Assessing health state utilities for people with myalgic encephalomyelitis/chronic fatigue syndrome in Australia using the EQ-5D-5L, AQoL-8D and EQ-5D-5L-psychosocial instruments.

PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition with a constellation of symptoms presenting as severe and profound fatigue of ≥ 6 months not relieved by rest. ME/CFS affects health-related quality of life (HRQoL), which can be measured using multi-attribute health state utility (HSU) instruments. The aims of this study were to quantify HSUs for people living with ME/CFS, and to identify an instrument that is preferentially sensitive for ME/CFS. METHODS: Cross-sectional national survey of people with ME/CFS using the AQoL-8D and EQ-5D-5L. Additional questions from the AQoL-8D were used as 'bolt-ons' to the EQ-5D-5L (i.e., EQ-5D-5L-Psychosocial). Disability and fatigue severity were assessed using the De Paul Symptom Questionnaire-Short Form (DSQ-SF). HSUs were generated using Australian tariffs. Mean HSUs were stratified for sociodemographic and clinical factors. Bland-Altman plots were used to compare the three HSU instruments. RESULTS: For the 198 participants, mean HSUs (95% confidence intervals) were EQ-5D-5L: 0.46 (0.42-0.50); AQoL-8D: 0.43 (0.41-0.45); EQ-5D-5L-Psychosocial: 0.44 (0.42-0.46). HSUs were substantially lower than population norms: EQ-5D-5L: 0.89; AQoL-8D: 0.77. As disability and fatigue severity increased, HSUs decreased in all three instruments. Bland-Altman plots revealed interchangeability between the AQoL-8D and EQ-5D-5LPsychosocial. Floor and ceiling effects of 13.5% and 2.5% respectively were observed for the EQ-5D-5L instrument only. CONCLUSIONS: ME/CFS has a profound impact on HRQoL. The AQoL-8D and EQ-5D-5L-Psychosocial can be used interchangeably: the latter represents a reduced participant burden.

The economic burden of myalgic encephalomyelitis/chronic fatigue syndrome in Australia.

Objective This study aimed to estimate costs of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to patients, government and Australian society. Methods Australian ME/CFS patients and their carers were recruited using convenience sampling. Patients completed an online retrospective cost diary, providing ME/CFS-related direct medical, non-medical and indirect costs. Informal care costs were collected directly from carers. Data from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule were linked to participant survey data. Annual per patient and total societal costs were estimated, broken down by category and presented in 2021 AUD. Factors associated with higher costs were investigated using generalised linear models. Results One hundred and seventy five patients (mean age 49 years s.d. 14, 79.4% female) completed the cost diary. Estimated total annual societal costs of ME/CFS in Australia ranged between $1.38 and $10.09 billion, with average annual total costs of $63 400/patient. Three-quarters of these costs were due to indirect costs ($46 731). Disability severity was the key factor associated with higher costs, particularly for indirect costs (being 2.27-fold higher for severe disability than no/mild disability). Conclusions ME/CFS poses a significant economic burden in Australia, owing mainly to high indirect and informal care costs.

Association of Calcaneal Bone Marrow Lesions and Plantar Fascia Imaging Biomarkers With Chronic Plantar Heel Pain: A Case-Control Study.

OBJECTIVE: To determine associations between chronic plantar heel pain (CPHP) and imaging biomarkers derived from magnetic resonance imaging (MRI) and ultrasonography. METHODS: We compared 218 participants with CPHP with 100 age- and sex-matched population controls. We assessed imaging biomarkers on MRI (calcaneal bone marrow lesions [BMLs], plantar fascia [PF] signal and thickness, spurs, and fat pad signal) and B-mode/power Doppler ultrasound (PF thickness, echogenicity, and vascularity). Covariate data collected included demographic characteristics, disease history, clinical measures, and physical activity by accelerometry. Data were analyzed using multivariable conditional logistic regression. RESULTS: Plantar calcaneal BML size (mm2 , odds ratio [OR] 1.03 [95% confidence interval (95% CI) 1.02-1.05]), larger plantar spurs (OR for spurs >5 mm 2.15 [95% CI 1.13-4.10]), PF signal (OR for signal penetrating >50% of the dorsoplantar width 12.12 [95% CI 5.36-27.42]), PF thickness (mm, OR for MRI 3.23 [95% CI 2.36-4.43] and ultrasound OR 3.78 [95% CI 2.69-5.32]), and echogenicity (diffusely hypoechoic OR 7.89 [95% CI 4.02-15.48] and focally hypoechoic OR 24.92 [95% CI 9.60-64.69]) were independently associated with CPHP. PF vascularity was uncommon, occurring exclusively in cases (cases with signal n = 47 [22%]). Combining imaging biomarkers into 1 model, plantar BMLs and PF imaging biomarkers, but not fat pad signal or heel spurs, were independently associated with CPHP. CONCLUSION: Calcaneal BMLs and PF imaging biomarkers are associated with CPHP. Further research is required to understand whether these different markers represent distinct phenotypes of heel pain, and if so, whether there are specific treatment implications.

MYC sensitises cells to apoptosis by driving energetic demand.

The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.

Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Australian primary care patients: only part of the story?

BACKGROUND: ME/CFS is a disorder characterized by recurrent fatigue and intolerance to exertion which manifests as profound post-exertional malaise. Prevalence studies internationally have reported highly variable results due to the 20 + diagnostic criteria. For Australia, the prevalence of ME/CFS based on current case definitions is unknown. OBJECTIVES: To report prevalence of ME/CFS in patients aged ≥ 13 years attending Australian primary care settings for years 2015-2019, and provide context for patterns of primary care attendance by people living with ME/CFS. METHODOLOGY: Conducted in partnership with the Patient Advisory Group, this study adopted a mixed methods approach. De-identified primary care data from the national MedicineInsight program were analyzed. The cohort were regularly attending patients, i.e. 3 visits in the preceding 2 years. Crude prevalence rates were calculated for years 2015-2019, by sex, 10-year age groups, remoteness and socioeconomic status. Rates are presented per 100,000population (95% confidence intervals (CI)). Qualitative data was collected through focus groups and in-depth 1:1 interview. RESULTS: Qualitative evidence identified barriers to reaching diagnosis, and limited interactions with primary care due to a lack of available treatments/interventions, stigma and disbelief in ME/CFS as a condition. In each year of interest, crude prevalence in the primary care setting ranged between 94.9/100,000 (95% CI: 91.5-98.5) and 103.9/100,000 population (95%CI: 100.3-107.7), equating to between 20,140 and 22,050 people living with ME/CFS in Australia in 2020. Higher rates were observed for age groups 50-59 years and 40-49 years. Rates were substantially higher in females (130.0-141.4/100,000) compared to males (50.9-57.5/100,000). In the context of the qualitative evidence, our prevalence rates likely represent an underestimate of the true prevalence of ME/CFS in the Australian primary care setting. CONCLUSION: ME/CFS affects a substantial number of Australians. Whilst this study provides prevalence estimates for the Australian primary care setting, the qualitative evidence highlights the limitations of these. Future research should focus on using robust case ascertainment criteria in a community setting. Quantification of the burden of disease can be used to inform health policy and planning, for this understudied condition.

Identifying subgroups of community-dwelling older adults and their prospective associations with long-term knee osteoarthritis outcomes.

OBJECTIVES: To identify subgroups of community-dwelling older adults and to assess their longitudinal associations with long-term osteoarthritis (OA) outcomes. METHODS: 1046 older adults aged 50-80 years were studied. At baseline, body mass index (BMI), pedometer-measured ambulatory activity (AA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) determined knee pain and information on comorbidities were obtained. Tibial cartilage volume and bone-marrow lesions (BMLs) were assessed using MRI at baseline and 10 years and total knee replacements (TKR) by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Latent class analysis was used to determine participant subgroups, considering baseline BMI, AA, pain and comorbidities, and linear mixed-effects or log-binomial models were used to assess the associations. RESULTS: Three subgroups/classes were identified: subgroup 1 (43%): Normal/overweight participants with higher AA, lower pain and lower comorbidities; subgroup 2 (32%): Overweight participants with lower AA, mild pain and higher comorbidities; subgroup 3 (25%): Obese participants with lower AA, mild pain and higher comorbidities. Subgroup 3 had greater cartilage volume loss (ß - 60.56 mm3, 95% CI - 105.91, - 15.21) and a higher risk of TKR (RR 3.19, 95% CI 1.75, 5.81), compared to subgroup 1. Subgroup 2 was not associated with cartilage volume change (ß 13.06 mm3, 95% CI - 30.87, 57.00) or risk of TKR (RR 1.16, 95% CI 0.56, 2.36), compared to subgroup 1. Subgroup membership was not associated with worsening BMLs. CONCLUSIONS: Our findings suggest the existence of homogeneous subgroups of participants and support the utility of identifying patterns of characteristics/risk factors that may cluster together and using them to identify subgroups of people who may be at a higher risk of developing and/or progressing OA. Key Points • Complex interplay among characteristics/factors leads to conflicting evidence between ambulatory activity and knee osteoarthritis. • Distinct subgroups are identifiable based on ambulatory activity, body mass index, knee pain, and comorbidities. • Identifying subgroups can be used to determine those who are at risk of developing/progressing osteoarthritis.

Cardiovascular and other competing causes of death among patients with cancer from 2006 to 2015: An Australian population-based study.

BACKGROUND: With improved cancer survivorship, cardiovascular disease (CVD) and other noncancer events compete with cancer as the underlying cause of death, but the risks of mortality in competing-risk settings have not been well characterized. METHODS: The authors identified 21,637 individuals who had a first cancer registered between 2006 and 2013, with follow-up to 2015, in the Australian population-based Tasmanian Cancer Registry. The cumulative incidence of deaths from specific competing events was assessed in competing-risk analyses. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) for deaths from noncancer causes were calculated for comparison with the general population. RESULTS: Overall, 8844 deaths were observed, with 1946 (22%) from competing events. The cumulative incidence of deaths from CVD increased significantly with age at first cancer diagnosis and exceeded other competing events at age ≥65 years. The risk of death from CVD was more common than expected in the first year of follow-up (SMR, 1.44 [95% confidence interval, 1.26-1.64]; AER, 36.8 per 10,000 person-years). The SMR and AER for CVD deaths varied by first cancer site, indicating increased risks after a first diagnosis of lung cancer, hematologic malignancy, and urinary tract cancer. For other noncancer events, the SMRs increased significantly for deaths from infectious disease and respiratory disease and were highest in the first year of follow-up. CONCLUSIONS: CVD was the leading cause of competing mortality among Tasmanian patients with cancer who were diagnosed from 2006 to 2013. The higher than expected occurrence of death from CVD and other noncancer events during the first year after a cancer diagnosis highlights the importance of early preventive interventions.

Temporal trends in competing mortality from second and subsequent primary cancers, 1980-2014: An Australian population-based study.

BACKGROUND: Subsequent primary cancers (SPCs) compete with first cancers and non-cancer events as the primary cause of death among cancer patients. We aimed to assess temporal trends in SPC mortality since 1980 among adult-onset cancer patients in competing risk models. METHODS: Patients registered with a first cancer in the population-based Tasmanian Cancer Registry, Australia, between 1980-2009 were followed up to December 2014. Cumulative incidence function (CIF) was used to estimate the cumulative incidence of cause-specific deaths in the presence of competing risks. The hazard ratios of SPC-specific deaths were assessed in two regression models: subdistribution hazard ratios from competing risk models (SHRs) and hazard ratios from Cox models (CHRs). RESULTS: Overall, 5339 (9.3%) of 57,288 patients developed SPCs and 2494 died from SPCs during the follow-up. While the cumulative incidence of first cancer deaths at 5, 10, 15 and 20-years gradually decreased over periods of first cancer diagnosis, the cumulative incidence of SPC deaths did not. The SHRs for SPC-specific deaths increased from the reference period 1980-1984 to a peak for first cancers diagnosed in 1995-1999 (SHR = 1.18, 95%CI 1.03-1.35), before a decrease in 2005-2009 (SHR = 0.82, 95%CI 0.70-0.95) in competing risk models. However, this pattern was not consistent in CHRs. For individuals with specific first cancers, those with a first prostate cancer in 1995-1999 ha d the greatest SPC mortality risk (SHR = 2.08, 95%CI 1.29-3.36). CONCLUSION: Competing risk models, but not Cox models, demonstrated temporal increases in SPC-specific mortality. Greater detection of non-fatal first prostate cancers appears to have contributed to this trend.

How Do MRI-Detected Subchondral Bone Marrow Lesions (BMLs) on Two Different MRI Sequences Correlate with Clinically Important Outcomes?

The aim of this study is to describe the association of bone marrow lesions (BMLs) present on two different MRI sequences with clinical outcomes, cartilage defect progression, cartilage volume loss over 2.7 years, and total knee replacement (TKR) over 13.3 years. 394 participants (50-80 years) were assessed at baseline and 2.7 years. BML presence at baseline was scored on T1-weighted fat-suppressed 3D gradient-recalled acquisition (T1) and T2-weighted fat-suppressed 2D fast spin-echo (T2) sequences. Knee pain, function, and stiffness were assessed using WOMAC. Cartilage volume and defects were assessed using validated methods. Incident TKR was determined by data linkage. BMLs were mostly present on both MRI sequences (86%). BMLs present on T2, T1, and both sequences were associated with greater knee pain and functional limitation (odds ratio = 1.49 to 1.70; all p < 0.05). Longitudinally, BMLs present on T2, T1, and both sequences were associated with worsening knee pain (ß = 1.12 to 1.37, respectively; p < 0.05) and worsening stiffness (ß = 0.45 to 0.52, respectively; all p < 0.05) but not worsening functional limitation or total WOMAC. BMLs present on T2, T1, and both sequences predicted site-specific cartilage defect progression (relative risk = 1.22 to 4.63; all p < 0.05) except at the medial tibial and inferior patellar sites. Lateral tibial and superior patellar BMLs present on T2, T1, and both sequences predicted site-specific cartilage volume loss (ß = - 174.77 to - 140.67; p < 0.05). BMLs present on T2, T1, and both sequences were strongly associated with incident TKR. BMLs can be assessed on either T2- or T1-weighted sequences with no clinical predictive advantage of either sequence.

Temporal trends in the risk of second primary cancers among survivors of adult-onset cancers, 1980 through 2013: An Australian population-based study.

BACKGROUND: The authors' systematic review indicated an increasing trend in the risk of second primary cancers (SPCs) from the 1980s to 2000 when considering studies from the United States and Australia. It is uncertain whether this trend has continued to increase since 2000. METHODS: The current study was a population-based study of 51,802 individuals with adult-onset cancers identified in the Tasmanian Cancer Registry. Patients with a first cancer diagnosis made between 1980 and 2009 were followed up to December 2013. SPC risks were quantified using standardized incidence ratios (SIRs) and absolute excess risks (AERs). Trends in SPC risk were assessed using multivariable Poisson models. RESULTS: With a median follow-up of 4.8 years (mean, 6.9 years), a total of 5339 SPCs were observed. The SIRs for any SPC increased from 0.98 (95% confidence interval, 0.90-1.07) after a first cancer diagnosis in 1980 through 1984 to 1.12 (95% confidence interval, 1.05-1.20) in 2005 through 2009. In multivariable Poisson models accounting for patient sex, age at the time of the first cancer diagnosis, follow-up interval, and first cancer type, the trend in SIRs increased significantly from 1980 through 2009 for all SPCs (P for trend <.001) and for specific SPCs of the head and neck, lung, digestive tract, and prostate (all P for trend <.05). From 2000 onward, the AER for specific SPCs after specific first cancers was highest for prostate cancer after first cancers of the urinary tract (AER, 54.3 per 10,000 person-years). CONCLUSIONS: In Tasmania, the risk of SPCs among survivors of adult-onset cancers has increased with periods of first cancer diagnosis from 1980 through 2009. Increased cancer screening and improved medical imaging may have contributed to the greater risk in recent years. Cancer 2018;124:1808-18. © 2018 American Cancer Society.

Individualized Fracture Risk Feedback and Long-term Benefits After 10 Years.

INTRODUCTION: This study aimed to determine if beneficial effects of individualized feedback of fracture risk on osteoporosis preventive behaviors and bone mineral density observed in a 2-year trial were sustained long-term. METHODS: This was a 10-year follow-up of a 2-year RCT in 470 premenopausal women aged 25-44 years, who were randomized to one of two educational interventions (the Osteoporosis Prevention and Self-Management Course [OPSMC] or an osteoporosis information leaflet) and received tailored feedback of their relative risk of fracture in later life (high versus normal risk groups). Bone mineral density of lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical activity, dietary calcium intake, calcium and vitamin D supplements, and smoking status were measured by questionnaires. RESULTS: From 2 to 12 years, the high-risk group had a smaller decrease in femoral neck bone mineral density (ß=0.023, 95% CI=0.005, 0.041 g/cm2) but similar lumbar spine bone mineral density change as the normal-risk group. They were more likely to use calcium (relative risk=1.66, 95% CI=1.22, 2.24) and vitamin D supplements (1.99, 95% CI=1.27, 3.11). The OPSMC had no effects on bone mineral density change. Both high-risk (versus normal-risk) and the OPSMC groups (versus leaflet) had a more favorable pattern of smoking behavior change (relative risk=1.85, 95% CI=0.70, 4.89 and relative risk=2.27, 95% CI=0.86, 6.01 for smoking cessation; relative risk=0.33, 95% CI=0.13, 0.80 and relative risk=0.28, 95% CI=0.10, 0.79 for commenced or persistent smoking). CONCLUSIONS: Feedback of high fracture risk to younger women was associated with long-term improvements in osteoporosis preventive behaviors and attenuated femoral neck bone mineral density loss. Therefore, this could be considered as a strategy to prevent osteoporosis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) NCT00273260.

Favourable outcomes for childhood acute lymphoblastic leukaemia in an isolated setting: The Tasmanian experience.

BACKGROUND: Tasmania is a large, relatively isolated island located south of mainland Australia with limited tertiary level paediatric oncology services. AIMS: To benchmark regional outcomes for childhood acute lymphoblastic leukaemia (ALL) against published international standards. METHODS: We undertook a retrospective cohort study, analysing the clinical characteristics and health outcomes of all children diagnosed with and treated for ALL in Tasmania, Australia between 2006 and 2015. RESULTS: Thirty-five patients aged less than 18 years were diagnosed with ALL in the study's 10-year period. Twenty-eight cases were precursor B cell in origin, with 7 cases of T-cell ALL. The great majority of children (30/35; 86%) received their entire first line treatment in Tasmania. Major treatment-related toxicities, including allergic drug reactions, and episodes of acute pancreatitis, deep venous thrombosis and bacterial sepsis, were managed locally, with one death secondary to overwhelming infection and multiorgan failure. The overall and event-free survival rates for childhood ALL were 30/35 (86%) and 28/35 (80%), respectively. CONCLUSIONS: These results compare favourably with published results from large international cooperative group trials based in developed countries. Continued local treatment with appropriate support from a dedicated specialist paediatric oncology unit is therefore justified.

Cancer risk management in Tasmanian women with BRCA1 and BRCA2 mutations.

Women carrying germline mutations in BRCA1 or BRCA2 have significantly increased lifetime risks of breast and tubo-ovarian cancer. To manage the breast cancer risk women may elect to have breast screening by MRI/mammogram from age 30, to take risk-reducing medication, or to have a prophylactic bilateral mastectomy. To manage the tubo-ovarian cancer risk, the only effective strategy is to have a bilateral salpingo-oophorectomy, recommended by age 40 (BRCA1) or 'around' age 40 (BRCA2). Early studies suggested that uptake of these cancer risk-reducing strategies was low. More recent studies have revealed higher rates of uptake, however it is unclear whether uptake is genuinely improving or whether the higher uptake rates reflect changes in the populations studied. In this study we surveyed 193 BRCA1/2 mutation carriers in the state of Tasmania to determine the uptake of cancer risk-reducing strategies and what factors might influence women's decisions in relation to both gynaecological and breast surgery. We observed that uptake of risk management strategies varied depending on the strength of the recommendation in the national guidelines. Uptake rates were > 90% for strategies which are strongly recommended, such as breast screening by MRI/mammogram and bilateral salpingo-oophorectomy, and were unaffected by demographic factors such as socio-economic disadvantage and educational achievement. Uptake rates were much lower for strategies which are presented in the guidelines as options for consideration and where patient choice and shared decision making are encouraged, such as prophylactic mastectomy (29%) and chemoprevention (1%) and in the case of prophylactic mastectomy, were influenced by both socio-economic advantage and educational achievement.

Associations of dietary patterns with bone mass, muscle strength and balance in a cohort of Australian middle-aged women.

Influences of dietary patterns on musculoskeletal health are poorly understood in middle-aged women. This cross-sectional analysis from a cohort of 347 women (aged 36-57 years) aimed to examine associations between dietary patterns and musculoskeletal health outcomes in middle-aged women. Diet was measured by the Cancer Council of Victoria FFQ. Total body bone mineral content (TB BMC), femoral neck and lumbar spine bone density (dual-energy X-ray absorptiometry), lower limbs muscle strength (LMS) and balance tests (timed up and go test, step test, functional reach test (FRT) and lateral reach test) were also measured. Exploratory factor analysis was used to identify dietary patterns and scores for each pattern generated using factor loadings with absolute values ≥0·20. Associations between food pattern scores and musculoskeletal outcomes were assessed using multivariable linear regression. Three dietary patterns were identified: 'Healthy' (high consumption of a plant-based diet - vegetables, legumes, fruit, tomatoes, nuts, snacks, garlic, whole grains and low intake of high-fat dairy products), 'high protein, high fat' (red meats, poultry, processed meats, potatoes, cruciferous and dark-yellow vegetables, fish, chips, spirits and high-fat dairy products) and 'Processed foods' (high intakes of meat pies, hamburgers, beer, sweets, fruit juice, processed meats, snacks, spirits, pizza and low intake of cruciferous vegetables). After adjustment for confounders, Healthy pattern was positively associated with LMS, whereas Processed foods pattern was inversely associated with TB BMC and FRT. The associations were not significant after accounting for multiple comparisons. There were no associations with any other outcomes. These results suggest that maintaining a healthy diet could contribute to bone acquisition, muscle strength and balance in adult life. However, while they provide some support for further investigating dietary strategies for prevention of age-related loss of muscle and deterioration in balance, the exploratory nature of the analyses means that confirmation in longitudinal studies and/or trials with pre-specified hypotheses is needed.

Temporal trends in the risk of developing multiple primary cancers: a systematic review.

BACKGROUND: Cancer survivors are at risk of developing second and subsequent primary cancers, referred to as multiple primary cancers (MPCs). It is not clear whether the risk of MPCs has increased over recent decades, but increasing use of radiological imaging and potentially harmful effects of certain cancer treatments raise this possibility. A systematic review was undertaken to assess whether there has been a temporal change in the risk of developing MPCs. METHODS: A systematic search to identify population-based studies of MPCs was performed in Medline/PubMed and Embase databases from inception to August 2016. Included studies were those reporting risk of MPCs for all sites combined following a first cancer at any site or a specific site, using standard incidence ratios (SIRs) or equivalent, and with analysis stratified by calendar years. RESULTS: We identified 28 articles eligible for inclusion, comprising 26 population-based studies and two monographs. MPC incidence was reported in nearly 6.5 million cancer survivors. For all first cancer sites combined, a higher rate of MPCs was reported in more recent than earlier calendar periods in four of the six relevant studies. The SIRs ranged from 1.14 for a first cancer diagnosis in the early 1980s to 1.21-1.46 in the late 1990s in the USA and Australia. Two studies from Italy and France showed no significant difference in SIRs across time periods 1978-2010 and 1989-2004. The remaining 22 studies reported various temporal trends in the risk of developing MPCs after a first cancer at a specific site, but most showed little change. CONCLUSION: Overall, the risk of developing MPCs appears to have increased since the 1980s when considering studies of all primary cancer sites combined from the USA and Australia but not from Europe. With the introduction of more routine nuclear medical imaging over the last 15 years, more studies are needed to confirm recent trends of MPC risk in adult cancer survivors.

A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial-mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study.

BACKGROUND: We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma. With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a "proof of concept" study. METHODS: Assessment of the effects of inhaled fluticasone propionate (FP; 500 µg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo). The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation ("hallmark" structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers). RESULTS: Epithelial activation, "clefts/fragmentation" in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance. From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study. CONCLUSION: Although only a pilot "proof of concept" study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways. A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important. Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD.

Effects of telephone health mentoring in community-recruited chronic obstructive pulmonary disease on self-management capacity, quality of life and psychological morbidity: a randomised controlled trial.

OBJECTIVES: To assess benefits of telephone-delivered health mentoring in community-based chronic obstructive pulmonary disease (COPD). DESIGN: Cluster randomised controlled trial. SETTING: Tasmanian general practices: capital city (11), large rural (3), medium rural (1) and small rural (16). PARTICIPANTS: Patients were invited (1207) from general practitioner (GP) databases with COPD diagnosis and/or tiotropium prescription, response rate 49% (586), refused (176) and excluded (criteria: smoking history or previous study, 68). Spirometry testing (342) confirmed moderate or severe COPD in 182 (53%) patients. RANDOMISATION: By random numbers code, block stratified on location, allocation by sequentially numbered, opaque and sealed envelopes. INTERVENTION: Health mentor (HM) group received regular calls to manage illness issues and health behaviours from trained community health nurses using negotiated goal setting: problem solving, decision-making and action planning. CONTROL: usual care (UC) group received GP care plus non-interventional brief phone calls. OUTCOMES: Measured at 0, 6 and 12 months, the Short Form 36 (SF-36) and St George's Respiratory Questionnaire (SGRQ, primary); Partners In Health (PIH) Scale for self-management capacity, Hospital Anxiety and Depression Scale (HADS), Center for Epidemiologic Studies-Depression (CES-D) questionnaire, Post-Traumatic Stress Disorder Checklist, Satisfaction with life and hospital admissions (secondary). RESULTS: 182 participants with COPD (age 68±8 years, 62% moderate COPD and 53% men) were randomised (HM=90 and UC=92). Mixed model regression analysis accounting for clustering, adjusting for age, gender, smoking status and airflow limitation assessed efficacy (regression coefficient, ß, reported per 6-month visit). There was no difference in quality of life between groups, but self-management capacity increased in the HM group (PIH overall 0.15, 95% CI 0.03 to 0.29; knowledge domain 0.25, 95% CI 0.00 to 0.50). Anxiety decreased in both groups (HADS A 0.35; 95% CI -0.65 to -0.04) and coping capacity improved (PIH coping 0.15; 95% CI 0.04 to 0.26). CONCLUSIONS: Health mentoring improved self-management capacity but not quality of life compared to regular phone contact, which itself had positive effects where decline is generally expected.