| 1. |
- Blennow Nordström, Erik, et al.
(författare)
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Neuropsychological outcome after cardiac arrest : results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2023
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Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.METHODS: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.RESULTS: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.CONCLUSIONS: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
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| 2. |
- Cuzick, Jack, et al.
(författare)
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Prevention and early detection of prostate cancer.
- 2014
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:11, s. e484-92
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
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| 3. |
- Assel, Melissa, et al.
(författare)
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Association Between Lead Time and Prostate Cancer Grade : Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening
- 2018
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 73:6, s. 961-967
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening. Objective: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time. Design, setting, and participants: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3–10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available. Outcome measurements and statistical analysis: Multivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age. Results and limitations: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10–1.16; p < 0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28–0.64; p < 0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation. Conclusions: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa. Patient summary: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis. The probability that a cancer will be of high grade at diagnosis increases with the lead time. Our findings provide evidence of grade progression, whereby a prostate followed over time would exhibit transitions from benign to low-grade to high-grade prostate cancer.
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| 4. |
- Donoso, Felipe, et al.
(författare)
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Pulmonary function in children and adolescents after esophageal atresia repair
- 2020
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Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 55:1, s. 206-213
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionRespiratory morbidity after esophageal atresia (EA) is common. The aims of this study were to assess pulmonary function, to identify risk factors for pulmonary function impairment (PFI), and to investigate the relations between respiratory morbidity, defined as medical treatment for respiratory symptoms or recent pneumonia and PFI after EA repair.Material and MethodsSingle center retrospective observational study including patients with EA who participated in the follow‐up program for 8‐ or 15‐year old patients from 2014 to 2018 and performed pulmonary function testing by body plethysmography, dynamic spirometry, impulse oscillometry, and diffusing capacity of the lungs. Univariate and multiple stepwise logistic regression with PFI as outcome were performed. Anastomotic leak, episodes of general anesthesia, extubation day, birth weight, age at follow up, gross classification, and abnormal reflux index were independent variables.ResultsIn total, 47 patients were included. PFI was found in 19 patients (41%) and 16 out of 19 patients (84%) had an obstructive pattern. Respiratory morbidity was found in 23 (52%, NA = 3) of the patients with no correlation to PFI. Birth weight, age at follow‐up, and episodes of general anesthesia were identified as risk factors for PFI.ConclusionRespiratory morbidity and PFI were common in children and adolescents after EA repair. The major component of PFI was obstruction of the airways. The risk for PFI increased with lower birth weight and older age at follow up. The poor correlation between respiratory morbidity and PFI motivates the need of clinical follow up including pulmonary function tests.
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| 5. |
- Ek, Pia, et al.
(författare)
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Exogenous protein kinases A and C, but not endogenous prostasome-associated protein kinase, phosphorylate semenogelins I and II from human semen
- 2002
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Ingår i: Journal of Andrology. - 0196-3635 .- 1939-4640. ; 23:6, s. 806-814
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Tidskriftsartikel (refereegranskat)abstract
- Semenogelins I and II are the quantitatively dominating proteinsin humansemen. They comprise the major part of the sperm-entrappinggel formed atejaculation, which subsequently liquefies dueto proteolysis of thegel-forming proteins by prostate-specificantigen (PSA). The mechanism behindgel formation and its physiologicalsignificance is not known. We have studiedphosphorylation anddephosphorylation of human semenogelins. Both werephosphorylatedby protein kinases A and C (PKA and PKC, respectively) at arateabout 5 times less than that of histone. For PKA, incorporated(32P)phosphateinto semenogelin approached a maximum above 1mol/mol. Correspondingvalues for phosphorylation of the semenogelins with PKCweregreater than 10. There was no change in the sensitivity ofphosphosemenogelinsto proteolysis by PSA. Serine (PKA) and serine andthreonine(PKC) were the phosphate-accepting amino acid residues, andallincorporated (32P)phosphate could be removed from the semenogelinswithhuman acid phosphatase. Nil or very little phosphate could bedetected inpurified semenogelins isolated from seminal plasma.In vivo, about half theprotein kinase activity in seminal plasmawas bound to prostasomes. PKA butnot PKC purified from prostasomescould phosphorylate specific substrates, butthey could phosphorylateeither of the semenogelins.
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| 6. |
- Elfwen, Ludvig, et al.
(författare)
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Direct or subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)-An initial pilot-study of a randomized clinical trial
- 2019
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Ingår i: Resuscitation. - : ELSEVIER IRELAND LTD. - 0300-9572 .- 1873-1570. ; 139, s. 253-261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the 'DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest' (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods: Resuscitated bystander witnessed OHCA patients > 18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results: In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion: In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.
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| 7. |
- Evans Axelsson, Susan, et al.
(författare)
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Targeting free prostate-specific antigen for in vivo imaging of prostate cancer using a monoclonal antibody specific for unique epitopes accessible on free prostate-specific antigen alone
- 2012
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 27:4, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected 125I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting 125I-labeled PSA30. Tissue uptake of 125I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, 18F-fluoro-deoxy-glucose (18F-FDG) or 18F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high 125I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either 18F-FDG or 18F-choline. Biodistribution of 125I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24–48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.
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| 8. |
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| 9. |
- Heimburg, Katarina, et al.
(författare)
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Agreement between self-reported and objectively assessed physical activity among out-of-hospital cardiac arrest survivors.
- 2023
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Low level of physical activity is a risk factor for new cardiac events in out-of-hospital cardiac arrest (OHCA) survivors. Physical activity can be assessed by self-reporting or objectively by accelerometery.AIM: To investigate the agreement between self-reported and objectively assessed physical activity among OHCA survivors HYPOTHESIS: Self-reported levels of physical activity will show moderate agreement with objectively assessed levels of physical activity.METHOD: Cross-sectional study including OHCA survivors in Sweden, Denmark, and the United Kingdom. Two questions about moderate and vigorous intensity physical activity during the last week were used as self-reports. Moderate and vigorous intensity physical activity were objectively assessed with accelerometers (ActiGraph GT3X-BT) worn upon the right hip for 7 consecutive days.RESULTS: Forty-nine of 106 OHCA survivors answered the two questions for self-reporting and had 7 valid days of accelerometer assessment. More physically active days were registered by self-report compared with accelerometery for both moderate intensity (median 5 [3:7] vs. 3 [0:5] days; p < 0.001) and vigorous intensity (1 [0:3] vs. 0 [0:0] days; p < 0.001). Correlations between self-reported and accelerometer assessed physical activity were sufficient (moderate intensity: rs = 0.336, p = 0.018; vigorous intensity: rs = 0.375, p = 0.008), and agreements were fair and none to slight (moderate intensity: k = 0.269, p = 0.001; vigorous intensity: k = 0.148, p = 0.015). The categorization of self-reported versus objectively assessed physical activity showed that 26% versus 65% had a low level of physical activity.CONCLUSION: OHCA survivors reported more physically active days compared with the results of the accelerometer assessment and correlated sufficiently and agreed fairly and none to slightly.
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| 10. |
- Högberg, Cecilia, et al.
(författare)
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Use of faecal immunochemical tests common in patients with suspected colorectal cancer but unrelated to travel distance to secondary care : a population-based study from Swedish primary care
- 2022
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724. ; 40:4, s. 459-465
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Tidskriftsartikel (refereegranskat)abstract
- Background Evidence is increasing for the use of faecal immunochemical tests (FITs) for occult blood as diagnostic tools when colorectal cancer can be suspected. FITs have been used for this purpose in Swedish primary care since around 2005 despite absence of supporting guidelines. To our knowledge, the extent of this use has not been studied. Objective To investigate the use of FITs as diagnostic tools, and if the use was related to patient age, sex and travel time from primary care to diagnostic facilities in secondary care. Design Population-based retrospective study using data from electronic health records. Setting and subjects Patients >= 18 years that provided FITs in primary care in five Swedish health care regions during 2015. Driving times from their primary care centres to secondary care were calculated. Main outcome measures The proportion of patients that provided FITs was calculated for each region, different age intervals and grouped driving times. Results 18,913 patients provided FITs. The proportion of listed patients in the five regions that provided FITs increased with age: 0.86-1.2% for ages <65 years, 3.6-4.1% for ages 65-79 years and 3.8-6.1% for ages >= 80 years. Differences between the regions were small. There was no overall correlation between the proportion of patients that provided FITs and driving time to secondary care. Conclusion FITs were used extensively in Swedish primary care with a higher use in older age groups. There was no tendency towards a higher use of FITs at primary care centres with longer driving times to secondary care.
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