Early detection of influenza outbreaks using the DC Department of Health's syndromic surveillance system

<p>Abstract</p> <p>Background</p> <p>Since 2001, the District of Columbia Department of Health has been using an emergency room syndromic surveillance system to identify possible disease outbreaks. Data are received from a number of local hospital emergency rooms and analyzed daily using a variety of statistical detection algorithms. The aims of this paper are to characterize the performance of these statistical detection algorithms in rigorous yet practical terms in order to identify the optimal parameters for each and to compare the ability of two syndrome definition criteria and data from a children's hospital versus vs. other hospitals to determine the onset of seasonal influenza.</p> <p>Methods</p> <p>We first used a fine-tuning approach to improve the sensitivity of each algorithm to detecting simulated outbreaks and to identifying previously known outbreaks. Subsequently, using the fine-tuned algorithms, we examined (i) the ability of unspecified infection and respiratory syndrome categories to detect the start of the flu season and (ii) how well data from Children's National Medical Center (CNMC) did versus all the other hospitals when using unspecified infection, respiratory, and both categories together.</p> <p>Results</p> <p>Simulation studies using the data showed that over a range of situations, the multivariate CUSUM algorithm performed more effectively than the other algorithms tested. In addition, the parameters that yielded optimal performance varied for each algorithm, especially with the number of cases in the data stream. In terms of detecting the onset of seasonal influenza, only "unspecified infection," especially the counts from CNMC, clearly delineated influenza outbreaks out of the eight available syndromic classifications. In three of five years, CNMC consistently flags earlier (from 2 days up to 2 weeks earlier) than a multivariate analysis of all other DC hospitals.</p> <p>Conclusions</p> <p>When practitioners apply statistical detection algorithms to their own data, fine tuning of parameters is necessary to improve overall sensitivity. With fined tuned algorithms, our results suggest that emergency room based syndromic surveillance focusing on unspecified infection cases in children is an effective way to determine the beginning of the influenza outbreak and could serve as a trigger for more intensive surveillance efforts and initiate infection control measures in the community.</p

Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer

<p>Abstract</p> <p>Background</p> <p>Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.</p> <p>Methods</p> <p>This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/²/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.</p> <p>Results</p> <p>Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (<it>DPYD</it>) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).</p> <p>Conclusion</p> <p>Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.</p

Early detection of subclinical left ventricular dysfunction after breast cancer radiation therapy using speckle-tracking echocardiography Association between cardiac exposure and longitudinal strain reduction (BACCARAT study)

International audienceBackground Breast cancer (BC) radiotherapy (RT) can induce cardiotoxicity, with adverse events often observed many years after BC RT. Subclinical left ventricular (LV) dysfunction can be detected early after BC RT with global longitudinal strain (GLS) measurement based on 2D speckle-tracking echocardiography. This 6-month follow-up analysis from the BACCARAT prospective study aimed to investigate the association between cardiac radiation doses and subclinical LV dysfunction based on GLS reduction.Methods The patient study group consisted of 79 BC patients (64 left-sided BC, 15 right-sided BC) treated with RT without chemotherapy. Echocardiographic parameters, including GLS, were measured before RT and 6 months post-RT. The association between subclinical LV dysfunction, defined as GLS reduction > 10%, and radiation doses to whole heart and the LV were performed based on logistic regressions. Non-radiation factors associated with subclinical LV dysfunction including age, BMI, hypertension, hypercholesterolemia and endocrine therapy were considered for multivariate analyses.Results A mean decrease of 6% in GLS was observed (-15.1% ± 3.2% at 6 months vs.-16.1% ± 2.7% before RT, p = 0.01). For left-sided patients, mean heart and LV doses were 3.1 ± 1.3 Gy and 6.7 ± 3.4 Gy respectively. For right-sided patients, mean heart dose was 0.7 ± 0.5 Gy and median LV dose was 0.1 Gy. Associations between GLS reduction > 10% (37 patients) and mean doses to the heart and the LV as well as the V20 were observed in univariate analysis (Odds Ratio = 1.37[1.01-1.86], p = 0.04 for Dmean Heart; OR = 1.14 [1.01-1.28], p = 0.03 for Dmean LV; OR = 1.08 [1.01-1.14], p = 0.02 for LV V20). In multivariate analysis, these associations did not remain significant after adjustment for non-radiation factors. Further exploratory analysis allowed identifying a subgroup of patients (LV V20 > 15%) for whom a significant association with subclinical LV dysfunction was found (adjusted OR = 3.97 [1.01-15.70], p = 0.048).Conclusions This analysis indicated that subclinical LV dysfunction defined as a GLS decrease > 10% is associated with cardiac doses, but adjustment for non-radiation factors such as endocrine therapy lead to no longer statistically significant relationships. However, LV dosimetry may be promising to identify high-risk subpopulations. Larger and longer follow-up studies are required to further investigate these associations. Trial registration ClinicalTrials.gov NCT02605512, Registered 6 November 2015-Retrospectively registered © 2019 The Author(s)

Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy A dosimetric evaluation based on individually-determined radiation dose (BACCARAT study)

International audienceBackground Intra-individual heterogeneity of cardiac exposure is an issue in breast cancer (BC) radiotherapy that was poorly considered in previous cardiotoxicity studies mainly based on mean heart dose (MHD). This dosimetric study analyzes the distribution of individually-determined radiation doses to the heart and its substructures including coronary arteries and evaluate whether MHD is a relevant surrogate parameter of dose for these substructures. Methods Data were collected from the BACCARAT prospective study that included left or right unilateral BC patients treated with 3D-Conformal Radiotherapy (RT) between 2015 and 2017 and followed-up for 2 years with repeated cardiac imaging examinations. A coronary computed tomography angiography (CCTA) was performed before RT for all patients. Registration of the planning CT and CCTA images allowed delineation of the coronary arteries on the planning CT images. Using the 3D dose matrix generated during treatment planning and the added coronary contours, dose distributions were generated for whole heart and the following substructures left ventricle (LV), left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA). A descriptive analysis of the physical doses in Gray (Gy) was performed, Dmean was the volume-weighted mean dose. Results Dose distributions were generated for 89 left-sided BC patients (MHD = 2.9 ± 1.5 Gy, Dmean-LAD = 15.7 ± 3.1 Gy) and 15 right-sided BC patients (MHD = 0.5 ± 0.1 Gy; Dmean-RCA = 1.2 ± 0.4 Gy). For left-sided BC patients, the ratio Dmean-LAD/MHD was around 5. Pearson correlation coefficients between MHD and Dmean for delineated substructures were all statistically significant. However, for all substructures, the coefficient of determination R 2 indicated that the proportion of the variance in Dmean of the substructure predictable from MHD was moderate to low (in particular R 2 = 0.45 for LAD). Among left-sided BC patients with MHD andlt; 3Gy, 56% of patients could nevertheless receive LAD doses above 40Gy (V40 andgt; 0). Conclusion Our study illustrates that MHD is not enough to predict with confidence individual patient dose to the LV and coronary arteries, in particular the LAD. For precise radiotherapy-induced cardiotoxicity studies it would be necessary to consider the distribution of doses within these cardiac substructures rather than just the MHD. Trial registration ClinicalTrials.gov NCT02605512, Registered 6 November 2015 - Retrospectively registered. © 2019 The Author(s)