| 1. |
- Pourhamidi, Kaveh, et al.
(författare)
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Evaluation of clinical tools and their diagnostic use in distal symmetric polyneuropathy
- 2014
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Ingår i: Primary care diabetes. - : Elsevier. - 1878-0210 .- 1751-9918. ; 8:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To compare the diagnostic usefulness of tuning fork, monofilament, biothesiometer and skin biopsies in peripheral neuropathy in individuals with varying glucose metabolism.METHODS: Normoglycaemic, impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) individuals were recruited. Nerve conduction studies (NCS) and thermal threshold tests were performed. Vibrotactile sense was tested with a biothesiometer and a 128-Hz tuning fork. Touch/pressure perception was examined with a 10-g monofilament. Skin biopsies were performed and intraepidermal nerve fibres were quantified. Distal symmetric polyneuropathy (DSPN) was defined as neuropathy disability score ≥2 and abnormal NCS. Thermal threshold tests were used to define small nerve fibre neuropathy (sDSPN) in cases where NCS (large nerve fibres) were normal.RESULTS: The prevalence of DSPN and sDSPN in the whole group (n=119) was 18% and 23%, respectively. For the biothesiometer, a cut-off of ≥24.5V had a sensitivity of 82% and specificity of 70% (AUC=0.81, 95% CI 0.71-0.91) when evaluating DSPN. An intraepidermal nerve fibre density cut-off of ≤3.39fibres/mm showed a sensitivity of 74% and specificity of 70% in the detection of sDSPN, whereas the sensitivity of the tuning fork and the biothesiometer were relatively low, 46% and 67%, respectively. When combining skin biopsies with the tuning fork, 10 more sDSPN cases were identified. Adding skin biopsy to the combination of the tuning fork and biothesiometer increased the sensitivity of finding sDSPN cases, but not DSPN, from 81% to 93%.CONCLUSION: Using a biothesiometer in clinical routine might be a sensitive method to detect large nerve fibre dysfunction in the lower extremity, whereas skin biopsies in combination with methods measuring vibrotactile sense could increase the diagnostic sensitivity of detecting peripheral neuropathy at an early stage.
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| 2. |
- Ahlsson, Anders, 1962-, et al.
(författare)
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A Swedish consensus on the surgical treatment of concomitant atrial fibrillation
- 2012
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Ingår i: Scandinavian Cardiovascular Journal. - London, United Kingdom : Informa Healthcare. - 1401-7431 .- 1651-2006. ; 46:4, s. 212-218
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Forskningsöversikt (refereegranskat)abstract
- Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open heart surgery and is associated with increased morbidity and mortality. According to international guidelines, symptomatic and selected asymptomatic patients should be offered concomitant surgical AF ablation in conjunction with valvular or coronary surgery. The gold standard in AF surgery is the Cox Maze III ("cut-and-sew") procedure, with surgical incisions in both atria according to a specified pattern, in order to prevent AF reentry circuits from developing. Over 90% of patients treated with the Cox Maze III procedure are free of AF after 1 year. Recent developments in ablation technology have introduced several energy sources capable of creating nonconducting atrial wall lesions. In addition, simplified lesion patterns have been suggested, but results with these techniques have been unsatisfactory. There is a clear need for standardization in AF surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all Swedish units for cardiothoracic surgery, has therefore reached a consensus on surgical treatment of concomitant AF. This consensus emphasizes adherence to the lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in nonparoxysmal AF.
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| 3. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 4. |
- Pourhamidi, Kaveh, et al.
(författare)
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Heat shock protein 27 concentrations are lower in patientswith type 1 diabetes mellitus than in healthy controls andcorrelates with large nerve fibre dysfunction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective Heat shock protein 27 (HSP27) may contribute to the survival of neurons. Our aims were to study whether HSP27 concentrations differ between individuals with and without type 1 diabetes, and evaluate the relationship between the progression of peripheral nerve dysfunction and HSP27 concentrations.Research Design and Methods Type 1 diabetes patients (n=27, 41% women; mean age 41±8 years) were recruited in 1992 with a follow-up in 2005; serum HSP27 concentrations were determined in baseline and follow-up samples and compared to non-diabetic controls (n=397, 34% women; mean age 43±14 years). The type 1 diabetes patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Reference data was used to standardise results for age, height and sex by calculating the Z-scores. Delta changes in HSP27 (follow-up HSP27 – baseline HSP27) and small and large nerve fibre function were used for correlation analyses.Results Type 1 diabetes patients had lower HSP27 concentrations at baseline (mean HSP27547 pg/ml, 95% CI 421, 711) and at follow-up (mean HSP27 538 pg/ml, 95% CI 417,693) compared to healthy controls (mean HSP27 785 pg/ml, 95% CI 732, 842; p<0.05 for both comparisons). Deteriorating large nerve fibre function correlated with delta HSP27 concentrations in type 1 diabetes (r=0.50, p=0.01).Conclusions Patients with type 1 diabetes had lower HSP27 concentrations than non-diabetic controls and progression of large nerve fibre dysfunction correlated with decreasing HSP27 concentrations during the follow-up period. This could be indicative ofinsufficient neuroprotection in type 1 diabetes.
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| 5. |
- Pourhamidi, Kaveh, et al.
(författare)
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Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy
- 2011
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 54:12, s. 3143-3149
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis High levels of serum heat shock protein 27 (sHSP27) have been associated with distal symmetric polyneuropathy in patients with type 1 diabetes. Our objective was to investigate the association between sHSP27, neuropathic signs and nerve function in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes.Methods Participants were recruited consecutively from the population-based Vasterbotten Intervention Program (NGT, n=39, IGT, n=29, and type 2 diabetes, n=51) and were matched for age and sex. sHSP27 levels were measured and nerve conduction studies were performed (peroneal and sural nerves). z Scores for each nerve conduction measure were calculated and compiled into a composite z score for the leg. Neuropathy disability score (NDS) was used to assess neuropathic signs.Results Patients with diabetes had significantly lower sHSP27 levels (geometric mean sHSP27 206 pg/ml, 95% CI 142, 299) than those with IGT (geometric mean sHSP27 455 pg/ml, 95% CI 319, 650, p<0.05) and controls (geometric mean sHSP27 361 pg/ml, 95% CI 282, 461, p<0.05). Participants with few signs of neuropathy (first tertile, NDS <= 2) had significantly higher sHSP27 levels (geometric mean sHSP27 401 pg/ml, 95% CI 310, 520) than participants with many signs (third tertile, NDS >= 7) (geometric mean sHSP27 192 pg/ml, 95% CI 128, 288, p=0.007). The highest sHSP27 tertile was associated with better nerve function, adjusted for age, sex, statin medication and HbA(1c) (OR 2.51, 95% CI 1.25, 5.05, p<0.05).Conclusions/interpretation High sHSP27 levels were associated with better nerve function and fewer neuropathic signs in NGT, IGT and type 2 diabetes.
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| 6. |
- Pourhamidi, Kaveh, 1985-
(författare)
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Peripheral nerve function : metabolic features, clinical assessment, and heat shock protein 27
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peripheral neuropathy is a common complication among patients with diabetes mellitus, but whether peripheral neuropathy is present in individuals with impaired glucose tolerance (IGT) is debatable. In order to identify and diagnose peripheral neuropathy correctly, it is important to evaluate diagnostic tools that can be implemented in routine health care to assess both large and small nerve fibre function. There is currently limited knowledge about neuroprotective factors that could be useful for measuring peripheral nerve function in individuals at risk of developing neuropathy such as those with diabetes mellitus. Thus, studies are needed to investigate potential neuroprotective factors in relation to peripheral nerve function in humans.Objectives: The overall goal of this thesis was to study the metabolic features and clinical assessment of peripheral nerve function and the potential relationship between the neuroprotective factor heat shock protein 27 (HSP27) and peripheral nerve function.Methods: Thirty-nine participants with normal glucose tolerance (NGT) and 29 participants with IGT were recruited from the population-based Västerbotten Intervention Programme in 2003–2004. Patients with type 2 diabetes mellitus (T2DM, n = 51) were recruited from primary health care centres. NGT and IGT individuals underwent two separate oral glucose tolerance tests to verify their glucose status. The peripheral nerve function in the lower limb was assessed by nerve conduction studies, neuropathy disability scoring, quantitative sensory tests, and skin biopsies with subsequent quantification of intraepidermal nerve fibre density (IENFD). The concentrations of HSP27 in serum were determined in the NGT, IGT, and T2DM individuals. Patients with type 1 diabetes mellitus (T1DM) were recruited from the Diabetes Clinic, Skåne University Hospital in Malmö, Sweden (n = 27) in 1992 and were followed-up in 2005. Baseline and follow-up concentrations of HSP27 were determined in T1DM patients as well as in healthy non-diabetic controls (n = 397). The T1DM patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Delta changes in HSP27 concentrations and small and large nerve fibre function were calculated.Results: There was no difference between IGT and NGT in sural nerve conduction, intraepidermal nerve fibre density, or thermal thresholds. The biothesiometer had a sensitivity of 82% and a specificity of 72% in identifying peripheral neuropathy with a cut-off value of ≥24.5 V at the medial malleolus. Adding the quantification of IENFD to the combination of the tuning fork and biothesiometer increased the diagnostic sensitivity from 81% to 95%, the negative predictive value from 87% to 94%, and the positive likelihood ratio from 1.8 to 1.9 when identifying small nerve fibre dysfunction. T2DM patients had lower HSP27 concentrations (mean HSP27 = 412 pg/mL, 95% CI 284–598 pg/mL) than NGT (mean HSP27 = 722 pg/mL, 95% CI 564–922 pg/mL) and IGT (mean HSP27 = 1010 pg/mL, 95% CI 638–1300 pg/mL) individuals (p <0.05 for both comparisons). T1DM patients had lower HSP27 concentrations at baseline (mean HSP27 = 547 pg/mL, 95% CI 421–711 pg/mL) and at follow-up (mean HSP27 = 538 pg/mL, 95% CI 417–693 pg/mL) compared to healthy controls (mean HSP27 = 785 pg/mL, 95% CI 732–842 pg/mL), p <0.05 for both comparisons). High concentrations of HSP27 were associated with better large nerve fibre function (Odds ratio = 2.51, 95% CI 1.25–5.05, p <0.05). Deteriorating large nerve fibre function correlated with decreasing HSP27 concentrations over time in T1DM patients (r = 0.50, p = 0.01).Conclusions: Measures of large and small nerve fibre function in IGT individuals do not differ significantly from NGT individuals. The existence of peripheral neuropathy as a consequence of IGT is not likely, and extensive control of neuropathy in IGT individuals is not advocated by this thesis. The biothesiometer is a useful clinical tool to identify peripheral neuropathy in routine health care. Quantification of IENFD using skin biopsies in combination with methods measuring vibrotactile sense, such as the biothesiometer and the tuning fork, increase the diagnostic usefulness of identifying small nerve fibre dysfunction. High HSP27 concentrations are associated with better peripheral large nerve fibre function. Patients with diabetes mellitus have lower HSP27 concentrations than healthy non-diabetic controls, and deterioration of large nerve fibre function correlates with a decrease in HSP27 concentrations over time in T1DM. This could be indicative of insufficient neuroprotection in patients with diabetes mellitus.
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| 7. |
- Sarwar, Nadeem, et al.
(författare)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
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Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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| 8. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 9. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 10. |
- Bergthorsdottir, Ragnhildur, 1971, et al.
(författare)
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Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency : a Swedish nationwide study
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown.Methods: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis.Results: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28).Conclusion: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.
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