Missing covariate data within cancer prognostic studies: a review of current reporting and proposed guidelines

Prognostic models play a crucial role in the clinical decision-making process. Unfortunately, missing covariate data impede the construction of valid and reliable models, potentially introducing bias, if handled inappropriately. The extent of missing covariate data within reported cancer prognostic studies, the current handling and the quality of reporting this missing covariate data are unknown. Therefore, a review was conducted of 100 articles reporting multivariate survival analyses to assess potential prognostic factors, published within seven cancer journals in 2002. Missing covariate data is a common occurrence in studies performing multivariate survival analyses, being apparent in 81 of the 100 articles reviewed. The percentage of eligible cases with complete data was obtainable in 39 articles, and was <90% in 17 of these articles. The methods used to handle incomplete covariates were obtainable in 32 of the 81 articles with known missing data and the most commonly reported approaches were complete case and available case analysis. This review has highlighted deficiencies in the reporting of missing covariate data. Guidelines for presenting prognostic studies with missing covariate data are proposed, which if followed should clarify and standardise the reporting in future articles

Vascular grading of angiogenesis: prognostic significance in breast cancer

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (κ = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P< 0.0001), node-negative patients (P< 0.0001) and node-positive patients (P< 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P< 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer. © 2000 Cancer Research Campaig

Is the association of birth weight with premenopausal breast cancer risk mediated through childhood growth?

Several studies have found positive associations between birth weight and breast cancer risk at premenopausal ages. The mechanisms underlying this association are not known, but it is possible that it may be mediated through childhood growth. We examined data from a British cohort of 2176 women born in 1946 and for whom there were prospective measurements of birth weight and of body size throughout life. In all, 59 breast cancer cases occurred during follow-up, 21 of whom were known to be premenopausal. Women who weighed at least 4 kg at birth were five times (relative risk (RR)=5.03; 95% confidence interval=1.13, 22.5) more likely to develop premenopausal breast cancer than those who weighed less than 3 kg (P-value for linear trend=0.03). This corresponded to an RR of 2.31 (0.95, 5.64) per 1 kg increase in birth weight. Birth weight was also a predictor of postnatal growth, that is, women who were heavy at birth remained taller and heavier throughout their childhood and young adulthood. However, the effect of birth weight on premenopausal breast cancer risk was only reduced slightly after simultaneous adjustment for height and body mass index (BMI) at age 2 years and height and BMI velocities throughout childhood and adolescence (adjusted RR=1.94 (0.74, 5.14) per 1 kg increase in birth weight). The pathways through which birth weight is associated with premenopausal breast cancer risk seem to be largely independent of those underlying the relation of postnatal growth to risk

Multidimensional severity assessment in bronchiectasis:An analysis of 7 European cohorts.

INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity

PET/CT without capacity limitations: a Danish experience from a European perspective

# The Author(s) 2011. This article is published with open access at Springerlink.com Objectives We report the 3-year clinical experience of a large new Danish PET/CT centre without capacity limitations in relation to national and European developments. Methods The use of PET/CT in cancer was registered from early 2006 to early 2009 to judge the impact on patient management and to compare it with national and European trends. Results 6056 PET/CT examinations were performed in 4327 patients. Activity increased by 86 examinations per month compared with the same month the year before. Referrals came primarily from oncology (23.0%), haematology (21.6%), surgery (12.6%), internal medicine (12.7%) and gynaecology (5.5%). Referral indications were diagnosis (31.3%), staging (22.3%), recurrence detection (21.2%), response evaluation (17.0%) and other (8.2%). Response from nearly 60 % of users showed that PET/CT caused a change in diagnosis and/or staging and/or treatment plan in 36.0 % of cases. During the study period, there was a steep increase in the national use of FDG and in the European use of PET/CT. Conclusions We recorded a constantly increasing use of PET/CT that caused a change in diagnosis and/or stagin

The Patient Health Questionnaire-9 for detection of major depressive disorder in primary care: consequences of current thresholds in a crosssectional study

<p>Abstract</p> <p>Background</p> <p>There is a need for brief instruments to ascertain the diagnosis of major depressive disorder. In this study, we present the reliability, construct validity and accuracy of the PHQ-9 and PHQ-2 to detect major depressive disorder in primary care.</p> <p>Methods</p> <p>Cross-sectional analyses within a large prospective cohort study (PREDICT-NL). Data was collected in seven large general practices in the centre of the Netherlands. 1338 subjects were recruited in the general practice waiting room, irrespective of their presenting complaint. The diagnostic accuracy (the area under the ROC curve and sensitivities and specificities for various thresholds) was calculated against a diagnosis of major depressive disorder determined with the Composite International Diagnostic Interview (CIDI).</p> <p>Results</p> <p>The PHQ-9 showed a high degree of internal consistency (ICC = 0.88) and test-retest reliability (correlation = 0.94). With respect to construct validity, it showed a clear association with functional status measurements, sick days and number of consultations. The discriminative ability was good for the PHQ-9 (area under the ROC curve = 0.87, 95% CI: 0.84-0.90) and the PHQ-2 (ROC area = 0.83, 95% CI 0.80-0.87). Sensitivities at the recommended thresholds were 0.49 for the PHQ-9 at a score of 10 and 0.28 for a categorical algorithm. Adjustment of the threshold and the algorithm improved sensitivities to 0.82 and 0.84 respectively but the specificity decreased from 0.95 to 0.82 (threshold) and from 0.98 to 0.81 (algorithm). Similar results were found for the PHQ-2: the recommended threshold of 3 had a sensitivity of 0.42 and lowering the threshold resulted in an improved sensitivity of 0.81.</p> <p>Conclusion</p> <p>The PHQ-9 and the PHQ-2 are useful instruments to detect major depressive disorder in primary care, provided a high score is followed by an additional diagnostic work-up. However, often recommended thresholds for the PHQ-9 and the PHQ-2 resulted in many undetected major depressive disorders.</p

Spinning Up A Daze: TESS Uncovers A Hot Jupiter Orbiting The Rapid Rotator TOI-778

NASA\u27s Transiting Exoplanet Survey Satellite (TESS) mission has been uncovering a growing number of exoplanets orbiting nearby, bright stars. Most exoplanets that have been discovered by TESS orbit narrow-line, slow-rotating stars, facilitating the confirmation and mass determination of these worlds. We present the discovery of a hot Jupiter orbiting a rapidly rotating (v sin (i) = 35.1 ± 1.0 km s⁻¹) early F3V-dwarf, HD 115447 (TOI-778). The transit signal taken from Sectors 10 and 37 of TESS\u27s initial detection of the exoplanet is combined with follow-up ground-based photometry and velocity measurements taken from Minerva-Australis, TRES, CORALIE, and CHIRON to confirm and characterize TOI-778 b. A joint analysis of the light curves and the radial velocity measurements yields a mass, a radius, and an orbital period for TOI-778 b of 2.76 (+0.24)/(-0.23)Mj, 1.370 ± 0.043 Rj, and ~4.63 days, respectively. The planet orbits a bright (V = 9.1 mag) F3-dwarf with M = 1.40 ± 0.05 M⊙, R = 1.70 ± 0.05 R⊙, and logg = 4.05 ± 0.17. We observed a spectroscopic transit of TOI-778 b, which allowed us to derive a sky-projected spin–orbit angle of 18° ± 11°, consistent with an aligned planetary system. This discovery demonstrates the capability of smaller-aperture telescopes such as MINERVA-Australis to detect the radial velocity signals produced by planets orbiting broad-line, rapidly rotating stars

TESS Delivers Five New Hot Giant Planets Orbiting Bright Stars From The Full-Frame Images

We present the discovery and characterization of five hot and warm Jupiters—TOI-628 b (TIC 281408474; HD 288842), TOI-640 b (TIC 147977348), TOI-1333 b (TIC 395171208, BD+47 3521A), TOI-1478 b (TIC 409794137), and TOI-1601 b (TIC 139375960)—based on data from NASA\u27s Transiting Exoplanet Survey Satellite (TESS). The five planets were identified from the full-frame images and were confirmed through a series of photometric and spectroscopic follow-up observations by the TESS Follow-up Observing Program Working Group. The planets are all Jovian size (RP = 1.01–1.77 RJ) and have masses that range from 0.85 to 6.33 MJ. The host stars of these systems have F and G spectral types (5595 ≤ Teff ≤ 6460 K) and are all relatively bright (9.5 \u3c V \u3c 10.8, 8.2 \u3c K \u3c 9.3), making them well suited for future detailed characterization efforts. Three of the systems in our sample (TOI-640 b, TOI-1333 b, and TOI-1601 b) orbit subgiant host stars ($\mathrm{log}$ g \u3c 4.1). TOI-640 b is one of only three known hot Jupiters to have a highly inflated radius (RP \u3e 1.7 RJ, possibly a result of its host star\u27s evolution) and resides on an orbit with a period longer than 5 days. TOI-628 b is the most massive, hot Jupiter discovered to date by TESS with a measured mass of ${6.31}_{-0.30}^{+0.28}$MJ and a statistically significant, nonzero orbital eccentricity of e = ${0.074}_{-0.022}^{+0.021}$. This planet would not have had enough time to circularize through tidal forces from our analysis, suggesting that it might be remnant eccentricity from its migration. The longest-period planet in this sample, TOI-1478 b (P = 10.18 days), is a warm Jupiter in a circular orbit around a near-solar analog. NASA\u27s TESS mission is continuing to increase the sample of well-characterized hot and warm Jupiters, complementing its primary mission goals