MR angiography with blood pool contrast agents

Contrast-enhanced magnetic resonance angiography (CE-MRA) with standard extracellular contrast material is well established for vascular imaging. Recently, the first blood pool contrast agent (BPA) has become clinically available. This paper reviews characteristics and classification of BPA as well as first clinical experience in various vascular territories. BPAs comprise gadolinium-based compounds, synthetic compounds, and ultrasmall superparamagnetic iron-oxide (USPIO) particles. Such BPAs are retained in blood with a prolonged time-window of enhancement as compared to extracellular gadolinium chelates. Promising results from USPIO at first-pass and steady-state angiography have been published, but no USPIO is approved yet. Gadofosveset is the first clinically approved BPA. After bolus injection, gadofosveset binds noncovalently to serum-albumine, thus enhancing relaxivity. First published results from carotid, coronary, renal, and peripheral angiography are encouraging; particularly helpful is prolonged enhancement during steady state. More BPAs have been clinically evaluated, but no approval has been granted. Bolus-injectable BPAs allow for first-pass CE-MRA similar to standard extracellular contrast media, but with higher relaxivity, allowing lower doses and reduced injection rates. An additional feature of BPA is the steady-state phase with a broad time window enabling high-resolution angiography or double-gated angiography of coronary arteries to compensate for the complex motion patter

Is Heroin-Assisted Treatment Effective for Patients with No Previous Maintenance Treatment? Results from a German Randomised Controlled Trial

Background/Aims: Until now, the medical prescription of diamorphine (heroin) has been suggested as suitable for patients who have failed previous maintenance treatments. The aim of this paper is to assess the effects of diamorphine on opioid-dependent patients with no previous maintenance treatment experience (NPME). Methods: The German heroin trial compared diamorphine versus methadone maintenance treatment and included 107 patients with NPME. This paper is a sub-analysis of these patients. Results: When comparing this subsample with the rest of the participants in the study, large baseline differences were found, showing a more severe drug use profile in patients with NPME. However, no differences were found in terms of treatment outcome and treatment retention. In the subsample with NPME, outcome measures on the reduction of illicit drug use were significantly better under diamorphine compared to methadone treatment, while there was no difference in health outcomes. Conclusion: Controlled studies are now necessary to examine whether diamorphine treatment could be considered as one of several options in treating severely opioid-dependent patients, regardless of previous maintenance treatment experience

Effects of heroin-assisted treatment on alcohol consumption: findings of the German randomized controlled trial

Alcohol has been suggested to be a risk factor for opioid-dependent patients in methadone maintenance treatment (MMT). Literature shows that MMT has limited effects on alcohol use. Nevertheless, a decrease in alcohol use was detected in the Swiss heroin-assisted treatment (HAT) study. In this article, we carry out an in-depth analysis of the German HAT trial with the aim of determining whether alcohol use was affected among patients undergoing HAT and MMT. Analysis was carried out using self-reported data on consumption units of alcohol used (CU), Addiction Severity Index composite scores (ASI CSs), and carbohydrate-deficient transferrin (CDT) measures. Results suggest significant reduction of CU and CDT in both groups, yet larger effects in the HAT group. ASI CS significantly decreased in the HAT but not in the MMT group. The greater benefit of HAT in reducing alcohol use may be due to the greater daily frequency of dispensing heroin coupled with a requirement of sobriety at each dosing occasion

Effects of Psychiatric Comorbidity on Treatment Outcome in Patients Undergoing Diamorphine or Methadone Maintenance Treatment

Background: Comorbid psychiatric disorders among opioid-dependent patients are associated with several negative outcome factors. However, outcomes of maintenance treatment have not been sufficiently established, and no evidence is available with respect to heroin-assisted treatment (HAT). Methods: For patients in the German heroin trial outcome measures were analyzed for HAT versus methadone maintenance treatment (MMT) both for patients with and without a comorbid diagnosis according to CIDI. Results: 47.2% of the sample had at least one comorbid psychiatric diagnosis, mainly neurotic, stress-related or somatoform (F4) or affective (F3) disorders. HAT had a better outcome than MMT concerning improvement of health and reduction of illicit drug use in both comorbid and non-comorbid patients, but weaker effects were found in the comorbid group. Conclusions:The better outcome of HAT also in comorbid patients suggests that psychiatric comorbidity should be an inclusion criterion for HAT. The weaker advantage of HAT may be due to pharmacological or methodological reasons

Acoustic and visual characterisation of methane-rich seabed seeps at Omakere Ridge on the Hikurangi Margin, New Zealand

Six active methane seeps and one cold-water reef that may represent a relict seep were mapped at Omakere Ridge on New Zealand's Hikurangi Margin during cruises SO191 and TAN0616. Hydroacoustic flares, interpreted to be bubbles of methane rising through the water column were identified in the area. The seep sites and the cold-water reef were characterised by regions of high backscatter intensity on sidescan sonar records, or moderate backscatter intensity where the seep was located directly below the path of the sidescan towfish. The majority of sites appear as elevated features (2–4 m) in multibeam swath data. Gas blanking and acoustic turbidity were observed in sub-bottom profiles through the sites. A seismic section across two of the sites (Bear's Paw and LM-9) shows a BSR suggesting the presence of gas hydrate as well as spots of high amplitudes underneath and above the BSR indicating free gas. All sites were ground truthed with underwater video observations, which showed the acoustic features to represent authigenic carbonate rock structures. Live chemosynthetic biotic assemblages, including siboglinid tube worms, vesicomyid clams, bathymodiolin mussels, and bacterial mats, were observed at the seeps. Cold-water corals were the most conspicuous biota of the cold-water reef but widespread vesicomyid clam shells indicated past seep activity at all sites. The correlation between strong backscatter features in sidescan sonar images and seep-related seabed features is a powerful tool for seep exploration, but differentiating the acoustic features as either modern or relict seeps requires judicial analysis and is most effective when supported by visual observations

Measuring quality of life in opioid dependent people : a systematic review of assessment instruments

Purpose Opioid dependence is a chronic relapsing disorder. Despite increasing research on quality of life (QOL) in people with opioid dependence, little attention has been paid to the instruments used. This systematic review examines the suitability of QOL instruments for use in opioid-dependent populations and the instruments’ quality. Methods A systematic search was performed in the databases Medline, PsycInfo, The Cochrane Library, and CINAHL. Articles were eligible if they assessed QOL of opioid-dependent populations using a validated QOL instrument. Item content relevance to opioid-dependent people was evaluated by means of content analysis, and instrument properties were assessed using minimum standards for patient-reported outcome measures. Results Eighty-nine articles were retrieved, yielding sixteen QOL instruments, of which ten were assessed in this review. Of the ten instruments, six were disease specific, but none for opioid dependence. Two instruments had good item content relevance. The conceptual and measurement model were described in seven instruments. Four instruments were developed with input from the respective target population. Eight instruments had low respondent and administrator burden. Psychometric properties were either not assessed in opioid-dependent populations or were inconclusive or moderate. Conclusions No instrument scored perfectly on both the content and properties. The limited suitability of instruments for opioid-dependent people hinders accurate and sensitive measurement of QOL in this population. Future research is in need of an opioid dependence-specific QOL instrument to measure the true impact of the disease on people’s lives and to evaluate treatment-related services

Switching opioid-dependent patients in substitution treatment from racemic methadone, levomethadone and buprenorphine to slow-release oral morphine: Analysis of the switching process in routine care

Since 2015 slow-release oral morphine (SROM) is approved for opioid substitution treatment (OST) in Germany. The SROMOS study (efficacy and tolerability of slow-release oral morphine in opioid substitution treatment) evaluates the efficacy and safety of SROM in routine care. This article describes the switching process from racemic methadone, levomethadone and buprenorphine to SROM.Between July 2016 and November 2017 180 patients in 23 study centers in Germany were included in the prospective, non-interventional, naturalistic observational study. Patients were already in OST and switched from a previous medication to SROM. The switching process was analyzed during a period of fourteen days.Data were available for 169 participants. The switching process had a different progression depending on premedication and pre dosage. On the fourteenth day of SROM treatment patients switched from racemic methadone took an average dosage of 922.2 mg/day, from levomethadone 801.0 mg/day and from buprenorphine 626.7 mg/day. Average conversion ratio racemic methadone to SROM was 1:11.8, levomethadone to SROM 1:17.4 and buprenorphine to SROM 1:58.0.This study provides the first data on the switching process from buprenorphine to SROM. Average dose ratio racemic methadone to SROM on the fourteenth day of treatment was considerably higher than recommended in the prescribing information

a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma

Background Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. Methods/Design ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and - in absence of available stem cells from earlier harvesting - undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3rd (arm A + B) and the 5th lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. Discussion This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. Trial registration: ISRCTN16345835 (date of registration 2010-08-24)