Bedre nytteverdi av blodkultur ved sepsis

Tema/problemstilling: Vårt kvalitetsforbedringsprosjekt er rettet mot behandling av pasienter med sepsis ved en indremedisinsk avdeling. Målet er å øke nytteverdien av blodkultur for å redusere bredspektret antibiotikabehandling. Kunnskapsgrunnlag: Det er sammenheng mellom bruk av bredspektrede antibiotika og resistensutvikling. Deeskalering, endring av antibiotikabehandlingen til et mer smalspektret regime etter blodkultursvar, er en strategi for å redusere bruk av bredspektrede antibiotika. Deeskalering hos sepsispasienter der blodkultursvaret med resistensbestemmelse tillater det er trygg praksis og anbefales i nasjonale retningslinjer for antibiotikabehandling i sykehus. Tiltak/kvalitetsindikator: Samtaler med leger på Diakonhjemmet og Ullevål sykehus bekrefter at flere pasienter blir stående unødvendig på bredspektret antibiotikabehandling etter at man har blodkultursvar, og at det kan være potensial for å sette i gang forbedringstiltak. Vi innfører et tiltak som sikrer direkte kontakt mellom mikrobiolog og aktuell kliniker. Vi har valgt indikatorer for å vurdere i hvor stor grad tiltak gjennomføres og positive og negative effekter av tiltaket. Ledelse/organisering: Vi har brukt PUKK-sirkelen og Kotters åtte punkter som verktøy for å strukturere prosjektperioden. Slik kan vi sette fokus på de delene av prosjektet som trenger ekstra oppmerksomhet. Vi vil forankre prosjektet i ledelsen gjennom god informasjon og forankring i sykehusets strategiplan. For å oppnå varig endring i praksis, vil vi blant annet gjennomføre halvårlige målinger etter at prosjektperioden er avsluttet. Konklusjon: Tiltaket vi foreslår bygger på allerede gjeldende systemer og vil kreve lite opplæring og ressurser. Effekten er lett målbar. Kunnskapsgrunnlaget viser også at intervensjoner for formidling av dyrkningssvar ved sepsis kan redusere bruken av bredspektret antibiotika uten skadelige bieffekter. Med bakgrunn i dette vil vi anbefale at tiltaket gjennomføres

Genome-wide association analysis of Parkinson's disease and schizophrenia reveals shared genetic architecture and identifies novel risk loci

Background Parkinson’s disease (PD) and schizophrenia (SCZ) are heritable brain disorders that both involve dysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between the disorders, and movement disturbances are common in SCZ patients before treatment with antipsychotic drugs. Despite this, little is known about shared genetic etiology between the disorders. Methods We analyzed recent large genome-wide associations studies (GWAS) on SCZ (n=77,096) and PD (n=417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants and improve statistical power for genetic discovery. Using a variety of biological resources, we functionally characterized the identified genomic loci. Results We observed genetic enrichment in PD conditional on associations with SCZ, and vice versa, indicating polygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified nine novel PD risk loci and one novel SCZ locus at conditional FDR<0.01. Further, we identified nine genomic loci jointly associated with PD and SCZ at conjunctional FDR<0.05. There was an even distribution of antagonistic and agonistic effect directions among the shared loci, in line with the insignificant genetic correlation between the disorders. 65 out of 67 genes mapped to the shared loci are expressed in the human brain and show cell-type specific expression profiles. Conclusions Altogether, the study increases the understanding of the genetic architectures underlying SCZ and PD, indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinical features between the disorders

Attitudes among parents of persons with autism spectrum disorder towards information about genetic risk and future health

Clinical relevance of genetic testing is increasing in autism spectrum disorder (ASD). Information about genetic risk may contribute to improved diagnostics, treatment and family planning, but may also be perceived as a burden. Knowledge about the families’ preferences with regard to genetic risk information is important for both health care professionals and policy makers. We investigated attitudes towards sharing information about genetic risk of ASD and knowledge about future health among parent members of the Norwegian Autism Association (N = 1455) using a questionnaire, and the relationships with parent and child characteristics, such as age, gender and ASD severity. Most preferred autonomy in deciding whom to inform about genetic risk of ASD (74.4%) and a minority supported extensive intra-familial disclosure of the genetic risk (41.1%). The majority agreed that it is an obligation to know as much as possible relevant for future health (58.0%) and only 51.7% agreed to a principle of a ‘right not to know’. In regression models, the attitudes were associated with opinions about benefits and harms of genetic testing (e.g., treatment, family planning, understanding of ASD pathology, insurance discrimination and family conflict). In sum, the findings show that most parents want to know as much as possible relevant for their children’s future health and keep their autonomy and intra-familial confidentiality about genetic risk information. Nearly half of the parents were not concerned with a “right not to know”. These attitudes can inform development of guidelines and bioethics in the age of genomic precision medicine