| 1. |
- Andersson, Ulrika, et al.
(författare)
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Associations between daily home blood pressure measurements and self-reports of lifestyle and symptoms in primary care: the PERHIT study
- 2024
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Ingår i: SCANDINAVIAN JOURNAL OF PRIMARY HEALTH CARE. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724. ; 42:3, s. 415-423
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore in a primary care setting the associations between patients' daily self-measured blood pressure (BP) during eight weeks and concurrent self-reported values of wellbeing, lifestyle, symptoms, and medication intake. We also explore these associations for men and women separately. Design and setting The study is a secondary post-hoc analysis of the randomised controlled trial PERson-centeredness in Hypertension management using Information Technology (PERHIT). The trial was conducted in primary health care in four regions in Southern Sweden. Patients Participants (n = 454) in the intervention group in the PERHIT-trial used an interactive web-based system for self-management of hypertension for eight consecutive weeks. Each evening, participants reported in the system their wellbeing, lifestyle, symptoms, and medication adherence as well as their self-measured BP and heart rate. Main outcome measures Association between self-reported BP and 10 self-report lifestyle-related variables. Results Self-reported less stress and higher wellbeing were similarly associated with BP, with 1.0 mmHg lower systolic BP and 0.6/0.4 mmHg lower diastolic BP (p < 0.001). Adherence to medication had the greatest impact on BP levels (5.2/2.6 mmHg, p < 0.001). Restlessness and headache were also significantly associated with BP, but to a lesser extent. Physical activity was only significantly associated with BP levels for men, but not for women. Conclusion In hypertension management, it may be important to identify patients with high-stress levels and low wellbeing. The association between medication intake and BP was obvious, thus stressing the importance of medication adherence for patients with hypertension.
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| 2. |
- Andersson, Ulrika, et al.
(författare)
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Variability in home blood pressure and its association with renal function and pulse pressure in patients with treated hypertension in primary care
- 2023
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Ingår i: Journal of Human Hypertension. - : SPRINGERNATURE. - 0950-9240 .- 1476-5527.
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure variability (BPV) represents a cardiovascular risk factor, regardless of mean level of blood pressure (BP). In this post-hoc analysis from the PERson-centredness in Hypertension management using Information Technology (PERHIT) study, we aimed to explore BPV in daily home measurements in hypertensive patients from primary care, to identify factors associated with high BPV and to investigate whether estimated glomerular filtration rate (eGFR) and pulse pressure, as markers of target organ damage (TOD), are associated with BPV. For eight consecutive weeks, 454 participants reported their daily BP and heart rate in their mobile phone, along with reports of lifestyle and hypertension-related factors. Systolic BP (SBP) values were used to calculate BPV with coefficient of variation (CV) as primary estimate. Background characteristics and self-reports were tested between fifths of CV in a linear regression model, adjusted for age and sex. Associations between BPV and eGFR and pulse pressure were tested with linear and logistic regression models. Higher home BPV was associated with higher age, BP, heart rate, and smoking. BPV was lower for participants with low alcohol consumption and treatment with calcium channel blockers. There was a significant association between BPV and pulse pressure (P = 0.015), and between BPV and eGFR (P = 0.049). Participants with high BPV reported more dizziness and palpitations. In conclusion, pulse pressure and eGFR were significantly associated with home BPV. Older age, high BP, heart rate, and smoking were associated with high BPV, but treatment with calcium channel blockers and low alcohol consumption was associated with low BPV. Trial registration: The study was registered with ClinicalTrials.gov [NCT03554382].
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| 3. |
- Connolly, Stuart J., et al.
(författare)
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Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
- 2024
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 390:19, s. 1745-1755
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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| 4. |
- Ekholm, Mikael
(författare)
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Haemostatic and inflammatory alterations in hypertension and hyperlipidaemia, and the impact of angiotensin II
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The process of atherosclerosis is multifactorial, and endothelial dysfunction is considered to precede atherosclerosis. Angiotensin (Ang) II, the main effector of renin-angiotensinaldosterone system (RAAS), is implicated in hypertension and has been shown to promote atherosclerosis. Familial combined hyperlipidaemia (FCHL) and familial hypercholesterolemia (FH) have been identified as risk factors for increased risk of cardiovascular heart disease and premature death. FCHL has a different phenotype compared to FH, but both lipid disorders are accompanied by subclinical atherosclerosis and endothelial dysfunction. We speculated that patients with hypertension and hyperlipidaemia were more sensitive to the potential proinflammatory and procoagulatory effects of Ang II than healthy individuals. The present research program was set up to investigate the extent to which the RAAS affects the inflammatory and thrombotic properties of individuals with hypertension and hyperlipidaemia. In Paper I we examined the impact of treatment with the ACE inhibitor ramipril on coagulation in patients with mild-to-moderate hypertension. We observed that ramipril attenuates thrombin generation in essential hypertension by reducing thrombin-antithrombin complex, and tended to reduce fibrinogen levels. In Paper II we wanted to clarify the impact of antihypertensive treatment per se. Therefore, we examined the effects of long-term treatment of ramipril compared to the alpha 1- adrenoceptor blocker doxazosin on inflammation and haemostasis in patients with mild-tomoderate hypertension. We found that antihypertensive treatment seems to exert a minor impact on systemic inflammation. Treatment with ramipril, but not doxazosin, appeared to reduce thrombin generation. This extended our previous findings in paper I suggesting that treatment with ramipril reduces thrombin generation in addition to the effects on blood pressure reduction alone. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects of lowering blood pressure. We also observed a decrease in t-PA antigen and a tendency to decreased PAI-1 activity in the doxazosin treated group, which would implicate beneficial effects by treatment with doxazosin in hypertensive patients regarding fibrinolysis. This may be of benefit in the treatment of patients with hypofibrinolysis, such as patients with FCHL. In Paper III we examined how an intravenous infusion of Ang II affected inflammation and haemostasis in patients with FCHL and healthy control subjects. In Paper IV we characterized the studied the patients with FCHL, in paper III, with respect to insulin resistance and in more detail regarding fibrinolysis. We also performed placebo experiments to make it possible to assess the influence of diurnal variations and to verify the stability of the experimental design. We found that FCHL had an increased systolic blood pressure response during infusion of Ang II compared to controls, indicating an increased vascular responsiveness in FCHL. Patients with FCHL exhibited a low-grade chronic inflammation, an impaired fibrinolysis, while the coagulation system seemed intact. FCHL shared several characteristics with the metabolic syndrome, including high triglyceride and low HDL cholesterol levels, insulin resistance and high body mass index. An infusion of Ang II increased systemic inflammation in a similar way in FCHL and controls. Ang II did not have any impact on thrombin generation, in either FCHL or controls. Ang II did not affect fibrinolysis in FCHL, whereas fibrinolysis was enhanced in healthy controls. The different responses to Ang II stimulation probably involved t-PA activity but not PAI-1 activity, and this suggests that patients with FCHL were incapable of increasing fibrinolysis in response to Ang II. We could not observe any short-term effects on PAI-1 activity, in either FCHL or controls. Our findings suggested that patients with FCHL had a low-grade chronic inflammation, impaired fibrinolysis and insulin resistance, contributing to the risk of cardiovascular heart disease and premature death in FCHL. We also suggested that Ang II acted as a proinflammatory and enhanced fibrinolysis, without impact on thrombin generation. However, taking the possible effects of diurnal variations of our coagulation markers, not taken into account in paper III, and analysing the impact of Ang II during the ongoing infusion time, post hoc analyses showed that thrombin generation instead increased, similarly in FCHL and controls. Hence, our new conclusion became that Ang II acts as a prothrombotic agent. In Paper V we examined how an intravenous infusion of Ang II affected inflammation and haemostasis in patients with FH and healthy controls. We also performed placebo experiments to make it possible to assess the influence of diurnal variations and to verify the stability of the experimental design. We found that patients with FH had higher systolic blood pressure than controls at baseline, whereas blood pressure responses were equal in FH and controls. FH showed an intact fibrinolysis and an increased thrombin generation potential compared to controls, but did not show any convincing signs of an on-going low-grade inflammation. A systemic infusion of Ang II caused an increase in systemic inflammation, fibrinolysis and possibly also thrombin generation similar in FH and control subjects. During Ang II infusion FH exhibited possible signs of an activated anticoagulant system. Our findings suggested that patients with FH had an affected coagulation system, rather than altered fibrinolysis or inflammation, contributing to the increased risk of cardiovascular heart disease and premature death in FH. Thus, blocking the renin-angiotensin-aldosterone system by an ACE inhibitor may prevent atherothrombotic complications in hypertensive patients beyond the effects on BP by reducing thrombin formation. Different mechanisms may contribute to the increased incidence of cardiovascular complications in patients with FCHL and FH. A beneficial effect of ACE inhibition in patients with FCHL might be to attenuate inflammation in combination with its documented positive influence on insulin resistance, while in patients with FH, may benefit be obtained mainly by reduced thrombin generation.
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| 5. |
- Jonsson, Eythor, 1982, et al.
(författare)
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Elbow hemiarthroplasty and total elbow arthroplasty provided a similar functional outcome for unreconstructable distal humeral fractures in patients aged 60 years or older: a multicenter randomized controlled trial
- 2024
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Ingår i: Journal of Shoulder and Elbow Surgery. - : Elsevier. - 1058-2746 .- 1532-6500. ; 33:2, s. 343-355
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Tidskriftsartikel (refereegranskat)abstract
- Background: Semiconstrained total elbow arthroplasty (TEA) is an established treatment for elderly patients with distal humeral fractures not amenable to stable internal fixation (unreconstructable). In recent years, there has been increasing interest in elbow hemiarthroplasty (EHA), a treatment option which does not entail restrictions on weight-bearing as opposed to TEA. These 2 treatments have not been compared in a randomized controlled trial (RCT). The aim of this study was to compare the functional outcome of EHA and TEA for the treatment of unreconstructable distal humeral fractures in elderly patients. Material and methods: This was a multicenter randomized controlled trial (RCT). Patients were included between January 2011 and November 2019 at one of 3 participating hospitals. The inclusion criteria were an unreconstructable distal humeral fracture, age ≥60 years and independent living. The final follow-up took place after ≥2 years. The primary outcome measure was the Disabilities of the Arm, Shoulder, and Hand (DASH) score. Secondary outcome measures were the Mayo Elbow Performance Score (MEPS), the EQ-5D index, range of motion (flexion, extension, pronation, and supination) and grip strength. Results: Forty patients were randomized to TEA (n = 20) and EHA (n = 20). Five patients died before completing the final follow-up, leaving 18 EHA and 17 TEA patients for analysis. There were 31 women. The mean age was 74.0 (SD, 8.5) years in the EHA group and 76.9 (SD, 7.6) in the TEA group (P = .30). The mean DASH score was 21.6 points in the EHA group and 27.2 in the TEA group (P = .39), a difference of −5.6 points (95% CI: −18.6 to 7.5). There were no differences between treatment with EHA and TEA for the mean values of the MEPS (85.0 vs. 88.2, P = .59), EQ-5D index (0.92 vs. 0.86, P = .13), extension (29° vs. 29°, P = .98), flexion (126° vs. 136°, P = .05), arc of flexion-extension (97° vs. 107°, P = .25), supination (81° vs. 75°, P = .13), pronation (78° vs. 74°, P = .16) or grip strength (17.5 kg vs. 17.2 kg, P = .89). There were 6 adverse events in each treatment group. Conclusion: In this RCT, both elbow hemiarthroplasty (EHA) and total elbow arthroplasty (TEA) resulted in a good and similar functional outcome for unreconstructable distal humeral fractures in elderly patients at a minimum of 2 years of follow-up.
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| 6. |
- Lundberg, Johan, et al.
(författare)
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Determinants and Outcomes of Suicidal Behavior Among Patients With Major Depressive Disorder
- 2023
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 80:12, s. 1218-1225
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Major depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples.OBJECTIVE To describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines.DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022.EXPOSURES Patients with MDD with and without records of suicidal behavior.MAIN OUTCOMES AND MEASURES The main outcomewas all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated.RESULTS A total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed.CONCLUSIONS AND RELEVANCE This cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.
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| 7. |
- Manninen, Mikael A., et al.
(författare)
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Early postglacial hunter-gatherers show environmentally driven "false logistic" growth in a low productivity environment
- 2023
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Ingår i: Journal of Anthropological Archaeology. - : Elsevier. - 0278-4165 .- 1090-2686. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Studies that employ probability distributions of radiocarbon dates to study past population size often use exponential increase in radiocarbon dates with time as a standard of comparison for detecting population fluctuations. We show that in the case of early postglacial interior Scandinavia, however, the summed probability distribution of radiocarbon dates has best fit with a S-shaped logistic growth curve. Despite the logistic growth model having solid grounding in ecological theory, we further argue that what our data indicate is not logistic growth in the population ecological sense but "false logistic" growth that mainly follows from climatic and environmental forcing. In the initial postglacial phase, 9500-7500 BCE, human settlement was located almost exclusively along the Scandinavian Atlantic coast and the use of the mountainous interior remained low. Thereafter the formation of separate inland adaptations resulted in population growth in tandem with increasing climatic warming and environmental productivity. Some millennia later, when environmental productivity started to decrease after the Holocene Thermal Maximum, hunter-gatherer population size in interior Scandi-navia reached a plateau that lasted at least 2000 years. Lowering productivity prevented any population growth that would be detectable in the available archaeological record.
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| 8. |
- Sehlin, Dag, et al.
(författare)
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Large Aggregates Are the Major Soluble Ab Species in AD Brain Fractionated with Density Gradient Ultracentrifugation
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Soluble amyloid-β (Aβ) aggregates of various sizes, ranging from dimers to large protofibrils, have been associated with neurotoxicity and synaptic dysfunction in Alzheimer's Disease (AD). To investigate the properties of biologically relevant Aβ species, brain extracts from amyloid β protein precursor (AβPP) transgenic mice and AD patients as well as synthetic Aβ preparations were separated by size under native conditions with density gradient ultracentrifugation. The fractionated samples were then analyzed with atomic force microscopy (AFM), ELISA, and MTT cell viability assay. Based on AFM appearance and immunoreactivity to our protofibril selective antibody mAb158, synthetic Aβ42 was divided in four fractions, with large aggregates in fraction 1 and the smallest species in fraction 4. Synthetic Aβ aggregates from fractions 2 and 3 proved to be most toxic in an MTT assay. In AβPP transgenic mouse brain, the most abundant soluble Aβ species were found in fraction 2 and consisted mainly of Aβ40. Also in AD brains, Aβ was mainly found in fraction 2 but primarily as Aβ42. All biologically derived Aβ from fraction 2 was immunologically discriminated from smaller species with mAb158. Thus, the predominant species of biologically derived soluble Aβ, natively separated by density gradient ultracentrifugation, were found to match the size of the neurotoxic, 80–500 kDa synthetic Aβ protofibrils and were equally detected with mAb158.
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| 9. |
- Wennergren, David, et al.
(författare)
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High reliability in classification of tibia fractures in the Swedish Fracture Register.
- 2016
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Ingår i: Injury. - 1879-0267. ; 47:2, s. 478-82
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Fracture Register (SFR) was started in 2011 and registers fractures of all types, treated either surgically or non-surgically. Twenty-six orthopaedic departments in Sweden are affiliated and a total of 84,000 fractures have been registered. The physician who establishes the diagnosis of the fracture registers and classifies it according to the AO/OTA classification. The accuracy of the classification of fractures is important for the reliability of the data in the SFR. This study aimed to evaluate how accurate the classification of tibia fractures in the register is.Three experienced trauma surgeons (raters) were presented with the radiographs of 114 patients with tibia fractures randomly allocated from the SFR. The raters classified the fractures independently and blinded to clinical patient information in two classification sessions with a time interval of one month. The AO/OTA classification coded by the three expert raters (our predefined gold standard) was compared with the classifications in the SFR. Inter- and intra-observer agreement was evaluated. The degree of agreement was reported using the approach of Landis and Koch.The accuracy of the SFR, defined as agreement between the SFR and the gold standard classification, was kappa=0.75 for the AO/OTA type and 0.56 for the AO/OTA group, corresponding to substantial and moderate agreement, respectively. Inter-observer agreement across the three expert raters was kappa=0.74 for the AO/OTA type and 0.53 for the AO/OTA group. Intra-observer agreement was kappa=0.74-0.79 for the AO/OTA type and 0.62-0.64 for the AO/OTA group.This study shows that the accuracy of classification of tibia fractures in the SFR was substantial for the AO/OTA type (kappa=0.75) and moderate for the AO/OTA group (kappa=0.56) as defined by Landis and Koch. This degree of accuracy is similar to that in previous studies. We interpret this as meaning that the results of this study demonstrate the high reliability of the data in the SFR and enable the SFR to be used for further scientific analysis.
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