Slow release oral morphine versus methadone for the treatment of opioid use disorder.

OBJECTIVE: To assess the efficacy of slow release oral morphine (SROM) as a treatment for opioid use disorder (OUD). DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: Three electronic databases were searched through 1 May 2018: the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. We also searched the following electronic registers for ongoing trials: ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Current Controlled Trials and the EU Clinical Trials Register. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included RCTs of all durations, assessing the effect of SROM on measures of treatment retention, heroin use and craving in adults who met the diagnostic criteria for OUD. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the random-effects model and expressed as risk ratios (RRs) or mean differences with 95% CIs. Heterogeneity was assessed (χ2 statistic) and quantified (I2 statistic) and a sensitivity analysis was undertaken to assess the impact of particular high-risk trials. RESULTS: Among 1315 records screened and four studies reviewed, four unique randomised trials met the inclusion criteria (n=471), and compared SROM with methadone. In the meta-analysis, we observed no significant differences between SROM and methadone in improving treatment retention (RR=0.98; 95%CI: 0.94 to 1.02, p=0.34) and heroin use (RR=0.96; 95% CI: 0.61 to 1.52, p=0.86). Craving data was not amenable to meta-analysis. Available data implied no differences in adverse events, heroin, cocaine or benzodiazepine use. CONCLUSIONS: Meta-analysis of existing randomised trials suggests SROM may be generally equal to methadone in retaining patients in treatment and reducing heroin use while potentially resulting in less craving. The methodological quality of the included RCTs was low-to-moderate.

Association of polymorphisms in pharmacogenetic candidate genes (OPRD1, GAL, ABCB1, OPRM1) with opioid dependence in European population: a case-control study.

It is becoming increasingly evident that genetic variants contribute to the development of opioid addiction. An elucidation of these genetic factors is crucial for a better understanding of this chronic disease and may help to develop novel therapeutic strategies. In recent years, several candidate genes were implicated in opioid dependence. However, most study findings have not been replicated and additional studies are required before reported associations can be considered robust. Thus, the major objective of this study was to replicate earlier findings and to identify new genetic polymorphisms contributing to the individual susceptibility to opioid addiction, respectively. Therefore, a candidate gene association study was conducted including 142 well-phenotyped long-term opioid addicts undergoing opioid maintenance therapy and 142 well-matched healthy controls. In both study groups, 24 single nucleotide polymorphisms predominantly located in pharmacogenetic candidate genes have been genotyped using an accurate mass spectrometry based method. The most significant associations with opioid addiction (remaining significant after adjustment for multiple testing) were observed for the rs948854 SNP in the galanin gene (GAL, p = 0.001) and the rs2236861 SNP in the delta opioid receptor gene (OPRD1, p = 0.001). Moreover, an association of the ATP binding cassette transporter 1 (ABCB1) variant rs1045642 and the Mu Opioid receptor (OPRM1) variant rs9479757 with opioid addiction was observed. The present study provides further support for a contribution of GAL and OPRD1 variants to the development of opioid addiction. Furthermore, our results indicate a potential contribution of OPRM1 and ABCB1 SNPs to the development of this chronic relapsing disease. Therefore it seems important that these genes are addressed in further addiction related studies.

Psychosocial workload and stress in the workers' representative.

BACKGROUND: Using a data set of works councils of trade union IG Metal, this paper investigates psychosocial stress and strain on this specific group in comparison to employees working in administration in general (leadership and non-leadership-role) and a national reference value. METHODS: For assessing psychosocial work factors on works councils within the sector represented by the trade union IG Metal in Germany, a research by using the German standard version of COPSOQ (Copenhagen Psychosocial Questionnaire) was performed. The instrument includes 87 single items forming 25 aspects of strain and stress. Results from the study group of works councils were compared to those from employees working in administration and to the general population mean (COPSOQ database). Statistical analysis included t-tests, analysis of variance and multiple comparisons of means. To be significant in terms of statistics, p<0.05 (two-tailed) and a minimum deviation of 5 or more points between groups' mean values identify the relevant values. RESULTS: All in all, 309 works councils from a national survey of the German chemical and metalworking industries took part in the study. 113 were full-time works council members (exempted from the duty to perform their regular work), 196 were voluntary members (acting as employee representatives on an honorary basis alongside their normal duties). Comparison between works councils and employees working in administration (leadership roles (N=1810) and non-leadership roles (N=2970)) and for employees in general (N=35.000) showed unfavourable values for works councils for most scales. Significantly higher values indicating higher strain and stress were found for the scales: emotional demands, work-privacy conflict, role conflicts, mobbing, cognitive stress symptoms and burnout. Unfavourable results were obtained for the aspects: quality of leadership, social support, sense of community and general health. Favourable findings were found on the scales: influence at work, quantity of social relations and the partly positive values for quantitative demands and commitment to the workplace. CONCLUSION: Compared to the reference groups, works council members perceive the psychosocial demands of working life as more exhausting for the majority of aspects. This allows several conclusions. One reason may be the extended tasks employee representatives face, an other may be that the education of most works council members does not seem appropriate to the high demands of their managerial and executive tasks.

[Outlines of interdisciplinary addiction research given by the example of medical imaging with PET, SPECT and fMRI regarding effects of psychotropic substances]. / Umrisse interdisziplinärer Suchtforschung am Beispiel medizinischer Bildgebung mittels PET, SPECT und fMRT zur Wirkung psychotroper Substanzen.

The addiction phenomenon provides a fertile ground for the application of the tools of medical imaging which contribute to the development of scientific conceptualization of the effect of psychotropic substances. Medical imaging as for instance PET (Positron Emission Tomography), SPECT (Single Photon Emission Tomography) or functional Magnetic Resonance Imaging (fMRI) are well established for the examination of functional activity in the living brain. Medical imaging permits the development of functional activation maps during perceptual, cognitive or emotional efforts with a high temporal and spatial resolution. Medical imaging devices have therefore also been used to help our understanding of many aspects of the pharmacokinetics and pharmacodynamics of abused drugs. Because Delta-9-Tetrahydrocannabinol and cocaine continue to be the most commonly used illicit drugs, their effects on the brain function are of major interest. The cannabinoid CB(1) receptor agonist Delta(9)-THC as for instance has also been suggested for treatment of Tourette syndrome (TS). This article provides an overview of present applications of medical imaging with PET, SPECT, and fMRI and its results regarding addiction-related research on Delta-9-Tetrahydrocannabinol and cocaine.

[Impact of slow-release oral morphine on drug abusing habits in Austria]. / Der Einfluss von retardiertem Morphin auf die Drogensituation in Osterreich.

A well-established possibility to treat opiate addiction is the participation in opiate maintenance treatment programmes. For this purpose the opioids methadone and buprenorphine have been evaluated and are used nowadays in many countries. However, since 1998 also the use of slow-release oral morphine (SROM) has been legally permitted in Austria. Our data show that these morphine preparations are frequently abused and are dominating the black market in the meantime. Especially the intravenous consumption of SROM goes along with highly dangerous side effects that exceed the risks of needle sharing alone. Special galenics are supposed to ensure a 24 h effect of the otherwise quickly metabolised morphine. If dissolved and injected, insoluble contents such as talcum cause microembolisms, leading to severe damages of the inner organs. Furthermore, SROM, i.e. a drug prescribed by physicians, has been proved to be the main responsible substance in most drug related deaths since its permission and has nearly replaced heroin. Forensic physicians play a major role in the profound examination of these cases, including extensive toxicological analyses and interpretation of results. For instance, a differentiation between a recent morphine and heroin consumption is certainly possible, provided appropriate methods are used. A reliable estimation of the current situation of drug abusing habits is a premise for adequate therapeutic offers and preventive measures. Thus, well-founded and comparable data have to be collected. To facilitate data report a standardized report form has been developed that includes an obligatory statement regarding morphine or heroin consumption. This should help to enlighten the ongoing discussion on the role of SRM in drug abuse cases. Our results indicate that the prescription of SROM in opiate maintenance therapy has to be handled very strictly and should be reserved for special patients only. A slackening of the Austrian law concerning SROM is therefore objected.

Sublingual buprenorphine and methadone maintenance treatment: a three-year follow-up of quality of life assessment.

This study was conducted to compare long-term outcome effects on the quality of life (QOL) of oral methadone with sublingual buprenorphine maintenance treatment. The QOL status of opioid-dependent patients was assessed using the German version ("Berlin Quality of Life Profile") of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opiate Withdrawal Scale (OWS). Urine tests were carried out randomly to detect additional consumption. In the first study period, 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years. The retention rate was 50% for methadone and 45% for buprenorphine (p = 0.786). Baseline values of the total sample (completers and noncompleters) QOL and somatic complaints did not show significant differences between the two treatment groups. QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job (p = 0.013), family, and total score of physical symptoms (p = 0.002), in which the completer group showed the more favorable values. Concerning physical symptoms at 36 months, logistic regression revealed significantly less stomach cramps (p = 0.037) and fatigue and tiredness (p = 0.034) in buprenorphine compared to the methadone. Moreover, the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines (p = 0.015) compared with methadone participants. It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine. In summary, regarding QOL and health status, the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients.

[Current consumer conditions among opioid addicts--implications for maintenance-treatment programmes provided by ambulatory drug treatment centers and physicians]. / Aktuelle Konsumformen bei Drogenabhängigkeit--Implikationen für Substitutionsprogramme in ambulanten Einrichtungen und bei behandelnden Arzten.

BACKGROUND: Anonymous evaluation of the current conditions of drug scene and drug consumption, entrance age, personal motives for drug consumption and satisfaction among opioid-dependent clients with treatments available within an ambulant maintenance treatment setting. METHODS: The questionnaire for the study was based on representative studies and covered 112 questions regarding drug consumption. In addition, an instrument of the "Hessische Landesstelle gegen die Suchtgefahren", which measures satisfaction of opioid clients regarding public drug-treatment centers, was used. RESULTS: A total of 158 opioid clients within an ambulant maintenance treatment setting were enrolled in the study. The mean age at first drug consumption was 15.1 (2.4) years for men and 15.2 (3.5) years for women. The Spearman correlation showed a significant positive correlation (r=0.284) between age and time of first drug consumption (p=0.019). Cannabis was the most frequent entrance drug (55.8%), followed by alcohol (33.8%), opioids (17.6%) and nicotine (11.8%). Additional consumption of benzodiazepines was observed in 44.7% of men and 39.7% of women, of cannabis in 74.5% of men and 52.4% of women, and of sustained-release morphine in 41.4% of men and 33.3% of women. Within the previous 6-12 months cocaine was consumed significantly less (p=0.024) by men (63.8%) than by women (90.5%). 93.3% of the drug users rated a follow-up assistance programme after withdrawal and 71.9% special care programmes for designer drugs very important. IMPLICATIONS: The present study supports the assumption of an earlier age of first drug consumption. In view of our findings on entrance age, and on polytoxicomanic consumption patterns and gender-specific differences, we believe that the objectives of substitution programmes can only be reached if programmes are adequately adapted to the actual conditions of the drug scene and are able to cooperate with other public drug-treatment systems.

Accuracy of spinal navigation for magerl screws.

The influence of a protocol of preoperative computed tomography scanning and a special registration technique was assessed on the accuracy of navigation for implanting Magerl C1-C2-screws. The use of navigation systems for implanting Magerl screws could help to decrease the risk of complications and to reduce the required skin incision. Two parameters conceivably affecting the accuracy are the protocol of preoperative computed tomography scanning and the registration technique. Four cervical spine segments of human cadavers were scanned with two computed tomography protocols. Registration was done based on anatomic landmarks or using a specially designed percutaneous registration device. For the accuracy check, the pointer tip was placed exactly on the markers. The displayed distance on the monitor was referred as an estimate of accuracy. Varying the computed tomography protocol did not significantly affect the accuracy. The mean accuracy was improved from 3 mm after anatomic pair-point matching to 1.5 mm after matching using the percutaneous registration device. The accuracy obtainable seems to be sufficient for implanting Magerl screws by using frameless stereotactic navigation. Three-millimeter slice thickness and 2-mm table increment is a proper protocol for preoperative computed tomography scanning. Fiducial markers improve the accuracy significantly.

Resolution requirements for monitor viewing of digital flat-panel detector radiographs: a contrast detail analysis.

With the introduction of digital flat-panel detector systems into clinical practice, the still unresolved question of resolution requirements for picture archiving communication system (PACS) workstation monitors has gained new momentum. This contrast detail analysis was thus performed to define the differences in observer performance in the detection of small low-contrast objects on clinical 1K and 2K monitor workstations. Images of the CDRAD 2.0 phantom were acquired at varying exposures on an indirect-type digital flat-panel detector. Three observers evaluated a total of 15 images each with respect to the threshold contrast for each detail size. The numbers of correctly identified objects were determined for all image subsets. No significant difference in the correct detection ratio was detected among the observers; however, the difference between the two types of workstations (1K vs 2K monitors) despite less than 3% was significant at a 95% confidence level. Slight but statistically significant differences exist in the detection of low-contrast nodular details visualized on 1K- and 2K-monitor workstations. Further work is needed to see if this result holds true also for comparison of clinical flat-panel detector images and may, for example, exert an influence on the diagnostic accuracy of chest X-ray readings.

Investigation of cerebrovascular disease with MR angiography: comparison of volume rendering and maximum intensity projection algorithms--initial assessment.

We assessed the clinical utility of the volume-rendering (VR) algorithm as a postprocessing technique of intracranial magnetic resonance angiography (MRA) for the evaluation of cerebrovascular disease in comparison with the maximum intensity projection (MIP) algorithm. VR and MIP images were compared with digital subtraction angiography (DSA). Volume-rendered views improved the perceptibility of intracranial vasculature and consequently augmented diagnostic confidence, improved the characterization of underlying vascular pathologies, and facilitated image interpretation. Volume rendering has the potential to expand the role of cerebral MRA in the diagnostic investigation and treatment planning of cerebrovascular disease.

Storage phosphor radiography of wrist fractures: a subjective comparison of image quality at varying exposure levels.

Image quality of storage phosphor radiographs acquired at different exposure levels was compared to define the minimal radiation dose needed to achieve images which allow for reliable detection of wrist fractures. In a study on 33 fractured anatomical wrist specimens image quality of storage phosphor radiographs was assessed on a diagnostic PACS workstation by three observers. Images were acquired at exposure levels corresponding to a speed classes 100, 200, 400 and 800. Cortical bone surface, trabecular bone, soft tissues and fracture delineation were judged on a subjective basis. Image quality was rated according to a standard protocol and statistical evaluation was performed based on an analysis of variance (ANOVA). Images at a dose reduction of 37% were rated sufficient quality without loss in diagnostic accuracy. Sufficient trabecular and cortical bone presentation was still achieved at a dose reduction of 62%. The latter images, however, were considered unacceptable for fracture detection. To achieve high-quality storage phosphor radiographs, which allow for a reliable evaluation of wrist fractures, a minimum exposure dose equivalent to a speed class of 200 is needed. For general-purpose skeletal radiography, however, a dose reduction of up to 62% can be achieved. A choice of exposure settings according to the clinical situation (ALARA principle) is recommended to achieve possible dose reductions.

Direct digital radiography versus storage phosphor radiography in the detection of wrist fractures.

AIM: To define the value of digital radiography with a clinical flat panel detector system for evaluation of wrist fractures in comparison with state of the art storage phosphor radiography. MATERIAL AND METHODS: Hard copy images of 26 fractured wrist specimens were acquired with the same exposure dose on a state of the art storage phosphor radiography system and a clinical flat panel detector. Image features like cortical bone surface, trabecular bone, soft tissues and fracture delineation were independently analysed by 4 observers using a standardised protocol. Image quality ratings were evaluated with an analysis of variance (ANOVA). RESULTS: Flat panel detector radiographs were rated superior with respect to cortical and trabecular bone representation as well as fracture evaluation, while storage phosphor radiographs produced better soft tissue detail. CONCLUSION: In some of the observed image quality aspects, the performance of caesium iodide/amorphous silicon flat panel detector exceeds state of the art storage phosphor radiography. This makes it well suited for skeletal imaging particularly in trauma as seen in the detection of wrist fractures.