Day hospital versus intensive outpatient mentalization-based treatment:3-year follow-up of patients treated for borderline personality disorder in a multicentre randomized clinical trial

Abstract Background Two types of mentalization-based treatment (MBT), day hospital MBT (MBT-DH) and intensive outpatient MBT (MBT-IOP), have been shown to be effective in treating patients with borderline personality disorder (BPD). This study evaluated trajectories of change in a multi-site trial of MBT-DH and MBT-IOP at 36 months after the start of treatment. Methods All 114 patients (MBT-DH n = 70, MBT-IOP n = 44) from the original multicentre trial were assessed at 24, 30 and 36 months after the start of treatment. The primary outcome was symptom severity measured with the Brief Symptom Inventory. Secondary outcome measures included borderline symptomatology, personality and interpersonal functioning, quality of life and self-harm. Data were analysed using multilevel modelling and the intention-to-treat principle. Results Patients in both MBT-DH and MBT-IOP maintained the substantial improvements made during the intensive treatment phase and showed further gains during follow-up. Across both conditions, 83% of patients improved in terms of symptom severity, and 97% improved on borderline symptomatology. No significant differences were found between MBT-DH and MBT-IOP at 36 months after the start of treatment. However, trajectories of change were different. Whereas patients in MBT-DH showed greater improvement during the intensive treatment phase, patients in MBT-IOP showed greater continuing improvement during follow-up. Conclusions Patients in both conditions showed similar large improvements over the course of 36 months, despite large differences in treatment intensity. MBT-DH and MBT-IOP were associated with different trajectories of change. Cost-effectiveness considerations and predictors of differential treatment outcome may further inform optimal treatment selection

Economic evaluation of day hospital versus intensive outpatient mentalization-based treatment alongside a randomized controlled trial with 36-month follow-up

Mentalization-based treatment (MBT) has demonstrated robust effectiveness in the treatment of borderline personality disorder (BPD) in both day hospital (MBT-DH) and intensive outpatient MBT (MBT-IOP) programs. Given the large differences in intensity and associated treatment costs, there is a need for studies comparing their cost-effectiveness. A health economic evaluation of MBT-DH versus MBT-IOP was performed alongside a multicenter randomized controlled trial with a 36-month follow-up. In three mental health-care institutions in the Netherlands, 114 patients were randomly allocated to MBT-DH (n = 70) or MBT-IOP (n = 44) and assessed every 6 months. Societal costs were compared with quality-adjusted life years (QALYs) gained and the number of months in remission over 36 months. The QALY gains over 36 months were 1.96 (SD = 0.58) for MBT-DH and 1.83 (SD = 0.56) for MBT-IOP; the respective number of months in remission were 16.0 (SD = 11.5) and 11.1 (SD = 10.7). Societal costs were €106,038 for MBT-DH and €91,368 for MBT-IOP. The incremental cost for one additional QALY with MBT-DH compared with MBT-IOP was €107,000. The incremental cost for 1 month in remission was almost €3000. Assuming a willingness-to-pay threshold of €50,000 for a QALY, there was a 33% likelihood that MBT-DH is more cost-effective than MBT-IOP in terms of costs per QALY. Although MBT-DH leads to slightly more QALYs and remission months, it is probably not cost-effective when compared with MBT-IOP for BPD patients, as the small additional health benefits in MBT-DH did not outweigh the substantially higher societal costs

Day hospital versus intensive outpatient mentalization-based treatment: 3-year follow-up of patients treated for borderline personality disorder in a multicentre randomized clinical trial

BackgroundTwo types of mentalization-based treatment (MBT), day hospital MBT (MBT-DH) and intensive outpatient MBT (MBT-IOP), have been shown to be effective in treating patients with borderline personality disorder (BPD). This study evaluated trajectories of change in a multi-site trial of MBT-DH and MBT-IOP at 36 months after the start of treatment.MethodsAll 114 patients (MBT-DH n = 70, MBT-IOP n = 44) from the original multicentre trial were assessed at 24, 30 and 36 months after the start of treatment. The primary outcome was symptom severity measured with the Brief Symptom Inventory. Secondary outcome measures included borderline symptomatology, personality and interpersonal functioning, quality of life and self-harm. Data were analysed using multilevel modelling and the intention-to-treat principle.ResultsPatients in both MBT-DH and MBT-IOP maintained the substantial improvements made during the intensive treatment phase and showed further gains during follow-up. Across both conditions, 83% of patients improved in terms of symptom severity, and 97% improved on borderline symptomatology. No significant differences were found between MBT-DH and MBT-IOP at 36 months after the start of treatment. However, trajectories of change were different. Whereas patients in MBT-DH showed greater improvement during the intensive treatment phase, patients in MBT-IOP showed greater continuing improvement during follow-up.ConclusionsPatients in both conditions showed sim

ALMA Long Baseline Observations of the Strongly Lensed Submillimeter Galaxy HATLAS J090311.6+003906 at z=3.042

We present initial results of very high resolution Atacama Large Millimeter/submillimeter Array (ALMA) observations of the $z$=3.042 gravitationally lensed galaxy HATLAS J090311.6+003906 (SDP.81). These observations were carried out using a very extended configuration as part of Science Verification for the 2014 ALMA Long Baseline Campaign, with baselines of up to 15 km. We present continuum imaging at 151, 236 and 290 GHz, at unprecedented angular resolutions as fine as 23 milliarcseconds (mas), corresponding to an un-magnified spatial scale of ~180 pc at z=3.042. The ALMA images clearly show two main gravitational arc components of an Einstein ring, with emission tracing a radius of ~1.5". We also present imaging of CO(10-9), CO(8-7), CO(5-4) and H2O line emission. The CO emission, at an angular resolution of ~170 mas, is found to broadly trace the gravitational arc structures but with differing morphologies between the CO transitions and compared to the dust continuum. Our detection of H2O line emission, using only the shortest baselines, provides the most resolved detection to date of thermal H2O emission in an extragalactic source. The ALMA continuum and spectral line fluxes are consistent with previous Plateau de Bure Interferometer and Submillimeter Array observations despite the impressive increase in angular resolution. Finally, we detect weak unresolved continuum emission from a position that is spatially coincident with the center of the lens, with a spectral index that is consistent with emission from the core of the foreground lensing galaxy.Comment: 9 pages, 5 figures and 3 tables, accepted for publication in the Astrophysical Journal Letter

The one health problem of azole resistance in Aspergillus fumigatus: current insights and future research agenda

Azole resistance is a concern for the management of diseases caused by Aspergillus fumigatus in humans. Azole fungicide use in the environment has been identified as a possible cause for development of resistance, which increases the complexity and number of stakeholders involved in this emerging problem. A workshop was held in Amsterdam early 2019 in which stakeholders, including medical and agricultural researchers, representatives from the government, public health, fungicide producers and end-users, reviewed the current evidence supporting environmental selection for resistance and to discuss which research and measures are needed to retain the effectiveness of the azole class for environmental and medical applications. This paper provides an overview of the latest insights and understanding of azole resistance development in the clinical setting and the wider environment. A One Health problem approach was undertaken to list and prioritize which research will be needed to provide missing evidence and to enable preventive intervention

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents

PURPOSEThere is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders.METHODSAfter a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved.RESULTSCombinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements.CONCLUSIONAn optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer.</p

An Overview of the 2014 ALMA Long Baseline Campaign

A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the Astrophysical Journal Letters; this version with small changes to affiliation

Post-2020 climate agreements in the major economies assessed in the light of global models

Integrated assessment models can help in quantifying the implications of international climate agreements and regional climate action. This paper reviews scenario results from model intercomparison projects to explore different possible outcomes of post-2020 climate negotiations, recently announced pledges and their relation to the 2 °C target. We provide key information for all the major economies, such as the year of emission peaking, regional carbon budgets and emissions allowances. We highlight the distributional consequences of climate policies, and discuss the role of carbon markets for financing clean energy investments, and achieving efficiency and equity