment have substantially improved overall survival. However, the cost of treating colorectal cancer places a significant economic burden on populations and healthcare systems. It is accepted that costs and what a health system charges may differ. This study aims to understand the expenditure on colorectal cancer globally. Specifically, this paper systematically reviews the literature to estimate the direct costs of each component in treating colorectal cancer, including primary care, diagnostics, surgery, chemotherapy, radiotherapy, and follow-up. MEDLINE, EMBASE, Web of Science, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database Guide, Econlit and grey literature from the January 1, 2000 to the February 1, 2020. The methodological quality of the included studies was assessed using the Evers' Consensus on Health Economic Criteria checklist. In total, 39,489 records were retrieved, and after appropriate culling of non-relevant articles, 15 studies were included. Costs for treating colorectal cancer varied due to heterogeneity between different studies despite comparing similar clinical settings and study perspectives. Studies that presented an average cost per patient demonstrated that surgical costs ranged from $1,149 to $34,606, chemotherapy ranged from $1,883 to $18,021 and radiotherapy ranged from $2,037 to $5,347 in 2018 USD. Identifying these costs can impact health care budgets and guide policymakers in making informed decisions for the future.