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Background: To evaluate the impact of cisplatin cumulative dose (CDDP-D) and smoking pack-years (PYs) on cause-specific survival (CSS) and overall survival (OS) in human papillomavirus-positive (HPV+) oropharyngeal carcinoma (OPSCC) using the eighth edition tumour-node-metastasis (TNM) staging classification (TNM8)., Patients and Methods: We reviewed patients with HPV+ OPSCC treated with high-dose CDDP and intensity-modulated radiotherapy between 2005 and 2015 at Princess Margaret Cancer Centre. CSS and OS were compared according to CDDP-D <200/=200/>200 mg/m 2 stratified by TNM8., Results: A total of 482 consecutive patients were evaluated (stage I/II/III: N = 189/174/119; CDDP-D <200/=200/>200 mg/m 2 : N = 112/220/150). Median follow-up duration was 5.1 years (range: 0.6-12.8). Five-year CSS and OS differed by stages I/II/III: 96%/85%/88% (p=0.005) and 93%/84%/78% (p = 0.001), respectively. Five-year CSS by CDDP-D <200/=200/>200 mg/m 2 was similar in stage I (98%/95%/95%, p = 0.74) and stage II (88%/84%/84%, p = 0.86) but different in stage III (76%/98%/84%, p = 0.02). Five-year OS by CDDP-D <200/=200/>200 mg/m 2 did not differ significantly among stages. In the multivariable analysis, CDDP-D <200 mg/m 2 did not influence CSS in the whole cohort versus = 200/>200 mg/m 2 (p=0.53/0.79, respectively) but was associated with reduced CSS in stage III subgroup versus =200 mg/m 2 (=200 mg/m 2 versus < 200 mg/m 2 hazard ratio [HR] = 0.08; 95% confidence interval [CI]: 0.01-0.67; p = 0.02). Higher smoking PYs had no effect on CSS (p = 0.34) but reduced OS in the whole cohort (HR = 1.14 [95% CI: 1.02-1.27], p=0.01)., Conclusion: CDDP-D correlated with neither survival nor disease-specific outcomes in this large and homogeneous HPV+ cohort, although reduced CSS was observed in stageIII HPV+ OPSCC receiving CDDP-D <200 mg/m 2 . Smoking PYs were negatively associated with OS but not with CSS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To define human papillomavirus (HPV) -positive oropharyngeal cancers (OPC) suitable for treatment deintensification according to low risk of distant metastasis (DM)., Patients and Methods: OPC treated with radiotherapy (RT) or chemoradiotherapy (CRT) from 2001 to 2009 were included. Outcomes were compared for HPV-positive versus HPV-negative patients. Univariate and multivariate analyses identified outcome predictors. Recursive partitioning analysis (RPA) stratified the DM risk., Results: HPV status was ascertained in 505 (56%) of 899 consecutive OPCs. Median follow-up was 3.9 years. HPV-positive patients (n = 382), compared with HPV-negative patients (n = 123), had higher local (94% v 80%, respectively, at 3 years; P < .01) and regional control (95% v 82%, respectively; P < .01) but similar distant control (DC; 90% v 86%, respectively; P = .53). Multivariate analysis identified that HPV negativity (hazard ratio [HR], 2.9; 95% CI, 2.0 to 5.0), N2b-N3 (HR, 2.9; 95% CI, 1.8 to 4.9), T4 (HR, 1.8; 95% CI, 1.2 to 2.9), and RT alone (HR, 1.8; 95% CI, 1.1 to 2.5) predicted a lower recurrence-free survival (RFS; all P < .01). Smoking pack-years > 10 reduced overall survival (HR, 1.72; 95% CI, 1.1 to 2.7; P = .03) but did not impact RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P = .65). RPA segregated HPV-positive patients into low (T1-3N0-2c; DC, 93%) and high DM risk (N3 or T4; DC, 76%) groups and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high DM risk (T3-4N3; DC, 72%) groups. The DC rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P = .02)., Conclusion: HPV-positive T1-3N0-2c patients have a low DM risk, but N2c patients from this group have a reduced DC when treated with RT alone and seem less suited for deintensification strategies that omit chemotherapy.

Purpose: The purpose of this study is to compare self-reported quality of life (QOL) scores in old and young patients with metastatic cancer using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire., Materials and Methods: Patients receiving palliative radiotherapy (RT) for bone metastases and brain metastases completed the QLQ-C15-PAL questionnaire prior to treatment. Using multiple linear regression analysis, a parametric test, the QLQ-C15-PAL scores were compared using 65 and 70 years as cutoff ages., Results: A total of 340 patients were referred for palliative RT for bone metastases (n = 190) or brain metastases (n = 150). Physical functioning and appetite were worse in the older group using either 65 or 70 years as the cutoff age. Age-related differences in the QLQ-C15-PAL scores varied as a function of age cutoff used and location of metastatic site irradiated., Conclusion: Based on the (EORTC) QLQ-C15-PAL, elderly advanced cancer patients have a different QOL profile. Similar observations have been reported with the (EORTC) QLQ-C30 questionnaire.

Methods using SPE followed by HPLC/MS/MS analysis were developed and validated for the determination of 39 pesticides in different aquatic environmental matrixes. The target pesticides included 12 carbamates, 15 organophosphates, and 12 phenyl ureas, out of which 16 are regulated in North America. Method detection limits were in the low ng/L range using the U.S. Environmental Protection Agency's protocol and multiple reaction monitoring (MRM) data acquisition, meeting the regulatory needs in the United States, Canada, and European Union. Isotope-labeled compounds were used as injection internal standards, as well as method surrogates to improve the data quality. QC/QA data (e.g., method recovery and within-run and between-run method precision) derived from multiyear monitoring activities were used to demonstrate method ruggedness. The same QC/QA data also showed that the method exerted no obvious matrix effect on the target analytes. Parameters that affect method performance, such as preservatives, pH values, sample storage time, and sample extract storage time, were also studied in detail. Accredited by the Canadian Association for Laboratory Accreditation and licensed by the Ontario government for drinking water analysis, these methods have been applied to the analysis of drinking water, ground water, and surface water samples collected in the province of Ontario, Canada, to ensure the pristine nature of Ontario's aquatic environment. Using the scheduled MRM (sMRM) data acquisition algorithm, it was demonstrated that sMRM improved the S/N of extracted ion chromatograms by at least two- to six-fold and, therefore, enhanced the short- and long-term instrument precision, demonstrated the ability to offer high throughput multiresidue analysis, and allowed the use of two MRM transitions for each compound to achieve higher confidence for compound identification.

Objectives: This study attempted to determine population-based trends in in-hospital patient fatality from acute myocardial infarction., Background: The in-hospital prognosis for patients with acute myocardial infarction should be improving as a result of adoption of treatments proved in randomized trials (e.g., thrombolytic, beta-adrenergic blocking and anticoagulant agents and aspirin). However, all trials are subject to selection biases, eligibility is limited for some therapies, and proved therapies may be underused even among eligible patients., Methods: Using administrative data from all general hospitals in Ontario, Canada, we analyzed 17,489, 17,839, 18,393, 18,794, 18,716 and 19,748 records of patients with a primary discharge diagnosis of myocardial infarction for fiscal years 1981, 1983, 1985, 1987, 1989 and 1991, respectively., Results: After age and gender adjustment, the overall relative reduction in in-hospital case fatality rates for the 10-year period was 26.9% (99% confidence interval [CI] 26.8% to 26.9%), corresponding to an absolute reduction of 6% (99% CI 5.6% to 6.4%). Age- and gender-standardized case fatality rate decreased from 22.3% in 1981 to 21.4% in 1985, followed by a highly significant decline to 16.3% in 1991. On the basis of the relation of comparative mortality to days of hospital stay, declining mortality was not an artifact of decreasing length of stay., Conclusions: There have been encouraging improvements in survival after acute myocardial infarction over the past 6 years. Further improvements may require development of new therapies that can be more widely applied to this patient population.

Unexplained variation in length of stay (LOS) following acute myocardial infarction (AMI) has been observed among American hospitals. We explored this phenomenon in the universal hospital care system of Ontario, Canada's largest province, analyzing general hospital discharge abstracts for all patients with a primary diagnosis of AMI. Case homogeneity was increased by excluding inter-hospital transfers, in-hospital deaths, patients with revascularization during the index admission and patients with severe comorbid conditions. This left 11,411 records of patients in 187 hospitals from April 1, 1990 to March 31, 1991. The mean length of stay was 9.9 days with standard deviation of 3.8. Available patient and hospital characteristics explained only 12% of the individual variation in LOS. Interinstitutional variation remained highly significant after controlling for patients' characteristics within the 87 hospitals admitting more than 50 cases per annum; these hospitals accounted for 84% of the eligible provincial admissions. The grand mean length of stay for 87 hospitals was 10 days, ranging from 6.6 to 12.9 days. Stepwise multiple linear regression analyses showed that lower caseload was associated with an increased length of hospitalization. Thus, despite Ontario's uniform system of hospital funding and medical insurance, a large amount of unexplained variation in length of stay exists for patients hospitalized with AMI, affecting thousands of bed-days per annum.

Objective: To compare clinicians' ratings of therapeutic effectiveness when different trial end points were presented as percent reductions in relative compared with absolute risk and as numbers of patients treated to avoid one adverse outcome., Design: Survey, with random allocation of two questionnaires., Setting: Toronto teaching hospitals., Respondents: Convenience sample of 100 faculty and housestaff in internal medicine and family medicine., Intervention: One questionnaire presented results for three end points of the Helsinki Heart Study as separate drug trials using only absolute differences in events; the other showed the same end points as relative differences. Both questionnaires included a fourth "trial," showing person-years of treatment needed to prevent one myocardial infarction., Main Outcome Measure: The "trials" were each rated on an 11-point scale, from treatment "harmful" to "very effective.", Results: Respondents' ratings of effectiveness varied with the end point. Controlling for end point, ratings of effectiveness by the 50 participants receiving absolute event data were lower than those by 50 participants responding to relative risk reductions (P < 0.001); however, no end-point difference was more than 0.6 scale points. For a "trial" reporting that 77 persons were treated for 5 years to prevent one myocardial infarction, mean ratings were 2.3 or 1.8 scale points lower, respectively (both P < 0.001), than when the same data were shown as relative or absolute risk reductions., Conclusions: Clinicians' views of drug therapies are affected by the common use of relative risk reductions in both trial reports and advertisements, by end-point emphasis, and, above all, by underuse of summary measures that relate treatment burden to therapeutic yields in a clinically relevant manner.