Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark.

BACKGROUND: Bone and joint infections (BJIs) are treated with intravenous antibiotics, which are burdensome and costly. No randomised controlled studies have compared if initial oral antibiotics are as effective as intravenous therapy. We aimed to investigate the efficacy and safety of initial oral antibiotics compared with initial intravenous antibiotics followed by oral antibiotics in children and adolescents with uncomplicated BJIs. METHODS: From Sept 15, 2020, to June 30, 2023, this nationwide, randomised, non-inferiority trial included patients aged 3 months to 17 years with BJIs who presented to one of the 18 paediatric hospital departments in Denmark. Exclusion criteria were severe infection (ie, septic shock, the need for acute surgery, or substantial soft tissue involvement), prosthetic material, comorbidity, previous BJIs, or antibiotic therapy for longer than 24 h before inclusion. Patients were randomly assigned (1:1), stratified by C-reactive protein concentration (<35 mg/L vs ≥35 mg/L), to initially receive either high-dose oral antibiotics or intravenous ceftriaxone (100 mg/kg per day in one dose). High-dose oral antibiotics were coformulated amoxicillin (100 mg/kg per day) and clavulanic acid (12·5 mg/kg per day) in three doses for patients younger than 5 years or dicloxacillin (200 mg/kg per day) in four doses for patients aged 5 years or older. After a minimum of 3 days, and upon clinical improvement and decrease in C-reactive protein, patients in both groups received oral antibiotics in standard doses. The primary outcome was sequelae after 6 months in patients with BJIs, defined as any atypical mobility or function of the affected bone or joint, assessed blindly, in all randomised patients who were not terminated early due to an alternative diagnosis (ie, not BJI) and who attended the primary outcome assessment. A risk difference in sequelae after 6 months of less than 5% implied non-inferiority of the oral treatment. Safety outcomes were serious complications, the need for surgery after initiation of antibiotics, and treatment-related adverse events in the as-randomised population. This trial was registered with ClinicalTrials.gov, NCT04563325. FINDINGS: 248 children and adolescents with suspected BJIs were randomly assigned to initial oral antibiotics (n=123) or initial intravenous antibiotics (n=125). After exclusion of patients without BJIs (n=54) or consent withdrawal (n=2), 101 patients randomised to oral treatment and 91 patients randomised to intravenous treatment were included. Ten patients did not attend the primary outcome evaluation. Sequelae after 6 months occurred in none of 98 patients with BJIs in the oral group and none of 84 patients with BJIs in the intravenous group (risk difference 0, one-sided 97·5% CI 0·0 to 3·8, pnon-inferiority=0·012). Surgery after randomisation was done in 12 (9·8%) of 123 patients in the oral group compared with seven (5·6%) of 125 patients in the intravenous group (risk difference 4·2%, 95% CI -2·7 to 11·5). We observed no serious complications. Rates of adverse events were similar across both treatment groups. INTERPRETATION: In children and adolescents with uncomplicated BJIs, initial oral antibiotic treatment was non-inferior to initial intravenous antibiotics followed by oral therapy. The results are promising for oral treatment of uncomplicated BJIs, precluding the need for intravenous catheters and aligning with the principles of antimicrobial stewardship. FUNDING: Innovation Fund Denmark and Rigshospitalets Forskningsfond.

Impact of COVID-19 Restrictions on Acute Gastroenteritis in Children: A Regional, Danish, Register-Based Study.

This study aimed to evaluate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) restrictions such as social distancing on the occurrence of acute gastroenteritis (AGE) among children. This study is a register-based study, including every child seen in the departments of paediatrics with the initial diagnosis of AGE in three neighbouring hospitals in Denmark, from March 2018 through February 2021. The study also included every positive stool sample for AGE-causing pathogens analysed in these three hospitals from children during the same period. The Wilcoxon rank-sum test was used to determine differences between the period during the SARS-CoV-2 restrictions and before. In all, 222,157 children were seen in the three paediatric departments during this period. Of these, 3917 children were diagnosed with AGE. We found a decrease of 46.6% in AGE-related visits per month after the SARS-CoV-2 restrictions were introduced compared to before (p-value < 0.001). Positive stool samples decreased by 38.2% (p-value = 0.008) during the restrictions. This study found that cases of paediatric AGE decreased significantly the during COVID-19 restrictions, suggesting that studies should be conducted to determine whether this reduction was a result of good hand hygiene and social distancing or just a result of altered health-seeking behaviour among children.

Addition of point-of-care test reduces antibiotic prescription in hospitalised children with suspected respiratory tract infection: A pre-test-post-test study.

AIM: Prompt and accurate aetiological diagnostics are needed if physicians are to improve and target antibiotic treatment. We aimed to investigate whether antibiotic-prescribing decisions are improved with availability of point-of-care polymerase chain reaction (POC-PCR) diagnostic testing of children with suspected respiratory tract infection, and if it had an impact on referral for additional medical procedures. METHODS: This was a single-centre one-group pre-test-post-test study. Children visiting our paediatric department with respiratory tract infection symptoms were included if the treating paediatrician was considering an antibiotic prescription. Throat swabs were analysed for pathogens using POC-PCR. The paediatrician registered treatment decisions, referrals for additional procedures and decisions about hospitalisation into a questionnaire before and after receiving the POC-PCR results. RESULTS: We included 95 children. The availability of results from POC-PCR analysis significantly changed the prescribed antibiotic treatment to non-antibiotic treatment in 46% (36%-56%) of the children and the reverse in 2% (1%-8%). Paediatricians referred significantly fewer patients to additional medical procedures with availability of POC-PCR. CONCLUSION: POC-PCR significantly reduced the odds of antibiotic prescription and referral for additional medical procedures. Thus, POC-PCR presents an opportunity to improve antibiotic-prescribing practices if it is combined with standard clinical evaluation.

Patient-Initiated Follow-Up (PIFU) as reorganized support for increased patient involvement - focus group discussions among patients' with inflammatory arthritis.

BACKGROUND: Inflammatory Arthritis is characterized by lifelong medical treatment and an unpredictable trajectory because of the fluctuating nature of the diseases. Proactive disease management is recommended, which includes close monitoring of disease activity that traditionally has been ensured by outpatient visits to rheumatologists at various fixed intervals. Internationally, there is a growing interest in how healthcare systems can be more flexible, individual-oriented and increasingly involve patients with lifelong diseases in their own treatment and care. We aimed to explore how patients with Inflammatory Arthritis with low disease activity or remission (DAS-CRP < 2.9) experience patient involvement in a reorganized follow-up care based on flexibility and patient-initiated contact. METHODS: We conducted a qualitative study based on four mixed group discussions focused on patients with inflammatory arthritis (rheumatoid arthritis [n = 21], axial spondyloarthritis [n = 3] and psoriatic arthritis [n = 1]) participating in a reorganized follow-up care. Changes in follow-up included access to a nurse and patient-initiated follow-up (PIFU). The analysis was based on content analysis. The reporting adheres to the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS: In total, 25 patients (20 females (80%), mean age 61.8 [range 28-79]) participated. We identified three categories. 1) Patient-Initiated Follow-Up do not affect patients' perceived support in disease control; this refers to patients' experience of more time available through better resource utilization, as well as trust that access to professional support would be available whenever needed. The category 2) Information is valued by patients to delineate responsibilities in a new patient role reflects patients' uncertainty in the transition to PIFU, combined with confusion about the distribution of responsibilities. 3) Patients need both extended perspectives of their arthritis and focused dialogue is about expanding patients' understanding of their arthritis by interaction over time with both a rheumatologist and a rheumatology nurse in a focused dialogue to involve the patient. CONCLUSIONS: Patients participating in PIFU welcome the flexibility and involvement. However, patients need relevant information to act adequately within a new patient role. Interaction with both rheumatologists and nurses, combined with sufficient time for dialogue, broaden patients' perspective, make opportunities for action visible, and contribute to patients' ability to participate in follow-up care.

Patient baseline interpersonal problems as moderators of outcome in two psychotherapies for bulimia nervosa.

Objective: We tested an aptitude by treatment interaction; namely, whether patients' baseline interpersonal problems moderated the comparative efficacy of cognitive-behavioral therapy (CBT) vs. interpersonal psychotherapy (IPT) for bulimia nervosa (BN). Method: Data derived from a randomized-controlled trial. Patients reported on their interpersonal problems at baseline; purge frequency at baseline, midtreatment, and posttreatment; and global eating disorder severity at baseline and posttreatment. We estimated the rate of change in purge frequency across therapy, and the likelihood of attaining clinically meaningful improvement (recovery) in global eating disorder severity by posttreatment. We then tested the interpersonal problem by treatment interactions as predictors of both outcomes. Results: Patients with more baseline overly communal/friendly problems showed steeper reduction in likelihood of purging when treated with CBT vs. IPT. Patients with more problems of being under communal/cold had similar reductions in likelihood of purging across both treatments. Patients with more baseline problems of being overly agentic were more likely to recover when treated with IPT vs. CBT, whereas patients with more problems of being under agentic were more likely to recover when treated with CBT vs. IPT. Conclusions: Interpersonal problems related to communion and agency may inform treatment fit among two empirically supported therapies for BN.

The danish regions pediatric triage model has a limited ability to detect both critically ill children as well as children to be sent home without treatment - a study of diagnostic accuracy.

BACKGROUND: The Danish Regions Pediatric Triage model (DRPT) was introduced in 2012 and subsequent implemented in most Danish acute pediatric departments. The aim was to evaluate the validity of DRPT as a screening tool to detect both the most serious acute conditions and the non-serious conditions in the acute referred patients in a pediatric department. METHOD: The study was prospective observational, with follow-up on all children with acute referral to pediatric department from October to December 2015. The DRPT was evaluated by comparison to a predefined reference standard and to the actual clinical outcomes: critically ill children and children returned to home without any treatment. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and likelihood for positive and negative test were calculated. RESULTS: Five hundred fifty children were included. The DRPT categorized 7% very urgent, 28% urgent, 29% standard and 36% non-urgent. The DRPT was equal to the reference standard in 31% of the children (CI: 27-35%). DRPT undertriaged 55% of the children (CI: 51-59%) and overtriaged 14% of the children (CI: 11-17%). For the most urgent patients the sensitivity of DRPT was 31% (CI: 20-48%) compared to the reference standard and 20% (CI: 7-41) for critically ill. For children with non-urgent conditions the specificity of DRPT was 66% (CI: 62-71%) compared to the reference standard and 68% (CI: 62-75%) for the children who went home with no treatment. In none of the analyses, the likelihood ratio of the negative test was less than 0.7 and the positive likelihood ratio only reached more than 5 in one of the analyses. DISCUSSION: This study is the first to evaluate the DRPT triage system. From the very limited validity studies of other well-established triage systems, it is difficult to judge whether the DRPT performs better or worse than the alternatives. The DRPT errs to the undertriage side. If the sensitivity is low, a number of the sickest children are undetected and this is a matter of concern. CONCLUSION: The DRPT is a triage tool with limited ability to detect the critically ill children as well as the children who can be returned to home without any treatment. TRIAL REGISTRATION: Not relevant.

Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts: implications for development of an atheroprotective vaccine.

Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use as an immunogen would be impractical for generalized use. Furthermore, when MDA is used to modify LDL, a wide variety of related MDA adducts are formed, both simple and more complex. To define the relevant epitopes that would reproduce the atheroprotective effects of immunization with MDA-LDL, we sought to determine the responsible immunodominant and atheroprotective adducts. We now demonstrate that fluorescent adducts of MDA involving the condensation of two or more MDA molecules with lysine to form malondialdehyde-acetaldehyde (MAA)-type adducts generate immunodominant epitopes that lead to atheroprotective responses. We further demonstrate that a T helper (Th) 2-biased hapten-specific humoral and cellular response is sufficient, and thus, MAA-modified homologous albumin is an equally effective immunogen. We further show that such Th2-biased humoral responses per se are not atheroprotective if they do not target relevant antigens. These data demonstrate the feasibility of development of a small-molecule immunogen that could stimulate MAA-specific immune responses, which could be used to develop a vaccine approach to retard or prevent atherogenesis.

Pain and discomfort in closure of femoral access coronary angiography. The CLOSuredEvices Used in everyday Practice (CLOSE-UP) pain sub study.

BACKGROUND: Pain and discomfort in relation to vascular closure are the predominant patient complaints after coronary angiography (CAG). No large-scale randomized studies have evaluated pain and discomfort after CAG with access site closure by manual compression versus a vascular closure device (VCD). AIM: To compare pain and discomfort after femoral artery closure by manual compression versus FemoSeal® VCD. METHODS: The study is a sub study to the CLOSE-UP study, a randomized, single centre comparison of FemoSeal(®) VCD versus manual compression after CAG. Pain and discomfort score was assessed immediately after the closure procedure, at time for mobilization, at discharge and after 14 days. RESULTS: 1014 patients were included and 1001 patients entered analysis. In-hospital follow-up was obtained for all patients and 14-day follow-up was completed for 96% of patients. The closure procedure lasted 1 (1-1) min in the FemoSeal(®)VCD group and 8 (6-10) min in the manual compression group. Pain and discomfort score at the procedure was significantly higher in the FemoSeal(®)VCD group. No differences in pain and discomfort were detected after leaving the catheterization laboratory. CONCLUSION: Closure of femoral access after CAG by the FemoSeal(®)VCD was associated with significantly more pain and discomfort compared with closure by manual compression. No difference in pain and discomfort was found at follow-up.

IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope.

The immunoglobulins expressed by chronic lymphocytic leukemia (CLL) B cells are highly restricted, suggesting they are selected for binding either self or foreign antigen. Of the immunoglobulin heavy-chain variable (IGHV) genes expressed in CLL, IGHV1-69 is the most common, and often is expressed with little or no somatic mutation, and restricted IGHD and IGHJ gene usage. We found that antibodies encoded by one particular IGHV1-69 subset, designated CLL69C, with the HCDR3 encoded by the IGHD3-3 gene in reading frame 2 and IGHJ6, specifically bound to oxidation-specific epitopes (OSE), which are products of enhanced lipid peroxidation and a major target of innate natural antibodies. Specifically, CLL69C bound immunodominant OSE adducts termed MAA (malondialdehyde-acetaldehyde-adducts), which are found on apoptotic cells, inflammatory tissues, and atherosclerotic lesions. It also reacted specifically with MAA-specific peptide mimotopes. Light chain shuffling indicated that non-stochastically paired L chain of IGLV3-9 contributes to the antigen binding of CLL69C. A nearly identical CLL69C Ig heavy chain was identified from an MAA-enriched umbilical cord phage displayed Fab library, and a derived Fab with the same HCDR3 rearrangement displayed identical MAA-binding properties. These data support the concept that OSE (MAA-epitopes), which are ubiquitous products of inflammation, may play a role in clonal selection and expansion of CLL B cells.

Preliminary results of a video-assisted psychotherapist workshop in alliance strategies.

This study examined the preliminary results of an integrative, video-assisted training workshop aimed at helping psychotherapists build strong therapeutic relationships with their clients. Participants were 57 clinicians across five community mental health clinics, who were randomly assigned to the brief alliance-training workshop (in which they participated prior to starting treatment with a new client) or to a delayed-training control condition. Outcomes assessed included therapist-reported use of alliance strategies during Session 1, therapist-rated alliance quality after Session 1, and client engagement across the first 4 weeks. In contrast to hypotheses, one-way analyses of variance and chi-square analyses revealed no statistically significant differences between the training and the delayed-training conditions. However, the therapist-reported impact of using the workshop's alliance strategies was positively correlated with therapist-rated alliance quality (r = .30, p = .03) and marginally correlated with number of sessions attended (r = .25, p = .06) across the two conditions. The findings hold promise for the utility of a brief alliance-focused workshop, and for collaborations between researchers and clinicians seeking to bridge science and practice.

The retail market for fresh cassava root tubers in the European Union (EU): the case of Copenhagen, Denmark--a chemical food safety issue?

BACKGROUND: A number of retail shops in Copenhagen sell fresh cassava roots. Cassava roots contain the toxic cyanogenic glucoside linamarin. A survey was made of the shop characteristics, origin of the roots, buyers, shop owner's knowledge of toxicity levels, and actual toxicity levels. RESULTS: Shops selling fresh cassava were shown mostly to be owned by persons originating in the Middle East or Afghanistan, buyers were found to predominantly be of African origin, and sellers' knowledge concerning the potential toxicity was found to be very restricted. Seventy-six per cent of the roots purchased had a total cyanogenic potentials (CNp) above the 50 mg HCN equivalents kg(-1) dry weight (d.w.) proposed as acceptable by an EU working group. Two of 25 roots purchased had CNp higher than 340 mg HCN eq. kg(-1) d.w. CONCLUSION: The EU has previously made risk assessments concerning cassava and cyanogenic compounds. In the light of the conclusions drawn, the EU needs to make decisions about how to deal with the regulation and control of fresh cassava roots imported to the European food market. Also cassava root products and cassava leaves should be considered.

ExStroke Pilot Trial of the effect of repeated instructions to improve physical activity after ischaemic stroke: a multinational randomised controlled clinical trial.

OBJECTIVES: To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity. DESIGN: Multicentre, multinational, randomised clinical trial with masked outcome assessment. SETTING: Stroke units in Denmark, China, Poland, and Estonia. PARTICIPANTS: 314 patients with ischaemic stroke aged >or=40 years who were able to walk-157 (mean age 69.7 years) randomised to the intervention, 157 (mean age 69.4 years) in the control group. INTERVENTIONS: Patients randomised to the intervention were instructed in a detailed training programme before discharge and at five follow-up visits during 24 months. Control patients had follow-up visits with the same frequency but without instructions in physical activity. MAIN OUTCOME MEASURES: Physical activity assessed with the Physical Activity Scale for the Elderly (PASE) at each visit. Secondary outcomes were clinical events. RESULTS: The estimated mean PASE scores were 69.1 in the intervention group and 64.0 in the control group (difference 5.0 (95% confidence interval -5.8 to 15.9), P=0.36. The intervention had no significant effect on mortality, recurrent stroke, myocardial infarction, or falls and fractures. CONCLUSION: Repeated encouragement and verbal instruction in being physically active did not lead to a significant increase in physical activity measured by the PASE score. More intensive strategies seem to be needed to promote physical activity after ischaemic stroke. TRIAL REGISTRATION: Clinical Trials NCT00132483.

Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.

Vascular lipid accumulation, lipoprotein oxidation, and macrophage lipid uptake in hypercholesterolemic zebrafish.

Lipid accumulation in arteries induces vascular inflammation and atherosclerosis, the major cause of heart attack and stroke in humans. Extreme hyperlipidemia induced in mice and rabbits enables modeling many aspects of human atherosclerosis, but microscopic examination of plaques is possible only postmortem. Here we report that feeding adult zebrafish (Danio rerio) a high-cholesterol diet (HCD) resulted in hypercholesterolemia, remarkable lipoprotein oxidation, and fatty streak formation in the arteries. Feeding an HCD supplemented with a fluorescent cholesteryl ester to optically transparent fli1:EGFP zebrafish larvae in which endothelial cells express green fluorescent protein (GFP), and using confocal microscopy enabled monitoring vascular lipid accumulation and the endothelial cell layer disorganization and thickening in a live animal. The HCD feeding also increased leakage of a fluorescent dextran from the blood vessels. Administering ezetimibe significantly diminished the HCD-induced endothelial cell layer thickening and improved its barrier function. Feeding HCD to lyz:DsRed2 larvae in which macrophages and granulocytes express DsRed resulted in the accumulation of fluorescent myeloid cells in the vascular wall. Using a fluorogenic substrate for phospholipase A(2) (PLA(2)), we observed an increased vascular PLA(2) activity in live HCD-fed larvae compared to control larvae. Furthermore, by transplanting genetically modified murine cells into HCD-fed larvae, we demonstrated that toll-like receptor-4 was required for efficient in vivo lipid uptake by macrophages. These results suggest that the novel zebrafish model is suitable for studying temporal characteristics of certain inflammatory processes of early atherogenesis and the in vivo function of vascular cells.

The role of innate immunity in atherogenesis.

Lipid peroxidation is a common event in health and is greatly accelerated in pro-inflammatory settings such as hypercholesterolemia. Consequently, oxidation-specific epitopes are generated, which are pro-inflammatory and immunogenic, leading to both adaptive and innate responses. Because innate immune mechanisms use conserved germline pattern recognition receptors (PRRs) that are preformed and present at birth, it is not obvious why they should bind to such epitopes. In this review, we put forward the hypothesis that because oxidation-specific epitopes are ubiquitous in both health and disease, and because they in essence represent "danger signals," they constitute a class of pathogen-associated molecular patterns leading to the natural selection of multiple innate PRRs that target such epitopes. We suggest that apoptotic cells, and the blebs and microparticles released from such cells, which are rich in oxidation-specific epitopes and thus pro-inflammatory, constitute an endogenous set of selecting antigens. In turn, natural antibodies, scavenger receptors, and soluble innate proteins, such as pentraxins, all represent PRRs that target such epitopes. We discuss the evidence for this hypothesis and the consequences of such responses in health and disease, such as atherosclerosis.

Patient interpersonal factors and the therapeutic alliance in two treatments for bulimia nervosa.

Although the therapeutic alliance is robustly associated with psychotherapy outcomes, less is known about factors that influence its development. This study examined the association between baseline patient interpersonal factors and patient-rated alliance in a randomized trial comparing cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT) for bulimia nervosa. Using hierarchical linear modeling, early and middle alliance were negatively associated with interpersonal distress and positively associated with interpersonal affiliation. Middle alliance was also related to treatment group interactions with rigidity, affiliation, and control. Overall, alliance growth was higher in IPT than CBT. Using group-based trajectory analysis, three divergent alliance trajectories emerged (high and improving, low and improving, and low and stable), with group mean differences between two of them in terms of interpersonal distress and hostile-submissiveness.

The ExStroke Pilot Trial: rationale, design, and baseline data of a randomized multicenter trial comparing physical training versus usual care after an ischemic stroke.

INTRODUCTION: A high level of physical activity is associated with a decreased risk of first stroke and physical activity modifies recognized stroke risk factors and is recommended for stroke survivors. Available research shows that stroke patients can increase their level of physical performance over a short period. When the intervention period is over, physical performance often declines towards baseline level. Currently, there is no evidence on the association between physical activity and the risk of recurrent stroke. The ExStroke Pilot Trial is a randomized clinical trial with the aim of increasing stroke patients' level of physical activity and secondarily to associate the level of physical activity to the risk of recurrent stroke, myocardial infarction, and all-cause mortality in the two groups. We describe the rationale, design, and baseline data of the ExStroke Pilot Trial. METHODS: Patients with ischemic stroke above 39 years were randomized to intervention or control group. The intervention group will, over a 2-year period, receive information on and verbal instruction to exercise by a physiotherapist or a physician. The control group will receive the department's usual care. Physical activity is assessed in both groups seven times during follow-up using the Physical Activity Scale for the Elderly (PASE) questionnaire, which quantifies the amount of physical activity done in the last seven days prior to interview. The PASE score constitutes the primary outcome measure. The secondary outcome is the time from randomization to recurrent stroke, myocardial infarction, or all-cause mortality. Further outcome measures include: time from randomization to recurrent stroke, myocardial infarction, and vascular death; recurrent stroke; modified Rankin Scale; quality of life; occurrence of falls and fractures. TRIAL STATUS: From 9 centers in 4 countries, 314 patients were included and follow-up is ongoing. Mean age and standard deviation (SD) of the study participants was 68.4 (11.9) years and 56.4% were male. Mean (SD) PASE score was 84.1 (55.9) and median (interquartile range) Scandinavian Stroke Scale score was 54 (51-58).

Level of physical activity in the week preceding an ischemic stroke.

BACKGROUND: Most observational studies investigating physical activity as a risk factor for stroke have concentrated on the years preceding a stroke event. In the present case control study we compared the reported level of physical activity performed during the week preceding an ischemic stroke with that of community controls. Furthermore we calculated the odds ratio for stroke based on the level of physical activity. SUBJECTS AND METHODS: Patients with an ischemic stroke were recruited consecutively from hospitals covering Copenhagen City. Community controls were recruited among participants of the Copenhagen City Heart Study and matched according to age and gender. The level of physical activity was assessed using The Physical Activity Scale for the Elderly (PASE), which quantifies the amount of physical activity done in the last 7 days. RESULTS: A total of 127 cases and 301 control subjects were included in the study. Mean (+/-SD) PASE scores for cases were 76.0 +/- 46.2 and 119.7 +/- 69.4 for controls (p < 0.001). For each 1-point increase in PASE score the odds ratio for ischemic stroke was 0.98 (0.98-0.99), equivalent to an odds ratio of 0.86 (95% CI: 0.82-0.90) for each 10-point increase. CONCLUSION: Stroke patients are less physically active in the week preceding an ischemic stroke when compared to age- and sex-matched controls. Increasing PASE score was inversely, log-linearly and significantly associated with odds ratio for ischemic stroke.

A diet-induced hypercholesterolemic murine model to study atherogenesis without obesity and metabolic syndrome.

OBJECTIVE: Western-type high-fat/high-cholesterol diets used to induce atherogenesis in low-density lipoprotein (LDL) receptor-deficient mice also lead to obesity with concomitant metabolic complications, eg, hypertriglyceridemia, hyperinsulinemia, and insulin resistance. Our aim was to design a diet inducing atherosclerosis through moderate hypercholesterolemia without associated parameters of the metabolic syndrome. METHODS AND RESULTS: Male LDL receptor-deficient mice were fed regular chow (RC; 0.01% cholesterol/4.4% fat), cholesterol-enriched regular chow (HC; 1% cholesterol/4.4% fat), or Western diet (WD 0.06% cholesterol/21% milk fat) for 28 weeks. HC-feeding led to elevated plasma (approximately 20.7 mmol/L [800 mg/dL]) and LDL cholesterol and accelerated atherosclerosis. Plasma triglycerides were unaffected. Compared with RC-fed controls, HC-fed mice had normal body weight gain and normal fasting levels of glucose, free fatty acids, and insulin. In contrast, WD-fed mice were extremely hypercholesterolemic (>41.4 mmol/L), obese, hypertriglyceridemic, hyperinsulinemic, insulin resistant, and showed adverse health such as skin/fur abnormalities and hepatic steatosis. Although atherosclerotic surface areas in the entire aorta were similar in HC-fed and WD-fed mice, lesions in aortic origin cross sections were significantly larger in WD-fed mice. However, morphology was similar in lesions of equal size. CONCLUSIONS: The HC diet induced moderate hypercholesterolemia and extensive atherosclerosis and should be useful to study specific aspects of atherogenesis in the absence of confounding effects of the metabolic syndrome.