| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Adare, A., et al.
(författare)
-
Measurement of High-p(T) single electrons from heavy-flavor decays in p+p collisions at root s=200 GeV
- 2006
-
Ingår i: Physical Review Letters. - 1079-7114. ; 97:25
-
Tidskriftsartikel (refereegranskat)abstract
- The momentum distribution of electrons from decays of heavy flavor (charm and bottom) for midrapidity |y|< 0.35 in p+p collisions at s=200 GeV has been measured by the PHENIX experiment at the BNL Relativistic Heavy Ion Collider over the transverse momentum range 0.3 < p(T)< 9 GeV/c. Two independent methods have been used to determine the heavy-flavor yields, and the results are in good agreement with each other. A fixed-order-plus-next-to-leading-log perturbative QCD calculation agrees with the data within the theoretical and experimental uncertainties, with the data/theory ratio of 1.71 +/- 0.02(stat)+/- 0.18(sys) for 0.3 < p(T)< 9 GeV/c. The total charm production cross section at this energy has also been deduced to be sigma(cc)=567 +/- 57(stat)+/- 193(sys) mu b.
|
|
| 3. |
|
|
| 4. |
- Lundgren, Markus, et al.
(författare)
-
Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
-
Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
|
|
| 5. |
- Beumer, B. R., et al.
(författare)
-
Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria
- 2022
-
Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 13:5, s. 2373-2382
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. Method: Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. Results: Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8months (IQR: 0.77–2.67). The median follow-up period was 5.1 95% CI [4.7–5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51–10.59], P<0.001) and body mass index (0.74 95% CI [0.59–0.89], P<0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07−1.94], P=0.018). Also the SMI was significant (HR 0.98 95% CI [0.96–0.99], P=0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log-rank: P=0.005) with 5year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02−2.05], P=0.036) and SMI were (HR 0.98 95% CI [0.95–0.99], P=0.035) significant. On the survival scale this translates to a 5year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. Conclusions: Overall, we can conclude that higher muscle mass contributes to a better long-term survival. However, for individual patients, low muscle mass should not be considered an absolute contra-indication for LT as its discriminatory performance was limited.
|
|
| 6. |
- Jahoor, Farook, et al.
(författare)
-
Metabolomics Profiling of Patients With A-β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis
- 2021
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:8, s. 1898-1909
-
Tidskriftsartikel (refereegranskat)abstract
- When stable and near-normoglycemic, patients with "A-β+" ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A-β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as having type 2 diabetes (T2D). Patients with KPD and patients with T1D had higher counterregulatory hormones and lower insulin-to-glucagon ratio than patients with T2D and control subjects. Compared with patients withT2D and control subjects, patients with KPD and patients with T1D had lower free carnitine and higher long-chain acylcarnitines and acetylcarnitine (C2) but lower palmitoylcarnitine (C16)-to-C2 ratio; a positive relationship between C16 and C2 but negative relationship between carnitine and β-hydroxybutyrate (BOHB); higher branched-chain amino acids (BCAAs) and their ketoacids but lower ketoisocaproate (KIC)-to-Leu, ketomethylvalerate (KMV)-to-Ile, ketoisovalerate (KIV)-to-Val, isovalerylcarnitine-to-KIC+KMV, propionylcarnitine-to-KIV+KMV, KIC+KMV-to-C2, and KIC-to-BOHB ratios; and lower glutamate and 3-methylhistidine. These data suggest that during DKA, patients with KPD resemble patients with T1D in having impaired BCAA catabolism and accelerated fatty acid flux to ketones-a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A-β+ KPD is marked by chronic but varying dysregulation of BCAA metabolism.
|
|
| 7. |
- Krawczyk, M., et al.
(författare)
-
Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry
- 2016
-
Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 100:11, s. 2372-2381
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. Methods. This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. Results. Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk ofmortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) onmortality (P = 0.071). The optimal cutoff for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. Conclusions. Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Bennet, Louise, et al.
(författare)
-
BMI and waist circumference cut-offs for corresponding levels of insulin sensitivity in a Middle Eastern immigrant versus a native Swedish population - The MEDIM population based study
- 2016
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to identify corresponding body mass index (BMI) and waist circumference cut-offs for equivalent levels of insulin sensitivity in a Middle Eastern immigrant population compared with native Swedes. Methods: Citizens of Malmö, Sweden aged 30 to 75 years, who were born in Iraq or Sweden, were in 2010-2012 invited to participate in a health examination including anthropometrics, oral glucose tolerance test, fasting samples and interviews concerning sociodemographic factors and lifestyle behaviours. Results: In total, 1176 individuals born in Iraq and 688 born in Sweden, without previously diagnosed type 2 diabetes, participated in the study. In normal weight participants (BMI < 25 kg/m2), 21.2% of Iraqis vs 9.3% of Swedes were insulin resistant. Corresponding figures in participants without abdominal obesity (waist circumference, men < 94 cm, women < 80 cm) were 28.2% of Iraqis vs 9.4% of Swedes. The age-adjusted insulin sensitivity index (ISI) for obese Swedes (BMI 30 kg/m2) corresponded in Iraqi men with BMI of 28.5 kg/m2, and in Iraqi women with BMI of 27.5 kg/m2. The ISI level in abdominally obese Swedes corresponded with waist circumference cut-offs of 84.0 cm and 71.0 cm in Iraqi men and women, respectively. In men only, larger waist circumference (P interaction = 0.026) presented a stronger association with impaired ISI in Iraqis as compared to Swedes. Conclusions: Our data shows that the impact of BMI and waist circumference on ISI is ethnic- and gender-specific, indicating a disturbed fat metabolism in Iraqi males in particular. Our data suggests that 10 cm lower cut-off values for abdominal obesity, than is currently recommended by major organisations, should be considered when estimating diabetes risk in Middle Eastern populations.
|
|
| 15. |
- Bennet, Louise, et al.
(författare)
-
Country of birth modifies the association of fatty liver index with insulin action in Middle Eastern immigrants to Sweden
- 2015
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 110:1, s. 66-74
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FLI >= 70) given country of origin and further to investigate the associations between ISI and FLI. Methods: In 2010-2012 we conducted a population-based study of individuals aged 30-75 years born in Iraq or Sweden, in whom anthropometrics, fasting blood samples and oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors characterized. Results: A higher proportion of Iraqis (N = 1085) than Swedes (N = 605) had a high probability of NAFLD (FLI >= 70, 32.5 vs. 22.6%, p < 0.001, age-and sex-adjusted data) and ISI was more severely impaired (70.7 vs. 95.9%, p < 0.001). Independently of traditional risk factors for NAFLD, being born in Iraqi increased the risk of FLI >= 70 (OR 1.59: 95% CI 1.15, 2.20). Furthermore, country of birth presented a stronger association between ISI and FLI >= 70 in Iraqis than in Swedes (P-interaction = 0.019). Conclusions: Our data indicate that immigrants from Iraq are at higher risk of NAFLD. The finding that country of birth modifies the relationship of FLI with ISI, suggests that liver fat may be a stronger determinant of impaired insulin action and increased risk of type 2 diabetes in Iraqis than in Swedes.
|
|
| 16. |
- Bennet, Louise, et al.
(författare)
-
Ethnic differences in the contribution of insulin action and secretion to type 2 diabetes in immigrants from the Middle East compared to native Swedes
- 2014
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 105:1, s. 79-87
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: We investigated insulin action (insulin sensitivity index, ISI) and insulin secretion (oral disposition indices, DIo) and studied metabolic, demographic and lifestyle-related risk factors for type 2 diabetes and insulin action, in the largest non-European immigrant group to Sweden, immigrants from Iraq and native Swedes.Methods: Population-based, cross-sectional study conducted 2010-2012 including residents 30-75 years of age born in Iraq or Sweden, in whom oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors were characterized.Results: In Iraqis compared to Swedes, ISI was more impaired (76.9 vs. 102.3, p < .001) whereas corrected insulin response CIR was higher (226.6 vs. 188.6, p = .016). However, insulin secretion was inadequate given the substantial insulin resistance, as indicated by lower DIo indices in Iraqis than in Swedes (DIo 12,712.9 vs. 14,659.2, p < .001). The crude ethnic difference in ISI was not offset by traditional risk factors like waist circumference, body mass index or family history of diabetes. In Iraqis, ISI conveyed somewhat higher odds of type 2 diabetes than in Swedes (odds ratio OR 0.98, 95% CI 0.97-0.99) vs. OR 0.95, 0.92-0.99), as indicated by an interaction between country of birth and ISI (P-interaction = .044).Conclusion: This study reports ethnic differences in the contribution of insulin action to type 2 diabetes. Our data suggests that the impaired insulin action observed in immigrants from the Middle East to Sweden is not fully explained by established risk factors.(C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
|
|
| 17. |
- Bennet, Louise, et al.
(författare)
-
Family history of diabetes and its relationship with insulin secretion and insulin sensitivity in Iraqi immigrants and native Swedes : a population-based cohort study
- 2018
-
Ingår i: Acta Diabetologica. - : Springer Milan. - 0940-5429 .- 1432-5233. ; 55:3, s. 233-242
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Middle Eastern immigrants to western countries are at high risk of developing type 2 diabetes. However, the heritability and impact of rst-degree family history (FH) of type 2 diabetes on insulin secretion and action have not been adequately described. Methods Citizens of Malmö, Sweden, aged 30–75 years born in Iraq or Sweden were invited to participate in this population- based study. Insulin secretion (corrected insulin response and oral disposition index) and action (insulin sensitivity index) were assessed by oral glucose tolerance tests.Results In total, 45.7% of Iraqis (616/1348) and 27.4% of native Swedes (201/733) had FH in parent(s), sibling(s) or single parent and sibling, i.e., FH+. Approximately 8% of Iraqis and 0.7% of Swedes had ≥ 3 sibling(s) and parent(s) with diabetes, i.e., FH++. Irrespective of family size, prediabetes and diabetes increased with family burden (FH− 29.4%; FH+ 38.8%; FH++ 61.7%) without signi cant di erences across ethnicities. With increasing level of family burden, insulin secretion rather than insulin action decreased. Individuals with a combination of ≥ 3 siblings and parents with diabetes presented with the lowest levels of insulin secretion.Conclusions The Iraqi immigrant population often present with a strong familial burden of type 2 diabetes with the worst glycemic control and highest diabetes risk in individuals with ≥ 3 siblings and parents with diabetes. Our data show that in a population still free from diabetes familial burden in uences insulin secretion to a higher degree than insulin action and may be a logical target for intervention.
|
|
| 18. |
- Bennet, Sean, et al.
(författare)
-
Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics
- 2018
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:10
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSerum levels of pro-inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. MethodsSerum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF), and IL-10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. Key ResultsIrritable bowel syndrome patients (n=246) had higher serum levels of IL-1, IL-6, IL-8, TNF, and IL-10 compared to HS (n=21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS-DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. Conclusions & InferencesSerum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Bennet, W, et al.
(författare)
-
Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation?
- 1999
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 48:10, s. 1907-1914
-
Tidskriftsartikel (refereegranskat)abstract
- The remarkable difference in success rates between clinical pancreas transplantation and islet transplantation is poorly understood. Despite the same histocompatibility barrier and similar immunosuppressive treatments in both transplantation procedures, human intraportal islet transplantation has a much inferior success rate than does vascularized pancreas transplantation. Thus far, little attention has been directed to the possibility that islets transplanted into the blood stream may elicit an injurious incompatibility reaction. We have tested this hypothesis in vitro with human islets and in vivo with porcine islets. Human islets were exposed to nonanticoagulated human ABO-compatible blood in surface-heparinized polyvinyl chloride tubing loops. Heparin and/or the soluble complement receptor 1 (sCR1) TP10 were tested as additives. Adult porcine islets were transplanted intraportally into pigs, and the liver was recovered after 60 min for immunohistochemical staining. Human islets induced a rapid consumption and activation of platelets. Neutrophils and monocytes were also consumed, and the coagulation and complement systems were activated. Upon histological examination, islets were found to be embedded in clots and infiltrated with CD11+ leukocytes. Furthermore, the cellular morphology was disrupted. When heparin and sCR1 were added to the blood, these events were avoided. Porcine islets retrieved in liver biopsies after intraportal islet allotransplantation showed a morphology similar to that of human islets perifused in vitro. Thus, exposure of isolated islets of Langerhans to allogenic blood resulted in significant damage to the islets, a finding that could explain the unsatisfactory clinical results obtained with intraportal islet transplantation. Because administration of heparin in combination with a soluble complement receptor abrogated these events, such treatment would presumably improve the outcome of clinical islet transplantation by reducing both initial islet loss and subsequent specific immune responses.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Cetinic, Ivan, et al.
(författare)
-
Shear wave elastography and shear wave dispersion correlated to biopsy at the scheduled follow-up of pediatric liver grafts
- 2023
-
Ingår i: Pediatric Transplantation. - 1397-3142. ; 27:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: It is unknown how shear wave dispersion (SWD) is displayed in pediatric liver transplant recipients and not fully elucidated how ultrasound shear wave elastography (2D-SWE) display within this cohort, which is important to determine to improve noninvasive surveillance of these patients. The study aimed to compare SWE and SWD values with histopathology in pediatric liver recipients.Methods: Forty-eight pediatric liver recipients were examined with SWE in conjunction with an elective liver biopsy (clinically without complication). Additionally, SWD values were measured in 21 children. SWE and SWD values were compared to histologically determined fibrosis graded as none-to-mild (F0-1) and moderate-to-severe (F2-4), and inflammation graded as low (grade 0-1) and high (grade 2-4).Results: Two children were excluded due to SWE IQR/median > 30% kPa. The mean age across 46 included patients was 10.9 years (range 1.4-18). The number of patients and median (range) SWE value (kPa) for each stage of fibrosis were: F0-1 [n = 23; 5.8 (3.2-16.1)], F2 [n = 22; 6.0 (4.5-25.9)], F3 [n = 1; 33.3], and F4 [n = 0]. Significantly higher SWE values and greater variability were registered in F2-4 vs. F0-1 (p = .05). Grade of fibrosis correlated weakly to SWE values (r = .3; p = .05), but not to SWD values (r = .2; p = .27). In patients with low-grade inflammation, median SWD was 13.7 m/s KHz (10.7-17.6). Only one patient had high-grade inflammation.Conclusions: Uncomplicated transplanted liver grafts in a small pediatric cohort revealed slightly increased SWE and SWD values compared to previously reported values in healthy children. This likely reflect both the fibrotic and inflammatory elements in the grafts; however, other confounders impacting the liver's viscoelastic properties are also probable factors.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Eriksson, Jan W., et al.
(författare)
-
Registry-based randomised clinical trials : a remedy for evidence-based diabetes care?
- 2022
-
Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 65:10, s. 1575-1586
-
Forskningsöversikt (refereegranskat)abstract
- This narrative review describes a new approach to navigation in a challenging landscape of clinical drug development in diabetes. Successful outcome studies in recent years have led to new indications and guidelines in type 2 diabetes, yet the number of clinical trials in diabetes is now declining. This is due to many environmental factors acting in concert, including the prioritisation of funding for other diseases, high costs of large randomised clinical trials, increase in regulatory requirements and limited entry of novel candidate drugs. There is a need for novel and cost-effective paradigms of clinical development to meet these and other challenges. The concept of registry-based randomised clinical trials (RRCTs) is an attractive option. In this review we focus on type 2 diabetes and the prevention of cardiovascular and microvascular comorbidities and mortality, using the Swedish SMARTEST trial as an example of an RRCT. We also give some examples from other disease areas. The RRCT concept is a novel, cost-effective and scientifically sound approach for conducting large-scale diabetes trials in a real-world setting.
|
|
| 36. |
- Gressens, Pierre, et al.
(författare)
-
Pitfalls in the Quest of Neuroprotectants for the Perinatal Brain.
- 2011
-
Ingår i: Developmental neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 33:3-4, s. 189-198
-
Tidskriftsartikel (refereegranskat)abstract
- Sick preterm and term newborns are highly vulnerable to neural injury, and thus there has been a major search for new, safe and efficacious neuroprotective interventions in recent decades. Preclinical studies are essential to select candidate drugs for clinical trials in humans. This article focuses on 'negative' preclinical studies, i.e. studies where significant differences cannot be detected. Such findings are critical to inform both clinical and preclinical investigators, but historically they have been difficult to publish. A significant amount of time and resources is lost when negative results or nonpromising therapeutics are replicated in separate laboratories because these negative results were not shared with the research community in an open and accessible format. In this article, we discuss approaches to strengthen conclusions from negative preclinical studies and, conversely, to reduce false-negative preclinical evaluations of potential therapeutic compounds. Without being exhaustive, we address three major issues in conducting and interpreting preclinical experiments, including: (a) the choice of animal models, (b) the experimental design, and (c) issues concerning statistical analyses of the experiments. This general introduction is followed by synopses of negative data obtained from studies of three potential therapeutics for perinatal brain injury: (1) the somatostatin analog octreotide, (2) an AMPA/kainate receptor antagonist, topiramate, and (3) a pyruvate derivative, ethyl pyruvate.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Jimenez-Moreno, A. Cecilia, et al.
(författare)
-
Patient Preferences in Rare Diseases: A Qualitative Study in Neuromuscular Disorders to Inform a Quantitative Preference Study
- 2021
-
Ingår i: Patient. - : Springer Science and Business Media LLC. - 1178-1653 .- 1178-1661.
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionIt has become increasingly important to include patient preference information in decision-making processes for drug development. As neuromuscular disorders represent multisystem, debilitating, and progressive rare diseases with few treatment options, this study aimed to explore unmet health care needs and patient treatment preferences for two neuromuscular disorders, myotonic dystrophy type 1 (DM1) and mitochondrial myopathies (MM) to inform early stages of drug development.MethodsFifteen semi-structured interviews and five focus group discussions (FGDs) were held with DM1 and MM adult patients and caregivers. Topics discussed included (1) reasons for study participation; (2) disease signs/symptoms and their impact on daily lives; (3) top desired benefits; and (4) acceptability of risks and tolerance levels for a hypothetical new treatment. Data were analyzed following a thematic ‘code’ approach.ResultsA total of 52 participants representing a wide range of disease severities participated. ‘Muscle strength’ and ‘energy and endurance’ were the disease-related unmet needs most often mentioned. Additionally, improved ‘balance’, ‘cognition’ and ‘gut function’ were the top desired treatment benefits, while ‘damage to the liver, kidneys or eyes’ was the most concerning risk. Factors influencing their tolerance to risks related to previously having experienced the risk and differentiation between permanent and temporary risks. A few differences were elicited between patients and caregivers.ConclusionsThis qualitative study provided an open forum to elicit treatment-desired benefits and acceptable risks to be established by patients themselves. These findings can inform decisions for developing new treatments and the design of clinical trials for DM1 and MM.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- McGale, Paul, et al.
(författare)
-
Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden
- 2011
-
Ingår i: Radiotherapy and Oncology. - Amsterdam : Elsevier. - 0167-8140 .- 1879-0887. ; 100:2, s. 167-175
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30 years. Material and methods: 72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976-2006 and followed prospectively. Radiation-related risk was studied by comparing women with left-sided and right-sided tumours. Results: 34,825 women (48%) received radiotherapy. Among unirradiated women tumour laterality had little relevance to heart disease. Among irradiated women mean dose to the whole heart was 6.3 Gy for left-sided tumours and 2.7 Gy for right-sided tumours. Mortality was similar in irradiated women with left-sided and right-sided tumours, but incidence ratios, left-sided versus right-sided, were raised: acute myocardial infarction 1.22 (95% CI 1.06-1.42), angina 1.25 (1.05-1.49), pericarditis 1.61 (1.06-2.43), valvular heart disease 1.54 (1.11-2.13). Incidence ratios for all heart disease were as high for women irradiated since 1990 (1.09 [1.00-1.19]) as for women irradiated during 1976-1989 (1.08 [0.99-1.17]), and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women (1.58 [1.19-2.10] versus 1.08 [1.01-1.15], p for difference = 0.01). Conclusions: Breast cancer radiotherapy has, at least until recently, increased the risk of developing ischaemic heart disease, pericarditis and valvular disease. Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 100 (2011) 167-175
|
|
| 45. |
- Mohamed, Siham A, et al.
(författare)
-
GWAS in people of Middle Eastern descent reveals a locus protective of kidney function-a cross-sectional study
- 2022
-
Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Type 2 diabetes is one of the leading causes of chronic kidney failure, which increases globally and represents a significant threat to public health. People from the Middle East represent one of the largest immigrant groups in Europe today. Despite poor glucose regulation and high risk for early-onset insulin-deficient type 2 diabetes, they have better kidney function and lower rates of all-cause and cardiovascular-specific mortality compared with people of European ancestry. Here, we assessed the genetic basis of estimated glomerular filtration rate (eGFR) and other metabolic traits in people of Iraqi ancestry living in southern Sweden.METHODS: Genome-wide association study (GWAS) analyses were performed in 1201 Iraqi-born residents of the city of Malmö for eGFR and ten other metabolic traits using linear mixed-models to account for family structure.RESULTS: The strongest association signal was detected for eGFR in CST9 (rs13037490; P value = 2.4 × 10-13), a locus previously associated with cystatin C-based eGFR; importantly, the effect (major) allele here contrasts the effect (minor) allele in other populations, suggesting favorable selection at this locus. Additional novel genome-wide significant loci for eGFR (ERBB4), fasting glucose (CAMTA1, NDUFA10, TRIO, WWC1, TRAPPC9, SH3GL2, ABCC11), quantitative insulin-sensitivity check index (METTL16), and HbA1C (CAMTA1, ME1, PAK1, RORA) were identified.CONCLUSIONS: The genetic effects discovered here may help explain why people from the Middle East have better kidney function than those of European descent. Genetic predisposition to preserved kidney function may also underlie the observed survival benefits in Middle Eastern immigrants with type 2 diabetes.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Siddiqui, Faiza, et al.
(författare)
-
Physical Activity in a Randomized Culturally Adapted Lifestyle Intervention
- 2018
-
Ingår i: American Journal of Preventive Medicine. - : Elsevier BV. - 0749-3797. ; 55:2, s. 187-196
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Middle Eastern immigrants exhibit high levels of physical inactivity and are at an increased risk for Type 2 diabetes. The primary aim of this study was to examine the changes in objectively assessed physical activity levels following a culturally adapted lifestyle intervention program. The secondary aim was to examine the association between objectively assessed physical activity and insulin sensitivity. Participants: Iraqi immigrants residing in Malmo, Sweden, exhibiting one or more risk factors for Type 2 diabetes. Intervention: The intervention group (n=50) was offered a culturally adapted lifestyle intervention comprising seven group sessions including a cooking class. The control group (n=46) received usual care. Main outcome measures: Raw accelerometry data were processed by validated procedures and daily mean physical activity intensity, vector magnitude high-pass filtered (VM-HPF), was inferred. Further inferences into the number of hours/day spent in sedentary (VM-HPF <48 milli-Gs [mGs] where G=9.8 m/sec(2)) and light- (48- <163 mGs); moderate- (163- <420 mGs); and vigorous-intensity (>= 420 mGs) activities were also calculated (year of analysis was 2016-2017). Results: No difference was observed between the two groups in terms of change over time in VM-HPF. There was a significant increase in the number of hours/day spent in light intensity physical activity in the intervention group compared with the control group (beta=0.023, 95% CI=0.001, 0.045, p=0.037). The intervention group also increased the time spent in sedentary activities, with the highest VM-HPF (36- < 48 mGs) within the sedentary behavior (B=0.022, 95% CI=0.002, 0.042, p=0.03). Higher VM-HPF was significantly associated with a higher insulin sensitivity index (beta=0.014, 95% CI=0.0004, 0.025, p=0.007). Conclusions: The findings favor the culturally adapted intervention approach for addressing low physical activity levels among Middle Eastern immigrants. Replacing sedentary time with light-intensity activities could be an achievable goal and will have potential beneficial effects for diabetes prevention among this sedentary group of immigrants. Trial registration: This study was registered at www.clinicaltrials.gov NCT01420198. Am J Prev Med 2018;55(2):187-196. (C) 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
|
|
| 49. |
|
|
| 50. |
- Soekhai, Vikas, et al.
(författare)
-
Methods for exploring and eliciting patient preferences in the medical product lifecycle: a literature review
- 2019
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 24:7, s. 1324-1331
-
Tidskriftsartikel (refereegranskat)abstract
- HighlightsPreference studies are becoming increasingly important within the medical product decision-making context.Currently, there is limited understanding of the range of methods to gain insights into patient preferences.We developed a compendium and taxonomy of preference exploration (qualitative) and elicitation (quantitative) methods.We identified 32 unique preference methods.Our results can serve as an important resource for determining which preference methods are most promising in the medical product lifecycle.
|
|
