Patient reported outcome measures (PROMs) in Radiotherapy: Qualitative results of a survey of healthcare professionals

Background: Radiotherapy provides an effective treatment modality in the management of various malignancies. However, many patients develop acute and long-term toxicities that present a significant burden to their quality of life1,2. Such toxicities are often underreported by clinicians, and therefore patient-reported outcome measures(PROMs) present a more robust assessment3. Despite the clear advantages of PROMs including stratified follow-up and evaluation of clinical effectiveness, safety and cost, barriers exist at patient, healthcare professional(HCP) and service levels3,4. Most commonly, perceived lack of time/PROMs training for HCPS, poor IT infrastructure and lack of PROMs integration into existing systems create barriers3. The NHS England Radiotherapy Service Specification calls for routine use of PROMS, which requires effective implementation within radiotherapy5. Several ‘enablers’ to PROMs implementation have been identified, including use of electronic PROMs, automatic data interpretation and HCP training3,4,6. This study aimed to identify current PROMs use within radiotherapy nationally, to evaluate current attitudes, barriers and enablers to PROMs use, and to develop practical recommendations to implement PROMs within UK radiotherapy services. The qualitative findings are presented here. Methods: An e-questionnaire consisting of 12 open and multiple-choice questions was developed. The questionnaire was piloted by radiotherapy professionals, and disseminated via email across all radiotherapy operational delivery network(ODN) managers, covering the entirety of England. 182 participants were recruited across a range of professions including therapeutic radiographers, nurses and researchers. A mixed-methods approach was utilised; thematic analysis of free-text responses provided qualitative data, whilst statistical analysis was performed on quantitative results. Results: Inductive thematic analysis of questionnaire responses resulted in identification of key themes related to the barriers and enablers of PROMs use within radiotherapy. Interestingly, identical themes emerged associated with participants’ perceptions of both barriers/enablers, with an additional theme identified pertaining to potential enablers of PROMs: Barriers - Themes: 1. I.T. Infrastructure 2. Time 3. Resources(Human/Financial) 4. Training/Education Enablers - Themes: 1. I.T. Infrastructure 2. Time 3. Resources(Human/Financial) 4. Training/Education 5. Standardisation Conclusion: Our findings further demonstrate the paucity of routine PROMs use within radiotherapy. Here, we provide recommendations to mitigate barriers and implement PROMs; such steps include HCP training on PROMs and development/integration of electronic systems. Standardisation of PROMs tools and centralised data storage is essential to assessing radiotherapy toxicity data nationally and informing practice. Referral pathways to existing specialist services are fundamental to ensuring PROMs data are used meaningfully. This study provides an important first step in driving PROMs implementation within UK radiotherapy services. References 1. Miller, K., Nogueira, L., Mariotto, A., Rowland, J., Yabroff, R., Alfano, C., et al. (2019). Cancer treatment and survivorship statistics 2019. CA: A Cancer Journal For Clincians. https://doi.org/10.3322/caac.21565 2. Macmillan Cancer Support. Cured – but at what cost? Long-term consequences of cancer and its treatment. [ Internet] (2013). Available at: https://www.macmillan.org.uk/documents/aboutus/newsroom/consequences_of_treatment_june2013.pdf [Accessed online 28th March 2021]. 3. Nguyen, H., Butow, P., Dhillon, H. & Sundaresan, P. (2020a). A review of the barriers to using Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs) in routine cancer care. Journal of Medical Radiation Sciences. 00, 1-10. Doi: 10.1002/jmrs.421 4. Kingsley, C. & Patel, S. (2017). Patient-reported outcome measures and patient-reported experience measures. British Journal of Anaesthesia. 17, 137-144. doi: 10.1093/bjaed/mkw060 5. National Health Service (NHS) England (2019). Service Specification 170091S: Adult External Beam Radiotherapy Services Delivered as Part of a Radiotherapy Network. Available at: https://www.england.nhs.uk/wp-content/uploads/2019/01/External-Beam-Radiotherapy-Services-Delivered-as-Part-of-a-Radiotherapy-Network-Adults.pdf [Accessed online 10th April 2021]. 6. Howell, D., Molloy, S., Wilkinson, K., Green, E., Orchard, K., Wang, K. & Liberty, J. (2015). Patient-reported outcomes in routine cancer clinical practice: a scoping review of use, impact on health outcomes, and implementation factors. Annals of Oncology. 26, 1846-1858. doi: 10.1093/annonc/mdv18

Oral rehydration therapies in Senegal, Mali, and Sierra Leone: A spatial analysis of changes over time and implications for policy

Background: Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes.Methods: We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access.Results: We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children.Conclusions: Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas

Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

Objective: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown. Methods: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (,8), medium (8-9), or high (.9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up. Results: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). Conclusions: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions

Earliest rock fabric formed in the Solar System preserved in a chondrule rim

Rock fabrics – the preferred orientation of grains – provide a window into the history of rock formation, deformation and compaction. Chondritic meteorites are among the oldest materials in the Solar System1 and their fabrics should record a range of processes occurring in the nebula and in asteroids, but due to abundant fine-grained material these samples have largely resisted traditional in situ fabric analysis. Here we use high resolution electron backscatter diffraction to map the orientation of sub-micrometre grains in the Allende CV carbonaceous chondrite: the matrix material that is interstitial to the mm-sized spherical chondrules that give chondrites their name, and fine-grained rims which surround those chondrules. Although Allende matrix exhibits a bulk uniaxial fabric relating to a significant compressive event in the parent asteroid, we find that fine-grained rims preserve a spherically symmetric fabric centred on the chondrule. We define a method that quantitatively relates fabric intensity to net compression, and reconstruct an initial porosity for the rims of 70-80% - a value very close to model estimates for the earliest uncompacted aggregates2,3. We conclude that the chondrule rim textures formed in a nebula setting and may therefore be the first rock fabric to have formed in the Solar System

Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742

Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study

Molly Franke, Megan Murray, and colleagues report that early cART reduces mortality among HIV-infected adults with tuberculosis and improves retention in care, regardless of CD4 count

Using observational data to emulate a randomized trial of dynamic treatment switching strategies

BACKGROUND: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).METHODS: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.RESULTS: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.CONCLUSIONS: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses

Oral rehydration therapies in Senegal, Mali, and Sierra Leone: a spatial analysis of changes over time and implications for policy.

BACKGROUND: Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes. METHODS: We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access. RESULTS: We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children. CONCLUSIONS: Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas

Long-term genetic consequences of mammal reintroductions into an Australian conservation reserve

Available online 05 January 2018Reintroduction programs aim to restore self-sustaining populations of threatened species to their historic range. However, demographic restoration may not reflect genetic restoration, which is necessary for the long-term persistence of populations. Four threatened Australian mammals, the greater stick-nest rat (Leporillus conditor), greater bilby (Macrotis lagotis), burrowing bettong (Bettongia lesueur) and western barred bandicoot (Perameles bougainville), were reintroduced at Arid Recovery Reserve in northern South Australia over the last 18 years. These reintroductions have been deemed successful based on population growth and persistence, however the genetic consequences of the reintroductions are not known. We generated large single nucleotide polymorphism (SNP) datasets for each species currently at Arid Recovery and compared them to samples collected from founders. We found that average genetic diversity in all populations at the Arid Recovery Reserve are close to, or exceeding, the levels measured in the founders. Increased genetic diversity in two species was achieved by admixing slightly diverged and inbred source populations. Our results suggest that genetic diversity in translocated populations can be improved or maintained over relatively long time frames, even in small conservation reserves, and highlight the power of admixture as a tool for conservation management.Lauren C. White, Katherine E. Moseby, Vicki A. Thomson, Stephen C. Donnellan, Jeremy J. Austi

Efavirenz versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes: A prospective study of HIV-positive individuals

Abstract Objective: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Design: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. Methods: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the “intention-to-treat” effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. Results: A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: −0.7%, 0.8%) and the AIDS-free survival difference was −0.3% (−1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm3 lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. Conclusion: Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival