| 1. |
- Kjellberg, A., et al.
(författare)
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Randomised, controlled, open label, multicentre clinical trial to explore safety and efficacy of hyperbaric oxygen for preventing ICU admission, morbidity and mortality in adult patients with COVID-19
- 2021
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction COVID-19 may cause severe pneumonitis and trigger a massive inflammatory response that requires ventilatory support. The intensive care unit (ICU)-mortality has been reported to be as high as 62%. Dexamethasone is the only of all anti-inflammatory drugs that have been tested to date that has shown a positive effect on mortality. We aim to explore if treatment with hyperbaric oxygen (HBO) is safe and effective for patients with severe COVID-19. Our hypothesis is that HBO can prevent ICU admission, morbidity and mortality by attenuating the inflammatory response. The primary objective is to evaluate if HBO reduces the number of ICU admissions compared with best practice treatment for COVID-19, main secondary objectives are to evaluate if HBO reduces the load on ICU resources, morbidity and mortality and to evaluate if HBO mitigates the inflammatory reaction in COVID-19. Methods and analysis A randomised, controlled, phase II, open label, multicentre trial. 200 subjects with severe COVID-19 and at least two risk factors for mortality will be included. Baseline clinical data and blood samples will be collected before randomisation and repeated daily for 7 days, at days 14 and 30. Subjects will be randomised with a computer-based system to HBO, maximum five times during the first 7 days plus best practice treatment or only best practice treatment. The primary endpoint, ICU admission, is defined by criteria for selection for ICU. We will evaluate if HBO mitigates the inflammatory reaction in COVID-19 using molecular analyses. All parameters are recorded in an electronic case report form. An independent Data Safety Monitoring Board will review the safety parameters. Ethics and dissemination The trial is approved by The National Institutional Review Board in Sweden (2020-01705) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative and any inconclusive results will be published in peer-reviewed scientific journals with open access.
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| 2. |
- Oscarsson, Nicklas, 1974
(författare)
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Hyperbaric oxygen treatment for pelvic radiation-induced injuries. From a multicenter randomized controlled trial to an experimental cell model
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction Cancer is affecting a growing number of persons. Still, the treatment and survival of cancer is improving. Radiation therapy is used in the treatment of cancer. Late radiation-induced injuries afflict 5–15% of irradiated patients. The urinary bladder and bowel may be affected after irradiation of cancer in the pelvic region. Symptoms can be severe, with impaired health related quality of life (HRQoL). Hyperbaric oxygen therapy (HBOT) involves breathing oxygen at high ambient pressure. HBOT can reverse radiation-induced injuries, alleviate patient-perceived symptoms, and improve HRQoL. We aimed to clarify the effects of HBOT on late radiation-induced injuries in the urinary bladder and bowel, and to clarify some of the underlying mechanisms through which HBOT exerts its effects. Methods A prospective cohort study assessed effects of HBOT on patient-perceived symptoms (Paper I). A rat study assessed reversal of radiation-induced stress with HBOT (Paper II). A methodological experiment assessed reversal of HBOT on cellular death induced by radiation (Paper III). A multi-center, randomized, controlled trial assessed patient-perceived symptoms, HRQoL, and objective clinical outcomes (Paper IV). Result HBOT can alleviate patient-perceived symptoms, reduce objective findings, and improve HRQoL in patients affected by late radiation-induced injuries (Paper I, IV). Oxidative stress and downstream effects, induced by the irradiation, can be reversed by HBOT (Paper II). Paper III outlines a method for studies on urothelial cells exposed to radiation and HBOT. Conclusion HBOT can reduce radiation-induced oxidative stress and inflammatory response. HBOT can reverse injuries induced by radiation therapy to the pelvic region, alleviate patient-perceived symptoms and lead to improved HRQoL.
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| 3. |
- Oscarsson, Nicklas, 1974, et al.
(författare)
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Hyperbaric oxygen treatment in radiation-induced cystitis and proctitis: A prospective cohort study on patient-perceived quality of recovery
- 2013
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Ingår i: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 87:4, s. 670-675
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Tidskriftsartikel (refereegranskat)abstract
- Purpose In this prospective cohort study, the effects of hyperbaric oxygen treatment (HBOT) were evaluated concerning patient-perceived symptoms of late radiation-induced cystitis and proctitis secondary to radiation therapy for pelvic cancer. Methods and Materials Thirty-nine patients, 35 men and 4 women with a mean age of 71 (range, 35-84) years were included after informed consent and institutional ethics approval. They had all been treated with radiation therapy for prostate (n=34), cervix (n=2), or rectal (n=3) cancer using external beam radiation at a dose of 25 to 75 Gy. Patients with hematuria requiring blood transfusion were excluded. The HBOT was delivered with 100% oxygen for 90 minutes at 2.0 to 2.4 atmospheres (ATA). Mean number of treatments was 36 (28-40). Symptoms were prospectively assessed using the Expanded Prostate Index Composite score before, during, and 6 to 12 months after HBOT. Results The HBOT was successfully conducted, and symptoms were alleviated in 76% for patients with radiation cystitis, 89% for patients with radiation proctitis, and 88% of patients with combined cystitis and proctitis. Symptom reduction was demonstrated by an increased Expanded Prostate Index Composite score in the urinary domain from 50 ± 16 to 66 ± 20 after treatment (P<.001) and in the bowel domain from 48 ± 18 to 68 ± 18 after treatment (P<.001). For 31% of the patients with cystitis and 22% with proctitis, there were only trivial symptoms after HBOT. The improvement was sustained at follow-up in both domains 6 to 12 months after HBOT. No severe side effects were observed related to HBOT, and treatment compliance was high. Conclusions HBOT can be an effective and safe treatment modality for late radiation therapy-induced soft tissue injuries in the pelvic region. © 2013 Elsevier Inc.
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| 4. |
- Oscarsson, Nicklas, 1974, et al.
(författare)
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Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model
- 2017
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Ingår i: Free Radical Biology and Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 103, s. 248-255
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Tidskriftsartikel (refereegranskat)abstract
- © 2017Purpose Radiotherapy is effective in the treatment of tumors in the pelvic area but is associated with side effects such as cystitis and proctitis. Hyperbaric Oxygen Therapy (HBOT) has emerged as a treatment modality for radiation-induced side effects. In a rat model for radiation cystitis, we studied the effects of HBOT on oxidative stress and pro-fibrotic factors. Materials and methods Sedated Sprague-Dawley rats underwent bladder irradiation of 20Gy with and without 20 sessions of HBOT during a fortnight. Control animals were treated with and without HBOT. All four groups of animals were euthanized 28 days later. Histopathological examinations, immunohistochemistry and quantitative polymerase chain reaction (qPCR) were used to analyze changes in oxidative stress (8-OHdG), anti-oxidative responses (SOD-1, SOD2, HO-1 and NRFα) and a panel of Th1-type and Th2-type cytokines (IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, TNF, TGF-β, IFN-γ) in the urinary bladder. Results Bladder irradiation increased the expression of 8-OHdG, SOD2, HO-1, NRFα, IL-10, TNF and tended to increase TGF-β. These changes were completely reversed by HBOT while HBOT in control animals had no effects on the studied markers for oxidative stress, anti-oxidative responses and Th1-type and Th2-type cytokines. Conclusions Radiation induced a significant elevation of oxidative stress, antioxidants and pro-fibrotic factors in our animal model for radiation cystitis that were completely reversed and normalized by HBOT. Our findings indicate that HBOT may prevent radiation-induced changes by affecting oxidative stress and inflammatory cascades induced by radiation. Summary Radiotherapy may cause the development of chronic inflammation and fibrosis, significantly impairing organ function. We hypothesized that bladder irradiation induces an oxidative stress reaction, thereby triggering the redox system and thus initiating an inflammatory and pro-fibrotic response. We aimed to assess whether these changes would be reversed by hyperbaric oxygen using an animal model for radiation cystitis. Our study show that hyperbaric oxygen may reverse oxidative stress and pro-inflammatory factors induced by radiation.
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| 5. |
- Oscarsson, Nicklas, 1974, et al.
(författare)
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Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial
- 2019
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 20:11, s. 1602-1614
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Elsevier Ltd Background: Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. Methods: We did a randomised, controlled, phase 2–3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen—A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18–80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30–40 sessions, 100% oxygen, breathed at a pressure of 240–250 kPa, for 80–90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6–8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. Findings: Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210–262) in the hyperbaric oxygen therapy group and 217 days (195–237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2–18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1–2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. Interpretation: Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. Funding: The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.
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| 6. |
- Rosén, Anders, 1970, et al.
(författare)
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Protein tau concentration in blood increases after SCUBA diving: an observational study
- 2022
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 122, s. 993-1005
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Tidskriftsartikel (refereegranskat)abstract
- Purpose It is speculated that diving might be harmful to the nervous system. The aim of this study was to determine if established markers of neuronal injury were increased in the blood after diving. Methods Thirty-two divers performed two identical dives, 48 h apart, in a water-filled hyperbaric chamber pressurized to an equivalent of 42 m of sea water for 10 min. After one of the two dives, normobaric oxygen was breathed for 30 min, with air breathed after the other. Blood samples were obtained before and at 30-45 and 120 min after diving. Concentrations of glial fibrillary acidic, neurofilament light, and tau proteins were measured using single molecule array technology. Doppler ultrasound was used to detect venous gas emboli. Results Tau was significantly increased at 30-45 min after the second dive (p < 0.0098) and at 120 min after both dives (p < 0.0008/p < 0.0041). Comparison of matching samples showed that oxygen breathing after diving did not influence tau results. There was no correlation between tau concentrations and the presence of venous gas emboli. Glial fibrillary acidic protein was decreased 30-45 min after the first dive but at no other point. Neurofilament light concentrations did not change. Conclusions Tau seems to be a promising marker of dive-related neuronal stress, which is independent of the presence of venous gas emboli. Future studies could validate these results and determine if there is a quantitative relationship between dive exposure and change in tau blood concentration.
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| 7. |
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| 8. |
- Rosén, Anders, 1970, et al.
(författare)
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Serum tau concentration after diving - an observational pilot study.
- 2019
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Ingår i: Diving and hyperbaric medicine. - : Diving and Hyperbaric Medicine Journal. - 1833-3516 .- 2209-1491. ; 49:2, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Increased concentrations of tau protein are associated with medical conditions involving the central nervous system, such as Alzheimer's disease, traumatic brain injury and hypoxia. Diving, by way of an elevated ambient pressure, can affect the nervous system, however it is not known whether it causes a rise in tau protein levels in serum. A prospective observational pilot study was performed to investigate changes in tau protein concentrations in serum after diving and also determine their relationship, if any, to the amount of inert gas bubbling in the venous blood.Subjects were 10 navy divers performing one or two dives per day, increasing in depth, over four days. Maximum dive depths ranged from 52-90 metres' sea water (msw). Air or trimix (nitrogen/oxygen/helium) was used as the breathing gas and the oxygen partial pressure did not exceed 160 kPa. Blood samples taken before the first and after the last dives were analyzed. Divers were monitored for the presence of venous gas emboli (VGE) at 10 to15 minute intervals for up to 120 minutes using precordial Doppler ultrasound.Median tau protein before diving was 0.200 pg·mL⁻¹ (range 0.100 to 1.10 pg·mL⁻¹) and after diving was 0.450 pg·mL⁻¹ (range 0.100 to 1.20 pg·mL⁻¹; P = 0.016). Glial fibrillary acidic protein and neurofilament light protein concentrations analyzed in the same assay did not change after diving. No correlation was found between serum tau protein concentration and the amount of VGE.Repeated diving to between 52-90 msw is associated with a statistically significant increase in serum tau protein concentration, which could indicate neuronal stress.
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