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1.
Data Brief ; 51: 109729, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37965592

RESUMEN

The Vänersborg Bridge in southwest Sweden is a single-leaf bascule bridge carrying railway traffic over a canal. The load consists of passing commuter trains, occasional freight trains and leaf openings to allow ships to pass on the canal. The bridge constructed from 1914 to 1916 was built by riveted truss members in steel. Over the years, several assessments and maintenance actions have been performed to keep the bridge in service. During autumn 2021, a long-term monitoring campaign was initiated with the installation of sensors to register the load effect and possible changes in the behaviour. In March 2023, the cloud-based service employed detected an abrupt change of behaviour. An emergency inspection revealed a large crack in one of the truss members in the counter-weight part. The published dataset contains sensor data from 64 registered bridge openings, comprising accelerations, strains, inclinations, and weather conditions. Data from before the fracture, during, and after are provided. During the bridge opening events, the data was recorded continuously with a sampling rate of 200 Hz. The evidence of damage in a real case scenario makes the dataset valuable for testing and evaluation of data-driven routines for infrastructure surveillance.

2.
Br J Anaesth ; 131(1): 11-13, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37149476

RESUMEN

Two recent case-control studies, both published in the British Journal of Anaesthesia, have shown that intake of pholcodine-containing cough medicines during the year preceding general anaesthesia significantly increased the risk of anaphylaxis caused by neuromuscular blocking agents. Both a French multicentre study and a single-centre study from Western Australia offer strong support to the pholcodine hypothesis for IgE-sensitisation to neuromuscular blocking agents. The European Medicines Agency, criticised for not taking preventive action at its first assessment of pholcodine in 2011, finally recommended a stop to sales of all pholcodine-containing medicines throughout the EU on December 1, 2022. Time will tell whether this reduces the incidence of perioperative anaphylaxis in the EU, as in Scandinavia.


Asunto(s)
Anafilaxia , Bloqueantes Neuromusculares , Unión Europea , Humanos , Bloqueantes Neuromusculares/efectos adversos , Inmunoglobulina E/inmunología
3.
Eur Clin Respir J ; 10(1): 2181291, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36861117

RESUMEN

Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality. Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables. Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age ≥70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality. Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.

4.
Anal Bioanal Chem ; 415(3): 481-492, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36400967

RESUMEN

Inorganic pyrophosphate (PPi) is a crucial extracellular mineralization regulator. Low plasma PPi concentrations underlie the soft tissue calcification present in several rare hereditary mineralization disorders as well as in more common conditions like chronic kidney disease and diabetes. Even though deregulated plasma PPi homeostasis is known to be linked to multiple human diseases, there is currently no reliable assay for its quantification. We here describe a PPi assay that employs the enzyme ATP sulfurylase to convert PPi into ATP. Generated ATP is subsequently quantified by firefly luciferase-based bioluminescence. An internal ATP standard was used to correct for sample-specific interference by matrix compounds on firefly luciferase activity. The assay was validated and shows excellent precision (< 3.5%) and accuracy (93-106%) of PPi spiked into human plasma samples. We found that of several anticoagulants tested only EDTA effectively blocked conversion of ATP into PPi in plasma after blood collection. Moreover, filtration over a 300,000-Da molecular weight cut-off membrane reduced variability of plasma PPi and removed ATP present in a membrane-enclosed compartment, possibly platelets. Applied to plasma samples of wild-type and Abcc6-/- rats, an animal model with established low circulating levels of PPi, the new assay showed lower variability than the assay that was previously in routine use in our laboratory. In conclusion, we here report a new and robust assay to determine PPi concentrations in plasma, which outperforms currently available assays because of its high sensitivity, precision, and accuracy.


Asunto(s)
Calcinosis , Difosfatos , Humanos , Ratas , Animales , Luciferasas de Luciérnaga , Adenosina Trifosfato
5.
FEBS J ; 290(2): 379-399, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35997626

RESUMEN

Cellobiohydrolases (CBHs) in the glycoside hydrolase family 7 (GH7) (EC3.2.1.176) are the major cellulose degrading enzymes both in industrial settings and in the context of carbon cycling in nature. Small carbohydrate conjugates such as p-nitrophenyl-ß-d-cellobioside (pNPC), p-nitrophenyl-ß-d-lactoside (pNPL) and methylumbelliferyl-ß-d-cellobioside have commonly been used in colorimetric and fluorometric assays for analysing activity of these enzymes. Despite the similar nature of these compounds the kinetics of their enzymatic hydrolysis vary greatly between the different compounds as well as among different enzymes within the GH7 family. Through enzyme kinetics, crystallographic structure determination, molecular dynamics simulations, and fluorometric binding studies using the closely related compound o-nitrophenyl-ß-d-cellobioside (oNPC), in this work we examine the different hydrolysis characteristics of these compounds on two model enzymes of this class, TrCel7A from Trichoderma reesei and PcCel7D from Phanerochaete chrysosporium. Protein crystal structures of the E212Q mutant of TrCel7A with pNPC and pNPL, and the wildtype TrCel7A with oNPC, reveal that non-productive binding at the product site is the dominating binding mode for these compounds. Enzyme kinetics results suggest the strength of non-productive binding is a key determinant for the activity characteristics on these substrates, with PcCel7D consistently showing higher turnover rates (kcat ) than TrCel7A, but higher Michaelis-Menten (KM ) constants as well. Furthermore, oNPC turned out to be useful as an active-site probe for fluorometric determination of the dissociation constant for cellobiose on TrCel7A but could not be utilized for the same purpose on PcCel7D, likely due to strong binding to an unknown site outside the active site.


Asunto(s)
Celulasa , Trichoderma , Celulosa 1,4-beta-Celobiosidasa/química , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Compuestos Cromogénicos , Celulosa/metabolismo , Simulación de Dinámica Molecular , Cinética , Celulasa/metabolismo
6.
Carbohydr Res ; 520: 108635, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35961080

RESUMEN

Sugars were derivatized with N,O-dimethylhydroxylamine (DMHA) using a simple procedure. The disaccharides lactose and chitobiose and the human milk tetrasaccharides lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) were used as examples. The ß-glycosylamines were formed exclusively in good yields (80-84%). The derivatives were very well suited for RP-HPLC, giving rise to single peaks for each sugar, without the usual complications caused by mutarotation. The LNT- and LNnT-derivatives separated very well on an ordinary RP-HPLC column, despite their close structural similarity. Also, three human milk pentasaccharides (LNF I, II and III) were derivatized with DMHA. Again, good separation of these isomers was obtained. The DMHA derivatization was easily reversed. The free oligosaccharides were recovered quantitatively by mild acidic hydrolysis. To demonstrate usefulness on a preparative scale, an LNDI-rich human milk oligosaccharide fraction was derivatized, and three HPLC fractions (one major and two minor) were collected. Hydrolysis and desalting gave saccharides LNDI, LNnDII, and LNDII, the latter mixed with minor amounts of LNnDI.


Asunto(s)
Oligosacáridos , Azúcares , Cromatografía Líquida de Alta Presión/métodos , Dimetilaminas , Humanos , Lactosa/análisis , Leche Humana/química , Oligosacáridos/química
7.
Int J Chron Obstruct Pulmon Dis ; 17: 1409-1421, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35761954

RESUMEN

Background: Patients with mild chronic obstructive pulmonary disease (COPD) account for more than half of the total COPD population but are often undiagnosed and sparsely studied. This real-world, longitudinal study compared the socioeconomic burden, clinical characteristics and treatment patterns in patients with mild COPD and age- and gender-matched controls. Patients and methods: Our population included mild COPD patients (forced expiratory volume in one second ≥80% of predicted value) and reference controls from 52 Swedish primary care centres over 15 years (2000-2014). We linked electronic medical record (EMR) data to Sweden's National Health Registries. The outcomes analyzed were socioeconomic status including annual income from work, presence of comorbidities and the use of medications. Results: 844 patients with mild COPD were included in this study and matched with 844 reference controls. Compared with the reference controls, mild COPD patients had a significantly lower annual income from work (mean difference, men: 12,559€ and women: 7143€) and were significantly less likely to be married or employed. The presence of comorbidities, including cardiovascular disease, anxiety and depression (only women) was significantly higher in mild COPD patients. The use of medications, such as proton pump inhibitors, antidepressants, central painkillers and sleep medications, was significantly higher in the mild COPD group. Conclusion: Mild COPD presents a considerable socioeconomic and clinical burden compared with reference controls The findings suggest that COPD constitutes a condition that influences health status even in mild disease clearly demanding an increased need for early detection and treatment.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Femenino , Volumen Espiratorio Forzado , Humanos , Estudios Longitudinales , Masculino , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Clase Social , Suecia/epidemiología
8.
Respir Med ; 185: 106483, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34077873

RESUMEN

OBJECTIVE: The ability to predict impending asthma exacerbations may allow better utilization of healthcare resources, prevention of hospitalization and improve patient outcomes. We aimed to develop models using machine learning to predict risk of exacerbations. METHODS: Data from 29,396 asthma patients was collected from electronic medical records and national registers covering clinical and epidemiological factors (e.g. comorbidities, health care contacts), between 2000 and 2013. Machine-learning classifiers were used to create models to predict exacerbations within the next 15 days. Model selection was done using the mean cross validation score of area under precision-recall curve (AUPRC). RESULTS: The most important predictors of exacerbation were comorbidity burden and previous exacerbations. Model validation on test data yielded an AUPRC = 0.007 (95% CI: ± 0.0002), indicating that historic clinical information alone may not be sufficient to predict a near future risk of asthma exacerbation. CONCLUSIONS: Supplementation with additional data on environmental triggers, (e.g. weather, pollen count, air quality) and from wearables, might be necessary to improve performance of the short-term predictive model to develop a more clinically useful tool.


Asunto(s)
Aprendizaje Automático , Medición de Riesgo/métodos , Estado Asmático/epidemiología , Adolescente , Adulto , Estudios de Cohortes , Comorbilidad , Interpretación Estadística de Datos , Progresión de la Enfermedad , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Predicción , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Riesgo , Estado Asmático/etiología , Suecia/epidemiología , Adulto Joven
9.
Artículo en Inglés | MEDLINE | ID: mdl-33776429

RESUMEN

PURPOSE: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD. PATIENTS AND METHODS: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000-2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis. RESULTS: In total 18,586 COPD patients were analyzed. A majority of the patients (60-70%) who either have had no exacerbation or frequent exacerbations (≥2/year) during the pre-index period remained in their group (ie, with 0 or ≥2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93-2.20]) and ≥2 (4.58 [4.33-4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥2/year) than in patients with no or one exacerbation annually (p<0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis. CONCLUSION: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Progresión de la Enfermedad , Costos de la Atención en Salud , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Suecia/epidemiología , Factores de Tiempo
10.
Artículo en Inglés | MEDLINE | ID: mdl-33758504

RESUMEN

PURPOSE: Chronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations. We aimed to develop a model that predicts a patient's risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data. PATIENTS AND METHODS: Patient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013. Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days. Exacerbations occurring within this period were considered as one event. Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC). To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported. The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset. RESULTS: The most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden. Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation. CONCLUSION: Our work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Progresión de la Enfermedad , Hospitalización , Humanos , Aprendizaje Automático , Atención Primaria de Salud , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Suecia/epidemiología
11.
Eur Respir J ; 57(2)2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32972982

RESUMEN

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.


Asunto(s)
Fracturas Óseas , Osteoporosis , Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Corticoesteroides/efectos adversos , Fracturas Óseas/inducido químicamente , Fracturas Óseas/epidemiología , Humanos , Osteoporosis/inducido químicamente , Osteoporosis/complicaciones , Osteoporosis/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Suecia/epidemiología
12.
NPJ Prim Care Respir Med ; 30(1): 47, 2020 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-33082331

RESUMEN

This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.


Asunto(s)
Corticoesteroides/efectos adversos , Broncodilatadores/efectos adversos , Diabetes Mellitus Tipo 2/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Anciano , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Incidencia , Masculino , Factores de Riesgo , Suecia/epidemiología
13.
FEBS Open Bio ; 10(12): 2605-2615, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33016476

RESUMEN

Leupeptin is a naturally occurring inhibitor of various proteases, in particular serine proteases. Following its discovery, the inhibitory properties of several other peptidyl argininals have been studied. The specificity of leupeptin is most likely due to the Leu-Leu-Argininal sequence, and its C-terminal aldehyde group has been suggested to enhance the binding efficiency and to be essential for function. The terminal aldehyde group makes the structure less vulnerable to carboxypeptidases. Here, we investigated whether the inhibitory function of leupeptin toward serine proteases is retained after oxidation or reduction of the aldehyde group. The oxidized form, which corresponds to the natural precursor, was shown to be superior to the reduced form in terms of inhibitory properties. However, the original leupeptin possessed enhanced inhibitory properties as compared with the oxidized form. Based on these results, new synthetic leupeptin analogues, 6-aminohexanoic acid (Ahx)-Phe-Leu-Arg-COOH and Ahx-Leu-Leu-Arg-COOH, were prepared by solid-phase peptide synthesis using the Fmoc strategy. In these analogues, the N-terminal capping acetyl group was replaced with a 6-aminohexanoyl group to allow conjugation. The structures of the modified leupeptin and the synthetic peptides were confirmed by mass spectrometry. Determination of the inhibitory properties against trypsin (IEC 3.4.21.4, Chymotrypsin IEC 3.4.21.1) revealed that these further modified tripeptides were tight binding inhibitors to their target enzyme, similar to the naturally occurring leupeptin, with Ki values generally in the micromolar range. The Ahx-Phe-Leu-Arg-COOH analogue was selected for conjugation to inorganic oxide nanoparticles and agarose gel beads. All conjugates exhibited inhibitory activity in the same range as for the free peptides.


Asunto(s)
Leupeptinas/farmacología , Péptido Hidrolasas/metabolismo , Inhibidores de Proteasas/farmacología , Cinética , Leupeptinas/síntesis química , Leupeptinas/química , Estructura Molecular , Oxidación-Reducción , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/química
14.
Artículo en Inglés | MEDLINE | ID: mdl-32099348

RESUMEN

Background: Life expectancy is significantly shorter for patients with chronic obstructive pulmonary disease (COPD) than the general population. Concurrent diseases are known to infer an increased mortality risk in those with COPD, but the effects of pharmacological treatments on survival are less established. This study aimed to examine any associations between commonly used drugs, comorbidities and mortality in Swedish real-world primary care COPD patients. Methods: Patients with physician-diagnosed COPD from a large primary care population were observed retrospectively, utilizing primary care records and mandatory Swedish national registers. The time to all-cause death was assessed in a stepwise multiple Cox proportional hazards regression model including demography, socioeconomic factors, exacerbations, comorbidities and medication. Results: During the observation period (1999-2009) 5776 (32.5%) of 17,745 included COPD patients died. Heart failure (hazard ratio [HR]: 1.88, 95% confidence interval [CI]: 1.74-2.04), stroke (HR: 1.52, 95% CI: 1.40-1.64) and myocardial infarction (HR: 1.40, 95% CI: 1.24-1.58) were associated with an increased risk of death. Use of inhaled corticosteroids (ICS; HR: 0.79, 95% CI: 0.66-0.94), beta-blockers (HR: 0.86, 95% CI: 0.76-0.97) and acetylsalicylic acid (ASA; HR: 0.87, 95% CI: 0.77-0.98) was dose-dependently associated with a decreased risk of death, whereas use of long-acting muscarinic antagonists (LAMA; HR: 1.33, 95% CI: 1.14-1.55) and N-acetylcysteine (NAC; HR: 1.26, 95% CI: 1.08-1.48) were dose-dependently associated with an increased risk of death in COPD patients. Conclusion: This large, retrospective, observational study of Swedish real-world primary care COPD patients indicates that coexisting heart failure, stroke and myocardial infarction were the strongest predictors of death, underscoring the importance of timely recognition and treatment of comorbidities. A decreased risk of death associated with the use of ICS, beta-blockers and ASA, and an increased risk associated with the use of LAMA and NAC, was also found.


Asunto(s)
Atención Primaria de Salud , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Fármacos del Sistema Respiratorio/administración & dosificación , Anciano , Anciano de 80 o más Años , Comorbilidad , Registros Electrónicos de Salud , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Esperanza de Vida , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Sistema de Registros , Fármacos del Sistema Respiratorio/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Suecia/epidemiología , Factores de Tiempo , Resultado del Tratamiento
15.
NPJ Prim Care Respir Med ; 29(1): 45, 2019 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-31822681

RESUMEN

The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000-2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.


Asunto(s)
Predicción , Glucocorticoides/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Anciano , Vías de Administración de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Estudios Retrospectivos , Distribución por Sexo , Factores Sexuales , Tasa de Supervivencia/tendencias , Suecia/epidemiología
16.
Cancers (Basel) ; 11(12)2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31842352

RESUMEN

Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

17.
ACS Omega ; 4(19): 18456-18464, 2019 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31720549

RESUMEN

A serine protease inhibitor was extracted from potato tubers. The inhibitor was conjugated to soluble, prefractionated dextran and titanium dioxide and zinc oxide nanoparticles. Conjugation to dextran was achieved by periodate oxidation of the dextran, followed by Schiff base coupling to inhibitor amino groups, and finally reduction, whereas the conjugation to the oxide particles was carried out by aminosilanization and carbonyldiimidazole activation. The inhibitory effect of the conjugated inhibitor was compared to that of free inhibitor in solution and with gelatin gel as a direct substrate. A certain degree of inhibitory activity was retained for both the dextran-conjugated and particle-conjugated inhibitors. In particular, the apparent K i value of the dextran-conjugated inhibitor was found to be in the same range as that for free inhibitor. The dextran conjugate retained a higher activity than the free inhibitor after 1 month of storage at room temperature.

18.
Eur Clin Respir J ; 6(1): 1660565, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31579437

RESUMEN

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.

19.
Anal Biochem ; 582: 113357, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31276650

RESUMEN

The interaction between pancreatic proteases and a serine protease inhibitor purified from potato tubers was investigated by chromatography-coupled light scattering measurements. The molar mass distribution in the chromatogram was compared to theoretical values calculated for the different possible combinations of complexes and free components by three different approaches, namely section analyses of the chromatograms, full mass average determination and mass distribution analysis. This revealed that the inhibitor was able to bind trypsin in a 2:1 complex, whereas the data for chymotrypsin clearly showed a limitation to 1:1 complex regardless of the molar ratio in the injected samples. The same experiment carried out with elastase and the potato inhibitor gave only weak indications of complex formation under the conditions used.


Asunto(s)
Quimotripsina/química , Complejos Multiproteicos/química , Elastasa Pancreática/química , Péptidos/química , Proteínas de Plantas/química , Inhibidores de Serina Proteinasa/química , Tripsina/química , Quimotripsina/antagonistas & inhibidores , Dispersión Dinámica de Luz/métodos , Cinética , Elastasa Pancreática/antagonistas & inhibidores , Unión Proteica , Solanum tuberosum/metabolismo
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