Cannabis-based medicines and medical cannabis for adults with cancer pain

Background: Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate‐to‐severe pain. This can have a major negative impact on their quality of life. Opioid (morphine‐like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids.Objectives: To evaluate the benefits and harms of cannabis‐based medicines, including medical cannabis, for treating pain and other symptoms in adults with cancer compared to placebo or any other established analgesic for cancer pain.Search methods: We used standard, extensive Cochrane search methods. The latest search date was 26 January 2023.Selection criteria: We selected double‐blind randomised, controlled trials (RCT) of medical cannabis, plant‐derived and synthetic cannabis‐based medicines against placebo or any other active treatment for cancer pain in adults, with any treatment duration and at least 10 participants per treatment arm.Data collection and analysis: We used standard Cochrane methods. The primary outcomes were 1. proportions of participants reporting no worse than mild pain; 2. Patient Global Impression of Change (PGIC) of much improved or very much improved and 3. withdrawals due to adverse events. Secondary outcomes were 4. number of participants who reported pain relief of 30% or greater and overall opioid use reduced or stable; 5. number of participants who reported pain relief of 30% or greater, or 50% or greater; 6. pain intensity; 7. sleep problems; 8. depression and anxiety; 9. daily maintenance and breakthrough opioid dosage; 10. dropouts due to lack of efficacy; 11. all central nervous system adverse events. We used GRADE to assess certainty of evidence for each outcome.Main results: We identified 14 studies involving 1823 participants. No study assessed the proportions of participants reporting no worse than mild pain on treatment by 14 days after start of treatment.We found five RCTs assessing oromucosal nabiximols (tetrahydrocannabinol (THC) and cannabidiol (CBD)) or THC alone involving 1539 participants with moderate or severe pain despite opioid therapy. The double‐blind periods of the RCTs ranged between two and five weeks. Four studies with a parallel design and 1333 participants were available for meta‐analysis.There was moderate‐certainty evidence that there was no clinically relevant benefit for proportions of PGIC much or very much improved (risk difference (RD) 0.06, 95% confidence interval (CI) 0.01 to 0.12; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 8 to 100). There was moderate‐certainty evidence for no clinically relevant difference in the proportion of withdrawals due to adverse events (RD 0.04, 95% CI 0 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 16 to endless). There was moderate‐certainty evidence for no difference between nabiximols or THC and placebo in the frequency of serious adverse events (RD 0.02, 95% CI −0.03 to 0.07). There was moderate‐certainty evidence that nabiximols and THC used as add‐on treatment for opioid‐refractory cancer pain did not differ from placebo in reducing mean pain intensity (standardised mean difference (SMD) −0.19, 95% CI −0.40 to 0.02).There was low‐certainty evidence that a synthetic THC analogue (nabilone) delivered over eight weeks was not superior to placebo in reducing pain associated with chemotherapy or radiochemotherapy in people with head and neck cancer and non‐small cell lung cancer (2 studies, 89 participants, qualitative analysis). Analyses of tolerability and safety were not possible for these studies.There was low‐certainty evidence that synthetic THC analogues were superior to placebo (SMD −0.98, 95% CI −1.36 to −0.60), but not superior to low‐dose codeine (SMD 0.03, 95% CI −0.25 to 0.32; 5 single‐dose trials; 126 participants) in reducing moderate‐to‐severe cancer pain after cessation of previous analgesic treatment for three to four and a half hours (2 single‐dose trials; 66 participants). Analyses of tolerability and safety were not possible for these studies.There was low‐certainty evidence that CBD oil did not add value to specialist palliative care alone in the reduction of pain intensity in people with advanced cancer. There was no difference in the number of dropouts due to adverse events and serious adverse events (1 study, 144 participants, qualitative analysis).We found no studies using herbal cannabis.Authors' conclusions: There is moderate‐certainty evidence that oromucosal nabiximols and THC are ineffective in relieving moderate‐to‐severe opioid‐refractory cancer pain. There is low‐certainty evidence that nabilone is ineffective in reducing pain associated with (radio‐) chemotherapy in people with head and neck cancer and non‐small cell lung cancer. There is low‐certainty evidence that a single dose of synthetic THC analogues is not superior to a single low‐dose morphine equivalent in reducing moderate‐to‐severe cancer pain. There is low‐certainty evidence that CBD does not add value to specialist palliative care alone in the reduction of pain in people with advanced cancer

Cannabis-based medicines and medical cannabis for adults with cancer pain

Background: Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate‐to‐severe pain. This can have a major negative impact on their quality of life. Opioid (morphine‐like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids.Objectives: To evaluate the benefits and harms of cannabis‐based medicines, including medical cannabis, for treating pain and other symptoms in adults with cancer compared to placebo or any other established analgesic for cancer pain.Search methods: We used standard, extensive Cochrane search methods. The latest search date was 26 January 2023.Selection criteria: We selected double‐blind randomised, controlled trials (RCT) of medical cannabis, plant‐derived and synthetic cannabis‐based medicines against placebo or any other active treatment for cancer pain in adults, with any treatment duration and at least 10 participants per treatment arm.Data collection and analysis: We used standard Cochrane methods. The primary outcomes were 1. proportions of participants reporting no worse than mild pain; 2. Patient Global Impression of Change (PGIC) of much improved or very much improved and 3. withdrawals due to adverse events. Secondary outcomes were 4. number of participants who reported pain relief of 30% or greater and overall opioid use reduced or stable; 5. number of participants who reported pain relief of 30% or greater, or 50% or greater; 6. pain intensity; 7. sleep problems; 8. depression and anxiety; 9. daily maintenance and breakthrough opioid dosage; 10. dropouts due to lack of efficacy; 11. all central nervous system adverse events. We used GRADE to assess certainty of evidence for each outcome.Main results: We identified 14 studies involving 1823 participants. No study assessed the proportions of participants reporting no worse than mild pain on treatment by 14 days after start of treatment.We found five RCTs assessing oromucosal nabiximols (tetrahydrocannabinol (THC) and cannabidiol (CBD)) or THC alone involving 1539 participants with moderate or severe pain despite opioid therapy. The double‐blind periods of the RCTs ranged between two and five weeks. Four studies with a parallel design and 1333 participants were available for meta‐analysis.There was moderate‐certainty evidence that there was no clinically relevant benefit for proportions of PGIC much or very much improved (risk difference (RD) 0.06, 95% confidence interval (CI) 0.01 to 0.12; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 8 to 100). There was moderate‐certainty evidence for no clinically relevant difference in the proportion of withdrawals due to adverse events (RD 0.04, 95% CI 0 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 16 to endless). There was moderate‐certainty evidence for no difference between nabiximols or THC and placebo in the frequency of serious adverse events (RD 0.02, 95% CI −0.03 to 0.07). There was moderate‐certainty evidence that nabiximols and THC used as add‐on treatment for opioid‐refractory cancer pain did not differ from placebo in reducing mean pain intensity (standardised mean difference (SMD) −0.19, 95% CI −0.40 to 0.02).There was low‐certainty evidence that a synthetic THC analogue (nabilone) delivered over eight weeks was not superior to placebo in reducing pain associated with chemotherapy or radiochemotherapy in people with head and neck cancer and non‐small cell lung cancer (2 studies, 89 participants, qualitative analysis). Analyses of tolerability and safety were not possible for these studies.There was low‐certainty evidence that synthetic THC analogues were superior to placebo (SMD −0.98, 95% CI −1.36 to −0.60), but not superior to low‐dose codeine (SMD 0.03, 95% CI −0.25 to 0.32; 5 single‐dose trials; 126 participants) in reducing moderate‐to‐severe cancer pain after cessation of previous analgesic treatment for three to four and a half hours (2 single‐dose trials; 66 participants). Analyses of tolerability and safety were not possible for these studies.There was low‐certainty evidence that CBD oil did not add value to specialist palliative care alone in the reduction of pain intensity in people with advanced cancer. There was no difference in the number of dropouts due to adverse events and serious adverse events (1 study, 144 participants, qualitative analysis).We found no studies using herbal cannabis.Authors' conclusions: There is moderate‐certainty evidence that oromucosal nabiximols and THC are ineffective in relieving moderate‐to‐severe opioid‐refractory cancer pain. There is low‐certainty evidence that nabilone is ineffective in reducing pain associated with (radio‐) chemotherapy in people with head and neck cancer and non‐small cell lung cancer. There is low‐certainty evidence that a single dose of synthetic THC analogues is not superior to a single low‐dose morphine equivalent in reducing moderate‐to‐severe cancer pain. There is low‐certainty evidence that CBD does not add value to specialist palliative care alone in the reduction of pain in people with advanced cancer

Supporting students gifted in mathematics through an innovative STEM talent programme

International audienceEurope is facing an insufficient number of suitably qualified university graduates in the STEM subjects, due to an insufficient number of students choosing to study these subjects and high dropout rates [Eurydice, 2011]. Furthermore, school-age students show a lack of understanding of the value of mathematics, and its potential use for solving real-life problems [Boaler, 2011]. We have been running an innovative talent programme, which gives teams of school students the opportunity to study open-ended and unstructured truly interdisciplinary problems. We present results, which show a remarkable increase in understanding of the students' appreciation of the value of mathematics. We believe such a programme not only teaches students the value of mathematics but will also aid their transition from school to university. </p

Sustainable Insights 2015: Band 1 der Schriftenreihe "Ressourceneffizienz und Nachhaltigkeit im Bergischen Städtedreieck"

Sustainable Insights 2015 - Kongress für Studierende und Werkstatt für verantwortungsvolles Wirtschaften 2015 Wie integrieren Unternehmen Nachhaltigkeitskonzepte in ihre Geschäftspolitik und wie realistisch ist die Umsetzung im Betriebsalltag? Wie bewerten Studierende verschiedener Fachrichtungen Strategien für eine bessere Ressourceneffizienz? Welche Lösungen erarbeiten sie gemeinsam mit Unternehmen? Zwei Tage Nachhaltigkeit im Praxistest – bei Sustainable Insights lernten über 100 Studierende, Young Professionals und Auszubildende aus ganz Deutschland engagierte Unternehmen kennen und entwickelten in Case Studies selbst eigene und praxisnahe Ideen. Diese Publikation dokumentiert den Kongress. Sustainable Insights fand 2015 zum ersten Mal statt, eine Wiederholung ist geplant. Veranstaltet wurde Sustainable Insights von der Neuen Effizienz und dem Team von Prof. Dr. Christine Volkmann, Inhaberin des UNESCOLehrstuhls für Entrepreneurship und Interkulturelles Management an der Bergischen Universität Wuppertal und Vorsitzende des Jackstädtzentrums für Unternehmertums- und Innovationsforschung. Schriftenreihe „Ressourceneffizienz und Nachhaltigkeit im Bergischen Städtedreieck“ Die Schriftenreihe, herausgegeben von der Neuen Effizienz, ist die Plattform für Forschung, Projekte und Veranstaltungen zu Nachhaltigkeit und Ressourceneffizienz im Bergischen Städtedreieck. Sie richtet sich an Wissenschaftler und Studierende, Unternehmer und Experten sowie die interessierte Öffentlichkeit. Die Schriftenreihe ist über den Hochschulschriftenserver der Bergischen Universität sowie www.neue-effizienz.de digital frei verfügbar („Open Access“)

Opioids for chronic low back pain: An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks of double‐blind duration

Background and Objective This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in non‐malignant chronic low back pain. Databases and Data Treatment Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to May 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks of double‐blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences or standardized mean differences. We added nine new studies with 2,980 participants for a total of 21 studies with 7,650 participants. Study duration ranged between 4 and 15 weeks. Studies with a parallel and cross‐over design: Based on very low to low‐quality evidence, opioids provided no clinically relevant pain relief of 50% or greater, but a clinically relevant reduction of disability compared to placebo. Enriched enrolment randomized withdrawal (EERW) design: Based on very low to low‐quality evidence, opioids provided a clinically relevant pain relief of 50% or greater, but not a clinically relevant reduction of disability compared to placebo. There was no clinically relevant harm with regard to serious adverse events by opioids compared to placebo in studies with parallel/cross‐over and EERW design. There was a relevant harm with regard to drop out rates due to adverse events in studies with parallel/cross‐over, but not in studies with EERW design. Conclusions Opioids may provide a safe and clinically relevant pain relief for 4–15 weeks in highly selected patients. Significance Within the context of randomized controlled trials of 4–15 weeks, opioids provided a clinically relevant pain relief of 30% or greater and a clinically relevant reduction of disability compared to placebo in non‐malignant chronic low back pain. Number needed to treat for an additional drop out due to side effects was 11 (95% confidence interval: 6–33). Assessment of abuse and addiction was incomplete. The frequency of serious adverse events including deaths did not differ from placebo

Opioids for chronic non‐cancer neuropathic pain. An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks duration

Background and Objective This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non‐cancer neuropathic pain. Databases and Data Treatment Clinicaltrials.gov, CENTRAL, PubMed and PsycINFO were searched from October 2013 to June 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks double‐blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD). We added four new studies with 662 participants for a total of 16 included studies with 2,199 participants. Study duration ranged between 4 and 12 weeks. Studies with a parallel and cross‐over design: Based on low to moderate quality evidence, opioids (buprenorphine, hydromorphone, morphine, oxycodone, tramadol) provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by opioids compared to placebo. Enriched enrolment randomized withdrawal design: Based on low to moderate quality evidence, tapentadol provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo in diabetic polyneuropathy. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by tapentadol compared to placebo. Conclusions Some opioids provided a short‐term substantial pain relief in highly selected patients in some neuropathic pain syndromes. Significance Some opioids (buprenorphine, morphine, oxycodone, tramadol, tapentadol) provide substantial pain relief compared to placebo in postherpetic neuralgia and peripheral neuropathies of different aetiologies for 4–12 weeks. There is insufficient evidence to support or refute the suggestion that these drugs are effective in other neuropathic pain conditions. The safety of opioids with regards to abuse and deaths in the studies analysed cannot be extrapolated to routine clinical care

Proteome data improves protein function prediction in the interactome of Helicobacter pylori

Helicobacter pylori is a common pathogen that is estimated to infect half of the human population, causing several diseases such as duodenal ulcer. Despite one of the first pathogens to be sequenced, its proteome remains poorly characterized as about one-third of its proteins have no functional annotation. Here, we integrate and analyze known protein interactions with proteomic and genomic data from different sources. We find that proteins with similar abundances tend to interact. Such an observation is accompanied by a trend of interactions to appear between proteins of similar functions, although some show marked cross-talk to others. Protein function prediction with protein interactions is significantly improved when interactions from other bacteria are included in our network, allowing us to obtain putative functions of more than 300 poorly or previously uncharacterized proteins. Proteins that are critical for the topological controllability of the underlying network are significantly enriched with genes that are up-regulated in the spiral compared with the coccoid form of H. pylori. Determining their evolutionary conservation, we present evidence that 80 protein complexes are identical in composition with their counterparts in Escherichia coli, while 85 are partially conserved and 120 complexes are completely absent. Furthermore, we determine network clusters that coincide with related functions, gene essentiality, genetic context, cellular localization, and gene expression in different cellular states

The EHEC-host interactome reveals novel targets for the translocated intimin receptor.

Enterohemorrhagic E. coli (EHEC) manipulate their human host through at least 39 effector proteins which hijack host processes through direct protein-protein interactions (PPIs). To identify their protein targets in the host cells, we performed yeast two-hybrid screens, allowing us to find 48 high-confidence protein-protein interactions between 15 EHEC effectors and 47 human host proteins. In comparison to other bacteria and viruses we found that EHEC effectors bind more frequently to hub proteins as well as to proteins that participate in a higher number of protein complexes. The data set includes six new interactions that involve the translocated intimin receptor (TIR), namely HPCAL1, HPCAL4, NCALD, ARRB1, PDE6D, and STK16. We compared these TIR interactions in EHEC and enteropathogenic E. coli (EPEC) and found that five interactions were conserved. Notably, the conserved interactions included those of serine/threonine kinase 16 (STK16), hippocalcin-like 1 (HPCAL1) as well as neurocalcin-delta (NCALD). These proteins co-localize with the infection sites of EPEC. Furthermore, our results suggest putative functions of poorly characterized effectors (EspJ, EspY1). In particular, we observed that EspJ is connected to the microtubule system while EspY1 appears to be involved in apoptosis/cell cycle regulation

A Second-generation Protein–Protein Interaction Network of Helicobacter pylori

Helicobacter pylori infections cause gastric ulcers and play a major role in the development of gastric cancer. In 2001, the first protein interactome was published for this species, revealing over 1500 binary protein interactions resulting from 261 yeast two-hybrid screens. Here we roughly double the number of previously published interactions using an ORFeome-based, proteome-wide yeast two-hybrid screening strategy. We identified a total of 1515 protein–protein interactions, of which 1461 are new. The integration of all the interactions reported in H. pylori results in 3004 unique interactions that connect about 70% of its proteome. Excluding interactions of promiscuous proteins we derived from our new data a core network consisting of 908 interactions. We compared our data set to several other bacterial interactomes and experimentally benchmarked the conservation of interactions using 365 protein pairs (interologs) of E. coli of which one third turned out to be conserved in both species