Safety and effectiveness of Buprenorphine-Naloxone sublingual tablet in the treatment of opioid use disorder

In 2007 buprenorphine-naloxone, a medication for the treatment of opioid use disorder, was launched in Germany. The medication consists of the combination of buprenorphine and naloxone in a 4:1 ratio and was developed because the mono-compound buprenorphine, a well-established medication in opioid dependence therapy, had been subject to diversion and misuse. A non-interventional post-authorization safety study was conducted from 2008 to 2010 to collect comprehensive reallife data on the treatment of opioid dependent patients with buprenorphine-naloxone in Germany. Three major articles, published in international peer-review journals, evaluated data from this study on safety, effectiveness and tolerance, predictive value of the first four weeks as well as risk of liver-enzyme elevation in the treatment of opioid dependent patients with buprenorphine-naloxone. The findings from these extensive evaluations indicate a high safety profile, a high effectiveness, tolerance and acceptability with substantial improvements in quality of life, mental and physical health. There was no evidence for an increased risk for liver-enzyme elevation even in patients with hepatitis C infections. In the first four weeks specific and general parameters with high predictive value were found that can be used as early signals to adjust the therapy plan in order to positively influence course and outcome of opioid dependence treatment with buprenorphine-naloxone in routine care.2007 wurde Buprenorphin-Naloxon, ein Medikament für die Behandlung der Opioidabhängigkeit, in Deutschland zugelassen. Das Medikament enthält die Kombination von Buprenorphin und Naloxon in einem Verhältnis von 4:1 und wurde aufgrund zunehmenden Missbrauchs von Buprenorphin, einem gut etablierten Medikament zur Behandlung der Opioidabhängigkeit, entwickelt. Eine nicht-interventionelle Sicherheitsstudie wurde von 2008 bis 2010 durchgeführt, um umfassende Daten zur Routinebehandlung von opioidabhängigen Patienten mit Buprenorphin-Naloxon in Deutschland zu erheben. Drei Hauptartikel, die in internationalen Peer-Review Fachzeitschriften publiziert wurden, analysierten die Daten der Studie hinsichtlich Sicherheit, Effektivität und Toleranz, vorhersagefähiger Variablen der ersten vier Wochen sowie das Risiko für erhöhte Leberenzymwerte in der Behandlung von opioidabhängigen Patienten mit Buprenorphin-Naloxon. Die Ergebnisse dieser umfangreichen Analysen weisen auf ein hohes Sicherheitsprofil, eine hohe Effektivität, Toleranz und Akzeptanz mit deutlichen Verbesserungen in der Lebensqualität sowie der psychischen und physischen Gesundheit hin. Es zeigten sich keine Anzeichen eines erhöhten Risikos für einen Anstieg der Leberenzymwerte sogar bei Patienten mit einer Hepatitis C Infektion. Die ersten vier Wochen haben einen hohen Vorhersagewert mit spezifischen und generellen Parametern, die als frühzeitige Signale genutzt werden können, um den Behandlungsplan anzupassen und damit Verlauf und Ausgang der Behandlung mit Buprenorphin-Naloxon in der Routinebehandlung positiv zu beeinflussen

Introducing Originality and Innovation in Engineering Teaching: The Hydraulic Design of Culverts

Recently the teaching of engineering design has become a presentation of standards and codes rather than the learning of sound design practices. Too many students request formulae and equations to solve a design exercise and they fail to develop any design originality. The present student attitude leads to young graduate engineers without critical ability and innovative flair. The writer has developed an innovative hydraulic design exercise based upon culvert design. Each design exercise could lead to more than one correct design per student in the class. Students have to learn basic design calculations based upon lecture material, notes, field visits and laboratory experiment. The practical component (laboratory, field visit) contributes significantly to their understanding of the complete system, including some basic safety and professional issues

Safety and effectiveness of Buprenorphine-Naloxone sublingual tablet in the treatment of opioid use disorder

In 2007 buprenorphine-naloxone, a medication for the treatment of opioid use disorder, was launched in Germany. The medication consists of the combination of buprenorphine and naloxone in a 4:1 ratio and was developed because the mono-compound buprenorphine, a well-established medication in opioid dependence therapy, had been subject to diversion and misuse. A non-interventional post-authorization safety study was conducted from 2008 to 2010 to collect comprehensive reallife data on the treatment of opioid dependent patients with buprenorphine-naloxone in Germany. Three major articles, published in international peer-review journals, evaluated data from this study on safety, effectiveness and tolerance, predictive value of the first four weeks as well as risk of liver-enzyme elevation in the treatment of opioid dependent patients with buprenorphine-naloxone. The findings from these extensive evaluations indicate a high safety profile, a high effectiveness, tolerance and acceptability with substantial improvements in quality of life, mental and physical health. There was no evidence for an increased risk for liver-enzyme elevation even in patients with hepatitis C infections. In the first four weeks specific and general parameters with high predictive value were found that can be used as early signals to adjust the therapy plan in order to positively influence course and outcome of opioid dependence treatment with buprenorphine-naloxone in routine care.2007 wurde Buprenorphin-Naloxon, ein Medikament für die Behandlung der Opioidabhängigkeit, in Deutschland zugelassen. Das Medikament enthält die Kombination von Buprenorphin und Naloxon in einem Verhältnis von 4:1 und wurde aufgrund zunehmenden Missbrauchs von Buprenorphin, einem gut etablierten Medikament zur Behandlung der Opioidabhängigkeit, entwickelt. Eine nicht-interventionelle Sicherheitsstudie wurde von 2008 bis 2010 durchgeführt, um umfassende Daten zur Routinebehandlung von opioidabhängigen Patienten mit Buprenorphin-Naloxon in Deutschland zu erheben. Drei Hauptartikel, die in internationalen Peer-Review Fachzeitschriften publiziert wurden, analysierten die Daten der Studie hinsichtlich Sicherheit, Effektivität und Toleranz, vorhersagefähiger Variablen der ersten vier Wochen sowie das Risiko für erhöhte Leberenzymwerte in der Behandlung von opioidabhängigen Patienten mit Buprenorphin-Naloxon. Die Ergebnisse dieser umfangreichen Analysen weisen auf ein hohes Sicherheitsprofil, eine hohe Effektivität, Toleranz und Akzeptanz mit deutlichen Verbesserungen in der Lebensqualität sowie der psychischen und physischen Gesundheit hin. Es zeigten sich keine Anzeichen eines erhöhten Risikos für einen Anstieg der Leberenzymwerte sogar bei Patienten mit einer Hepatitis C Infektion. Die ersten vier Wochen haben einen hohen Vorhersagewert mit spezifischen und generellen Parametern, die als frühzeitige Signale genutzt werden können, um den Behandlungsplan anzupassen und damit Verlauf und Ausgang der Behandlung mit Buprenorphin-Naloxon in der Routinebehandlung positiv zu beeinflussen

A noncanonical PWI domain in the N-terminal helicase-associated region of the spliceosomal Brr2 protein

The spliceosomal RNA helicase Brr2 is required for the assembly of a catalytically active spliceosome on a messenger RNA precursor. Brr2 exhibits an unusual organization with tandem helicase units, each comprising dual RecA-like domains and a Sec63 homology unit, preceded by a more than 400-residue N-terminal helicase-associated region. Whereas recent crystal structures have provided insights into the molecular architecture and regulation of the Brr2 helicase region, little is known about the structural organization and function of its N-terminal part. Here, a near-atomic resolution crystal structure of a PWI-like domain that resides in the N-terminal region of Chaetomium thermophilum Brr2 is presented. CD spectroscopic studies suggested that this domain is conserved in the yeast and human Brr2 orthologues. Although canonical PWI domains act as low-specificity nucleic acid-binding domains, no significant affinity of the unusual PWI domain of Brr2 for a broad spectrum of DNAs and RNAs was detected in band-shift assays. Consistently, the C. thermophilum Brr2 PWI-like domain, in the conformation seen in the present crystal structure, lacks an expanded positively charged surface patch as observed in at least one canonical, nucleic acid-binding PWI domain. Instead, in a comprehensive yeast two-hybrid screen against human spliceosomal proteins, fragments of the N-terminal region of human Brr2 were found to interact with several other spliceosomal proteins. At least one of these interactions, with the Prp19 complex protein SPF27, depended on the presence of the PWI-like domain. The results suggest that the N-terminal region of Brr2 serves as a versatile protein-protein interaction platform in the spliceosome and that some interactions require or are reinforced by the PWI-like domain

Hydraulic Performances of Minimum Energy Loss Culverts in Australia

Culverts are among the most common hydraulic structures. Modern designs do not differ from ancient structures and are often characterised by significant afflux at design flows. A significant advance was the development of the Minimum Energy Loss (MEL) culverts in the late 1950s. The design technique allows a drastic reduction in upstream flooding associated with lower costs. The development and operational performances of this type of structure is presented. The successful operation of MEL culverts for more than 40 years is documented with first-hand records during and after floods. The experiences demonstrate the design soundness while highlighting the importance of the hydraulic expertise of the design engineers

Languages ordered by the subword order

We consider a language together with the subword relation, the cover relation, and regular predicates. For such structures, we consider the extension of first-order logic by threshold- and modulo-counting quantifiers. Depending on the language, the used predicates, and the fragment of the logic, we determine four new combinations that yield decidable theories. These results extend earlier ones where only the language of all words without the cover relation and fragments of first-order logic were considered

Hydraulic engineering in the 21st century: Where to?

For centuries, hydraulic engineers were at the forefront of science. The last forty years marked a change of perception in our society with a focus on environmental sustainability and management, particularly in developed countries. Herein, the writer illustrates his strong belief that the future of hydraulic engineering lies upon a combination of innovative engineering, research excellence and higher education of quality. This drive continues a long tradition established by eminent scholars like Arthur Thomas IPPEN, John Fisher KENNEDY and Hunter ROUSE

Concurrent Outbreak of Norovirus Genotype I and Enterotoxigenic Escherichia coli on a U.S. Navy Ship following a Visit to Lima, Peru

An outbreak of norovirus (NoV) genotype I and Enterotoxigenic Escherichia coli (ETEC) occurred among US Navy Ship personnel following a visit to Lima, Peru, in June 2008. Visiting a specific area in Lima was significantly associated with illness. While ETEC and NoV are commonly recognized as causative agents of outbreaks, co-circulation of both pathogens has been rarely observed in shipboard outbreaks

A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair

Bulky DNA lesions in transcribed strands block RNA polymerase II (RNAPII) elongation and induce a genome-wide transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but how transcription is restored in the genome following DNA repair remains unresolved. Here, we find that the TCR-specific CSB protein loads the PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. Although dispensable for TCR-mediated repair, PAF1C is essential for transcription recovery after UV irradiation. We find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress. The transcription-coupled repair pathway removes transcription-blocking DNA lesions, but how transcription is restored following DNA repair is not clear. Here the authors reveal that the PAF1 complex, while dispensable for the repair process, restores transcription after DNA damage.Cancer Signaling networks and Molecular Therapeutic