ABSTRACT
BACKGROUND: Patients with mental disorders are more likely to be frequent emergency department (ED) users than patients with somatic illnesses. There is little information about recurrent ED visitors (≥four ED visits/year) due to mental health problems in Switzerland. Therefore, our aim was to investigate the prevalence of recurrent ED visits due to mental disorders and to determine which mental disorders and risk factors were associated with recurrent ED visits. METHODS: In a retrospective analysis, we investigated patients suffering from mental health problems between January and December 2015 who presented more than once in the ED of a tertiary care hospital. ED patients who sought out the ED due to mental disorders were grouped in a recurrent group with at least four ED visits per year or in a control group visiting the ED twice or three times within a year. The primary endpoint was to assess the prevalence of recurrent ED patients due to acute symptoms of mental disorders. As secondary endpoints, we investigated which mental disorders and risk factors were associated with recurrent ED visits. RESULT: Of 33,335 primary ED visits, 642 ED visits (1.9%) were by 177 visitors suffering from acute mental health problems. Forty-five (25.4%) of these 177 patients were recurrent ED visitors; 132 (74.6%) visited the ED twice or three times (control). Patients with personality disorders had a four-times higher risk (p = 0.011) of being a recurrent ED visitor. Recurrent ED visitors with mental disorders had significantly more in-house admissions (p < 0.001), self-mutilations (p < 0.001), acute drug toxicity (p = 0.007) and were more often persons of single status (p = 0.045). Although recurrent ED visitors more often had an outpatient general physician or psychiatrist, they visited the ED more frequently within office hours (p < 0.001). CONCLUSION: A quarter of frequent ED users with mental disorders are recurrent ED visitors and were more likely to suffer from personality disorders. Recurrent ED visits are associated with higher rates of self-mutilation, acute drug toxicity, and a greater number of in-house admissions.
ABSTRACT
Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH) by delivery of naked DNA/minicircle (MC)-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU). Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3.6-kb native Pah promoter/enhancer sequence. This vector, delivered via hydrodynamic injection, yielded therapeutic liver PAH activity and sustained correction of blood phenylalanine comparable to viral or synthetic liver promoters. Therapeutic efficacy was seen with vector copy numbers of <1 vector genome per diploid hepatocyte genome and was achieved at a vector dose that was significantly lowered. Partial hepatectomy and subsequent liver regeneration was associated with >95% loss of vector genomes and PAH activity in liver, demonstrating that MC vectors had not integrated into the liver genome. In conclusion, MC vectors, which do not have a defined size-limitation, offer a favorable safety profile for hepatic gene therapy due to their non-integration in combination with native promoters.
