Endpoints in pediatric pain studies

Assessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the effects of analgesic drugs. Here, we review current and promising new endpoints used in pediatric pain assessment studies

Topical NSAIDs for chronic musculoskeletal pain in adults

Background: Use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) to treat chronic musculoskeletal conditions has become widely accepted because they can provide pain relief without associated systemic adverse events. This review is an update of 'Topical NSAIDs for chronic musculoskeletal pain in adults', originally published in Issue 9, 2012. Objectives: To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs for chronic musculoskeletal pain in adults. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and our own in-house database; the date of the last search was February 2016. We also searched the references lists of included studies and reviews, and sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' web sites. Selection criteria: We included randomised, double-blind, active or inert carrier (placebo) controlled trials in which treatments were administered to adults with chronic musculoskeletal pain of moderate or severe intensity. Studies had to meet stringent quality criteria and there had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. Data collection and analysis: Two review authors independently assessed studies for inclusion and extracted data. We used numbers of participants achieving each outcome to calculate risk ratio and numbers needed to treat (NNT) or harm (NNH) compared to carrier or other active treatment. We were particularly interested to compare different formulations (gel, cream, plaster) of individual NSAIDs. The primary outcome was 'clinical success', defined as at least a 50% reduction in pain, or an equivalent measure such as a 'very good' or 'excellent' global assessment of treatment, or 'none' or 'slight' pain on rest or movement, measured on a categorical scale. Main results: We identified five new studies for this update, which now has information from 10,631 participants in 39 studies, a 38% increase in participants from the earlier review; 33 studies compared a topical NSAID with carrier. All studies examined topical NSAIDs for treatment of osteoarthritis, and for pooled analyses studies were generally of moderate or high methodological quality, although we considered some at risk of bias from short duration and small size. In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier for reducing pain; about 60% of participants had much reduced pain. With topical diclofenac, the NNT for clinical success in six trials (2343 participants) was 9.8 (95% confidence interval (CI) 7.1 to 16) (moderate quality evidence). With topical ketoprofen, the NNT for clinical success in four trials (2573 participants) was 6.9 (5.4 to 9.3) (moderate quality evidence). There was too little information for analysis of other individual topical NSAIDs compared with carrier. Few trials compared a topical NSAID to an oral NSAID, but overall they showed similar efficacy (low quality evidence). These efficacy results were almost completely derived from people with knee osteoarthritis. There was an increase in local adverse events (mostly mild skin reactions) with topical diclofenac compared with carrier or oral NSAIDs, but no increase with topical ketoprofen (moderate quality evidence). Reporting of systemic adverse events (such as gastrointestinal upsets) was poor, but where reported there was no difference between topical NSAID and carrier (very low quality evidence). Serious adverse events were infrequent and not different between topical NSAID and carrier (very low quality evidence). Clinical success with carrier occurred commonly - in around half the participants in studies lasting 6 to 12 weeks. Both direct and indirect comparison of clinical success with oral placebo indicates that response rates with carrier (topical placebo) are about twice those seen with oral placebo. A substantial amount of data from completed, unpublished studies was unavailable (up to 6000 participants). To the best of our knowledge, much of this probably relates to formulations that have never been marketed. Authors' conclusions: Topical diclofenac and topical ketoprofen can provide good levels of pain relief beyond carrier in osteoarthritis for a minority of people, but there is no evidence for other chronic painful conditions. There is emerging evidence that at least some of the substantial placebo effects seen in longer duration studies derive from effects imparted by the NSAID carrier itself, and that NSAIDs add to that

Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis

A previous systematic review reported that topical NSAIDs were effective in relieving pain in chronic conditions like osteoarthritis and tendinitis. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. Studies were identified by searching electronic databases, and writing to manufacturers. We identified randomised, double blind trials comparing topical NSAID with either placebo or another active treatment, in adults with chronic pain. The primary outcome was a reduction in pain of approximately 50% at two weeks, and secondary outcomes were local and systemic adverse events and adverse event-related withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative harm and number-needed-to-harm (NNH) were calculated, and the effects of trial quality, validity and size, outcome reported, and condition treated, were examined by sensitivity analyses. Twelve new trials were added to 13 trials from a previous review. Fourteen double blind placebo-controlled trials had information from almost 1,500 patients. Topical NSAID was significantly better than placebo with relative benefit 1.9 (95% confidence interval 1.7 to 2.2), NNT 4.6 (95% confidence interval 3.8 to 5.9). Results were not affected by trial quality, validity or size, outcome reported, or condition treated. Three trials with 764 patients comparing a topical with an oral NSAID found no difference in efficacy. Local adverse events (6%), systemic adverse events (3%), or the numbers withdrawing due to an adverse event were the same for topical NSAID and placebo. Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks. Larger and longer trials are necessary to fully elucidate the place of topical NSAIDs in clinical practice

Acute Pain and a Motivational Pathway in Adult Rats: Influence of Early Life Pain Experience

The importance of neonatal experience upon behaviour in later life is increasingly recognised. The overlap between pain and reward pathways led us to hypothesise that neonatal pain experience influences reward-related pathways and behaviours in adulthood

Synthesis of novel organometal halides with elements of group 13 and 14 of the periodic system and attempts to prepare organogermanoles

Im ersten Teil der Arbeit steht die Darstellung und strukturelle Charakterisierung von Organometallhalogeniden der 13. Gruppe des Periodensystems im Mittelpunkt der Untersuchungen. Durch Fluorierung von [MeAlN(2,6-i-Pr2C6H3)]3 (1) mittels Me3SnF und BF3·OEt2 werden die terminal gebundenen Methyl-Gruppen durch Halogenatome ausgetauscht und [FAlN(2,6-i-Pr2C6H3)]3·3 THF (7) und [Me2SnN(2,6-i-Pr2C6H3)]2 (8) (nur mit Me3SnF erhältlich), als Nebenprodukt, isoliert. Die Reaktionen von 1 mit Bortrihalogeniden in THF ergeben die entsprechenden Verbindungen [ClAlN(2,6-i-Pr2C6H3)]3·3 THF (9) und [BrAlN(2,6-i-Pr2C6H3)]3·3 THF (10). Eine entsprechende Iod-Verbindung kann nicht isoliert werden. Die Reaktion von 1 mit H3B·THF führt lediglich zu [MeAlN(2,6-i-Pr2C6H3)]3×3 THF (11).Im zweiten Teil der Arbeit wird die Darstellung von monoorganylsubstituierten Germaniumhalogeniden beschrieben. Als Ligandensystem zur Stabilisierung derselben wird der Terphenyl-Ligand 2,6-Bis(2 ,6 -dimethylphenyl)phenyl ausgewählt. Diese sind durch Reaktion von n-BuLi und 2,6-Bis(2 ,6 -dimethylphenyl)-1-iodbenzol (12) und anschließender Umsetzung mit einem Germaniumtetrahalogenid erhältlich. Durch stöchiometrische Reaktionen mit dem Lithiumsalz von 12 sind 2,6-Bis(2 ,6 -dimethylphenyl)-phenylgermaniumtrichlorid (13), 2,6-Bis(2 ,6 -dimethylphenyl)-phenylgermaniumtribromid (14) und 2,6-Bis(2 ,6 -dimethylphenyl)-phenylgermaniumtriiodid (15) in hohen Ausbeuten darstellbar. Mit Me3SnF als Fluorierungsmittel kann 13 fluoriert und das 2,6-Bis(2 ,6 -dimethylphenyl)phenylgermaniumtrifluorid (16) erhalten werden. Auf gleiche Weise wird DippN(SiMe3)GeF3 (17) dargestellt. Verbindungen 16 und 17 sind flüssige Substanzen mit relativ hohen Siedepunkten.Im anschließenden Teil werden Versuche zur Darstellung von Germanolen beschrieben. Um Kondensationsreaktionen zu verhindern, werden DippN(SiMe3)GeBr3 bzw. Verbindung 13 verwendet. Jedoch zeigen alle Versuche, dass als Produkte nur adamantanartige Gerüste als Hauptprodukte isoliert werden können.Abschließend werden niedervalente Elemente der 14. Gruppe auf ihre Reaktivität untersucht. Durch Reaktion von (Dipp)2NacNacGe(BH3)H mit H3Al×NMe3 kann (Dipp)2NacNacAlHBH2 (20) isoliert werden, wobei erstmalig eine Aluminium-Bor-Bindung mit der formalen Oxidationsstufe II für beide Elemente bestimmt werden kann

Disputatio inauguralis illustrium iuris controversiarum centuriam exhibens

quam ... pro summis honoribus ... utroque in iure doctoralibus rite obtinendis ... publice instituendae expono Bernhard. Hohmeister Hannovera-Brunsvigus ad diem anni Epoch. Christ. M D C XXVIIDruckjahr nach der Datierung im TitelEnthält 100 ThesenTitelvariante gemäss MommsenDiss. iur. Basel, 162

Kritische Erfolgsfaktoren für die Auswahl eines IT-Serviceproviders am Beispiel der gesetzlichen Unfallversicherungen

Seit der Einführung des E‑Government Gesetzes ist das Thema in deutschen Verwaltungen omnipräsent. Die durch das Onlinezugangsgesetz (OZG) verpflichtende Bereitstellung von Online-Services erhöht den Druck auf die Verwaltungen zusätzlich. Ganzheitliche Veränderungen der Organisation sind nötig, um sich an den Bedarf der veränderten Umwelt anzupassen. Die Bürger*innen erwarten von den Verwaltungen Komfort in der Kommunikation und digitale Verarbeitung aller Anliegen wie im privaten oder beruflichen Umfeld. Eine Unterstützung bei der Umsetzung der Anforderungen des OZG bzw. des E-Governments können IT-Serviceprovider darstellen. Diese sind in der Lage, zentralisierte, skalierbare Soft- und Hardwarelösungen bereitzustellen und Defizite im vorhandenen Know-How sowie Ressourcenengpässe im öffentlichen Sektor zu kompensieren. Entscheidend dafür ist die rechtskonforme und zukunftssichere Auswahl eines IT-Serviceproviders. Dieser Forschungsbeitrag identifiziert und analysiert die für die Auswahl eines IT-Serviceproviders maßgeblichen kritischen Erfolgsfaktoren im Umfeld der gesetzlichen Unfallversicherungen Deutschlands. Aus Sicht der Wissenschaft trägt dieser Artikel somit zu einer breiteren Diskussion im Bereich Strategien zu e‑Government bzw. E‑Governance sowie Umsetzung des OZG bei. Für die Praxis wird aufgezeigt, wie ein strategischer Mehrwert aus der Neuausrichtung der gesetzlichen Unfallversicherungen hin zu einer modernen Verwaltung entstehen kann, um zukünftigen Entscheidungsträger*innen weitsichtige Entscheidungen zu ermöglichen und den Bürger*innen optimierte Services anbieten zu können.AIM Austrian Institute of Management Gmb

The invasive Korean bush mosquito Aedes koreicus (Diptera: Culicidae) in Germany as of 2020

BACKGROUND: The Korean bush mosquito Aedes koreicus was recently reported to have established a population in western Germany (Wiesbaden) in 2016. The species is difficult to distinguish morphologically from its close relative, the invasive Japanese bush mosquito Ae. japonicus, which is already widely distributed in many parts of Germany, including the area colonised by Ae. koreicus. Genetic confirmation of morphologically identified “Ae. japonicus” collection material, however, had only been done exceptionally before the German Ae. koreicus population became known. METHODS: Dried archived “Ae. japonicus” specimens both from the municipality of Wiesbaden and from deliberately and randomly selected distribution sites all over Germany were re-examined morphologically and genetically for admixture by Ae. koreicus. Moreover, cemeteries in the greater Wiesbaden area were sampled in 2019 and 2020 to check for Ae. koreicus spread. Korean and Japanese bush mosquitoes submitted to the German citizen science mosquito monitoring scheme “Mueckenatlas” in 2019 and 2020 were also subjected to particularly thorough species identification. The ND4 DNA sequences generated in this study in the context of species identification were phylogenetically compared to respective GenBank entries of Ae. koreicus. As a by-product, several genetic markers were evaluated for their suitability to identify Ae. koreicus. RESULTS: Aedes koreicus specimens could be identified in mosquito collection material and submissions from Wiesbaden from 2015 onwards, suggesting establishment to have happened in the same year as Ae. japonicus establishment. Detections of Ae. koreicus from 2019 and 2020 in Wiesbaden indicate a negligible enlargement of the populated area as described for 2018. Two Ae. koreicus specimens were also submitted from the city of Munich, southern Germany, in 2019 but further specimens could not be identified during immediate local inspections. Comparison of ND4 sequences generated in this and other studies demonstrate a high degree of homology, suggesting that this DNA region is not informative enough for clarification of origins and relationships of Ae. koreicus populations. For genetic identification of Ae. koreicus, PCR primers used for classical CO1 barcoding were found to lead to mismatches and produce no or incorrect amplicons. Alternative CO1 primers or a validated ND4 marker should be used instead. CONCLUSIONS: Aedes koreicus is probably introduced into Germany every now and then but rarely succeeds in becoming established. As with most European populations, the German population is characterised by a limited expansion tendency. Since Ae. koreicus is a potential vector, however, Asian bush mosquitoes found at new places should be examined quite carefully and known distribution areas of Ae. japonicus regularly checked for the presence of Ae. koreicus