The role of screening expectations in modifying short-term psychological responses to low-dose computed tomography lung cancer screening among high-risk individuals

Objective This study aimed to examine the relationship between pre-screening expectations and psychological responses to low-dose computerised tomography (LDCT) screening among high-risk individuals in the United Kingdom Lung Cancer Screening (UKLS) pilot trial. Methods Prior to screening, high-risk individuals randomised into the intervention arm of the UKLS were asked about their expected screening test result. Their actual LDCT scan result was compared with their baseline screening expectation to determine the level of congruence. Levels of concern about and perceived accuracy of the result were assessed in a questionnaire two weeks following receipt of their test result. Results The sample included 1589 participants. Regardless of their expected results, patients who required follow-up investigations after their initial LDCT scan were the most concerned about their result (p < 0.001). Participants who expected to require follow-up, but did not need it, perceived the test to be least accurate (p = 0.006). Conclusions Lung cancer screening participants who require follow-up or who have unexpected negative results can be identified for supportive interventions. Practical Implications: These findings can be used to ensure that any future LDCT lung cancer screening programme is tailored to identify and support those high-risk individuals who may benefit from additional help

Experimental and modeled thermoregulatory costs of repeated sublethal oil exposure in the Double-crested Cormorant, \u3ci\u3ePhalacrocorax auritus\u3c/i\u3e

To fully understand the impact of oil exposure, it is important to understand sublethal effects like how increased thermoregulatory costs may affect survival and reproduction. However, it is difficult and time-consuming to measure these effects in wild animals. We present a novel use of a bioenergetics model, Niche Mapper™, to estimate thermoregulatory impacts of oiling, using data from captive Double-crested Cormorants (Phalacrocorax auritus) experimentally exposed to oil. Oiled cormorants had significant increases in surface body temperatures following exposure. Niche Mapper accurately predicted surface temperatures and metabolic rates for unoiled and oiled cormorants and predicted 13–18% increased daily energetic demands due to increased thermoregulatory costs of oiling, consistent with increased food consumption observed in experimentally oiled cormorants. We show that Niche Mapper can provide valuable insight into sublethal oiling effects by quantifying the extent to which thermoregulatory costs divert energy resources away from important life processes like maintenance, reproduction and migration

Understanding older women's decision making and coping in the context of breast cancer treatment

Background: Primary endocrine therapy (PET) is a recognised alternative to surgery followed by endocrine therapy for a subset of older, frailer women with breast cancer. Choice of treatment is preference-sensitive and may require decision support. Older patients are often conceptualised as passive decision-makers. The present study used the Coping in Deliberation (CODE) framework to gain insight into decision making and coping processes in a group of older women who have faced breast cancer treatment decisions, and to inform the development of a decision support intervention (DSI). Methods: Semi-structured interviews were carried out with older women who had been offered a choice of PET or surgery from five UK hospital clinics. Women's information and support needs, their breast cancer diagnosis and treatment decisions were explored. A secondary analysis of these interviews was conducted using the CODE framework to examine women's appraisals of health threat and coping throughout the deliberation process. Results: Interviews with 35 women aged 75-98 years were analysed. Appraisals of breast cancer and treatment options were sometimes only partial, with most women forming a preference for treatment relatively quickly. However, a number of considerations which women made throughout the deliberation process were identified, including: past experiences of cancer and its treatment; scope for choice; risks, benefits and consequences of treatment; instincts about treatment choice; and healthcare professionals' recommendations. Women also described various strategies to cope with breast cancer and their treatment decisions. These included seeking information, obtaining practical and emotional support from healthcare professionals, friends and relatives, and relying on personal faith. Based on these findings, key questions were identified that women may ask during deliberation. Conclusions: Many older women with breast cancer may be considered involved rather than passive decision-makers, and may benefit from DSIs designed to support decision making and coping within and beyond the clinic setting

Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample

Background: While ovarian cancer is recognised as having identifiable early symptoms, understanding of the key determinants of symptom awareness and early presentation is limited. A population-based survey of ovarian cancer awareness and anticipated delayed presentation with symptoms was conducted as part of the International Cancer Benchmarking Partnership (ICBP). Methods: Women aged over 50 years were recruited using random probability sampling (n = 1043). Computer-assisted telephone interviews were used to administer measures including ovarian cancer symptom recognition, anticipated time to presentation with ovarian symptoms, health beliefs (perceived risk, perceived benefits/barriers to early presentation, confidence in symptom detection, ovarian cancer worry), and demographic variables. Logistic regression analysis was used to identify the contribution of independent variables to anticipated presentation (categorised as < 3 weeks or ≥ 3 weeks). Results: The most well-recognised symptoms of ovarian cancer were post-menopausal bleeding (87.4%), and persistent pelvic (79.0%) and abdominal (85.0%) pain. Symptoms associated with eating difficulties and changes in bladder/bowel habits were recognised by less than half the sample. Lower symptom awareness was significantly associated with older age (p ≤ 0.001), being single (p ≤ 0.001), lower education (p ≤ 0.01), and lack of personal experience of ovarian cancer (p ≤ 0.01). The odds of anticipating a delay in time to presentation of ≥ 3 weeks were significantly increased in women educated to degree level (OR = 2.64, 95% CI 1.61 – 4.33, p ≤ 0.001), women who reported more practical barriers (OR = 1.60, 95% CI 1.34 – 1.91, p ≤ 0.001) and more emotional barriers (OR = 1.21, 95% CI 1.06 – 1.40, p ≤ 0.01), and those less confident in symptom detection (OR = 0.56, 95% CI 0.42 – 0.73, p ≤ 0.001), but not in those who reported lower symptom awareness (OR = 0.99, 95% CI 0.91 – 1.07, p = 0.74). Conclusions: Many symptoms of ovarian cancer are not well-recognised by women in the general population. Evidence-based interventions are needed not only to improve public awareness but also to overcome the barriers to recognising and acting on ovarian symptoms, if delays in presentation are to be minimised

Long-term psychosocial outcomes of low-dose CT screening: results of the UK Lung Cancer Screening randomised controlled trial

National Institute for Health Research Health Technology Assessment programme, grant reference no. HTA 09/61/01

The UK Lung Screen (UKLS): Demographic Profile of First 88,897 Approaches Provides Recommendations for Population Screening

The UK Lung Cancer Screening trial (UKLS) aims to evaluate low-dose computed tomography (LDCT) lung cancer population screening in the United Kingdom. In UKLS, a large population sample ages 50 to 75 years is approached with a questionnaire to determine lung cancer risk. Those with an estimated risk of at least 5% of developing lung cancer in the next 5 years (using the Liverpool Lung project risk model) are invited to participate in the trial. Here, we present demographic, risk, and response rate data from the first 88,897 individuals approached. Of note, 23,794 individuals (26.8% of all approached) responded positively to the initial questionnaire; 12% of these were high risk. Higher socioeconomic status correlated positively with response, but inversely with risk (P < 0.001). The 50- to 55-year age group was least likely to participate, and at lowest cancer risk. Only 5% of clinic attendees were ages ≤60 years (compared with 47% of all 88,897 approached); this has implications for cost effectiveness. Among positive responders, there were more ex-smokers than expected from population figures (40% vs. 33%), and fewer current smokers (14% vs. 17.5%). Of note, 32.7% of current smokers and 18.4% of ex-smokers were designated as high risk. Overall, 1,452 of 23,794 positive responders (6.1%) were deemed high risk and attended a recruitment clinic. UKLS is the first LDCT population screening trial, selecting high-risk subjects using a validated individual risk prediction model. Key findings: (i) better recruitment from ex- rather than current smokers, (ii) few clinic attendees ages early 50s, and (iii) representative number of socioeconomically deprived people recruited, despite lower response rates

Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe.

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39-61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the "Initiative for European Lung Screening (IELS)"-a large international group of physicians and other experts concerned with lung cancer-agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached

Recommendations for implementing lung cancer screening with low-dose computed tomography in Europe

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached

Two-stage Genome-wide Methylation Profiling in Childhood-onset Crohn's Disease Implicates Epigenetic Alterations at the VMP1/MIR21 and HLA Loci

Background: As a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohn's disease (CD) and is especially pertinent to early onset disease. Methods: The Illumina 450K platform was applied to assess epigenome-wide methylation profiles in circulating leukocyte DNA in discovery and replication pediatric CD cohorts and controls. Data were corrected for differential leukocyte proportions. Targeted replication was performed in adults using pyrosequencing. Methylation changes were correlated with gene expression in blood and intestinal mucosa. Results: We identified 65 individual CpG sites with methylation alterations achieving epigenome-wide significance after Bonferroni correction (P &#60; 1.1 × 10−7), and 19 differently methylated regions displaying unidirectional methylation change. There was a highly significant enrichment of methylation changes around GWAS single nucleotide polymorphisms (P = 3.7 × 10−7), notably the HLA region and MIR21. Two-locus discriminant analysis in the discovery cohort predicted disease in the pediatric replication cohort with high accuracy (area under the curve, 0.98). The findings strongly implicate the transcriptional start site of MIR21 as a region of extended epigenetic alteration, containing the most significant individual probes (P = 1.97 × 10−15) within a GWAS risk locus. In extension studies, we confirmed hypomethylation of MIR21 in adults (P = 6.6 × 10−5, n = 172) and show increased mRNA expression in leukocytes (P &#60; 0.005, n = 66) and in the inflamed intestine (P = 1.4 × 10−6, n = 99). Conclusions: We demonstrate highly significant and replicable differences in DNA methylation in CD, defining the disease-associated epigenome. The data strongly implicate known GWAS loci, with compelling evidence implicating MIR21 and the HLA region.</p

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course