Lower Hazard Of Death Research Articles

Timing of Adjuvant Chemotherapy and Impact on Survival for Resected Gastric Cancer.

Because postoperative convalescence often prolongs the interval between surgery and chemotherapy in patients undergoing treatment for advanced gastric cancer, this study assesses the survival impact of timing of adjuvant chemotherapy (AC) in patients undergoing curative resection for gastric cancer. The 2003-2012 ACS NCDB was analyzed for patients treated with gastrectomy for stages 1-3 gastric cancer. Treatment groups were stratified by time to initiation of AC: initiation of chemotherapy within 8weeks postoperatively, between 8 and 12weeks postoperatively, after 12weeks postoperatively, and no chemotherapy. Univariate and multivariate analyses were performed. Of 7942 patients undergoing gastrectomy, 29% received AC. Of those who received AC, 58% initiated AC within 8weeks, 28% initiated AC between 8 and 12weeks, and 14% received AC after 12weeks. Among patients who received AC, median survival was not significantly different between time cohorts, even when stratified by pathologic stage. Median survival was longer for chemotherapy cohorts when compared with the no chemotherapy cohort, specifically in patients with pathologic stages 2 and 3 disease. In multivariable analysis, patients who received AC had a 27-29% lower hazard of death (p<.0001), with administration of AC at any time, compared with patients who did not receive AC, but had no difference in hazard when comparing delayed AC to earlier administration of AC. Time to initiation of AC does not impact survival. With improved survival over patients who did not receive AC, even delayed initiation of chemotherapy should be offered, when appropriate.

Response to neoadjuvant chemotherapy and impact on survival for resected gastric cancer.

122 Background: This study assesses the survival impact of perioperative chemotherapy, with further analysis of pathologic response to neoadjuvant chemotherapy (NAC), in patients undergoing gastrectomy for gastric cancer (GC) in a large US sample. Methods: Using the 2003-2012 ACS National Cancer Database, 16,128 patients underwent gastrectomy for cancer. Treatment groups were categorized as: NAC, adjuvant chemotherapy, and surgery only. Patients receiving NAC were further categorized as: down-staged, no response, and disease progression. Univariate and multivariate analyses were performed to estimate the impact of treatment on overall survival. Results: Of patients undergoing gastrectomy, 36.6% received NAC, 19.5% received adjuvant chemotherapy, and 43.9% underwent surgery only. Median time of survival was longer in patients with more advanced disease who underwent either NAC or adjuvant chemotherapy versus surgery alone (see Table). In multivariate analysis, patients who received NAC had 20% lower hazard of death than surgery only patients (HR = 0.80, p &lt; 0.0001). Within the NAC cohort (N = 5,909), 47.7% were down-staged, 36.5% had no response, and 15.7% demonstrated disease progression. Having a pathologic response to NAC was associated with having private insurance (OR = 1.22, p &lt; 0.0001), higher socioeconomic status (OR = 1.21, p = 0.003), treatment in the central US (p &lt; 0.0001, both), and undergoing proximal gastrectomy (OR = 1.59, p &lt; 0.0001). Among patients who received NAC, median time of survival was longer if NAC down-staged patients to stages 0 or 1, with no survival difference in advanced stage disease. Conclusions: Neoadjuvant chemotherapy elicits a survival benefit in patients with advanced GC. Pathologic response is achieved in nearly half of patients undergoing NAC and is associated with improved survival, although only when down-staging to early stage disease. [Table: see text] [Table: see text]

A multi-institutional phase II study of high-dose hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: Long-term outcomes in patients (pts) with hepatocellular carcinoma (HCC).

376 Background: Retrospective reports of PBT in hepatocellular carcinoma (HCC) demonstrate local control (LC) rates exceeding 85%. We prospectively replicate these findings and explore predictors of overall survival (OS) in pts with unresectable HCC receiving high dose, HF-PBT. Methods: Pts were enrolled on an NCI sponsored, multi-institutional, phase II study (NCT00976898). Key eligibility were unresectable HCC; Child’s A/B; ECOG PS 0-2; no extrahepatic disease; no prior RT. Maximum tumor size was 12 cm if solitary, 10 cm if 2 tumors, and 6 cm if 3. PBT was given in 15 fractions to a maximum total dose of 67.5 GyE. Sample size was calculated to demonstrate &gt; 80% LC at 2 yrs (LC-2). Results: From 2009-2015, 44 patients were treated. Median age was 70 years (53-89) and 37 (84.1%) were male. 35 (79.5%) pts had Child A or no cirrhosis. 32 (72.7%) pts had 1 tumor, 12 (27.2%) had multiple tumors. Median longest tumor dimension was 5.0 cm (range 1.9-12.0). Median baseline AFP was 18.6 ng/mL (range 1.3-66081) and 29 pts (67.4%) had elevated AFP ( &gt; 7.9 ng/mL). Median RT dose delivered was 58.0 GyE (range 40.5-67.5). 1 pt (2%) had grade 3 RT related toxicity (thrombocytopenia). With a median follow up 21.8 mo among 28 survivors, the LC-2 was 94.8% (95% CI 84.5-99.1%). mOS was 49.9 mo (95% CI 17.8 months- upper limit not reached) and mPFS was 13.9 mo (95% CI 8.4-49.9). OS did not differ by CLIP score, PS, prior treatment, vascular thrombus, baseline AFP, size, or dose. Median AFP change from baseline to 3 mo post treatment was a 32.8% reduction. Median time to AFP nadir in pts with elevated baseline levels was 3.9 mo (0-30.5). % decrease in AFP from baseline to 6 mo post-treatment was significantly associated with lower hazard of death. (HR = 0.993, p = 0.016). Conclusions: High dose hypofractionated proton beam therapy demonstrated a high local control rate for HCC with favorable safety profiles, supporting the ongoing evaluation of radiation in HCC in phase III studies. AFP decrease from baseline to 6 months post-radiation is associated with improved overall survival. Clinical trial information: NCT00976898.

Association of Fitness in Young Adulthood With Survival and Cardiovascular Risk: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear. To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD). Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up. The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated. Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = -0.24; 95% CI, -0.45 to -0.03; P = .02) and significantly better lobal longitudinal strain (β = -0.09; 95% CI, -0.14 to -0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found. Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.

Abstract 9958: Fitness in Young Adulthood is Independently Associated With Improved Survival and Cardiovascular Risk: The CARDIA study

Introduction: Though cardiorespiratory fitness (CRF) is a well-established prognostic marker in older adults, the relationship between changes in CRF during early adulthood and long-term cardiovascular structure, function, and events remain unknown. Hypothesis: CRF and its change over time in young adults is associated with long-term outcome and cardiovascular disease (CVD). Methods: 4,872 American adults age 18-30 years underwent treadmill exercise testing at a baseline study visit in 1985-1986, and 2,472 individuals who underwent repeat treadmill testing 7 years later in CARDIA. Participants were followed for a median of 26.9 years, with assessment of obesity, echocardiographic left ventricular (LV) mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Incident CVD (cardiovascular death, heart failure, myocardial infarction, peripheral artery disease and stroke) and all-cause mortality were uniformly adjudicated. Results: From 4,872 individuals, 273 (5.6%) died and 193 (4%) experienced CVD events at a median 26.9 year follow-up. After full adjustment, each additional minute of baseline exercise test duration was associated with a 13% lower hazard of death (hazard ratio HR 0.87, 95% CI 0.81-0.92, P&lt;0.0001) and a 9% lower hazard of CVD (HR 0.91, 95% CI 0.84-0.98, P=0.008). Higher baseline fitness was associated with decreased risk of LV hypertrophy (P=0.009) and higher global longitudinal strain (P&lt;0.0001) at Year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by Year 7 was associated with a 20% increased hazard of death and CVD, along with a greater probability of LV hypertrophy and more impaired strain. There was no association between change in fitness and CAC. Conclusions: Higher fitness at baseline and improvement in fitness early in adulthood are favorably associated with CVD and mortality risk. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction, but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.

Hepatocellular Carcinoma in the Setting of Chronic Hepatitis B Virus Infection: Tumor Recurrence and Survival Rates After Liver Transplantation

BackgroundHigher rates of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection have been reported. This can influence their selection for LT and post-LT monitoring. ObjectiveThe aim of this work was to compare the rates of post-LT HCC recurrence and survival in HBV and non-HBV patients with the use of the United Network for Organ Sharing (UNOS) database. MethodsAfter accessing the UNOS database, we analyzed patients with HCC stage T2 who underwent LT from cadaveric donors on or after August 24, 1998. Propensity score matching based on age, Model for End-Stage Liver Disease (MELD), and donor risk index was used to match HBV-HCC patients to HCC patients with other underlying liver diseases: hepatitis C virus (HCV), alcoholic liver disease (ALD), both HCV + ALD, and nonalcoholic steatohepatitis (NASH). Kaplan-Meier plots and multivariable analysis (with the use of propensity score, age, sex, and race) were used to assess post-LT HCC recurrence and overall survival. ResultsA total of 4,480 HCC patients were matched. Their average age was 57 ± 7.8 years and average calculated MELD score was 13. Within 5 years of LT, 5.5% of patients had HCC recurrence and 20% died. HBV-HCC patients had 1.9 and 1.8 times higher hazard of tumor recurrence compared with ALD and NASH patients, respectively, and a 32% lower hazard of death than patients with HCV + ALD. There was no evidence of any other significant difference in HCC recurrence or survival among the etiology groups. ConclusionsHCC recurrence and survival rates following LT for HCC patients with chronic HBV infection are similar to those of HCC patients with other underlying liver diseases. These findings support LT as a viable option for HCC-HBV patients.

Light-intensity physical activities and mortality in the United States general population and CKD subpopulation.

Sedentary behavior is associated with increased mortality in the general population. Whether replacing sedentary behavior with low- or light-intensity activities confers a survival benefit in the general or CKD populations is unknown. This observational analysis of the 2003-2004 National Health and Nutrition Examination Survey examined the associations of low- and light-intensity activities with mortality. On the basis of the number of counts/min recorded by an accelerometer, durations of sedentary (<100/min), low (100-499/min), light (500-2019/min), and moderate/vigorous (≥2020/min) activity were defined and normalized to 60 minutes. The mortality associations of 2 min/hr less sedentary duration in conjunction with 2 min/hr more (tradeoff) spent in one of the low, light, or moderate/vigorous activity durations while controlling for the other two activity durations were examined in multivariable Cox regression models in the entire cohort and in the CKD subgroup. Of the 3626 participants included, 383 had CKD. The mean sedentary duration was 34.4±7.9 min/hr in the entire cohort and 40.8±6.8 in the CKD subgroup. Tradeoff of sedentary duration with low activity duration was not associated with mortality in the entire cohort or the CKD subgroup. Tradeoff of sedentary duration with light activity duration was associated with a lower hazard of death in the entire cohort (hazard ratio, 0.67; 95% confidence interval, 0.48 to 0.93) and CKD subgroup (hazard ratio, 0.59; 95% confidence interval, 0.35 to 0.98). Tradeoff of sedentary duration with moderate/vigorous activity duration had a nonsignificant lower hazard in the entire cohort and CKD subgroup. Patients with CKD are sedentary nearly two thirds of the time. Interventions that replace sedentary duration with an increase in light activity duration might confer a survival benefit.

Spatial analysis of under-5 mortality and potential risk factors in the Basse Health and Demographic Surveillance System, the Gambia.

To describe the spatial pattern in under-5 mortality rates in the Basse Health and Demographic Surveillance System (BHDSS) and to test for associations between under-5 deaths and biodemographic and socio-economic risk factors. Using data on child survival from 2007 to 2011 in the BHDSS, we mapped under-5 mortality by km(2) . We tested for spatial clustering of high or low death rates using Kulldorff's spatial scan statistic. Associations between child death and a variety of biodemographic and socio-economic factors were assessed with Cox proportional hazards models, and deviance residuals from the best-fitting model were tested for spatial clustering. The overall death rate among children under 5 was 0.0195 deaths per child-year. We found two spatial clusters of high death rates and one spatial cluster of low death rates; children in the two high clusters died at a rate of 0.0264 and 0.0292 deaths per child-year, while in the low cluster, the rate was 0.0144 deaths per child-year. We also found that children born to Fula mothers experienced, on average, a higher hazard of death, whereas children born in the households in the upper two quintiles of asset ownership experienced, on average, a lower hazard of death. After accounting for the spatial distribution of biodemographic and socio-economic characteristics, we found no residual spatial pattern in child mortality risk. This study demonstrates that significant inequality in under-5 death rates can occur within a relatively small area (1100 km(2) ). Risks of under-5 mortality were associated with mother's ethnicity and household wealth. If high mortality clusters persist, then equity concerns may require additional public health efforts in those areas.

Associations between depression and all-cause and cause-specific risk of death: A retrospective cohort study in the Veterans Health Administration

ObjectiveDepression may be associated with increased mortality risk, but there are substantial limitations to existing studies assessing this relationship. We sought to overcome limitations of existing studies by conducting a large, national, longitudinal study to assess the impact of depression on all-cause and cause-specific risk of death. MethodsWe used Cox regression models to estimate hazard ratios associated with baseline depression diagnosis (N=849,474) and three-year mortality among 5,078,082 patients treated in Veterans Health Administration (VHA) settings in fiscal year (FY) 2006. Cause of death was obtained from the National Death Index (NDI). ResultsBaseline depression was associated with 17% greater hazard of all-cause three-year mortality (95% CI hazard ratio [HR]: 1.15, 1.18) after adjusting for baseline patient demographic and clinical characteristics and VHA facility characteristics. Depression was associated with a higher hazard of three-year mortality from heart disease, respiratory illness, cerebrovascular disease, accidents, diabetes, nephritis, influenza, Alzheimer's disease, septicemia, suicide, Parkinson's disease, and hypertension. Depression was associated with a lower hazard of death from malignant neoplasm and liver disease. Depression was not associated with mortality due to assault. ConclusionsIn addition to being associated with suicide and injury-related causes of death, depression is associated with increased risk of death from nearly all major medical causes, independent of multiple major risk factors. Findings highlight the need to better understand and prevent mortality seen with multiple medical disorders associated with depression.

Preliminary results of trial NPC‐0501 evaluating the therapeutic gain by changing from concurrent‐adjuvant to induction‐concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma

A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.

Regression discontinuity designs in epidemiology: causal inference without randomized trials.

When patients receive an intervention based on whether they score below or above some threshold value on a continuously measured random variable, the intervention will be randomly assigned for patients close to the threshold. The regression discontinuity design exploits this fact to estimate causal treatment effects. In spite of its recent proliferation in economics, the regression discontinuity design has not been widely adopted in epidemiology. We describe regression discontinuity, its implementation, and the assumptions required for causal inference. We show that regression discontinuity is generalizable to the survival and nonlinear models that are mainstays of epidemiologic analysis. We then present an application of regression discontinuity to the much-debated epidemiologic question of when to start HIV patients on antiretroviral therapy. Using data from a large South African cohort (2007-2011), we estimate the causal effect of early versus deferred treatment eligibility on mortality. Patients whose first CD4 count was just below the 200 cells/μL CD4 count threshold had a 35% lower hazard of death (hazard ratio = 0.65 [95% confidence interval = 0.45-0.94]) than patients presenting with CD4 counts just above the threshold. We close by discussing the strengths and limitations of regression discontinuity designs for epidemiology.

Impact of anticholinergic load of medications on the length of stay of cancer patients in hospice care.

An important goal of hospice care is to relieve pain and suffering of terminal cancer patients. Anticholinergic medications are effective in the symptom palliation among terminal cancer patients. However, use of these medications has been associated with increased risk of side effects, which might lead to premature mortality. Short lengths of stay in hospice care leave patients with a higher level of unmet needs. The study was conducted to examine the effect of increasing anticholinergic load on the length of stay of cancer patients in hospice care in the USA. The National Home and Hospice Care Survey 2007 was used as the data source. The Cox proportional hazards model was used to investigate the risk of death among users of moderate and high anticholinergic load compared with users of low anticholinergic load in presence of other prognostic factors. Cancer patients on a moderate anticholinergic load had a 12.7% lower hazard of death (P = 0.0244), while those on a high anticholinergic load had a 15.6% lower hazard of death (P = 0.0071) as compared with those patients on a low anticholinergic load. Among other prognostic factors, non-elderly age group, male gender, white race, metropolitan hospice agency, non-profit hospice agency, severe activities of daily living dependency and cognitive impairment were significantly associated with a higher probability of death. These results provide no evidence for increasing anticholinergic load increasing mortality in cancer patients using hospice care. Thus, high anticholinergic load might have conferred a protective effect on the patients because of better symptom control.

Wilms tumor survival in Kenya

PurposeSurvival from Wilms Tumor (WT) exceeds 90% at 5years in developed nations, whereas at last report, 2-year event-free survival (EFS) in Kenya reached only 35%. To clarify factors linked to these poor outcomes in Kenya, we established a comprehensive web-based WT registry, comprised of patients from the four primary hospitals treating childhood cancers. Materials and methodsWT patients diagnosed between January 2008 and January 2012 were identified. Files were abstracted for demographic characteristics, treatment regimens, and enrollment in the Kenyan National Hospital Insurance Fund (NHIF). Children under 15years of age having both a primary kidney tumor on imaging and concordant histology consistent with WT were included. ResultsTwo-year event-free survival (EFS) was 52.7% for all patients (n=133), although loss to follow up (LTFU) was 50%. For the 33 patients who completed all scheduled standard therapy, 2-year EFS was 94%. Patients enrolled in NHIF tended to complete more standard therapy and had a lower hazard of death (Cox 0.192, p < 0.001). ConclusionSurvival of Kenyan WT patients has increased slightly since last report. Notably, WT patients completing all phases of standard therapy experienced 2-year survival approaching the benchmarks of developed nations. Efforts in Kenya should be made to enhance compliance with WT treatment through NHIF enrollment.

Systematic review and indirect treatment comparison (ITC) of dabrafenib (Dab) and trametinib (Tram) versus first-line (1L) treatments for metastatic melanoma (MM).

e20012 Background: In PhIII randomized controlled trials (RCTs), Dab and Tram have shown significant improvement in the primary endpoint of progression-free survival (PFS) as monotherapies vs dacarbazine (DTIC) in 1L patients (pts) with BRAF V600E+ MM. Overall survival (OS) in these studies was confounded by crossover of DTIC pts to active treatment (trt) upon disease progression. This study compares PFS and OS for Dab and Tram with other 1L MM trts. Methods: Embase, MEDLINE, CCTR, and conferences were systematically searched through 10/2012 for relevant RCTs. Comparators were DTIC, vemurafenib (Vem), and ipilimumab (Ipi). Using random-effects network meta-analysis, Dab and Tram were compared directly (D) vs DTIC and indirectly (I) vs Vem and DTIC+Ipi. Results: 48 studies (147 publications) met inclusion criteria; 4studies (1,603 pts) contributed data to current network meta-analysis.Both Dab and Tram showed statistically significant reduction in the risk of progression directly vs DTIC and indirectly vs DTIC+Ipi and comparable PFS indirectly vs Vem (no statistically significant difference). Dab and Tram also demonstrated a statistically nonsignificant but numerically lower hazard of death directly vs DTIC and indirectly vs Vem and DTIC+Ipi. Conclusions: Using ITC, 1L trt of MM with Dab and Tram monotherapies was statistically significantly better than DTIC and DTIC+Ipi for PFS, with comparable efficacy to Vem for PFS and OS. Results must be interpreted cautiously given methodological assumptions and immature OS data for Dab and Tram. H2H studies remain gold standard for comparing trts. [Table: see text]

Association between guideline-adherent imaging and overall survival following second-line targeted therapy for metastatic renal cell carcinoma.

e15538 Background: NCCN guidelines recommend imaging at 2-6 months after initiation of targeted therapy for metastatic renal cell carcinoma (mRCC). This study assessed the association between guideline-adherent imaging and overall survival in mRCC. Methods: Thirty-six community-based medical oncologists/hematologists reviewed charts for ≤ 15 mRCC patients each. Included patients were aged ≥ 18 years and initiated 2nd targeted therapy in 2010 or later. Patients alive up to month 6 were categorized into 3 groups based on time of first imaging test: early (0-60 days), guideline-adherent (61-180 days), and delayed(&gt; 180 days). Overall survival (OS) was compared using multivariable Cox proportional hazards models adjusted for age, gender, duration of mRCC, prior treatments, comorbidities, metastatic sites, 1st targeted therapy, ECOG and MSKCC status, 2nd targeted therapy, and progression status (based on symptoms or imaging) in the first 6 months on 2nd line therapy. Reasons for imaging were also assessed. Results: Among the 192 patients included in the analysis, 25 received early imaging, 136 received guideline-adherent imaging, and 31 received delayed imaging. First imaging tests were more likely due to worsening symptoms or changes in a palpable mass, as opposed to routine monitoring, among patients with delayed vs. guideline adherent imaging (20.0% vs. 7.1%, P = 0.005). After adjusting for baseline characteristics, guideline-adherent imaging was associated with a 64% lower hazard of death compared to delayed imaging (hazard ratio (HR) = 0.36, 95% confidence interval (CI) 0.14 to 0.93, P = 0.035). Adjusted 1-year survival was 82% in the guideline-adherent compared to 67% in the delayed imaging group. The hazard of death did not differ between those with early vs. guideline-adherent imaging (HR = 1.05, 95% CI 0.35-3.12, P = 0.927). Conclusions: Among patients surviving 6 months after the initiation of 2nd targeted therapy for mRCC, timely first imaging within 2-6 months, consistent with guidelines, was associated with significantly prolonged overall survival compared to delayed imaging. Further investigation is warranted with larger samples.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the European Prospective Investigation into Nutrition and Cancer cohort study

In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.

Changing Mortality Profile among HIV-Infected Patients in Rio de Janeiro, Brazil: Shifting from AIDS to Non-AIDS Related Conditions in the HAART Era

IntroductionWe describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ).MethodsAdult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients’ medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling.ResultsA total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7–9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986–1991 to 1.35/100PYs in 2007–2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause.ConclusionsOur results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.

Factors Associated With 90-Day Death After Emergency Department Discharge for Atrial Fibrillation

More than 10% of patients treated in the emergency department (ED) for atrial fibrillation die within a year of the visit. We sought to describe the post-ED care of an older population of atrial fibrillation patients who were discharged home from the ED and to assess patient characteristics and processes of care associated with risk of death within 90 days of discharge. This retrospective cohort analysis included patients aged 65 years or older with a primary ED diagnosis of atrial fibrillation who were treated at all nonpediatric EDs in the province of Ontario, Canada, between April 2007 and March 2010. Only the index emergency visit for each patient was included, and patients admitted to the hospital were excluded. We evaluated the association of postdischarge outpatient care and medications, ED cardioversion, and site volumes of atrial fibrillation patients with adjusted hazard of 90-day death. Among 12,772 qualifying index ED visits, there were 417 (3.3%; 95% confidence interval [CI] 3.0% to 3.6%) deaths within 90 days of the visit. Patients with no follow-up care had a significantly increased hazard of death (hazard ratio [HR] 2.27; 95% CI 1.50 to 3.43) relative to those who consulted a family physician, as did patients prescribed a calcium-channel blocker (HR 1.55; 95% CI 1.15 to 2.09) relative to a β-blocker. A filled warfarin prescription was associated with a lower hazard of death (HR 0.70; 95% CI 0.51 to 0.95). Higher site volumes (HR 0.66; 95% CI 0.41 to 1.08), cardioversion (HR 0.69; 95% CI 0.42 to 1.15), and follow-up care by a specialist only (HR 0.75; 95% CI 0.51 to 1.12) were not associated with 90-day mortality. Among older atrial fibrillation patients discharged from the ED in the province of Ontario, lack of follow-up care had the strongest association with subsequent mortality. If validated, these results suggest that as proportionately more of these patients are discharged from EDs in future, the focus should go beyond ED care itself to the care subsequent to the emergency visit.

The Brazilian Family Health Program and secondary stroke and myocardial infarction prevention: a 6-year cohort study.

We compared the incidence of recurrent or fatal cardiovascular disease in patients using Brazil's government-run Family Health Program (FHP) with those using non-FHP models of care. From 2005 to 2010, we followed outpatients discharged from city public hospitals after a first ever stroke for stroke recurrence and myocardial infarction, using data from all city hospitals, death certificates, and outpatient monitoring in state-run and private units. In the follow-up period, 103 patients in the FHP units and 138 in the non-FHP units had exclusively state-run care. Stroke or myocardial infarction occurred in 30.1% of patients in the FHP group and 36.2% of patients in non-FHP care (rate ratio [RR] = 0.85; 95% confidence interval [CI] = 0.61, 1.18; P = .39); 37.9% of patients in FHP care and 54.3% in non-FHP care (RR = 0.68; 95% CI = 0.50, 0.92; P = .01) died. FHP use was associated with lower hazard of death from all causes (hazard ratio [HR] = 0.58; P = .005) after adjusting for age and stroke severity. The absolute risk reduction for death by all causes was 16.4%. FHP care is more effective than is non-FHP care at preventing death from secondary stroke and myocardial infarction.

Quality of Care along the Cancer Continuum: Does Receiving Adequate Lymph Node Evaluation for Colon Cancer Lead to Comprehensive Postsurgical Care?

Among surgically treated patients with colon cancer, lower long-term mortality has been demonstrated in those with 12 or more lymph nodes evaluated. We examined whether patients receiving adequate lymph node evaluation were also more likely to receive comprehensive postsurgical care, leading to lower mortality. We used the 1992 to 2007 Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify surgically treated American Joint Committee on Cancer (AJCC) stage III colon cancer patients. We used chi-square analyses and logistic regression to evaluate the association between adequate (≥12) lymph node evaluation and receipt of postsurgical care (adjuvant chemotherapy, surveillance colonoscopy, CT scans, and CEA testing) and Cox proportional hazards regression to evaluate 10-year all-cause mortality, adjusting for postsurgical care. Among 17,906 surgically treated stage III colon cancer patients, adequate (≥12) lymph node evaluation was not associated with receiving comprehensive postsurgical care after adjustment for patient and tumor characteristics (p > 0.05 for all). Initially, adequate lymph node evaluation was associated with lower all-cause mortality (hazard ratio [HR] 0.88; 95% CI [0.85 to 0.91]), but among 3-year survivors, the impact of adequate lymph node evaluation on lower mortality was diminished (HR 0.94; 95% CI [0.88 to 1.01]). However, receiving comprehensive postsurgical care was associated with continued lower mortality in 3-year survivors. Adequate lymph node evaluation for colon cancer was associated with lower mortality among all patients. However, among 3-year survivors, the association between lymph node evaluation and lower hazard of death was no longer significant, while postsurgical care remained strongly associated with lower long-term mortality, indicating that postsurgical care may partially explain the relationship between lymph node evaluation and mortality.