| 1. |
- Nolte, I. M., et al.
(författare)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
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| 2. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants
- 2009
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Ingår i: Pediatric Research. - 1530-0447 .- 0031-3998. ; 65:5, s. 574-9
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Tidskriftsartikel (refereegranskat)abstract
- In preterm infants, low levels of insulin like growth factor 1 (IGF-I) have been associated with impaired growth and retinopathy of prematurity. Our objective was to study safety and pharmacokinetics of i.v. administered rhIGF-I with its binding protein 3 (rhIGFBP-3) to preterm infants. At 3 d chronological age, an i.v. 3 h infusion of rhIGF-I/rhIGFBP-3 was administered followed by serial measurements of IGF-I and IGFBP-3. Infants were evaluated for physiologic safety measurements. The individual dose of rhIGF-I ranged from 1 to 12 microg/kg. The study was conducted at Queen Silvia Children's Hospital, Gothenburg, Sweden, between January and November 2007. Five patients (3 F) with mean (range) post menstrual age 27 wk (26-29) and birth weight 1022 g (810-1310) participated. IGF-I and IGFBP-3 levels before infusion were median (range) 18 (12-28) and 771 (651-1047) ng/mL, respectively. Immediately after study drug infusion, serum IGF-I and IGFBP-3 levels were 38 (25-59) and 838 (754-1182) ng/mL, respectively. Median (range) half-life for IGF-I and IGFBP-3 was 0.79 (0.59-1.42) and 0.87 (0.85-0.94) hours, respectively. Blood glucose, insulin, sodium, potassium, and physiologic safety measures were within normal ranges. The rhIGF-I/rhIGFBP-3 equimolar proportion was effective in increasing serum IGF-I levels and administration under these study conditions was safe and well tolerated.
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| 3. |
- Friberg, A. S., et al.
(författare)
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Impact of previous depression on the risk of suicide among prostate cancer patients
- 2023
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 62:1, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrior studies of suicide risk among prostate cancer patients are conflicting. We compared the risk of suicide in prostate cancer patients to cancer-free men including adjustment for clinical stage, socioeconomic position, somatic comorbidity, and previous depression.Materials and methodsA cohort of 37,527 men diagnosed with prostate cancer in Denmark during 1998-2011 was identified in the Danish Prostate Cancer Registry (DaPCaR) and compared with 357,384 cancer-free men matched by age at the time of diagnosis. The primary outcome was death from suicide. Data were analyzed using cumulative incidence functions and multivariable Cox regression models.ResultsAmong prostate cancer patients, 3813 had a previous depression, defined as filed antidepressant prescription within three years before diagnosis. In the study period, 108 prostate cancer patients were registered with suicide as the cause of death, hereof 26 with previous depression. There was no difference in the cumulative incidence of suicide between prostate cancer patients and cancer-free men. There was no effect modification of previous depression on the risk of suicide (p = .12). The hazard ratio (HR) for suicide varied with time since diagnosis. A sensitivity analysis showed that the risk of suicide was highest within the first year of diagnosis where prostate cancer patients had a 1.70-fold increased hazard compared with cancer-free men (95% CI, 1.11-2.59). Men with prostate cancer and previous depression had a three-fold increased hazard for suicide compared with prostate cancer patients without a history of depression (HR 2.84, 95% CI, 1.82-4.45).ConclusionThe absolute risk of suicide is low following a prostate cancer diagnosis. Time since diagnosis and a history of depression was associated with the highest risk of suicide. Healthcare professionals should be aware of an increased risk of suicide among men with previous depression, especially in the immediate aftermath of the diagnosis.
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| 4. |
- Kloprogge, F., et al.
(författare)
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Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. A search in PubMed, Embase, ClinicalTrials. gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing < 15 kg and 15-25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7. Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.
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| 5. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 6. |
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| 7. |
- Agvall, B., et al.
(författare)
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Characteristics, management and outcomes in patients with CKD in a healthcare region in Sweden: a population-based, observational study
- 2023
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Ingår i: Bmj Open. - London : BMJ Publishing Group Ltd. - 2044-6055. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo describe chronic kidney disease (CKD) regarding treatment rates, comorbidities, usage of CKD International Classification of Diseases (ICD) diagnosis, mortality, hospitalisation, evaluate healthcare utilisation and screening for CKD in relation to new nationwide CKD guidelines. DesignPopulation-based observational study. SettingHealthcare registry data of patients in Southwest Sweden. ParticipantsA total cohort of 65 959 individuals aged >18 years of which 20 488 met the criteria for CKD (cohort 1) and 45 470 at risk of CKD (cohort 2). Primary and secondary outcome measuresData were analysed with regards to prevalence, screening rates of blood pressure, glucose, estimated glomerular filtration rate (eGFR), Urinary-albumin-creatinine ratio (UACR) and usage of ICD-codes for CKD. Mortality and hospitalisation were analysed with logistic regression models. ResultsOf the CKD cohort, 18% had CKD ICD-diagnosis and were followed annually for blood pressure (79%), glucose testing (76%), eGFR (65%), UACR (24%). UACR follow-up was two times as common in hypertensive and cardiovascular versus diabetes patients with CKD with a similar pattern in those at risk of CKD. Statin and renin-angiotensin-aldosterone inhibitor appeared in 34% and 43%, respectively. Mortality OR at CKD stage 5 was 1.23 (CI 0.68 to 0.87), diabetes 1.20 (CI 1.04 to 1.38), hypertension 1.63 (CI 1.42 to 1.88), atherosclerotic cardiovascular disease (ASCVD) 1.84 (CI 1.62 to 2.09) associated with highest mortality risk. Hospitalisation OR in CKD stage 5 was 1.96 (CI 1.40 to 2.76), diabetes 1.15 (CI 1.06 to 1.25), hypertension 1.23 (CI 1.13 to 1.33) and ASCVD 1.52 (CI 1.41 to 1.64). ConclusionsThe gap between patients with CKD by definition versus those diagnosed as such was large. Compared with recommendations patients with CKD have suboptimal follow-up and treatment with renin-angiotensin-aldosterone system inhibitor and statins. Hypertension, diabetes and ASCVD were associated with increased mortality and hospitalisation. Improved screening and diagnosis of CKD, identification and management of risk factors and kidney protective treatment could affect clinical and economic outcomes.
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| 8. |
- Albrektsson, Tomas, 1945, et al.
(författare)
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Histologic investigations on 33 retrieved Nobelpharma implants.
- 1993
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Ingår i: Clinical materials. - 0267-6605. ; 12:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Thirty Nobelpharma implants were retrieved from 17 patients despite a remaining clinical stability, after between 1 and 16 years of clinical function. The reasons for implant removal were bone resorption in combination with soft tissue disorders, psychological causes, implant fracture and post mortem cases. When measured at the cortical passage, there was an average of 84.9% direct bone-to-implant contact and 81.8% average surface bone area in individual threads as evaluated in a computerized morphometric system at the light microscopic level.
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| 9. |
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| 10. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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