A B S T R A C T PurposeTo describe trends in the aggressiveness of end-of-life (EOL) cancer care in a universal health care system in Ontario, Canada, between 1993 and2004, and to compare with findings reported in the United States. MethodsA population-based, retrospective, cohort study that used administrative data linked to registry data. Aggressiveness of EOL care was defined as the occurrence of at least one of the following indicators: last dose of chemotherapy received within 14 days of death; more than one emergency department (ED) visit within 30 days of death; more than one hospitalization within 30 days of death; or at least one intensive care unit (ICU) admission within 30 days of death. ResultsAmong 227,161 patients, 22.4% experienced at least one incident of potentially aggressive EOL cancer care. Multivariable analyses showed that with each successive year, patients were significantly more likely to encounter some aggressive intervention (odds ratio, 1.01; 95% CI, 1.01 to 1.02). Multiple emergency department (ED) visits, ICU admissions, and chemotherapy use increased significantly over time, whereas multiple hospital admissions declined (P Ͻ .05). Patients were more likely to receive aggressive EOL care if they were men, were younger, lived in rural regions, had a higher level of comorbidity, or had breast, lung, or hematologic malignancies. Chemotherapy and ICU utilization were lower in Ontario than in the United States. ConclusionAggressiveness of cancer care near the EOL is increasing over time in Ontario, Canada, although overall rates were lower than in the United States. Health system characteristics and patient or physician cultural factors may play a role in the observed differences.

ObjectivesFluoroquinolone-associated tendon ruptures are a recognised complication, but other severe collagen-associated adverse events may also be possible. Our objectives were to confirm the association of fluoroquinolones and tendon rupture, to clarify the potential association of fluoroquinolones and retinal detachment, and to test for a potentially lethal association between fluoroquinolones and aortic aneurysms.SettingPopulation-based longitudinal cohort study in Ontario, Canada.ParticipantsOlder adults turning 65 years between April 1 1997 and March 31 2012 were followed until primary outcome, death, or end of follow-up (March 31 2014). Fluoroquinolone prescriptions were measured as a time-varying covariate, with patients considered at risk during and for 30 days following a treatment course.Primary outcome measuresSevere collagen-associated adverse events defined as tendon ruptures, retinal detachments and aortic aneurysms diagnosed in hospital and emergency departments.ResultsAmong the 1 744 360 eligible patients, 657 950 (38%) received at least one fluoroquinolone during follow-up, amounting to 22 380 515 days of treatment. The patients experienced 37 338 (2.1%) tendon ruptures, 3246 (0.2%) retinal detachments, and 18 391 (1.1%) aortic aneurysms. Severe collagen-associated adverse events were more common during fluoroquinolone treatment than control periods, including tendon ruptures (0.82 vs 0.26/100-person years, p<0.001), retinal detachments (0.03 vs 0.02/100-person-years, p=0.003) and aortic aneurysms (0.35 vs 0.13/100-person-years, p<0.001). Current fluoroquinolones were associated with an increased hazard of tendon rupture (HR 3.13, 95% CI 2.98 to 3.28; adjusted HR 2.40, 95% CI 2.24 to 2.57) and an increased hazard of aortic aneurysms (HR 2.72, 95% CI 2.53 to 2.93; adjusted HR2.24, 95% CI 2.02 to 2.49) that were substantially greater in magnitude than the association of these outcomes with amoxicillin. The hazard of retinal detachment was marginal (HR 1.28, 95% CI 0.99 to 1.65; adjusted HR 1.47, 95% CI 1.08 to 2.00) and not greater in magnitude than that observed with amoxicillin.ConclusionsFluoroquinolones are associated with subsequent tendon ruptures and may also contribute to aortic aneurysms.

Inhaled corticosteroid (ICS) use is associated with an increased risk of pneumonia. This study was performed to determine if ICS use is associated with an increased risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) or tuberculosis (TB).We conducted a population-based nested case-control study using linked laboratory and health administrative databases in Ontario, Canada, including adults aged ≥66 years with treated obstructive lung disease ( asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD overlap syndrome) between 2001 and 2013. We estimated odds ratios comparing ICS use with nonuse among NTM-PD and TB cases and controls using conditional logistic regression.Among 417 494 older adults with treated obstructive lung disease, we identified 2966 cases of NTM-PD and 327 cases of TB. Current ICS use was associated with NTM-PD compared with nonuse (adjusted OR (aOR) 1.86, 95% CI 1.60-2.15) and was statistically significant for fluticasone (aOR 2.09, 95% CI 1.80-2.43), but not for budesonide (aOR 1.19, 95% CI 0.97-1.45). There was a strong dose-response relationship between incident NTM-PD and cumulative ICS dose over 1 year. There was no significant association between current ICS use and TB (aOR 1.43, 95% CI 0.95-2.16).This study suggests that ICS use is associated with an increased risk of NTM-PD, but not TB.

Background-Prior studies have shown an association between fast food restaurants and adolescent body size. Less is known about the influence of neighborhood food stores on a child's body size. We hypothesized that in the inner-city, minority community of East Harlem, New York, the presence of convenience stores and fast food restaurants near a child's home is associated with increased risk for childhood obesity as measured by body mass index (BMI).

Quantitative cerebral blood flow (CBF) values can be obtained from dynamic susceptibility contrast (DSC) MR perfusion studies using the standard singular value decomposition (sSVD) deconvolution algorithm. Reports in the literature from simulation and in vivo studies suggest that CBF estimates obtained using sSVD deconvolution depend on the arterial-tissue delay (ATD). By contrast, Fourier transform (FT) deconvolution produces CBF estimates that are independent of ATD. The diagnostic reliability of quantitative CBF measurements to define areas of normal tissue flow and tissue at risk is brought into doubt by such gross sensitivity to the specifics of the decon- Quantitative cerebral blood flow (CBF) values can be obtained from dynamic susceptibility contrast (DSC) MR perfusion studies using the standard singular value decomposition (sSVD) deconvolution algorithm. However, it has been reported (1-4) that the CBF values determined using sSVD approaches depend on the arterial-tissue delay (ATD) between the first nonzero signal components of the arterial, c a (t), and tissue, c VOI (t), contrast agent concentrations. Changes in ATD can occur in the presence of physiological or experimental effects, e.g., whether c a (t) is determined from an unaffected vessel with normal flow or an affected vessel with abnormal flow, and which slice in an interleaved multislice study contains that vessel (Fig. 1).Wu et al. (4) quantitatively demonstrated the effect of ATD on CBF estimates using a fixed c a (t) and manually repositioning both simulated and in vivo measurements of c VOI (t). Typical CBF MEASURED /CBF TRUE ratios obtained using sSVD and Fourier transform (FT) deconvolution are reproduced in Fig. 2 for -4 sec Յ ATD Յ ϩ6 sec, and tissue mean transit time (MTT) in the range 6 sec to 24 sec (3) for simulated datasets. In this example, the sSVD CBF MEA -SURED values change with ATD and are overestimated by as much as 100% for ATD Ͻ 0 sec for tissues with long MTT. The FT estimates are unaffected by ATD. CBF is generally underestimated for both algorithms for ATD Ͼ 0 sec, with the underestimation greatest for tissues having short MTT.Such gross sensitivity of quantitative CBF measurements with the simple repositioning of the tissue signals is in contradiction to convolution theory (5) and casts doubt on the accuracy of SVD-based deconvolution techniques used to correctly identify areas of normal flow and tissue at risk. In this article we will demonstrate that the variation in quantitative CBF measurements as a function of ATD is an algorithmic artifact associated with the implementation of the sSVD algorithm. In addition, we will introduce and demonstrate a reformulated implementation of the timedomain SVD algorithm (rSVD) that provides CBF estimates equivalent to those obtained from the frequency-domain FT deconvolution algorithm, regardless of MTT and ATD. Preliminary results from this study have been previously presented (6). Independent proof that the variation of CBF estimates with ATD values was an artifact of the sta...

On November 16, 2011, the U.S. Food and Drug Administration (FDA) granted full approval to ruxolitinib, (Jakafi; Incyte Corp.), an inhibitor of the Janus kinases 1 and 2, for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, postpolycythemia vera myelofibrosis, and postessential thrombocythemia myelofibrosis. This approval was based on the results of 2 large randomized phase III trials that enrolled patients with intermediate-2 or high-risk myelofibrosis and compared ruxolitinib with placebo (study 1) or best available therapy (study 2). The primary efficacy endpoint was the proportion of patients who experienced a reduction in spleen volume of ≥35% at 24 weeks (study 1) or 48 weeks (study 2). The key secondary endpoint in study 1 was the proportion of patients who experienced a ≥50% improvement from baseline in myelofibrosis total symptom score at 24 weeks. The results of these studies showed that a greater proportion of patients treated with ruxolitinib experienced a ≥35% reduction in spleen volume as compared with those treated with placebo (42% vs. 1%, P &lt; 0.0001) or best available therapy (29% vs. 0%, P &lt; 0.0001). A greater proportion of patients in study 1 experienced a ≥50% reduction in the myelofibrosis total symptom score during treatment with ruxolitinib than with placebo (46% vs. 5%, P &lt; 0.0001). Ruxolitinib treatment was associated with an increased incidence of grades III and IV anemia, thrombocytopenia, and neutropenia. This is the first drug approved for myelofibrosis. Clin Cancer Res; 18(12); 3212–7. ©2012 AACR.

BackgroundLittle is known about the long-term health effects of ambient ultrafine particles (<0.1 μm) (UFPs) including their association with respiratory disease incidence. In this study, we examined the relationship between long-term exposure to ambient UFPs and the incidence of lung cancer, adult-onset asthma, and chronic obstructive pulmonary disease (COPD).MethodsOur study cohort included approximately 1.1 million adults who resided in Toronto, Canada and who were followed for disease incidence between 1996 and 2012. UFP exposures were assigned to residential locations using a land use regression model. Random-effect Cox proportional hazard models were used to estimate hazard ratios (HRs) describing the association between ambient UFPs and respiratory disease incidence adjusting for ambient fine particulate air pollution (PM2.5), NO2, and other individual/neighbourhood-level covariates.ResultsIn total, 74,543 incident cases of COPD, 87,141 cases of asthma, and 12,908 cases of lung cancer were observed during follow-up period. In single pollutant models, each interquartile increase in ambient UFPs was associated with incident COPD (HR = 1.06, 95% CI: 1.05, 1.09) but not asthma (HR = 1.00, 95% CI: 1.00, 1.01) or lung cancer (HR = 1.00, 95% CI: 0.97, 1.03). Additional adjustment for NO2 attenuated the association between UFPs and COPD and the HR was no longer elevated (HR = 1.01, 95% CI: 0.98, 1.03). PM2.5 and NO2 were each associated with increased incidence of all three outcomes but risk estimates for lung cancer were sensitive to indirect adjustment for smoking and body mass index.ConclusionsIn general, we did not observe clear evidence of positive associations between long-term exposure to ambient UFPs and respiratory disease incidence independent of other air pollutants. Further replication is required as few studies have evaluated these relationships.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-017-0276-7) contains supplementary material, which is available to authorized users.

BackgroundWait times are an important measure of access to various health care sectors and from a patient’s perspective include several stages in their care. While mechanisms to improve wait times from specialty care have been developed across Canada, little is known about wait times from primary to specialty care. Our objectives were to calculate the wait times from when a referral is made by a family physician (FP) to when a patient sees a specialist physician and examine patient and provider factors related to these wait times.MethodsOur study used the Electronic Medical Record Administrative data Linked Database (EMRALD) which is a linkage of FP electronic medical record (EMR) data to the Ontario, Canada administrative data. The EMR referral date was linked to the administrative physician claims date to calculate the wait times. Patient age, sex, socioeconomic status, comorbidity and FP continuity of care and physician age, sex, practice location, practice size and participation in a primary care delivery model were examined with respect to wait times.ResultsThe median waits from medical specialists ranged from 39 to 76 days and for surgical specialists from 33 days to 66 days. With a few exceptions, patient factors were not associated with wait times from primary care to specialty care. Similarly physician factors were not consistently associated with wait times, except for FP practice location and size.ConclusionsActual wait times for a referral from a FP to seeing a specialist physician are longer than those reported by physician surveys. Wait times from primary to specialty care need to be included in the calculation of surgical and diagnostic wait time benchmarks in Canada.