Feasibility and success rates of response enhancing strategies in a stepwise prevention program for cardiometabolic diseases in primary care

Background Prevention programs for cardiometabolic diseases (CMD), including cardiovascular disease, diabetes mellitus and chronic kidney disease are feasible, but evidence for the cost-effectiveness of selective CMD prevention programs is lacking. Response rates have an important role in effectiveness, but methods to increase response rates have received insufficient attention. The aim of the current study is to determine the feasibility and the success rate of a variety of response enhancing strategies to increase the participation in a selective prevention program for CMD. Methods The INTEGRATE study is a Dutch randomised controlled trial to assess the effectiveness and cost-effectiveness of a stepwise program for CMD prevention. During the INTEGRATE study we developed ten different response enhancing strategies targeted at different stages of non-response and different patient populations and evaluated these in 29 general practices. Results A face-to-face reminder by the GP increased the response significantly. Digital reminders targeted at patients with an increased CMD risk showed a positive trend towards participation. Sending invitations and reminders by e-mail generated similar response rates, but at lower costs and time investment than the standard way of dissemination. Translated materials, information gatherings at the practice, self-management toolkits, reminders by telephone, information letters, local media attention and SMS text reminders did not increase the response to our program. Conclusions Inviting or reminding patients by e-mail or during GPs consultation may enhance response rates in a selective prevention program for CMD. Different response-enhancing strategies have different patient target populations and implementation issues, therefore practice characteristics need to be taken into account when implementing such strategies. Trial registration Dutch trial Register number NTR4277. Registered 26 November 2013.

Transient signs in bedrock rivers of the southernmost Brazilian and Uruguayan shields

<p>The Earth’s surface is a result of tectonic and erosional processes shaping landscapes and preserving transient signs of different evolutionary stages. These transient signs are produced by a gradual adjustment of rivers to an equilibrium stage through channel incision and uplift. The processes effects have different magnitudes according to lithologic contrasts and base level changes that combined influence in disequilibrium phases of bedrock rivers. A integrate study of geomorphic indices in bedrock rivers of the southernmost Brazilian and Uruguayan Shields is developed to identify key signs of transience associated to those surface process and compared between the contrasting drainage basins results. These indices are combined to published thermochronology ages to build a landscape evolution model of these shields. The study area is essentially composed by igneous-metamorphic rocks of Precambrian ages of the Dom Feliciano Belt amalgamated during the Proterozoic-Phanerozoic boundary in the Brasiliano Orogeny. Digital elevation models are used to extract geomorphic indices through interactive MATLAB tools and compared the erosional stages and uplifted regions. This study reveals lineament structures signatures aligned with knickpoints as indicator of the suture zones of distinct terranes in the area. These terranes also feature different erosional stages according to hypsometric results. Thermochronological data support the tectonic framework of three uplift phases starting by the exhumation of western terranes during Devonian ages. A second stage is connected to an uplift preceding the Pangea breakup with the reactivation of Brasiliano Orogeny lineaments. And, the third phase is associated with plate flexural responses of the adjacent oceanic crust during the Cenozoic Era. Finally, the evolutionary model shows strong transient signs in the north region of the studied area indicating a locus of a possible stronger uplift process. In this part of the Dom Feliciano Belt all exhumation phase are evidenced by transient signs of disequilibrium. Differently, the southern region in the Uruguayan Shield shows a more denudated landscape with more mature stages of erosional process.</p>

Protocol for an International, Multi-Centre, Retrospective Study to Describe Treatment Pathways, Outcomes and Resource Use in Patients with Multiple Myeloma (INTEGRATE)

Introduction The incidence of multiple myeloma (MM) has increased globally in the past decade and is predicted to increase in developing countries due to ageing populations and improvements in diagnosis. Studies outlining the relationship between long-term patient outcomes and treatment strategies remain limited. As a result, there is a need for data on treatment effectiveness with long-term patient outcomes such as time to next treatment and overall survival, as well as toxicity, and healthcare resource utilization in developing countries. The real-world INTEGRATE study seeks to address this gap by providing data on long-term outcomes, and management strategies in developing countries. Methods The INTEGRATE study (ENCePP registration number: EUPAS21846) is a global, multi-centre, retrospective, observational study ongoing in 8 countries representing different clinical settings (Argentina, China, Russia, South Africa, South Korea, Taiwan, Turkey, Saudi Arabia). This study is collecting data from patients with newly diagnosed MM (NDMM) or with relapsed/refractory MM (RRMM), by means of a retrospective review of electronic or paper medical records. Patients aged ≥18 years who are alive or deceased, diagnosed with symptomatic NDMM and/or RRMM between 01 January 2010 and 31 December 2011, and who completed ≥1 full line of treatment have been included in the study. Patients with smouldering myeloma, monoclonal gammopathy of unknown significance, without enough data, or enrolled in a clinical trial have been excluded. Study design is summarized in the figure. The primary endpoint is time to next treatment after each line of therapy for both the NDMM and RRMM populations. Secondary endpoints include reporting patient demographic and clinical characteristics, treatment patterns, and clinical outcomes (relapse rate, overall survival rate, number of relapses for each line of therapy). The sample size (N=2000) has been determined based on local feasibility and incidence within each country. A sample of at least 50 patients should provide reliable estimates of the primary endpoint at country level. Subgroup analyses will be performed to describe the outcomes associated with different treatment regimens, including autologous and non-autologous stem cell transplant. Results The study is expected to enrol 2000 patients in all countries by December 2019. As of 09 July 2019, a total of 1731 patients have been enrolled with most patients enrolled in Taiwan, Turkey, Russia and South Korea. Once complete, the results will be reported at future scientific meetings. Conclusion This large study based on a diverse population of patients will provide a unique data set with long-term patient outcomes in MM in developing countries. Ultimately, this real-world information regarding treatment effectiveness, toxicity, and resource use in developing countries will support decision making for both clinicians and payers. Figure Disclosures Alsharif: Algoryth: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Beksac:Takeda: Consultancy; Janssen&Janssen: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Verburgh:Roche: Research Funding; Takeda: Research Funding. Wu:Takeda: Employment. Zhang:Takeda: Employment. Wan:Takeda: Employment.

Evaluation of circulating VEGF based biomarkers in INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG).

64 Background: The INTEGRATE study evaluated activity of regorafinib (REG) v placebo (PBO) in 147 eligible patients with refractory AOGC. REG was highly effective in prolonging progression free survival (PFS). Differences between regions (i.e. Australia New Zealand/Canada (ANZ/CAN) vs Korea) were found in the magnitude of effect, but REG was effective across all regions and subgroups. We report on an exploratory analysis of VEGF biomarkers to identify predictive/prognostic markers. Methods: Protein biomarkers IL8, VEGF-A,-B,-C-D, soluble(s)VEGFR-1,-2-3 were analysed in plasma at baseline (BL) by multiplex immunoassays (Bio-Plex,BioRad) or ELISA (Abnova). Spearman statistics were used to quantify correlations between markers. Wilcoxon Rank-Sum tests were used to compare markers across regions. The prognostic and predictive value of markers was determined using cox proportional hazards analysis of PFS. Results: There were moderate-to-strong correlations between BL levels of IL8 and VEGF-C (ρ = 0.68), IL8 and VEGF-D (ρ = 0.66), VEGF-A and VEGF-C (ρ = 0.68), VEGF-A and sVEGFR-1 (ρ = 0.54); and a modest negative correlation between VEGF-D and sVEGRF-1 (ρ = -0.33). The regions differed according to BL levels of: VEGF-A (higher in ANZ/CAN; p = 0.0015), VEGF-B (higher in Korea; p = 0.0003), VEGF-D (higher in Korea; p <.0001), and sVEGFR-1 (higher in ANZ/CAN; p <.0001). Adjusting for treatment group, there were statistically significant negative associations between PFS and BL IL8 (p = 0.047), VEGF-A (p = 0.037) and sVEGFR-1 (p = 0.045). There was no convincing statistical evidence that any BL plasma biomarker modified the effect of REG. The effect of region on effectiveness of REG was maintained when evaluated in conjunction with BL biomarkers individually and in combination. Conclusions: Highplasma IL8, VEGF-A and sVEGFR-1 may be adverse prognostic factors. A predictive VEGF blood based biomarker remains elusive. A broader biomarker study including markers beyond the VEGF axis and tissue based markers is ongoing. Clinical trial information: ACTRN12612000239864.