Malnutrition and clinical outcomes post alloSCT.

BACKGROUND: Malnutrition has been linked with higher risk of poor outcomes post-allogeneic stem cell transplantation (alloSCT); however, few studies have used a validated nutrition assessment tool such as the Patient Generated Subjective Global Assessment (i.e., PG-SGA) to measure nutritional status and investigate associations with long-term clinical outcomes. The present study aimed to assess the incidence of malnutrition prior to alloSCT and determine whether there was an association between nutritional status pre-transplant and post-transplant clinical outcomes including acute kidney injury, graft-versus-host disease, intensive care admission, need for haemodialysis and survival. METHODS: A retrospective analysis of 362 patients (213 males:149 females, mean ± SD age = 47.8 ± 14.1 years) who underwent alloSCT from 2008 to 2013 was conducted. Data on clinical outcomes were obtained for 5 years post-transplant. RESULTS: Fifteen percent (n = 56) of patients were identified as malnourished pre-admission. Malnutrition was associated with longer hospital stay (p = 0.007), increased requirement for haemodialysis (p = 0.016) and increased admissions to the intensive care unit (p = 0.003). There was no association between malnutrition and acute kidney injury, graft-versus-host disease or survival. Following multivariate analyses, malnutrition remained significantly associated with increased admission rates to the intensive care unit (odds ratio = 3.8, 95% confidence interval = 1.3-10.5, p = 0.011) and increased length of hospital stay > 30 days (odds ratio = 3.6. 95% confidence interval = 1.8-7.4, p ≤ 0.001). CONCLUSIONS: These findings add importance to the need for nutrition screening and assessment to be routinely undertaken for patients prior to alloSCT and throughout hospitalisation to provide early nutrition intervention for the prevention of malnutrition, poor clinical outcomes and increased healthcare costs.

Navajo Nation Stores Show Resilience During COVID-19 Pandemic.

On April 8, 2020, the Navajo Nation issued an administrative order limiting business operations. Facing high coronavirus disease 2019 (COVID-19) rates and limited food infrastructure, a survey was conducted among Navajo Nation store managers to assess: (1) COVID-19 adaptations; (2) challenges; (3) changes in customer volume and purchasing; and (4) suggestions for additional support. Purposive sampling identified 29 stores in Navajo communities. Representatives from 20 stores (19 store managers/owners, 1 other; 7 grocery, and 13 convenience/other stores) were interviewed by phone or in-person to reach saturation (new information threshold < 5%). Responses were coded using frequencies and inductive thematic analysis. All 20 stores implemented COVID-19 guidelines (Centers for Disease Control and Prevention [CDC]/Navajo Nation) and most received orientation/support from local chapters, community organizations, or health centers. Stores implemented staff policies (50%, handwashing, vaccinations, protective personal equipment (PPE), sick leave, temperature checks), environmental changes (50%, hand sanitizer, checkout dividers), customer protocols (40%, limit customers, mask requirements, closed restrooms), and deep cleaning (40%). Most stores (65%) reported challenges including stress/anxiety, changing guidelines, supply chain and customer compliance; 30% reported infection or loss of staff. Weekday customer volume was slightly higher vs. pre-COVID, but weekend lower. Stores reported consistent or more healthy food purchases (50%), more nonfood essentials (20%), or shelf-stable foods (10%). Desired support included further orientation (30%), leadership support (20%), overtime/time to learn guidelines (20%), and signage/handouts (15%). Despite a high COVID-19 burden and limited food store infrastructure, Navajo Nation stores adapted by implementing staff, environmental and customer policies. Local support, staffing, and small store offerings were key factors in healthy food access.

Implementation of Indigenous Food Tax Policies in Stores on Navajo Nation.

In 2014, the Navajo Nation Healthy Diné Nation Act (HDNA) was enacted and permanently approved in 2020; HDNA places a 2% surtax on unhealthy foods and beverages, while other 2014 legislation exempted healthy food items from the 6% regular sales tax. Little is known about Navajo Nation store manager/owner perspectives toward the HDNA and how best to support stores to implement the legislation. Purposive sampling was used to ensure a balanced sample of correct HDNA implementers, incorrect HDNA implementers, and stores which made healthy store changes over the past 6 years. Three community-based interviewers collected surveys by phone or in-person. Frequency of closed-ended questions was quantified, and open-ended responses were coded using thematic analysis. Of 29 identified sample stores, 20 were interviewed to reach saturation. Eleven of 20 stores made changes improving their healthy food environments. Barriers included lack of equipment (6/20) and low consumer demand (5/20). Facilitators included consumer awareness and increased produce supply options (5/20). Sixteen of 20 stores supported HDNA continuation. Facilitators to HDNA implementation included orientation and informational materials (6/20) and promotion of tax-free items (5/20). Barriers included confusion about the tax (6/20) and tax exemption (5/20). Suggestions for support included printed materials (6/20) and store training (5/20). HDNA benefits included greater awareness of healthy choices among staff (7/20) and customer-community members (2/20). Most managers and owners expressed receiving support for healthy store changes and HDNA, but also identified a need for added resources and support. Findings inform legislative action to promote timely and appropriate uptake of HDNA, and support equitable, healthy food systems.

Shopper Purchasing Trends at Small Stores on the Navajo Nation since the Passage of the Healthy Diné Nation Act Tax: A Multi-Year Cross-sectional Survey.

Background: In 2014, the Navajo Nation passed the Healthy Diné Nation Act (HDNA), which applies an additional 2% tax on unhealthy foods and beverages and a waiver of Navajo sales tax on healthy foods and beverages. However, the HDNA's impact on purchasing behavior has not been explored. Objectives: We assessed beverage and produce purchasing trends among shoppers at small Navajo stores between 2017 and 2019, shopper characteristics associated with buying water, and whether HDNA awareness was associated with purchasing behaviors. Methods: A total of 332 shoppers at 34 stores in 2017 and 274 shoppers at 44 stores in 2019 were surveyed to assess HDNA awareness and same-day purchasing of water, sugar-sweetened beverages (SSBs), fruits, and vegetables. Hypotheses were tested using chi-square analyses and multivariate analysis. Results: Water purchasing among respondents increased significantly from 2017 to 2019 (24.4% to 32.8%; P = 0.03). Shoppers in 2019 were 1.5 times more likely to purchase water compared with 2017 (adjusted P = 0.01). There was a trend toward reduced SSB purchasing (85.8% in 2017, 80.3% in 2019, P = 0.068), while produce purchasing remained unchanged over time, at approximately 17%. Shoppers were more likely to buy water if they relied on that store for the majority of their groceries (P = 0.006) and if they did not have their own transportation to get to the store (P = 0.004). Most shoppers (56.6%) were aware of the HDNA; of these, 35.6% attributed healthier habits to the HDNA, most commonly buying more healthy drinks (49.2%), fewer unhealthy drinks (37.7%), more healthy snacks (31.1%), and fewer unhealthy snacks (26.2%). Conclusions: Shopper habits at small stores located on the Navajo Nation have shifted towards healthier purchasing from 2017 to 2019. Shoppers who were aware of the HDNA reported purchasing more healthy and fewer unhealthy food and drinks as a result of this legislation.

The improvement in overall survival from unrelated donor transplantation in Australia and New Zealand is driven by a reduction in non-relapse mortality: A study from the ABMTRR.

Unrelated donors (UDs) are the commonest source for allogeneic transplantation (alloSCT), with higher non-relapse mortality (NRM) than siblings. We analyzed data from the Australasian Bone Marrow Transplant Recipient Registry from adults receiving a first UD alloSCT during 2001-2015, to determine whether and how NRM has changed. Predictors of outcome were determined using cox regression, accounting for time-interactions and competing risks. A total of 2308 patients met inclusion criteria. Changes over time included increasing age, utilization of peripheral blood cells, reduced intensity conditioning, and T-cell depletion. Three-year OS increased significantly from 44% in 2001-2005 to 58% in 2011-2015 (p < 0.001). This was attributed to a reduction in NRM from 35% to 24% (p < 0.001) with no change in relapse. Factors associated with increased NRM included age, male sex, CMV seropositivity, HLA mismatch, transplant more than 6 months from diagnosis, and T-cell depletion when administered during 2001-2005. Survival following UD SCT has improved by almost 15% over the past decade, driven by improvements in NRM. This has occurred despite increasing recipient age and appears to be due to better donor selection, reduced delays to transplantation, and improved prevention and management of GVHD.

Bacterial Contact-Dependent Inhibition Protein Binds near the Open Lateral Gate in BamA Prior to Toxin Translocation.

Contact-dependent inhibition (CDI) is a mechanism of interbacterial competition in Gram-negative bacteria. The critical component of CDI systems is a large protein named CdiA; it forms a filament on the bacterial cell surface and contains a toxin domain at its C-terminal end. Upon binding to a receptor protein on the surface of a neighboring cell, CdiA delivers the toxin domain through the outer membrane of the neighboring bacterium. The mechanism of that delivery process is poorly understood. We have characterized how CdiA from E. coli EC93 binds to its receptor, BamA, to understand how this binding event might initiate the process of toxin delivery. BamA is an essential protein that assembles ß-barrel proteins into the outer membranes of all Gram-negative bacteria; this assembly process depends on BamA's unique ability to open laterally in the lipid bilayer through a gate in its own membrane-embedded ß-barrel. Through site-specific photo-cross-linking and mutational analysis, we demonstrate that the BamA-CdiA interaction depends on a small number of non-conserved amino acids on the extracellular surface of BamA, but the protein interface extends over a region near BamA's lateral gate. We further demonstrate that BamA's lateral gate can open without disrupting the interaction with CdiA. CdiA thus appears to initially engage BamA in a manner that could allow it to utilize BamA's lateral gate in subsequent steps in the toxin translocation process.

Changes in food pricing and availability on the Navajo Nation following a 2% tax on unhealthy foods: The Healthy Diné Nation Act of 2014.

INTRODUCTION: In 2014, the Navajo Nation Healthy Diné Nation Act (HDNA) was passed, combining a 2% tax on foods of 'minimal-to-no-nutritional value' and waiver of 5% sales tax on healthy foods, the first-ever such tax in the U.S. and globally among a sovereign tribal nation. The aim of this study was to measure changes in pricing and food availability in stores on the Navajo Nation following the implementation of the HDNA. METHODS: Store observations were conducted in 2013 and 2019 using the Nutrition Environment Measurement Survey-Stores (NEMS-S) adapted for the Navajo Nation. Observations included store location, type, whether healthy foods or HDNA were promoted, and availability and pricing of fresh fruits and vegetables, canned items, beverages, water, snacks and traditional foods. Differences between 2013 and 2019 and by store type and location were tested. RESULTS: The matched sample included 71 stores (51 in the Navajo Nation and 20 in border towns). In 2019, fresh produce was available in the majority of Navajo stores, with 71% selling at least 3 types of fruit and 65% selling at least 3 types of vegetables. Compared with border town convenience stores, Navajo convenience stores had greater availability of fresh vegetables and comparable availability of fresh fruit in 2019. The average cost per item of fresh fruit decreased by 13% in Navajo stores (from $0.88 to $0.76) and increased in border stores (from $0.63 to $0.73), resulting in comparable prices in Navajo and border stores in 2019. While more Navajo stores offered mutton, blue corn and wild plants in 2019 compared to 2013, these changes were not statistically significant. DISCUSSION: The findings suggest modest improvements in the Navajo store environment and high availability of fruits and vegetables. Navajo stores play an important role in the local food system and provide access to local, healthy foods for individuals living in this rural, tribal community.

A phase 3 double-blind study of the addition of tocilizumab vs placebo to cyclosporin/methotrexate GVHD prophylaxis.

We determined the efficacy of tocilizumab (TCZ) in preventing grade 2-4 acute graft-versus-host disease (aGVHD) in patients with acute leukemia or myelodysplasia undergoing matched sibling donor (MSD) or volunteer unrelated donor (VUD) allogeneic stem cell transplantation after myeloablative or reduced-intensity conditioning across 5 Australian centers. A total of 145 patients (50 MSD, 95 VUD) were randomly assigned to placebo or TCZ on day -1. All patients received T-cell-replete peripheral blood stem cell grafts and graft-versus-host disease (GVHD) prophylaxis with cyclosporin/methotrexate. A planned substudy analyzed the VUD cohort. With a median follow-up of 746 days, the incidence of grade 2-4 aGVHD at day 100 for the entire cohort was 36% for placebo vs 27% for TCZ (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.38-1.26; P = .23) and 45% vs 32% (HR, 0.61; 95% CI, 0.31-1.22; P = .16) for the VUD subgroup. The incidence of grade 2-4 aGVHD at day 180 for the entire cohort was 40% for placebo vs 29% for TCZ (HR, 0.68; 95% CI, 0.38-1.22; P = .19) and 48% vs 32% (HR, 0.59; 95% CI, 0.30-1.16; P = .13) for the VUD subgroup. Reductions in aGVHD were predominantly in grade 2 disease. For the entire cohort, transplant-related mortality occurred in 8% vs 11% of placebo-treated vs TCZ-treated patients, respectively (P = .56), and overall survival was 79% vs 71% (P = .27). Median day to neutrophil and platelet engraftment was delayed by 2 to 3 days in TCZ-treated patients, whereas liver toxicity and infectious complications were similar between groups. In this phase 3 randomized double-blind trial, TCZ showed nonsignificant trends toward reduced incidence of grade 2-4 aGVHD in recipients from HLA-matched VUDs but no improvements in long term-survival.

Successful implementation of the Healthy Diné Nation Act in stores on the Navajo Nation.

In 2014, the Navajo Nation Council passed the Healthy Diné Nation Act (HDNA), a 2% tax on unhealthy foods and beverages and a waiver of the 5% sales tax on healthy foods and water, to support health promotion and disease prevention among the Navajo people. Very little research has assessed implementation accuracy of food or beverage taxes and none were implemented within a sovereign Tribal nation. This study assessed the accuracy of HDNA tax implementation among 47 stores located on the Navajo Nation. A pair of tax-exempt items [e.g. a bottle of water and fresh fruit] and a pair of HDNA-tax eligible items [e.g. sugary beverage and candy bar] were purchased between July-December 2019. Receipts were retained to assess taxation. A total of 87.2% of stores accurately implemented the 2% tax on unhealthy items while 55.3% of the stores accurately implemented the 6% tax waiver on healthy items. In all, 51.1% of the stores accurately applied both taxes. There were no significant differences across store type (convenience or grocery stores and trading posts) or geographic region. In conclusion, almost all stores on the Navajo Nation accurately applied a 2% tax on unhealthy foods and beverages, while the proportion of stores applying a waiver on healthy foods was lower. Successful HDNA tax implementation among stores remains an important priority in achieving the goal to support health promotion and disease prevention among Navajo communities.

Community Outreach for Navajo People Living with Diabetes: Who Benefits Most?

INTRODUCTION: The Community Outreach and Patient Empowerment (COPE) intervention provides integrated outreach through community health representatives (CHRs) to people living with diabetes in Navajo Nation. The aim of this study was to identify groups for whom the intervention had the greatest effect on glycated hemoglobin A1c (HbA1c). METHODS: We analyzed de-identified data extracted from routine health records dated from December 1, 2010, through August 31, 2014, to compare net change in HbA1c among COPE patients and non-COPE patients. We used linear mixed models to assess whether the intervention was modified by age, sex, preferred language, having a primary care provider, baseline HbA1c, or having a mental health condition. RESULTS: Age, having a primary care provider, and baseline HbA1c significantly modified HbA1c levels. Among patients aged 64 or younger, COPE participation was associated with a net decrease in HbA1c of 0.77%; among patients aged 65 or older, the net decrease was 0.49% (P = .03). COPE participation was associated with a steeper decrease in HbA1c among patients without a primary care physician (net decrease, 0.99%) than among patients with a primary care provider (net decrease, 0.57%) (P = .03). COPE patients with a baseline HbA1c >9% had a net decrease of 0.70%, while those with a baseline HbA1c ≤9% had a net decrease of 0.34% (P = .01). We found no significant differences based on sex, preferred language, or having a mental health condition. CONCLUSION: Findings suggest that the COPE intervention was robust and equitable, benefiting all groups living with diabetes in Navajo Nation, but conferring the greatest benefit on the most vulnerable.

Community-based outreach associated with increased health utilization among Navajo individuals living with diabetes: a matched cohort study.

BACKGROUND: Navajo community members face high rates of diabetes mellitus and other chronic diseases. The Navajo Community Health Representative Outreach Program collaborated with healthcare providers and academic partners to implement structured and coordinated outreach to patients living with diabetes. The intervention, called Community Outreach and Patient Empowerment or COPE, provides home-based health coaching and community-clinic linkages to promote self-management and engagement in healthcare services among patients living with diabetes. The purpose of this study was to evaluate how outreach by Navajo Community Health Representatives ("COPE Program") affected utilization of health care services among patients living with diabetes. METHODS: De-identified data from 2010 to 2014 were abstracted from electronic health records at participating health facilities. In this observational cohort study, 173 cases were matched to 2880 controls. Healthcare utilization was measured as the number of times per quarter services were accessed by the patient. Changes in utilization over 4 years were modeled using a difference-in-differences approach, comparing the trajectory of COPE patients' utilization before versus after enrollment with that of the control group. The model was estimated using generalized linear mixed models for count outcomes, controlling for clustering at the patient level and the service unit level. RESULTS: COPE enrollees showed a 2.5% per patient per quarter (pppq) greater increase in total utilization (p = 0.001) of healthcare services than non-COPE enrollees; a 3.2% greater increase in primary care visits (p = 0.024); a 6.3% greater increase in utilization of counseling and behavioral health services (p = 0.013); and a 9.0% greater increase in pharmacy visits (p <  0.001). We found no statistically significant differences in utilization trends of inpatient, emergency room, specialty outpatient, dental, laboratory, radiology, or community encounter services among COPE participants versus control. CONCLUSIONS: A structured intervention consisting of Community Health Representative outreach and coordination with clinic-based providers was associated with a modest increase in health care utilization, including primary care and counseling services, among Navajo patients living with diabetes. Community health workers may provide an important linkage to enable patients to access and engage in clinic-based health care. TRIAL REGISTRATION: NCT03326206, registered 10/31/2017, retrospectively registered.

Community-clinic linkages: qualitative provider perspectives on partnering with community health representatives in Navajo Nation.

OBJECTIVE: To understand providers' opinions about the Community Outreach and Patient Empowerment (COPE) Project designed to strengthen Navajo Community Health Representative (CHR) outreach to individuals living with diabetes. DESIGN: This was a qualitative study nested within a larger evaluation of a programme intervention. SETTING: The study took place in Navajo Nation and evaluated a programme initiative designed to strengthen collaboration between CHRs and clinic-based healthcare providers and provide structured outreach to individuals living with diabetes in Navajo Nation. The CHR Programme is a formal community health worker programme that exists in most tribal healthcare systems across the USA. PARTICIPANTS: Healthcare providers involved in the programme took part in one-on-one interviews. ANALYSIS: We used thematic analysis for this study. A team of three study staff used open-coding to create a codebook. Coded material were summarised and patterns were identified and tied into a narrative using concept mapping. The study design and instrument construction were guided by a Community Health Advisory Panel. RESULTS: A total of 13 interviews were completed. Providers acknowledged CHRs as an asset to the clinical team and were enthusiastic about the COPE coaching materials, mentioning they provided a consistent message to CHRs and the community. Providers that led COPE trainings with CHRs valued the face-to-face time and opportunity to build relationships. Providers (n=4) supported CHRs' access to electronic health record to record patient visits and streamline referrals. Among their requests were having designated personnel to manage referrals with CHRs and a formal system to record modules CHRs have completed. CONCLUSION: Providers participating in COPE activities valued the work of CHRs and endorsed further strengthening relationships and communication with CHRs. Healthcare programmes should consider systems changes to integrate community health workers into clinic-based teams. TRIAL REGISTRATION NUMBER: NCT03326206; Results.

Qualitative evaluation of a community health representative program on patient experiences in Navajo Nation.

BACKGROUND: Community Health Representatives (CHRs) overcome health disparities in Native communities by delivering home care, health education, and community health promotion. The Navajo CHR Program partners with the non-profit Community Outreach and Patient Empowerment (COPE), to provide home-based outreach to Navajo clients living with diabetes. COPE has created an intervention (COPE intervention) focusing on multiple levels of improved care including trainings for CHRs on Motivational Interviewing and providing CHRs with culturally-appropriate education materials. The objective of this research is to understand the participant perspective of the CHR-COPE collaborative outreach through exploring patient-reported outcomes (PROs) of clients who consent to receiving the COPE intervention (COPE clients) using a qualitative methods evaluation. METHODS: Seven COPE clients were selected to participate in semi-structured interviews one year after finishing COPE to explore their perspective and experiences. Qualitative interviews were recorded, transcribed, and coded to identify themes. RESULTS: Clients revealed that health education delivered by CHRs facilitated lifestyle changes by helping them understand key health indicators and setting achievable goals through the use of accessible material and encouragement. Clients felt comfortable with CHRs who respected traditional practices and made regular visits. Clients also appreciated when CHRs educated their family members, who in turn were better able to support the client in their health management. Finally, CHRs who implemented the COPE intervention helped patients who were unable to regularly see a primary care doctor for critical care and support in their disease management. CONCLUSION: The COPE-CHR collaboration facilitated trusting client-CHR relationships and allowed clients to better understand their diagnoses. Further investment in materials that respect traditional practices and aim to educate clients' families may foster these relationships and improve health outcomes. TRIAL REGISTRATION: clinicaltrials.gov: NCT03326206. Registered 9/26/2017 (retrospectively registered).

Integrating community health representatives with health care systems: clinical outcomes among individuals with diabetes in Navajo Nation.

BACKGROUND: We studied the impact of Community Outreach and Patient Empowerment (COPE) intervention to support Community Health Representatives (CHR) on the clinical outcomes of patients living with diabetes in the Navajo Nation extending into the States of Arizona, Utah, and New Mexico. The COPE intervention integrated CHRs into healthcare teams by providing a structured approach to referrals and home visits. METHODS: We abstracted routine clinical data from the Indian Health Service's information system on individuals with diabetes mellitus seen at participating clinical sites from 2010 to 2014. We matched 173 COPE participants to 2880 patients with similar demographic and clinical characteristics who had not participated in COPE. We compared the changes in clinical outcomes between the two groups using linear mixed models. RESULTS: Over the four years of the study, COPE patients had greater improvements in glycosylated hemoglobin (- 0.56%) than non-COPE participants (+ 0.07%) for a difference in differences of 0.63% (95% confidence interval (CI): 0.50, 0.76). Low-density lipoprotein fell more steeply in the COPE group (- 10.58 mg/dl) compared to the non-COPE group (- 3.18 mg/dl) for a difference in differences of 7.40 mg/dl (95%CI: 2.00, 12.80). Systolic blood pressure increased slightly more among COPE (2.06 mmHg) than non-COPE patients (0.61 mmHg). We noted no significant change for body mass index in either group. CONCLUSION: Structured outreach by Community Health Representatives as part of an integrated care team was associated with improved glycemic and lipid levels in the target Navajo population. TRIAL REGISTRATION: Trial registration: NCT03326206. Registered 31 October 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT03326206.

Correction to: Glycemic control and healthcare utilization following pregnancy among women with pre-existing diabetes in Navajo Nation.

In the original publication of this article [1] an author's name needs to be revised from Katrina Nelson to Adrianne Katrina Nelson.

Pegylated interferon-2α invokes graft-versus-leukemia effects in patients relapsing after allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (SCT) is a curative therapy for patients with hematological malignancies related largely to an immunological graft-versus-leukemia (GVL) effect mediated by donor T cells and natural killer cells. Relapse of disease after SCT represents failure of GVL and is now the major cause of treatment failure. We sought to augment GVL effects in patients (n = 29) relapsing after SCT in a prospective phase I/II clinical trial of dose-escalated pegylated interferon-2α (peg-IFNα). The administration of peg-IFNα after reinduction chemotherapy, with or without subsequent donor lymphocyte infusion (DLI), resulted in a 2-year overall survival (OS) of 31% (95% confidence interval, 17.3%-49.2%), which rejects the null hypothesis of 7% generated by observations in an institutional historical cohort. As expected, peg-IFNα was associated with graft-versus-host disease (GVHD) and hematological toxicity, which was manageable with scheduled dose modifications. Progression-free survival (PFS) was greatest in patients who experienced GVHD, although the majority of those patients still eventually progressed. Higher PFS and OS were associated with pretreatment proportions of immune cell populations with regulatory function, including mucosal invariant T cells, regulatory T cells, and plasmacytoid dendritic cells, independent of any association with GVHD. Peg-IFNα administration after relapse thus constitutes a logical strategy to invoke GVL effects and should be studied in a larger, multicenter cohort. This trial was registered at www.anzctr.org.au as #ACTRN12612000728831.