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- Boman, Kurt, et al.
(författare)
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Healthcare resource utilization associated with heart failure with preserved versus reduced ejection fraction : a retrospective population-based cohort study in Sweden
- 2017
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Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 346-346
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from two Swedish counties.Methods: Patients with HF were identified via electronic medical records (EMRs) from primary and/or secondary care in Uppsala and Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify HFpEF (defined as ejection fraction ≥50%) and HFrEF (defined as <50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. Patients were followed from date of first diagnosis (index date) to end of study period or EMR collection, date of death or loss to follow-up for other reasons, whichever came first. Unadjusted all-cause and cardiovascular disease (CVD)-related hospitalization rates were assessed using a Cox proportional hazards model, accounting for age, sex, setting of first diagnosis (primary vs secondary care), HF phenotype and NT-proBNP level.Results: In total, 8702 patients with HF were identified. HF phenotype was known in 3167 patients; 64.6% had HFrEF, 35.4% had HFpEF. Patients with HFrEF were younger (mean±SD: 69.9±13.7 vs 74.2±12.6 years) with a lower Charlson comorbidity index (1.65 vs 1.83) than those with HFpEF. All-cause hospitalization rates were marginally lower for HFrEF than for HFpEF (mean [95% CI] proportion of patients hospitalized within 1 year of diagnosis, 72.5 [70.1–74.8]% vs 73.8 [70.7–77.0]%; hazard ratio [HR] over whole follow-up period, 0.87 [0.79–0.97], p=0.0093). The proportion of patients hospitalized was higher for those diagnosed in secondary care than in primary care, particularly within 1 year of diagnosis (1-year rate, 69.6 [68.3–71.0]% vs 59.1 [56.8–61.4]%; HR, 1.15 [1.07–1.23], p=0.0002). Similar trends were observed for CVD-related hospitalization rates for HFrEF vs HFpEF (1-year rate, 69.5 [67.1–71.9]% vs 70.7 [67.5–74.0]%; HR, 0.89 [0.81–0.99], p=0.0309) and for patients diagnosed in secondary vs primary care (1-year rate, 66.6 [65.3–68.0]% vs 56.2 [53.8–58.5]%; HR, 1.15 [1.07–1.24], p=0.0001). Numbers of hospitalizations and outpatient visits decreased with time after diagnosis for HFrEF, but increased slightly for HFpEF after 2 years (Figure). The mean±SD total number of all-cause days of hospitalization during the first year after diagnosis was lower in patients with HFrEF vs HFpEF (19.9±26.1 vs 26.3±34.5 days), while the number of HF-related days of hospitalization was similar (16.0±22.4 vs 17.2±24.0 days).Conclusions: Number and duration of hospital stays were significantly lower over time in patients with HFrEF than HFpEF; this may be explained by the comorbidity burden in the latter group.
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- Wikstrom, G., et al.
(författare)
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Drug treatment patterns in patients newly diagnosed with heart failure : a retrospective population-based cohort study in Sweden
- 2017
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Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 55-55
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Limited data are available on longitudinal drug treatment patterns in newly diagnosed patients with heart failure (HF) with preserved (HFpEF), reduced (HFrEF) and unknown ejection fraction (EF) in Sweden. We evaluated drug treatment patterns in these patients based on ESC 2012 guidelines, which recommend treatment with angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), ?-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs) for HFrEF (ESC does not make recommendations for HFpEF or unknown EF).Methods: Patients were identified via electronic medical records from primary and/or secondary care in Västerbotten, linked via unique identifiers to the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data identified HFrEF (<50%) and HFpEF (≥50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. The date of the first diagnosis was defined as the index date. A 10-year look-back period was used to exclude prevalent HF cases. ATC codes were identified from drug prescriptions. Patients with a 4-year look-back and 2 years of follow-up were included.Results: Overall, 4357 patients were included (mean± SD age, 76.6± 12.6 years; 27.7% aged ≥85 years; HFrEF, 24.6%; HFpEF, 12.9%; unknown EF, 62.5%). At the index date, 63.0% of patients were treated with an ACEi or an ARB, 62.3% with a BB and 16.0% with an MRA; 18.5% were not receiving treatment. The most common treatment groups (monotherapy or combinations) were: ACEi + BB (HFrEF, 20.5%; HFpEF, 21.0%; unknown EF, 23.5%); BB monotherapy (HFrEF, 12.1%; HFpEF, 14.0%; unknown EF, 15.6%); and ARB + BB (HFrEF, 8.5%; HFpEF, 12.3%; unknown EF, 12.3%) (Figure). The majority of patients receiving an ACEi or ARB at the index date continued to do so for the following 2 years (ACEi, 63.6%; ARB, 60.9%); most of these were receiving doses lower than those recommended by the ESC (70.8% and 88.9%, respectively). A small proportion of patients receiving an ACEi at the index date switched to an ARB over the 2-year period (4.1%) and vice versa (2.6%). Most patients were not receiving the recommended ESC dose before switching (ACEi, 81.8%; ARB, 77.8%). Similarly, most patients who discontinued an ACEi (37.3%) or ARB (39.1%) were not receiving the recommended dose before discontinuation (ACEi, 64.8%; ARB, 87.4%).Conclusions: A large proportion of patients with HF in Sweden do not receive drug combinations recommended by the ESC. Furthermore, few patients are prescribed ESC-recommended doses of HF drugs and few undergo up-titration of treatment before switching. These findings are remarkable for HFrEF, for which guidelines are established. These findings may be partly reflective of the high proportion of elderly patients studied.
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- Blixt, Maria, et al.
(författare)
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MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma
- 2022
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- Retinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. The aim was to elucidate the events that result in carcinogenesis and identify the cancer cell-of-origin. We used the chicken retina, a well-established model for studying retinal neurogenesis, and established human embryonic stem cell-derived retinal organoids as model systems. We over-expressed MYCN by electroporation of piggyBac genome-integrating expression vectors. We found that over-expression of MYCN induced tumorigenic growth with high frequency in RB1-proficient chicken retinas and human organoids. In both systems, the tumorigenic cells expressed markers for undifferentiated cone photoreceptor/horizontal cell progenitors. The over-expression resulted in metastatic retinoblastoma within 7–9 weeks in chicken. Cells expressing MYCN could be grown in vitro and, when orthotopically injected, formed tumours that infiltrated the sclera and optic nerve and expressed markers for cone progenitors. Investigation of the tumour cell phenotype determined that the potential for neoplastic growth was embryonic stage-dependent and featured a cell-specific resistance to apoptosis in the cone/horizontal cell lineage, but not in ganglion or amacrine cells. We conclude that MYCN over-expression is sufficient to drive tumorigenesis and that a cell-specific resistance to apoptosis in the cone/horizontal cell lineage mediates the cancer phenotype.
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