Radiation Reveal: Moving from research engagement to involvement.

Here, we report on the process of a highly impactful and successful creative, collaborative, and multi-partner public engagement project, Radiation Reveal. It brought together ten young adults aged 17-25-year-olds with experience of radiotherapy with researchers at Cancer Research UK RadNet City of London across three 2-hour online workshops. Our aims were to 1) initiate discussions between young adults and radiation researchers, and 2) identify what people wish they had known about radiotherapy before or during treatment. These aims were surpassed; other benefits included peer support, participants' continued involvement in subsequent engagement projects, lasting friendships, creation of support groups for others, and creation and national dissemination of top ten tips for medical professionals and social media resources. A key learning was that this project required a dedicated and (com)passionate person with connections to national cancer charities. When designing the project, constant feedback is also needed from charities and young adults with and without radiotherapy experience. Finally, visually capturing discussions and keeping the door open beyond workshops further enhanced impact. Here, we hope to inform and inspire people to help project the patient voice in all we do.

Integrated supervised consumption services and hepatitis C testing and treatment among people who inject drugs in Toronto, Canada: A cross-sectional analysis.

Despite the availability of publicly funded hepatitis C (HCV) treatment in Canada, treatment gaps persist, particularly among people who inject drugs. We estimate correlates of HCV care cascade engagement (testing, diagnosis, and treatment) among people who inject drugs in Toronto, Canada and examine the effect of accessing differing supervised consumption service (SCS) models on self-reported HCV testing and treatment. This is a cross-sectional baseline analysis of 701 people who inject drugs surveyed in the Toronto, Ontario integrated Supervised Injection Services (OiSIS-Toronto) study between November 2018 and March 2020. We examine correlates of self-reported HCV care cascade outcomes including SCS model, demographic, socio-structural, drug use, and harm reduction characteristics. Overall, 647 participants (92%) reported ever receiving HCV testing, of whom 336 (52%) had been diagnosed with HCV. Among participants who reported ever being diagnosed with HCV, 281 (84%) reported chronic HCV, of whom 130 (46%) reported HCV treatment uptake and 151 (54%) remained untreated. Compared to those with no SCS use, participants who had ever injected at an integrated SCS model with co-located HCV care had greater prevalence of both ever receiving HCV testing (adjusted prevalence ratio [aPR]: 1.12, 95% confidence interval [CI]: 1.02-1.24) and ever receiving HCV treatment (aPR: 1.67, 95% CI: 1.04-2.69). Over half of participants diagnosed with chronic HCV reported remaining untreated. Our findings suggest that integrated SCS models with co-located HCV care represent key strategies for linkage to HCV care, but that more is needed to support scale-up.

Impact of direct-acting antiviral treatment on health utility in patients with chronic hepatitis C in hospital and community settings.

BACKGROUND: Direct-acting antiviral agents (DAAs) have transformed chronic hepatitis C (CHC) treatment. Continued affordable access to DAAs requires updated cost-effectiveness analyses (CEA). Utility is a preference-based measure of health-related quality of life (HRQoL) used in CEA. This study evaluated the impact of DAAs on utilities for patients with CHC in two clinical settings. METHODS: This prospective longitudinal study included patients aged ≥18 years, diagnosed with CHC and scheduled to begin DAA treatment, from two tertiary care hospital clinics and four community clinics in Toronto, Calgary, and Montreal. Patients completed two utility instruments (EQ-5D-5L and Health Utilities Index 2/3 (HUI2/3)) before treatment, 6 weeks after treatment initiation, and 12 weeks and 1 year after treatment completion. We measured utilities for all patients, and for hospital-based and community-based groups. RESULTS: Between 2017 and 2020, 209 patients (126 hospital-based, 83 community-based; average age 53 years; 65% male) were recruited, and 143 completed the 1-year post-treatment assessment. Pre-treatment, utilities were (mean ± standard deviation) 0.77 ± 0.21 (EQ-5D-5L), 0.69 ± 0.24 (HUI2) and 0.58 ± 0.34 (HUI3). The mean changes at 1-year post-treatment were 0.035, 0.038 and 0.071, respectively. While utilities for hospital-based patients steadily improved, utilities for the community-based cohort improved between baseline and 12-weeks post-treatment, but decreased thereafter. DISCUSSION: This study suggests that utilities improve after DAA treatment in patients with CHC in a variety of settings. However, community-based patients may face challenges related to comorbid health and social conditions that are not meaningfully addressed by treatment. Our study is essential for valuing health outcomes in CHC-related CEA.

Outcome of an elective readmission policy in patients receiving acute myeloid leukaemia consolidation therapy and implications for an outpatient management programme.

Safe outpatient management of acute leukaemia consolidation cycles may enable substantial savings in admission costs. Safety involves the prompt administration of antibiotics in patients with neutropenic fever. Our unit in a metropolitan tertiary referral hospital analysed a cohort of patients spanning a 10-year period, with two key observations: (i) a high proportion of patients living a substantial distance from hospital and (ii) the high incidence and generally prompt onset of fever after severe neutropenia, suggesting this broad applicability of this approach is unfeasible without addressing travel issues and potentially reducing and/or delaying neutropenic fever with prophylactic antibiotics.

Predictors and outcomes of dose reduction of methotrexate and cyclosporin graft-versus-host disease prophylaxis following allogeneic haemopoietic cell transplantation.

BACKGROUND: Concern regarding dose-related toxicities of methotrexate (MTX) and cyclosporin (CYA) graft-versus-host disease (GVHD) prophylaxis occasionally leads to dose alterations post allogeneic haemopoietic cell transplant (alloHCT). AIMS: To clarify causes of MTX and CYA dose alteration and assess impact on patient outcomes, including GVHD, relapse, non-relapse mortality (NRM) and overall survival (OS). METHODS: Analysis of retrospective data was performed in a single tertiary centre of patients who underwent alloHCT for any indication and who received GVHD prophylaxis with CYA and MTX between the years 2011 and 2015. Univariate analysis was conducted using the log-rank test for OS and using competing risk regression for NRM, relapse and GVHD. Fisher exact tests were used to determine if an association existed between each of the pre-transplant variables and MTX alteration. Multivariate models for OS and NRM were constructed using Cox proportional hazards modelling and competing risk regression respectively. RESULTS: Fifty-four (28%) of 196 had MTX alterations and 61/187 (33%) had CYA alterations. Reasons for MTX alteration included mucositis, renal or liver impairment, fluid overload and sepsis. Causes of CYA alteration were numerous, but most commonly due to acute kidney impairment. MTX alteration was associated with inferior OS (hazard ratio 2.4; P = <0.001) and higher NRM (odds ratio (OR) 4.6; P < 0.001) at 6 years post-landmark. CYA alteration was associated with greater NRM (OR 2.7; P = 0.0137) at 6 years. GVHD rates were unaffected by dose alteration. CONCLUSIONS: Our findings suggest dose alteration in MTX and CYA GVHD prophylaxis is associated with adverse survival outcomes in alloHCT, without a significant impact on GVHD rates.

Mental health impact of cuts to local government spending on cultural, environmental and planning services in England: a longitudinal ecological study.

BACKGROUND: Over the past decade, there have been significant and unequal cuts to local authority (LA) budgets, across England. Cultural, environmental and planning (CEP) budgets have been cut by 17% between 2011 and 2019. This funding supports services such as parks, leisure centres, community development and libraries, all of which have potential to influence population mental health. We therefore investigated whether cuts to CEP services have affected mental health outcomes and the extent to which they have contributed to mental health inequalities between areas. METHODS: Using fixed effects regression applied to longitudinal LA-level panel data in England, we assessed whether trends in CEP spend were associated with trends in mental health outcomes, between 2011 and 2019. The exposure was CEP spend and the primary outcome was the LA-average Small Area Mental Health Index (SAMHI). Additionally, we considered subcategories of CEP spend as secondary exposures, and antidepressant prescription rate and self-reported anxiety levels as secondary outcomes, both aggregated to LA-level. We adjusted all models for confounders and conducted subgroup analysis to examine differential mental health effects of spending cuts based on the level of area deprivation. RESULTS: The average decrease in CEP spend of 15% over the period was associated with a 0.036 (95% CI: 0.005, 0.067) increase in SAMHI score, indicating worsening mental health. Amongst subcategories of CEP spending, cuts to planning and development services impacted mental health trends the most, with a 15% reduction in spend associated with a 0.018 (95% CI: 0.005, 0.031) increase in the SAMHI score. The association between cuts in CEP and deteriorating mental health was greater in more affluent areas. CONCLUSION: Cuts to spending on cultural, environmental, planning and development services were associated with worsening population mental health in England. Impacts were driven by cuts to planning and development services in particular. Reinvesting in these services may contribute to improved public mental health.

Inequalities in local government spending on cultural, environmental and planning services: a time-trend analysis in England, Scotland, and Wales.

BACKGROUND: Local government provides Cultural, Environmental, and Planning (CEP) services, such as parks, libraries, and waste collection, that are vital for promoting health and wellbeing. There have been significant changes to the funding of these services over the past decade, most notably due to the UK government's austerity programme. These changes have not affected all places equally. To understand potential impacts on health inequalities, we investigated geographical patterning of recent CEP spending trends. METHODS: We conducted a time trend analysis using routinely available data on local government expenditure. We used generalised estimating equations to determine how expenditure trends varied across 378 local authorities (LAs) in Great Britain between 2009/10 and 2018/19 on the basis of country, deprivation, rurality, and local government structure. We investigated the gross expenditure per capita on CEP services, and the CEP expenditure as a proportion of total local authority budgets. We present the estimated annual percentage change in these spend measures. RESULTS: Expenditure per capita for CEP services reduced by 36% between 2009/10 and 2018/19. In England, the reduction in per capita spending was steepest in the most deprived quintile of areas, falling by 7.5% [95% CI: 6.0, 8.9] per year, compared to 4.5% [95% CI: 3.3, 5.6] per year in the least deprived quintile. Budget cuts in Scotland and Wales have been more equitable, with similar trends in the most and least deprived areas. Welsh LAs have reduced the proportion of total LA budget spent on CEP services the most (-4.0% per year, 95% CI: -5.0 to -2.9), followed by Scotland (-3.0% per year, 95% CI: -4.2 to -1.7) then England (-1.4% per year, 95% CI: -2.2 to -0.6). In England, rural and unitary LAs reduced their share of spending allocated to CEP more than urban and two-tier structured LAs, respectively. CONCLUSION: Funding for cultural, environmental and planning services provided by local government in the UK has been cut dramatically over the last decade, with clear geographical inequalities. Local areas worst affected have been those with a higher baseline level of deprivation, those with a single-tier local government structure, and English rural local authorities. The inequalities in cuts to these services risk widening geographical inequalities in health and wellbeing.

Disadvantage in early-life and persistent asthma in adolescents: a UK cohort study.

OBJECTIVE: To determine how early-life risk factors explain socioeconomic inequalities in persistent asthma in adolescence. METHODS: We did a causal mediation analysis using data from 7487 children and young people in the UK Millennium Cohort Study. Persistent asthma was defined as having a diagnosis reported at any two or more time points at 7, 11 or 14 years. The main exposure was maternal education, a measure of early-life socioeconomic circumstances (SECs), used to calculate the relative index of inequality. We assessed how blocks of perinatal (maternal health behaviours, infant characteristics and duration of breastfeeding, measured at 9 months) and environmental risk factors (family housing conditions; potential exposure to infections through childcare type and sibling number, and neighbourhood characteristics, measured at 3 years) mediated the total effect of childhood SECs on persistent asthma risk, calculating the proportion mediated and natural indirect effect (NIE) via blocks of mediators. RESULTS: At age 14 the overall prevalence of persistent asthma was 15%. Children of mothers with lower educational qualifications were more likely to have persistent asthma, with a clear social gradient (degree plus: 12.8% vs no qualifications: 20.3%). The NIE gives the effect of SECs acting only via the mediators and shows a 31% increased odds of persistent asthma when SECs are fixed at the highest level, and mediators at the level which would naturally occur at the lowest SECs versus highest SECs (NIE OR 1.31, 95% CI 1.04 to 1.65). Overall, 58.9% (95% CI 52.9 to 63.7) of the total effect (OR 1.70, 95% CI 1.20 to 2.40) of SECs on risk of persistent asthma in adolescence was mediated by perinatal and environmental characteristics. CONCLUSIONS: Perinatal characteristics and the home environment in early life are more important in explaining socioeconomic inequalities in persistent asthma in British adolescents than more distal environmental exposures outside the home.

Neighborhood environment and socioeconomic inequalities in cancer admissions: a prospective study using UK Biobank and linked hospital records.

PURPOSE: Neighborhood environments may influence cancer risk. Average population effect estimates might mask differential effects by socioeconomic position. Improving neighborhood environments could inadvertently widen health inequalities if important differences are overlooked. METHODS: Using linked records of hospital admissions in UK Biobank, we assessed associations between admission with a primary diagnosis of cancer (any/breast/colorectal), and exposure to neighborhood greenspace, physical activity facilities, and takeaway food stores, and whether household income and area deprivation modify these associations. We used adjusted Cox proportional hazards models, and estimated relative excess risks due to interaction (RERI) to assess effect modification. RESULTS: Associations between neighborhood exposures and cancer-related hospitalizations were weak to null overall, but with some evidence of effect modification. Most notably, more greenspace near home was associated with 16% lower hazard of cancer-related hospital admission in deprived areas (95% CI 2-29%). This was further pronounced for people in low-income households in deprived areas, and for breast cancer. CONCLUSION: In deprived neighborhoods, increasing the amount of greenspace may help reduce cancer-related hospitalizations. Examining effect modification by multiple socioeconomic indicators can yield greater insight into how social and environmental factors interact to influence cancer incidence. This may help avoid perpetuating cancer inequalities when designing neighborhood environment interventions.

Time Costs and Out-of-Pocket Costs in Patients With Chronic Hepatitis C in a Publicly Funded Health System.

OBJECTIVES: Chronic hepatitis C (CHC) infection affects more than 70 million people worldwide and imposes considerable health and economic burdens on patients and society. This study estimated 2 understudied components of the economic burden, patient out-of-pocket (OOP) costs and time costs, in patients with CHC in a tertiary hospital clinic setting and a community clinic setting. METHODS: This was a multicenter, cross-sectional study with hospital-based (n = 174) and community-based (n = 101) cohorts. We used a standardized instrument to collect healthcare resource use, time, and OOP costs. OOP costs included patient-borne costs for medical services, nonprescription drugs, and nonmedical expenses related to healthcare visits. Patient and caregiver time costs were estimated using an hourly wage value derived from patient-reported employment income and, where missing, derived from the Canadian census. Sensitivity analysis explored alternative methods of valuing time. Costs were reported in 2020 Canadian dollars. RESULTS: The mean 3-month OOP cost was $55 (95% confidence interval [CI] $21-$89) and $299 (95% CI $170-$427) for the community and hospital cohorts, respectively. The mean 3-month patient time cost was $743 (95% CI $485-$1002) (community) and $465 (95% CI $248-$682) (hospital). The mean 3-month caregiver time cost was $31 (95% CI $0-$63) (community) and $277 (95% CI $174-$380) (hospital). Patients with decompensated cirrhosis bore the highest costs. CONCLUSIONS: OOP costs and patient and caregiver time costs represent a considerable economic burden to patient with CHC, equivalent to 14% and 21% of the reported total 3-month income for the hospital-based and community-based cohorts, respectively.

Service utilization patterns and characteristics among clients of integrated supervised consumption sites in Toronto, Canada.

INTRODUCTION: Supervised consumption services (SCS), intended to reduce morbidity and mortality among people who inject drugs, have been implemented in a variety of delivery models. We describe and compare access to and uptake of co-located and external services among clients accessing harm reduction-embedded (HR-embedded) and community health center-embedded (CHC-embedded) SCS models. METHODS: Cross-sectional baseline data were collected between November 2018 and March 2020 as part of a cohort of people who inject drugs in Toronto, Canada designed to evaluate one HR-embedded and two CHC-embedded SCS. This analysis was restricted to clients who reported accessing these SCS more than once in the previous 6 months. Participants were classified as HR-embedded or CHC-embedded SCS clients based on self-reported usage patterns. Client characteristics, as well as access to onsite services and referral and uptake of external services, were compared by SCS model. RESULTS: Among 469 SCS clients, 305 (65.0%) primarily used HR-embedded SCS and 164 (35.0%) primarily used CHC-embedded SCS. Compared to clients accessing CHC-embedded SCS, clients accessing HR-embedded SCS were somewhat younger (37.6 vs. 41.4, p < 0.001), more likely to report fentanyl as their primary injected drug (62.6% vs. 42.7%, p < 0.001), and visited SCS more often (49.5% vs. 25.6% ≥ daily, p < 0.001). HR-embedded SCS clients were more likely to access harm reduction services onsite compared to CHC-embedded SCS clients (94.8% vs. 89.6%, p = 0.04), while CHC-embedded SCS clients were more likely to access non-harm reduction services onsite (57.3% vs. 26.6%, p < 0.001). For external services, HR-embedded SCS clients were more likely to receive a referral (p = 0.03) but less likely to report referral uptake (p = 0.009). CONCLUSIONS: Clients accessing HR-embedded and CHC-embedded SCS were largely demographically similar but had different drug and SCS use patterns, with CHC-embedded SCS clients using the site less frequently. While clients of CHC-embedded SCS reported greater access to ancillary health services onsite, external service use remained moderate overall, underscoring the importance of co-location and support for clients with system navigation. Importantly, lack of capacity in services across the system may impact ability of staff to make referrals and/or the ability of clients to take up a referral.

The Ontario Integrated Supervised Injection Services Cohort Study of People Who Inject Drugs in Toronto, Canada (OiSIS-Toronto): Cohort Profile.

The Ontario Integrated Supervised Injection Services cohort in Toronto, Canada (OiSIS-Toronto) is an open prospective cohort of people who inject drugs (PWID). OiSIS-Toronto was established to evaluate the impacts of supervised consumption services (SCS) integrated within three community health agencies on health status and service use. The cohort includes PWID who do and do not use SCS, recruited via self-referral, snowball sampling, and community/street outreach. From 5 November 2018 to 19 March 2020, we enrolled 701 eligible PWID aged 18+ who lived in Toronto. Participants complete interviewer-administered questionnaires at baseline and semi-annually thereafter and are asked to consent to linkages with provincial healthcare administrative databases (90.2% consented; of whom 82.4% were successfully linked) and SCS client databases. At baseline, 86.5% of participants (64.0% cisgender men, median ([IQR] age= 39 [33-49]) had used SCS in the previous 6 months, of whom most (69.7%) used SCS for <75% of their injections. A majority (56.8%) injected daily, and approximately half (48.0%) reported fentanyl as their most frequently injected drug. As of 23 April 2021, 291 (41.5%) participants had returned for follow-up. Administrative and self-report data are being used to (1) evaluate the impact of integrated SCS on healthcare use, uptake of community health agency services, and health outcomes; (2) identify barriers and facilitators to SCS use; and (3) identify potential enhancements to SCS delivery. Nested sub-studies include evaluation of "safer opioid supply" programs and impacts of COVID-19.

Mental health and prolonged exposure to unaffordable housing: a longitudinal analysis.

PURPOSE: When housing is insufficient, or poor quality, or unaffordable there are well established health effects. Despite the pervasiveness of housing affordability problems (widely referred to as Housing Affordability Stress-HAS), little quantitative work has analysed long-term mental health effects. We examine the mental health effects of (prolonged and intermittent) patterns of exposure to housing affordability problems. METHODS: We analysed a large, nationally representative longitudinal population sample of individuals, following them over five-year periods to assess the relative mental health effects of different patterns of exposure to housing affordability problems. To maximise the number of observations and the robustness of findings, we used 15 years (2002-2016) of data, across three pooled exposure windows. Longitudinal regression analysis with Mundlak adjustment was used to estimate the association between prolonged (constant over a 5-year period) and intermittent exposure to HAS, and mental health (as measured using the SF-36 MCS). RESULTS: We found that, on average, both prolonged and intermittent exposure were associated with lower mental health (Beta = - 1.338 (95% CI - 2.178-0.488) and Beta = - 0.516 (95% CI - 0.868-0.164), respectively). When we additionally adjusted for baseline mental health, thereby accounting for initial mental health status, coefficients were attenuated but remained significant. CONCLUSIONS: Both prolonged and intermittent exposure to HAS negatively impact mental health, irrespective of baseline mental health. Interventions that target affordable housing would benefit population mental health. Mental health interventions should be designed with people's housing context in mind.

Mobilizing a Whole Community: Policy and Strategy Implications of an Integrated Local System Response to a Global Health Crisis.

The East Toronto Health Partners (ETHP) include more than 50 organizations working collaboratively to create an integrated system of care in the east end of Toronto. This existing partnership proved invaluable as a platform for a rapid, coordinated local response to the COVID-19 pandemic. Months after the first wave of the pandemic began, with the daily numbers of COVID-19 cases finally starting to decline, leaders from ETHP provided preliminary reflections on two critical questions: (1) How were existing integration efforts leveraged to mobilize a response during the COVID-19 crisis? and (2) How can the response to the initial wave of COVID-19 be leveraged to further accelerate integration and better address subsequent waves and system improvements once the pandemic abates?

Responses to a Social Media Campaign Promoting Safe Fish Consumption Among Women.

We used a framework to systematically evaluate which Facebook advertisements promoting safe fish consumption increased traffic to our website. Keeping images and headlines constant, we tested 11 message types in 5 categories between 2 audiences over a 24-hour weekday period. We identified clear preferences in 9 of 10 comparisons and evidence to suggest that more women prefer presentation of question format compared with narratives, marketing compared with patient education copy, and uncertain compared with certain copy. Our test of messages on a social media platform is a quick and inexpensive way to select the most engaging public health messages for broad dissemination.

Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse.

BACKGROUND/AIMS: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR. METHODS: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling. RESULTS: On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3-4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1-2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405). CONCLUSION: Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3-4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.

From client to co-worker: a case study of the transition to peer work within a multi-disciplinary hepatitis c treatment team in Toronto, Canada.

BACKGROUND: Despite the integration of peer workers into harm reduction services, there is little documentation regarding the experience of this integration or of models in which peers are fully integrated as members of health care teams. The purpose of this study was to gain an in-depth understanding of the transition from client to support worker from the perspective of two individuals who received treatment for hepatitis C at a multi-disciplinary, community-based program, grounded in a harm reduction approach to substance use. METHODS: A participatory case study design was selected. Interviews were conducted with two current peer workers who were also involved in the study design, analysis and writing. Data was coded and analyzed using an inductive approach to identify emergent themes. RESULTS: Five primary themes emerged during our analysis of the facilitators and challenges of the transition from client to support worker: (1) the role of prior experience, (2) changes in substance use practices, (3) shifts in relationships with community members and friends, (4) supportive organizational and structural factors, and (5) role transition as a journey. In some cases, themes overlapped and contained elements that were both facilitating and challenging. CONCLUSIONS: The transition from client to co-worker is a gradual process and one that is supported by, and in turn helps to support, a number of other personal transitions. The cases examined here suggest that a model of peer employment with broad qualification criteria, sufficient transition timelines, flexible job responsibilities, a solid investment in the inclusion of people with lived experience, and a harm reduction framework will support successful integration of current and/or former clients into health care teams.

Prognostic Limitations of Donor T Cell Chimerism after Myeloablative Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Donor T cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients and determined its sensitivity and specificity for relapse-free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT. The area under the receiver operating characteristic curve for RFS6 was .68, demonstrating only modest utility as a predictive biomarker, although this was greater than RFS12 at .62. Using a D100chim threshold of 65%, the specificity for RFS6 was 96.6%; however, sensitivity was poor at 26.7%. This equated to a negative predictive value of 88.5% and positive predictive value of 57.1%. Changing the threshold for D100chim to 75% or 85% modestly improved the sensitivity of D100chim for RFS6; however, this was at the expense of specificity. D100chim is specific but lacks sensitivity as a prognostic biomarker of early RFS after myeloablative alloSCT for AML or MDS. Caution is required when using D100chim to guide treatment decisions including immunologic manipulation, which may expose patients to unwarranted graft-versus-host disease.

Effect of scattered-site housing using rent supplements and intensive case management on housing stability among homeless adults with mental illness: a randomized trial.

IMPORTANCE: Scattered-site housing with Intensive Case Management (ICM) may be an appropriate and less-costly option for homeless adults with mental illness who do not require the treatment intensity of Assertive Community Treatment. OBJECTIVE: To examine the effect of scattered-site housing with ICM services on housing stability and generic quality of life among homeless adults with mental illness and moderate support needs for mental health services. DESIGN, SETTING, AND PARTICIPANTS: The At Home/Chez Soi project was an unblinded, randomized trial. From October 2009 to July 2011, participants (N = 1198) were recruited in 4 Canadian cities (Vancouver, Winnipeg, Toronto, and Montreal), randomized to the intervention group (n = 689) or usual care group (n = 509), and followed up for 24 months. INTERVENTIONS: The intervention consisted of scattered-site housing (using rent supplements) and off-site ICM services. The usual care group had access to existing housing and support services in their communities. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of days stably housed during the 24-month period following randomization. The secondary outcome was generic quality of life, assessed by a EuroQoL 5 Dimensions (EQ-5D) health questionnaire. RESULTS: During the 24 months after randomization, the adjusted percentage of days stably housed was higher among the intervention group than the usual care group, although adjusted mean differences varied across sites. [table: see text] The mean change in EQ-5D score from baseline to 24 months among the intervention group was not statistically different from the usual care group (60.5 [95%CI, 58.6 to 62.5] at baseline and 67.2 [95%CI, 65.2 to 69.1] at 24 months for the intervention group vs 62.1 [95% CI, 59.9 to 64.4] at baseline and 68.6 [95%CI, 66.3 to 71.0] at 24 months for the usual care group, difference in mean changes, 0.10 [95%CI, −2.92 to 3.13], P=.95). CONCLUSIONS AND RELEVANCE: Among homeless adults with mental illness in 4 Canadian cities, scattered site housing with ICM services compared with usual access to existing housing and community services resulted in increased housing stability over 24 months, but did not improve generic quality of life. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN42520374.

Breast cancer screening of women aged 70-74 years: results from a natural experiment across Australia.

There is a lack of evidence regarding the optimal age at which to cease mammographic screening for breast cancer. This ecological study compared Australian state and territory level screening participation rates and cancer outcomes from 1996 to 2005 to identify the extent to which screening women aged 70-74 results in smaller, earlier stage breast cancers. With each 10 % absolute increase in screening participation, there was no significant difference in cancer incidence, but the incidence of large cancers was 8 % lower (IRR = 0.92, 95 % CI 0.90-0.94, p < 0.001); there was some evidence of reduced nodal involvement at diagnosis (IRR 0.97, 95 % CI 0.95-0.99, p = 0.004) but this estimate was sensitive to assumptions regarding missing data. Increased mammographic screening of women aged 70-74 years reduces the incidence of large (>15 mm) cancers-and possibly cancers with nodal involvement-without a concomitant increase in overall cancer incidence.