| 1. |
- Janson, Christer, et al.
(författare)
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Identifying the associated risks of pneumonia in COPD patients : ARCTIC an observational study
- 2018
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Ingår i: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia. This study assessed the risk of pneumonia associated with ICS in patients with COPD.Methods: Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014). Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed. Patients were categorized by airflow limitation severity.Results: A total of 6623 patients with COPD and 48,566 controls were analyzed. Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4. 48-5.06). ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s >= 50% versus patients not using ICS. Asthma was an independent risk factor for pneumonia in the COPD population. Multivariate analysis identified independent predictors of pneumonia in the overall population. The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62).Conclusions: Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further.
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| 2. |
- Jansson, Christer, et al.
(författare)
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Real-world evidence effect of budesonide+formoterol Spiromax on patients with asthma and chronic obstructive pulmonary disease in Sweden
- 2019
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Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: Despite improved asthma and chronic obstructive pulmonary disease (COPD) management, treatment remains inadequate in many patients. Understanding the impact of current treatment in settings outside of controlled trials would add important clinical decision-making information. This study evaluated costs and outcomes associated with budesonide+formoterol (BF) Spiromax® initiation among real-world Swedish patients with asthma and/or COPD.Methods:In this retrospective observational analysis of Swedish patients with asthma and/or COPD, data were collected from the National Patient Register, National Dispensed Drug Register, and Cause of Death Register 1 year before and after initiating BF Spiromax (index date). Outcomes included exacerbation occurrence, treatment patterns, inpatient care, and healthcare costs.Results: The study included 576 patients (asthma: 51.6%; COPD: 32.8%; and asthma and COPD: 15.6%). Following BF Spiromax initiation in asthma patients, there were significant decreases in exacerbations (41.1% to 30.0%; P < 0.001), mean comorbidity-related inpatient visits (0.5 to 0.2; P < 0.001), and inpatient days (1.9 to 0.6; P = 0.006), and a trend toward fewer asthma-related inpatient visits (mean, 0.2 to 0.1; P = 0.056) and asthma-related inpatient days (mean, 0.7 to 0.3; P = 0.060). Increased inpatient utilization was observed in patients with COPD or both diagnoses. All-cause and asthma-/COPD-related medication costs decreased in all groups.Conclusions: After switching to BF Spiromax, asthma patients had fewer exacerbations and hospital visits versus the prior year and COPD patients showed an increase in all-cause and COPD-related healthcare resource utilization. All-cause and asthma-/COPD-related medication costs decreased in all groups after switching to BF Spiromax.
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| 3. |
- Larsson, Kjell, et al.
(författare)
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Impact of COPD diagnosis timing on clinical and economic outcomes : the ARCTIC observational cohort study
- 2019
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1176-9106 .- 1178-2005. ; 14, s. 995-1008
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis.Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.
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| 4. |
- Lisspers, Karin, et al.
(författare)
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Economic burden of COPD in a Swedish cohort : the ARCTIC study
- 2018
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 13, s. 275-285
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Tidskriftsartikel (refereegranskat)abstract
- Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting.Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed.Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population ((sic)13,179) versus the reference population ((sic)2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (similar to(sic)28,000 per patient) were the largest economic burden in COPD patients of working age during 2013.Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.
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| 5. |
- Ställberg, Björn, Docent, et al.
(författare)
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Real-world retrospective cohort study ARCTIC shows burden of comorbidities in Swedish COPD versus non-COPD patients
- 2018
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Ingår i: npj Primary Care Respiratory Medicine. - : SPRINGERNATURE. - 2055-1010. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014. These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population. A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population. A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs. 30.7%). Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients. Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients ((sic) 27,692) vs. reference population ((sic) 5141) (p < 0.0001). The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.
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| 6. |
- Uhde, Milica
(författare)
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Programming of cardiovascular and metabolic functions by thyroid hormone signaling
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Thyroid Hormones (TH) regulate myriad processes, such as development, metabolism and cardiovascular functions, by controlling gene expression through binding to nuclear thyroid hormone receptors, TRα and TRβ. While patients with mutations in the TRβ gene are well known, patients with TRα mutations have only recently been identified. To determine potential phenotypes of such patients, our lab previously created a mutant mouse line (TRα 1+/m), in which the receptor affinity to TH is reduced. TRα1+/m mice display a wide range of abnormalities including hypermetabolism and mild bradycardia, contrary to what was predicted from receptor-mediated hypothyroidism. The aim of this thesis is to analyze the unexpected metabolic and cardiac phenotype in greater detail. Furthermore, it aims to elucidate the physiological phenotype of offspring from TRα1 mutant mothers. Hepatic glycogen content serves as a readout of the metabolic status of mammals. In paper I we show that hypermetabolism leads to completely depleted glycogen storage in adult TRα1 mutants. Furthermore we show that the livers of these mice compensate for this loss by upregulating glucose production over glucose degradation, in contrast to what is observed in T3-treated animals, thus raising the possibility that additional TR-mediated regulatory mechanisms are at play. Remarkably, exposure to high maternal thyroid hormone fully restored glycogen levels in the TRα1+/m adult mice, demonstrating that genetic and maternal factors orchestrate the glycogen set point of the embryo. Studies from our lab showed that cardiomyocytes isolated from the TRα1+/m mice exhibit signs of severe hypothyroidism. Surprisingly, TRα1+/m animals are only slightly bradycardic despite a striking reduction in expression of the pacemaker gene, Hcn2, which in itself can induce a marked reduction of heart rate, paper II. We show that the autonomic regulation of heart rate in TRα1+/m mice fails to switch from sympathetic to parasympathetic tone in response to environmental stimuli such as temperature. In paper III, we find that impaired thyroid hormone signaling during development leads to an irreversible reduction in parvalbumin cell number in the hypothalamus, and that these cells regulate blood pressure and temperature-dependent changes in the heart rate. These data reveal a novel link between thyroid hormones and central regulation of the cardiovascular system. Recent studies suggest that maternal factors during pregnancy, such as hormones and nutrients, epigenetically affect the development of the embryo, with long-lasting effects on offspring metabolism and behavior. In paper IV we show that TRα1+/m mutant dams produce male wild type offspring that have a metabolically favorable outcome characterized by their decreased body fat mass, increased lean mass and elevated glucose utilization. However, these mice display an increased voluntary wheel-running behavior, reminiscent of animal models of Attention Deficit Hyperactivity Disorder and addictive behavior. We provide evidence that a likely cause of this phenotype is decreased expression of genes involved in regulation of reward circuits and that at least one of these genes is epigenetically regulated. Moreover, we show that the phenotype is transmitted to the second generation, through the paternal line. In conclusion, we show that proper thyroid hormone signaling is important during development to i) program the glycogen set point of the embryo; ii) regulate development of a novel hypothalamic cell population that controls cardiovascular functions; and iii) epigenetically regulate gene expression in the wild type embryo with long-lasting consequence for metabolism and behavior.
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| 7. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Use of subcutaneous and intravenous trastuzumab : real-world experience from three hospitals in Sweden
- 2019
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Ingår i: Future Oncology. - : Future Medicine Ltd.. - 1479-6694 .- 1744-8301. ; 15:23, s. 2733-2741
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We aimed to describe the use of subcutaneous (sc.) trastuzumab use in a real-world setting.Patients & methods: This retrospective cohort study evaluated electronic medical records of patients with early breast cancer and trastuzumab use from January 2010 to February 2018 in three hospitals in Sweden.Results: In total, 363 patients received trastuzumab during study period. Of these, 217 (59.8%) patients started treatment with sc. trastuzumab and 146 (40.2%) with intravenous trastuzumab. After sc. trastuzumab approval, use of sc. trastuzumab increased from 70.2% in 2014 to 100% in 2017. Since 2013, 34 of 35 (97.4%) patients who started with intravenous trastuzumab switched to sc. formulation.Conclusion: Trastuzumab sc. quickly became the prevailing formulation for treatment in HER2-positive early breast cancer.
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