Time from presentation to pre-diagnostic chest X-ray in patients with symptomatic lung cancer: a cohort study using electronic patient records from English primary care.

BACKGROUND: National guidelines in England recommend prompt chest X-ray (within 14 days) in patients presenting in general practice with unexplained symptoms of possible lung cancer, including persistent cough, shortness of breath, or weight loss. AIM: To examine time to chest X-ray in symptomatic patients in English general practice before lung cancer diagnosis, and explore demographical variation. DESIGN AND SETTING: Retrospective cohort study using routinely collected general practice, cancer registry, and imaging data from England. METHOD: Patients with lung cancer who presented symptomatically in general practice in the year pre-diagnosis and who had a pre-diagnostic chest X-ray were included. Time from presentation to chest X-ray (presentation-test interval) was determined and intervals classified based on national guideline recommendations as concordant (≤14 days) or non-concordant (>14 days). Variation in intervals was examined by age, sex, smoking status, and deprivation. RESULTS: In a cohort of 2102 patients with lung cancer, the median presentation-test interval was 49 (interquartile range [IQR] 5-172) days. Of these, 727 (35%) patients had presentation-test intervals of ≤14 days (median 1 [IQR 0-6] day) and 1375 (65%) had presentation-test intervals of >14 days (median 128 [IQR 52-231] days). Intervals were longer among patients who smoke (equivalent to 63% longer than non-smokers; P<0.001), older patients (equivalent to 7% longer for every 10 years from age 27; P = 0.013), and females (equivalent to 12% longer than males; P = 0.016). CONCLUSION: In symptomatic primary care patients who underwent chest X-ray before lung cancer diagnosis, only 35% were tested within the timeframe recommended by national guidelines. Patients who smoke, older patients, and females experienced longer intervals. These findings could help guide initiatives aimed at improving timely lung cancer diagnosis

Identifying opportunities for timely diagnosis of bladder and renal cancer via abnormal blood tests: a longitudinal linked data study.

BACKGROUND: Understanding pre-diagnostic test use could reveal diagnostic windows where more timely evaluation for cancer may be indicated. AIM: To examine pre-diagnostic patterns of results of abnormal blood tests in patients with bladder and renal cancer. DESIGN AND SETTING: A retrospective cohort study using primary care and cancer registry data on patients with bladder and renal cancer who were diagnosed between April 2012 and December 2015 in England. METHOD: The rates of patients with a first abnormal result in the year before cancer diagnosis, for 'generic' (full blood count components, inflammatory markers, and calcium) and 'organ-specific' blood tests (creatinine and liver function test components) that may lead to subsequent detection of incidental cancers, were examined. Poisson regression was used to detect the month during which the cohort's rate of each abnormal test started to increase from baseline. The proportion of patients with a test found in the first half of the diagnostic window was examined, as these 'early' tests might represent opportunities where further evaluation could be initiated. RESULTS: Data from 4533 patients with bladder and renal cancer were analysed. The monthly rate of patients with a first abnormal test increased towards the time of cancer diagnosis. Abnormalities of both generic (for example, high inflammatory markers) and organ-specific tests (for example, high creatinine) started to increase from 6-8 months pre-diagnosis, with 25%-40% of these patients having an abnormal test in the 'early half' of the diagnostic window. CONCLUSION: Population-level signals of bladder and renal cancer can be observed in abnormalities in commonly performed primary care blood tests up to 8 months before diagnosis, indicating the potential for earlier diagnosis in some patients

Spatial and Temporal Variation of Offshore Wind Power and its Values Along the Central California Coast

The analysis of the spatiotemporal variability of wind power remains limited during the planning stage of an offshore wind farm. This study provides a framework to investigate how offshore wind power varies along the Central California Coast over diurnal and seasonal time scales, which is critical for reliability and functionality of the grid system. We find that offshore wind power in this region peaks during evening hours across all seasons and maximizes in spring and summer. The timing of peak offshore wind power production better aligns with that of peak demand across California than solar and land-based wind power production, highlighting its potential to fill the supply gap when demand is high and power production from other renewable energy sources is low. We further assess the value of offshore wind power using demand-based and wholesale market metrics. Both metrics indicate high potential value of offshore wind power over most areas in this region. Finally, we show that the estimate of power production is significantly biased when using mean wind speeds that do not account for temporal variability, leading to potentially inaccurate predictions about locations that are expected to produce the most power. These results reiterate the importance in considering spatiotemporal variability in wind power for accurately calculating the value of offshore wind development

Perturbations and operator trace functions

We study the spectral functional tr f(D+A) for a suitable function f, a self-adjoint operator D having compact resolvent, and a certain class of bounded self-adjoint operators A. Such functionals were introduce by Chamseddine and Connes in the context of noncommutative geometry. Motivated by the physical applications of these functionals, we derive a Taylor expansion of them in terms of G\^ateaux derivatives. This involves divided differences of f evaluated on the spectrum of D, as well as the matrix coefficients of A in an eigenbasis of D. This generalizes earlier results to infinite dimensions and to any number of derivatives.Comment: 13 pages; To appear in J. Funct. Ana

Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study

Objective: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer. Design: Qualitative analysis of semistructured in-depth interviews. Data were analysed iteratively and thematically, informed by the Model of Pathways to Treatment. Participants and setting: Pancreatic cancer occurs rarely in younger adults, therefore patients aged ≥40 years were recruited from nine hospitals after being referred to hospital with symptoms suggestive of pancreatic cancer; all were participants in a cohort study. Interviews were conducted soon after referral, and where possible, before diagnosis. Results: Twenty-six interviews were conducted (cancer n=13 (pancreas n=9, other intra-abdominal n=4), non-cancer conditions n=13; age range 48–84 years; 14 women). Time from first symptoms to first presentation to healthcare ranged from 1 day to 270 days, median 21 days. We identified three main themes. Initial symptom appraisal usually began with intermittent, non-specific symptoms such as tiredness or appetite changes, attributed to diet and lifestyle, existing gastrointestinal conditions or side effects of medication. Responses to initial symptom appraisal included changes in meal type or frequency, or self-medication. Symptom changes such as alterations in appetite and enjoyment of food or weight loss usually prompted further appraisal. Triggers to seek help included a change or worsening of symptoms, particularly pain, which was often a ‘tipping point’. Help-seeking was often encouraged by others. We found no differences in symptom appraisal and help-seeking between people diagnosed with cancer and those with other conditions. Conclusions: Greater public and healthcare professional awareness of the combinations of subtle and intermittent symptoms, and their evolving nature, is needed to prompt timelier help-seeking and investigation among people with symptoms of pancreatic cancer

Missed opportunities for diagnosing brain tumours in primary care: a qualitative study of patient experiences.

BACKGROUND: Brain tumours are uncommon, and have extremely poor outcomes. Patients and GPs may find it difficult to recognise early symptoms because they are often non-specific and more likely due to other conditions. AIM: To explore patients' experiences of symptom appraisal, help seeking, and routes to diagnosis. DESIGN AND SETTING: Qualitative study set in the East and North West of England. METHOD: In-depth interviews with adult patients recently diagnosed with a primary brain tumour and their family members were analysed thematically, using the Model of Pathways to Treatment as a conceptual framework. RESULTS: Interviews were carried out with 39 patients. Few participants (n = 7; 18%) presented as an emergency without having had a previous GP consultation; most had had one (n = 15; 38%), two (n = 9; 23%), or more (n = 8; 21%) GP consultations. Participants experienced multiple subtle 'changes' rather than 'symptoms', often noticed by others rather than the patient, which frequently led to loss of interest or less ability to engage with daily living activities. The most common changes were in cognition (speaking, writing, comprehension, memory, concentration, and multitasking), sleep, and other 'head feelings' such as dizziness. Not all patients experienced a seizure, and few seizures were experienced 'out of the blue'. Quality of communication in GP consultations played a key role in patients' subsequent symptom appraisal and the timing of their decision to re-consult. CONCLUSION: Multiple subtle changes and frequent GP visits often precede brain tumour diagnosis, giving possible diagnostic opportunities for GPs. Refined community symptom awareness and GP guidance could enable more direct pathways to diagnosis, and potentially improve patient experiences and outcomes

Factors affecting ammonium uptake in streams - an inter-biome perspective

The Lotic Intersite Nitrogen experiment (LINX) was a coordinated study of the relationships between North American biomes and factors governing ammonium uptake in streams. Our objective was to relate inter-biome variability of ammonium uptake to physical, chemical and biological processes. 2. Data were collected from 11 streams ranging from arctic to tropical and from desert to rainforest. Measurements at each site included physical, hydraulic and chemical characteristics, biological parameters, whole-stream metabolism and ammonium uptake. Ammonium uptake was measured by injection of \u275~-ammonium and downstream measurements of 15N-ammonium concentration. 3. We found no general, statistically significant relationships that explained the variability in ammonium uptake among sites. However, this approach does not account for the multiple mechanisms of ammonium uptake in streams. When we estimated biological demand for inorganic nitrogen based on our measurements of in-stream metabolism, we found good correspondence between calculated nitrogen demand and measured assimilative nitrogen uptake. 4. Nitrogen uptake varied little among sites, reflecting metabolic compensation in streams in a variety of distinctly different biomes (autotrophic production is high where allochthonous inputs are relatively low and vice versa). 5. Both autotrophic and heterotrophic metabolism require nitrogen and these biotic processes dominate inorganic nitrogen retention in streams. Factors that affect the relative balance of autotrophic and heterotrophic metabolism indirectly control inorganic nitrogen uptake

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia.

BACKGROUND: Rural Australians have poorer survival for most common cancers, due partially to later diagnosis. Internationally, several initiatives to improve cancer outcomes have focused on earlier presentation to healthcare and timely diagnosis. We aimed to measure the effect of community-based symptom awareness and general practice-based educational interventions on the time to diagnosis in rural patients presenting with breast, prostate, colorectal or lung cancer in Western Australia. METHODS: 2 × 2 factorial cluster randomised controlled trial. Community Intervention: cancer symptom awareness campaign tailored for rural Australians. GP intervention: resource card with symptom risk assessment charts and local cancer referral pathways implemented through multiple academic detailing visits. Trial Area A received the community symptom awareness and Trial Area B acted as the community campaign control region. Within both Trial Areas general practices were randomised to the GP intervention or control. PRIMARY OUTCOME: total diagnostic interval (TDI). RESULTS: 1358 people with incident breast, prostate, colorectal or lung cancer were recruited. There were no significant differences in the median or ln mean TDI at either intervention level (community intervention vs control: median TDI 107.5 vs 92 days; ln mean difference 0.08 95% CI -0.06-0.23 P=0.27; GP intervention vs control: median TDI 97 vs 96.5 days; ln mean difference 0.004 95% CI -0.18-0.19 P=0.99). There were no significant differences in the TDI when analysed by factorial design, tumour group or sub-intervals of the TDI. CONCLUSIONS: This is the largest trial to test the effect of community campaign or GP interventions on timeliness of cancer diagnosis. We found no effect of either intervention. This may reflect limited dose of the interventions, or the limited duration of follow-up. Alternatively, these interventions do not have a measurable effect on time to cancer diagnosis

The risk of oesophago-gastric cancer in symptomatic patients in primary care: A large case-control study using electronic records

BACKGROUND: Over 15 000 new oesophago-gastric cancers are diagnosed annually in the United Kingdom, with most being advanced disease. We identified and quantified features of this cancer in primary care. METHODS: Case-control study using electronic primary-care records of the UK patients aged ≥40 years was performed. Cases with primary oesophago-gastric cancer were matched to controls on age, sex and practice. Putative features of cancer were identified in the year before diagnosis. Odds ratios (ORs) were calculated for these features using conditional logistic regression, and positive predictive values (PPVs) were calculated. RESULTS: A total of 7471 cases and 32 877 controls were studied. Sixteen features were independently associated with oesophago-gastric cancer (all P5% in patients ≥55 years was for dysphagia. In patients <55 years, all PPVs were <1%. CONCLUSION: Symptoms of oesophago-gastric cancer reported in secondary care were also important in primary care. The results should inform guidance and commissioning policy for upper GI endoscopy

Evaluating diagnostic strategies for early detection of cancer: the CanTest framework

Abstract: Background: Novel diagnostic triage and testing strategies to support early detection of cancer could improve clinical outcomes. Most apparently promising diagnostic tests ultimately fail because of inadequate performance in real-world, low prevalence populations such as primary care or general community populations. They should therefore be systematically evaluated before implementation to determine whether they lead to earlier detection, are cost-effective, and improve patient safety and quality of care, while minimising over-investigation and over-diagnosis. Methods: We performed a systematic scoping review of frameworks for the evaluation of tests and diagnostic approaches. Results: We identified 16 frameworks: none addressed the entire continuum from test development to impact on diagnosis and patient outcomes in the intended population, nor the way in which tests may be used for triage purposes as part of a wider diagnostic strategy. Informed by these findings, we developed a new framework, the ‘CanTest Framework’, which proposes five iterative research phases forming a clear translational pathway from new test development to health system implementation and evaluation. Conclusion: This framework is suitable for testing in low prevalence populations, where tests are often applied for triage testing and incorporated into a wider diagnostic strategy. It has relevance for a wide range of stakeholders including patients, policymakers, purchasers, healthcare providers and industry