Function and activity capacity at 1 year after the admission to intensive care unit for COVID-19.

OBJECTIVE: To describe hand grip strength, walking speed, functional mobility, and postural control at one year following intensive care unit admission for COVID-19, and to find any predictors that are associated with impaired hand grip strength, walking speed, functional mobility, or postural control at the 1-year follow-up. DESIGN: Retrospective cross-sectional and longitudinal observational study. SETTING: Intensive care unit and outpatient research clinic at Sahlgrenska University Hospital. PARTICIPANTS: Of the 105 individuals in "The Gothenburg Recovery and Rehabilitation after COVID-19 and Intensive Care Unit" cohort, 78 participated in this study. MAIN MEASURES: Descriptive statistics for hand grip strength, walking speed, functional mobility, and postural control were presented and binary logistic regressions were performed to find their significant predictors. RESULTS: At 1-year following intensive care unit admission for COVID-19, impaired hand grip strength was found in 24.4% for the right hand and 23.1% for the left hand. Walking speed, functional mobility, and postural control were found to be impaired in 29.5%, 21.8%, and 5.1%, respectively. For impaired walking speed, longer length of stay at intensive care unit and presence of diabetes mellitus were risk factors. Diabetes mellitus was found to be the risk factor for impaired functional mobility. CONCLUSION: In this study, 45% of the participants showed impairment in function, activity capacity or both. These results suggest that individuals who recovered after intensive care unit admission for COVID-19 would benefit from receiving long-term follow-up to enable identification of those with need of physical health assistance and rehabilitation.

Warfarin intake in relation to diagnosis reduces mortality in patients with colorectal cancer - a register-based study.

BACKGROUND: Several studies have analyzed the effect of anticoagulants on cancer survival, with varying results. This study aimed to assess the effect of warfarin on survival in patients with colorectal cancer (CRC) in relation to timing of warfarin initiation. METHODS: Data on 10,051 individuals aged ≥45 years in the Västra Götaland Region of Sweden, and diagnosed with CRC between 2000 and 2009, were obtained from the Swedish National Cancer Register. Those who received warfarin treatment (n= 1,216) during the study period were labeled cases and those who did not (n= 8,873) were labeled controls. For statistical analysis, National Cancer Register data were merged with mortality data from the Swedish National Cause of Death register and data from the regional warfarin treatment register. RESULTS: Hazard rates for CRC-specific mortality were lower in cases than in controls. When warfarin was used for any reason at any time, cases had a significantly lower CRC-specific mortality than controls among both women (hazard ratio [HR] 0.71; 95 % confidence interval [CI] 0.59-0.85; p= 0.0002) and men (HR 0.61; 95 % CI 0.52-0.72; p < 0001). Warfarin treatment after CRC diagnosis reduced CRC-specific mortality by 80 %; however, when warfarin was given before or ≥5 years after diagnosis, CRC-specific mortality did not significantly decrease. The number needed to treat to avoid one death was four. CONCLUSION: Use of warfarin early after diagnosis in patients with CRC was associated with improved survival.

Symptoms at stroke onset as described by patients: a qualitative study.

BACKGROUND: Stroke is a common and severe disease that requires prompt care. Symptom expressions as one-sided weakness and speech difficulties are common and included in public stroke campaigns. For some patients stroke can present with subtle and less common symptoms, difficult to interpret. The symptom severity assessed by the National Institutes of Health Stroke Scale has decreased, and symptoms at onset may have changed. Therefore, we aimed to investigate how patients describe their symptoms at the onset of a first-time stroke. METHODS: The study used a qualitative descriptive design and conventional content analysis. Data were collected through recorded interviews with 27 patients aged 18 years and older hospitalised with a first-time stroke between October 2018 and April 2020. Data were analysed on a manifest level. RESULTS: Symptoms at stroke onset were presented in two themes: Altered Reality and Discomfort and Changed Body Functions and described in five categories. Various types of symptoms were found. All symptoms were perceived as sudden, persistent, and never experienced before and this appear as a "red thread" in the result. Regardless of symptom expressions, no specific symptom was described as more severe than another. CONCLUSIONS: Stroke symptoms were described with a variety of expressions. Many described complex symptoms not typical of stroke, which can make it difficult to recognise the symptoms as a stroke and delay medical care. Public stroke campaigns should emphasize the importance of seeking medical care at the slightest suspicion of stroke and could be designed to help achieve this.

Cover crop cultivation strategies in a Scandinavian context for climate change mitigation and biogas production - Insights from a life cycle perspective.

Cover crop cultivation can be a vital strategy for mitigating climate change in agriculture, by increasing soil carbon stocks and resource efficiency within the cropping system. Another mitigation option is to harvest the cover crop and use the biomass to replace greenhouse gas-intensive products, such as fossil fuels. Harvesting cover crop biomass could also reduce the risk of elevated N2O emissions associated with cover crop cultivation under certain conditions, which would offset much of the mitigation potential. However, harvesting cover crops also reduces soil carbon sequestration potential, as biomass is removed from the field, and cultivation of cover crops requires additional field operations that generate greenhouse gas emissions. To explore these synergies and trade-offs, this study investigated the life cycle climate effect of cultivating an oilseed radish cover crop under different management strategies in southern Scandinavia. Three alternative scenarios (Incorporation of biomass into soil; Mowing and harvesting aboveground biomass; Uprooting and harvesting above- and belowground biomass) were compared with a reference scenario with no cover crop. Harvested biomass in the Mowing and Uprooting scenarios was assumed to be transported to a biogas plant for conversion to upgraded biogas, with the digestate returned to the field as an organic fertiliser for the subsequent crop. The climate change mitigation potential of cover crop cultivation was found to be 0.056, 0.58 and 0.93 Mg CO2-eq ha-1 in the Incorporation, Mowing and Uprooting scenario, respectively. The Incorporation scenario resulted in the highest soil carbon sequestration, but also the greatest soil N2O emissions. Substitution of fossil diesel showed considerable mitigation potential, especially in the Uprooting scenario, where biogas production was highest. Sensitivity analysis revealed a strong impact of time of cover crop establishment, with earlier establishment leading to greater biomass production and thus greater mitigation potential.

Quantitative imaging of doxorubicin diffusion and cellular uptake in biomimetic gels with human liver tumor cells.

Novel tumor-on-a-chip approaches are increasingly used to investigate tumor progression and potential treatment options. To improve the effect of any cancer treatment it is important to have an in depth understanding of drug diffusion, penetration through the tumor extracellular matrix and cellular uptake. In this study, we have developed a miniaturized chip where drug diffusion and cellular uptake in different hydrogel environments can be quantified at high resolution using live imaging. Diffusion of doxorubicin was reduced in a biomimetic hydrogel mimicking tissue properties of cirrhotic liver and early stage hepatocellular carcinoma (373 ± 108 µm2/s) as compared to an agarose gel (501 ± 77 µm2/s, p = 0.019). The diffusion was further lowered to 256 ± 30 µm2/s (p = 0.028) by preparing the biomimetic gel in cell media instead of phosphate buffered saline. The addition of liver tumor cells (Huh7 or HepG2) to the gel, at two different densities, did not significantly influence drug diffusion. Clinically relevant and quantifiable doxorubicin concentration gradients (1-20 µM) were established in the chip within one hour. Intracellular increases in doxorubicin fluorescence correlated with decreasing fluorescence of the DNA-binding stain Hoechst 33342 and based on the quantified intracellular uptake of doxorubicin an apparent cell permeability (9.00 ± 0.74 × 10-4 µm/s for HepG2) was determined. Finally, the data derived from the in vitro model were applied to a spatio-temporal tissue concentration model to evaluate the potential clinical impact of a cirrhotic extracellular matrix on doxorubicin diffusion and tumor cell uptake.

Comparison of the analgesic effects of "superficial" and "deep" repetitive transcranial magnetic stimulation in patients with central neuropathic pain: a randomized sham-controlled multicenter international crossover study.

ABSTRACT: We directly compared the analgesic effects of "superficial" and 'deep" repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in patients with central neuropathic pain. Fifty-nine consecutive patients were randomly assigned to active or sham "superficial" (using a figure-of-8 [F8]-coil) or "deep" (using a Hesed [H]-coil) stimulation according to a double-blind crossover design. Each treatment period consisted of 5 daily stimulation sessions and 2 follow-up visits at 1 and 3 weeks after the last stimulation session. The primary outcome was the comparison of the mean change in average pain intensity over the course of the treatment (group × time interaction). Secondary outcomes included neuropathic symptoms (NPSI), pain interference, patient global impression of change (PGIC), anxiety, depression, and catastrophizing. In total, 51 patients participated in at least one session of both treatments. There was a significant interaction between "treatment" and "time" (F = 2.7; P = 0.0024), indicating that both figure-8 (F8-coil) and H-coil active stimulation induced significantly higher analgesic effects than sham stimulation. The analgesic effects of both types of coils had a similar magnitude but were only moderately correlated ( r = 0.39, P = 0.02). The effects of F8-coil stimulation appeared earlier, whereas the effects of H-coil stimulation were delayed, but tended to last longer (up to 3 weeks) as regards to several secondary outcomes (PGIC and total NPSI score). In conclusion, "deep" and "superficial" rTMS induced analgesic effects of similar magnitude in patients with central pain, which may involve different mechanisms of action.

Paradoxical heat sensation as a manifestation of thermal hypesthesia: a study of 1090 patients with lesions of the somatosensory system.

ABSTRACT: Paradoxical heat sensation (PHS) is the perception of warmth when the skin is cooled. Paradoxical heat sensation rarely occurs in healthy individuals but more frequently in patients suffering from lesions or disease of the peripheral or central nervous system. To further understand mechanisms and epidemiology of PHS, we evaluated the occurrence of PHS in relation to disease aetiology, pain levels, quantitative sensory testing parameters, and Neuropathic Pain Symptom Inventory (NPSI) items in patients with nervous system lesions. Data of 1090 patients, including NPSI scores from 404 patients, were included in the analysis. We tested 11 quantitative sensory testing parameters for thermal and mechanical detection and pain thresholds, and 10 NPSI items in a multivariate generalised linear model with PHS, aetiology, and pain (yes or no) as fixed effects. In total, 30% of the neuropathic patients reported PHS in contrast to 2% of healthy individuals. The frequency of PHS was not linked to the presence or intensity of pain. Paradoxical heat sensation was more frequent in patients living with polyneuropathy compared with central or unilateral peripheral nerve lesions. Patients who reported PHS demonstrated significantly lower sensitivity to thermal perception, with lower sensitivity to normally painful heat and cold stimuli. Neuropathic Pain Symptom Inventory scores were lower for burning and electric shock-like pain quality for patients with PHS. Our findings suggest that PHS is associated with loss of small thermosensory fibre function normally involved in cold and warm perception. Clinically, presence of PHS could help screening for loss of small fibre function as it is straightforward to measure or self-reported by patients.

Fast track to stroke unit for patients not eligible for acute intervention, a case-control register study on 1066 patients.

Stroke patients not eligible for acute intervention often have low priority and may spend long time at the emergency department (ED) waiting for admission. The aim of this retrospective case-control register study was to evaluate outcomes for such "low priority" stroke patients who were transported via Fast Track directly to the stroke unit, according to pre-specified criteria by emergency medical service (EMS). The outcomes of Fast Track patients, transported directly to stroke unit (cases) were compared with the outcomes of patients who fulfilled these critera for Fast Track, but instead were transported to the ED (controls). In all, 557 cases and 509 controls were identified. The latter spent a mean time of 237 min in the ED before admission. The 90-day mortality rate was 12.9% for cases and 14.7% for controls (n.s.). None of the secondary outcome events differed significantly between the groups: 28-day mortality rate; death rate during hospitalisation; proportion of pneumonias, falls or pressure ulcers; or health-related outcomes according to the EQ-5D-5L questionnaire. These findings indicates that the Fast Track to the stroke unit by an EMS is safe for selected stroke patients and could avoid non-valuable time in the ED.

Energy performance of compressed biomethane gas production from co-digestion of Salix and dairy manure: factoring differences between Salix varieties.

Biogas from anaerobic digestion is a versatile energy carrier that can be upgraded to compressed biomethane gas (CBG) as a renewable and sustainable alternative to natural gas. Organic residues and energy crops are predicted to be major sources of bioenergy production in the future. Pre-treatment can reduce the recalcitrance of lignocellulosic energy crops such as Salix to anaerobic digestion, making it a potential biogas feedstock. This lignocellulosic material can be co-digested with animal manure, which has the complementary effect of increasing volumetric biogas yield. Salix varieties exhibit variations in yield, composition and biomethane potential values, which can have a significant effect on the overall biogas production system. This study assessed the impact of Salix varietal differences on the overall mass and energy balance of a co-digestion system using steam pre-treated Salix biomass and dairy manure (DaM) to produce CBG as the final product. Six commercial Salix varieties cultivated under unfertilised and fertilised conditions were compared. Energy and mass flows along this total process chain, comprising Salix cultivation, steam pre-treatment, biogas production and biogas upgrading to CBG, were evaluated. Two scenarios were considered: a base scenario without heat recovery and a scenario with heat recovery. The results showed that Salix variety had a significant effect on energy output-input ratio (R), with R values in the base scenario of 1.57-1.88 and in the heat recovery scenario of 2.36-2.94. In both scenarios, unfertilised var. Tordis was the best energy performer, while the fertilised var. Jorr was the worst. Based on this energy performance, Salix could be a feasible feedstock for co-digestion with DaM, although its R value was at the lower end of the range reported previously for energy crops.

Utilizing a microfluidic platform to investigate drug-eluting beads: Binding and release of amphiphilic antidepressants.

Drug-eluting beads made of responsive polyelectrolyte networks are used in the treatment of liver cancer. Aggregates of loaded drugs in complex with the networks dissolve upon release, causing swelling of the network. According to a recent mechanism the release and swelling rates are controlled by the mass transport of drug through a depletion layer created in the microgel. We hypothesise that the mechanism, in which the stability of the drug aggregates and the swelling properties of the network play crucial roles, offers means to control the release profile also for other drugs. To test this, we investigated the loading and release properties of amitriptyline, chlorpromazine and doxepin in polyacrylate, hyaluronate and DCbead™ microgels in a microfluidic setup. Loaded drugs could be released to a medium with physiological ionic strength and pH. The binding strength increased with decreasing critical micelle concentration of the drugs and increasing linear charge density of network chains. Microgels displayed drug-rich core/swollen shell coexistence, and swelled during release at a rate in agreement with the depletion layer mechanism, indicating its generality. The results demonstrate the potential of microgels as vehicles for amphiphilic drugs and the usefulness of the microfluidics method for in vitro studies of such systems.

Prepregnancy overweight and obesity and long-term risk of venous thromboembolism in women.

Overweight and obesity rates have increased in recent decades, particularly among the younger population. The long-term consequences of obesity with respect to early venous thromboembolism (VTE) in women have not been established. The aim was to investigate the association between body mass index (BMI) in early pregnancy as a proxy for non-pregnant weight and long-term post-pregnancy risk of VTE in women. This registry-based prospective cohort study analysed data from the Swedish Medical Birth Registry, linked to the National Patient and the National Cause of Death Registries for information on post-pregnancy long-term risk of VTE. Cox proportional hazards model were used to determine the association between BMI at baseline and VTE events during follow-up starting 1 year after baseline. The mean age at registration was 27.5 (standard deviation, 4.9) years. During a median follow-up duration of 12 years (interquartile range, 6-21 years) starting 1 year after the first antenatal visit, 1765 and 2549 women had a deep vein thrombosis and/or pulmonary embolism. The risk of VTE linearly increased with increasing BMI. Compared to women with 20 ≤ BMI < 22.5 kg/m2, women with high normal weight, i.e. with a BMI of 22.5-25.0 kg/m2, had an adjusted hazard ratio (HR) of 1.30 (95% confidence interval [CI] 1.19-1.41), whereas those with a BMI of 30-35 kg/m2 and ≥ 35 kg/m2 (severe obesity) had an adjusted HR of 2.35 (95% CI 2.04-2.70) and 3.47 (95% CI 2.82-4.25, respectively. Using BMI in early pregnancy as a proxy for pre-pregnancy or non-pregnant BMI in young women, we found a significantly increased risk of post-pregnancy long-term risk of VTE even in those with high normal BMI, compared with lean women, whereas those with severe obesity had a markedly high risk.

Health-related quality of life in stroke survivors: a 5-year follow-up of The Fall Study of Gothenburg (FallsGOT).

BACKGROUND: There are limited data on long-term prevalence and predictors of health-related quality of life (HRQoL) in stroke survivors. Therefore, the aim was to describe the prevalence of impaired HRQoL, and to identify factors in acute stroke that are associated with impaired HRQoL, 5 years after stroke. METHODS: The 305 (60.5%) stroke survivors of the original 504 participants from The Fall Study of Gothenburg were invited to participate in a 5-year follow-up including assessment of HRQoL using the EuroQol 5 Dimensions 3 Levels questionnaire (EQ-5D-3L). To identify baseline predictors of impaired HRQoL, based on the EQ-5D-3L's five dimensions, univariate and multivariate logistic regression analyses were performed. RESULTS: A total of 129 participants (42.3% of the survivors) completed the questionnaire at a median follow-up time of 58 months. At baseline, their mean age was 70.6 years, and they had a median NIHSS score of 1. The median (interquartile range [IQR]) EQ-5D-3L index score was 0.87 (0.71-0.93) and the median (IQR) EQ-visual analogue scale was 70 (49.8-88). In total, 102 (79%) participants were classified as having impaired HRQoL, stated primarily (among 68.5%) related to Pain/Discomfort. Higher age was identified as a predictor of impaired HRQoL related to Mobility (Odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01-1.10) and Self-Care (OR 1.09, 95% CI 1.02-1.17), and longer hospital stay at baseline was identified as a predictor related to Mobility (OR 1.09, 95% CI 1.01-1.18), Self-Care (OR 1.10, 95% CI 1.02-1.18)) and Usual Activities. (OR 1.10, 95% CI 1.03-1.18). CONCLUSION: At 5 years after stroke, four out of five participants (79%) reported impaired HRQoL related to any of the five dimensions assessed by using the EQ-5D-3L. Most reported, impaired HRQoL was related to Pain/Discomfort. Higher age and longer hospital care period at index stroke were associated with impaired HRQoL. The findings could assist to identify individuals at high risk of low HRQoL, who might benefit from special attention and psychological support.

From straw to salmon: a technical design and energy balance for production of yeast oil for fish feed from wheat straw.

BACKGROUND: Aquaculture is a major user of plant-derived feed ingredients, such as vegetable oil. Production of vegetable oil and protein is generally more energy-intensive than production of the marine ingredients they replace, so increasing inclusion of vegetable ingredients increases the energy demand of the feed. Microbial oils, such as yeast oil made by fermentation of lignocellulosic hydrolysate, have been proposed as a complement to plant oils, but energy assessments of microbial oil production are needed. This study presents a mass and energy balance for a biorefinery producing yeast oil through conversion of wheat straw hydrolysate, with co-production of biomethane and power. RESULTS: The results showed that 1 tonne of yeast oil (37 GJ) would require 9.2 tonnes of straw, 14.7 GJ in fossil primary energy demand, 14.6 GJ of process electricity and 13.3 GJ of process heat, while 21.5 GJ of biomethane (430 kg) and 6 GJ of excess power would be generated simultaneously. By applying economic allocation, the fossil primary energy demand was estimated to 11.9 GJ per tonne oil. CONCLUSIONS: Fossil primary energy demand for yeast oil in the four scenarios studied was estimated to be 10-38% lower than for the commonly used rapeseed oil and process energy demand could be met by parallel combustion of lignin residues. Therefore, feed oil can be produced from existing non-food biomass without causing agricultural expansion.

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.

Cumulative incidence and risk factors of myocardial infarction during 20 years of follow-up: comparing two cohorts of middle-aged men born 30 years apart.

OBJECTIVE: To study cumulative incidence and predictors of myocardial infarction (MI) in two random general population samples consisting of middle-aged Swedish men born 30 years apart. METHOD: Results from the "Study of Men Born In 1913" and the "Study of Men Born In 1943", two longitudinal cohort studies performed in the same geographic area and using the same methodology were compared. Both cohorts were followed prospectively from 50 to 70 years of age. MI was defined as first myocardial infarction, fatal or non-fatal. RESULTS: Men born in 1943 had a 34% lower cumulative risk of first MI [HR 0.66 (0.50-0.88), p = 0.0051] during follow-up as compared to men born in 1913. Interaction analysis showed that hypertension had a significantly higher impact on risk of MI in cohort 1943 than in cohort 1913 [HR 2.33 (95% CI 1.41-3.83)] and [HR 1.10 (0.74-1.62)], p = 0.0009 respectively. The population attributable risk for hypertension was 2.5-fold higher in the cohort of men born in 1943 as compared to men born in 1913, and diabetes mellitus and sedentary lifestyle attributed more to MI risk in cohort 1943 than in cohort 1913. On the contrary, smoking and total cholesterol have less attributable risk to MI in cohort 1943 than in cohort 1913. CONCLUSION: Despite declining incident MI and improved cardiovascular prevention in general, hypertension remains an increasingly important attributable risk factor to MI together with diabetes mellitus and sedentary lifestyle over time.

Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study.

BACKGROUND: Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment. OBJECTIVES: To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years). METHODS: A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates. RESULTS: We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment. CONCLUSION: Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.

Fatigue in stroke survivors: a 5-year follow-up of the Fall study of Gothenburg.

Longer term knowledge of post-stroke fatigue (PSF) is limited. Our aim was to describe the prevalence of, and to identify baseline predictors associated with, PSF 5 years after stroke. We undertook a follow-up of stroke survivors from the 504 consecutively recruited participants in the observational "The Fall Study of Gothenburg", conducted between 2014 and 2016. The dependent variable, PSF, was assessed using the Swedish version of the Fatigue Assessment Scale (S-FAS) and defined as having a S-FAS score ≥ 24. The S-FAS questionnaire was mailed to potential participants in August 2020. The independent variables, previously obtained from medical records, included age; sex; comorbidities; stroke severity; hospital length of stay; body mass index (BMI); number of medications and lifestyle factors at index stroke. To identify predictors of PSF, univariable and multivariable logistic regression analyses were performed. Of the 305 eligible participants, 119 (39%) responded with complete S-FAS. Mean age at index stroke was 71 (SD 10.4) years and 41% were female. After a mean of 4.9 years after stroke, the prevalence of PSF was 52%. Among those with PSF, almost two thirds were classified as having both physical and mental PSF. In the multivariable analysis, only high BMI predicted PSF with an odds ratio of 1.25 (95% CI 1.11-1.41, p < 0.01). In conclusion, half of the participants reported PSF 5 years after index stroke and higher body mass index was identified as a predictor. The findings from this study are important for healthcare professionals, for planning health-related efforts and rehabilitation of stroke survivors.ClinicalTrials.gov, Identifier NCT02264470.

Pulmonary embolism and deep venous thrombosis after COVID-19: long-term risk in a population-based cohort study.

Background: Venous thromboembolism (VTE) (pulmonary embolism (PE) or deep venous thrombosis (DVT)) is common during acute COVID-19. Long-term excess risk has not yet been established. Objective: To study long-term VTE risk after COVID-19. Methods: Swedish citizens aged 18-84 years, hospitalized and/or testing positive for COVID-19 between January 1, 2020, and September 11, 2021 (exposed), stratified by initial hospitalization, were compared to matched (1:5) non-exposed population-derived subjects without COVID-19. Outcomes were incident VTE, PE or DVT recorded within 60, 60-<180, and ≥180 days. Cox regression was used for evaluation and a model adjusted for age, sex, comorbidities and socioeconomic markers developed to control for confounders. Results: Among exposed patients, 48,861 were hospitalized for COVID-19 (mean age 60.6 years) and 894,121 were without hospitalization (mean age 41.4 years). Among patients hospitalized for COVID-19, fully adjusted hazard ratios (HRs) during 60-<180 days were 6.05 (95% confidence interval (CI) 4.80─7.62) for PE and 3.97 (CI 2.96─5.33) for DVT, compared to non-exposed with corresponding estimates among COVID-19 without hospitalization 1.17 (CI 1.01─1.35) and 0.99 (CI 0.86─1.15), based on 475 and 2,311 VTE events, respectively. Long-term (≥180 days) HRs in patients hospitalized for COVID-19 were 2.01 (CI 1.51─2.68) for PE and 1.46 (CI 1.05─2.01) for DVT while non-hospitalized had similar risk to non-exposed, based on 467 and 2,030 VTE events, respectively. Conclusions: Patients hospitalized for COVID-19 retained an elevated excess risk of VTE, mainly PE, after 180 days, while long-term risk of VTE in individuals with COVID-19 without hospitalization was similar to the non-exposed.

Heart failure outcomes in low-risk patients with atrial fibrillation: a case-control study of 680 523 Swedish individuals.

AIMS: Knowledge of long-term outcomes in patients with atrial fibrillation (AF) remains limited. We sought to evaluate the risk of new-onset heart failure (HF) in patients with AF and a low cardiovascular risk profile. METHODS AND RESULTS: Data from the Swedish National Patient Register were used to identify all patients with a first-time diagnosis of AF without underlying cardiovascular disease at baseline between 1987 and 2018. Each patient was compared with two controls without AF from the National Total Population Register. In total, 227 811 patients and 452 712 controls were included. During a mean follow-up of 9.1 (standard deviation 7.0) years, the hazard ratio (HR) for new-onset HF was 3.55 [95% confidence interval (CI) 3.51-3.60] in patients compared with controls. Women with AF (18-34 years) had HR for HF onset 24.6 (95% CI 7.59-80.0) and men HR 9.86 (95% CI 6.81-14.27). The highest risk was within 1 year in patients 18-34 years, HR 103.9 (95% CI 46.3-233.1). The incidence rate within 1 year increased from 6.2 (95% CI 4.5-8.6) per 1000 person-years in young patients (18-34 years) to 142.8 (95% CI 139.4-146.3) per 1000 person-years among older patients (>80 years). CONCLUSIONS: Patients studied had a three-fold higher risk of developing HF compared with controls. Young patients, particularly women, carry up to 100-fold increased risk to develop HF within 1 year after AF. Further studies in patients with AF and low cardiovascular risk profile are needed to prevent serious complications such as HF.