Sibship and dispensing patterns of asthma medication in young children : a population based study

Purpose: Our aim was to study the association between sibship and dispensing patterns of asthma medication in young children, focusing on incidence and persistence, and taking sibship status, asthma diagnoses, and siblings’ medication into account. Methods: A register-based cohort study including all children (n=50,546) born in Stockholm, Sweden 2006–2007, followed up during 2006–2014. Exposure was sibling status; outcome was incidence of dispensed asthma medication and persistence over time. A Cox-model was used to study the association between sibship and asthma medication. Persistence was defined using two different time windows (4- and 18-months) in a refill sequence model including siblings’ and unrelated control children’s medication. Results: After one year of age, the adjusted hazard ratio of dispensed asthma medication was 0.85 (95%CI 0.80–0.90) among children with siblings compared to singletons. The estimated proportion of children with persistent controller medication was 7.2% (4-month model) and 64.5% (18-month model). When including the siblings’ controller medication, the estimated proportion was 8.8% (4-months) and 7.8% for control children (relative risk, RR 0.89, 95%CI 0.81-0.98). The persistence was lower for those with siblings compared to singletons (adj. RR 0.72, 95%CI 0.62-0.85 for 4-months) with similar estimates for older, younger, and full siblings and regardless of asthma diagnoses. Conclusions: Siblings have different dispensing patterns of asthma medications compared to singletons regardless of asthma diagnoses. After including the siblings’ asthma medication and compared with control children, the proportion of children with persistent medication increased which may indicate that siblings share asthma medications.Swedish Research Council for Health, Working Life and WelfareStrategic Research Program in EpidemiologyStockholm County CouncilSwedish Heart Lung FoundationSwedish Research CouncilAccepte

Brukarens roll i välfärdsforskning och utvecklingsarbete

Tekstene er fra forelesninger samt fra doktorantkurset "Brukarmedverkan i forskning och utvecklingsarbete inom hälso- och sjukvård, socialt arbete och omsorg". Kurset ble avholdt våren 2009.Fra omslag: På 1980-talet blev ”brukare” ett modeord i offentlig förvaltning och förvaltningsforskning. Termen betecknar den som använder sig av välfärdsservice (jfr. engelskans service user), eller ”slutmottagare” av offentlig nyttighet eller åtgärd. Brukare av välfärdstjänster vet hur hjälp och service fungerar i praktiken och kan därför ge synnerligen viktig återkoppling enligt devisen: ”Den som har skorna på fötterna vet var de skaver”. Välfärdsorganisationer har all anledning att involvera brukare i planering och policyarbete i syfte att utveckla förmågan att göra rätt saker. Det finns inte mycket dokumentation och forskning kring brukarmedverkan i utvecklingsarbete och forskning på välfärdsområdet. I synnerhet saknas kunskap om hur välfärdstjänster tas emot och realiseras i brukarens livssammanhang. En ambition i doktorandkursen ”brukarmedverkan i forskning och utvecklingsarbete inom hälso- och sjukvård, socialt arbete och omsorg” var att samla och presentera kunskaper på området. Kursen genomfördes våren 2009 i ett unikt samarbete mellan Karlstads Universitet, Sheffield University i England, Högskolan i Hedmark i Norge, Hälsohögskolan i Jönköping och Högskolan i Borås/FoU Sjuhärad Välfärd. Texterna i denna bok härrör från kursens föreläsningar och paperarbeten. De ger många exempel på hur brukare kan involveras i forskning och utvecklingsarbete, och presenterar en rad praktiska metoder för brukarsamverkan. Boken rekommenderas till välfärdens politiker och yrkespersoner, till studenter som förbereder sig för välfärdens yrken liksom till forskare och utvecklingsarbetare som vill utveckla samarbete med brukare och brukarorganisationer. Den vänder sig givetvis även till brukare och brukarorganisationer som vill engagera sig i forskning och utvecklingsarbete

Functional characterisation of receptors for cysteinyl leukotrienes in smooth muscle

Functional Characterisation of Receptors for Cysteinyl Leukotrienes in Smooth Muscle by Eva Wikström Jonsson, Experimental Asthma- and Allergy Research, Institute of Environmental Medicine and Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden The cysteinyl leukotrienes (leukotriene C4, D4 and E4) have potent biological actions which significantly contribute to the airway obstruction in asthma. Several of these effects are blocked by drugs known as CysLT1-receptor antagonists, which have been introduced as new treatment for asthma. However, there are actions of leukotrienes which are not sensitive to these antagonists, suggesting the presence of additional receptor subtypes. It was the aim of this Thesis to extend the knowledge about receptors for cysteinyl leukotrienes. Three different isolated smooth muscle preparations kept in organ baths under non-flow conditions were characterised with respect to responsiveness to cysteinyl leukotrienes and sensitivity to purported CysLT1-receptor antagonists. In addition, the study involved evaluation of a leukotriene E4 analogue, BAY u9773, suggested to inhibit responses which cannot be blocked by CysLT1-receptor antagonists. Responses sensitive to BAY u9773 have provisionally been considered to be mediated by CysLT2-receptors. In the guinea pig ileum, BAY u9773 but not the selective CysLT, receptor antagonist ICI 198,615 concentration-dependently inhibited the contractile response to leukotriene C4 in a fashion suggesting competitive antagonism. In sheep trachealis muscle, BAY u9773 antagonised contractions induced by leukotriene C4 and leukotriene D4 in a similar manner, whereas ICI 198,615 did not. The observations support that leukotriene C4 in the guinea pig ileum, and leukotriene C4 as well as leukotriene D4 in sheep trachealis muscle, mediated contractions via activation of CysLT2-receptors. In guinea pig lung parenchyma, however, the effects of BAY u9773 and conventional cysteinyl leukotriene receptor antagonists (ICI 198,615, FPL 55712) were more complex. First, a contraction was evoked when BAY u9773 was added to the preparation. This contraction could be inhibited by antagonists of CysLT1- and TP-receptors, suggesting that BAY u9773 acted as an agonist at these two receptors. Second, pretreatment with BAY u9773 inhibited a distinct but relatively minor component of the contractile response to leukotriene C4 and D4. The effects of BAY u9773 and ICI 198,615 were similar in guinea pig lung parenchyma. The findings suggest that the receptor mediating the major part of the contractile response to exogenous cysteinyl leukotrienes in guinea pig lung parenchyma was different from the currently defined CysLTrreceptor. The data suggested that BAY u9773 was a partial agonist at cysteinyl leukotriene receptors, which presumably contributed to its profile of activity as a combined CysLT1- and CysLT2-receptor antagonist. In addition to contracting guinea pig lung parenchyma, leukotriene C4 and lipoxin A4 also evoked release of thromboxane A2. This release was sensitive to CysLT1-receptor antagonists and contributed to part of the contractile response. Finally, the investigations included a characterisation of the role of leukotrienes and other mediators in antigen-induced contractions of lung parenchyma from actively sensitised guinea pigs. Combination of antihistamines and drugs which inhibit the formation of leukotrienes or antagonise CysLT1-receptors, blocked the major component of the antigen-induced contraction. The findings are similar to those observed in isolated human bronchi and support that guinea pig lung parenchyma may be used as a model to investigate mediator mechanisms of relevance to asthma. Keywords: cysteinyl leukotrienes, leukotriene receptor, histamine, antigen, smooth muscle, lipoxin, thromboxane, Schultz-Dale reaction Stockholm 1998 ISBN 91-628-2897-

Brukarens roll i välfärdsforskning och utvecklingsarbete

Fra omslag: På 1980-talet blev ”brukare” ett modeord i offentlig förvaltning och förvaltningsforskning. Termen betecknar den som använder sig av välfärdsservice (jfr. engelskans service user), eller ”slutmottagare” av offentlig nyttighet eller åtgärd. Brukare av välfärdstjänster vet hur hjälp och service fungerar i praktiken och kan därför ge synnerligen viktig återkoppling enligt devisen: ”Den som har skorna på fötterna vet var de skaver”. Välfärdsorganisationer har all anledning att involvera brukare i planering och policyarbete i syfte att utveckla förmågan att göra rätt saker. Det finns inte mycket dokumentation och forskning kring brukarmedverkan i utvecklingsarbete och forskning på välfärdsområdet. I synnerhet saknas kunskap om hur välfärdstjänster tas emot och realiseras i brukarens livssammanhang. En ambition i doktorandkursen ”brukarmedverkan i forskning och utvecklingsarbete inom hälso- och sjukvård, socialt arbete och omsorg” var att samla och presentera kunskaper på området. Kursen genomfördes våren 2009 i ett unikt samarbete mellan Karlstads Universitet, Sheffield University i England, Högskolan i Hedmark i Norge, Hälsohögskolan i Jönköping och Högskolan i Borås/FoU Sjuhärad Välfärd. Texterna i denna bok härrör från kursens föreläsningar och paperarbeten. De ger många exempel på hur brukare kan involveras i forskning och utvecklingsarbete, och presenterar en rad praktiska metoder för brukarsamverkan. Boken rekommenderas till välfärdens politiker och yrkespersoner, till studenter som förbereder sig för välfärdens yrken liksom till forskare och utvecklingsarbetare som vill utveckla samarbete med brukare och brukarorganisationer. Den vänder sig givetvis även till brukare och brukarorganisationer som vill engagera sig i forskning och utvecklingsarbete

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months. Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications