| 1. |
- 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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| 2. |
- Singh, K. P., et al.
(författare)
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Clinical standards for the management of adverse effects during treatment for TB
- 2023
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 27:7, s. 506-519
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitiv-ity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person -centred, consensus-based approach to minimise the impact of AE TB treatment.
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| 3. |
- Borisov, S, et al.
(författare)
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Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report
- 2019
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 54:6
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Tidskriftsartikel (refereegranskat)abstract
- The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.
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| 6. |
- Arkema, EV, et al.
(författare)
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Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments?
- 2015
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:6, s. 1212-1217
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Tidskriftsartikel (refereegranskat)abstract
- To estimate the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) both with and without exposure to biological therapy and to directly compare the risks between therapies.MethodsData from the Swedish National Population Registers, Tuberculosis Register and the Swedish Biologics Register were used to conduct a prospective population-based national cohort study (2002–2011). We estimated the rate of incident TB in the general population and in a cohort of biological-naïve and biological-exposed patients diagnosed with RA. Cox models were used to estimate HRs with particular attention to risks by calendar and follow-up time and individual biologics.ResultsCompared to the general population, RA patients not exposed to biologicals had a fourfold increased risk of TB (HR 4.2; 95% CI 2.7 to 6.7), which did not decline over calendar time. In contrast, the risk of TB in the biological-exposed RA population decreased since 2002 compared with biological-naïve; from HR=7.9 (95% CI 3.3 to 18.9) in 2002–2006 to HR=2.4 (95% CI 0.9 to 6.1) in 2007–2011. The HRs for most recent exposure to adalimumab and infliximab compared with etanercept were 3.1 (95% CI 0.8 to 12.5) and 2.7 (95% CI 0.7 to 10.9), respectively, and the HR for etanercept compared with biological-naïve RA was 1.7 (95% CI 0.6 to 4.6).ConclusionsIn the past decade, the risk of TB has decreased among biological-exposed RA patients but remains higher than in biological-naïve RA patients. Most cases of TB in RA occur in biological-naïve RA patients, underscoring the elevated risk also in these patients.
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| 16. |
- Jones, RB, et al.
(författare)
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Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 399-405
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Tidskriftsartikel (refereegranskat)abstract
- Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV.MethodsWe conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR <15 mL/min were excluded from the study.ResultsAt baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI −7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3).ConclusionMMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate.Trial registration numberNCT00414128.
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| 17. |
- Levin, A., et al.
(författare)
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Novel insights into the disease transcriptome of human diabetic glomeruli and tubulointerstitium
- 2020
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 35:12, s. 2059-2072
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Tidskriftsartikel (refereegranskat)abstract
- Background. Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, affecting similar to 30% of the rapidly growing diabetic population, and strongly associated with cardiovascular risk. Despite this, the molecular mechanisms of disease remain unknown. Methods. RNA sequencing (RNAseq) was performed on paired, micro-dissected glomerular and tubulointerstitial tissue from patients diagnosed with DN [n = 19, 15 males, median (range) age: 61 (30-85) years, chronic kidney disease stages 1-4] and living kidney donors [n = 20, 12 males, median (range) age: 56 (30-70) years]. Results. Principal component analysis showed a clear separation between glomeruli and tubulointerstitium transcriptomes. Differential expression analysis identified 1550 and 4530 differentially expressed genes, respectively (adjusted P < 0.01). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted activation of inflammation and extracellular matrix (ECM) organization pathways in glomeruli, and immune and apoptosis pathways in tubulointerstitium of DN patients. Specific gene modules were associated with renal function in weighted gene co-expression network analysis. Increased messengerRNA (mRNA) expression of renal damage markers lipocalin 2 (LCN) and hepatitis A virus cellular receptor1 (HAVCR1) in the tubulointerstitial fraction was observed alongside higher urinary concentrations of the corresponding proteins neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in DN patients. Conclusions. Here we present the first RNAseq experiment performed on paired glomerular and tubulointerstitial samples from DN patients. We show that prominent disease-specific changes occur in both compartments, including relevant cellular processes such as reorganization of ECM and inflammation (glomeruli) as well as apoptosis (tubulointerstitium). The results emphasize the potential of utilizing high-throughput transcriptomics to decipher disease pathways and treatment targets in this high-risk patient population.
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| 21. |
- Ohd, JN, et al.
(författare)
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Evaluation of the latent tuberculosis screening and treatment strategy for asylum seekers in Stockholm, Sweden 2015-2018: a record linkage study of the care cascade
- 2021
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 57:3
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Tidskriftsartikel (refereegranskat)abstract
- About 90% of active tuberculosis (TB) cases in Sweden are foreign born and are mainly due to latent TB infection (LTBI) reactivation. The aim of this study was to assess the current migrant LTBI screening programme with regards to test results and completion of the care cascade.MethodA retrospective cohort of all 14173 individuals attending a health examination was established for the Stockholm Region 2015–2018 through record-linkage of data extracted from the Swedish Migration Authority and medical records. Screening results, referrals to specialist care and treatment initiation were ascertained through automated data extraction for the entire cohort. Detailed cascade steps, including treatment completion, were analysed through manual data extraction for a subsample of all persons referred to specialist care in the period 2016–2017.ResultsOf 5470 patients screened with an interferon-gamma release assay (IGRA), 1364 (25%) were positive, of whom 358 (26%) initiated LTBI treatment. An increased trend in IGRA-positivity was seen for increased age and TB-incidence in country of origin. Among the IGRA positive patients, 604 (44%) were referred to specialist care. Lower age was the main referral predictor. In the subsample of 443 patients referred to specialist care in 2016–2017, 386 (87%) were invited, of whom 366 (95%) attended. Of 251 patients (69%) recommended for LTBI treatment, 244 (97%) started such treatment and of those 221 (91%) completed it.ConclusionThe low attrition in patient-dependent cascade steps shows that the voluntary approach works well. Low LTBI treatment attainment is due to the current conservative local treatment policy, which means the vast majority are IGRA-tested without an intention to treat for LTBI.
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| 24. |
- Shedrawy, J, et al.
(författare)
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Cost-effectiveness of the latent tuberculosis screening program for migrants in Stockholm Region
- 2021
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Ingår i: The European journal of health economics : HEPAC : health economics in prevention and care. - : Springer Science and Business Media LLC. - 1618-7601. ; 22:3, s. 445-454
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe majority of tuberculosis (TB) cases in Sweden occur among migrants from endemic countries through activation of latent tuberculosis infection (LTBI). Sweden has LTBI-screening policies for migrants that have not been previously evaluated. This study aimed to assess the cost-effectiveness of the current screening strategy in Stockholm.MethodsA Markov model was developed to predict the costs and effects of the current LTBI-screening program compared to a scenario of no LTBI screening over a 50-year time horizon. Epidemiological and cost data were obtained from local sources when available. The primary outcomes were incremental cost-effectiveness ratio (ICER) in terms of societal cost per quality-adjusted life year (QALY).ResultsScreening migrants in the age group 13–19 years had the lowest ICER, 300,082 Swedish Kronor (SEK)/QALY, which is considered cost-effective in Sweden. In the age group 20–34, ICER was 714,527 SEK/QALY (moderately cost-effectives) and in all age groups above 34 ICERs were above 1,000,000 SEK/QALY (not cost-effective). ICER decreased with increasing TB incidence in country of origin.ConclusionScreening is cost-effective for young cohorts, mainly between 13 and 19, while cost-effectiveness in age group 20–34 years could be enhanced by focusing on migrants from highest incidence countries and/or by increasing the LTBI treatment initiation rate. Screening is not cost-effective in older cohorts regardless of the country of origin.
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| 25. |
- Silva, CS, et al.
(författare)
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High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 727300-
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Tidskriftsartikel (refereegranskat)abstract
- Upon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.
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| 26. |
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| 27. |
- Sundbaum, Johanna, et al.
(författare)
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Tuberculosis in biologic-naïve patients with rheumatoid arthritis - risk factors and tuberculosis characteristics
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, suppl 1, s. 969-969
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of tuberculosis (TB) has decreased in biologic disease modifying anti-rheumatic drugs (bDMARDs) treated rheumatoid arthritis (RA) patients, but remains unaltered 4-fold increased in bio-naïve RA patients compared to the general population in Sweden (1). In absolute numbers, most TB cases in contemporary RA patients occur in the group of bio-naïve patients. Knowledge about risk factors for TB and TB characteristics in bio-naïve RA patients is still limited.Objectives: To investigate risk factors for TB and TB characteristics in bio-naïve RA patients.Methods: Population-based case-control study. A national bio-naïve RA cohort was identified from the National Patient Register and the Swedish Rheumatology Quality Register. RA cases with TB were identified by linkage to the Swedish Tuberculosis Register (with mandatory TB registration) 2001-2014 (n=42). For each case, four matched RA controls without TB were identified. Clinical data were obtained from medical records. Univariate and multivariable logistic regression analyses were used to estimate risk for TB expressed as adjusted (adj) odds ratio (OR) with 95% confidence intervals (CI).Results: After review of the medical records and validation of diagnoses, 31 cases with RA and TB and 122 controls remained in the study. The TB cases had a median of 3 (1-6) reported TB risk factors, and almost 90% were born before 1950. Only one case was screened for TB (with negative result of tuberculin skin test). Active TB occurred at a mean of 15 years after RA diagnosis, and all except three cases were considered as reactivation of latent TB. Exposure to leflunomide (5 cases, 4 controls) (adj OR 6.02; 95% CI 1.47-24.65) and azathioprine (5 cases, 6 controls) (adj OR 3.85; 95% CI 1.06-13.79) were associated with increased risk for TB. Methotrexate, used in 67.7% of cases and 73.9% of controls, was not associated with increased risk of TB (adj OR 0.83; 95% CI 0.34-1.98). Exposure to corticosteroids was more common among cases than controls (74.2% vs 53.8%, p= 0.04), and was associated with an adj OR for TB of 2.44 (95% CI 1.00-5.92). No significant differences were identified between prednisolone-treated cases and controls in terms of maximum dose ever of prednisolone, treatment duration before TB, or cumulative dose of prednisolone during the last year before diagnosis of TB. Obstructive pulmonary disease was the only comorbidity linked to an increased TB risk (adj OR 3.94; 95% CI 1.45-10.69). Pulmonary TB dominated (84%) followed by TB lymphadenitis (19%). Treatment success was 94%, comparable to TB patients in general.Conclusion: Several RA-associated risk factors may contribute to increased TB risk in bio-naïve RA patients (treatment with leflunomide, azathioprine, or prednisolone and concomitant obstructive lung disease). We could not confirm previous findings of an association with the use of moderate to high doses of prednisolone (≥15 mg). TB risk seems difficult to predict with precision in the individual bio-naïve patient based on RA-associated risk factors. To further decrease the TB risk in RA patients TB screening should also be considered in the group of bio-naïve patients.
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| 28. |
- van den Elsen, SHJ, et al.
(författare)
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Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:6, s. e035350-
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Tidskriftsartikel (refereegranskat)abstract
- Global multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls.Methods and analysisPatients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0 and t=5 hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7 days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2 months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM.Ethics and disseminationEthical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal.Trial registration numberClinicalTrials.gov Registry (NCT03409315).
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| 29. |
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| 30. |
- Borgstrom, E. W., et al.
(författare)
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CD4(+) T cell proliferative responses to PPD and CFP-10 associate with recent M. tuberculosis infection
- 2020
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Ingår i: Tuberculosis. - : Elsevier BV. - 1472-9792 .- 1873-281X. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- Interferon-gamma release assays cannot differentiate latent from active tuberculosis (TB), nor identify the recently infected with increased risk of active disease. The objective of this study was to identify biomarkers of recent infection following exposure to tuberculosis, to increase the positive predictive value for incipient TB. Contacts to patients with pulmonary TB were tested repeatedly with interferon-gamma release assays and flow-cytometry. Proliferative CD4(+) T cell responses to purified protein derivative (PPD) and 11 M. tuberculosis antigens were analysed. The individual probability of recent and remote infection was estimated using clinical data in a novel mathematical model and compared with CD4(+) responses in a prediction model. The most specific prediction of recent infection was high CD4(+) proliferative responses to CFP-10 and PPD and a low CD4(+) response to ESAT-6. CD4(+) proliferative responses to Rec85a, Rec85b and Rv1284 were also observed in recent infection, but did not reach significance in the prediction model. Conclusions: High CD4(+) proliferative responses to CFP-10 and PPD and a low response to ESAT-6 may be used as biomarkers to improve positive predictive values for recent LTBI and thus, increased risk of incipient TB. Rec85a, Rec85b and Rv1284 are also of interest to study further in this context.
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| 34. |
- Getahun, H, et al.
(författare)
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Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries
- 2015
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:6, s. 1563-1576
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Tidskriftsartikel (refereegranskat)abstract
- Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone.
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| 41. |
- Jonsson, J, et al.
(författare)
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Increased risk of active tuberculosis during pregnancy and postpartum: a register-based cohort study in Sweden
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:3
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Tidskriftsartikel (refereegranskat)abstract
- Studies investigating the risk of active tuberculosis (TB) in association with pregnancy have not been conclusive. We aimed to investigate this risk in a large retrospective register-based cohort study in Sweden.MethodsData from women of 15–49 years of age who had given birth in Sweden between 2005 and 2013 were extracted from the national childbirth register and linked to the national TB register. Cohort time was divided into three exposure periods: during pregnancy, six months (180 days) postpartum and time neither pregnant nor postpartum. We calculated incidence rates (IRs) per 100 000 person-years for each period and incidence rate ratios (IRRs) with IRs neither pregnant nor postpartum as the reference.ResultsThe cohort included 649 342 women, of whom 553 were registered as cases of active TB, 389 when neither pregnant nor postpartum, 85 during pregnancy and 79 when postpartum. Overall IRs were 9, 12 and 17 cases per 100 000 person-years, respectively, giving IRR 1.4, 95% CI 1.1–1.7 (during pregnancy) and IRR 1.9, 95% CI 1.5–2.5 (when postpartum). Stratification by TB incidence in country of origin showed that the increased risk was concentrated amongst women from countries with a TB incidence of 100 or higher, where IRs per 100 000 person-years were 137 (when neither pregnant nor postpartum), 182 (during pregnancy) and 233 (when postpartum).ConclusionWe show a significant increase in risk of active TB during both pregnancy and postpartum in women from high incidence countries and recommend TB screening in pregnant women belonging to this risk group.
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| 42. |
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| 43. |
- Kjellberg, A, et al.
(författare)
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Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:11, s. e061870-
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Tidskriftsartikel (refereegranskat)abstract
- Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL.Methods and analysisA randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board.Ethics and disseminationThe trial is approved by the Swedish National Institutional Review Board (2021–02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access.Trial registration numberNCT04842448.
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| 47. |
- Levin, A., et al.
(författare)
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The role of dendrin in IgA nephropathy
- 2023
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 38:2, s. 311-321
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Tidskriftsartikel (refereegranskat)abstract
- Background Immunoglobulin A nephropathy (IgAN) and its systemic variant IgA vasculitis (IgAV) damage the glomeruli, resulting in proteinuria, hematuria and kidney impairment. Dendrin is a podocyte-specific protein suggested to be involved in the pathogenesis of IgAN. Upon cell injury, dendrin translocates from the slit diaphragm to the nucleus, where it is suggested to induce apoptosis and cytoskeletal changes, resulting in proteinuria and accelerated disease progression in mice. Here we investigated gene and protein expression of dendrin in relation to clinical and histopathological findings to further elucidate its role in IgAN/IgAV. Methods Glomerular gene expression was measured using microarray on 30 IgAN/IgAV patients, 5 patients with membranous nephropathy (MN) and 20 deceased kidney donors. Dendrin was spatially evaluated on kidney tissue sections by immunofluorescence (IF) staining (IgAN patients, n = 4; nephrectomized kidneys, n = 3) and semi-quantified by immunogold electron microscopy (IgAN/IgAV patients, n = 21; MN, n = 5; living kidney donors, n = 6). Histopathological grading was performed according to the Oxford and Banff classifications. Clinical data were collected at the time of biopsy and follow-up. Results Dendrin mRNA levels were higher (P = .01) in IgAN patients compared with MN patients and controls and most prominently in patients with preserved kidney function and fewer chronic histopathological changes. Whereas IF staining did not differ between groups, immunoelectron microscopy revealed that a higher relative nuclear dendrin concentration in IgAN patients was associated with a slower annual progression rate and milder histopathological changes. Conclusion Dendrin messenger RNA levels and relative nuclear protein concentrations are increased and associated with a more benign phenotype and progression in IgAN/IgAV patients.
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| 48. |
- Lonnroth, K, et al.
(författare)
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Towards tuberculosis elimination: an action framework for low-incidence countries
- 2015
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 45:4, s. 928-952
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.
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| 49. |
- Manojlovic, M., et al.
(författare)
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Microparticles expressing myeloperoxidase as potential biomarkers in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)
- 2020
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Ingår i: Journal of Molecular Medicine. - : SPRINGER HEIDELBERG. - 0946-2716 .- 1432-1440. ; 98:9, s. 1279-1286
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Tidskriftsartikel (refereegranskat)abstract
- To investigate presence of circulating myeloperoxidase-positive microparticles (MPO(+)MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS >= 1). Concentrations of MPO(+)MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (p< 0.001,p< 0.01,p< 0.001, respectively), while concentrations of PTX3(+)and HMGB1(+)MPO(+)MPs were significantly higher in active AAV compared to patients in remission. MPO(+)MPs expressing either PTX3 or HMGB1 were associated with BVAS (r= 0.5,p< 0.001;r= 0.3,p= 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (p< 0.001), correlating strongly with BVAS (r= 0.7,p< 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO(+)MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO(+)MPs were associated with disease activity in the investigated patients. Key messages Myeloperoxidase-positive microparticles (MPO+MPs) are increased in plasma from patients with ANCA-associated vasculitis. Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls. MPO+MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.
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| 50. |
- Nickander, J, et al.
(författare)
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Stress native T1 and native T2 mapping compared to myocardial perfusion reserve in long-term follow-up of severe Covid-19
- 2023
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 4159-
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Tidskriftsartikel (refereegranskat)abstract
- Severe Covid-19 may cause a cascade of cardiovascular complications beyond viral pneumonia. The severe inflammation may affect the microcirculation which can be assessed by cardiovascular magnetic resonance (CMR) imaging using quantitative perfusion mapping and calculation of myocardial perfusion reserve (MPR). Furthermore, native T1 and T2 mapping have previously been shown to identify changes in myocardial perfusion by the change in native T1 and T2 during adenosine stress. However, the relationship between native T1, native T2, ΔT1 and ΔT2 with myocardial perfusion and MPR during long-term follow-up in severe Covid-19 is currently unknown. Therefore, patients with severe Covid-19 (n = 37, median age 57 years, 24% females) underwent 1.5 T CMR median 292 days following discharge. Quantitative myocardial perfusion (ml/min/g), and native T1 and T2 maps were acquired during adenosine stress, and rest, respectively. Both native T1 (R2 = 0.35, p < 0.001) and native T2 (R2 = 0.28, p < 0.001) correlated with myocardial perfusion. However, there was no correlation with ΔT1 or ΔT2 with MPR, respectively (p > 0.05 for both). Native T1 and native T2 correlate with myocardial perfusion during adenosine stress, reflecting the coronary circulation in patients during long-term follow-up of severe Covid-19. Neither ΔT1 nor ΔT2 can be used to assess MPR in patients with severe Covid-19.
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