Managing exacerbations of chronic obstructive pulmonary disease - An investigation of treatment decisions from a primary care perspective

The paper II of this thesis is not available in Munin. Paper II: Laue, J., Melbye, H., Risør, M. B.: “Self-treatment of acute exacerbations of chronic obstructive pulmonary disease requires more than symptom recognition – A qualitative study of COPD patients’ perspectives on self-treatment”. Published version available in BMC Fam Pract. 2017; 18: 8. Exacerbations of chronic obstructive pulmonary disease (COPD) compose a considerable burden for both patients and health care systems. Optimal management in primary care, including self-treatment of COPD exacerbations with antibiotics and oral corticosteroids, is considered to be one key for providing good care for patients at reasonable costs. This thesis aimed to explore treatment of COPD exacerbations with antibiotics and/or oral corticosteroids and hospitalization from different primary care perspectives, e.g. guidelines, general practitioners and patients. A systematic review of treatment criteria for antibiotics and oral corticosteroids in national and international COPD guidelines, and an assessment of the underlying evidence for these recommendations composed the first part of the project. The results showed that the recommended treatment criteria were mostly based on respiratory symptoms, and that the studies the recommendations are based on are often conducted with patients that are not representative for a primary care setting. The second study explored COPD patients’ perspective on self-treatment with antibiotics and oral corticosteroids through a thematic analysis of 12 semi-structured in-depths interviews. We found that concerns with the medications’ adverse effects play a key role in CODD patients’ decisions to initiate self-treatment with antibiotics and/or oral corticosteroids. The nature of the patient-physician relationship including the patients’ understanding of legitimacy to seek help is important to their help seeking behaviour when feeling insecure about the need for treatment or in case of treatment failure. The third study investigated GPs’ accounts of their decision-making regarding treatment with antibiotics and oral corticosteroids and hospitalization through a thematic analysis of seven focus group discussions. The results show that one main driver of GPs’ decision-making are worries about having overlooked a severe underlying illness. GPs consider at holistic understanding of illness and the patients’ own experiential knowledge important to make reasonable decisions for the individual patient under medical uncertainty. Moreover, GPs’ decisions depend on the availability and reliability of other formal and informal carers, and the healthcare systems’ organization and sociocultural ‘code of conduct’. Overall, the findings of this thesis support an integrative and collaborative approach to management of COPD exacerbations. The heterogeneous, versatile and often individualized nature of COPD exacerbations requires a flexible framework to decision-making that integrates both medical knowledge and other types of knowledge that are grounded in human experience and relationships. Such an integrative understanding of knowledge may guide future clinical research and guideline development in considering primary care evidence and expertise from primary care stakeholders and patients to a larger extent, and may also facilitate collaborative management of COPD exacerbations that allows for sharing expertise and responsibility between patients and the involved carers.Forverringer av kronisk obstruktiv lungesykdom (KOLS) er en betydelig byrde for pasienter og helsesystemer. Optimal behandling av KOLS forverringer i primærhelsetjenesten, inkludert egenbehandling med antibiotika og orale kortikosteroider, ansees som meget viktig for å sikre god behandling og samtidig redusere den økonomiske byrden. Denne avhandlingen ønsker å øke kunnskapen om behandling av KOLS pasienter med eksaserbasjoner i primærhelsetjenesten ved å utforske tre forskjellige perspektiver (retningslinjer, pasienter og allmennleger) på dette fenomenet. Denne avhandlingen er basert på tre studier. Første studie er en systematisk review av behandlingskriterier for antibiotika og orale kortikosteroider i nasjonale og internasjonale KOLS retningslinjer og en kritisk evaluering av evidensen som anbefalingene er basert på. Resultatene viser at behandlingskritene er hovedsakelig basert på respiratoriske symptomer og at evidensen er i lite grad overførbar til en primærhelsetjenestekontekst. I den andre studien ble KOLS pasienters erfaringer med egenbehandling utforsket ved tematisk analyse av 12 semi-strukturerte dybde-intervjuer. Hovedfunnene viser at bekymringer for medisinenes bivirkninger spiller en viktig rolle i pasientens beslutninger angående behandlingsstart, og at lege-pasient forholdet inkludert pasientens forståelse av eget ansvar for behandlingen kan påvirke i stor grad om og når pasienter søker hjelp ved usikkerhet eller når behandlingen ikke virker. Målet for den tredje studien var å utforske allmennlegers beslutninger på behandling av KOLS eksaserbasjoner med antibiotika og orale kortikosteroider, og innleggelser, ved tematisk analyse av 7 fokusgruppeintervjuer fra forskjellige europeiske land og Hongkong. Hovedfunnene viser at usikkerhet og redsel for å ha oversett alvorlig sykdom er sterke pådrivere i allmennlegers beslutninger. Allmennlegene syntes at en holistisk forståelse av sykdommen og å involvere pasienters erfaringsbasert kunnskap i beslutningene er viktig for adekvat behandling av den enkelte pasienten. Samlet støtter resultatene av de tre studiene integrativ og samhandlingsbasert behandling av KOLS pasienter med eksaserbasjoner. De heterogene, komplekse og ofte individualiserte KOLS eksaserbasjoner krever en fleksibel ramme for beslutninger som integrerer både biomedisinsk kunnskap og andre typer kunnskap som er basert på menneskers erfaring og relasjoner. En slik integrativ forståelse av kunnskap vil kunne guide fremtidig klinisk forskning og utvikling av retningslinjer i å ta større hensyn til medisinsk kunnskap og ekspertise fra primærhelsetjenesten og pasienter, og vil også kunne fremme samhandling basert på deling av kunnskap og ansvar mellom pasienter og helsepersonell, og helsepersonell imellom

Hybrid umbilical cord blood banking: literature review.

PURPOSE Interest gaps between public and private umbilical cord blood banks have led to the introduction of hybrid banking options. Hybrid models combine features of private and public banks as well as interests of parents, children and of patients, in order to find an optimized solution. While several different models of hybrid banks exist, there is a lack of literature about this novel model of cord blood stem cell banking. Therefore, the aim of this literature review is to assess different options of umbilical cord blood banking and whether hybrid banking could be a valuable alternative to the existing public and private cord blood banking models. METHODS We performed a systematic literature search, using five main databases. Five hybrid models regarding their advantages as well as their challenges are discussed in this review. RESULTS We found that a wealth of literature exists about public cord blood banking, while private and hybrid banking are understudied. Different modalities of hybrid cord blood banking are being described in several publications, providing the basis to assess different advantages and disadvantages as well as practicability. CONCLUSION Hybrid banks, especially the sequential model, seem to have potential as an alternative to the existing banking models worldwide. A previously conducted survey among pregnant women showed a preference for hybrid banking, if such an option was available. Nevertheless, opinions among stakeholders differ and more research is needed to evaluate, if hybrid banking provides the expected benefits

Self-treatment of acute exacerbations of chronic obstructive pulmonary disease requires more than symptom recognition – a qualitative study of COPD patients’ perspectives on self-treatment

Source at http://dx.doi.org/10.1186/s12875-017-0582-8 Background: Self-treatment of acute exacerbations of COPD with antibiotics and/or oral corticosteroids has emerged as a promising strategy to reduce hospitalization rates, mortality and health costs. However, for reasons little understood, the effect of self-treatment, particularly when not part of comprehensive self-management programs, remains unclear. Therefore, this study aims to get insight into the patients’ perspective on self-treatment of acute exacerbations of COPD, focusing specifically on how patients decide for the right moment to start treatment with antibiotics and/or oral corticosteroids, what they consider important when making this decision and aspects which might interfere with successful implementation. Methods: We interviewed 19 patients with chronic obstructive pulmonary disease using qualitative semi-structured interviews, and applied thematic analysis for data analysis. Results: Patients were well equipped with experiential knowledge to recognize and promptly respond to worsening COPD symptoms. Worries regarding potential adverse effects of antibiotics and oral corticosteroids played an important role in the decision to start treatment and could result in hesitation to start treatment. Although selftreatment represented a practical and appreciated option for some patients with predictable symptom patterns and treatment effect, all patients favoured assistance from a medical professional when their perceived competence reached its limits. However, a feeling of obligation to succeed with self-treatment or distrust in their doctors or the health care system could keep patients from timely help seeking. Conclusion: COPD patients regard self-treatment of exacerbations with antibiotics and/or oral corticosteroids as a valuable alternative. How they engage in self-treatment depends on their concerns regarding the medications’ adverse effects as well as on their understanding of and preferences for self-treatment as a means of health care. Caregivers should address these perspectives in a collaborative approach when offering COPD patients the opportunity for self-treatment of exacerbations

How do general practitioners implement decision-making regarding COPD patients with exacerbations? An international focus group study

Purpose: To explore the decision-making of general practitioners (GPs) concerning treatment with antibiotics and/or oral corticosteroids and hospitalization for COPD patients with exacerbations. Methods: Thematic analysis of seven focus groups with 53 GPs from urban and rural areas in Norway, Germany, Wales, Poland, Russia, the Netherlands, and Hong Kong. Results: Four main themes were identified. 1) Dealing with medical uncertainty: the GPs aimed to make clear medical decisions and avoid unnecessary prescriptions and hospitalizations, yet this was challenged by uncertainty regarding the severity of the exacerbations and concerns about overlooking comorbidities. 2) Knowing the patient: contextual knowledge about the individual patient provided a supplementary framework to biomedical knowledge, allowing for more differentiated decision-making. 3) Balancing the patients’ perspective: the GPs considered patients’ experiential knowledge about their own body and illness as valuable in assisting their decision-making, yet felt that dealing with disagreements between their own and their patients’ perceptions concerning the need for treatment or hospitalization could be difficult. 4) Outpatient support and collaboration: both formal and informal caregivers and organizational aspects of the health systems influenced the decision-making, particularly in terms of mitigating potentially severe consequences of “wrong decisions” and concerning the negotiation of responsibilities. Conclusion: Fear of overlooking severe comorbidity and of further deteriorating symptoms emerged as a main driver of GPs’ management decisions. GPs consider a holistic understanding of illness and the patients’ own judgment crucial to making reasonable decisions under medical uncertainty. Moreover, GPs’ decisions depend on the availability and reliability of other formal and informal carers, and the health care systems’ organizational and cultural code of conduct. Strengthening the collaboration between GPs, other outpatient care facilities and the patients’ social network can ensure ongoing monitoring and prompt intervention if necessary and may help to improve primary care for COPD patients with exacerbations

Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition

Selective targeting of aneuploid cells is an attractive strategy for cancer treatment(1). Here, we mapped the aneuploidy landscapes of ~1,000 human cancer cell lines, and analyzed genetic and chemical perturbation screens(2–9) to reveal aneuploidy-associated cellular vulnerabilities. We identified and validated an increased sensitivity of aneuploid cancer cells to genetic perturbation of core components of the spindle assembly checkpoint (SAC), which ensures the proper segregation of chromosomes during mitosis(10). Surprisingly, we also found aneuploid cancer cells to be less sensitive to short-term exposures to multiple SAC inhibitors. Indeed, aneuploid cancer cells became increasingly more sensitive to SAC inhibition (SACi) over time. Aneuploid cells exhibited aberrant spindle geometry and dynamics, and kept dividing in the presence of SACi, resulting in accumulating mitotic defects, and in unstable and less fit karyotypes. Therefore, although aneuploid cancer cells could overcome SACi more readily than diploid cells, their long-term proliferation was jeopardized. We identified a specific mitotic kinesin, KIF18A, whose activity was perturbed in aneuploid cancer cells. Aneuploid cancer cells were particularly vulnerable to KIF18A depletion, and KIF18A overexpression restored their response to SACi. Our study reveals a novel, therapeutically-relevant, synthetic lethal interaction between aneuploidy and the SAC

Hybrid cord blood banking in a private-public-partnership: Women's perspectives.

BACKGROUND The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public foreign donor banks and private family-directed donor banks. Recently, our department has introduced a third banking model within a private-public-partnership. This hybrid banking allows for storage of family-directed CB units, while also getting Human leukocyte antigen (HLA)-typed and included in the national stem cell donor registry. So if the need arises, the HLA-compatible CB unit can be released to an unrelated recipient as a foreign donor stem cell graft. OBJECTIVES The aim of this study was to evaluate women's perspectives on the different CB banking options as well as retrospective satisfaction with their decisions. METHODS We performed a prospective survey study in postpartum women, using a validated questionnaire. RESULTS A total of 157 women were included in this survey study; 68% of them decided to have their UCB stored or donated. Among those women, 25% of them opted for hybrid storage, 72% of respondents stored UCB publicly, and 3% decided for private family-directed storage. CONCLUSIONS Our study shows the potential of hybrid banking as an attractive UCB storage option, as an alternative to family-directed banking rather than a substitute for public donation. Hybrid storage potentially combines advantages of family-directed banking as well as unrelated CB donation expanding the number of registered CB units available for transplantation and giving every pregnant woman the possibility to store UCB

When should acute exacerbations of COPD be treated with systemic corticosteroids and antibiotics in primary care: a systematic review of current COPD guidelines.

Not all patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) benefit from treatment with systemic corticosteroids and antibiotics. The aim of the study was to identify criteria recommended in current COPD guidelines for treating acute exacerbations with systemic corticosteroids and antibiotics and to assess the underlying evidence. Current COPD guidelines were identified by a systematic literature search. The most recent guidelines as per country/organisation containing recommendations about treating acute exacerbations of COPD were included. Guideline development and criteria for treating acute exacerbations with systemic corticosteroids and antibiotics were appraised. Randomised controlled trials directly referred to in context with the recommendations were evaluated in terms of study design, setting, and study population. A total of 19 COPD guidelines were included. Systemic corticosteroids were often universally recommended to all patients with acute exacerbations. Criteria for treatment with antibiotics were mainly an increase in respiratory symptoms. Objective diagnostic tests or clinical examination were only rarely recommended. Only few criteria were directly linked to underlying evidence, and the trial patients represented a highly specific group of COPD patients. Current COPD guidelines are of little help in primary care to identify patients with acute exacerbations probably benefitting from treatment with systemic corticosteroids and antibiotics in primary care, and might contribute to overuse or inappropriate use of either treatment

Migration health research in Norway: a scoping review

Aims: To provide an overview of published research on migration and health conducted in Norway and identify gaps in the research field. Methods: Applying a scoping review methodology, we searched Medline for articles on migration health in Norway published between 2008 and 2020, and assessed them according to research topic, methodology, user-involvement and characteristics of the populations studied (country or area of origin, type of migrant/immigrant status). Results: Of the 707 articles retrieved, 303 met the inclusion criteria. Most studies (77%) were within the clinical disciplines reproductive health, mental health, infectious diseases and cardiovascular diseases, or on socio-cultural aspects and the use of healthcare services. One third of the papers (36%) pulled participants from various geographic backgrounds together or did not specify the geographic background. Among those who did so, participants were mostly from The Middle East, South and Southeast Asia and sub-Saharan Africa. Only 14% of the articles specified the type of migrant/immigrant status and those included refugees, asylum seekers and undocumented migrants. A total of 80% of the papers used quantitative methods, of which 15 described an intervention; 15 papers (5%) described different types of user-involvement. Conclusions: Our findings suggest gaps in research related to migrant subgroups, such as those from Eastern-Europe and labour and family reunification migrants. Future studies should further investigate the self-identified health needs of different migrant groups, and might also benefit from a methodological shift towards more intervention studies and participatory approaches.</b

Long-Term Varicella Zoster Virus Immunity in Paediatric Liver Transplant Patients Can Be Achieved by Booster Vaccinations&mdash;A Single-Centre, Retrospective, Observational Analysis

Varicella is one of the most common vaccine-preventable infections after paediatric solid organ transplantation; thus, vaccination offers simple and cheap protection. However, children with liver disease often progress to liver transplantation (LT) before they reach the recommended vaccination age. As a live vaccine, varicella zoster virus (VZV) vaccination after transplantation is controversial; however, many case series demonstrate that vaccination may be safe and effective in paediatric liver transplant recipients. Only limited data exists describing long-term vaccination response in such immunocompromised patients. We investigated retrospectively vaccination response in paediatric patients before and after transplantation and describe long-term immunity over ten years, including the influence of booster-vaccinations. In this retrospective, single-centre study, 458 LT recipients were analysed between September 2004 and June 2021. Of these, 53 were re-transplantations. Patients with no available vaccination records and with a history of post-transplant lymphoproliferative disease, after hematopoietic stem cell transplantation and clinical chickenpox were excluded from this analysis (n = 198). In total, data on 207 children with a median annual follow-up of 6.2 years was available: 95 patients (45.9%) were unvaccinated prior to LT. Compared to healthy children, the response to vaccination, measured by seroconversion, is weaker in children with liver disease: almost 70% after one vaccination and 93% after two vaccinations. One year after transplantation, the mean titres and the number of children with protective antibody levels (VZV IgG &ge; 50 IU/L) decreased from 77.5% to 41.3%. Neither diagnosis, gender, nor age were predictors of vaccination response. Booster-vaccination was recommended for children after seroreversion using annual titre measurements and led to a significant increase in mean titre and number of protected children. Response to vaccination shows no difference from monotherapy with a calcineurin inhibitor to intensified immunosuppression by adding prednisolone or mycophenolate mofetil. Children with liver disease show weaker seroconversion rates to VZV vaccination compared to healthy children. Therefore, VZV-na&iuml;ve children should receive basic immunization with two vaccine doses as well as those vaccinated only once before transplantation. An average of 2&ndash;3 vaccine doses are required in order to achieve a long-term seroconversion and protective antibody levels in 95% of children