Impact of Geographical Distance from Quaternary Treatment Center on Clinical Trial Participation, Intensive Induction Chemotherapy, and Outcomes in Patients with Newly Diagnosed Acute Myeloid Leukemia.

INTRODUCTION: Care for patients with acute myeloid leukemia (AML) is centralized in the Ontario single-payer public healthcare system, with intensive induction chemotherapy and clinical trials only offered at specialized cancer centers with large catchment areas. METHODS: We therefore conducted a retrospective single-center review of all AML patients assessed at a large specialized cancer center in Ontario, Canada. RESULTS: Between 2012 and 2017, 1,310 patients were assessed by our center for upfront AML therapy. The median distance was 33.1 km, with 29% of patients living more than 50 km away from the center. There was no significant difference in probability of intensive induction chemotherapy or clinical trial by distance from center, both in univariate and multivariable analysis adjusting for age, sex, cytogenetics and molecular testing, and performance status. There was no significant difference in overall survival by distance from center on univariate and multivariable analysis. CONCLUSION: In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, participation in clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single-payer environment.

Utilisation and outcomes of allogeneic hematopoietic cell transplantation in Ontario, Canada, and New York State, USA: a population-based retrospective cohort study.

OBJECTIVE: Allogeneic haematopoietic cell transplantation (HCT) is a potentially curative treatment for haematologic and oncologic diseases. There is a perception that the United States of America (USA) offers greater access to expensive therapies such as HCT. Alternatively, Canada is thought to suffer from protracted wait times, but lower spending. Our objective was to compare HCT utilisation and short-term outcomes in Ontario (ON), Canada, and New York State (NY), USA. DESIGN, SETTING AND PARTICIPANTS: We conducted a population-based cohort study using administrative health data to identify all residents of ON and NY who underwent allogeneic HCT between 2012 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were age and sex standardised HCT utilisation rates, in-hospital mortality, hospital length of stay (LOS) and readmission rates in ON and NY. Secondary outcomes included comparing ON and NY HCT recipients with respect to demographic characteristics and patient wealth (using neighbourhood income quintile). RESULTS: We identified 547 HCT procedures in ON and 1361 HCT procedures performed in NY. HCT recipients in ON were younger than NY (mean age 49.0 vs 51.6 years; p<0.001) and a lower percentage of ON recipients resided in affluent neighbourhoods compared with NY (47.2% vs 52.6%; p=0.026). Utilisation of HCT was 14.4 per 1 million population per year in ON and 26.7 per 1 million per year in NY (p<0.001). The magnitude of the ON-NY difference in utilisation was larger for older patients. In-hospital mortality, LOS and readmission rates were lower in ON than NY in both unadjusted and adjusted analyses. CONCLUSIONS: We found significantly lower utilisation of HCT in ON compared with NY, particularly among older patients. Higher in-hospital mortality in NY relative to ON requires further study. These differences are thought provoking for patients, healthcare providers and policy-makers in both jurisdictions.

Serum Ferritin and Glucose Homeostasis in Women With Recent Gestational Diabetes.

OBJECTIVES: Serum markers of iron storage have been linked to type 2 diabetes; however, the mechanism underlying this association is unclear. In pregnancy, increased serum ferritin has been reported in women with gestational diabetes (GDM), a patient population at high risk of future type 2 diabetes. However, in the years after pregnancy, it is not known if ferritin relates to their diabetes risk or the pathophysiologic determinants thereof (insulin sensitivity and beta-cell function). Therefore, we sought to characterize the relationship between ferritin and glucose homeostasis in the early postpartum years in women with and without recent GDM. METHODS: At both 1 and 3 years postpartum, 340 women (105 with recent GDM) underwent serum ferritin measurement and an oral glucose tolerance test that enabled assessment of insulin sensitivity and/or resistance (Matsuda index and Homeostasis Model Assessment [HOMA-IR]), beta-cell function (Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-IR) and glucose tolerance. RESULTS: Serum ferritin did not differ between women who had GDM and their peers at either 1 or 3 years postpartum. Baseline-adjusted change in ferritin between 1 and 3 years correlated with the concomitant change in C-reactive protein (r=0.21, p=0.0002) but was not associated with measures of insulin sensitivity and/or resistance, beta-cell function or glycemia. On adjusted analyses, neither baseline ferritin nor its change from 1 to 3 years was independently associated with any of the following metabolic outcomes at 3-years postpartum: Matsuda index, HOMA-IR, Insulin Secretion-Sensitivity Index-2, insulinogenic index/HOMA-IR, fasting glucose, 2-h glucose or glucose intolerance. CONCLUSIONS: Serum ferritin is not associated with glucose homeostasis in the early years after a GDM pregnancy.

Sharing post-AML consolidation supportive therapy with local centers reduces patient travel burden without compromising outcomes.

Acute myeloid leukemia (AML) is frequently treated with induction and consolidation chemotherapy. Consolidation chemotherapy can be delivered on an ambulatory basis, requiring some patients to travel long distances for treatment at specialized centers. We developed a shared care model where patients receive consolidation chemotherapy at a quaternary center, but post-consolidation supportive care at local hospitals. To evaluate the impact of our model on patient travel and outcomes we conducted a retrospective analysis of AML and acute promyelocytic leukemia patients receiving consolidation over four years at our quaternary center. 73 patients received post-consolidation care locally, and 344 at the quaternary center. Gender, age and cytogenetic risk did not significantly differ between groups. Shared care patients saved mean round trip distance of 146.5km±99.6 and time of 96.7min±63.4 compared to travelling to quaternary center. There was no significant difference in overall survival between groups, and no increased hazard of death for shared care patients. 30, 60, and 90day survival from start of consolidation was 98.6%, 97.2%, and 95.9% for shared care and 98.8%, 97.1%, and 95.3% for quaternary center patients. Thus, a model utilizing regional partnerships for AML post-consolidation care reduces travel burden while maintaining safety.

Psychiatric disorders in Ehlers-Danlos syndrome are frequent, diverse and strongly associated with pain.

Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary connective tissue disorders characterized by joint hypermobility, widespread musculoskeletal pain and tissue fragility. Psychiatric disorders and psychosocial impairment are common, yet poorly characterized, findings in EDS patients. We investigated the frequency and types of psychiatric disorders and their relationship to systemic manifestations in a cohort of 106 classic and hypermobility type EDS patients. In this retrospective study, extensive medical chart review was performed for patients referred at two genetics clinics who were diagnosed with EDS. Statistical analysis was undertaken to determine the frequency of psychiatric disorders and association with systemic findings. Psychiatric disorders were found in 42.5% of the EDS cohort, with 22.7% of patients affected with 2 or more psychiatric diagnoses. Anxiety and depression were most commonly reported, with frequencies of 23.6 and 25.5%, respectively. A variety of other psychiatric diagnoses were also identified. Abdominal pain [odds ratio (OR) 7.38], neuropathic pain (OR 4.07), migraines (OR 5.21), joint pain (OR 2.85) and fatigue (OR 5.55) were significantly associated with the presence of a psychiatric disorder. The presence of any pain symptom was significantly associated with having a psychiatric disorder (OR 9.68). Muscle pain (OR 2.79), abdominal pain (OR 5.78), neuropathic pain (OR 3.91), migraines (OR 2.63) and fatigue (OR 3.78) were significantly associated with having an anxiety or mood disorder. Joint hypermobility and the classic dermatological features of EDS showed no significant association with having a psychiatric disorder. Our findings demonstrate a high frequency of psychiatric disorders and an association with pain symptoms in EDS.

Mitochondrial DNA damage by bleomycin induces AML cell death.

Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA. We identified bleomycin as an agent that damaged mtDNA in AML cells at concentrations that induced cell death. Bleomycin also induced mtDNA damage in primary AML samples. Consistent with the observed mtDNA damage, bleomycin reduced mt mass and basal oxygen consumption in AML cells. We also demonstrated that the observed mtDNA damage was functionally important for bleomycin-induced cell death. Finally, bleomycin delayed tumor growth in xenograft mouse models of AML and anti-leukemic concentrations of the drug induced mtDNA damage in AML cells preferentially over normal lung tissue. Taken together, mtDNA-targeted therapy may be an effective strategy to target AML cells and bleomycin could be useful in the treatment of this disease.

Sustainability of Routine Notification and Request legislation on eye bank tissue supply and corneal transplantation wait times in Canada.

OBJECTIVE: To assess whether provinces with Routine Notification and Request (RNR) legislation have sustained increases in corneal tissue supply and decreases in wait times for corneal transplantation surgery. DESIGN: Cross-sectional survey of Canadian corneal transplant (CT) surgeons and eye banks. PARTICIPANTS: Canadian CT surgeons and representatives from the 10 Canadian eye banks. METHODS: Voluntary and anonymous surveys were distributed between July and October 2009. Eligible CT surgeons were defined as ophthalmologists who practice in Canada; currently perform Penetrating keratoplasty (PKP), Deep anterior lamellar keratoplasty (DALK), Deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet membrane endothelial keratoplasty (DMEK); and have obtained tissues from a Canadian eye bank. RESULTS: From 2006 to 2009, for provinces with RNR legislation and where data are available, mean wait times from date of diagnosis to date of CT surgery have increased: in Ontario, from 31 ± 34 weeks to 36 ± 27 weeks; in British Columbia, from 39 ± 20 weeks to 42 ± 35 weeks; in Manitoba, from 32 ± 23 weeks to 49 ± 36 weeks. In addition, the amount of corneal tissue in RNR provinces suitable for transplant, with the exception of British Columbia, has declined between 2006 and 2008: in Ontario, 1186 tissues to 999 tissues (16% decline); in Manitoba, 92 tissues to 83 tissues (10% decline); in New Brunswick, 129 tissues to 98 tissues (24% decline). CONCLUSION: Although initially effective, RNR legislation has not sustained an increase in corneal tissue availability nor has it shortened wait times in most provinces. Incorporation of community hospitals into the RNR catchment, improved enforcement, and continued education of hospital staff regarding the RNR process may be effective in making this legislation more sustainable in the long term.