First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis

Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer TKIs requires the definition of the optimal first-line TKI for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase (CP) CML. This systematic review of randomized controlled trials (RCTs) compares the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Ph+ CP CML, concentrating on OS, progression-free survival (PFS), and hematological and nonhematological adverse events. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Seven RCTs published between 1990 and 2019 (involving 3262 participants) satisfied the eligibility criteria. Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS. Second- and third-generation TKIs improved 3-month major molecular responses (relative risk [RR], 4.28; 95% confidence interval [CI], 2.20-8.32) and other efficacy outcomes, decreased accelerated/blastic-phase transformations (RR, 0.44; 95% CI, 0.26-0.74), but were associated with more cases of thrombocytopenia (RR, 1.57; 95% CI, 1.20-2.05), cardiovascular events (RR, 2.54; 95% CI, 1.49-4.33), and pancreatic (RR, 2.29; 95% CI, 1.32-3.96) and hepatic effects (RR, 3.51; 95% CI 1.55-7.92). GRADE showed that the certainty of the evidence ranged from high to moderate. This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities

Management of lymphoma survivor patients in Italy: an evaluation by Fondazione Italiana Linfomi

Several outpatient models for the follow-up of cancer survivors have been developed worldwide. A multidisciplinary approach is often necessary to guarantee the best monitoring of long-term toxicities. Guidelines also indicate a close education on healthy lifestyles. In this context, we have analyzed the Italian follow-up modalities of lymphoma survivors, with the aim to have a starting line to hypothesize and plan the best model for Italian hematology centers

Optical Density Of Bone Repair After Implantation Of Homogenous Demineralized Dentin Matrix In Diabetic Rabbits

This research evaluated the bone repair process after implantation of homogenous demineralized dentin matrix (HDDM) in surgical defects in the parietal bone of rabbits with alloxan-induced diabetes, using a polytetrafluorethylene (PTFe) barrier for guided bone regeneration. Thirty-six rabbits were used and divided into four groups: control (C, n = 12), diabetic (D, n = 12, left parietal bone), diabetic with PTFe (DPTFe, same 12 rabbits, right parietal bone), and diabetic with PTFe associated to HDDM (D-PTFe+HDDM, n = 12). Bone defects were created in the parietal bone of the rabbits and the experimental treatments were performed, where applicable. The rabbits were sacrificed after 15, 30, 60 and 90 days. The bone defects were examined radiographically and by optical density (ANOVA and Tukey test, p < .05). The radiographic findings showed that the D-PTFe+HDDM group presented greater radiopacity and better trabecular bone arrangement when compared to that of the C, D and D-PTFe groups. The statistical analysis showed significant differences in the optical density of the newly formed bone among the studied groups. It was possible to conclude that HDDM was biocompatible in diabetic rabbits.223275280Abreu, P.P., Morosolli, A., Araújo, M.M., Carvalho, V.A.P., Gomes, M.F., Effects of autogenous demineralized dentin matrix on dental socket wound healing process in human (2004) Braz Oral Res, 18, p. 52. , SupplCarvalho, V.A.P., Tosello, D.O., Salgado, M.A.C., Gomes, M.F., Histomorphometric analysis of homogenous demineralized dentin matrix as osteopromotive material in rabbit mandibules (2004) Int J Oral Maxillofac Implants, 19 (5), pp. 679-686Gomes, M.F., Anjos, M.J.S., Nogueira, T.O., Catanzaro-Guimarães, S.A., Autogenous demineralized dentin matrix for tissue engineering applications: Radiographic and histomorphometric studies (2002) Int J Oral Maxillofac Implants, 17 (4), pp. 488-497Gomes, M.F., Silva, M.J.S., Nogueira, T.O., Catanzaro-Guimarães, S.A., Histologic evaluation of the osteoinductive property of autogenous demineralized dentin matrix on surgical bone defects in rabbit skulls using human amniotic membrane for guided bone regeneration (2001) Int J Oral Maxillofac Implants, 16 (4), pp. 563-571Guyton, A.C., Hall, J.E., (2006) Insulin, Glucagon, and Diabetes mellitus, pp. 827-840. , Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed, Elsevier;Fiorellini, J.P., Nevins, M.L., Norkin, A., Weber, H.P., Karimbux, N.Y., The effect of insulin therapy on osseointegration in a diabetic rat model (1999) Clin Oral Implants Res, 10 (5), pp. 362-368Lu, H., Kraut, D., Gerstenfeld, L.C., Graves, D.T., Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation (2003) Endocrinology, 144 (1), pp. 346-352Nevins, M.L., Karimbux, N.Y., Weber, H.P., Giannobile, W.V., Fiorellini, J.P., Wound healing around endosseous implants in experimental diabetes (1998) Int J Oral Maxillofac Implants, 13 (5), pp. 620-629Claro, F.A., Lima, J.R., Salgado, M.A.C., Gomes, M.F., Porous Polyethylene for tissue engineering applications in diabetic rats treated with calcitonin: Histomorphometric analysis (2005) Int J Oral Maxillofac Implants, 20 (2), pp. 211-219Catanzaro-Guimarães, S.A., Catanzaro Guimarães, B.P., Garcia, R.B., Alle, N., Osteogenic potential of autogenic demineralized dentin implanted in bony defects in dogs (1986) Int J Oral Maxillofac Surg, 15 (2), pp. 160-169Bessho, K., Tagawa, T., Murata, M., Purification of rabbit bone morphogenetic protein derived from bone, dentin, and wound tissue after tooth extraction (1990) J Oral Maxillofac Surg, 48 (2), pp. 162-169Nakashima, M., Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix (1994) Arch Oral Biol, 39 (12), pp. 1085-1089Catanzaro-Guimarães SA. Possibility to reinforce bone repair with decalcified dentin matrix. In: Gesellschaft für orale Implantologie (ed.). Jahrbuch für Orale Implatologie. Berlin: Quintessenz1993. p. 33-

Multicolor photometry of clusters of galaxies: A3284, A3305, A1942

We present complete multicolor photometry in the Gunn system for the three clusters of galaxies A3284, A3305 and A1942 at redshift z~0.2. INVENTORY magnitudes and colours have been obtained for over 1,000 objects in the three fields down to g=24, and with a good completeness level in the detections (85% or better) about one magnitude brighter. By fitting with King profiles the r counts we derived the total number of galaxies and the core radius down to the r magnitude limit in each cluster. These are N_TOT_=146 galaxies and R_c_=0.24 Mpc for A3284, N_TOT_=129 and R_c_=0.20 Mpc for A3305, N_TOT_=130 and R_c_=0.24 Mpc for A1942. The observed mean redshift of the clusters is z=0.150+/-0.001 for A3284, z=0.157+/-0.001 for A3305, and z=0.226+/-0.001 for A1942. The c-m diagrams and the g-i colour distribution as well as the two-colour diagrams are used to single out early-type galaxies and spirals on the basis of their different photometric properties. This approach aimed at a self-consistent classification of galaxies on the basis of photometric indicators will be further developed for a systematic study of the galaxy population in distant clusters

The impact generated by public and charity-funded research in the UK: A systematic literature review

Objective: To identify, synthesize and critically assess the empirical evidence of the impact generated by public and charity funded health research in the United Kingdom. Methods: We conducted a systematic literature review of the empirical evidence published in English in peer-reviewed journals between 2006 and 2017. Studies meeting the inclusion criteria were selected and their findings were analysed using the Payback Framework into five main categories: knowledge, benefits to future research and research use, benefits from informing policy and product development, health and health sector benefits and broader economic benefits. We assessed the studies for risk of selection, reporting and funding bias. Results: Thirteen studies met the inclusion criteria. The majority of the studies (10 out of 13) assessed impact at multiple domains including the main 5 key themes of the Payback Framework. All of them showed a positive impact of funded research on outcomes. Of those studies, one presented low risk of bias (8%), 6 studies were classified as presenting moderate risk of bias (46%) and 6 studies presented high risk of bias (46%). Conclusions: Empirical evidence on the impact of public and charity funded research is still limited and subject to funding and selection bias. More work is needed to establish the causal effects of funded research on academic outcomes, policy, practice and the broader economy

Telerehabilitation and recovery of motor function: a systematic review and meta-analysis

Recent advances in telecommunication technologies have boosted the possibility to deliver rehabilitation via the internet (i.e. telerehabilitation). Several studies have shown that telerehabilitation is effective to improve clinical outcomes in disabling conditions. The aim of this review was to determine whether telerehabilitation was more effective than other modes of delivering rehabilitation to regain motor function, in different populations of patients. We searched PubMed, Embase and the Cochrane library retrieving 2360 records. Twelve studies were included involving different populations (i.e. neurological, total knee arthroplasty (TKA), cardiac) of patients. Inconclusive finding were found on the effect of telerehabilitation for neurological patients (SMD = 0.08, CI 95% = −0.13, 0.29), while both for cardiac (SMD = 0.24, CI 95% = 0.04, 0.43) and TKA patients (Timed Up and Go test: MD = −5.17, CI 95% = −9.79, −0.55) the results were in favour of telerehabilitation. Conclusive evidence on the efficacy of telerehabilitation for treatment of motor function, regardless of pathology, was not reached. Nevertheless, a strong positive effect was found for patients following orthopaedic surgery, suggesting that the increased intensity provided by telerehabilitation is a promising option to be offered to patients. More and higher quality research is needed in this field especially with neurological patients

Retrospective Chart Review of Dabrafenib Plus Trametinib in Patients with Metastatic BRAF V600-Mutant Melanoma Treated in the Individual Patient Program (DESCRIBE Italy)

Background: Real-world data on extended follow-up of patients with BRAF V600-mutant metastatic melanoma are limited. We investigated dabrafenib plus trametinib (dab + tram) outside of a clinical trial setting (Individual Patient Program; DESCRIBE Italy). Objective: To describe the baseline features, treatment patterns, efficacy, and safety outcomes in patients with BRAF V600-mutant unresectable or metastatic melanoma who had received dab + tram as part of the Managed Access Program (MAP) in Italy. Patients and methods: An observational, retrospective chart review was conducted in Italian patients with BRAF V600-mutant unresectable stage III/IV melanoma receiving dab + tram as part of the MAP. Baseline features, treatment patterns, efficacy, and safety outcomes were evaluated. Results: Overall, 499 patients were included in this analysis. BRAF V600E mutation was seen in 81.4% of patients. Overall response rate achieved in 243 of the 390 evaluable patients was 62.3% (95% CI 57.5-67.1). Median progression-free survival (PFS) was 9.3 months (95% CI 8.6-10.6). Subgroup analyses revealed that patients with normal lactate dehydrogenase (LDH) and ≤ three metastatic sites without brain metastases at baseline had better outcomes. With normal LDH at baseline, median PFS for patients with one or two metastatic sites other than cerebral was 18 months. No new safety signals were observed. Treatment was permanently discontinued because of treatment-emergent adverse events (TEAEs) in 9.2% of patients, and pyrexia (27.3%) was the most common TEAE, with a lower incidence than that in the phase 3 studies of dab + tram. Conclusion: Treatment of BRAF V600E-mutant metastatic melanoma with dab + tram in the real-world setting was effective and safe, including the unselected population with several patients having a high tumor burden - concordant with the results of the pivotal phase 3 studies of dab + tram

Understanding factors associated with the translation of cardiovascular research: A multinational case study approach

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Funders of health research increasingly seek to understand how best to allocate resources in order to achieve maximum value from their funding. We built an international consortium and developed a multinational case study approach to assess benefits arising from health research. We used that to facilitate analysis of factors in the production of research that might be associated with translating research findings into wider impacts, and the complexities involved. Methods: We built on the Payback Framework and expanded its application through conducting co-ordinated case studies on the payback from cardiovascular and stroke research in Australia, Canada and the United Kingdom. We selected a stratified random sample of projects from leading medical research funders. We devised a series of innovative steps to: minimize the effect of researcher bias; rate the level of impacts identified in the case studies; and interrogate case study narratives to identify factors that correlated with achieving high or low levels of impact. Results: Twenty-nine detailed case studies produced many and diverse impacts. Over the 15 to 20 years examined, basic biomedical research has a greater impact than clinical research in terms of academic impacts such as knowledge production and research capacity building. Clinical research has greater levels of wider impact on health policies, practice, and generating health gains. There was no correlation between knowledge production and wider impacts. We identified various factors associated with high impact. Interaction between researchers and practitioners and the public is associated with achieving high academic impact and translation into wider impacts, as is basic research conducted with a clinical focus. Strategic thinking by clinical researchers, in terms of thinking through pathways by which research could potentially be translated into practice, is associated with high wider impact. Finally, we identified the complexity of factors behind research translation that can arise in a single case. Conclusions: We can systematically assess research impacts and use the findings to promote translation. Research funders can justify funding research of diverse types, but they should not assume academic impacts are proxies for wider impacts. They should encourage researchers to consider pathways towards impact and engage potential research users in research processes. © 2014 Wooding et al.; licensee BioMed Central Ltd.RAND Europe and HERG, with subsequent funding from the NHFA, the HSFC and the CIHR. This research was also partially supported by the Policy Research Programme in the English Department of Health

development of a new clinical nomogram including velocity rate of disease progression to predict outcome in metastatic colorectal cancer patients treated with bevacizumab beyond progression a subanalysis from tribe trial

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Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK