Comparisons of recycled manure solids and wood shavings/sawdust as bedding material-Implications for animal welfare, herd health, milk quality, and bedding costs in Swedish dairy herds.

Increasing shortages and costs of common bedding materials have led dairy farmers in Sweden to consider using recycled manure solids (RMS), which are readily available and low cost, as an alternative bedding material. The main risks are effects on udder health and milk quality, but RMS could also affect animal welfare and claw health. The advantages and disadvantages of using RMS bedding have not been fully investigated, and findings in other countries cannot be directly applied to Swedish conditions and climate. This observational cross-sectional study investigated the use of RMS as bedding, regarding associations with certain aspects of animal welfare, herd health, milk quality, and bedding costs in Swedish dairy herds. Thirty-four dairy farms using RMS or wood shavings/sawdust (each n = 17) were compared. Each farm was visited 2 times during the housing period from 2020 to 2021, once from October to December and once from March to May. Dairy barns were observed, animal welfare was assessed, and freestall dimensions were measured. Farm owners were interviewed about housing system characteristics, herd performance, and herd management. Data on milk production and herd health were obtained from the Swedish official milk recording scheme for the indoor period from October to March. The prevalence of claw disorders and abnormal claw conformation were collected from the national claw health database for the period from October to May. On each farm visit, composite samples of unused bedding outside the barn and used bedding material from the freestalls, respectively, were taken for total bacterial count and DM analysis. Samples of bulk tank milk for determination of total bacterial count were taken in connection to the visits. In addition, samples of unused and used bedding material and manure from alleys for analysis of 3 Treponema species associated with digital dermatitis (DD) were gathered and analyzed. Total bacterial count was significantly higher in unused (8.50 log10 cfu/g) and used RMS bedding (9.75 log10 cfu/g) than in wood shavings/sawdust (used 4.74; unused 8.63 log10 cfu/g), but there were no significant differences in bulk milk total bacterial count (median 4.07 vs. 3.89 log10 cfu/mL) or SCC (median 243,800 vs. 229,200 cells/mL). The aspects of animal welfare assessed did not differ significantly between the 2 bedding systems, whereas the prevalence of total claw disorders (25.9% vs. 38.0% of trimmed cows), dermatitis (6.9% vs. 16.2% of trimmed cows) and sole ulcers (2.0% vs. 4.0% of trimmed cows) were significantly lower in the RMS herds. Treponema spp. were not detected in unused RMS material, but all RMS herds had presence of DD recorded at foot trimming. An economic assessment based on the interview results and price level from winter 2021 revealed that the costs of RMS bedding varied with amount of RMS produced. Thus, RMS is a potential alternative bedding material for dairy cows in Sweden and can be a profitable option for large dairy herds. However, the high level of total bacteria in the material requires attention to bedding and milking routines as well as regular monitoring of herd health.

Young children's voices in an unlocked Sweden during the COVID-19 pandemic.

AIMS: During the COVID-19 pandemic, Sweden was one of the few countries that rejected lockdowns in favour of recommendations for restrictions, including careful hand hygiene and social distancing. Preschools and primary schools remained open. Several studies have shown negative impacts of the pandemic on children, particularly high levels of anxiety. The study aim was to explore how Swedish school-aged children aged 6-14 years, experienced the COVID-19 pandemic and their perceived anxiety. METHODS: In total, 774 children aged 6-14 years and their guardians answered an online questionnaire containing 24 questions, along with two instruments measuring anxiety: the Children's Anxiety Questionnaire and the Numerical Rating Scale. A convergent parallel mixed-methods design was used for analysing the quantitative and qualitative data. Each data source was first analysed separately, followed by a merged interpretative analysis. RESULTS: The results showed generally low levels of anxiety, with no significant sex differences. Children who refrained from normal social activities or group activities (n=377) had significantly higher levels of anxiety. Most of the children were able to appreciate the bright side of life, despite the social distancing and refraining from activities, which prevented them from meeting and hugging their loved ones. CONCLUSIONS: These Swedish children generally experienced low levels of anxiety, except those who refrained from social activities. Life was nonetheless mostly experienced as normal, largely because schools remained open. Keeping life as normal as possible could be one important factor in preventing higher anxiety and depression levels in children during a pandemic.

Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression.

It has been suggested that the superiority of antidepressants over placebo in controlled trials is merely a consequence of side effects enhancing the expectation of improvement by making the patient realize that he/she is not on placebo. We explored this hypothesis in a patient-level post hoc-analysis including all industry-sponsored, Food and Drug Administration-registered placebo-controlled trials of citalopram or paroxetine in adult major depression that used the Hamilton Depression Rating Scale (HDRS) and included a week 6 symptom assessment (n=15). The primary analyses, which compared completers on active treatment without early adverse events to completers on placebo (with or without adverse events) with respect to reduction in the HDRS depressed mood item showed larger symptom reduction in patients given active treatment, the effect sizes being 0.48 for citalopram and 0.33 for paroxetine. In actively treated subjects reporting early adverse events, who also outperformed those given placebo, the severity of the adverse events did not predict response. Several sensitivity analyses, for example, including (i) those using change of the sum of all HDRS-17 items as effect parameter, (ii) those excluding all subjects with adverse events (that is, also those on placebo) and (iii) those based on the intention-to-treat population, were all in line with the primary analyses. The finding that both paroxetine and citalopram are clearly superior to placebo also when not producing adverse events, as well as the lack of association between adverse event severity and response, argue against the theory that antidepressants outperform placebo solely or largely because of their side effects.

Neonatal gut colonization by Staphylococcus aureus strains with certain adhesins and superantigens is negatively associated with subsequent development of atopic eczema.

BACKGROUND: Insufficient early immune stimulation may predispose to atopic disease. Staphylococcus aureus, a skin and gut colonizer, produces the B-cell mitogen protein A and T-cell-activating superantigens. Early gut colonization by S. aureus strains that possess the superantigens encoded by the enterotoxin gene (egc) cluster and elastin-binding protein is negatively associated with development of atopic eczema. OBJECTIVES: To investigate (i) whether these findings could be replicated in a second birth cohort, FARMFLORA, and (ii) whether nasal colonization by S. aureus also relates to subsequent atopic eczema development. METHODS: Faecal samples and nasal swabs from infants in the FARMFLORA birth cohort (n = 65) were cultured for S. aureus. Individual strains were distinguished by random amplified polymorphic DNA and assessed for adhesin and superantigen gene carriage by polymerase chain reaction. Atopic eczema at 18 months of age was related to nasal and gut S. aureus colonization patterns during the first 2 months of life (well before onset of eczema). RESULTS: Staphylococcus aureus colonization per se was unrelated to subsequent eczema development. However, gut S. aureus strains from the infants who subsequently developed atopic eczema less frequently carried the ebp gene, encoding elastin-binding protein, and superantigen genes encoded by egc, compared with strains from children who remained healthy. Nasal colonization by S. aureus was less clearly related to subsequent eczema development. CONCLUSIONS: The results precisely replicate our previous observations and may suggest that mucosal colonization by certain S. aureus strains provides immune stimulation that strengthens the epithelial barrier and counteracts the development of atopic eczema.

Risk of homelessness after discharge from psychiatric wards in Denmark: a nationwide register-based cohort study.

OBJECTIVE: To examine the absolute and relative risk of homelessness following discharge from psychiatric wards in Denmark. METHODS: A nationwide, register-based, cohort study including people aged 18+ years discharged from psychiatric wards in Denmark between 1 January 2001 and 31 December 2015. We analysed associations between psychiatric diagnoses and risk of homelessness using survival analysis. RESULTS: A total of 126 848 psychiatric in-patients were included accounting for 94 835 person-years. The incidence of homelessness one year following discharge was 28.18 (95% CI 26.69-29.75) and 9.27 (95% CI 8.45-10.16) per 1000 person-years at risk in men and women respectively. The one-year cumulative probability of first homelessness after discharge from psychiatric wards was 1.58% (95% CI 1.48-1.68) in males and 0.55% (95% CI 0.50-0.61) in females. Substance use disorders increased the risk of homelessness after discharge with adjusted incidence rate ratios of 6.60 (95% CI 5.19-8.40) (men) and 13.06 (95% CI 9.31-18.33) (women), compared with depressive disorders. Prior history of homelessness was an important predictor for homelessness following discharge. CONCLUSIONS: The first year following discharge from psychiatric wards is a high-risk period of homelessness, especially when having a substance use disorder or a prior history of homeless shelter contact. Improved efforts to prevent homelessness are needed.

An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223.

Background: Baseline clinical variables are prognostic for overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). Their prognostic and predictive value with agents targeting bone metastases, such as radium-223, is not established. Patients and methods: The radium-223 ALSYMPCA trial enrolled patients with CRPC and symptomatic bone metastases. Prognostic potential of baseline variables was assessed using Cox models. Percentage changes in biomarker levels from baseline were evaluated during the trial period; changes from baseline to week 12 were evaluated for association with OS and surrogacy. Results: Eastern Cooperative Oncology Group performance status, total alkaline phosphatase (tALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) at baseline were associated with OS (P ≤ 0.0003) in the intent-to-treat population (radium-223, N = 614; placebo, N = 307). tALP declined from baseline within 4 weeks after beginning radium-223, by week 12 declining in 87% of radium-223 and 23% of placebo patients (P < 0.001). LDH declined in 51% and 34% (P = 0.003), whereas PSA declined in 27% and 14% (P = 0.160). Mean tALP change from baseline was 32.2% decrease with radium-223 and 37.2% increase with placebo. Radium-223 patients with tALP decline from baseline to week 12 (confirmed ≥3 weeks from week 12) had 55% lower risk of death (hazard ratio = 0.45; 95% CI 0.34-0.61) versus those with no confirmed tALP decline. Proportional treatment effect (PTE) values for tALP, LDH, and PSA changes from baseline at week 12 as OS surrogate markers were 0.34 (95% CI: 0-0.746), 0.07 (95% CI: 0-0.211), and 0 (95% CI: 0-0.082), respectively. Conclusions: Significant tALP declines (versus placebo) occurred as early as 4 weeks after beginning radium-223 therapy. tALP or LDH declines at 12 weeks correlated with longer OS, but did not meet statistical surrogacy requirements. Dynamic changes in tALP and LDH during radium-223 treatments may be useful to monitor, but do not serve as surrogates for survival.

Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression.

The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants.

Incidence of early anxiety aggravation in trials of selective serotonin reuptake inhibitors in depression.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) may aggravate anxiety and agitation during the first days of treatment but the frequency of such reactions remains unknown. METHOD: We analysed patient-level data from placebo-controlled trials of sertraline, paroxetine or citalopram in depressed adults. Somatic anxiety, psychic anxiety and psychomotor agitation as assessed using the Hamilton Depression Rating Scale (HDRS) were analysed in all trials (n = 8262); anxiety-related adverse events were analysed in trials investigating paroxetine and citalopram (n = 5712). RESULTS: After one but not two weeks, patients on an SSRI were more likely than those on placebo to report enhanced somatic anxiety (adjusted risk 9.3% vs. 6.7%); likewise, mean rating of somatic anxiety was higher in the SSRI group. In contrast, patients receiving an SSRI were less likely to report aggravation of psychic anxiety (adjusted risk: 7.0% vs. 8.5%) with mean rating of psychic anxiety and agitation being lower in the SSRI group. The adverse event 'nervousness' was more common in patients given an SSRI (5.5% vs. 2.5%). Neither aggravation of HDRS-rated anxiety nor anxiety-related adverse events predicted poor antidepressant response. CONCLUSION: Whereas an anxiety-reducing effect of SSRIs is notable already during the first week of treatment, these drugs may also elicit an early increase in anxiety in susceptible subjects that however does not predict a poor subsequent response to treatment.

Inverse relationship between erythrocyte size and platelet reactivity in elderly.

Previous work indicates that erythrocytes (RBCs) accumulate ß-amyloid X-40 (Aß40) in individuals with Alzheimer disease (AD) and to a lesser extent in healthy elderly. The toxin damages RBCs and increases their mean corpuscular volume (MCV). Furthermore, AD platelets demonstrate lower reactivity. This study investigated interactions between RBCs and platelets. Older individuals with moderate hypertension (n = 57) were classified into two groups, depending on MCV in whole blood: The MCVhigh group comprised individuals with higher MCV (n = 27; 97 ± 3(SD) fl) and MCVlow group had relatively lower MCV (n = 30; 90 ± 3(SD) fl). Flow cytometry was used to determine platelet reactivity, i.e., the surface binding of fibrinogen after provocation. Adenosine diphosphate (ADP) and a thrombin receptor-activating protein (TRAP-6) were used as agonists. Subsequently, blood cells were divided according to density into 17 subfractions. Intra-RBC Aß40 content was analyzed and in all platelet populations surface-bound fibrinogen was determined to estimate platelet in vivo activity. We found Aß40 inside RBCs of approximately 50% of participants, but the toxin did not affect MCV and platelet reactivity. In contrast, MCV associated inversely with platelet reactivity as judged from surface-attached fibrinogen after ADP (1.7 µmol/L) (p < 0.05) and TRAP-6 provocation (57 µmol/L (p = 0.01) and 74 µmol/L (p < 0.05)). In several density fractions (nos. 3, 4, 8, 11-13 (p < 0.05) and nos. 5-7 (p < 0.01)) MCV linked inversely with platelet-attached fibrinogen. In our community-dwelling sample, enhanced MCV associated with decreased platelet reactivity and lower in vivo platelet activity. It resembles RBCs and platelet behavior in AD-type dementia.

Alpha emitter radium-223 and survival in metastatic prostate cancer.

BACKGROUND: Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. METHODS: In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. RESULTS: At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. CONCLUSIONS: In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study.

BACKGROUND: Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P). PATIENTS AND METHODS: Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study. RESULTS: Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21-2.74]}. Findings were similar for FACT-P total score [24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08-2.65)]. A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004). CONCLUSIONS: QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

Gastric fluid cytokines are associated with chorioamnionitis and white blood cell counts in preterm infants.

AIM: The aim of this study was to determine whether the concentration of cytokines in the gastric fluid at birth was associated with chorioamnionitis or funisitis and with the white blood cell counts of very premature newborns. METHODS: We retrieved gastric fluid from 27 preterm infants with a gestational age of <29 weeks within 1 h of birth and used enzyme-linked immunosorbent assay to measure the concentrations of interleukin (IL)-1beta, epithelial cell-derived neutrophil-activating peptide (ENA)-78, IL-8 and growth-related oncogene (Gro)-alpha. The presence of histologic chorioamnionitis or funisitis in the placentas and the highest white blood cell count of the infants during the first week of life were compared to the cytokine concentrations. RESULTS: Gastric fluid concentrations of IL-1beta, ENA-78, IL-8 and Gro-alpha were strongly associated with chorioamnionitis and funisitis. In addition, chorioamnionitis and funisitis and gastric aspirate cytokine levels were associated with the highest white blood cell counts of the infants during the first week of life. CONCLUSION: This study suggests that levels of inflammatory cytokines in the gastric fluid of premature infants at birth can be used to assess the exposure of the infants to antenatal inflammation.

Risk factors for miscarriage from a prevention perspective: a nationwide follow-up study.

OBJECTIVE: To identify modifiable risk factors for miscarriage and to estimate the preventable proportion of miscarriages that could be attributed to these. DESIGN: Nationwide observational follow-up study. SETTING: Denmark. POPULATION: Ninety-one thousand four hundred and twenty seven pregnancies included in the Danish National Birth Cohort between 1996 and 2002. METHODS: Information on potentially modifiable risk factors before and during pregnancy was collected by means of computer-assisted telephone interviews and linkage with Danish registers, ensuring almost complete follow-up of pregnancy outcome. Modifiable risk factors for miscarriage were identified by multiple Cox regression analysis, which provided the background for our estimations of population attributable fractions. In all, 88,373 pregnancies had full information on all covariates and were included in this analysis. MAIN OUTCOME MEASURES: Miscarriage before 22 completed weeks of gestation. RESULTS: The potentially modifiable pre-pregnant risk factors associated with increased miscarriage risk were: age of 30 years or more at conception, underweight, and obesity. During pregnancy the modifiable risk factors were: alcohol consumption, lifting of >20 kg daily, and night work. We estimated that 25.2% of the miscarriages might be prevented by reduction of all these risk factors to low risk levels. Modification of risk factors acting before and during pregnancy could lead to prevention of 14.7 and 12.5%, respectively, of the miscarriages. Maternal age at conception and alcohol consumption were the most important risk factors. CONCLUSIONS: Miscarriage risk is increased by multiple potentially modifiable risk factors and a considerable proportion of miscarriages may be preventable.

Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin.

The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24-72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.

Platelets and acute cerebral infarction.

Stroke is worldwide a leading cause of death and disability. Its etiology is regarded as heterogeneous. Platelets are implicated in its pathophysiology, but our understanding of their specific role is incomplete. Only sparse and conflicting information exists about platelet reactivity and activity in acute stroke. Some scientists take the view that platelets activate in conjunction with acute cerebral infarctions. Others put forward evidence corroborating the contrary notion. Increased soluble P-selectin as a sign of platelet and/or endothelial activity seems to be a feature of the disease. The latter point of view is opposed by other researchers. Due to these conflicting opinions, this study is devoted to platelet characteristics in acute cerebral infarctions. We studied subjects (n = 72; age 74 ± 10(SD) years; 31 females) having acute stroke. As controls served atrial fibrillation (AF) patients (n = 58; age 69 ± 7(SD) years; 12 females) subject to electrical cardioversion, a flow cytometer was put to use for measuring platelet reactivity and activity. After agonist provocation, both platelet bound P-selectin and fibrinogen were employed as estimates of platelet reactivity. Dilutions of a thrombin-receptor-activating peptide (TRAP-6) (74 and 57 µmol/l) (P-selectin and fibrinogen) and ADP (8.5 and 1.7 µmol/l) (fibrinogen only) were put to use as platelet agonists. Membrane-bound P-selectin without agonist stimulation served as a measure of in vivo platelet activation. Soluble P-selectin, as determined from a commercial ELISA, was used to assess platelet and/or endothelial activity. In acute stroke neither platelet-bound P-selectin nor fibrinogen after stimulation, i.e. reactivity, differed from AF controls. In contrast, lower platelet activity as judged from surface attached and circulating P-selectin without agonist stimulation proved to be a feature of cerebral infarctions. The p-values were p < 0.001 and p < 0.01, respectively. It is concluded that acute stroke is not associated with platelet reactivity platelets circulate less activated during the disease. It is evident that the mechanisms reflecting platelet reactivity and activity being investigated in this study play minor roles in stroke pathophysiology. New powerful platelet inhibitory drugs are currently introduced. To avoid major bleeding studies on platelet, behavior in acute stroke are necessary before including these medications in stroke treatment protocols.

Adolescents' experiences of Help Overcoming Pain Early-A school based person-centred intervention for adolescents with chronic pain.

To illuminate adolescents' experiences of Help Overcoming Pain Early (HOPE), a person-centred intervention delivered in a school setting by school nurses. Twenty-one adolescents with chronic pain recruited from secondary school, who had completed the HOPE intervention, were included in the interview study. The HOPE intervention was built on person-centred ethics and consisted of four meetings between school nurses and adolescents on the subject of stress and pain management. A qualitative method using content analysis with an inductive approach was employed. In the interviews, the adolescents describe how they reclaim their lives with the help of HOPE. They use different strategies and parts of the intervention to move on with their lives. A trustful relationship, as that with the school nurse, was essential to dare to change. The overarching theme summarizes in Becoming myself again and is built up by three sub-themes: Trust a pillar for growth, Making sense of my life with pain, and Putting myself into the world again. A person-centred intervention such as HOPE applied in a school context is promising for promoting confidence in adolescents with chronic pain. A trust-building process emerged, in terms of both the adolescents' trust in the healthcare staff they meet and their confidence in their own ability to handle and influence their situation, which in the long term can promote trust in themselves as a person.

Psychometric evaluation of the electronic faces thermometer scale for pain assessment in children 8-17 years old: A study protocol.

It is often a challenge for a child to communicate their pain, and their possibilities to do so should be strengthened in healthcare settings. Digital self-assessment provides a potential solution for person-centered care in pain management and promotes child participation when a child is ill. A child's perception of pain assessment differs when it is assessed using digital or analog formats. As we move into the digital era, there is an urgent need to validate digital pain assessment tools, including the newly developed electronic Faces Thermometer Scale (eFTS). This study protocol describes three studies with the overall aim to evaluate psychometric properties of the eFTS for assessing pain in children 8-17 years of age. A multi-site project design combining quantitative and qualitative methods will be used for three observational studies. Study 1: 100 Swedish-speaking children will report the level of anticipated pain from vignettes describing painful situations in four levels of pain and a think-aloud method will be used for data collection. Data will be analyzed with phenomenography as well as descriptive and comparative statistics. Study 2: 600 children aged 8-17 years at pediatric and dental settings in Sweden, Denmark, Iceland, and USA will be included. Children will assess their pain intensity due to medical or dental procedures, surgery, or acute pain using three different pain Scales for each time point; the eFTS, the Faces Pain Scale Revised, and the Coloured Analogue Scale. Descriptive and comparative statistics will be used, with subanalysis taking cultural context into consideration. Study 3: A subgroup of 20 children out of these 600 children will be purposely included in an interview to describe experiences of grading their own pain using the eFTS. Qualitative data will be analyzed with content analysis. Our pilot studies showed high level of adherence to the study procedure and rendered only a small revision of background questionnaires. Preliminary analysis indicated that the instruments are adequate to be used by children and that the analysis plan is feasible. A digital pain assessment tool contributes to an increase in pain assessment in pediatric care. The Medical Research Council framework for complex interventions in healthcare supports a thorough development of a new scale. By evaluating psychometric properties in several settings by both qualitative and quantitative methods, the eFTS will become a well-validated tool to strengthen the child's voice within healthcare.