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.

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.

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.

Seasonal not annual rainfall determines grassland biomass response to carbon dioxide.

The rising atmospheric concentration of carbon dioxide (CO2) should stimulate ecosystem productivity, but to what extent is highly uncertain, particularly when combined with changing temperature and precipitation. Ecosystem response to CO2 is complicated by biogeochemical feedbacks but must be understood if carbon storage and associated dampening of climate warming are to be predicted. Feedbacks through the hydrological cycle are particularly important and the physiology is well known; elevated CO2 reduces stomatal conductance and increases plant water use efficiency (the amount of water required to produce a unit of plant dry matter). The CO2 response should consequently be strongest when water is limiting; although this has been shown in some experiments, it is absent from many. Here we show that large annual variation in the stimulation of above-ground biomass by elevated CO2 in a mixed C3/C4 temperate grassland can be predicted accurately using seasonal rainfall totals; summer rainfall had a positive effect but autumn and spring rainfall had negative effects on the CO2 response. Thus, the elevated CO2 effect mainly depended upon the balance between summer and autumn/spring rainfall. This is partly because high rainfall during cool, moist seasons leads to nitrogen limitation, reducing or even preventing biomass stimulation by elevated CO2. Importantly, the prediction held whether plots were warmed by 2 °C or left unwarmed, and was similar for C3 plants and total biomass, allowing us to make a powerful generalization about ecosystem responses to elevated CO2. This new insight is particularly valuable because climate projections predict large changes in the timing of rainfall, even where annual totals remain static. Our findings will help resolve apparent differences in the outcomes of CO2 experiments and improve the formulation and interpretation of models that are insensitive to differences in the seasonal effects of rainfall on the CO2 response.

Clinical diaries in COPD: compliance and utility in predicting acute exacerbations.

BACKGROUND: Daily diaries are often used to collect data on disease activity, but are burdensome and compliance may be poor. Their use in chronic obstructive pulmonary disease (COPD) and impact on the prevention and treatment of exacerbations is poorly researched. METHODS: We investigated diary-keeping in COPD and ascertained items that best predicted emergency attendances for exacerbations. Participants in the active limb of a clinical trial in COPD kept daily diaries rating breathlessness, cough, sputum, physical activity, and use of reliever medication. RESULTS: Data on 55 participants, 67% of whom were female, showed that overall compliance with diary-keeping was 62%. Participants educated to primary school level only had lower compliance (P = 0.05). Twenty patients had at least one emergency attendance, in whom the relative risk of an acute exacerbation for an increase in item score rose from six days prior to hospitalization, most sharply in the last two days. Even for optimal combinations of items, the positive predictive value was poor, the best combination being cough, activity level, and inhaler use. CONCLUSION: Good compliance can be achieved using daily diaries in COPD, although this is worse in those with a poor educational level. Diary-keeping is not accurate in predicting acute exacerbations, but could be substantially simplified without loss of efficiency.

Transition planning for youth with sickle cell disease: embedding neuropsychological assessment into comprehensive care.

OBJECTIVE: Sickle cell disease (SCD) conveys a high risk of neuropsychological impairment due to chronic anemia, hypoxemia, cerebrovascular ischemia and stroke, in addition to causing pain and other biomedical complications. Few families accessed neuropsychological testing via the traditional referral system. In this paper, we describe a successful alternative strategy for addressing cognitive and behavioral needs of youth with SCD. METHOD: The Sickle Cell Disease Program for Learning and Neuropsychological Evaluation (SCD-PLANE) was embedded in 2007 into the SCD Comprehensive Clinic of Children's Hospitals and Clinics of Minnesota. SCD-PLANE includes brief neuropsychological testing, individualized recommendations, patient education and advocacy, interdisciplinary collaboration, and follow-through to assure patients' access to recommended resources. The purpose of SCD-PLANE is to identify and recommend interventions for cognitive, academic, emotional, behavioral, or social problems affecting child development and transition to adulthood. RESULTS: Access to neuropsychological testing improved dramatically and is well accepted by SCD patients and families. Test results reveal increased risk of problems with executive function, speed of processing, graphomotor function, academic achievement, and parent-reported anxious/depressed symptoms, despite normal intelligence and language abilities. Patients' needs had not been previously identified or served by schools or other community agencies. CONCLUSIONS: The SCD-PLANE, providing brief neuropsychological testing embedded within routine annual visits to SCD Comprehensive Clinic, is an effective approach to detect unmet developmental, educational, and behavioral needs within an underserved high-risk population. As youth move towards adulthood, considering cognitive, academic, and mental health status facilitates successful health care transitions.

Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial.

OBJECTIVES: To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting. DESIGN: Cluster randomised controlled parallel group trial. SETTING: Ambulance service in Hobart, Tasmania, Australia. PARTICIPANTS: 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years. INTERVENTIONS: High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting. MAIN OUTCOME MEASURE: Prehospital or in-hospital mortality. RESULTS: In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure -33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen. CONCLUSIONS: Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Register ACTRN12609000236291.

Influence of warming on soil water potential controls seedling mortality in perennial but not annual species in a temperate grassland.

In a water-limited system, the following hypotheses are proposed: warming will increase seedling mortality; elevated atmospheric CO2 will reduce seedling mortality by reducing transpiration, thereby increasing soil water availability; and longevity (i.e. whether a species is annual or perennial) will affect the response of a species to global changes. Here, these three hypotheses are tested by assessing the impact of elevated CO2 (550 micromol mol(-1) and warming (+2 degrees C) on seedling emergence, survivorship and establishment in an Australian temperate grassland from autumn 2004 to autumn 2007. Warming impacts on seedling survivorship were dependent upon species longevity. Warming reduced seedling survivorship of perennials through its effects on soil water potential but the seedling survivorship of annuals was reduced to a greater extent than could be accounted for by treatment effects on soil water potential. Elevated CO2 did not significantly affect seedling survivorship in annuals or perennials. These results show that warming will alter recruitment of perennial species by changing soil water potential but will reduce recruitment of annual species independent of any effects on soil moisture. The results also show that exposure to elevated CO2 does not make seedlings more resistant to dry soils.

Flowering phenology in a species-rich temperate grassland is sensitive to warming but not elevated CO2.

* Flowering is a critical stage in plant life cycles, and changes might alter processes at the species, community and ecosystem levels. Therefore, likely flowering-time responses to global change drivers are needed for predictions of global change impacts on natural and managed ecosystems. * Here, the impact of elevated atmospheric CO2 concentration ([CO2]) (550 micromol mol(-1)) and warming (+2 masculineC) is reported on flowering times in a native, species-rich, temperate grassland in Tasmania, Australia in both 2004 and 2005. * Elevated [CO2] did not affect average time of first flowering in either year, only affecting three out of 23 species. Warming reduced time to first flowering by an average of 19.1 d in 2004, acting on most species, but did not significantly alter flowering time in 2005, which might be related to the timing of rainfall. Elevated [CO2] and warming treatments did not interact on flowering time. * These results show elevated [CO2] did not alter average flowering time or duration in this grassland; neither did it alter the response to warming. Therefore, flowering phenology appears insensitive to increasing [CO2] in this ecosystem, although the response to warming varies between years but can be strong.

Warming and free-air CO2 enrichment alter demographics in four co-occurring grassland species.

Species differ in their responses to global changes such as rising CO(2) and temperature, meaning that global changes are likely to change the structure of plant communities. Such alterations in community composition must be underlain by changes in the population dynamics of component species. Here, the impact of elevated CO(2) (550 micromol mol(-1)) and warming (+2 degrees C) on the population growth of four plant species important in Australian temperate grasslands is reported. Data collected from the Tasmanian free-air CO(2) enrichment (TasFACE) experiment between 2003 and 2006 were analysed using population matrix models. Population growth of Themeda triandra, a perennial C(4) grass, was largely unaffected by either factor but population growth of Austrodanthonia caespitosa, a perennial C(3) grass, was reduced substantially in elevated CO(2) plots. Warming and elevated CO(2) had antagonistic effects on population growth of two invasive weeds, Hypochaeris radicata and Leontodon taraxacoides, with warming causing population decline. Analysis of life cycle stages showed that seed production, seedling emergence and establishment were important factors in the responses of the species to global changes. These results show that the demographic approach is very useful in understanding the variable responses of plants to global changes and in elucidating the life cycle stages that are most responsive.

Observed and perceived parental overprotection in relation to psychosocial adjustment in preadolescents with a physical disability: the mediational role of behavioral autonomy.

The purpose of this study was to tes a mediational model of associations between parental overprotectiveness (OP), behavioral autonomy. and psychosocial adjustment in 68 families with 8- and 9-year-old preadolescents with spipa bifida and a demographically matched sample of 68 families with able-bodied children. Measures included questionnaire and observational assessments of parental OP; parent and child reports of behavioral autonomy; and parent, child, and teacher reports of preadolescent adjustment. On the basis of both questionnaire and observational measures of OP, mothers and fathers of children with spina bifida were significantly more overprotective than their counterparts in the able-bodied sample, although this group difference was partially mediated by children's cognitive ability. Across samples, mothers were more likely to be overprotective than fathers. Both questionnaire and observational measures of parental OP were associated with lower levels of preadolescent decision-making autonomy as well as with parents being less willing to grant autonomy to their offspring in the future. For the questionnaire measure of OP, and only for the spina bifida sample. the mediational model was supported such that parental OP was associated with less behavioral autonomy, which was, in turn, associated with more externalizing problems. Findings are discussed in relation to the literature on parenting, autonomy development, and pediatric psychology.