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| 2. |
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| 3. |
- Azevedo, Flavio, et al.
(författare)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
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Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 4. |
- Butler, C. C., et al.
(författare)
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Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial
- 2020
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 395:10217, s. 42-52
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Tidskriftsartikel (refereegranskat)abstract
- Background Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. Methods We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. Findings Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1.29, 95% Bayesian credible interval [BCrI] 1.20-1.39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1.13 to 1.72. The estimated absolute mean benefit from oseltamivir was 1.02 days (95% [BCrI] 0.74-1.31) overall, and in the prespecified subgroups, ranged from 0.70 (95% BCrI 0.30-1.20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3.20 (95% BCrI 1.00-5.50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. Interpretation Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 5. |
- Van Bavel, Jay J., et al.
(författare)
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National identity predicts public health support during a global pandemic
- 2022
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Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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| 6. |
- Schwartz, K. L., et al.
(författare)
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Best practice guidance for antibiotic audit and feedback interventions in primary care: a modified Delphi study from the Joint Programming Initiative on Antimicrobial resistance: Primary Care Antibiotic Audit and Feedback Network (JPIAMR-PAAN)
- 2023
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Ingår i: Antimicrobial Resistance and Infection Control. - 2047-2994. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrimary care is a critical partner for antimicrobial stewardship efforts given its high human antibiotic usage. Peer comparison audit and feedback (A & F) is often used to reduce inappropriate antibiotic prescribing. The design and implementation of A & F may impact its effectiveness. There are no best practice guidelines for peer comparison A & F in antibiotic prescribing in primary care.ObjectiveTo develop best practice guidelines for peer comparison A & F for antibiotic prescribing in primary care in high income countries by leveraging international expertise via the Joint Programming Initiative on Antimicrobial Resistance-Primary Care Antibiotic Audit and Feedback Network.MethodsWe used a modified Delphi process to achieve convergence of expert opinions on best practice statements for peer comparison A & F based on existing evidence and theory. Three rounds were performed, each with online surveys and virtual meetings to enable discussion and rating of each best practice statement. A five-point Likert scale was used to rate consensus with a median threshold score of 4 to indicate a consensus statement.ResultsThe final set of guidelines include 13 best practice statements in four categories: general considerations (n = 3), selecting feedback recipients (n = 1), data and indicator selection (n = 4), and feedback delivery (n = 5).ConclusionWe report an expert-derived best practice recommendations for designing and evaluating peer comparison A & F for antibiotic prescribing in primary care. These 13 statements can be used by A & F designers to optimize the impact of their quality improvement interventions, and improve antibiotic prescribing in primary care.
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| 7. |
- Kathiresan, Sekar, et al.
(författare)
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Common variants at 30 loci contribute to polygenic dyslipidemia
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
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| 8. |
- Bongard, E., et al.
(författare)
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Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC(4) E): the ALIC(4) E protocol
- 2018
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. Methods and analysis Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5days. We aim to recruit at least 2500 participants 1year presenting with influenza-like illness (ILI), with symptom duration 72hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12-64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (48hours/>48-72hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. Ethics and dissemination Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations.
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| 9. |
- Kuokkanen, S, et al.
(författare)
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A putative vulnerability locus to multiple clerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2
- 1996
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 13:4, s. 477-480
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by multifocal damage of myelin in the central nervous system (CNS). The prevalence of this putative autoimmune disease is 0.1% in individuals of northern European origin. Family, adoption and twin studies implicate genetic factors in the aetiology. MS is widely speculated to be a multifactorial disorder with a complex mode of inheritance. Despite many studies of candidate genes, only an association with HLA-DR2-DQ6 has been generally detected, and the number of susceptibility genes remains unknown. The chronic variant of experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease in rodents, represents a relevant animal model for MS given the chronic relapsing disease course and inflammatory changes of CNS observed in these demyelinating disorders. Susceptibility to EAE is also influenced by the major histocompatibility complex (MHC). Human syntenic regions to murine loci predisposing to EAE were tested as candidate regions for genetic susceptibility of MS. Three chromosomal regions (1p22-q23, 5p14-p12 and Xq13.2-q22) were screened in 21 Finnish multiplex MS families most originating from a high risk region in western Finland. Several markers yielded positive lod scores on 5p14-p12, syntenic to the murine locus Eae2. Our data provide evidence for a predisposing locus for MS on 5p14-p12.
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| 10. |
- Li, X., et al.
(författare)
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Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC(4)E trial in 15 European countries
- 2023
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Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7598 .- 1618-7601. ; 24:6, s. 909-922
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Tidskriftsartikel (refereegranskat)abstract
- Background Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries. Methods Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers' and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed. Results The healthcare payers' expected ICERs of oseltamivir were euro22,459 per QALY gained in adults/adolescents and euro13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is euro8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged euro1-euro35 per patient). Conclusion Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers' perspective (if willingness-to-pay per QALY gained > euro22,459) and cost-saving in adults/adolescents from a societal perspective.
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| 11. |
- Michalsen, B. O., et al.
(författare)
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Regional and national antimicrobial stewardship activities: a survey from the Joint Programming Initiative on Antimicrobial Resistance-Primary Care Antibiotic Audit and Feedback Network (JPIAMR-PAAN)
- 2023
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Ingår i: Jac-Antimicrobial Resistance. - 2632-1823. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Antibiotic overuse and misuse in primary care are common, highlighting the importance of antimicrobial stewardship (AMS) efforts in this setting. Audit and feedback (A&F) interventions can improve professional practice and performance in some settings. Objectives and methods To leverage the expertise from international members of the Joint Programming Initiative on Antimicrobial Resistance - Primary care Antibiotic Audit and feedback Network (JPIAMR-PAAN). Network members all have experience of designing and delivering A&F interventions to reduce inappropriate antibiotic prescribing in primary care settings. We aim to introduce the network and explore ongoing A&F activities in member regions. An online survey was administered to all network members to collect regional information. Results Fifteen respondents from 11 countries provided information on A&F activities in their country, and national/regional antibiotic stewardship programmes or policies. Most countries use electronic medical records as the primary data source, antibiotic appropriateness as the main outcome of feedback, and target GPs as the prescribers of interest. Funding sources varied across countries, which could influence the frequency and quality of A&F interventions. Nine out of 11 countries reported having a national antibiotic stewardship programme or policy, which aim to provide systematic support to ongoing AMS efforts and aid sustainability. Conclusions The survey identified gaps and opportunities for AMS efforts that include A&F across member countries in Europe, Canada and Australia. JPIAMR-PAAN will continue to leverage its members to produce best practice resources and toolkits for antibiotic A&F interventions in primary care settings and identify research priorities.
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| 12. |
- Ouchi, D., et al.
(författare)
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Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries
- 2022
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Ingår i: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 39:3, s. 398-405
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Tidskriftsartikel (refereegranskat)abstract
- Lay Summary Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms. Background Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. Objective We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. Methods Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. Results A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 +/- 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). Conclusion Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.
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| 13. |
- van Buul, Laura W, et al.
(författare)
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The Development of a Decision Tool for the Empiric Treatment of Suspected Urinary Tract Infection in Frail Older Adults: A Delphi Consensus Procedure.
- 2018
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1538-9375 .- 1525-8610. ; 19:9, s. 757-764
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Tidskriftsartikel (refereegranskat)abstract
- Nonspecific signs and symptoms combined with positive urinalysis results frequently trigger antibiotic therapy in frail older adults. However, there is limited evidence about which signs and symptoms indicate urinary tract infection (UTI) in this population. We aimed to find consensus among an international expert panel on which signs and symptoms, commonly attributed to UTI, should and should not lead to antibiotic prescribing in frail older adults, and to integrate these findings into a decision tool for the empiric treatment of suspected UTI in this population.A Delphi consensus procedure.An international panel of practitioners recognized as experts in the field of UTI in frail older patients.In 4 questionnaire rounds, the panel (1) evaluated the likelihood that individual signs and symptoms are caused by UTI, (2) indicated whether they would prescribe antibiotics empirically for combinations of signs and symptoms, and (3) provided feedback on a draft decision tool.Experts agreed that the majority of nonspecific signs and symptoms should be evaluated for other causes instead of being attributed to UTI and that urinalysis should not influence treatment decisions unless both nitrite and leukocyte esterase are negative. These and other findings were incorporated into a decision tool for the empiric treatment for suspected UTI in frail older adults with and without an indwelling urinary catheter.A decision tool for suspected UTI in frail older adults was developed based on consensus among an international expert panel. Studies are needed to evaluate whether this decision tool is effective in reaching its aim: the improvement of diagnostic evaluation and treatment for suspected UTI in frail older adults.
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| 14. |
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| 15. |
- Harbin, N. J., et al.
(författare)
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Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis
- 2021
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 39:4, s. 527-532
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Tidskriftsartikel (refereegranskat)abstract
- Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of >= 30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. Design Secondary analysis of randomized controlled trial data. Setting Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. Subjects A total of 277 ILI patients aged one year or older and symptom duration of <= 72 h. Main outcome measures Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. Results At baseline, 20% (55/277) had CRP concentrations >= 30mg/L (range 0-210). CRP concentration >= 30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration >= 30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). Conclusion There was no association between CRP concentration of >= 30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.
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| 16. |
- Hartman, Esther A R, et al.
(författare)
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Effect of a multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for suspected urinary tract infections in frail older adults (ImpresU): pragmatic cluster randomised controlled trial in four European countries.
- 2023
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 0959-535X .- 1756-1833. ; 380
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate whether antibiotic prescribing for suspected urinary tract infections in frail older adults can be reduced through a multifaceted antibiotic stewardship intervention.Pragmatic, parallel, cluster randomised controlled trial, with a five month baseline period and a seven month follow-up period.38 clusters consisting of one or more general practices (n=43) and older adult care organisations (n=43) in Poland, the Netherlands, Norway, and Sweden, from September 2019 to June 2021.1041 frail older adults aged 70 or older (Poland 325, the Netherlands 233, Norway 276, Sweden 207), contributing 411 person years to the follow-up period.Healthcare professionals received a multifaceted antibiotic stewardship intervention consisting of a decision tool for appropriate antibiotic use, supported by a toolbox with educational materials. A participatory-action-research approach was used for implementation, with sessions for education, evaluation, and local tailoring of the intervention. The control group provided care as usual.The primary outcome was the number of antibiotic prescriptions for suspected urinary tract infections per person year. Secondary outcomes included the incidence of complications, all cause hospital referrals, all cause hospital admissions, all cause mortality within 21 days after suspected urinary tract infections, and all cause mortality.The numbers of antibiotic prescriptions for suspected urinary tract infections in the follow-up period were 54 prescriptions in 202 person years (0.27 per person year) in the intervention group and 121 prescriptions in 209 person years (0.58 per person year) in the usual care group. Participants in the intervention group had a lower rate of receiving an antibiotic prescription for a suspected urinary tract infection compared with participants in the usual care group, with a rate ratio of 0.42 (95% confidence interval 0.26 to 0.68). No differences between intervention and control group were observed in the incidence of complications (<0.01 v 0.05 per person year), hospital referrals (<0.01 v 0.05), admissions to hospital (0.01 v 0.05), and mortality (0 v 0.01) within 21 days after suspected urinary tract infections, nor in all cause mortality (0.26 v 0.26).Implementation of a multifaceted antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infections in frail older adults.ClinicalTrials.gov NCT03970356.
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| 17. |
- Junttila, T T, et al.
(författare)
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Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells
- 2005
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Ingår i: Cancer Research. - 1538-7445. ; 65:4, s. 1384-1393
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Tidskriftsartikel (refereegranskat)abstract
- ErbB1 and ErbB2 receptors are well-characterized targets for anticancer drugs, but the clinical relevance of the related ErbB4 receptor is unknown. Here, we have assessed the clinical significance of the proteolytically cleavable ErbB4 isoforms in breast cancer patients and investigated their functions in vitro. The expression of transcripts encoding the cleavable ErbB4 isoforms associated with estrogen receptor-{alpha} (ER) expression (P < 0.001) and a high histologic grade of differentiation (P ≤ 0.002) in real-time reverse transcription-PCR analysis of 62 breast cancer samples. Despite high ErbB4 mRNA expression levels in a subset of samples, ErbB4 gene amplification was not observed. High ErbB4 protein expression levels, as assessed by immunohistochemistry, associated with a favorable outcome in ER-positive cases from a series of 458 breast cancer patients (P = 0.01), whereas no association between ErbB4 expression and survival was found among women with ER-negative cancer (P = 0.86). However, nuclear ErbB4 immunoreactivity was associated with poor survival as compared with women whose cancer had membranous ErbB4 staining (P = 0.04). In vitro, overexpression of a cleavable ErbB4 isoform in ER-positive breast cancer cells resulted in translocation of a proteolytically released intracellular ErbB4 receptor fragment into the nucleus, as well as, enhanced proliferation, anchorage-independent growth, and estrogen response element–mediated transcriptional activity. These results suggest that the association of ErbB4 expression with clinical outcome is dependent on the subcellular localization of ErbB4 and that a proteinase-cleavable ErbB4 isoform promotes growth of ER-positive breast cancer and enhances ER-mediated gene transcription.
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| 18. |
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| 19. |
- Li, X., et al.
(författare)
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Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC(4)E Trial
- 2021
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Ingår i: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 41:8, s. 685-699
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone. Methods Resource use data were extracted from participants' daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed. Results Patients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: euro17 [0-95% Crl: 16-19] vs. euro24 [5-100% Crl: 18-29]; healthcare provider: euro37 [28-67] vs. euro44 [25-55]; healthcare payers: euro54 [45-85] vs. euro68 [45-81]; and society: euro423 [399-478] vs. euro451 [390-478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences. Conclusion The average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant.
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| 20. |
- Verheij, T. J., et al.
(författare)
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Clinical presentation, microbiological aetiology and disease course in patients with flu-like illness: A post hoc analysis of randomised controlled trial data
- 2022
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Ingår i: British Journal of General Practice. - 0960-1643. ; 72:716
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Tidskriftsartikel (refereegranskat)abstract
- Background There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. Aim To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found. Design and setting Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care (n = 3266) in 15 European countries. Method Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. Results Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. Conclusion Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-andsee policy in most of these patients with flu-like illness seems the best option. © 2022 Royal College of General Practitioners. All rights reserved.
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| 21. |
- Wanat, M., et al.
(författare)
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Transformation of primary care during the COVID-19 pandemic: experiences of healthcare professionals in eight European countries
- 2021
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Ingår i: British Journal of General Practice. - : Royal College of General Practitioners. - 0960-1643 .- 1478-5242. ; 71:709
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Tidskriftsartikel (refereegranskat)abstract
- Background I'm Tian/care has a crucial role in responding to the COVID-19 pandemic as the first point of patient care and gatekeeper to secondary care. Qualitative studies exploring the experiences of healthcare professionals during the COVID-19 pandemic have mainly focused on secondary care. Aim To gain an understanding of the experiences of European primary care professionals (PCPs) working during the first peak of the COVID-19 pandemic. Design and setting An exploratory qualitative study, using semi structured interviews in primary care in England, Belgium, the Netherlands. Ireland. Germany, Poland, Greece, and Sweden, between April and July 7020. Method Interviews were audiorecorded, transcribed, and analysed using a combination of inductive and deductive thematic analysis techniques. Results Fighty interviews were conducted with PCPs. PCPs had to make their own decisions on how to rapidly transform services in relation to COVID-19 and non-COVID-19 care. Despite being overwhelmed with guidance. they often lacked access to practical training. Consequently. PCPs turned to their colleagues for moral support and information to try to quickly adjust to new ways of working, including remote care. arid to deal with uncertainty. Conclusion PCPs rapidly transformed primary care delivery despite a number of challenges. Representation of primary care at policy level and engagement with local primary care champions are needed to facilitate easy and coordinated access to practical information on how to adapt services, ongoing training, and access to appropriate mental health support services for PCPs. Preservation of autonomy and responsiveness of primary care are critical to preserve the ability for rapid transformation in any future crisis of care delivery.
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| 22. |
- Aberg, Fredrik, et al.
(författare)
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A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease
- 2021
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Ingår i: HEPATOLOGY COMMUNICATIONS. - : John Wiley & Sons. - 2471-254X. ; 5:6, s. 1021-1035
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Tidskriftsartikel (refereegranskat)abstract
- The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Hartman, E. A. R., et al.
(författare)
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Decisions on antibiotic prescribing for suspected urinary tract infections in frail older adults: a qualitative study in four European countries
- 2022
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Ingår i: Age and ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 51:6
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Tidskriftsartikel (refereegranskat)abstract
- Background a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. Objectives (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. Methods we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. Results participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. Conclusions decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.
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| 27. |
- Hartman, E. A. R., et al.
(författare)
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Multifaceted antibiotic stewardship intervention using a participatory-action-research approach to improve antibiotic prescribing for urinary tract infections in frail elderly (ImpresU): study protocol for a European qualitative study followed by a pragmatic cluster randomised controlled trial
- 2021
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Almost 60% of antibiotics in frail elderly are prescribed for alleged urinary tract infections (UTIs). A substantial part of this comprises prescriptions in case of non-specific symptoms or asymptomatic bacteriuria, for which the latest guidelines promote restrictiveness with antibiotics. We aim to reduce inappropriate antibiotic use for UTIs through an antibiotic stewardship intervention (ASI) that encourages to prescribe according to these guidelines. To develop an effective ASI, we first need a better understanding of the complex decision-making process concerning suspected UTIs in frail elderly. Moreover, the implementation approach requires tailoring to the heterogeneous elderly care setting. Methods and analysis First, we conduct a qualitative study to explore factors contributing to antibiotic prescribing for UTIs in frail elderly, using semi-structured interviews with general practitioners, nursing staff, patients and informal caregivers. Next, we perform a pragmatic cluster randomised controlled trial in elderly care organisations. A multifaceted ASI is implemented in the intervention group; the control group receives care as usual. The ASI is centred around a decision tool that promotes restrictive antibiotic use, supported by a toolbox with educational materials. For the implementation, we use a modified participatory-action-research approach, guided by the results of the qualitative study. The primary outcome is the number of antibiotic prescriptions for suspected UTIs. We aim to recruit 34 clusters with in total 680 frail elderly residents >= 70 years. Data collection takes place during a 5-month baseline period and a 7-month follow-up period. Finally, we perform a process evaluation. The study has been delayed for 6 months due to COVID-19 and is expected to end in July 2021. Ethics and dissemination Ethical approvals and/or waivers were obtained from the ethical committees in Poland, the Netherlands, Norway and Sweden. The results will be disseminated through publication in peer-reviewed journals and conference presentations.
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| 28. |
- Heltveit-Olsen, S. R., et al.
(författare)
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Experiences and management strategies of Norwegian GPs during the COVID-19 pandemic: a longitudinal interview study
- 2023
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 41:1, s. 2-12
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Tidskriftsartikel (refereegranskat)abstract
- Objective When the COVID-19 pandemic reached Norway, primary health care had to reorganize to ensure safe patient treatment and maintain infection control. General practitioners (GPs) are key health care providers in the municipalities. Our aim was to explore the experiences and management strategies of Norwegian GPs during the COVID-19 pandemic - over time, and in the context of a sudden organizational change. Design Longitudinal qualitative interview study with two interview rounds. The first round of interviews was conducted from September-December 2020, the second round from January-April 2021. In the first interview round, we performed eight semi-structured interviews with GPs from eight municipalities in Norway. In the second round, five of the GPs were re-interviewed. Consecutive interviews were performed 2-4 months apart. To analyze the data, we used thematic analysis. Results The COVID-19 pandemic required GPs to balance several concerns, such as continuity of care and their own professional efforts. Several GPs experienced challenges in the collaboration with the municipality and in relation to defining their own professional position. Guided by The Norwegian Association of General practitioners, The Norwegian College of General Practice and collegial support, they found viable solutions and ended up with a feeling of having adapted to a new normal. Conclusions Although our study demonstrates that the GPs adapted to the changing conditions, the current municipal health care models are not ideal. There is a need for clarification of responsibilities between GPs and the municipality to facilitate a more coordinated future pandemic response.
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| 29. |
- Heltveit-Olsen, Silje Rebekka, et al.
(författare)
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Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU)
- 2022
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Methenamine hippurate is a urinary antiseptic used as preventive treatment for recurrent urinary tract infections (UTIs) in some Scandinavian countries. However, the scientific evidence for the preventive effect and safety for longer-term use is limited. The aim of this study is to assess whether methenamine hippurate can reduce the incidence of UTIs in older women with recurrent UTIs. Methods and analysis The ImpresU consortium is a collaboration between Norway, Sweden, Poland and the Netherlands. The study is a randomised, controlled, triple-blind phase IV clinical trial. Women ≥70 years with recurrent UTIs are screened for eligibility in a general practice setting. We aim to include 400 women in total, with 100 recruited from each collaborating country. The participants are randomised to treatment with methenamine hippurate 1 g or placebo tablets two times per day for a treatment period of 6 months, followed by a drug-free follow-up period of 6 months. The primary outcome is number of antibiotic treatments for UTIs during the treatment period. The secondary outcomes include number of antibiotic treatments for UTIs during the follow-up period and self-reported symptom of severity and duration of UTI episodes. Differences in complications between the treatment groups are measured as safety outcomes. We also aim to investigate whether strain characteristics or phylogenetic subgroups of Escherichia coli present in the urine culture at inclusion have a modifying effect on the outcomes. Ethics and dissemination Ethical approvals are obtained in all participating countries. The results will be communicated in peer-reviewed journals and at scientific conferences. Trial registration number ClinicalTrials.gov Registry (NCT04077580); EudraCT: 2018-002235-15.
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| 30. |
- Hoste, M. E., et al.
(författare)
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The experiences of patients ill with COVID-19-like symptoms and the role of testing for SARS-CoV-2 in supporting them: A qualitative study in eight European countries during the first wave of the pandemic
- 2023
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Ingår i: European Journal of General Practice. - 1381-4788. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAccess to testing during the first wave of the COVID-19 pandemic was limited, impacting patients with COVID-19-like symptoms. Current qualitative studies have been limited to one country or were conducted outside Europe.ObjectivesTo explore - in eight European countries - the experiences of patients consulting in primary care with COVID-19-like symptoms during the first wave of the pandemic.MethodsSixty-six semi-structured interviews, informed by a topic guide, were conducted by telephone or in person between April and July 2020. Patients with COVID-19-like symptoms were purposively recruited in primary care sites in eight countries and sampled based on age, gender, and symptom presentation. Deductive and inductive thematic analysis techniques were used to develop a framework representing data across settings. Data adequacy was attained by collecting rich data.ResultsSeven themes were identified, which described the experiences of patients consulting. Two themes are reported in this manuscript describing the role of COVID-19 testing in this experience. Patients described significant distress due to their symptoms, especially those at higher risk of complications from COVID-19, and those with severe symptoms. Patients wanted access to testing to identify the cause of their illness and minimise the burden of managing uncertainty. Some patients testing positive for COVID-19 assumed they would be immune from future infection.ConclusionPatients experiencing novel and severe symptoms, particularly those with comorbidities, experienced a significant emotional and psychological burden due to concerns about COVID-19. Testing provided reassurance over health status and helped patients identify which guidance to follow. Testing positive for SARS-CoV-2 led to some patients thinking they were immune from future infection, thus influencing subsequent behaviour.
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| 31. |
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| 32. |
- Kanberg, Nelly, et al.
(författare)
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Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up.
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19.Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15).One hundred patients with mild (n=24), moderate (n=28), and severe (n=48) COVID-19 were followed for a median (IQR) of 225 (187-262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r=0·53, p < 0·001) and GFAp (r=0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n=40), "brain-fog" (n=29), and changes in cognition (n=25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase.The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury.The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project.
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| 33. |
- Lampi, Elina, 1967, et al.
(författare)
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Interventions for prudent antibiotic use in primary healthcare: an econometric analysis
- 2020
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Rational antibiotic prescribing is crucial to combat antibiotic resistance. Optimal strategies to improve antibiotic use are not known. Strama, the Swedish strategic program against antibiotic resistance, has been successful in reducing antibiotic prescription rates. This study investigates whether two specific interventions directed toward healthcare centers, an informational visit and a self-evaluation meeting, played a role in observed reduction in rates of antibiotic prescriptions in primary healthcare. Methods The study was a retrospective, observational, empirical analysis exploiting the variation in the timing of the interventions and considering past prescriptions through use of estimations from dynamic panel data models. Primary healthcare data from 2011 to 2014 were examined. Data were from public and private primary healthcare centers in western Sweden. The key variables were prescription of antibiotics and indicator variables for the two interventions. Results The first intervention, an educational information intervention, decreased the number of prescriptions among public healthcare centers, but this effect was only temporary. We found no proof that the second intervention, a self-evaluation meeting at the healthcare center, had an impact on the reduction of prescriptions. Conclusions Single educational interventions aimed at influencing rates of antibiotic prescriptions have limited impact. A multifaceted approach is needed in efforts to reduce the use of antibiotics in primary health care.
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| 34. |
- Lourido, J, et al.
(författare)
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Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care
- 2002
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 62:4, s. 285-292
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hyper- as well as hypoglycemia may be detrimental for brain energy metabolism and even a moderate increase in blood glucose concentration can affect outcome adversely. During physiological conditions, glucose concentration obtained from microdialysis of subcutaneous adipose tissue adequately reflects plasma glucose concentration. This study examines whether this correlation is also obtained during intensive care in patients with severe injuries. Methods.. The study included 62 patients with severe traumatic brain injuries. All patients received one 30 mm microdialysis catheter (CMA 60, CMA Microdialysis) inserted into periumbilical subcutaneous adipose tissue. The probe was perfused (0.3 mul/min) with a Ringer solution from a microinfusion Pump and analyzed for glucose, lactate, and glycerol. The Study included 2.434 simultaneous analyses of glucose concentration in arterial blood and subcutaneous adipose tissue. Results.' The correlation coefficient for glucose concentration in blood and interstitial fluid was 0.743 for the whole material. The cot-relation was relatively poor for 1-6h after insertion of the probes, During this period. a continuous increase in the Subcutaneous level Of glucose and decreases in lactate and glycerol were noted. Conclusions: The correlation between blood glucose concentration and glucose Concentration in subcutaneous adipose tissue was not as good during intensive care as in normal humans. The poor correlation during the first 6h probably reflects a stress reaction (and possibly local vasoconstriction). Microdialysis of subcutaneous adipose tissue permits frequent bedside analyses of the biochemical composition of the extracellular fluid and may be of value during routine intensive care provided the methodological limitations are recognized.
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| 35. |
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| 36. |
- Pussinen, PJ, et al.
(författare)
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Periodontitis decreases the antiatherogenic potency of high density lipoprotein.
- 2004
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 45:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis, a consequence of persistent bacterial infection and chronic inflammation, has been suggested to predict coronary heart disease (CHD). The aim of this study was to investigate the impact of periodontitis on HDL structure and antiatherogenic function in cholesterol efflux in vitro. HDL was isolated from 30 patients (age 43.6 +/- 6.1 years, mean +/- SD) with periodontitis before and after (3.2 +/- 1.4 months) periodontal treatment. The capacity of HDL for cholesterol efflux from macrophages (RAW 264.7), HDL composition, and key proteins of HDL metabolism were determined. After periodontal treatment, phospholipid transfer protein (PLTP) activity was 6.2% (P<0.05) lower, and serum HDL cholesterol concentration, PLTP mass, and cholesteryl ester transfer protein activity were 10.7% (P<0.001), 7.1% (P=0.078), and 19.4% (P<0.001) higher, respectively. The mean HDL2/HDL3 ratio increased from 2.16 +/- 0.87 to 3.56 +/- 0.48 (P<0.05). HDL total phospholipid mass and sphingomyelin-phosphatidylcholine ratio were 7.4% (P<0.05) and 36.8% (P<0.001) higher, respectively. The HDL-mediated cholesterol efflux tended to be higher after periodontal treatment; interestingly, this increase was significant (P<0.05) among patients whose C-reactive protein decreased (53.7% reduction, P=0.015) and who were positive by PCR for Actinobacillus actinomycetemcomitans. These results suggest that periodontitis causes similar, but milder, changes in HDL metabolism than those that occur during the acute-phase response and that periodontitis may diminish the antiatherogenic potency of HDL, thus increasing the risk for CHD.
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| 37. |
- Pussinen, PJ, et al.
(författare)
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Severe periodontitis enhances macrophage activation via increased serum lipopolysaccharide.
- 2004
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 24:11, s. 2174-2180
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation. METHODS AND RESULTS: LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30+/-0.19 versus 1.48+/-0.28 mmol/L; P=0.002) and HDL/LDL ratio (0.31+/-0.01 versus 0.34+/-0.10; P=0.048), but lower serum LPS concentration (1.70+/-0.49 versus 0.98+/-0.50 ng/mL; P=0.004) and autoantibodies to beta2-glycoprotein I (0.11+/-0.06 versus 0.09+/-0.04 ELISA units; P=0.022) after treatment. CONCLUSIONS: Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.
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| 38. |
- Rystedt, Karin, et al.
(författare)
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Is C-reactive protein associated with influenza A or B in primary care patients with influenza-like illness? A cross-sectional study.
- 2020
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Ingår i: Scandinavian journal of primary health care. - : Informa UK Limited. - 1502-7724 .- 0281-3432. ; 38:4, s. 447-53
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Tidskriftsartikel (refereegranskat)abstract
- Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. An accurate, cheap and easy to use biomarker might enhance targeting influenza-specific management in primary care. The aim of this study was to investigate if C-reactive protein (CRP) is associated with influenza A or B, confirmed with PCR testing, in patients presenting with ILI.Cross-sectional study.Primary care in Lithuania, Norway and Sweden.A total of 277 patients at least 1year of age consulting primary care with ILI during seasonal influenza epidemics.Capillary blood CRP analysed as a point-of-care test and detection of influenza A or B on nasopharyngeal swabs in adults, and nasal and pharyngeal swabs in children using PCR.The prevalence of positive tests for influenza A among patients was 44% (121/277) and the prevalence of influenza B was 21% (58/277). Patients with influenza A infection could not be identified based on CRP concentration. However, increasing CRP concentration in steps of 10mg/L was associated with a significantly lower risk for influenza B with an adjusted odds ratio of 0.42 (0.25-0.70; p<.001). Signs of more severe symptoms like shortness of breath, sweats or chills and dizziness were associated with higher CRP.There was no association between CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. Hence, CRP testing should be avoided in ILI, unless bacterial pneumonia is suspected. Key points Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. There was no association between concentration of CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. A consequence is that CRP testing should be avoided in ILI, unless bacterial pneumonia or similar is suspected.
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| 39. |
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| 40. |
- Sundvall, H., et al.
(författare)
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Prevalence and initiation of statin therapy in the oldest old-a longitudinal population-based study
- 2022
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 78:9, s. 1459-1467
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To investigate the prevalence and initiation of statins as well as treatment intensity in the oldest old, with younger olds as a reference. Methods A population-based cohort was used, including record-linked data from the Total Population Register, the Swedish Prescribed Drug Register, and the Swedish Patient Register. In each year over the study period (2009-2015), statin use was described in individuals 85 years or older and 65-84 years of age, and initiation rates were calculated among individuals with no statin treatment during a preceding 3-year period. Results A total of 1,764,836 individuals >= 65 years in 2009, increasing to 2,022,764 in 2015, were included in the analyses. In individuals 85 years or older, the prevalence of statin therapy increased from 11% in 2009 to 16% in 2015, the corresponding initiation rates being 1.3% and 1.7%, respectively. Corresponding prevalence and incidence figures in 65-84-year-olds were 23 to 25% and 3.0 to 3.3%, respectively. Overall, the proportion of individuals initiating statin with high-intensity treatment (atorvastatin >= 40 mg or rosuvastatin >= 20 mg) in the oldest old increased from 1 to 36% during the study period, and a similar increase was seen in the younger age group. Over the study years, the presence of an established indication for statin treatment varied between 70 and 76% in the oldest old and between 30 and 39% in the younger olds. Conclusion Prevalence and initiation of statin therapy are increasing among the oldest old, despite the fact that randomized controlled trials focusing on this age group are lacking and safety signals are difficult to detect.
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| 41. |
- Sundvall, H., et al.
(författare)
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Use of statins in the elderly according to age and indicationa cross-sectional population-based register study
- 2019
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 75:7, s. 959-967
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo investigate statin use in the elderly by age (80 vs. 65-79years) in relation to established indications.MethodsA population-based cohort, including data from four registers, encompassing inhabitants in Region Vastra Gotaland, Sweden, was used. Statin users were defined as those filling statin prescriptions 75% of the year 2010. Primary care and hospital diagnoses in 2005-2010 regarding ischemic heart disease, stroke, transient ischemic attacks, and diabetes were considered established indications.ResultsA total of 278,205 individuals were analyzed. In individuals aged 80 and 65-79years (n=81,885 and n=196,320, respectively), 17% (95% confidence interval 17%; 18%) and 23% (23%; 23%) respectively, were statin users. Among the statin users, 74% (73%; 74%) of those aged 80 and 60% (59%; 60%) of those aged 65-79years had 1 established indication. Conversely, of those with 1 established indication, 30% (30%; 31%) and 53% (52%; 53%) were on statins in the respective age groups. Logistic regression revealed that age, nursing home residence, and multi-dose drug dispensing were the most prominent negative predictors for statin use; adjusted odds ratios (95% confidence interval): 0.45 (0.44; 0.46), 0.39 (0.36; 0.42), and 0.47 (0.44; 0.49), respectively.ConclusionsIn the oldest old (80years), statin users were fewer and had more often an established indication, suggesting that physicians extrapolate scientific evidence for beneficial effects in younger age groups to the oldest, but require a more solid ground for treatment. As the oldest old, nursing home residents, and those with multi-dose drug-dispensing were statin users to a lesser extent, physicians may often refrain from treatment in those with lower life expectancy, either due to age or to severely reduced health status. In both age groups, our results however also indicate some over- as well as undertreatment.
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| 42. |
- Sundvall, Mats, et al.
(författare)
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Identification of murine loci associated with susceptibility to chronic experimental autoimmune encephalomyelitis
- 1995
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 10:3, s. 313-317
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Tidskriftsartikel (refereegranskat)abstract
- B10.RIII mice develop chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after immunization with the myelin basic protein (MBP) peptide 89−101. The disease is associated with the major histocompatibility complex (MHC) (eae1). We have now investigated the importance of non−MHC regions for the EAE susceptibility in a cross between RIIIS/J and B10.RIII mice which share the MHC region but differ in disease susceptibility. Linkage analysis using microsatellite markers spanning the genome identified a region (eae2) on chromosome 15 which showed linkage to disease (P=0.0002). Our data also suggest linkage to a second region (eae3) on chromosome 3 (P=0.0024), and provide evidence for locus interactions between eae2 and eae3. These results provide clues to the genetic basis of multiple sclerosis.
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| 44. |
- Wanat, M., et al.
(författare)
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Patients’ and clinicians’ perspectives on the primary care consultations for acute respiratory infections during the first wave of the COVID-19 pandemic: an eight-country qualitative study in Europe
- 2022
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Ingår i: BJGP Open. - 2398-3795. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The impact of the COVID-19 pandemic on patients’ and clinicians’ perceptions of healthcare-seeking behaviour and delivery of care is unclear. The pandemic accelerated the use of remote care, and understanding its benefits and drawbacks may inform its implementation during current and future healthcare emergencies. Aim: To explore patients’ and primary care professionals’ (PCPs) experiences of primary care delivery in the first wave of the pandemic. Design & setting: Qualitative study using semi-structured interviews in primary care in eight European countries (England, Ireland, Belgium, the Netherlands, Greece, Poland, Sweden, and Germany). Method: A total of 146 interviews were conducted with 80 PCPs and 66 patients consulting for respiratory tract infection (RTI) symptoms, in eight European countries. Data were collected between April and July 2020, and analysed using thematic analysis. Results: It was found that patients accepted telemedicine when PCPs spent time to understand and address their concerns, but a minority preferred in-person consultations. PCPs felt that remote consultations created emotional distance between themselves and patients, and they reported having to manage diverse COVID-19-related medical and social concerns. Conclusion: Remote consultations for RTI symptoms may be acceptable long term if both groups are happy to use this format, but it is important that PCPs take time to address patients’ concerns and provide safety-netting advice.
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| 45. |
- Wanat, M., et al.
(författare)
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Supporting Primary Care Professionals to Stay in Work During the COVID-19 Pandemic: Views on Personal Risk and Access to Testing During the First Wave of Pandemic in Europe
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimising primary care professionals' (PCPs) risk of SARS-CoV-2 infection is crucial to ensure their safety as well as functioning health care system. PCPs' perspectives on the support they needed in the early stages of a public health crisis can inform future preparedness. Aim: To understand PCPs' experiences of providing care during the COVID-19 pandemic, with focus on personal risk from COVID-19 and testing. Design and Setting: Qualitative study using semi-structured interviews with PCPs in England, Belgium, the Netherlands, Ireland, Germany, Poland, Greece and Sweden, between April and July 2020. Method: Interviews were analysed using a combination of inductive and deductive thematic analysis techniques. Results: Eighty interviews were conducted, showing that PCPs tried to make sense of their risk of both contracting and severity of COVID-19 by assessing individual risk factors and perceived effectiveness of Personal Protective Equipment (PPE). They had limited access to PPE yet continued providing care as their "duty." Some PCPs felt that they were put in high-risk situations when patients or colleagues were not flagging symptoms of COVID-19. Not having access to testing in the initial stages of the pandemic was somewhat accepted but when available, was valued. Conclusion: Access to adequate PPE and testing, as well as training for staff and education for patients about the importance of ensuring staff safety is crucial. Given PCPs' varied response in how they appraised personal risk and their tolerance for working, PCPs may benefit from the autonomy in deciding how they want to work during health emergencies.
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