Analysis of lung cancer risk model (PLCOM2012 and LLPv2) performance in a community-based lung cancer screening programme.

INTRODUCTION: Low-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCOM2012 and Liverpool Lung Project model (LLPv2)) and National Lung Screening Trial (NLST) eligibility criteria in a community-based screening programme. METHODS: Ever-smokers aged 55-74, from deprived areas of Manchester, were invited to a Lung Health Check (LHC). Individuals at higher risk (PLCOM2012 score ≥1.51%) were offered annual LDCT screening over two rounds. LLPv2 score was calculated but not used for screening selection; ≥2.5% and ≥5% thresholds were used for analysis. RESULTS: PLCOM2012 ≥1.51% selected 56% (n=1429) of LHC attendees for screening. LLPv2 ≥2.5% also selected 56% (n=1430) whereas NLST (47%, n=1188) and LLPv2 ≥5% (33%, n=826) selected fewer. Over two screening rounds 62 individuals were diagnosed with LC; representing 87% (n=62/71) of 6-year incidence predicted by mean PLCOM2012 score (5.0%). 26% (n=16/62) of individuals with LC were not eligible for screening using LLPv2 ≥5%, 18% (n=11/62) with NLST criteria and 7% (n=5/62) with LLPv2 ≥2.5%. NLST eligible Manchester attendees had 2.5 times the LC detection rate than NLST participants after two annual screens (≈4.3% (n=51/1188) vs 1.7% (n=438/26 309); p<0.0001). Adverse measures of health, including airflow obstruction, respiratory symptoms and cardiovascular disease, were positively correlated with LC risk. Coronary artery calcification was predictive of LC (adjOR 2.50, 95% CI 1.11 to 5.64; p=0.028). CONCLUSION: Prospective comparisons of risk prediction tools are required to optimise screening selection in different settings. The PLCOM2012 model may underestimate risk in deprived UK populations; further research focused on model calibration is required.

Spirometry performed as part of the Manchester community-based lung cancer screening programme detects a high prevalence of airflow obstruction in individuals without a prior diagnosis of COPD.

BACKGROUND: COPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme. METHODS: Ever smokers, age 55-74, resident in three deprived areas of Manchester were invited to a 'Lung Health Check' (LHC) based in convenient community locations. Spirometry was incorporated into the LHCs alongside lung cancer risk estimation (Prostate, Lung, Colorectal and Ovarian Study Risk Prediction Model, 2012 version (PLCOM2012)), symptom assessment and smoking cessation advice. Those at high risk of lung cancer (PLCOM2012 ≥1.51%) were eligible for annual low-dose CT screening over two screening rounds. Airflow obstruction was defined as FEV1/FVC<0.7. Primary care databases were searched for any prior diagnosis of COPD. RESULTS: 99.4% (n=2525) of LHC attendees successfully performed spirometry; mean age was 64.1±5.5, 51% were women, 35% were current smokers. 37.4% (n=944) had airflow obstruction of which 49.7% (n=469) had no previous diagnosis of COPD. 53.3% of those without a prior diagnosis were symptomatic (n=250/469). After multivariate analysis, the detection of airflow obstruction without a prior COPD diagnosis was associated with male sex (adjOR 1.84, 95% CI 1.37 to 2.47; p<0.0001), younger age (p=0.015), lower smoking duration (p<0.0001), fewer cigarettes per day (p=0.035), higher FEV1/FVC ratio (<0.0001) and being asymptomatic (adjOR 4.19, 95% CI 2.95 to 5.95; p<0.0001). The likelihood of screen detected lung cancer was significantly greater in those with evidence of airflow obstruction who had a previous diagnosis of COPD (adjOR 2.80, 95% CI 1.60 to 8.42; p=0.002). CONCLUSIONS: Incorporating spirometry into a community-based targeted lung cancer screening programme is feasible and identifies a significant number of individuals with airflow obstruction who do not have a prior diagnosis of COPD.

Implementing lung cancer screening: baseline results from a community-based 'Lung Health Check' pilot in deprived areas of Manchester.

We report baseline results of a community-based, targeted, low-dose CT (LDCT) lung cancer screening pilot in deprived areas of Manchester. Ever smokers, aged 55-74 years, were invited to 'lung health checks' (LHCs) next to local shopping centres, with immediate access to LDCT for those at high risk (6-year risk ≥1.51%, PLCOM2012 calculator). 75% of attendees (n=1893/2541) were ranked in the lowest deprivation quintile; 56% were high risk and of 1384 individuals screened, 3% (95% CI 2.3% to 4.1%) had lung cancer (80% early stage) of whom 65% had surgical resection. Taking lung cancer screening into communities, with an LHC approach, is effective and engages populations in deprived areas.

Second round results from the Manchester 'Lung Health Check' community-based targeted lung cancer screening pilot.

We report results from the second annual screening round (T1) of Manchester's 'Lung Health Check' pilot of community-based lung cancer screening in deprived areas (undertaken June to August 2017). Screening adherence was 90% (n=1194/1323): 92% of CT scans were classified negative, 6% indeterminate and 2.5% positive; there were no interval cancers. Lung cancer incidence was 1.6% (n=19), 79% stage I, treatments included surgery (42%, n=9), stereotactic ablative radiotherapy (26%, n=5) and radical radiotherapy (5%, n=1). False-positive rate was 34.5% (n=10/29), representing 0.8% of T1 participants (n=10/1194). Targeted community-based lung cancer screening promotes high screening adherence and detects high rates of early stage lung cancer.

Incidental extra-cardiac findings on clinical CMR.

AIMS: Cardiac magnetic resonance (CMR) imaging benefits from a large field of view, but consequently captures incidental extra-cardiac findings (IEFs). There is a relative paucity of data for CMR in this regard. Our objectives were to assess the frequency and significance of IEFs reported from clinically indicated CMR scans, and additionally to ascertain if reporting rates differed between radiologist and cardiologist in a 'real-world' setting. METHODS AND RESULTS: A total of 714 patients were included for the study. All patients were referred to a single tertiary cardiac unit for clinically indicated scans. The clinical reports were retrospectively reviewed for reported IEF, and classified as 'minor', or 'major' depending on the need of further investigation or clinical correlation. A total of 180 IEFs were reported in 154 (21.6%) patients. Ninety IEFs were considered minor, and 90 major. Of the latter, eight (1.1%) were considered highly significant. Two hundred scans were reported by a consultant radiologist, and 514 by cardiologists. There was no significant difference in the rates of IEF reporting between the two specialties (P = 0.38). CONCLUSION: IEFs are common, requiring further investigation in a substantial minority. The incidence of highly significant findings in this study was low (∼1%), and similar to the reported incidence in the computed tomography literature. No significant difference was found between the reporting rates of IEFs between different specialties.

Radiation dose threshold for coronary artery calcium score with MDCT: how low can you go?

OBJECTIVES: To evaluate the lowest radiation exposure threshold at which coronary calcium scoring (CCS) remains accurate. METHODS: A prospective study of 43 consecutive eligible patients referred for CCS underwent imaging in accordance with the manufacturer's recommended protocol. Dedicated software was used to generate 8 series of images simulating tube currents ranging from 20 to 300 mA. These images were randomised and read in blinded fashion to determine the lowest tube current at which the CCS remained accurate. The minimum mA was correlated with 6 different patients' biometric parameters: bodyweight, body mass index, AP and lateral thoracic diameters, average thoracic diameter and the scout attenuation coefficient (SAC). The 95% confidence interval for each parameter was used to calculate tube current threshold levels and hence stratified CCS protocols were derived. RESULTS: Spearman's correlation coefficients of the minimum tube current for the 6 parameters were: 0.66, 0.63, 0.65, 0.74, 0.77 and 0.86 respectively (p < 0.001). SAC offered the largest potential reduction in mean effective dose from 1.86 mSv to 0.88 mSv. CONCLUSION: CCS with at least 50% reduction in radiation exposure and below 1 mSv is feasible if CT scout projections are utilised effectively.

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence.

OBJECTIVE: To compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA-cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants. METHODS: Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N=36) or placebo (twice daily; N=37) for 12-weeks under double-blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions. RESULTS: There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA-cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0-2 MA-positive urines), but not heavier (3-6 MA-positive urines) MA use during baseline (OR=2.81, 95% CI=1.61-4.93, p<0.001 for MA-free week with bupropion among light users). Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost five cigarettes per day (p=0.0002). CONCLUSION: Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light-MA users is warranted.

Detection of medullary thyroid cancer with MIBG imaging for pheochromocytoma.

A medullary thyroid cancer (MTC)/multiple endocrine neoplasia syndrome was suspected in a patient having an metaiodobenzylguanidine (MIBG) scan while she was being investigated for pheochromocytoma. After surgery, this was confirmed histologically. Although MIBG scanning cannot be used as a screening tool for MTC because of its poor sensitivity for detection of MTC, this case report highlights that one should always scrutinize the thyroid gland while interpreting MIBG scans.

Coincident Giant Cavernous Angioma and Large Middle Cerebral Artery Aneurysm.

Cavernous angiomas although relatively common lesions rarely reach a large size. They have a well documented association with AVMs, capillary telangiectases and venous angiomas but are not specifically associated with intracerebral aneurysms. We present a case of what we believe to be the 4th largest reported giant cavernous angioma to present in adulthood. This cavernous angioma also happened to be associated with a large intracerebral aneurysm, an association not previously reported. The sometimes confusing nomenclature of cavernous angiomas and other similar vascular malformations is also discussed.

Cocaine dependence and acute cocaine induce decreases of monocyte proinflammatory cytokine expression across the diurnal period: autonomic mechanisms.

Cocaine dependence is associated with an increased risk of infectious diseases. The innate immune system triggers effector pathways to combat microbial pathogens through expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). It is not known whether cocaine alters the capacity of monocytes to respond to a bacterial challenge in humans. In cocaine-dependent volunteers and control subjects, we analyzed monocyte TNF-alpha and IL-6 expression at rest and in response to the bacterial ligand, lipopolysaccharide (LPS), over a 24-h period. In addition, the in vivo effects of cocaine (40 mg) versus placebo on monocyte expression of TNF-alpha and IL-6 were profiled over 48 h. Cocaine-dependent volunteers showed a decrease in the capacity of monocytes to express TNF-alpha and IL-6 compared with control subjects. Moreover, acute infusion of cocaine induced a further decline in the responsiveness of monocytes to LPS, which persisted after cocaine had cleared from the blood. Heart rate variability analyses showed that increases of sympathetic activity along with vagal withdrawal were associated with decreases in monocyte expression of TNF-alpha. Cocaine alters autonomic activity and induces protracted decreases in innate immune mechanisms. Targeting sympathovagal balance might represent a novel strategy for partial amelioration of impairments of innate immunity in cocaine dependence.

Variation in neurophysiological function and evidence of quantitative electroencephalogram discordance: predicting cocaine-dependent treatment attrition.

Cocaine treatment trials suffer from a high rate of attrition. We examined pretreatment neurophysiological factors to identify participants at greatest risk. Twenty-five participants were divided into concordant and discordant groups following electroencephalogram (EEG) measures recorded prior to a double-blind, placebo-controlled treatment trial. Three possible outcomes were examined: successful completion, dropout, and removal. Concordant (high perfusion correlate) participants had an 85% rate of successful completion, while discordant participants had a 15% rate of successful completion. Twenty-five percent of dropouts and 50% of participants removed were discordant (low perfusion correlate), while only 25% of those who completed were discordant. Failure to complete the trial was not explained by depression, craving, benzoylecgonine levels or quantitative electroencephalogram (QEEG) power; thus cordance may help identify attrition risk.

Comparing HIPAA practices in two multi-hospital systems.

The comparison of HIPAA compliance efforts at two multi-hospital networks (Children's Health System and Carilion Health System) suggests a framework for classifying practices and for facilitating the integration of further case studies into a national library of HIPAA practices.