CONTEXT In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome. OBJECTIVE To assess the association between age at diagnosis... Show moreCONTEXT In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome. OBJECTIVE To assess the association between age at diagnosis and breast cancer outcome in postmenopausal women with hormone receptor-positive breast cancer. DESIGN, SETTING, AND PATIENTS Study analysis of 9766 patients enrolled in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) randomized clinical trial between January 2001 and January 2006. Age at diagnosis was categorized as younger than 65 years (n=5349), 65 to 74 years (n=3060), and 75 years or older (n=1357). MAIN OUTCOME MEASURES Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse. RESULTS During median follow-up of approximately 5.1 years, there were a total of 1043 deaths. Disease-specific mortality, as a proportion of all-cause mortality, decreased with categorical age group (78% [<65 years], 56% [65-74 years], and 36% [≥75 years]; P < .001). In multivariable analyses, compared with patients younger than 65 years, disease-specific mortality increased with age for patients aged 65 to 74 years (hazard ratio [HR], 1.25; 95% CI, 1.01-1.54); and patients aged 75 years or older (HR, 1.63; 95% CI, 1.23-2.16) (P < .001). Similarly, breast cancer relapse increased with age for patients aged 65-74 years (HR, 1.07; 95% CI, 0.91-1.25 and patients aged 75 years or older (HR, 1.29; 95% CI, 1.05-1.60) (P = .06). Other-cause mortality increased with age in patients aged 65 to 74 years (HR, 2.66; 95% CI, 1.96-3.63) and patients aged 75 years or older (HR, 7.30; 95% CI, 5.29-10.07) (P < .001). CONCLUSION Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher disease-specific mortality. Show less
Otten, M.H.; Prince, F.H.M.; Armbrust, W.; Cate, R. ten; Hoppenreijs, E.P.A.H.; Twilt, M.; ... ; Suijlekom-Smit, L.W.A. van 2011
CONTEXT Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary... Show moreCONTEXT Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging. OBJECTIVE To compare the 2 recommended lung cancer staging strategies. DESIGN, SETTING, AND PATIENTS Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography. INTERVENTION Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread. MAIN OUTCOME MEASURES The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications. RESULTS Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P = .11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P = .02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P = .47) and 94% (62/66; 95% CI, 85%-98%) (P = .02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P = .02). The complication rate was similar in both groups. CONCLUSIONS Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00432640. Show less
Context Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary... Show moreContext Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging. Objective To compare the 2 recommended lung cancer staging strategies. Design, Setting, and Patients Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography. Intervention Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread. Main Outcome Measures The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications. Results Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P=.11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P=.02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P=.47) and 94% (62/66; 95% CI, 85%-98%) (P=.02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P=.02). The complication rate was similar in both groups. Conclusions Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies. Trial Registration clinicaltrials.gov Identifier: NCT00432640 JAMA. 2010;304(20):2245-2252 www.jama.com Show less
Korver, A.M.H.; Konings, S.; Dekker, F.W.; Beers, M.; Wever, C.C.; Frijns, J.H.M.; ... ; DECIBEL Collaborative Study Grp 2010
Context Newborn hearing screening programs have been implemented in many countries because it was thought that the earlier permanent childhood hearing impairment is detected, the less... Show moreContext Newborn hearing screening programs have been implemented in many countries because it was thought that the earlier permanent childhood hearing impairment is detected, the less developmentally disadvantaged children would become. To date, however, no strong evidence exists for universal introduction of newborn hearing screening. Objective To study the effect of newborn hearing screening vs distraction hearing screening, conducted at 9 months of age, on development, spoken communication, and quality of life. Design, Setting, and Participants Between 2002 and 2006, all 65 regions in the Netherlands replaced distraction hearing screening with newborn hearing screening. Consequently, the type of hearing screening offered was based on availability at the place and date of birth and was independent of developmental prognoses of individual children. All children born in the Netherlands between 2003 and 2005 were included. At the age of 3 to 5 years, all children with permanent childhood hearing impairment were identified. Evaluation ended December 2009. Main Outcome Measures Performance (education and spoken and signed communication), development (general and language), and quality of life. Results During the study period, 335 560 children were born in a newborn hearing screening region and 234 826 children in a distraction hearing screening region. At follow-up, 263 children in newborn hearing screening regions (0.78 per 1000 children) and 171 children in distraction hearing screening regions (0.73 per 1000 children) had been diagnosed with permanent childhood hearing impairment. Three hundred one children (69.4%) participated in analysis of general performance measures. There was no difference between groups in the primary mode of communication or type of education. Analysis of extensive developmental outcomes included 80 children born in newborn hearing screening regions and 70 in distraction hearing screening regions. Multivariate analysis of variance showed that overall, children in newborn hearing screening regions had higher developmental outcome scores compared with children in distraction hearing screening regions (Wilks lambda = 0.79; F-12=2.705; P=.003). For social development, the mean between-group difference in quotient points was 8.8(95% CI, 0.8 to 16.7) and for gross motor development, 9.1(95% CI, 1.1 to 17.1). For quality of life, the mean between-group difference was 5.3 (95% CI, 1.7 to 8.9), also in favor of children in newborn hearing screening regions. Conclusion Compared with distraction hearing screening, a newborn hearing screening program was associated with better developmental outcomes at age 3 to 5 years among children with permanent childhood hearing impairment. JAMA. 2010; 304(15): 1701-1708 Show less
Context Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences... Show moreContext Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. Objective To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. Data Sources and Study Selection The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. Data Extraction Individual data on 55 287 participants with 542 494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25 977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. Results Among 55 287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51 837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age-and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n=70 events/235; 38.4/1000 person-years; P<.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n=28 deaths/333; 7.7/1000 person-years; P=.005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. Conclusions Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater. JAMA. 2010; 304(12): 1365-1374 Show less
