| 1. |
- Bengtsson, Caroline, et al.
(författare)
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Nasal polyposis is a risk factor for nonadherence to CPAP treatment in sleep apnea: the population-based DISCOVERY study
- 2023
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Ingår i: JOURNAL OF CLINICAL SLEEP MEDICINE. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 19:3, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: The aim was to evaluate nasal polyposis as a risk factor for nonadherence to continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). Methods: This was a population-based, longitudinal analysis of patients starting CPAP treatment for OSA in the Swedish quality registry Swedevox between 2010 and 2018. Data were cross-linked with national registries. The impact of nasal polyposis on CPAP adherence was analyzed using uni-and multivariable logistic and linear regression models. Relevant confounders (age, sex, usage of nasal and oral steroids) were identified using a direct acyclic graph. Results: Of 20,521 patients with OSA on CPAP treatment (29.5% females), 331 (1.6%) had a diagnosis of nasal polyposis at baseline. At the 1-year follow-up, nasal polyposis was associated with an increased risk of CPAP usage < 4 hours/night (unadjusted odds ratio [OR] 1.21; 95% confidence interval [CI] 0.95-1.55); adjusted OR 1.38; 95% CI 1.08-1.77). In this group, unadjusted nocturnal mean CPAP usage was 15.4 minutes (95% CI-31.62 to 0.83) shorter and was an adjusted 24.1 minutes (95% CI-40.6 to-7.7) shorter compared with patients with OSA without nasal polyposis. Conclusions: Nasal polyposis is associated with reduced CPAP usage per night. These results highlight the importance of diagnosing nasal polyposis in patients with OSA before the start of CPAP treatment. Treatment of the condition may improve adherence, efficacy, and patient outcomes.
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| 2. |
- Bengtsson, Caroline, et al.
(författare)
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Sinonasal outcome test-22 and peak nasal inspiratory flow : valuable tools in obstructive sleep apnoea
- 2020
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Ingår i: Rhinology. - 0300-0729 .- 1996-8604. ; 58:4, s. 341-348
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sinonasal complaints contribute to low adherence to continuous positive airway pressure (CPAP) treatment. We aimed to investigate sinonasal health in obstructive sleep apnoea (OSA) patients, using the sinonasal outcome test-22 (SNOT-22), and to analyse whether SNOT-22 is affected by CPAP adherence. We also aimed to investigate whether peak nasal inspiratory flow (PNIF) was able to predict adherence to CPAP. Methods:The study population comprised 197 OSA patients (60 females) initiating CPAP treatment The SNOT-22, PNIF and the Epworth Sleepiness Scale were assessed at baseline and follow-up. One-night polygraphy, the Hospital Anxiety and Depression Scale, peak expiratory flow and health-related issues were assessed at baseline. At follow-up, the patients were categorised into adherent (>4 hours/night) and non-adherent (<4 hours/night) to CPAP treatment. Results: The average time for following up CPAP treatment was (mean +/- SD) 24.0 +/- 23.9 days and it did not differ significantly between the groups.The SNOT-22 score was elevated among all OSA patients, 36.1 +/- 19.4.There was a larger improvement in the SNOT-22 score at follow-up among adherent CPAP users compared with non-adherent users (-10.4 +/- 13.9 vs. -3.2 +/- 15.4). A PNIF value of < 100 litres/min increased the risk of non-adherence to CPAP with an adjusted odds ratio (OR) of 2.40 ((95% CI 1.16-5.00)). Conclusions: The SNOT-22 was elevated in patients with OSA, indicating a considerable sinonasal disease burden.The SNOT-22 improved with good CPAP adherence. A low PNIF value was able to predict poor CPAP adherence. Both the SNOT-22 and PNIF can be valuable tools in the evaluation of OSA patients and in the management of CPAP treatment.
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| 3. |
- Bengtsson, Johan
(författare)
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Negative symptoms, repetitive transcranial magnetic stimulation and heart rate variability in schizophrenia and depression
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Negative symptoms comprise anhedonia, avolition, and blunted affect. Although first described in schizophrenia, these symptoms share phenomenology with the depressive state. Pharmacological treatment has not been successful in reducing negative symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment option for moderate to severe depression. There have also been attempts to treat negative symptoms in both schizophrenia and depression with rTMS.Cardiovascular disease is common in schizophrenia and depression. Heart rate variability (HRV) is an established proxy for cardiac autonomic functioning and numerous studies have found lower HRV in patients with schizophrenia and depression. The impact of psychopharmacological treatment on HRV has been extensively studied and anticholinergic compounds have been found to decrease HRV.Lastly, since the most commonly used rTMS depression targets are also the brain regions involved in central autonomic regulation, there is reason to consider a potential effect of rTMS on HRV.The overall aim of this thesis was to investigate negative symptoms, rTMS, and HRV in schizophrenia and depression.Study I was a validation study of a Swedish translation of the Clinical Assessment Interview for Negative Symptoms (CAINS). Thirty-four patients with schizophrenia were interviewed and it was concluded that the Swedish version of the CAINS exhibited acceptable psychometric properties.Study II was a double-blind randomized controlled trial of rTMS for negative symptoms in schizophrenia and depression. There was a significant decrease of negative symptoms in the depression group, but not in the schizophrenia group. There were no effects on overall depressive symptoms in either group.Study III assessed determinants of HRV in schizophrenia, depression, and healthy controls. The results indicated lower HRV in both patient groups, even after controlling for several factors, and also that anticholinergic burden impacted HRV.In Study IV, the relationship between HRV and the functional and structural connectivity of the anterior cingulate cortex was investigated in patients with schizophrenia and compared with that in healthy controls. It was found that connectivity with the cerebellum might play a role in the autonomic modulation network in patients with schizophrenia.Lastly, in Study V, the effect of a treatment course with rTMS on HRV was investigated in patients with depression, as well as HRV’s relationship to symptom change. No effects on HRV were detected, nor any correlations between HRV and symptom change. Further, baseline HRV could not predict treatment response.
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| 4. |
- Eberhardson, Michael, et al.
(författare)
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Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
- 2022
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.
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| 5. |
- Mårild, Karl, 1982, et al.
(författare)
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Histologic activity in inflammatory bowel disease and risk of serious infections : A nationwide study
- 2024
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 22:4, s. 831-846
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear.METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses.RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61).CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD.
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| 6. |
- Petersdorf, Effie W., et al.
(författare)
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HLA-B leader and survivorship after HLA-mismatched unrelated donor transplantation
- 2020
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:3, s. 362-369
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic cell transplantation (HCT) from HLA-mismatched unrelated donors can cure life-threatening blood disorders, but its success is limited by graft-versus-host disease (GVHD). HLA-B leaders encode methionine (M) or threonine (T) at position 2 and give rise to TT, MT, or MM genotypes. The dimorphic HLA-B leader informs GVHD risk in HLA-B-mismatched HCT. If the leader influences outcome in other HLA-mismatched transplant settings, the success of HCT could be improved for future patients. We determined leader genotypes for 10 415 patients receiving a transplant between 1988 and 2016 from unrelated donors with one HLA-A, HLA-B, HLA-C, HLA-DRB1, or HLA-DQB1 mismatch. Multivariate regression methods were used to evaluate risks associated with patient leader genotype according to the mismatched HLA locus and with HLA-A, HLA-B, HLA-C, HLA-DRB1, or HLA-DQB1 mismatching according to patient leader genotype. The impact of the patient leader genotype on acute GVHD and mortality varied across different mismatched HLA loci. Nonrelapse mortality was higher among HLA-DQB1-mismatched MM patients compared with HLA-DQB1-mismatched TT patients (hazard ratio, 1.35; P = .01). Grades III to IV GVHD risk was higher among HLA-DRB1-mismatched MM or MT patients compared with HLA-DRB1-mismatched TT patients (odds ratio, 2.52 and 1.51, respectively). Patients tolerated a single HLA-DQB1 mismatch better than mismatches at other loci. Outcome after HLA-mismatched transplantation depends on the HLA-B leader dimorphism and the mismatched HLA locus. The patient's leader variant provides new information on the limits of HLA mismatching. The success of HLA-mismatched unrelated transplantation might be enhanced through the judicious selection of mismatched donors for a patient's leader genotype.
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| 7. |
- Petersdorf, Effie W., et al.
(författare)
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HLA-DQ heterodimers in hematopoietic cell transplantation
- 2022
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 139:20, s. 3009-3017
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Tidskriftsartikel (refereegranskat)abstract
- HLA-DQ heterodimers increase the susceptibility to autoimmune diseases, but their role in hematopoietic cell transplantation is unknown. We tested the hypothesis that outcome after HLA-matched and HLA-DQ-mismatched hematopoietic cell transplantation is influenced by HLA-DQ heterodimers. Heterodimers were defined in 5164 HLA-matched and 520 HLA-DQ-mismatched patients and their transplant donors according to well-established crystallographic criteria. Group 1 (G1) heterodimers are any DQA1*02/03/04/05/06a paired with any DQB1*02/03/040. Group 2 (G2) heterodimers are DQA1*01a paired with any DQB1*05/060. Multivariable models identified significantly higher relapse risk in G1G2 and G2G2 compared with G1G1 HLA-matched patients with malignant disease; risk increased with an increasing number of G2 molecules. In HLA-DQ-mismatched transplantation for malignant diseases, matching or mismatching for G2 increased relapse risk. G2 lowered disease-free survival after both HLA-matched and HLA-DQ-mismatched transplantation. A paradigm based on HLA-DQ heterodimers provides a functional definition of the hematopoietic cell transplantation barrier and a means to lower risks for future patients.
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| 8. |
- Petersdorf, Effie W., et al.
(författare)
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Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation : a retrospective cohort study
- 2020
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Ingår i: The Lancet Haematology. - : ELSEVIER SCI LTD. - 2352-3026. ; 7:1, s. E50-E60
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Tidskriftsartikel (refereegranskat)abstract
- Background: The success of unrelated haemopoietic cell transplantation (HCT) is limited by graft-versus-host disease (GVHD), which is the main post-transplantation challenge when HLA-matched donors are unavailable. A sequence dimorphism in exon 1 of HLA-B gives rise to leader peptides containing methionine (Met; M) or threonine (Thr; T), which differentially influence natural killer and T-cell alloresponses. The main aim of the study was to evaluate the role of the leader dimorphism in GVHD after HLA-B-mismatched unrelated HCT.Methods: We did a retrospective cohort study of 33 982 patients who received an unrelated HCT done in Australia, Europe, japan, North America, and the UK between jan 1, 1988, and Dec 31, 2016. Data were contributed by participants of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation. All cases were included and there were no exclusion criteria. Multivariate regression models were used to assess risks associated with HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 mismatching. Among the 33 982 transplantations, the risks of GVHD associated with HLA-B M and T leaders were established in 17 100 (50.3%) HLA-matched and 1457 (4.3%) single HLA-B-mismatched transplantations using multivariate regression models. Leader frequencies were defined in 2 004 742 BeTheMatch US registry donors.Findings: Between jan 20, 2017, and March 11, 2019, we assessed 33 982 HCTs using multivariate regression models for the role of HLA mismatching on outcome. Median follow-up was 1841 days (IQR 909-2963). Mortality and GVHD increased with increasing numbers of HLA mismatches. A single HLA-B mismatch increased grade 3-4 acute GVHD (odds ratio [OR] 1.89, 95% CI 1. 53-2.33; p<0.0001). Among the single HLA-B-mismatched transplantations, acute GVHD risk was higher with leader mismatching than with leader matching (OR 1.73, 1.02-2.94; p=0 .042 for grade 2-4) and with an M leader shared allotype compared with a T leader shared allotype (OR 1.98, 1.39-2.81; p=0.0001 for grade 3-4). The preferred HLA-B-mismatched donor is leader-matched and shares a T leader allotype. The majority (1836 939 [91.6%]) of the 2004742 US registry donors have the TT or MT genotype.Interpretation: The HLA-B leader informs GVHD risk after HLA-B-mismatched unrelated HCT and differentiates high-risk HLA-B mismatches from those with lower risk. The leader of the matched allotype could be considered to be as important as the leader of the mismatched allotype for GVHD. Prospective identification of leader-matched donors is feasible for most patients in need of a HCT, and could lower GVHD and increase availability of HCT therapy. These findings are being independently validated and warrant further research in prospective trials.
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| 9. |
- Petersdorf, Effie W., et al.
(författare)
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Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:24, s. 2712-2718
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1-matched and -mismatched unrelated donors. PATIENTS AND METHODS Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1-matched or -mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient's mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients. RESULTS In HLA-A, -B, -C, -DRB1,-DQB1-matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; P = .001) and severe acute GVHD (OR, 1.32; P = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor's mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient's mismatched HLA-DPB1 allotype. CONCLUSION The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1-matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.
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| 10. |
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