Are pharmacological randomised controlled clinical trials relevant to real-life asthma populations? A protocol for an UNLOCK study from the IPCRG

[Excerpt] Introduction: Asthma has a high prevalence worldwide with a high incidence in primary care settings in many countries.1 It is by definition a variable disease with a broad spectrum of clinical phenotypes, in which management and treatment can be difficult.2–8 The aim of asthma treatment is optimal control of the disease, which according to Global Initiative for Asthma (GINA) guidelines implies both symptom control and prevention of exacerbations.1 Despite several treatment options, studies show that about half of the patients have poor asthma control.2,3 When asthma is not controlled, it decreases the quality of life, increases the risk of exacerbations and premature death and is a high cost for the society.2,3 [...]The IPCRG provided funding for this research project as an UNLOCK Group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. Novartis has no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This study will include data from the Optimum Patient Care Research Database and is undertaken in collaboration with Optimum Patient Care and the Respiratory Effectiveness Group.info:eu-repo/semantics/publishedVersio

The prevalence of comorbidities in COPD patients, and their impact on health status and COPD symptoms in primary care patients: a protocol for an UNLOCK study from the IPCRG

[Abstract] Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality with high social and economic costs. The prevalence of COPD has been reported to vary between 6 and 26.1% worldwide.1 COPD has also been associated with a high prevalence of one or more comorbid conditions, which have an impact on health status and mortality.2–5 Although several diseases have been studied as COPD comorbidities6,7 few studies have looked at the issue of multimorbidity in COPD.8–10 COPD, like other chronic disorders, has been associated with comorbidities that increase in number and severity with age, and are more prevalent among deprived social groups.5,8 There is evidence that comorbidities increase the risk for exacerbations, reduce health status, and increase the risk of mortality.5,8 COPD guidelines (e.g., GOLD recommendations) still consider the diagnosis and management of comorbidities from an individual disease point of view.11 Consequently, health services focus on individual diseases rather than multimorbidity.10–13 A better knowledge of the prevalence and impact of multimorbidity facing COPD patients in primary care would help to evaluate whether a different approach (i.e., multimorbidity) should be taken. [...]The IPCRG provided funding for this research project as an UNLOCK Group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. Novartis has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study will include data from the Optimum Patient Care Research Database, and is undertaken in collaboration with Optimum Patient Care and the Respiratory Effectiveness Group, which will provide the data for this initiative without charge to the UNLOCK Group.info:eu-repo/semantics/publishedVersio

Binding of C4b-binding protein: A molecular mechanism of serum resistance of Neisseria gonorrhoeae

We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-binding protein (C4bp). Microbial surface-bound C4bp demonstrated cofactor activity. We constructed gonococcal strains with hybrid porin (Por) molecules derived from each of the major serogroups (Por1A and Por1B) of N. gonorrhoeae, and showed that the loop 1 of Por1A is required for C4bp binding. Por1B loops 5 and 7 of serum-resistant gonococci together formed a negatively charged C4bp-binding domain. C4bp-Por1B interactions were ionic in nature (inhibited by high salt or by heparin), whereas the C4bp-Por1A bond was hydrophobic. Only recombinant C4bp mutant molecules containing the NH2-terminal alpha-chain short consensus repeat (SCR1) bound to both Por1A and Por1B gonococci, suggesting that SCR1 contained Por binding sites. C4bp alpha-chain monomers did not bind gonococci, indicating that the polymeric form of C4bp was required for binding. Using fAb fragments against C4bp SCR1, C4bp binding to Por1A and Por1B strains was inhibited in a complement-dependent serum bactericidal assay. This resulted in complete killing of these otherwise fully serum resistant strains in only 10% normal serum, underscoring the importance of C4bp in mediating gonococcal serum resistance

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Marknadsorientering av socialtjänstens individ- och familjeomsorg : om villkor, processer och konsekvenser

Since the end of the 1980s, the introduction of market mechanisms in the public sector has been a dominant feature in Sweden. The same is true for the social services in several municipalities, where business style behaviour and organisation, and competition have become salient features of market-oriented social services. The aim of the study is to describe and analyse: the structural conditions for market oriented personal social services; how social workers pursue client centred work in market oriented personal social services; the consequences of this market orientation on the personal social services. The empirical study is a case study of the personal social services in the municipality of Linköping. The purchaser-provider model in Linköping is one of the most advanced and discussed in Sweden. The research comprises a quantitative pilot study and a qualitative main study. The main study is based on twenty semi-structured interviews with experienced social workers and their immediate superiors. The analysis of the interviews reveals that the personal social services are only achieving to a lesser extent the ends that a quasi-market, theoretically, should achieve. The conditions that have to be satisfied to achieve the ends of the quasi-market are only partly met. Bureaucratic control is one important reason why the personal social services are imperfect as a quasi- market. The re-organisation has resulted in a number of, to some extent, positive consequences. The re-organisation has, however, also resulted in some negative consequences. In the thesis these are categorised in terms of fragmentation, antagonism and obscurity. A linguistic change, in market oriented personal social services, appears to have influenced social workers to think and act differently in relation to their work. The most important conclusion drawn from the study is that the market oriented personal social services partly function as a responsive quasi-market for strong, rational and well- informed clients. However, in relation to the most vulnerable, it is failing in many respects.digitalisering@um