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2.
PLoS One ; 16(4): e0249861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33836037

RESUMO

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce. METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction. RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001). CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.

3.
Scand J Gastroenterol ; : 1-7, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794731

RESUMO

BACKGROUND: Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohn's disease (CD) are still limited. AIM: To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. METHODS: Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (≥3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI ≤4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. RESULTS: Of 114 included patients, 107 (94%) had failed ≥ 1 and 58 (51%) ≥ 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. CONCLUSIONS: In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option.

4.
J Crohns Colitis ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33730755

RESUMO

Inflammatory bowel disease [IBD] is a complex chronic disorder with no clear aetiology and no known cure. Despite recent advances in overall disease management and improved therapeutics, patients with IBD still experience a substantial burden. Furthermore, as the incidence continues to increase in developing areas of the world, it is expected that the burden of IBD to society will increase and exert tremendous pressure on healthcare systems worldwide. Therefore, new strategies to prevent the global increase of IBD are urgently required. Data are being progressively acquired on the period preceding disease diagnosis, which support the concept that IBD has a preclinical period that may reveal the triggers of disease and may be amenable to early intervention. Having a better knowledge of this preclinical period will increase the potential not only for improved understanding of disease pathogenesis and improved therapeutics, but also for disease prediction and prevention.

5.
United European Gastroenterol J ; 9(2): 177-192, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33704918

RESUMO

BACKGROUND: There are concerns that individuals with chronic immune-mediated diseases are at increased risk of COVID-19 and related severe adverse outcome, including intensive care admission or death. We aimed to explore the absolute and relative risk of severe COVID-19 in inflammatory bowel disease (IBD). METHODS: This population-based cohort study used nationwide registers in Sweden, with 67,292 individuals with a diagnosis of IBD 1969-2017 (Crohn's disease, n = 21,599; ulcerative colitis: n = 43,622; IBD-unclassified: n = 2071) and alive on 1 February 2020. Patients with IBD were matched to up to five controls from the general population (n = 297,910). Cox regression estimated hazard ratios (HRs) for (i) hospital admission with laboratory-confirmed COVID-19 as the primary diagnosis, and (ii) severe COVID-19 (composite outcome consisting of (a) COVID-19 intensive care admission, or (b) death from COVID-19 or (c) death within 30 days of COVID-19 hospital admission), were calculated. Analyses were conditioned on age, sex, calendar period, and county and adjusted for other comorbidities. RESULTS: Between 1 February and 31 July 2020, 179 (0.27%) IBD patients and 500 (0.17%) general population controls were admitted to hospital with COVID-19 (adjusted HR [aHR] = 1.43; 95% CI = 1.19-1.72). The corresponding numbers for severe COVID-19 was 65 (0.10%) and 183 (0.06%; aHR = 1.11; 95% CI = 0.81-1.52). Adjusted HRs were similar in Crohn's disease and ulcerative colitis. In a propensity score-matched model taking comorbidity into account until 2016, the increased risk for COVID-19 hospital admission remained (aHR = 1.32; 1.12-1.56), but there was no increased risk of severe COVID-19 (aHR = 1.12; 0.85-1.47). CONCLUSIONS: While individuals with IBD were more likely to be admitted to hospital for COVID-19 than the general population, the risk of severe COVID-19 was not higher.


Assuntos
Doenças Inflamatórias Intestinais , Adolescente , Adulto , /diagnóstico , /mortalidade , Comorbidade , Estudos Transversais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Suécia/epidemiologia , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-33627380

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD. METHODS: This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up. RESULTS: Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC (n = 28), ICC (n = 28), and ECC (n = 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC. CONCLUSIONS: Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC. IMPACT: Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.

8.
Scand J Gastroenterol ; 56(4): 410-421, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33632044

RESUMO

BACKGROUND: It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). METHODS: A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. RESULTS: Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. CONCLUSIONS: The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

9.
J Crohns Colitis ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33640971

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is linked to psychiatric morbidity, but few studies have assessed general population comparators. We aimed to investigate the risk of psychiatric morbidity and suicide in adult-onset IBD patients. METHODS: Nationwide population-based cohort study in Sweden (1973-2013). We studied the risk of psychiatric disorders and suicide in 69,865 adult-onset IBD patients (ulcerative colitis, UC: n=43,557; Crohn's disease, CD: n=21,245; and IBD-unclassified: n=5063) compared to 3,472,913 general population references and 66,292 siblings. RESULTS: During a median follow-up of 11 years, we found 7,465 (10.7%) first psychiatric disorders in IBD (incidence rate, IR/1000 person-years 8.4) and 306,911 (9.9%) in the general population (IR 6.6), resulting in 1.8 extra psychiatric morbidity per 100 patients followed-up for 10 years and a hazard ratio (HR) of 1.3 (95% confidence interval, 95%CI=1.2-1.3). The highest risk of overall psychiatric morbidity was seen in the first year after IBD diagnosis (HR=1.4, 95%CI=1.2-1.6) and in patients with extraintestinal manifestations (HR=1.6, 95%CI=1.5-1.7). Psychiatric morbidity was more common in all IBD subtypes (HRs 1.3 to 1.5). An increased risk of suicide attempts was observed among all IBD types (HRs=1.2 to 1.4), whereas completed suicide was explicitly associated with CD (HR=1.5) and elderly-onset (diagnosed at the age of >60 years) IBD (HR=1.7). CONCLUSION: Adult-onset IBD was associated with an increased risk of psychiatric disorders and suicide attempts. Psychological follow-up should be provided to patients with IBD, especially those with extraintestinal manifestations and elderly-onset IBD. This follow-up should transpire within the first year after IBD diagnosis.

10.
Dis Colon Rectum ; 64(3): 301-312, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395139

RESUMO

BACKGROUND: To avoid a permanent stoma, restorative surgery is performed after the colectomy. Previous studies have shown that less than half of patients with ulcerative colitis undergo restorative surgery. OBJECTIVE: The primary aim was to explore the association between socioeconomic status and restorative surgery after colectomy. DESIGN: This was a nationwide register-based cohort study. SETTINGS: The study was conducted in Sweden. PATIENTS: All Swedish patients with ulcerative colitis who underwent colectomy between 1990 and 2017 at the age of 15 to 69 years were included. MAIN OUTCOME MEASURES: The main outcome was restorative surgery, and the secondary outcome was failure of the reconstruction (defined as the need for a new ileostomy after the reconstruction or nonreversal of a defunctioning stoma within 2 years of the reconstruction). To calculate HRs for restorative surgery after colectomy, as well as failure after restorative surgery, multivariable Cox regression models were performed (adjusted for sex, year of colectomy, colorectal cancer diagnosis, education, civil status, country of birth, income (quartiles 1 to 4, where Q4 represents highest income), hospital volume, and stratified by age). RESULTS: In all, 5969 patients with ulcerative colitis underwent colectomy, and of those, 2794 (46.8%) underwent restorative surgery. Restorative surgery was more common in patients with a high income at the time of colectomy (quartile 1, reference; quartile 2, 1.09 (0.98-1.21); quartile 3, 1.20 (1.07-1.34); quartile 4, 1.27 (1.13-1.43)) and less common in those born in a Nordic country than in immigrants born in a non-Nordic country (0.86 (0.74-0.99)), whereas no association was seen with educational level and civil status. There was no association between socioeconomic status and the risk of failure after restorative surgery. LIMITATIONS: The study was restricted to register data. CONCLUSIONS: Restorative surgery in ulcerative colitis appears to be more common in patients with a high income and patients born in a non-Nordic country, indicating inequality in the provided care. See Video Abstract at http://links.lww.com/DCR/B433. LA CIRUGA RESTAURADORA ES MS COMN EN PACIENTES CON COLITIS ULCEROSA CON INGRESOS ALTOS UN ESTUDIO POBLACIONAL: ANTECEDENTES:Para evitar un estoma permanente, se realiza una cirugía reparadora después de la colectomía. Estudios anteriores han demostrado que menos de la mitad de los pacientes con colitis ulcerosa se someten a cirugía reconstituyente.OBJETIVO:El objetivo principal fue explorar la asociación entre el nivel socioeconómico y la cirugía reconstituyente después de la colectomía.DISEÑO:Estudio de cohorte basado en registros a nivel nacional.MARCO:Suecia.PACIENTES:Todos los pacientes Suecos con colitis ulcerosa que se sometieron a colectomía desde el 1990 a 2017 a la edad de 15 a 69 años.MEDIDAS DE RESULTADOS PRINCIPALES:El resultado principal fue la cirugía restaurativa y el resultado secundario fue el fracaso de la reconstrucción (definida como la necesidad de una nueva ileostomía después de la reconstrucción o la no-reversión de un estoma disfuncional dentro de los dos años posteriores a la reconstrucción). Para calcular los cocientes de riesgo para la cirugía restauradora después de la colectomía, así como el fracaso después de la cirugía restauradora, se realizaron modelos de regresión de Cox multivariables (ajustados por sexo, año de colectomía, diagnóstico de cáncer colorrectal, educación, estado civil, país de nacimiento e ingresos (cuartiles 1- 4; donde Q4 representa los mayores ingresos), volumen de hospitales y estratificado por edad).RESULTADOS:En total 5969 pacientes con colitis ulcerosa se sometieron a colectomía, y de ellos 2794 (46,8%) se sometieron a cirugía restauradora. La cirugía restauradora fue más común en pacientes con altos ingresos en el momento de la colectomía (referencia del cuartil 1, cuartil 2: 1,09 (0,98-1,21), cuartil 3: 1,20 (1,07-1,34), cuartil 4: 1,27 (1,13-1,43)), y menos común en los nacidos en un país nórdico que en los inmigrantes nacidos en un país no-nórdico (0,86 (0,74-0,99)), mientras que no se observó asociación con el nivel educativo y el estado civil. No hubo asociación entre el nivel socioeconómico y el riesgo de fracaso después de la cirugía reparadora.LIMITACIONES:Restricción para registrar datos.CONCLUSIONES:La cirugía reparadora en colitis ulcerosa parece ser más común en pacientes con ingresos altos y en pacientes nacidos en un país no-nórdico, lo que indica desigualdad en la atención brindada. Consulte Video Resumen en http://links.lww.com/DCR/B433.

11.
Aliment Pharmacol Ther ; 53(4): 471-483, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33340426

RESUMO

BACKGROUND: Comparisons of second-line anti-tumour necrosis factor (TNF) agents and vedolizumab are sparse. AIM: To evaluate the effectiveness of anti-TNF agents compared to vedolizumab as second-line biologics in inflammatory bowel disease (IBD). METHODS: A propensity score-matched cohort was created using Swedish nationwide registers. Patients with Crohn's disease or ulcerative colitis, exposed to first-line anti-TNF treatment, who initiated a second anti-TNF agent or vedolizumab in 2014-2016 (N = 1363) were included. The primary outcome was drug survival at 12 months. Secondarily, we assessed survival without IBD-related hospitalisation, IBD-related surgery, antibiotics, or hospitalisation because of infection, and also corticosteroid exposure. RESULTS: After 1:1 propensity score matching, 400 patients (Crohn's disease, N = 198; ulcerative colitis, N = 202) remained. For Crohn's disease, drug survival was 73% in the vedolizumab group vs 74% in the anti-TNF group (difference: 1 percentage point; 95% confidence interval [CI]:-11-13; P = 0.87). Survival without IBD-related hospitalisation (82% vs 88%), surgery (82% vs 89%), antibiotics (65% vs 71%), hospitalisation due to infection (95% vs 88%) and corticosteroids (58% vs 48%) were not statistically significantly different between groups. For ulcerative colitis, drug survival was 69% in the vedolizumab group vs 62% in the anti-TNF group (difference: -7 percentage points; 95% CI: -20 to 6; P = 0.30). Vedolizumab-treated patients had lower survival without IBD-related hospitalisation (82% vs 93%, P = 0.02). Survival without colectomy (93% vs 97%), antibiotics (81% vs 70%), hospitalisation due to infection (92% vs 92%) and corticosteroids (58% vs 48%) were not statistically significantly different. CONCLUSIONS: Based on Swedish clinical practice, the effectiveness and safety of second-line anti-TNF and vedolizumab at 12 months appeared largely similar.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Preparações Farmacêuticas , Anticorpos Monoclonais Humanizados , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Suécia/epidemiologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
12.
Inflamm Bowel Dis ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33295628

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is associated with disturbed mucosal innate lymphoid cell (ILC) composition, which is correlated to the degree of intestinal inflammation. However, it remains unclear whether circulating ILCs are dysregulated in patients with IBD. METHODS: Blood samples from 53 patients with Crohn's disease (CD), 43 patients with ulcerative colitis (UC), and 45 healthy control subjects (HC) were analyzed by flow cytometry for markers of ILC subsets (ILC1, ILC2, and ILC precursors [ILCp]) and selected IBD-relevant proteins, as predicted by previous genome-wide association studies. A dimensionality reduction approach to analyzing the data was used to characterize circulating ILCs. RESULTS: The frequency of ILCp expressing the ILC3 activation markers NKp44 and CD56 was increased in CD versus HC and UC (NKp44) or in CD versus HC (CD56), whereas the CD45RA+ ILCp were reduced in CD versus UC. Furthermore, the activation marker HLA-DR was increased on ILC1 and ILC2 in CD versus HC. Interestingly, the IBD-related protein SLAMF1 was upregulated on ILC2 from both CD and UC samples as compared with HC samples. In active CD, SLAMF1+ ILC2 frequency was negatively correlated with disease severity (Harvey-Bradshaw index). The characterization of SLAMF1+ ILC2 revealed a higher expression of the ILC2 markers CRTH2, CD161, and GATA3 as compared with SLAMF1- ILC2. CONCLUSIONS: In line with the systemic nature of CD inflammation, our findings point toward the activation of ILCs in the blood of patients with CD. Furthermore, in active CD, circulating SLAMF1+ ILC2 are increased in patients with less active disease, introducing SLAMF1+ ILC2 as interesting therapeutic targets deserving further exploration.

13.
14.
J Crohns Colitis ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245360

RESUMO

BACKGROUND/AIM: Patients with inflammatory bowel disease (IBD) have more work disability than the general population. We aimed to estimate the monetary cost of IBD for the individual through assessment of earnings in relation to diagnosis. METHODS: Through linkage of national registers we identified patients aged 30-55 years at first IBD diagnosis in Sweden 2002-2011, and same-sex IBD-free siblings. We estimated taxable earnings and disposable income from 5 years before to 5 years after diagnosis. RESULTS: The 5,961 patients (27% Crohn's disease, 68% ulcerative colitis, 4.3% IBD unclassified) had similar taxable earnings as their 7,810 siblings until the year of diagnosis, when earnings decreased and remained lower than in siblings during follow-up. The adjusted difference in earnings over the entire 5-year period after diagnosis was -5% (-8,212€; 95%CI: -11,458 to-4,967). The difference was larger in women than in men, and larger in Crohn's disease than in ulcerative colitis. When stratifying for sex and IBD subtype and comparing earnings during each year of follow-up, the median annual earnings were lower in women with Crohn's disease and ulcerative colitis than in their sisters during all years of follow-up, whereas the men had similar annual taxable earnings as their brothers. The disposable income was similar between patients and siblings during the investigated time period. CONCLUSION: From the year of diagnosis and at least 5 years onwards, patients with IBD had 5% lower earnings than siblings, mainly explained by differences between women with IBD and their sisters. However, there were no differences in disposable income.

15.
J Pharm Biomed Anal ; 191: 113574, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32896810

RESUMO

Archived dried blood spots (DBS) following newborn screening are an attractive resource for interrogating early-life biology using untargeted metabolomics. Therefore, they have the potential to substantially aid etiological studies, particularly for rare and low-frequency childhood diseases and disorders. However, metabolite quantification in DBS is hindered by variation sources not present in serum and plasma samples such as the hematocrit effect and unknown initial blood volumes. Hemoglobin (Hb) is an appropriate correlate for hematocrit in experimentally-generated DBS punches. However, since many biorepositories worldwide archive DBS at 4-5 °C, there is a need to validate the utility of Hb for DBS archived under refrigeration. We evaluated two simple spectroscopic methods for measuring Hb in DBS stored at 4 +/- 2 °C for up to 21 years, obtained from the newborn screening program at the Karolinska University Hospital, Sweden. Spearman correlation analysis and Akaike Information Criterion model selection found that measurement of a Hb sodium lauryl sulfate complex at 540 nm better described nuisance variation than Hb measured at 404 nm, or using age of spot alone. This is the first study to profile metabolites and to propose a normalization factor for metabolite measurements from DBS archived for decades at 4 °C.

16.
Aliment Pharmacol Ther ; 52(4): 655-668, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32902894

RESUMO

BACKGROUND: There are limited data on population-wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC). AIM: To estimate the societal cost of actively treated CD and UC in Sweden. METHODS: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010-2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave. RESULTS: The mean annual societal costs per working-age patient (18-64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator), respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator, respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working-age CD patients as compared to UC patients was related to greater utilisation of anti-TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators. CONCLUSION: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population.


Assuntos
Colite Ulcerativa , Doença de Crohn , Custos de Cuidados de Saúde , Recursos em Saúde , Licença Médica , Absenteísmo , Adolescente , Adulto , Colite Ulcerativa/economia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Licença Médica/economia , Licença Médica/estatística & dados numéricos , Suécia/epidemiologia , Fator de Necrose Tumoral alfa/uso terapêutico , Trabalho/economia , Trabalho/estatística & dados numéricos , Adulto Jovem
18.
Aging (Albany NY) ; 12(15): 15222-15259, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788422

RESUMO

Immunoglobulin G (IgG) is the most abundant serum antibody which structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. Composition of the IgG N-glycome changes with age of an individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is known to be affected by both genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of IgG, analyzed in 5 different populations totaling 10,482 IgG glycomes, and of IgG's fragment crystallizable region (Fc), analyzed in 2,579 samples from 27 populations sampled across the world. Country of residence associated with many N-glycan features and the strongest association was with monogalactosylation where it explained 38% of variability. IgG monogalactosylation strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators, and with the expected lifespan. Subjects from developing countries had low levels of IgG galactosylation, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.

19.
Scand J Gastroenterol ; 55(10): 1163-1170, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32815414

RESUMO

OBJECTIVE: To examine the role of eosinophils in the pre-diagnostic phase of inflammatory bowel disease (IBD), we studied the influence of genetic and shared environmental risk factors in a twin cohort of IBD. MATERIAL AND METHODS: We analysed eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in faecal samples from twin pairs with Crohn's disease (n = 37) or ulcerative colitis (n = 21) and from external healthy controls (n = 44). Eosinophils stained with eosinophil peroxidase (EPO) were quantified in rectal biopsies. Ratios with 95% confidence intervals were calculated. RESULTS: Twins with Crohn' disease displayed higher levels of EDN (Ratio = 2.98, 1.65-5.37) and ECP (Ratio 1.83, 1.24-2.70) than their healthy siblings. Levels did not differ between healthy twin-siblings and external controls (EDN, Ratio = 1.52, 0.79-2.94 and ECP, Ratio = 0.93, 0.56-1.54). Higher levels of EDN (Ratio = 2.43, 1.13-5.24) and ECP (Ratio = 1.53, 0.92-2.53) were observed among twins with ulcerative colitis vs their healthy siblings. Levels did not differ between healthy twin-siblings and external controls (EDN, Ratio = 1.08, 0.51-2.25 and ECP, Ratio = 1.29, 0.74-2.26). Using intra-class correlation coefficient (ICC), we found no agreement in levels of EDN or ECP in discordant pairs, except for ECP in monozygotic Crohn's disease pairs (ICC = 0.63). In contrast, agreement was observed in monozygotic pairs concordant for Crohn's disease (EDN, ICC = 0.67 and ECP, ICC = 0.66). The number of eosinophils in rectum was increased in twins with ulcerative colitis vs their healthy sibling (Ratio = 2.22, 1.50-3.27). CONCLUSIONS: Activation of eosinophils in IBD seems to be a consequence of inflammation rather than an effect of genetic and shared environmental risk factors alone.

20.
United European Gastroenterol J ; 8(8): 949-960, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32715989

RESUMO

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice. AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

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