Reduksjon i potensielt uheldig legemiddelbruk blant sykehjemsbeboere : - et kvalitetsforbedringsprosjekt

Bakgrunn 40 000 nordmenn bor på sykehjem, og dette er en gruppe som får mange medisiner. På grunn av aldersforandringer, interaksjoner og liknende regnes mange av disse medisinene som uheldige for eldre. Vi har ønsket å lage et prosjekt som skal redusere forekomsten av uheldig medikamentforskrivning til eldre på sykehjem. Kunnskapsgrunnlag Vi har gjort et systematisk litteratursøk som dokumenterer at potensielt uheldig forskrivning er et velkjent problem over store deler av verden, noe som gjenspeiles i norske data. Flere forskergrupper har definert hvilke medikamenter som er mest problematiske i aldersgruppen. Av disse har vi valgt å bruke NorGeP-listen. Tiltak, kvalitetsindikator og metode Vårt tiltak er medikamentgjennomgang ved farmasøyt. En farmasøyt skal gå gjennom medikamentkurven til pasienter ved sykehjemmet, og så delta på previsitten med tilsynslege og sykepleier, hvor en skal diskutere om medisinen bør kontinueres eller seponeres. Resultatindikatoren vår er å gjøre en opptelling av antall brudd på NorGeP-listen før og etter, hos et tilfeldig utvalg av pasientene. Prosessindikatoren er en kontinuerlig opptelling av forbruket av visse nevroleptika på sykehjemmet. Organisering/ledelse Vi ser for oss at prosjektet bør drives kommunalt, med en ledergruppe bestående av helsesjef/kommunelege og avdelingssykepleier fra sykehjemmet. Den viktigste ledelsesutfordringen er knyttet til det å motivere tilsynslege og sykepleiere. Vurdering Vi mener at prosjektet vårt er viktig, praktisk gjennomførbart, økonomisk bærekraftig – og det kan gi mange pasienter en bedre livskvalitet

Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

Purpose: A phase I study was conducted to investigate the safety, tolerability, and immunological responses to vaccination with a combination of telomerase-derived peptides GV1001 (hTERT: 611-626) and p540 (hTERT: 540-548) using granulocyte-macrophage colony-stimulating factor (GM-CSF) or tuberculin as adjuvant in patients with cutaneous melanoma. Experimental design: Ten patients with melanoma stages UICC IIb-IV were vaccinated 8times intradermally with either 60 or 300nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300nmole GV1001 in combination with tuberculin PPD23 injections. HLA typing was not used as an inclusion criterion. Peptide-specific immune responses were measured by delayed-type hypersensitivity (DTH) reactions, in vitro T cell proliferation assays, and cytotoxicity (51-Chromium release) assays for a selected number of clones subsequently generated. Results: Vaccination was well tolerated in all patients. Peptide-specific immune response measured by DTH reactions and in vitro response could be induced in a dose-dependent fashion in 7 of 10 patients. Cloned T cells from the vaccinated patients showed proliferative responses against both vaccine peptides GV1001 and p540. Furthermore, T cell clones were able to specifically lyse p540-pulsed T2 target cells and various pulsed and unpulsed tumor cell lines. Conclusion: These results demonstrate that immunity to hTERT can be generated safely and effectively in patients with advanced melanoma and therefore encourage further trial

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Online Course Innovations: The "Great Debate" & "MBA Orientation"

Recently, the one-week MBA Orientation was revised, and the Debate was introduced as a new exercise in AU’s online MBA project management courses. Expertise of team members in course production and online innovations was invaluable in enabling these course improvements with the students in mind. Two papers, addressing online debate, learning outcomes, and evaluating student learning were subsequently published in Online Classroom. Co-team leaders, Kam Jugdev, Maureen Hutchison, and Carrie Markowski, will share their experiences in developing teaching innovations, assessing learning outcomes with these approaches, and the joy of collaborative writing and publishing

Using the debate as a teaching tool in the online classroom

N

Online Course Innovations: The "Great Debate" & "MBA Orientation"

The MBA Orientation has undergone dramatic changes to better meet new students' needs in an online environment. "The Great Debate" has also been introduced as an online activity in some of the MBA courses. Both innovations have been well-received! Kam Jugdev, Maureen Hutchison, and Carrie Markowski subsequently published two papers about these online course improvements in the Online Classroom. Kam and Maureen look forward to sharing these experiences at the Lunch 'N' Learn and will also talk about the joy of collaborative publications that are practitioner-oriented

Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

A phase I study was conducted to investigate the safety, tolerability, and immunological responses to vaccination with a combination of telomerase-derived peptides GV1001 (hTERT: 611-626) and p540 (hTERT: 540-548) using granulocyte-macrophage colony-stimulating factor (GM-CSF) or tuberculin as adjuvant in patients with cutaneous melanoma

Infection with chicken anaemia virus impairs the generation of pathogen-specific cytotoxic T lymphocytes

Infection with chicken anaemia virus (CAV), a circovirus, can result in immunosuppression and subsequent increased susceptibility to secondary infections. This is the first report of impairment of pathogen-specific cytotoxic T lymphocytes (CTL) after natural and experimental infection of chickens with CAV and Marek's disease virus (MDV) or reticuloendotheliosis virus (REV). MDV- and REV-specific CTL were generated at 7 days post infection by 9–30-day-old-chickens that were positive for maternal antibodies to CAV at 9–17 days of age. Replication of CAV could not be demonstrated in these chickens using quantitative real-time polymerase chain reaction (PCR) and reverse transcriptase (RT)–PCR assays. In contrast, REV-specific CTL failed to develop when chickens negative for maternal antibodies at 9–17 days of age were infected. Infection with CAV at 45 days of age after CAV maternal antibodies had waned also caused a decreased REV-specific CTL response. In these chickens increased levels of CAV DNA of up to 10(7) copy numbers per µg DNA and increased relative transcript levels of CAV by up to a factor of 10(6) were detected by quantitative real-time PCR and RT–PCR. Interleukin (IL)-1β and IL-2 mRNA levels were not significantly affected by CAV infection at 7 or 14 days p.i. Similar assays for interferon-γ (IFN-γ) transcripts demonstrated a 10-fold increase in IFN-γ mRNA levels at 7 days post infection following REV or REV + CAV infection, while CAV alone caused a two- to fourfold increase. These results show a strong link between CAV antibody status, CAV replication, and the ability to generate REV-specific CTL. It is likely that the immunosuppressive effects of subclinical infection have previously been underestimated

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research