Objective: To describe health care resource utilization (HCRU) and associated costs in adult patients referred for specialist asthma care in Southwest Finland, by disease severity and blood ...eosinophil count (BEC).
Methods: This non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from patients >18 years of age on the hospital register of the Hospital District of Southwest Finland. Data extraction was from January 1, 2004 to December 31, 2015; the index date was the first hospital visit within this period with an International Classification of Diseases-10 diagnosis code for asthma or acute severe asthma. Patients were categorized by asthma severity (based on medication use) and BEC (<300 or ≥300 cells/μL). Total and asthma-related HCRU and estimated costs were recorded the year following index and for calendar years 2004-2015.
Results: Overall, 14,398 patients were included; 388 had severe asthma at index. BEC was available for 3781 patients; 1434 had a BEC ≥300 cells/μL and 2347 had a BEC <300 cells/μL. A total of 1241 patients had severe asthma; 270 patients had severe eosinophilic asthma (severe asthma and a BEC ≥300 cells/μL). Patients with severe versus non-severe asthma had higher total- and asthma-related outpatient visits, inpatient days, emergency room visits and costs per patient year; those with BEC ≥300 cells/μL versus <300 cells/μL had more outpatient visits. All recorded HCRU and associated costs were highest in patients with severe eosinophilic asthma.
Conclusion: This study demonstrated a substantial burden associated with severe and/or eosinophilic asthma for adults in Finland.
Background
Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high‐fat meals. Intestinal ...alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes.
Methods
Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short‐chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high‐fat diet for 11 weeks.
Results
Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly.
Conclusion
Deprivation of protective intestinal factors may increase the risk of inflammation in the gut – a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation‐driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion.
High serum lipopolysaccharide (LPS) activity in normoalbuminuric patients with type 1 diabetes (T1D) predicts the progression of diabetic nephropathy (DN), but the mechanisms behind this remain ...unclear. We observed that treatment of cultured human podocytes with sera from normoalbuminuric T1D patients with high LPS activity downregulated 3-phosphoinositide-dependent kinase-1 (PDK1), an activator of the Akt cell survival pathway, and induced apoptosis. Knockdown of PDK1 in cultured human podocytes inhibited antiapoptotic Akt pathway, stimulated proapoptotic p38 MAPK pathway, and increased apoptosis demonstrating an antiapoptotic role for PDK1 in podocytes. Interestingly, PDK1 was downregulated in the glomeruli of diabetic rats and patients with type 2 diabetes before the onset of proteinuria, further suggesting that reduced expression of PDK1 associates with podocyte injury and development of DN. Treatment of podocytes in vitro and mice in vivo with LPS reduced PDK1 expression and induced apoptosis, which were prevented by inhibiting the Toll-like receptor (TLR) signaling pathway with the immunomodulatory agent GIT27. Our data show that LPS downregulates the cell survival factor PDK1 and induces podocyte apoptosis, and that blocking the TLR pathway with GIT27 may provide a non-nephrotoxic means to prevent the progression of DN.
Objectives:
Little is known about the epidemiology and healthcare burden of pediatric intestinal failure (IF). We aimed to assess the incidence, prevalence, healthcare resource utilization (HCRU), ...and related costs of pediatric short bowel syndrome (SBS) using follow‐up data from the largest hospital district in Finland.
Methods:
This retrospective registry study utilized electronic healthcare data covering all pediatric patients with SBS‐IF born between 2010 and 2019 at the Hospital District of Helsinki and Uusimaa in Finland. Patients were followed from birth until the end of 2020 and compared to control patients, all from the same hospital system.
Results:
In total, 38 patients with SBS‐IF and 1:5 matched controls were included, with median follow‐up time of almost 6 years from birth. Over half of the patients were born early preterm (gestational age ≤30 weeks). The incidence of pediatric SBS‐IF was 24 per 100,000 live births. The HCRU was higher compared to controls and most of the inpatient days incurred during the first year of the SBS‐IF patients’ life. The average hospital‐based HCRU costs were €221,000 for the first year and €57,000 for whole follow‐up annually. The costs were higher for the early preterm patients and accumulated mainly from inpatient days.
Conclusions:
SBS‐IF is a rare disease with a relatively low number of patients treated at each hospital district. The burden on the hospital system, as well as the patient's family, is especially high at the onset as the newborns with SBS‐IF spend a significant part of their first year of life in the hospital.
We investigated the stability of T2 low status, based on low levels of T2 biomarkers, and exacerbation rates in T2 low and non-T2 low asthma from clinical retrospective data of severe uncontrolled ...asthma patients. Knowledge of the T2 low biomarker profile is sparse and biomarker stability is uncharted. Secondary care patients with severe uncontrolled asthma and at least two blood eosinophil counts (BEC) and fractional exhaled nitric oxide (FeNO) measured for determination of type 2 inflammation status were evaluated from a follow-up period of 4 years. Patients were stratified into four groups: T2 low
(
= 31; BEC < 150 cells/µL and FeNO < 25 ppb), non-T2 low
(
= 138; BEC > 150 cells/µL and/or FeNO > 25 ppb), T2 low
(
= 66; BEC < 300 cells/µL and FeNO < 25 ppb), and non-T2 low
(
= 103; BEC > 300 cells/µL and/or FeNO > 25 ppb). Exacerbation rates requiring hospital care, stability of biomarker status, and cumulative OCS and ICS doses were assessed during follow-up. Among patients with severe uncontrolled asthma, 18% (
= 31) were identified as T2 low
, and 39% (
= 66) as T2 low
. In these groups, the low biomarker profile was stable in 55% (
= 11) and 72% (
= 33) of patients with follow-up measures. Exacerbation rates were different between the T2 low and non-T2 low groups: 19.7 95% CI: 4.3-45.6 in T2 low
vs. 8.4 4.7-13.0 in non-T2 low
per 100 patient-years. BEC and FeNO are useful biomarkers in identifying T2 low severe uncontrolled asthma, showing a stable follow-up biomarker profile in up to 72% of patients. Repeated monitoring of these biomarkers is essential in identifying and treating patients with T2 low asthma.
Comprehensive follow-up data from the largest hospital district in Finland was used to assess hospital-based healthcare resource utilization (HCRU) and expenses, incidence and prevalence, survival, ...and effect of comorbidities/complications on survival of adult patients with intestinal failure due to short bowel syndrome (SBS-IF).
This study utilized electronic healthcare data covering all ≥18-year-old patients with SBS-IF at the Hospital District of Helsinki and Uusimaa in Finland between 2010 and 2019. Patients were followed from SBS-IF onset until the end of 2020 or death and compared to birth year and sex-matched control patients without SBS-IF.
The study included 77 patients with SBS-IF (cases) and 363 controls. Cases had high HCRU; the cumulative expenses were about tenfold compared to the controls, at the end of the study (€123,000 vs. €14,000 per patient). The expenses were highest during the first year after SBS-IF onset (€53,000 per patient). Of the cases with a median age 62.5 years, 51.9% died during study time. The median survival was 4.4 years from SBS-IF onset and cases died 13.5 times more likely during the follow-up compared to controls. Mortality risk was lower in female cases (hazard ratio (HR) 0.46; 95% confidence intervals (CI) 0.24, 0.9) and higher with presence of comorbidities (Charlson comorbidity index HR 1.55; 95% CI 1.2, 2.0) and mesenteric infarction (HR 4.5; 95% CI 1.95, 10.36). The incidence of adult SBS-IF was 0.6 per 100,000 adults.
Our study demonstrates a high demand for healthcare support and elevated mortality in adult SBS-IF-patients. Our results suggest that the presence of comorbidities is a key driver for mortality.
The burden associated with chronic obstructive pulmonary disease (COPD) is substantial. The objectives of this study were to describe healthcare resource utilization (HCRU) and HCRU-associated costs ...in patients with COPD in Finland, according to disease severity and blood eosinophil count (BEC).
This non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from the specialist care hospital register. Data extraction was from first hospital visit with a COPD diagnosis (index date) from January 1, 2004 until December 31, 2015 or death. Patients (aged >18 years with ≥1 report of post-bronchodilation forced expiratory volume in 1 s (FEV
)/forced vital capacity (FVC) ratio <0.7) were categorized as having non-severe or severe COPD (FEV
>50% or ≤50% of reference, respectively). Patients who were initially non-severe but progressed to severe were classified as having progressing COPD. Patients without spirometry registry data were classified as having clinically verified COPD. Patients were grouped according to BEC (≥300 cells/μL, <300 cells/μL or BEC unknown). HCRU, estimated associated costs and mortality were evaluated according to COPD severity and BEC.
There were 9042 patients with COPD; 340 non-severe, 326 progressing, 394 severe, and 7982 clinically verified. BEC was available for 31.8% of patients. The mean follow-up time was 3.7-6.5 years in the classified patient-groups. All-cause mortality was 46% during follow-up. Severe COPD was associated with more COPD-related HCRU and higher mortality than non-severe COPD. Patients with BEC ≥300 cells/μL had higher overall HCRU but improved survival compared with those with BEC <300 cells/μL. Overall direct costs were similar across COPD severity categories, 3300-3900€/patient-year, although COPD-related costs were higher in patients with severe versus non-severe COPD.
This study demonstrated a substantial burden associated with severe and/or eosinophilic COPD for patients in Finland.
Research on code reviews has often focused on defect counts instead of defect types, which offers an imperfect view of code review benefits. In this paper, we classified the defects of nine ...industrial (C/C++) and 23 student (Java) code reviews, detecting 388 and 371 defects, respectively. First, we discovered that 75 percent of defects found during the review do not affect the visible functionality of the software. Instead, these defects improved software evolvability by making it easier to understand and modify. Second, we created a defect classification consisting of functional and evolvability defects. The evolvability defect classification is based on the defect types found in this study, but, for the functional defects, we studied and compared existing functional defect classifications. The classification can be useful for assigning code review roles, creating checklists, assessing software evolvability, and building software engineering tools. We conclude that, in addition to functional defects, code reviews find many evolvability defects and, thus, offer additional benefits over execution-based quality assurance methods that cannot detect evolvability defects. We suggest that code reviews may be most valuable for software products with long life cycles as the value of discovering evolvability defects in them is greater than for short life cycle systems.
Naming the pain in requirements engineering Fernández, D. Méndez; Wagner, S.; Kalinowski, M. ...
Empirical software engineering : an international journal,
10/2017, Letnik:
22, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Requirements Engineering (RE) has received much attention in research and practice due to its importance to software project success. Its interdisciplinary nature, the dependency to the customer, and ...its inherent uncertainty still render the discipline difficult to investigate. This results in a lack of empirical data. These are necessary, however, to demonstrate which practically relevant RE problems exist and to what extent they matter. Motivated by this situation, we initiated the
Naming the Pain in Requirements Engineering
(NaPiRE) initiative which constitutes a globally distributed, bi-yearly replicated family of surveys on the status quo and problems in practical RE. In this article, we report on the qualitative analysis of data obtained from 228 companies working in 10 countries in various domains and we reveal which contemporary problems practitioners encounter. To this end, we analyse 21 problems derived from the literature with respect to their relevance and criticality in dependency to their context, and we complement this picture with a cause-effect analysis showing the causes and effects surrounding the most critical problems. Our results give us a better understanding of which problems exist and how they manifest themselves in practical environments. Thus, we provide a first step to ground contributions to RE on empirical observations which, until now, were dominated by conventional wisdom only.
Naming the pain in requirements engineering D. Méndez Fernández; Wagner, S; Kalinowski, M ...
Empirical software engineering : an international journal,
10/2017, Letnik:
22, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Requirements Engineering (RE) has received much attention in research and practice due to its importance to software project success. Its interdisciplinary nature, the dependency to the customer, and ...its inherent uncertainty still render the discipline difficult to investigate. This results in a lack of empirical data. These are necessary, however, to demonstrate which practically relevant RE problems exist and to what extent they matter. Motivated by this situation, we initiated the Naming the Pain in Requirements Engineering (NaPiRE) initiative which constitutes a globally distributed, bi-yearly replicated family of surveys on the status quo and problems in practical RE. In this article, we report on the qualitative analysis of data obtained from 228 companies working in 10 countries in various domains and we reveal which contemporary problems practitioners encounter. To this end, we analyse 21 problems derived from the literature with respect to their relevance and criticality in dependency to their context, and we complement this picture with a cause-effect analysis showing the causes and effects surrounding the most critical problems. Our results give us a better understanding of which problems exist and how they manifest themselves in practical environments. Thus, we provide a first step to ground contributions to RE on empirical observations which, until now, were dominated by conventional wisdom only.
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