Search

For many biopharmaceuticals, subcutaneous (sc) administration is the only viable route. However, there is no in vitro method available accurately predicting the absorption profiles of subcutaneously injected pharmaceuticals. In this work, we show that a recently developed microfluidics method for interaction studies (MIS) has the potential to be useful in this respect. The method utilises the responsiveness of polyelectrolyte microgel networks to oppositely charged molecules as a means to monitor the interaction between peptides and hyaluronic acid (HA), a major constituent of the subcutaneous extracellular matrix. We use the method to determine parameters describing the strength of interaction between peptide and HA as well as the peptide's aggregation tendency and transport properties in HA networks. The results from MIS studies of the peptide drugs exenatide, pramlintide, vancomycin, polymyxin B, lanreotide, MEDI7219 and AZD2820 are compared with results from measurements with the commercially available SCISSOR system and in vivo absorption and bioavailability data from the literature. We show that both MIS and SCISSOR reveal differences in the peptides' diffusivity and tendency to aggregate in the presence of HA. We show that MIS is particularly good at discriminating between peptides forming aggregates stabilised by non-electrostatic forces in the presence of HA, and peptides forming complexes stabilised by electrostatic interactions with HA. The method provides two parameters that can be used to quantify the peptides' aggregation tendency, the one describing the peptide packing density in complexes with HA and the other the apparent diffusivity upon release in a medium of physiological ionic strength and pH. The order of the peptides when ranked by increasing binding strength at pH 7.4 determined with MIS is shown to be in agreement with the order when ranked by the apparent 1st order absorption rate constant (k a ) after sc administration in humans: lanreotide (Autogel) < exenatide (IRF) < AZD2820 < pramlintide < lanreotide (IRF) (IRF: Immediate release formulation). A correlation is found between the 1st order release rate constant determined with SCISSOR and k a for lanreotide (Autogel), exenatide and AZD2820. A mechanism relating the magnitude of k a to the peptides' charge is proposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the analgesic effects of H-coil repetitive transcranial magnetic stimulation (rTMS) primarily targeting the hand area of the primary motor cortex (M1) in patients with peripheral neuropathic pain. Given that the H-coil has a wider reach than conventional coils, there is a possibility that targeting the hand motor cortex also may stimulate prefrontal areas. Thus, we also aimed to examine whether rTMS with an M1 target could produce effects on psychologic outcomes., Materials and Methods: In total, 17 patients were randomly assigned to receive active or sham H-coil rTMS in a counterbalanced order. After a nine-week washout period, they crossed over to either active or sham rTMS, according to a double-blind crossover design. Each treatment period consisted of five daily rTMS sessions and a one- and three-week follow-up visit. The primary outcome was average usual pain intensity. Secondary outcomes included pain unpleasantness, dynamic and static mechanical allodynia, anxiety and depression, sleep, pain catastrophizing, function, and patients' impression of change. Effects of rTMS were investigated using linear mixed model analyses., Results: We found two significant interactions between treatment and time, indicating that active H-coil rTMS induced significant analgesic effects (t [134] = -2.18; p = .03; d = -0.10) and significant reductions in anxiety and depression compared with sham stimulation over the treatment course (t [73] = -2.14; p = .04; d = -0.09). The analgesic effect occurred two weeks after the treatment, and the effect on anxiety and depression occurred three weeks after treatment. No other significant interactions were found for the secondary variables., Conclusions: Five days of H-coil rTMS targeting the hand area of M1 induced statistically significant effects on pain intensity. Moreover, rTMS improved symptoms of anxiety and depression, possibly because of the wide and deep reach of the H-coil., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT05488808., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declarations. Competing interests: None declared. Ethics approval: The study complies with the Helsinki Declaration. Written informed consent was obtained from all participants, except for the screening examination in 1963 where only oral informed consent was given (standard procedure at the time). The Research Ethics Board in Gothenburg, later the National Research Ethics Authority, approved the study protocol on several occasions (DNR 157–93, 0067–03, and DNR 649–13). Patient and public involvement: Patient and/or public were not involved in the design, conduct, reporting, or dissemination plans of this research. Patient consent for publication: Not applicable. Provenance and peer review: Not commissioned, externally peer reviewed., (© 2023. The Author(s).)

Subcutaneous (SC) injection is a common route of administration for drug compounds with poor oral bioavailability. However, bioavailability is often variable and incomplete, and there is as yet no standard accepted medium for simulation of the human SC environment. In this work we evaluate a FRAP based method for quantitative determination of local self-diffusion coefficients within extracellular matrix (ECM) mimetic hydrogels, potentially useful as in vitro models for drug transport in the ECM after SC injection. Gels were made consisting of either agarose, cross-linked collagen (COL) and hyaluronic acid (HA) or cross-linked HA. The diffusivities of uncharged FITC-dextran (FD4), the highly charged poly-lysine (PLK20) and poly-glutamic acid (PLE20) as well as the GLP-1 analogue exenatide were determined within the gels using FRAP. The diffusion coefficients in uncharged agarose gels were in the range of free diffusion in PBS. The diffusivity of cationic PLK20 in gels containing anionic HA was substantially decreased due to strong electrostatic interactions. Peptide aggregation could be observed as immobile fractions in experiments with exenatide. We conclude that the FRAP method provides useful information of peptides' interactions and transport properties in hydrogel networks, giving insight into the mechanisms affecting absorption of drug compounds after subcutaneous injection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Per Hansson reports financial support was provided by Sweden’s Innovation Agency. Helen Sjogren reports a relationship with Ferring Pharmaceuticals Inc that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Patients with congenital heart disease (CHD) have an increased risk of developing acquired cardiovascular diseases. However, the risk of venous thromboembolism (VTE) in patients with CHD is unknown. We aimed to investigate the incidence and risk of VTE in patients with CHD compared with matched controls without CHD., Methods and Results: Data from Swedish health registers were used to identify all patients with CHD between 1970 and 2017 in Sweden. Each patient with CHD was matched with 10 controls from the Swedish Total Population Register. The primary outcome of the study was an event of VTE. Follow-up was from birth until VTE, death, or the end of the study (2017). Cox proportional hazard models were used to investigate the risk of VTE in patients with CHD and controls. A total of 67 814 patients with CHD and 583 709 matched controls were identified and included in the study. During a mean follow-up of 15.9 (SD ± 12.5) years, 554 (0.8%) patients with CHD and 1571 (0.3%) controls developed VTE. The risk of VTE was 3.3 [95% confidence interval [CI] 2.6-3.4) times higher in patients with CHD than in controls. Patients with conotruncal defects had the highest risk of VTE (hazard ratio 7.06, 95% CI 5.52-9.03)., Conclusion: In our nationwide study, we found that the risk of VTE in patients with CHD was more than three times higher than in matched controls. The highest risk of VTE was in patients with the most complex lesions. Further research is crucial to clarify the underlying risk factors and prevent VTE in patients with CHD., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals., Methods and Results: The updated LIFE-CVD (i.e. LIFE-CVD2) models were derived using individual participant data from 44 cohorts in 13 countries (687 135 individuals without established CVD, 30 939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1 657 707 individuals (61 311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95% confidence interval 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (Clinical Practice Research Datalink) and the Netherlands (Extramural LUMC Academic Network). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example, a 50-year-old smoking woman with a systolic blood pressure (SBP) of 140 mmHg was estimated to gain 0.9 years in the low-risk region vs. 1.6 years in the very high-risk region from lifelong 10 mmHg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low-risk region to 4.8 years in the very high-risk region., Conclusion: By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines., Competing Interests: Conflict of interest: Due to the very long author list, these will be provided per author using ICMJE forms at the revision stage, if applicable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024. The Author(s).)

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 µm 2 /s) as compared to an agarose gel (501 ± 77 µm 2 /s, p = 0.019). The diffusion was further lowered to 256 ± 30 µm 2 /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., (© 2023. The Author(s).)

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

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 N 2 O 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 CO 2 -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 N 2 O 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

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., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., Competing Interests: All authors have completed the ICMJE uniform disclosure form. Luis Jara-Palomares: has received support for the present manuscript from MSD; grants from Leo Pharma; honoraria from Actelion Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Leo Pharma, MSD, Pfizer, ROVI, and Bristol-Myers Squibb. Isabelle Mahé: has received grants from BMS Pfizer; honoraria from BMS Pfizer, Leo Pharma, and Sanofi; support for attending meetings/travel from BMS Pfizer and Leo Pharma. Andrea Marshall: my institution received unrestricted educational grant from Bayer AG for the select-D trial. Remedios Otero Candelera: LEO-PHARMA was partially involved in the financial support to Hispalis Study without interfering in the intellectual conception, design and data analysis; received financial support for attendance to congresses and scientific meetings, payment to conferences or advisory board from BAYER HISPANIA, MSD, LEO-PHARMA and ROV; participated on a Data Safety Monitoring Board or Advisory Board. Frederikus Klok: has received research support from Bayer, Bristol-Myers Squibb, Actelion, Boston Scientific, Leo Pharma, PharmX, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe program, all outside this work and paid to his institution. Marieke Kruip: has received an unrestricted research grant from Sobi; research grants from Netherlands Thrombosis Foundation and the Netherlands Organization for Health Research and Development; speakers fee from Sobi, Roche, and BMS; all grants and fees are paid to her institution (Erasmus MC). Carin van der Rijt: has received a payment to the institution from the Netherlands Organization for Health Research and Development for a project on deprescription of medication at the end of life; is Chair of the Dutch Association for Professional Palliative Care (unpaid); is member of the Supervisory Board of the Foundation Roparun (attendance fee is paid). Eric Geijteman: has received an internal grant from the Erasmus MC (50.000 euro). This is a payment to finance this study (together with an interview- and questionnaire study about the perspectives of patient, caregivers and healthcare professionals on anticoagulation therapy). All other authors report no conflict of interest., (© 2023 The Author(s).)

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/m 2 , women with high normal weight, i.e. with a BMI of 22.5-25.0 kg/m 2 , 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/m 2 and ≥ 35 kg/m 2 (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., (© 2023. Springer Nature Limited.)

Abstract: Pain radiating from the spine into the leg is commonly referred to as "sciatica," "Sciatica" may include various conditions such as radicular pain or painful radiculopathy. It may be associated with significant consequences for the person living with the condition, imposing a reduced quality of life and substantial direct and indirect costs. The main challenges associated with a diagnosis of "sciatica" include those related to the inconsistent use of terminology for the diagnostic labels and the identification of neuropathic pain. These challenges hinder collective clinical and scientific understanding regarding these conditions. In this position paper, we describe the outcome of a working group commissioned by the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) which was tasked with the following objectives: (1) to revise the use of terminology for classifying spine-related leg pain and (2) to propose a way forward on the identification of neuropathic pain in the context of spine-related leg pain. The panel recommended discouraging the term "sciatica" for use in clinical practice and research without further specification of what it entails. The term "spine-related leg pain" is proposed as an umbrella term to include the case definitions of somatic referred pain and radicular pain with and without radiculopathy. The panel proposed an adaptation of the neuropathic pain grading system in the context of spine-related leg pain to facilitate the identification of neuropathic pain and initiation of specific management in this patient population., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

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., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Although injury burden prompts elite athletics (track and field) athletes to engage in injury management, little is known about their health literacy. We investigated musculoskeletal (MS) health literacy in world-leading athletics athletes and associations with prechampionship injury acknowledgement by reduction of training load in different socioeconomic environments., Methods: Adult and youth athletics athletes (n=1785) preparing for World Championships were invited to complete the Literacy in Musculoskeletal Problems instrument and report acknowledgement of injury by reduction in training load during prechampionship tapering. Their socioeconomic standing was estimated through the Human Development Index of their home country. Demographic differences were examined using χ 2 tests and determinants of injury acknowledgement assessed using logistic regression., Results: Complete data were obtained from 780 athletes (43.7%) with 26% demonstrating sufficient MS health literacy, higher in adult (41%) than youth (13%) athletes (p<0.001). Adult athletes at the uppermost socioeconomic level showed higher MS health literacy than athletes at lower socioeconomic levels (p<0.001). At the uppermost socioeconomic level, adult athletes with sufficient MS health literacy had increased likelihood of acknowledging an injury by reduction in training load compared with peers demonstrating insufficient MS health literacy (OR=2.45; 95% CI 1.33-4.53). Athletes at middle socioeconomic levels with sufficient MS health literacy had decreased likelihood for acknowledging an injury during tapering (OR=0.29; 95% CI 0.11-0.78)., Conclusions: The prevalence of sufficient MS health literacy in world-leading athletics athletes is low. Associations between MS health literacy and injury acknowledgement in these athletes vary with the resourcefulness of the socioeconomic environment, implying that health literacy and resources for medical and performance support should be ascertained concurrently., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023 The Authors. Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis.)

In this study, we examined knowledge and understanding of sport-related injuries among youth athletics (track and field) athletes and assessed their needs in managing any health problems. Qualitative data were collected via 12 focus groups with youth athletes (16-19 years) studying at Swedish sports high schools with an athletics specialism. All focus group discussions were audiorecorded and transcribed before being analysed using a thematic analysis approach. Four researchers independently reviewed the transcripts, generated codes and developed themes. Three overarching themes related to the athletes' knowledge and understanding of sport-related injury were developed: (1) awareness of injuries, (2) perception of injuries, and (3) factors contributing to injuries. The youth athletes were typically uncertain about how to acknowledge a sport-related injury. They expressed that knowledge about injuries was obtained in part by reflecting on the lived experiences of their peers. It was also demonstrated that there appears to be a 'culture of acceptance' regarding injury occurrence. In contrast, causes of injuries were viewed as dependent on multiple factors (eg, lack of context-specific knowledge about training practices). Regarding athletes' needs in managing injuries, an additional three themes were developed: (1) creating functioning elite sports environments, (2) application of knowledge and (3) fostering athletes. An apparent lack of structure and organisation related to the school environment was identified as an important issue to review to create opportunities for sustainable athletic development. The study identified areas that can be improved in Swedish sports high schools with an athletic specialism and could be applied in other youth sports contexts. The results of this study guide school stakeholders, alongside the sport governing bodies who have the mandate to influence activities in youth sports contexts, whereby special attention should be directed towards improving the social environment for youth athletes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To examine whether universal prevention via a digital health platform can reduce the injury incidence in athletics athletes aged 12-15 years and if club size had an influence on the effect of the intervention., Methods: This was a cluster randomised trial where young athletics athletes were randomised through their club following stratification by club size into intervention (11 clubs; 56 athletes) and control (10 clubs; 79 athletes) groups. The primary endpoint was time from baseline to the first self-reported injury. Intervention group parents and coaches were given access to a website with health information adapted to adolescent athletes and were encouraged to log in and explore its content during 16 weeks. The control group continued training as normal. Training exposure and injury data were self-reported by youths/parents every second week, that is, eight times. The primary endpoint data were analysed using the log-rank test. Cox proportional hazards regression was used to analyse the second study aim with intervention status and club size included in the explanatory models., Results: The proportion of completed training reports was 85% (n=382) in the intervention group and 86% (n=545) in the control group. The injury incidence was significantly lower (HR=0.62; χ 2 =3.865; p=0.049) in the intervention group. The median time to first injury was 16 weeks in the intervention group and 8 weeks in the control group. An interaction effect between the intervention and stratification factor was observed with a difference in injury risk between athletes in the large clubs in the intervention group versus their peers in the control group (HR 0.491 (95% CI 0.242 to 0.998); p=0.049)., Conclusions: A protective effect against injury through universal access to health information adapted for adolescent athletes was observed in youth athletics athletes. The efficacy of the intervention was stronger in large clubs., Trial Registration Number: NCT03459313., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cancer is a risk factor for venous thromboembolism (VTE). We aimed to define sex-specific risk of preceding cancer in patients with a first-time VTE by conducting a nationwide Swedish registry-based study including 298 172 patients with VTE and 1 185 079 matched controls. This included 44 685 patients with a diagnosis of cancer at/or within 1 year before a VTE diagnosis. Female patients with VTE had a higher multivariable adjusted odds ratios of preceding cancer than male patients with VTE (5.5 [99% confidence interval 5.4-5.7] vs 3.9 [3.8-4.0]). The highest risk of cancer in patients with VTE were found for pancreatic cancer (women: 19.6 [15.8-24.4]; men: 17.2 [13.7-21.6]) and brain cancer (women: 17.4 [12.9-23.4]; men: 17.5 [13.8-22.2]). Weak associations were seen between VTE and bladder/urothelial cancer (women: 1.31 [1.12-1.53]; men: 1.34 [1.23-1.47]), prostate cancer (men: 2.17 [2.07-2.27]), malignant melanoma (women: 2.51 [2.07-3.05]; men: 2.67 [2.23-3.18]), and kidney cancer (women: 3.20 [2.49-4.11]; men: 3.33 [2.79-4.07]). In conclusion, associations with VTE were weak for bladder/urothelial cancer and kidney cancer, and strong for pancreatic, brain, and biliary cancers.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke., Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank., Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min -1 ·1.73 m -2 , compared with those with eGFR between 60 and 105 mL·min -1 ·1.73 m -2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min -1 ·1.73 m -2 , with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min -1 ·1.73 m -2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min -1 ·1.73 m -2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD., Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Volume changes of responsive microgels can probe interactions between polyelectrolytes and species of opposite charges such as peptides and proteins. We have investigated a microfluidics method to synthesize highly responsive, covalently crosslinked, hyaluronic acid microgels for such purposes. Sodium hyaluronate (HA), pre-modified with ethylacrylamide functionalities, was crosslinked in aqueous droplets created with a microfluidic technique. We varied the microgel properties by changing the degree of modification and concentration of HA in the reaction mixture. The degree of modification was determined by 1 H NMR. Light microscopy was used to investigate the responsiveness of the microgels to osmotic stress in aqueous saline solutions by simultaneously monitoring individual microgel species in hydrodynamic traps. The permeability of the microgels to FITC-dextrans of molecular weights between 4 and 250 kDa was investigated using confocal laser scanning microscopy. The results show that the microgels were spherical with diameters between 100 and 500 µm and the responsivity tunable by changing the degree of modification and the HA concentration. Microgels were fully permeable to all investigated FITC-dextran probes. The partitioning to the microgel from an aqueous solution decreased with the increasing molecular weight of the probe, which is in qualitative agreement with theories of homogeneous gel networks.

Agricultural land use and management practices affect the global climate due to greenhouse gas (GHG) fluxes and changes in land surface properties. Increased albedo has the potential to counteract the radiative forcing and warming effect of emitted GHGs. Thus considering albedo could be important to evaluate and improve agricultural systems in light of climate change, but the albedo of individual practices is usually not known. This study quantified the albedo of individual crops under regional conditions, and evaluated the importance of albedo change for the climate impact of current crop production using life cycle assessment (LCA). Seven major crops in southern Sweden were assessed relative to a land reference without cultivation, represented by semi-natural grassland. Crop-specific albedo data were obtained from a MODIS product (MCD43A1 v6), by combining its spatial response pattern with geodata on agricultural land use 2011-2020. Fluxes of GHGs were estimated using regional data and models, including production of inputs, field operations, and soil nitrogen and carbon balances. Ten-year mean albedo was 6-11% higher under the different crops than under the reference. Crop-specific albedo varied between years due to weather fluctuations, but differences between crops were largely consistent. Increased albedo countered the GHG impact from production of inputs and field operations by 17-47% measured in GWP 100 , and the total climate impact was warming. Using a time-dependent metric, all crops had a net cooling impact on global mean surface temperature on shorter timescales due to albedo (3-12 years under different crops), but a net warming impact on longer timescales due to GHG emissions. The methods and data presented in this study could support increasingly comprehensive assessments of agricultural systems. Further research is needed to integrate climatic effects of land use on different spatial and temporal scales, and direct and indirect consequences from a systems perspective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Among patients assessed by the emergency medical service (EMS) and hospitalized with a final diagnosis of stroke, to describe delays, patient characteristics, actions taken and outcome in relation to the early recognition of stroke by the EMS clinician., Methods: Patients admitted to any of six stroke units in Region Västra Götaland, Sweden, with a final diagnosis of stroke from 1 January 2013 to 31 December 2015 were included. Data on follow-up were retrieved from the Swedish Stroke Register., Results: In all, 5467 patients were included. Stroke was recognized by the EMS clinician in 4396 cases (80.4%). The mean difference in the time from dialling 112 until arrival at the stroke unit was 556 min shorter when stroke was recognized, while the mean difference in the time from dialling 112 until a preliminary report from a computed tomography (CT) scan was 219 min shorter as compared with the patients in whom stroke was not recognized. After adjustment for age, sex, neurological deficits and coma, a lack of suspicion of stroke on EMS arrival was associated with an increased risk of death during three months of follow-up (odds ratio 1.66; 95% confidence interval 1.19-2.32; p = .003)., Conclusion: Among patients with a stroke, more than 80% were recognized by the EMS clinician. Early recognition of stroke was associated with a markedly shorter time until arrival at the stroke unit and until the preliminary report of a CT scan. A lack of early stroke recognition was associated with an increased risk of death., (© 2022 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Reduced left ventricular ejection fraction (LVEF) is associated with increased mortality after acute myocardial infarction (AMI). However, the prognostic impact of elevated systolic pulmonary artery pressure (sPAP) in the very elderly patients after AMI is lacking. We aimed to study the impact of elevated sPAP on one- and five-year all-cause mortality after AMI in very elderly patients, 80 years of age and older. Of a total number of 353 patients (≥ 80 years) who were hospitalized with acute coronary syndrome, 162 patients presenting with AMI and with available data of sPAP on echocardiography were included and followed-up for 5 years. The survival analyses were performed using Cox-Regression models adjusted for conventional risk factors including LVEF. Altogether 66 of 162 patients (41%) had ST-segment elevation MI, and 121 (75%) of patients were treated with percutaneous coronary intervention in the acute phase. Echocardiography during the admission revealed that 78 patients (48%) had a LVEF ≤ 45% and 66 patients (41%) had a sPAP ≥ 40 mmHg. After one and five years of follow-up, 23% (n = 33) and 53% (n = 86) of patients died, respectively. A multivariable Cox-Regression analysis showed that the elevated sPAP (≥ 40 mmHg) was an independent predictor of increased mortality in both one and five years after AMI; HR of 2.63 (95%, CI 1.19-5.84, P 0.017) and HR of 2.08 (95%, CI 1.25-3.44, P 0.005) respectively, whereas LVEF ≤ 45% did not show any statistically significant impact, neither on one- nor on five-year mortality (HR 1.3, 95% CI 0.6-2.9, p = 0.469) and (HR 1.4, 95% CI 0.8-2.4, p = 0.158), respectively. Elevated sPAP was an independent risk factor for one- and five-year all-cause mortality after AMI in very elderly patients and sPAP seems to be a better prognostic predictor for all-cause mortality than LVEF. The risk of all-cause mortality after AMI increased with increasing sPAP., (© 2022. The Author(s).)

Abstract: Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Subcutaneous injection is one of the most common approaches for administering biopharmaceuticals unsuitable for oral delivery. However, there is a lack of methods to predict the behavior of biopharmaceuticals within the extracellular matrix of the subcutaneous tissue. In this work, we present a novel miniaturized microfluidic-based in vitro method able to investigate interactions between drug molecules and the polymers of the subcutaneous extracellular matrix. To validate the method, microgels consisting of, respectively, covalently cross-linked hyaluronic acid, polyacrylic acid, and commercially available DC Bead™, were exposed to three model substances: cytochrome C, protamine sulfate and amitriptyline hydrochloride. These components were chosen to include systems with widely different physiochemical properties (charge, size, self-assembly, etc.) The experimental results were compared with theoretical predictions from a gel model developed earlier. The results show that the method is suitable as a rapid screening method for automated, large-scale, probing of interactions between biopolymers and drug molecules, with small consumption of material., (Copyright © 2022. Published by Elsevier B.V.)

Background: Knowledge on differences in patients who present with deep vein thrombosis (DVT) and those with pulmonary embolism (PE) is incomplete., Objective: To determine comorbidities and temporary provoking factors in patients with a first-time PE or DVT., Methods: This was a nationwide Swedish registry-based, retrospective, case-control study including 298 172 patients with first-time venous thromboembolism (VTE) and 1 185 079 controls matched for age, sex, and county of residence, free of VTE at the time of matching., Results: Patients with PE were older than those with DVT (mean age, 69 vs 66 years) and included slightly more women (PE, 53.4% vs DVT, 52.1%). After multivariable adjustment for comorbidities (within 7 years) and temporary provoking factors (within 3 months), heart failure (PE: adjusted odds ratio [aOR], 2.64 [99% confidence interval [CI], 2.55-2.73]; DVT: aOR, 1.66 [99% CI, 1.60-1.72]), ischemic heart disease (PE: aOR, 1.51 [99% CI, 1.47-1.56]; DVT: aOR, 1.01 [99% CI, 0.98-1.04]), and chronic obstructive pulmonary disease (PE: aOR, 2.51 [99% CI, 2.40-2.63]; DVT, 1.54 [99% CI, 1.47-1.62]) were among diseases that showed higher odds ratios in patients with PE than in those with DVT, compared with controls. Comorbidities registered within 6 months were associated with higher aORs than those within 7 years. The highest population attributable risks for PE were for cancer (13.0%) and heart failure (11.7%)., Conclusion: Cardiopulmonary diseases, particularly with recent onset, imply a higher risk for PE, whereas orthopedic surgery and lower-extremity fractures carry a higher risk of DVT., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Hydrogels of varying complexity are routinely used as scaffolds and 3D structures for in vitro tumor models to increase physiological relevance within pre-clinical cancer research. Relatively simple hydrogels such as agarose are well characterised, meanwhile biomimetic gels containing collagen and fibrin(ogen) have been studied to a much lesser extent. In this study, hydrogels mimicking the biophysical characteristics of liver cancer progression were investigated in terms of their UV-properties and influence on diffusion coefficients of different substances. UV-imaging technology was used to both visualize and quantify the diffusion process in a simple and rapid way. In general, agarose gel diffusion agreed well with predictions using the Stokes-Einstein equation meanwhile the biomimetic gels reduced diffusion coefficients by up to 70%. For doxorubicin, spatio-temporal tissue concentration modelling was used to translate in vitro diffusion to the more clinical context of tumor penetration in a solid liver tumor supplied by arterial blood., (Copyright © 2022. Published by Elsevier B.V.)

Background: Body iron stores (BISs) have been proposed to be related to the development of cardiovascular diseases. However, results from epidemiological studies are conflicting. Knowledge on the long-term impact of BIS on cardiovascular outcomes in the general population is lacking., Purpose: The aim of this study was to explore the relationship between BIS and coronary heart disease (CHD) including death due to CHD., Methods: This investigation is part of 'The Study of Men Born in 1943', a longitudinal prospective study of men living in the city of Gothenburg, Sweden. This random population sample was examined in 1993 (all at 50 years of age at baseline). A medical examination was performed, and questionnaires were used to evaluate lifestyle factors. Biomarkers for iron stores (serum ferritin and serum transferrin receptor) was analysed from frozen blood samples in 2014. All hospital admissions were registered through national registers during the entire follow-up from 1993 to 2014. HRs were estimated by Cox proportional-hazard regression analyses., Results: During the 21 years follow-up period, 120 participants (15.2%) developed CHD and 16 patients (2%) died due to CHD. The all-cause mortality was 15.2% (n=120) including 40 cardiovascular deaths (5.1%). In a multivariable Cox regression analysis, the daily smoking, hypertension and the increased resting heart rate was independent predictors of CHD, while no significant association was found between BIS and risk of CHD., Conclusions: In a cohort of middle-aged men from the general population with well validated and prospectively collected data, we did not find any association between serum ferritin or serum transferrin receptor as markers of BIS and CHD events after 21 years of follow-up., Trail Registration Number: NCT03138122., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The analgesic action of localized vibration (LV), which is used in rehabilitation medicine to treat various clinical conditions, is usually attributed to spinal gate control, but is actually more complex. The aim of this review is: 1) to provide neurophysiological insights into the mechanisms underlying the ways in which afferent activity set up by LV induces analgesia through interactions with the nociceptive system throughout the nervous system; 2) to give a broader vision of the different effects induced by LV, some of them still related to basic science speculation., Evidence Acquisition: The Medline, EMBASE, AMED, Cochrane Library, CINAHL, Web of Science and ROAD databases were searched for animal and human neurophysiological and neurohormonal studies related to the direct effects of LV on nociceptive transmission and pain perception and were supplemented by published books and theses., Evidence Synthesis: The spinal gate control mechanism through Aβ-fibers activation seems to be the most effective antinociceptive system activated by LV at frequencies between 100 and 250 Hz (high-frequency LV [HF-LV]) when applied in the same segment as the pain. A gating effect can be obtained also when it is applied contralaterally to the painful site or to adjacent dermatomes. Kinesthetic illusions of movement induced by HF-LV may induce a stronger analgesic effect. Activation of C-mechanoreceptors induced by a massage-like LV of low frequency and low intensity may interfere with pain through the activation of the limbic system. This action does not involve any gating mechanism. Frequency is more important than intensity as different frequencies induce activity in different cortical and cerebellar areas; these activations may be related to plastic cortical changes tentatively reversing pain-related maladaptive disorganization. Distraction/shift of attention or cortisol-mediated stress-induced analgesia are not involved in LV analgesic action in humans for both LF and HF. The release of opioidergic neuropeptides (analgesia not reversed by naloxone) as well as a reduction in substance P in the CSF does not seem to play a major role in the HF-LV action. Decrease in calcitonin and TRPV1 expression in the trigeminal ganglia in animals has been induced by HF-LV but the role of LF-LV is not completely deciphered. Both high and low LV induce the release of oxytocin, which may induce antinociceptive responses in animals and contribute to controlling pain in humans., Conclusions: Although many aspects of LV-induced pain alleviation deserve more in-depth basic and translational studies, there are sound neurophysiological reasons for using LV in the therapeutic armamentarium of pain control. Laboratory animal and human data indicate that LV relieves pain not only by acting on the spinal gate, but also at higher levels of the nervous system.

Nerve conduction studies (NCS) are an essential aspect of the assessment of patients with peripheral neuropathies. However, conventional NCS do not reflect activation of small afferent fibers, including Aδ and C fibers. A definitive gold standard for laboratory evaluation of these fibers is still needed and therefore, clinical evaluation remains fundamental in patients with small fiber neuropathies (SFN). Several clinical and research techniques have been developed for the assessment of small fiber function, such as (i) microneurography, (ii) laser evoked potentials, (iii) contact heat evoked potentials, (iv) pain-related electrically evoked potentials, (v) quantitative thermal sensory testing, (vi) skin biopsy-intraepidermal nerve fiber density and (vii) corneal confocal microscopy. The first five are physiological techniques, while the last two are morphological. They all have advantages and limitations, but the combined use of an appropriate selection of each of them would lead to gathering invaluable information for the diagnosis of SFN. In this review, we present an update on techniques available for the study of small afferent fibers and their clinical applicability. A summary of the anatomy and important physiological aspects of these pathways, and the clinical manifestations of their dysfunction is also included, in order to have a minimal common background., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: The prevalence of dementia is growing rapidly worldwide. The early identification and treatment of cognitive decline could reduce the burden on the health care system. Our objective was to investigate whether factors measured at an examination at age 50 predict cognitive impairment (CI) 23 years later., Materials & Methods: In 1993 we enrolled a randomly selected sample of 798 men, 50 years of age, from the general population. They all underwent a physical examination, provided blood samples and filled out questionnaires addressing lifestyle and psychosocial factors. Cognitive testing was offered to all participants still alive in 2016, at age 73., Results: A total of 333 men participated in the cognitive study, of which 80 (24.0%) performed at a level corresponding to mild cognitive impairment, and four (1.2%) at a level consistent with severe cognitive impairment. After the first step in the multivariable analysis, hypertension, heavy smoking, high intake of alcohol, financial stress, difficulty falling asleep, and cogwheel rigidity were associated with cognitive impairment. After further adjustment, only wide waist circumference measured in cm (OR 1.04, 95% CI 1.00-1.08, p = .04), leg pendulousness (OR 41.97, 95% CI 3.27-538.62, p = .004) and self-assessed hidden irritability (OR 2.18, 95% CI 1.10-4.32, p = .03) at baseline, remained as being associated with cognitive impairment 23 years later., Conclusions: Extrapyramidal symptoms such as leg pendulousness, at the age of 50, may be an indicator for very early identification of future cognitive decline., (© 2021 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Polyelectrolyte microgels may undergo volume phase transition upon loading and the release of amphiphilic molecules, a process important in drug delivery. The new phase is "born" in the outermost gel layers, whereby it grows inward as a shell with a sharp boundary to the "mother" phase (core). The swelling and collapse transitions have previously been studied with microgels in large solution volumes, where they go to completion. Our hypothesis is that the boundary between core and shell is stabilized by thermodynamic factors, and thus that collapsed and swollen phases should be able to also coexist at equilibrium. We investigated the interaction between sodium polyacrylate (PA) microgel networks (diameter: 400-850 µm) and the amphiphilic drug amitriptyline hydrochloride (AMT) in the presence of NaCl/phosphate buffer of ionic strength (I) 10 and 155 mM. We used a specially constructed microscopy cell and micromanipulators to study the size and internal morphology of single microgels equilibrated in small liquid volumes of AMT solution. To probe the distribution of AMT micelles we used the fluorescent probe rhodamine B. The amount of AMT in the microgel was determined by a spectrophotometric technique. In separate experiments we studied the binding of AMT and the distribution between different microgels in a suspension. We found that collapsed, AMT-rich, and swollen AMT-lean phases coexisted in equilibrium or as long-lived metastable states at intermediate drug loading levels. In single microgels at I = 10 mM, the collapsed phase formed after loading deviated from the core-shell configuration by forming either discrete domains near the gel boundary or a calotte shaped domain. At I = 155 mM, single microgels, initially fully collapsed, displayed a swollen shell and a collapsed core after partial release of the AMT load. Suspensions displayed a bimodal distribution of swollen and collapsed microgels. The results support the hypothesis that the boundary between collapsed and swollen phases in the same microgel is stabilized by thermodynamic factors.

We aimed to identify determinants in acute stroke that are associated with falls during the stroke unit stay. In order to enable individualized preventive actions, this knowledge is fundamental. Based on local and national quality register data on an unselected sample of 5065 stroke patients admitted to a stroke unit at a Swedish university hospital, univariable and multivariable logistic regression analyses were performed. The dependent variable was any fall during stroke unit stay. The independent variables related to function, activity, personal factors, time to assessment, comorbidities and treatments. Determinants of falls were: being male (odds ratio (OR) 2.25, 95% confidence interval (95% CI) 1.79-2.84), haemorrhagic stroke (OR 1.39, 95% CI 1.05-1.86), moderate stroke symptoms according to the National Institutes of Health Stroke Scale (NIHSS score 2-5 vs. NIHSS score 0-1) (OR 1.43, 95% CI 1.08-1.90), smoking (OR 1.70, 95% CI 1.29-2.25), impaired postural control in walking (OR 4.61, 95% CI 3.29-6.46), impaired postural control in standing (OR 1.60, 95% CI 1.25-2.05), stroke-related arm- and hand problems, OR 1.45, 95% CI 1.11-1.91), impaired cognition (OR 1.43, 95% CI 1.04-1.95), and urinary tract infection (OR 1.91, 95% CI 1.43-2.56). The findings from this study are useful in clinical practice and might help to improve patient safety after stroke., (© 2021. The Author(s).)

Aims: Atrial fibrillation (AF) is associated with arterial thromboembolism, mainly ischaemic stroke, while venous thromboembolism (VTE) in AF is less well studied. The aim of this study, therefore, was to examine the relationship between AF and VTE, including pulmonary embolism (PE) and deep venous thrombosis (DVT)., Methods and Results: AF cases without previous VTE, ischaemic stroke or pulmonary arterial hypertension were identified from the Swedish Inpatient Registry between 1987 and 2013 and compared to two population controls per case without AF matched for age, sex, and county with respect to the incidence of VTE, PE, and DVT. In total, 463 244 AF cases were compared to 887 336 population controls. In both men and women, VTE rates were higher among AF patients the first 30 days after an AF diagnosis [40.2 vs. 5.7 in men and 55.7 vs. 6.6 in women per 1000 person-years at risk, respectively; hazard ratios 6.64 (95% confidence interval, 5.74-7.69) and 7.56 (6.47-8.83)]; and then decreasing, simultaneously with an increasing number of AF patients being treated with oral anticoagulation. VTE risk was similar to controls after 9 months in men but remained slightly elevated in women., Conclusion: AF is strongly associated with an increased risk of VTE during the first months after diagnosis. Introduction of anticoagulant therapy soon after AF diagnosis might reduce the risk of VTE as well as of ischaemic stroke., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Hypothesis: Common amphiphilic drug molecules often have a more rigid nonpolar part than conventional surfactants. The rigidity is expected to influence the self-assembling properties and possibly give rise to aggregation patterns different from that of regular surfactants., Experiments: We have investigated self-assembling properties of the hydrochloride salts of adiphenine (ADP), pavatrine (PVT), and amitriptyline (AMT) at concentrations up to 50 wt% using small-angle x-ray scattering, dynamic light scattering, cryo-transmission electron microscopy, and surface tension measurements., Findings: All drugs form small micelles of oblate spheroidal shape at concentrations above the critical micelle concentrations (CMC). The micelles grow weakly in size up to about 20 wt%, where the aggregation number reaches a maximum followed by a slight decrease in size at higher drug concentrations. We observe a correlation between the decrease in micelle size at high concentrations and an increasing charge of the micelles, as the degree of ionization increases with increasing drug concentration and decreasing pH. In contrast to what has previously been reported, the aggregation behavior of all studied drugs resembles the closed association behavior of conventional surfactants with a short aliphatic chain as hydrophobic tail group i.e. the micelles are always small in size and lack a second CMC. CMC values were determined with surface tension measurements, including also lidocaine hydrochloride (LDC) and chlorpromazine hydrochloride (CHL)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is the most important cause of death and life-years lost in Sweden today. Cardiovascular risk prediction is a cornerstone in primary prevention; the use of antihypertensive and lipid-lowering therapy is guided by absolute cardiovascular risk. The Systematic COronary Risk Evaluation (SCORE) model has been the most widely applied model in Sweden for almost two decades. Recently, an updated model called SCORE2 was published. The new risk prediction model is based on contemporary data, predicts the risk of incident cardiovascular disease in addition to cardiovascular mortality, and accounts for competing risks, thus overcoming some major limitations with SCORE. Sweden is classified as a moderate-risk country according to the new model; here we report the risk chart for moderate-risk countries translated into Swedish.

Objective: To determine the incidence of physical inactivity and factors prior to stroke and in acute stroke that are associated with physical inactivity 1 year after stroke Design: Prospective longitudinal cohort Patients: A total of 190 consecutively included individuals with acute stroke Methods: A follow-up questionnaire, relating to physical activity level using the Saltin-Grimby Physical Activity Scale, was sent to participants in The Fall Study of Gothenburg 1 year after stroke. Predictors of physical inactivity at baseline were identified using univariable and multivariable logistic regression analyses., Results: Physical inactivity 1 year after stroke was reported by 70 (37%) of the 190 patients who answered the questionnaire and was associated with physical inactivity before the stroke, odds ratio (OR) 4.07 (95% confidence interval (95% CI) 1.69-9.80, p = 0.002); stroke severity (assessed by National Institutes of Health Stroke Scale (NIHSS), score 1-4), OR 2.65 (95% CI) 1.04-6.80, p = 0.042) and fear of falling in acute stroke, OR 2.37 (95% CI 1.01-5.60, p = 0.048)., Conclusion: Almost 4 in 10 participants reported physical inactivity 1 year after stroke. Physical inactivity before the stroke, stroke severity and fear of falling in acute stroke are the 3 main factors that predict physical inactivity 1 year after stroke.

Objective: To test whether contralateral sensory abnormalities in the clinically unaffected area of patients with unilateral neuropathic pain are due to the neuropathy or pain mechanisms., Methods: We analyzed the contralateral clinically unaffected side of patients with unilateral painful or painless neuropathy (peripheral nerve injury [PNI], postherpetic neuropathy [PHN], radiculopathy) by standardized quantitative sensory testing following a validated protocol. Primary outcome was the independent contribution of the following variables on the contralateral sensory function using generalized linear regression models: pain intensity, disease duration, etiology, body area, and sensory patterns in the most painful area., Results: Among 424 patients (PNI n = 256, PHN n = 78, radiculopathy n = 90), contralateral sensory abnormalities were frequent in both painful (n = 383) and painless (n = 41) unilateral neuropathy, demonstrating sensory loss for thermal and mechanical nonpainful stimuli and both sensory loss and gain for painful test stimuli. Analysis by etiology revealed contralateral pinprick hyperalgesia in PHN and PNI. Analysis by ipsilateral sensory phenotype demonstrated mirror-image pinprick hyperalgesia in both mechanical and thermal hyperalgesia phenotypes. Pain intensity, etiology, and affected body region predicted changes in only single contralateral somatosensory parameters. Disease duration had no impact on the contralateral sensory function., Conclusion: Mechanisms of sensory loss seem to spread to the contralateral side in both painful and painless neuropathies. Contralateral spread of pinprick hyperalgesia was restricted to the 2 ipsilateral phenotypes that suggest sensitization; this suggest a contribution of descending net facilitation from supraspinal areas, which was reported in rodent models of neuropathic pain but not yet in human patients., (© 2021 American Academy of Neurology.)