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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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7. |
- Montgomery, Scott, 1961-, et al.
(författare)
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Infections in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 388-388
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Previous studies suggest that susceptibility to infections is not raised among multiple sclerosis (MS) patients in general, but certain specific infections, such as those of the urinary or respiratory tract, are more common in patients with higher disability. However, contemporary MS cohorts to a higher degree are treated with newer disease-modifying treatments (DMTs) that exert stronger effects on the immune defence. Here we investigated the rate of infections in patients before and after MS diagnosis as compared with a matched MS-free population.Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register. MS patients were matched to 10 MS-free individuals by age, sex, and region of residence. Incidence rates per 10,000 person-years and incidence rate ratios (IRRs) of first infection by site and type were calculated after the MS diagnosis date.Results: In total, 6,602 MS patients were identified and compared with 61,828 without MS (female, 69%; median age, 40 years). During the year before MS diagnosis, MS patients showed higher proportions of urinary and kidney infections, meningitis and encephalitis, and bacterial infections compared with the MS-free cohort.After MS diagnosis, an increased risk of non-serious (IRR 1.65; 95% CI 1.56-1.75) and serious (admitted to hospital) infections (IRR 2.59; 95% CI 2.33-2.89) was detected among MS patients relative to the MS-free cohort. The risk of some bacterial (IRR 2.23; 95% CI 1.98-2.52) and some viral infections (IRR 1.70; 95% CI 1.48-1.96) was higher in MS patients of both sexes while only males showed an increased risk of fungal infections (IRR 1.91; 95% CI 1.26-2.89). Relative to the MS-free cohort, MS patients had an increased risk of all infection types, such as meningitis and encephalitis (IRR 6.16; 95% CI 4.47-8.48), other opportunistic infections (IRR 2.72; 95% CI 2.08-3.55), urinary and kidney infections (IRR 2.44; 95% CI 2.24-2.66), herpes virus (IRR 2.32; 95% CI 1.77-3.05), pneumonia and influenza (IRR 1.92; 95% CI 1.66-2.23), and skin infections (IRR 1.89; 95% CI 1.65-2.16).Conclusions: After MS diagnosis, patients had higher incidences of non-serious and serious infections compared with a cohort without MS. MS patients had an increased risk of being diagnosed during follow-up with most infection types compared with controls. This risk was particularly high for meningitis and encephalitis.
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8. |
- Montgomery, Scott, 1961-, et al.
(författare)
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Risk of osteoporosis and fractures in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 387-388
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: While multiple sclerosis (MS) is usually diagnosed in young adults, many individuals living with the diagnosis are above age 40 years. Osteoporosis and fractures, which are morbidities generally associated with ageing but also physical inactivity, were determined in patients before and after MS diagnosis and compared with a matched MS-free population.Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register and matched with 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years and incidence rate ratios (IRRs; vs the MS-free cohort) of osteoporosis and fractures by sex and age at event were calculated after MS diagnosis based on ICD-10 codes from inpatient and outpatient specialist care.Results: In total, 6,602 MS patients were identified and compared with 61,828 without MS (female, 69%; median age, 40 years). Before MS diagnosis, MS patients showed significantly increased proportions of osteoporosis (0.5% vs 0.3%) and fractures (12.6% vs 11.4%) compared with the MS-free cohort.After diagnosis, MS patients had an increased risk of osteoporosis (IRR 1.69; 95% confidence interval [CI] 1.22-2.35). The increased risk of osteoporosis among MS patients was observed for both sexes (females, IRR 1.60; 95% CI 1.13-2.28 and males, IRR 2.56; 95% CI 1.04-6.31), as well as in the older age strata 40-59 years (IRR 2.39; 95% CI 1.47-3.89) and ⩾60 years (IRR 1.69; 95% CI 1.06-2.70), but not among those aged < 40 years. Similarly, an increased risk of fractures among MS patients (IRR 1.37; 95% CI 1.24-1.51) was shown for both females (IRR 1.40; 95% CI 1.25-1.58) and males (IRR 1.29; 95% CI 1.07-1.55), as well as the age strata 40-59 years (IRR 1.52; 95% CI 1.31-1.76) and ⩾60 years (IRR 1.92; 95% CI 1.58-2.33), but not those aged < 40 years.Conclusions: The risk of osteoporosis and fractures was moderately increased in MS patients of both sexes and in the older age groups, which may relate to physical inactivity and an increased risk of falls.
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- Piehl, F., et al.
(författare)
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Cardiovascular disease in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 49-50
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The cardiovascular disease (CVD) rate among multiple sclerosis (MS) patients has been shown to be elevated; however, studies involving more recently diagnosed patients are rare. Here we estimated the rate of CVD in patients before and after MS diagnosis as compared with a matched MS-free population.Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register. MS patients were matched with 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years (PY) and incidence rate ratios (IRR) of cardiovascular outcomes were calculated after MS diagnosis (equivalent date for those without MS) and among those with no history of CVD before this date.Results: In total, 6,602 MS patients and 61,828 without MS (female, 69%; median age, 40 years) were identified. Before MS diagnosis, patients showed higher proportions of stroke (2.0% vs 0.6%), transient ischaemic attack (TIA) (0.4% vs 0.2%) and peripheral vascular disease (0.3% vs 0.2%) compared with the MS-free cohort. The year before MS diagnosis, larger proportions were prescribed diuretics (8.4% vs 6.9%), peripheral vasodilators (1.4% vs 1.0%), lipid-modifying agents (5.6% vs 4.8%), and calcium channel blockers (3.7% vs 3.1%).After MS diagnosis, patients had a higher risk of major adverse cardiovascular events (MACE) (IRR 1.35; 95% confidence interval [CI] 1.06-1.71), heart failure (HF) (IRR 1.36; 95% CI 1.02-1.80), and TIA (IRR 1.59; 95% CI 1.05-2.42) compared with the MS-free cohort. The risk of bradycardia (IRR, 2.61; 95% CI 1.14-5.97) was higher only in MS patients with no history of CVD. CVD incidence rates in MS patients were comparable between sexes except for the HF rate, which was higher among males (28.28 per 10,000 PY, 95% CI 18.79-40.87) than females (11.81 per 10,000 PY, 95% CI 7.71-17.30). The relative risk of MACE (IRR 2.40; 95% CI 1.15-5.00), TIA (IRR 7.03; 95% CI 2.62 -18.87), HF (IRR 3.28; 95% CI 1.46-7.37), and bradycardia (IRR 4.51; 95% CI 1.54-13.20) were higher among younger MS patients (aged < 40 years at diagnosis).Conclusions: After MS diagnosis, MS patients showed an increased incidence of MACE, TIA, and HF compared with those without MS, irrespective of CVD history. The age-matched rela-tive risk was particularly high among younger MS patients. In particular, the relative risk of bradycardia was only higher among younger patients and patients with no history of CVD.
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10. |
- Piehl, F., et al.
(författare)
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Risk of comorbidity in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 102-102
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Substantial progress in the treatment of multiple sclerosis (MS) has been made since the 1990s. However, the presence of comorbidity and the impact of treatment are less defined. Here we determined rates of comorbidity before and after MS diagnosis as compared with a matched MS-free population.Methods: A national incident MS cohort diagnosed in 2008-2016 was identified in the Swedish National Patient Register with data further linked to the national Prescribed Drug Register and Cause of Death Register. In addition, a sub-cohort of MS patients was identified in the electronic medical records (EMR) of the Karolinska University Hospital. MS patients were matched with and compared to 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years and incidence rate ratios (IRR) of comorbidities were calculated after MS diagnosis.Results: In total, 6,602 MS patients were identified in the national cohort and were compared with 61,828 MS-free controls (female, 69%; median age, 40 years), while a sub-cohort from one hospital of 1,289 patients had a MS diagnosis recorded in EMR and was compared with 11,721 individuals without MS (female, 68%; median age, 37 years). The national MS cohort had higher proportions before MS diag-nosis compared with MS-free controls of autoimmune disease (1.3% vs 0.7%), bladder dysfunction (1.2% vs 0.2%), retinal disorders (2.4% vs 1.2%) and epilepsy (1.5% vs 0.8%). Similar patterns were observed for the single-hospital cohort, except for epilepsy. Bipolar disorder was more common among single-hospital MS patients (1.6% vs 0.7%).After MS diagnosis, patients in the national cohort had higher IR compared with MS-free controls of autoimmune disease (IRR 3.60; 95% confidence interval [CI], 2.88-4.51), bladder dysfunction (IRR 47.44; 95% CI, 36.81-61.14) and epilepsy (IRR 2.36; 95% CI, 1.75-3.17). Similar patterns were observed in the single-hospital cohort. Toxic liver disease was higher (IRR 3.51; 95% CI 1.37-8.98) in the MS cohort in the national cohort only, while bipolar disorder was higher only in the single-hospital cohort (IRR 1.88; 95% CI 1.10-3.22).Conclusions: Before a diagnosis of MS, patients already displayed an increased rate of comorbidity compared with MS-free controls. After diagnosis, patients with MS continued to display increased risk of several comorbidities, some of which may be explained by surveillance bias due to more frequent contact with healthcare.
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- Fehmi, Janev, et al.
(författare)
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Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis
- 2023
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3 March
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Tidskriftsartikel (refereegranskat)abstract
- Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.
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- Gray, Howard W. I., et al.
(författare)
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Comparative biogeography and the evolution of population structure for bottlenose and common dolphins in the Indian Ocean
- 2021
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 48:7, s. 1654-1668
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Tidskriftsartikel (refereegranskat)abstract
- Aim: In the marine environment, where there are few physical boundaries to gene flow, there is often nevertheless intraspecific diversity with consequences for effective conservation and management. Here, we compare two closely related dolphin species with a shared distribution in the Indian Ocean (IO) to better understand the biogeographic drivers of their population structure.Location: Global oceans and seas with a focus on the Indian OceanTaxon: Tursiops sp. and Delphinus sp.Methods: Bayesian, ordination, assignment, statistical and phylogenetic analyses to assess phylogeography, connectivity and population structure using microsatellite and mitochondrial DNA genetic markers.Results: Both Tursiops sp. and Delphinus sp. showed population structure across the western IO and, in each case, populations in the Arabian Sea (off India, Pakistan and Oman) were most differentiated. Comparisons with other populations worldwide revealed independent lineages in this geographic region for both genera. For T. aduncus, (for which multiple sites within the IO could be compared), Bayesian modelling best supported a scenario of expansion southwards following a bottleneck event resulting in differentiation between the northern and western IO. For Delphinus, the same pattern is even more pronounced. Populations in the Arabian Sea region of the north-western IO show genetic isolation for each of the two genera, consistent with other studies of cetacean species in this region.Main conclusions: We propose that changes in the intensity of the southwest monsoon during the climate cycles of the Pleistocene could have affected regional patterns of productivity and represent an important biogeographic driver promoting the observed patterns of differentiation and population dynamics seen in our focal species. Patterns of population genetic structure are consistent with phenotypic differences, suggesting an influence from distinct habitats and resources, and emphasising the need for effective conservation measures in this geographic region.
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- Castelo-Branco, A., et al.
(författare)
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Treatment patterns in patients with multiple sclerosis : a single hospital cohort study in Sweden
- 2021
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 732-732
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: An increasing number of disease-modifying therapies (DMT) for multiple sclerosis (MS) has led to switching between treatments.Objectives: In a Swedish MS cohort study, we analysed switching treatment patterns, including prescribed symptomatic medications, before and after an MS diagnosis.Methods: A national incident MS cohort diagnosed in 2008–2016 in the Swedish National Patient Register was linked to the national Prescribed Drug Register. A subcohort in the electronic medical records (EMR) of the Karolinska University Hospital was analysed for medication usage.Results: Patients with an MS diagnosis in the EMR cohort (n=1289) were identified (female, 68.2%; mean age (standard deviation), 38.8 (12.2) years). Prescribed symptomatic medications in the year before cohort entry included analgesics (23.2%), antidepressants (13.9%), opioids (13.4%), systemic corticosteroids (11.2%), and anxiolytics (10.0%). In the 4 years after cohort entry, medications included analgesics (65.2%), systemic antibacterials (55.9%), anti-inflammatory and antirheumatics (50.1%), antidepressants (34.8%), anxiolytics (21.1%), antiepileptics (19.1%) and ophthalmic drugs (16.6%). Of 1289 patients, 1040 were prescribed a DMT (80.7%). Median time (months, interquartile range) to first usage of new DMTs by age group was 1.71, 0.82–4.30 (<40 years); 1.87, 0.95–7.00 (40–59 years); and 3.96, 1.15–12.16 (⩾60 years). The most common DMTs (n=patients) were first-line (n=1054): interferons (55.9%), rituximab (15.7%), dimethyl fumarate (9.1%), natalizumab (7.4%), glatiramer acetate (7.1%), fingolimod (3.5%); second-line (n=551): rituximab (29.4%), natalizumab (19.4%), dimethyl fumarate (17.6%), fingolimod (16.3%), glatiramer acetate (7.8%), interferons (3.1%), teriflunomide (2.2%); third-line (n=184): rituximab (51.1%), natalizumab (13.0%), interferons (9.8%), fingolimod (9.8%), dimethyl fumarate (6.0%).Conclusions: These data indicate high usage of prescribed symp-tomatic medications before and after the MS diagnosis, which may indicate the consequences of prodromal and early sympto-matic MS. Most patients were treated with a DMT within months of diagnosis, with predominant initial use of interferons, and switching to more potent agents in later lines of therapy. Prescribing patterns are changing and expected to evolve further with earlier use of powerful agents.
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- Norberg, Åke, et al.
(författare)
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Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers
- 2007
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Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 107:1, s. 24-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts.METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored.RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged.CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.
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- Sandberg, Kenneth, 1945, et al.
(författare)
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Prenatal nicotine exposure transiently alters the lung mechanical response to hypoxia in young lambs
- 2007
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Ingår i: Respir Physiol Neurobiol. - : Elsevier BV. - 1569-9048. ; 156:3, s. 283-92
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Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that fetal nicotine exposure alters the lung mechanical response to hypoxia (10% O(2)) 10 lambs were exposed during the last fetal trimester to a low dose nicotine (LN) and 10 to a moderate dose (MN) (maternal dose 0.5 and 1.5mg/(kgday) free base, respectively). There were 10 controls (C). At 12 days, minute ventilation increased significantly less in MN compared with LN but not with C. In contrast to C and LN, MN did not show anticipated increases in dynamic compliance, specific compliance and FRC or decrease in lung resistance but had signs of airway hyperreactivity during hypoxia. Nicotine exposure did not alter the cardiovascular response. These adverse effects decreased with advancing age. In summary, prenatal nicotine exposure alters the lung mechanical response to hypoxia. We speculate that prenatal nicotine-induced alterations of lung mechanics during hypoxia may contribute to an increased vulnerability to hypoxic stress during infancy.
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