Victorian Lung Cancer Service Redesign Project: impacts of a quality improvement collaborative on timeliness and management in lung cancer.

BACKGROUND: Lung cancer management is characterised by a high disease burden, poor survival and substantial variation in management and outcomes. Service redesign provides opportunities for quality improvement (QI) and this improvement may be leveraged across multiple sites using QI collaboration. AIM: This initiative targeted Quality Improvement (QI) in lung cancer management, engaging a QI collaborative using service redesign methodologies in five Victorian hospitals. QI targets included timeliness from referral and diagnosis to treatment, multi-disciplinary meeting (MDM) presentation and supportive care screening. Redesign strategies targeted process sustainability through enhanced team capability. METHODS: This study engaged a prospective quality improvement cohort design targeting newly diagnosed tissue confirmed lung cancer with 6-month pre-intervention period and 6-month redesign implementation period, between September 2016 and August 2017, evaluated using Interrupted Time Series Analysis. Hospital sites included three regional and two metropolitan hospitals in Victoria. QI redesign targeted time intervals from referral to first specialist appointment (FSA), referral to diagnosis, diagnosis to first treatment (any intent), MDM documented in medical records and Supportive Care Screening Tool documented in medical records. RESULTS: There was a marked reduction in referral to FSA interval across all sites, with median (interquartile range) falling from 6 (0-15) to 4 (1-10) days, and proportion seen by a specialist within 14 days increased from 74.3% to 84.2%. The interval between diagnosis and treatment was not substantively changed in the 6-month implementation period. The proportion of subjects with documented presentation to the MDM increased from 61% to 67%. The proportion for which Supportive Care Screening documentation remained low at 26.3% post-intervention. CONCLUSIONS: Data-driven redesign initiatives enable identification and analysis of clinical practice variation and may be utilised to enhance timeliness of cancer care and improve local data service capabilities.

Higher than expected CO2 fertilization inferred from leaf to global observations.

Several lines of evidence point to an increase in the activity of the terrestrial biosphere over recent decades, impacting the global net land carbon sink (NLS) and its control on the growth of atmospheric carbon dioxide (ca ). Global terrestrial gross primary production (GPP)-the rate of carbon fixation by photosynthesis-is estimated to have risen by (31 ± 5)% since 1900, but the relative contributions of different putative drivers to this increase are not well known. Here we identify the rising atmospheric CO2 concentration as the dominant driver. We reconcile leaf-level and global atmospheric constraints on trends in modeled biospheric activity to reveal a global CO2 fertilization effect on photosynthesis of 30% since 1900, or 47% for a doubling of ca above the pre-industrial level. Our historic value is nearly twice as high as current estimates (17 ± 4)% that do not use the full range of available constraints. Consequently, under a future low-emission scenario, we project a land carbon sink (174 PgC, 2006-2099) that is 57 PgC larger than if a lower CO2 fertilization effect comparable with current estimates is assumed. These findings suggest a larger beneficial role of the land carbon sink in modulating future excess anthropogenic CO2 consistent with the target of the Paris Agreement to stay below 2°C warming, and underscore the importance of preserving terrestrial carbon sinks.

Identifying areas at risk of drought-induced tree mortality across South-Eastern Australia.

South-East Australia has recently been subjected to two of the worst droughts in the historical record (Millennium Drought, 2000-2009 and Big Dry, 2017-2019). Unfortunately, a lack of forest monitoring has made it difficult to determine whether widespread tree mortality has resulted from these droughts. Anecdotal observations suggest the Big Dry may have led to more significant tree mortality than the Millennium drought. Critically, to be able to robustly project future expected climate change effects on Australian vegetation, we need to assess the vulnerability of Australian trees to drought. Here we implemented a model of plant hydraulics into the Community Atmosphere Biosphere Land Exchange (CABLE) land surface model. We parameterized the drought response behaviour of five broad vegetation types, based on a common garden dry-down experiment with species originating across a rainfall gradient (188-1,125 mm/year) across South-East Australia. The new hydraulics model significantly improved (~35%-45% reduction in root mean square error) CABLE's previous predictions of latent heat fluxes during periods of water stress at two eddy covariance sites in Australia. Landscape-scale predictions of the greatest percentage loss of hydraulic conductivity (PLC) of about 40%-60%, were broadly consistent with satellite estimates of regions of the greatest change in both droughts. In neither drought did CABLE predict that trees would have reached critical PLC in widespread areas (i.e. it projected a low mortality risk), although the model highlighted critical levels near the desert regions of South-East Australia where few trees live. Overall, our experimentally constrained model results imply significant resilience to drought conferred by hydraulic function, but also highlight critical data and scientific gaps. Our approach presents a promising avenue to integrate experimental data and make regional-scale predictions of potential drought-induced hydraulic failure.

Follow-up of a Large Prospective Cohort in the United States Using Linkage With Multiple State Cancer Registries.

All states in the United States now have a well-established cancer registry. Linkage with these registries may be a cost-effective method of follow-up for cancer incidence in multistate cohort studies. However, the sensitivity of linkage with the current network of state registries for detecting incident cancer diagnoses within cohort studies is not well-documented. We examined the sensitivity of registry linkage among 39,368 men and women from 23 states who enrolled in the Cancer Prevention Study-3 cohort during 2006-2009 and had the opportunity to self-report cancer diagnoses on a questionnaire in 2011. All participants provided name and birthdate, and 94% provided a complete social security number. Of 378 cancer diagnoses between enrollment and 2010 identified through self-report and verified with medical records, 338 were also detected by linkage with the 23 state cancer registries (sensitivity of 89%, 95% confidence interval (CI): 86, 92). Sensitivity was lower for hematologic cancers (69%, 95% CI: 41, 89) and melanoma (70%, 95% CI: 57, 81). After excluding hematologic cancers and melanoma, sensitivity was 94% (95% CI: 91, 97). Our results indicate that linkage with multiple cancer registries can be a sensitive method for ascertaining incident cancers, other than hematologic cancers and melanoma, in multistate cohort studies.

The American Cancer Society's Cancer Prevention Study 3 (CPS-3): Recruitment, study design, and baseline characteristics.

BACKGROUND: Prospective cohort studies contribute importantly to understanding the role of lifestyle, genetic, and other factors in chronic disease etiology. METHODS: The American Cancer Society (ACS) recruited a new prospective cohort study, Cancer Prevention Study 3 (CPS-3), between 2006 and 2013 from 35 states and Puerto Rico. Enrollment took place primarily at ACS community events and at community enrollment "drives." At enrollment sites, participants completed a brief survey that included an informed consent, identifying information necessary for follow-up, and key exposure information. They also provided a waist measure and a nonfasting blood sample. Most participants also completed a more comprehensive baseline survey at home that included extensive medical, lifestyle, and other information. Participants will be followed for incident cancers through linkage with state cancer registries and for cause-specific mortality through linkage with the National Death Index. RESULTS: In total, 303,682 participants were enrolled. Of these, 254,650 completed the baseline survey and are considered "fully" enrolled; they will be sent repeat surveys periodically for at least the next 20 years to update exposure information. The remaining participants (n = 49,032) will not be asked to update exposure information but will be followed for outcomes. Twenty-three percent of participants were men, 17.3% reported a race or ethnicity other than "white," and the median age at enrollment was 47 years. CONCLUSIONS: CPS-3 will be a valuable resource for studies of cancer and other outcomes because of its size; its diversity with respect to age, ethnicity, and geography; and the availability of blood samples and detailed questionnaire information collected over time. Cancer 2017;123:2014-2024. © 2017 American Cancer Society.

Lung cancer interval times from point of referral to the acute health sector to the start of first treatment.

Objective The aim of the present study was to compare lung cancer diagnostic and treatment intervals with agreed target measures across three large public health services in Victoria and assess any differences in interval times by treatment type and health service. Methods A retrospective medical record audit of 78 patients admitted with a new diagnosis of lung cancer was conducted. Interval times from referral to diagnosis, diagnosis to first treatment and referral to first treatment were recorded in three treatment types: surgery, chemotherapy and radiotherapy. Results There was a significant difference in the mean number of days from referral to diagnosis by treatment type. Patients who underwent surgery waited significantly longer (mean (± s.d.) 41.6±38.4 days) to obtain a diagnosis than those who received radiotherapy (15.1±18.6 days). Only 47% of surgical patients obtained a diagnosis within the recommended 28 days. Moreover, only 45% and 44% of patients, respectively, met the diagnosis-to-treatment target of 14 days and referral-to-treatment target of 42 days. Conclusion The present study highlights the effect of treatment type on lung cancer referral interval times. It demonstrates the benefits of using evidenced-based interval target times to benchmark and compare performance outcomes in lung cancer. What is known about the topic? Lung cancer is the leading cause of cancer mortality in Australia and has the lowest 5-year survival rate of all cancer types. Delays in the diagnosis of lung cancer can change the prognosis from potentially curable to incurable, particularly in faster-growing tumours. What does this paper add? This study reveals treatment type was a greater factor in explaining variations in diagnosis and treatment than health service. Surgical patients were consistently lower in meeting the recommended interval targets across referral to diagnosis, diagnosis to treatment and referral to treatment. What are the implications for practitioners? This study demonstrates the value of using evidenced-based interval target times to benchmark and compare performance outcomes in lung cancer. Such measures may further improve prognostic outcomes in lung cancer by reducing unwanted delays.

British Society of Prosthodontics Debate on the Implications of the Minamata Convention on Mercury to Dental Amalgam--Should our Patients be Worried?.

In 2013, the Minamata Convention on Mercury called for a global phase-down of amalgam use, with a view to reduce environmental mercury pollution. This will significantly impact UK dentistry, given the still extensive use of amalgam in U.K. general dental practice. However, until now there has been little national discussion or debate. In Spring 2015, The British Society of Prosthodontics dedicated a significant part of its Annual Conference to debating the implications of this issue. Clinical case examples were discussed with audience interaction and voting facilitated using innovative Audience Response System Technology. A remarkable range of concerns and opinions were given. The debate elicited specific concerns amongst clinicians regarding the suitability of mercury-free alternatives to amalgam; particularly where cavities are large and extend beneath the gingival anatomy. There are also anecdotal reports of Dental Foundation (DF) dentists not being adequately taught the use of dental amalgam in undergraduate dental schools. CPD/CLINICAL RELEVANCE: Many clinicians, especially those treating patients for whom moisture control is challenging, feel that amalgam should remain available for clinicians to choose in certain clinical circumstances for the restoration of posterior teeth, even in the event of a complete phase-down.

Fire in Australian savannas: from leaf to landscape.

Savanna ecosystems comprise 22% of the global terrestrial surface and 25% of Australia (almost 1.9 million km2) and provide significant ecosystem services through carbon and water cycles and the maintenance of biodiversity. The current structure, composition and distribution of Australian savannas have coevolved with fire, yet remain driven by the dynamic constraints of their bioclimatic niche. Fire in Australian savannas influences both the biophysical and biogeochemical processes at multiple scales from leaf to landscape. Here, we present the latest emission estimates from Australian savanna biomass burning and their contribution to global greenhouse gas budgets. We then review our understanding of the impacts of fire on ecosystem function and local surface water and heat balances, which in turn influence regional climate. We show how savanna fires are coupled to the global climate through the carbon cycle and fire regimes. We present new research that climate change is likely to alter the structure and function of savannas through shifts in moisture availability and increases in atmospheric carbon dioxide, in turn altering fire regimes with further feedbacks to climate. We explore opportunities to reduce net greenhouse gas emissions from savanna ecosystems through changes in savanna fire management.

Audit of referral pathways in the diagnosis of lung cancer: a pilot study.

This pilot study sought to describe the diagnostic pathways for patients with lung cancer and explore the feasibility of a medical record audit for this purpose. An audit of 25 medical records of patients with a confirmed diagnosis of lung cancer was conducted, at a single outer metropolitan hospital in Victoria. Patients were presented to secondary care from general practice (n=17, 68%), the emergency department (n=3, 12%) or specialist rooms (n=1, 4%). Those who journeyed through general practice experienced the longest median intervals to diagnosis (20 days, interquartile range 7-47). The majority of patients (n=15, 60%) were referred by a specialist to a multidisciplinary team after a diagnosis had been confirmed but before treatment commenced. These patients waited a median of 20 days from their first specialist appointment to a multidisciplinary team appointment. This research illustrated that a variety of pathways to diagnosis exist. Critically, it requires patient data and additional auditing of primary, public and private health sector records to determine generalisability of findings and the effectiveness of a medical record audit as a data collection tool.

Interactive treatment planning in toothwear: are we doing it right?

UNLABELLED: Toothwear is now common, especially in younger patients, with high demand for the restoration of the damaged teeth which is likely to increase further over time. Fixed prosthodontic options range from direct composite resin to conventional tooth preparation and cemented indirect restorations. This paper summarizes the views of a variety of clinicians on a plan delivered to a patient with toothwear in secondary care and explores the possible reasons for the variation in decision-making in the treatment of toothwear. CLINICAL RELEVANCE: With levels of toothwear increasing, the clinician needs to be aware of the different treatment modalities which are appropriate.

Control-IQ Technology Use in Individuals With High Insulin Requirements: Results From the Multicenter Higher-IQ Trial.

BACKGROUND: Control-IQ technology version 1.5 allows for a wider range of weight and total daily insulin (TDI) entry, in addition to other changes to enhance performance for users with high basal rates. This study evaluated the safety and performance of the updated Control-IQ system for users with basal rates >3 units/h and high TDI in a multicenter, single arm, prospective study. METHODS: Adults with type 1 diabetes (T1D) using continuous subcutaneous insulin infusion (CSII) and at least one basal rate over 3 units/h (N = 34, mean age = 39.9 years, 41.2% female, diabetes duration = 21.8 years) used the t:slim X2 insulin pump with Control-IQ technology version 1.5 for 13 weeks. Primary outcome was safety events (severe hypoglycemia and diabetic ketoacidosis (DKA)). Central laboratory hemoglobin A1c (HbA1c) was measured at system initiation and 13 weeks. Participants continued using glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose transport protein 2 (SGLT-2) inhibitors, or other medications for glycemic control and/or weight loss if on a stable dose. RESULTS: All 34 participants completed the study. Fifteen participants used a basal rate >3 units/h for all 24 hours of the day. Nine participants used >300 units TDI on at least one day during the study. There were no severe hypoglycemia or DKA events. Time in range 70-180 mg/dL was 64.8% over the 13 weeks, with 1.0% time <70 mg/dL. Hemoglobin A1c decreased from 7.69% at baseline to 6.87% at 13 weeks (-0.82%, P < .001). CONCLUSIONS: Control-IQ technology version 1.5, with wider range of weight and TDI input and enhancements for users with high insulin requirements, was safe in individuals with T1D in this study.

Dental extractions prior to radiotherapy to the jaws for reducing post-radiotherapy dental complications.

BACKGROUND: Radiotherapy as part of head and neck cancer treatment leaves patients requiring much dental rehabilitation in a compromised environment that is difficult for the patient and the dental team to manage. OBJECTIVES: To assess the effects of maintaining the patient's natural dentition during radiotherapy in comparison to extracting teeth before radiotherapy in areas that are difficult to access by the patient and the dentist, should reduction in mouth opening occur after radiotherapy to the jaws. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 22 November 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 11), MEDLINE via OVID (1946 to 22 November 2012), EMBASE via OVID (1980 to 22 November 2012), CANCERLIT via PubMed (1950 to 22 November 2012), CINAHL via EBSCO (1980 to 22 November 2012) and reference lists of articles. We advertised for currently ongoing studies via the Cochrane Oral Health Group website and the Cochrane Oral Health Group Twitter feed.  SELECTION CRITERIA: Randomised controlled trials comparing extraction of teeth prior to radiotherapy with leaving teeth in situ during radiotherapy to the jaws. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the results of the searches for inclusion in the review.  MAIN RESULTS: No randomised controlled trials were found. AUTHORS' CONCLUSIONS: There are no randomised controlled trials to assess the effect of extracting teeth prior to radiotherapy compared to leaving teeth in the mouth during radiotherapy to the jaws.

Soil respiration-driven CO2 pulses dominate Australia's flux variability.

The Australian continent contributes substantially to the year-to-year variability of the global terrestrial carbon dioxide (CO2) sink. However, the scarcity of in situ observations in remote areas prevents the deciphering of processes that force the CO2 flux variability. In this study, by examining atmospheric CO2 measurements from satellites in the period 2009-2018, we find recurrent end-of-dry-season CO2 pulses over the Australian continent. These pulses largely control the year-to-year variability of Australia's CO2 balance. They cause two to three times larger seasonal variations compared with previous top-down inversions and bottom-up estimates. The pulses occur shortly after the onset of rainfall and are driven by enhanced soil respiration preceding photosynthetic uptake in Australia's semiarid regions. The suggested continental-scale relevance of soil-rewetting processes has substantial implications for our understanding and modeling of global climate-carbon cycle feedbacks.

Avoiding and managing the failure of conventional crowns and bridges.

UNLABELLED: The replacement of crowns and bridges is a common procedure for many dental practitioners. When correctly planned and executed, fixed prostheses will provide predictable function, aesthetics and value for money. However, when done poorly, they are more likely to fail prematurely and lead to irreversible damage to the teeth and supporting structures beneath. Sound diagnosis, assessment and technical skills are essential when dealing with failed or failing fixed restorations. These skills are essential for the 21st century dentist. This paper, with treated clinical examples, illustrates the areas of technical skill and clinical decisions needed for this type of work. It also provides advice on how the risk of premature failure can, in general, be further reduced. The article also confirms the very real risk in the UK of dento-legal problems when patients experience unexpected problems with their crowns and bridges. CLINICAL RELEVANCE: This paper outlines clinical implications of failed fixed prosthodontics to the dental surgeon. It also discusses factors that we can all use to predict and reduce the risk of premature restoration failure. Restoration design, clinical execution and patient factors are the most frequent reasons for premature problems. It is worth remembering (and informing patients) that the health of the underlying supporting dental tissue is often irreversibly compromised at the time of fixed restoration failure.

An exploratory study of Internet-initiated sexual offenses and the chat room sex offender: has the Internet enabled a new typology of sex offender?

This exploratory study examined 51 participants convicted of an Internet-initiated sex offense in which they attempted to entice an adolescent into a sexual relationship using an Internet chat room. All participants were convicted of a sex offense and subject to an evaluation as a part of sentencing requirements in Colorado. Clinical and behavioral data were obtained from each subject's offense-specific evaluation and chat room transcripts. The results of the study found that 90% of the participants were apprehended as a result of an Internet sex sting. The authors conclude that Internet chat room sex offenders constitute a separate group characterized by less severe criminogenic factors than other sex offenders (rapists, child molesters). It can be hypothesized that chat room sex offenders avoid relationships and spend a significant amount of time in online chat rooms as a primary social and sexual outlet, and engage in other sexually compulsive behaviors. Within this offender group, it was discovered that two subgroups exist: a contact-driven group motivated to engage in offline sexual behavior with an adolescent and a fantasy-driven group motivated to engage an adolescent in online cybersex without an express intent to meet offline. The chat room sex offender presents a significant clinical issue to treatment providers as a live victim does not exist. Thus, it is unclear if Internet sex stings prevent incidents of child sexual exploitation and may result in convictions of individuals who may never have abused a child. The data suggest a tentative sex offender typology, including subtypes, which need to be replicated in future studies.

Bleaching and bonding for the older patient.

UNLABELLED: Older people who remain reasonably well may wish to maintain or enhance their dental and oral appearance, preferably at minimal biologic and financial costs. Bleaching and bonding represents a very good treatment option and a sensible strategy for this group. Bleaching addresses the discoloration, while direct composite bonding can improve the shape of worn, or otherwise unaesthetic, teeth without damaging the structure or health of the residual tooth tissue. This pragmatic treatment is well tolerated by older patients. The visual and functional improvements are greatly appreciated by this group, partly because of the non-destructive and affordable nature of the benefits. CLINICAL RELEVANCE: Bleaching and bonding represents a proven, sensible, pragmatic, affordable and practical approach to managing the aesthetic problems of older patients, and the benefits are achievable without destroying their residual sound tooth tissue.

PEGS: An efficient tool for gene set enrichment within defined sets of genomic intervals.

Many biological studies of transcriptional control mechanisms produce lists of genes and non-coding genomic intervals from corresponding gene expression and epigenomic assays. In higher organisms, such as eukaryotes, genes may be regulated by distal elements, with these elements lying 10s-100s of kilobases away from a gene transcription start site. To gain insight into these distal regulatory mechanisms, it is important to determine comparative enrichment of genes of interest in relation to genomic regions of interest, and to be able to do so at a range of distances. Existing bioinformatics tools can annotate genomic regions to nearest known genes, or look for transcription factor binding sites in relation to gene transcription start sites. Here, we present PEGS ( Peak set Enrichment in Gene Sets). This tool efficiently provides an exploratory analysis by calculating enrichment of multiple gene sets, associated with multiple non-coding elements (peak sets), at multiple genomic distances, and within topologically associated domains. We apply PEGS to gene sets derived from gene expression studies, and genomic intervals from corresponding ChIP-seq and ATAC-seq experiments to derive biologically meaningful results. We also demonstrate an extended application to tissue-specific gene sets and publicly available GWAS data, to find enrichment of sleep trait associated SNPs in relation to tissue-specific gene expression profiles.

Multi-decadal increase of forest burned area in Australia is linked to climate change.

Fire activity in Australia is strongly affected by high inter-annual climate variability and extremes. Through changes in the climate, anthropogenic climate change has the potential to alter fire dynamics. Here we compile satellite (19 and 32 years) and ground-based (90 years) burned area datasets, climate and weather observations, and simulated fuel loads for Australian forests. Burned area in Australia's forests shows a linear positive annual trend but an exponential increase during autumn and winter. The mean number of years since the last fire has decreased consecutively in each of the past four decades, while the frequency of forest megafire years (>1 Mha burned) has markedly increased since 2000. The increase in forest burned area is consistent with increasingly more dangerous fire weather conditions, increased risk factors associated with pyroconvection, including fire-generated thunderstorms, and increased ignitions from dry lightning, all associated to varying degrees with anthropogenic climate change.

Impact of Radiotherapy on the Efficacy and Toxicity of anti-PD-1 Inhibitors in Metastatic NSCLC.

BACKGROUND: The impact of radiotherapy (RT) on the efficacy and toxicity of immune checkpoint inhibitors (ICIs) in patients with metastatic non-small-cell lung cancer (NSCLC) is unclear. MATERIALS AND METHODS: We identified patients with metastatic NSCLC treated with the anti-programmed death 1 antibodies nivolumab or pembrolizumab between January 2016 and May 2019 at 3 tertiary centers, who were also treated with palliative RT either during or within 3 months of starting anti-programmed death 1 treatment. Patient demographics, tumor characteristics, and treatment history were collected. Response rates, progression-free survival (PFS), and overall survival (OS) were analyzed and correlated with RT use. RESULTS: A total of 269 patients were identified, with a median follow-up of 19.4 months. The median age was 70 years (range, 35-90 years), and they were 63% male, 60% smokers, and 65% had adenocarcinoma histology. At the commencement of ICI treatment, the majority (86%) had ≥ 1 line of prior therapy and 34% had brain metastases. A total of 102 (38%) patients received RT within 3 months of starting ICI or subsequently during ICI treatment. Of patients that received RT, 86 (84%) received conventional hypofractionated RT, and, in the majority, 81 (79%) the intent of RT was symptom control. The use of RT did not increase grade 3/4 immune-related adverse events. The overall median PFS was 2.0 months (95% confidence interval, 1.3-2.6 months) and the median OS was 9.0 months (95% confidence interval, 6.4-9.5 months). There were no significant differences in median PFS (3.0 vs. 2.0 months; P = .515) and median OS (9.0 vs. 9.0 months; P = .917) in the patients who received RT versus those that did not. CONCLUSIONS: In patients with metastatic NSCLC, the addition of RT to ICI was not associated with increased toxicity or improved survival.