Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV

PURPOSE Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival. PATIENTS AND METHODS Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival. RESULTS Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression. CONCLUSION MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.

All-ceramic or metal-ceramic tooth-supported fixed dental prostheses (FDPs)? A systematic review of the survival and complication rates. Part I: Single crowns (SCs).

OBJECTIVE To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported single crowns (SCs) and to describe the incidence of biological, technical and esthetic complications. METHODS Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL) searches (2006-2013) were performed for clinical studies focusing on tooth-supported fixed dental prostheses (FDPs) with a mean follow-up of at least 3 years. This was complimented by an additional hand search and the inclusion of 34 studies from a previous systematic review [1,2]. Survival and complication rates were analyzed using robust Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS Sixty-seven studies reporting on 4663 metal-ceramic and 9434 all-ceramic SCs fulfilled the inclusion criteria. Seventeen studies reported on metal-ceramic crowns, and 54 studies reported on all-ceramic crowns. Meta-analysis of the included studies indicated an estimated survival rate of metal-ceramic SCs of 94.7% (95% CI: 94.1-96.9%) after 5 years. This was similar to the estimated 5-year survival rate of leucit or lithium-disilicate reinforced glass ceramic SCs (96.6%; 95% CI: 94.9-96.7%), of glass infiltrated alumina SCs (94.6%; 95% CI: 92.7-96%) and densely sintered alumina and zirconia SCs (96%; 95% CI: 93.8-97.5%; 92.1%; 95% CI: 82.8-95.6%). In contrast, the 5-year survival rates of feldspathic/silica-based ceramic crowns were lower (p<0.001). When the outcomes in anterior and posterior regions were compared feldspathic/silica-based ceramic and zirconia crowns exhibited significantly lower survival rates in the posterior region (p<0.0001), the other crown types performed similarly. Densely sintered zirconia SCs were more frequently lost due to veneering ceramic fractures than metal-ceramic SCs (p<0.001), and had significantly more loss of retention (p<0.001). In total higher 5 year rates of framework fracture were reported for the all-ceramic SCs than for metal-ceramic SCs. CONCLUSIONS Survival rates of most types of all-ceramic SCs were similar to those reported for metal-ceramic SCs, both in anterior and posterior regions. Weaker feldspathic/silica-based ceramics should be limited to applications in the anterior region. Zirconia-based SCs should not be considered as primary option due to their high incidence of technical problems.

All-ceramic or metal-ceramic tooth-supported fixed dental prostheses (FDPs)? A systematic review of the survival and complication rates. Part II: Multiple-unit FDPs.

OBJECTIVE To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported fixed dental prostheses (FDPs) and to describe the incidence of biological, technical and esthetic complications. METHODS Medline (PubMed), Embase and Cochrane Central Register of Controlled Trials (CENTRAL) searches (2006-2013) were performed for clinical studies focusing on tooth-supported FDPs with a mean follow-up of at least 3 years. This was complemented by an additional hand search and the inclusion of 10 studies from a previous systematic review [1]. Survival and complication rates were analyzed using robust Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS Forty studies reporting on 1796 metal-ceramic and 1110 all-ceramic FDPs fulfilled the inclusion criteria. Meta-analysis of the included studies indicated an estimated 5-year survival rate of metal-ceramic FDPs of 94.4% (95% CI: 91.2-96.5%). The estimated survival rate of reinforced glass ceramic FDPs was 89.1% (95% CI: 80.4-94.0%), the survival rate of glass-infiltrated alumina FDPs was 86.2% (95% CI: 69.3-94.2%) and the survival rate of densely sintered zirconia FDPs was 90.4% (95% CI: 84.8-94.0%) in 5 years of function. Even though the survival rate of all-ceramic FDPs was lower than for metal-ceramic FDPs, the differences did not reach statistical significance except for the glass-infiltrated alumina FDPs (p=0.05). A significantly higher incidence of caries in abutment teeth was observed for densely sintered zirconia FDPs compared to metal-ceramic FDPs. Significantly more framework fractures were reported for reinforced glass ceramic FDPs (8.0%) and glass-infiltrated alumina FDPs (12.9%) compared to metal-ceramic FDPs (0.6%) and densely sintered zirconia FDPs (1.9%) in 5 years in function. However, the incidence of ceramic fractures and loss of retention was significantly (p=0.018 and 0.028 respectively) higher for densely sintered zirconia FDPs compared to all other types of FDPs. CONCLUSIONS Survival rates of all types of all-ceramic FDPs were lower than those reported for metal-ceramic FDPs. The incidence of framework fractures was significantly higher for reinforced glass ceramic FDPs and infiltrated glass ceramic FDPs, and the incidence for ceramic fractures and loss of retention was significantly higher for densely sintered zirconia FDPs compared to metal-ceramic FDPs.

Drought coping and adaptation strategies: Understanding adaptations to climate change in agro-pastoral livestock production in Makueni district, Kenya

Using drought as a lens, this article analyses how agro-pastoralists in Makueni district, Kenya adapt their livestock production to climate variability and change. Data were collected from a longitudinal survey of 127 agro-pastoral households. Approximately one-third of the households have inadequate feeds, and livestock diseases are major challenges during non-drought and drought periods. Agro-pastoralists’ responses to drought are reactive and mainly involve intensifying exploitation of resources and the commons. Proactive responses such as improving production resources are few. Poverty, limited responses to market dynamics and inadequate skills constrain adaptations. Many agro-pastoralists’ attachment to livestock deters livestock divestment, favouring disadvantageous sales that result in declining incomes. To improve adaptive capacity, interventions should expose agro-pastoralists to other forms of savings, incorporate agro-pastoralists as agents of change by building their capacity to provide extension services, and maintain infrastructure. Securing livestock mobility, pasture production and access is crucial under the variable social-ecological conditions.

Guidelines for WB3 Part III: Stakeholder workshop 2: Selection and decision on prevention and mitigation strategies to be implemented

These guidelines were developed in the context of working block 3 of the DESIRE project. They address the facilitators in the 18 DESIRE study sites and support them in conducting stakeholder workshops aiming at the selection and decision on mitigation strategies to be implemented in the study site context. The decision-making process is supported by a multi-objective decision support system (MODSS) Software called 'Facilitator'.

A methodology for appraising and selecting strategies to mitigate desertification based on stakeholder participation and global best practices

The main aim of the methodology presented in this paper is to provide a framework for a participatory process for the appraisal and selection of options to mitigate desertification and land degradation. This methodology is being developed within the EU project DESIRE (www.desire-project.eu/) in collaboration with WOCAT (www.wocat.org). It is used to select promising conservation strategies for test-implementation in each of the 16 degradation and desertification hotspot sites in the Mediterranean and around the world. The methodology consists of three main parts: In a first step, prevention and mitigation strategies already applied at the respective DESIRE study site are identified and listed during a workshop with representatives of different stakeholders groups (land users, policy makers, researchers). The participatory and process-oriented approach initiates a mutual learning process among the different stakeholders by sharing knowledge and jointly reflecting on current problems and solutions related to land degradation and desertification. In the second step these identified, locally applied solutions (technologies and approaches) are assessed with the help of the WOCAT methodology. Comprehensive questionnaires and a database system have been developed to document and evaluate all relevant aspects of technical measures as well as implementation approaches by teams of researchers and specialists, together with land users. This research process ensures systematic assessing and piecing together of local information, together with specific details about the environmental and socio-economic setting. The third part consists of another stakeholder workshop where promising strategies for sustainable land management in the given context are selected, based on the best practices database of WOCAT, including the evaluated locally applied strategies at the DESIRE sites. These promising strategies will be assessed with the help of a selection and decision support tool and adapted for test-implementation at the study site.

Guidelines for WB3 Part I: Desertification and land degradation: Identification of existing and potential prevention and mitigation strategies

These guidelines are a working instrument for conducting and moderating stakeholder workshops with a participatory approach to initiate a mutual learning process among local and external stakeholders. The overall aim of the workshop is to identify promising (existing and potential) strategies for land and water conservation for the selected study site. DESIRE (Desertification Mitigation and Remediation of Land) is a European Integrated Project. The DESIRE WB 3 methodology was developed by CDE and is based on experiences from Learning for Sustainability (LforS) and WOCAT.

Stable coronary artery disease: revascularisation and invasive strategies

Stable coronary artery disease is the most common clinical manifestation of ischaemic heart disease and a leading cause of mortality worldwide. Myocardial revascularisation is a mainstay in the treatment of symptomatic patients or those with ischaemia-producing coronary lesions, and reduces ischaemia to a greater extent than medical treatment. Documentation of ischaemia and plaque burden is fundamental in the risk stratification of patients with stable coronary artery disease, and several invasive and non-invasive techniques are available (eg, fractional flow reserve or intravascular ultrasound) or being validated (eg, instantaneous wave-free ratio and optical coherence tomography). The use of new-generation drug-eluting stents and arterial conduits greatly improve clinical outcome in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PCI is feasible, safe, and effective in many patients with stable coronary artery disease who remain symptomatic despite medical treatment. In patients with multivessel and left main coronary artery disease, the decision between PCI or CABG is guided by the local Heart Team (team of different cardiovascular specialists, including non-invasive and invasive cardiologists, and cardiac surgeons), who carefully judge the possible benefits and risks inherent to PCI and CABG. In specific subsets, such as patients with diabetes and advanced, multivessel coronary artery disease, CABG remains the standard of care in view of improved protection against recurrent ischaemic adverse events.

National competence center for wildlife diseases in Switzerland: Mandate, development and current strategies.

The need for wildlife health surveillance has become increasingly recognized. However, comprehensive programs which cover a wide spectrum of species, pathogens and geographic areas are still lacking in most European countries and practical examples of systems in place remain scarce. This article provides an overview of the organization of wildlife health surveillance in Switzerland, with a focus on the development, current strategies and the activities of the national program carried out by the Centre for Fish and Wildlife Health (FIWI), University of Bern. This documentation may stimulate on-going discussions on the design and development of national wildlife health surveillance programs in other countries. Investigations into wildlife health in Switzerland date back to the 1950s. The FIWI acts as a national competence center for wildlife diseases on mandate of the Swiss federal authorities. The mandate includes four main activities: disease diagnostics, research, consulting and teaching. In line with this, the FIWI has made continuous efforts to strengthen a national network of field partners and implemented strategies to facilitate long-term and metastudies.

Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa.

BACKGROUND Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. METHODS We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. RESULTS Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. CONCLUSIONS In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.