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1.
Br J Sports Med ; 57(22): 1419-1427, 2023 Nov.
Article En | MEDLINE | ID: mdl-37793699

The WHO has called for action to integrate physical activity promotion into healthcare settings, yet there is a lack of consensus on the competencies required by health professionals to deliver effective movement behaviour change support. The objective of this study was to establish key competencies relevant for all health professionals to support individuals to change their movement behaviours. Consensus was obtained using a three-phase Delphi process. Participants with expertise in physical activity and sedentary behaviour were asked to report what knowledge, skills and attributes they believed health professionals should possess in relation to movement behaviour change. Proposed competencies were developed and rated for importance. Participants were asked to indicate agreement for inclusion, with consensus defined as group level agreement of at least 80%. Participants from 11 countries, working in academic (55%), clinical (30%) or combined academic/clinical (13%) roles reached consensus on 11 competencies across 3 rounds (n=40, n=36 and n=34, respectively). Some competencies considered specific to certain disciplines did not qualify for inclusion. Participants agreed that health professionals should recognise, take ownership of, and practise interprofessional collaboration in supporting movement behaviour change; support positive culture around these behaviours; communicate using person-centred approaches that consider determinants, barriers and facilitators of movement behaviours; explain the health impacts of these behaviours; and recognise how their own behaviour influences movement behaviour change support. This consensus defines 11 competencies for health professionals, which may serve as a catalyst for building a culture of advocacy for movement behaviour change across health disciplines.


Exercise , Health Personnel , Humans , Delphi Technique , Sedentary Behavior , Consensus
2.
BMC Public Health ; 22(1): 1784, 2022 09 20.
Article En | MEDLINE | ID: mdl-36127688

BACKGROUND: An implementation gap exists between the evidence supporting physical activity in the prevention and management of long-term medical conditions and clinical practice. Person-centred conversations, i.e. focussing on the values, preferences and aspirations of each individual, are required from healthcare professionals. However, many currently lack the capability, opportunity, and motivation to have these conversations. This study uses the Behaviour Change Wheel (BCW) to inform the development of practical and educational resources to help bridge this gap. METHODS: The BCW provides a theoretical approach to enable the systematic development of behaviour change interventions. Authors followed the described eight-step process, considered results from a scoping review, consulted clinical working groups, tested and developed ideas across clinical pathways, and agreed on solutions to each stage by consensus. RESULTS: The behavioural diagnosis identified healthcare professionals' initiation of person-centred conversations on physical activity at all appropriate opportunities in routine medical care as a suitable primary target for interventions. Six intervention functions and five policy categories met the APEASE criteria. We mapped 17 Behavioural Change Techniques onto BCW intervention functions to define intervention strategies. CONCLUSIONS: This study uses the BCW to outline a coherent approach for intervention development to improve healthcare professionals' frequency and quality of conversations on physical activity across clinical practice. Time-sensitive and role-specific resources might help healthcare professionals understand the focus of their intervention. Educational resources aimed at healthcare professionals and patients could have mutual benefit, should fit into existing care pathways and support professional development. A trusted information source with single-point access via the internet is likely to improve accessibility. Future evaluation of resources built and coded using this framework is required to establish the effectiveness of this approach and help improve understanding of what works to change conversations around physical activity in clinical practice.


Behavior Therapy , Exercise , Behavior Therapy/methods , Communication , Delivery of Health Care , Humans , Motivation
3.
BMJ Open Sport Exerc Med ; 8(2): e001280, 2022.
Article En | MEDLINE | ID: mdl-35813130

Objectives: Healthcare is a fundamental action area in population efforts to address the global disease burden from physical inactivity. However, healthcare professionals lack the knowledge, skills and confidence to have regular conversations about physical activity. This study aimed to: (1) understand the requirements of healthcare professionals and patients from a resource to support routine physical activity conversations in clinical consultations and (2) develop such a resource. Methods: This study used codesign principles across two phases, actively involving relevant stakeholders in an iterative development process. The preparatory phase included a scoping literature review and workshops with multidisciplinary healthcare professionals and patients. The Delphi phase included the development of a draft resource, a three-stage modified online Delphi study and an external review. Results: The scoping review highlighted the importance of addressing time restrictions, a behaviour change skill deficit, the need for resources to fit into existing systems and meeting patient expectations. Consultation included 69 participants across two clinical workshops. They recommended using the internet, valued guidance on all aspects of physical activity conversations and were concerned about how to use a person-centred approach. The Delphi phase, including 15 expert participants, met agreement criteria in two stages to develop the resource. Conclusion: This mixed-methods study delivered an online resource that was codesigned with and based on the requirements of healthcare professionals and patients. The resource presents condition-specific '1-minute', '5-minute' and 'more minute' person-centred and evidence-based conversation templates on physical activity in an accessible and usable format to meet the needs of real-life clinical practice.

4.
Br J Sports Med ; 56(8): 427-438, 2022 Apr.
Article En | MEDLINE | ID: mdl-34649919

INTRODUCTION: The benefits of physical activity for people living with long-term conditions (LTCs) are well established. However, the risks of physical activity are less well documented. The fear of exacerbating symptoms and causing adverse events is a persuasive barrier to physical activity in this population.This work aimed to agree clear statements for use by healthcare professionals about medical risks of physical activity for people living with LTCs through expert consensus. These statements addressed the following questions: (1) Is increasing physical activity safe for people living with one or more LTC? (2) Are the symptoms and clinical syndromes associated with common LTCs aggravated in the short or long term by increasing physical activity levels? (3) What specific risks should healthcare professionals consider when advising symptomatic people with one or more LTCs to increase their physical activity levels? METHODS: Statements were developed in a multistage process, guided by the Appraisal of Guidelines for Research and Evaluation tool. A patient and clinician involvement process, a rapid literature review and a steering group workshop informed the development of draft symptom and syndrome-based statements. We then tested and refined the draft statements and supporting evidence using a three-stage modified online Delphi study, incorporating a multidisciplinary expert panel with a broad range of clinical specialties. RESULTS: Twenty-eight experts completed the Delphi process. All statements achieved consensus with a final agreement between 88.5%-96.5%. Five 'impact statements' conclude that (1) for people living with LTCs, the benefits of physical activity far outweigh the risks, (2) despite the risks being very low, perceived risk is high, (3) person-centred conversations are essential for addressing perceived risk, (4) everybody has their own starting point and (5) people should stop and seek medical attention if they experience a dramatic increase in symptoms. In addition, eight symptom/syndrome-based statements discuss specific risks for musculoskeletal pain, fatigue, shortness of breath, cardiac chest pain, palpitations, dysglycaemia, cognitive impairment and falls and frailty. CONCLUSION: Clear, consistent messaging on risk across healthcare will improve people living with LTCs confidence to be physically active. Addressing the fear of adverse events on an individual level will help healthcare professionals affect meaningful behavioural change in day-to-day practice. Evidence does not support routine preparticipation medical clearance for people with stable LTCs if they build up gradually from their current level. The need for medical guidance, as opposed to clearance, should be determined by individuals with specific concerns about active symptoms. As part of a system-wide approach, consistent messaging from healthcare professionals around risk will also help reduce cross-sector barriers to engagement for this population.


Cognitive Dysfunction , Exercise , Consensus , Health Personnel , Humans
5.
PLoS One ; 16(9): e0257802, 2021.
Article En | MEDLINE | ID: mdl-34559846

BACKGROUND: In 2017 Public Health England and Sport England commissioned a Consultant-led Sport and Exercise Medicine (SEM) pilot to test the feasibility and acceptability of embedding physical activity interventions in secondary care clinical pathways. The aim of this paper is to report qualitative findings exploring the experience of healthcare professionals (HCPs) and patients involved in the Active Hospital pilot. METHODS: Qualitative data was collected by semi-structured interviews with Active Hospital pilot SEM Consultants, and staff and patients involved in three clinical pathways. Interviews with SEM Consultants explored the experience of developing and implementing the pilot. Interviews with staff and patients explored the experience of delivering and receiving Active Hospital interventions. Data were analysed thematically. RESULTS: Interviews identified the importance of the Active Hospital pilot being Consultant-led for the following reasons; i) having trusting relationships with decision makers, ii) having sufficient influence to effect change, iii) identifying champions within the system, and iv) being adaptable to change and ensuring the programme fits within the wider strategic frameworks. HCPs emphasised the importance of the Active Hospital interventions fitting easily within existing work practices, the need for staff training and to tailor interventions for individual patient needs. The Active Hospital pilot was well received by patients, however a lack of dedicated resource and capacity to deliver the intervention was highlighted as a challenge by both patients and HCPs. CONCLUSION: The SEM Consultants' ability to navigate the political climate of a large National Health Service (NHS) Trust with competing agendas and limited resource was valuable. The interventions were well received and a valued addition to usual clinical care. However, implementation and ongoing delivery of the pilot encountered challenges including lack of capacity within the system and delays with recruiting to the delivery teams in each pathway.


Exercise/physiology , Health Personnel/psychology , Patients/psychology , England , Feasibility Studies , Hospitals , Humans , Interviews as Topic , Male , Occupational Health , Qualitative Research , State Medicine
6.
FASEB J ; 33(7): 8043-8054, 2019 07.
Article En | MEDLINE | ID: mdl-30916999

Resolution of inflammation is poorly understood in Achilles tendon disorders. Herein, we investigated the bioactive lipid mediator profiles of tendon-derived stromal cells isolated from patients with Achilles tendinopathy (AT) or Achilles rupture (AR) under baseline and IL-1ß-stimulated conditions. We also determined whether incubating these cells with 2 of the mediators produced by tendon-derived stromal cells, 15-epi-Lipoxin A4 (15-epi-LXA4) or maresin (MaR)-1, moderated their proinflammatory phenotype. Under baseline conditions, AT cells showed concurrent increased levels of proinflammatory eicosanoids and proresolving mediators compared with AR cells. IL-1ß treatment induced profound prostaglandin E2 release in AR compared with AT cells. Incubation of IL-1ß treated AT and AR tendon-derived stromal cells in 15-epi-LXA4 or MaR1 reduced proinflammatory eicosanoids and potentiated the release of proresolving mediators. These mediators also induced specialized proresolving mediator (SPM) biosynthetic enzymes arachidonate lipoxygenase (ALOX) 12 and ALOX15 and up-regulated the proresolving receptor ALX compared with vehicle-treated cells. Incubation in 15-epi-LXA4 or MaR1 also moderated the proinflammatory phenotype of AT and AR cells, regulating podoplanin, CD90, signal transducer and activator of transcription (STAT)-1, IL-6, IFN regulatory factor (IRF) 5, and TLR4 and suppressed c-Jun N-terminal kinase 1/2/3, Lyn, STAT-3, and STAT-6 phosphokinase signaling. In summary, we identify proresolving mediators that are active in AT and AR and propose SPMs, including 15-epi-LXA4 or MaR1, as a potential strategy to counterregulate inflammatory processes in these cells.-Dakin, S. G., Colas, R. A., Newton, J., Gwilym, S., Jones, N., Reid, H. A. B., Wood, S., Appleton, L., Wheway, K., Watkins, B., Dalli, J., Carr, A. J. 15-Epi-LXA4 and MaR1 counter inflammation in stromal cells from patients with Achilles tendinopathy and rupture.


Achilles Tendon/injuries , Docosahexaenoic Acids/pharmacology , Inflammation Mediators/pharmacology , Lipoxins/pharmacology , Rupture/pathology , Stromal Cells/drug effects , Tendinopathy/pathology , Achilles Tendon/pathology , Adult , Aged , Arachidonate 12-Lipoxygenase/metabolism , Arachidonate 15-Lipoxygenase/metabolism , Biopsy , Cells, Cultured , Eicosanoids/metabolism , Female , Gene Expression Profiling , Humans , Interleukin-1beta/pharmacology , Male , Middle Aged , Signal Transduction/drug effects , Stromal Cells/metabolism , Stromal Cells/pathology
7.
Br J Sports Med ; 52(12): 807-812, 2018 Jun.
Article En | MEDLINE | ID: mdl-29858468

OBJECTIVE: Interventions to promote walking have focused on individual or group-based approaches, often via the randomised controlled trial design. Walking can also be promoted using population health approaches. We systematically reviewed the effectiveness of population approaches to promote walking among individuals and populations. DESIGN: A systematic review. DATA SOURCES: 10 electronic databases searched from January 1990 to March 2017. ELIGIBILITY CRITERIA: Eligibility criteria include pre-experimental and postexperimental studies of the effects of population interventions to change walking, and the effects must have been compared with a 'no intervention', or comparison group/area/population, or variation in exposure; duration of ≥12 months of follow up; participants in free-living populations; and English-language articles. RESULTS: 12 studies were identified from mostly urban high-income countries (one focusing on using tax, incentivising the loss of parking spaces; and one using policy only, permitting off-leash dogs in city parks). Five studies used mass media with either environment (n=2) or community (n=3) approaches. Four studies used environmental changes that were combined with policies. One study had scaled up school-based approaches to promote safe routes to schools. We found mass media, community initiatives and environmental change approaches increased walking (range from 9 to 75 min/week).


Health Promotion/methods , Walking , Environment , Health Policy , Humans , Mass Media , Motivation , Program Evaluation , Public Health , Schools
8.
Br J Sports Med ; 52(6): 359-367, 2018 Mar.
Article En | MEDLINE | ID: mdl-29118051

BACKGROUND: Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture. METHODS: We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers. RESULTS: Tendinopathic and ruptured Achilles highly expressed CD14+ and CD68+ cells and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased PTGS2 and interleukin-8 expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells. CONCLUSIONS: Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease.


Achilles Tendon/physiopathology , Inflammation/pathology , Rupture/pathology , Tendinopathy/pathology , Achilles Tendon/cytology , Adult , Aged , Biomarkers/analysis , Biopsy , Cells, Cultured , Female , Hamstring Muscles/cytology , Humans , Male , Middle Aged , Stromal Cells/cytology , Young Adult
12.
Br J Sports Med ; 51(15): 1165-1166, 2017 Aug.
Article En | MEDLINE | ID: mdl-27601448
13.
15.
Int J Sports Physiol Perform ; 12(8): 1012-1016, 2017 Sep.
Article En | MEDLINE | ID: mdl-27967263

Meeting the energy demands of prolonged arduous expeditions and endurance sport may be a significant barrier to success. Expedition rowing is associated with high levels of body-mass loss, reflecting the challenge of meeting energy expenditure in this exacting environment. PURPOSE: To use the doubly labeled water (DLW) technique to calculate the total energy expenditure (TEE) and body-composition changes of two 28-y-old healthy male athletes during a 50-d continuous and unsupported row around Great Britain. METHODS: A measured dose of DLW was taken at the start of 2 separate study periods (days 5-19 and 34-48) followed by sequential urine collection, which was analyzed on return to land. RESULTS: Mean TEE was 15.3 MJ/d: athlete 1, 16.4 MJ/d; athlete 2, 14.9 MJ/d. Athlete 1 lost 11.2 kg and athlete 2 lost 14.9 kg of body mass during the row. Average energy provision was 19.1 MJ per 24-h ration pack. CONCLUSIONS: These results highlight the difficulty of maintaining energy balance during expedition rowing. A starvation state was observed despite dietary provision in excess of estimated energy expenditure, indicating that nutritional strategy rather than caloric availability was at fault. The authors recommend that future expeditions prioritize thorough testing and the individualization of rations to ensure that they are both palatable and practical during the weeks to months at sea.


Body Composition/physiology , Energy Metabolism/physiology , Expeditions , Starvation/etiology , Water Sports/physiology , Adult , Body Mass Index , Diet , Humans , Male , United Kingdom
16.
PLoS Negl Trop Dis ; 10(8): e0004888, 2016 Aug.
Article En | MEDLINE | ID: mdl-27486661

BACKGROUND: Dengue fever is a ubiquitous arboviral infection in tropical and sub-tropical regions, whose incidence has increased over recent decades. In the absence of a rapid point of care test, the clinical diagnosis of dengue is complex. The World Health Organisation has outlined diagnostic criteria for making the diagnosis of dengue infection, which includes the use of the tourniquet test (TT). PURPOSE: To assess the quality of the evidence supporting the use of the TT and perform a diagnostic accuracy meta-analysis comparing the TT to antibody response measured by ELISA. DATA SOURCES: A comprehensive literature search was conducted in the following databases to April, 2016: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, BIOSIS, Web of Science, SCOPUS. STUDY SELECTION: Studies comparing the diagnostic accuracy of the tourniquet test with ELISA for the diagnosis of dengue were included. DATA EXTRACTION: Two independent authors extracted data using a standardized form. DATA SYNTHESIS: A total of 16 studies with 28,739 participants were included in the meta-analysis. Pooled sensitivity for dengue diagnosis by TT was 58% (95% Confidence Interval (CI), 43%-71%) and the specificity was 71% (95% CI, 60%-80%). In the subgroup analysis sensitivity for non-severe dengue diagnosis was 55% (95% CI, 52%-59%) and the specificity was 63% (95% CI, 60%-66%), whilst sensitivity for dengue hemorrhagic fever diagnosis was 62% (95% CI, 53%-71%) and the specificity was 60% (95% CI, 48%-70%). Receiver-operator characteristics demonstrated a test accuracy (AUC) of 0.70 (95% CI, 0.66-0.74). CONCLUSION: The tourniquet test is widely used in resource poor settings despite currently available evidence demonstrating only a marginal benefit in making a diagnosis of dengue infection alone. REGISTRATION: The protocol for this systematic review was registered at PROSPERO: CRD42015020323.


Dengue/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Tourniquets , Diagnosis, Differential , Humans , Sensitivity and Specificity
17.
Cochrane Database Syst Rev ; (8): CD011857, 2016 Aug 22.
Article En | MEDLINE | ID: mdl-27545762

BACKGROUND: Influenza is an infectious virus affecting both humans and animals. In humans, symptoms present as fever, cough, sore throat, runny nose, headache, muscle and joint pain, and malaise. The epidemiological profile of influenza is influenced by multiple factors, including transmissibility of the virus and the susceptibility of the population. Annually, influenza is estimated to infect 5% to 10% of adults, with higher rates in winter seasons in countries with seasonal variation. Exercise could be an intervention to enhance immune response and limit influenza incidence and its related complications. OBJECTIVES: To assess the efficacy and safety of short and long-term exercise prior to influenza vaccination in enhancing influenza prevention in adults. SEARCH METHODS: We searched CENTRAL (2015, Issue 11), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 3 November 2015), Embase (1974 to 3 November 2015), CINAHL (1981 to 3 November 2015), LILACS (Latin American and Caribbean Health Sciences, 1982 to 3 November 2015), PEDro (1980 to 3 November 2015), SPORTDiscus (1985 to 3 November 2015), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (November 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) of short- and long-term exercise prior to influenza vaccination for the general adult population were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and checked data from the included trials using a standard form. We used the random-effects model due to differences in the type, duration, intensity and frequency of exercise in the analysis. MAIN RESULTS: We included six trials published between 2007 and 2014 that randomised 599 adult participants. Study size ranged from 46 to 158 participants. Participants were aged between 18 years and 80 years; we could not derive gender proportions, as participants' sex was not reported in all studies. One study was available in abstract form only.We did not find a significant difference in outcomes between people who exercised and those who did not exercise before receiving influenza vaccination.Pre-vaccination exercises included endurance activities such as walking or using a treadmill, and resistance activities included biceps curls and lateral raises. Five of the studies provided one session of exercise between 25 and 50 minutes. In five studies, exercise was undertaken on the same day as the vaccination. One study provided exercise over a period of eight weeks before vaccination, with one 2½ hour supervised session, plus daily home exercise practice of 45 minutes. Exercise intensity ranged from 55% to 85% of maximal heart rate. Control group participants undertook a range of activities, including quiet rest, sitting, reading, meditation or unspecified activity.One study reported numbers of people who contracted influenza; no significant difference was reported between exercise and no-exercise participants. None of the included studies reported complications related to influenza illness. Only one study, which we assessed as providing low-quality evidence, reported numbers of people who experienced adverse events. This study reported no significant difference in outcomes between people who exercised and those who did not. No studies reported numbers of working days or days lost related to influenza illness. Only two studies reported participant-centred outcomes.Overall, study quality was unclear; we assessed five of the six included studies to have at least four unclear 'Risk of bias' domains (allocation concealment, blinding of outcome assessment, selective reporting and other bias). Insufficient reporting in four studies about selective reporting did not provide enough information to enable judgement; only two studies were included in trials registers. AUTHORS' CONCLUSIONS: From the available evidence, we found that exercising before influenza vaccination is neither beneficial nor harmful. However, study data were limited and of low quality. Small sample sizes, study design limitations, exercise types, and focus on biochemical rather than participant-centred outcomes strongly influenced our findings.


Exercise , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Vaccination , Adult , Aged , Aged, 80 and over , Humans , Incidence , Influenza Vaccines/adverse effects , Influenza, Human/complications , Influenza, Human/epidemiology , Middle Aged , Randomized Controlled Trials as Topic , Resistance Training/methods , Time Factors , Walking
18.
Hypertension ; 68(1): 78-87, 2016 07.
Article En | MEDLINE | ID: mdl-27217408

Previous studies report benefits of exercise for blood pressure control in middle age and older adults, but longer-term effectiveness in younger adults is not well established. We performed a systematic review and meta-analysis of published randomized control trials with meta-regression of potential effect modifiers. An information specialist completed a comprehensive search of available data sources, including studies published up to June 2015. Authors applied strict inclusion and exclusion criteria to screen 9524 titles. Eligible studies recruited younger adults with a cardiovascular risk factor (with at least 25% of cohort aged 18-40 years); the intervention had a defined physical activity strategy and reported blood pressure as primary or secondary outcome. Meta-analysis included 14 studies randomizing 3614 participants, mean age 42.2±6.3 (SD) years. At 3 to 6 months, exercise was associated with a reduction in systolic blood pressure of -4.40 mm Hg (95% confidence interval, -5.78 to -3.01) and in diastolic blood pressure of -4.17 mm Hg (95% confidence interval, -5.42 to -2.93). Intervention effect was not significantly influenced by baseline blood pressure, body weight, or subsequent weight loss. Observed intervention effect was lost after 12 months of follow-up with no reported benefit over control, mean difference in systolic blood pressure -1.02 mm Hg (95% confidence interval, -2.34 to 0.29), and in diastolic blood pressure -0.91 mm Hg (95% confidence interval, -1.85 to 0.02). Current exercise guidance provided to reduce blood pressure in younger adults is unlikely to benefit long-term cardiovascular risk. There is need for continued research to improve age-specific strategies and recommendations for hypertension prevention and management in young adults.


Blood Pressure Determination/methods , Exercise Therapy/methods , Hypertension/therapy , Prehypertension/therapy , Adolescent , Adult , Age Factors , Cardiovascular Diseases/prevention & control , Female , Humans , Hypertension/diagnosis , Male , Prehypertension/diagnosis , Prognosis , Randomized Controlled Trials as Topic , Risk Assessment , Severity of Illness Index , Stroke/prevention & control , Treatment Outcome , Young Adult
19.
Thorax ; 65(3): 201-7, 2010 Mar.
Article En | MEDLINE | ID: mdl-19825784

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP. METHODS: A prospective, observational cohort study was carried out in two university hospital intensive care units recruiting 73 patients with clinically suspected VAP, and a semi-urban primary care practice recruiting a reference group of 21 age- and sex-matched volunteers. Growth of pathogens at >10(4) colony-forming units (cfu)/ml of bronchoalveolar lavage fluid (BALF) distinguished VAP from "non-VAP". Inflammatory mediators were quantified in BALF and serum. Mediators showing significant differences between patients with and without VAP were analysed for diagnostic utility by receiver operator characteristic (ROC) curves. RESULTS: Seventy-two patients had recoverable lavage-24% had VAP. BALF interleukin-1beta (IL-1beta), IL-8, granulocyte colony-stimulating factor and macrophage inflammatory protein-1alpha were significantly higher in the VAP group (all p<0.005). Using a cut-off of 10 pg/ml, BALF IL-1beta generated negative likelihood ratios for VAP of 0.09. In patients with BALF IL-1beta <10 pg/ml the post-test probability of VAP was 2.8%. Using a cut-off value for IL-8 of 2 ng/ml, the positive likelihood ratio was 5.03. There was no difference in cytokine levels between patients with sterile BALF and those with growth of <10(4) cfu/ml. CONCLUSIONS: BALF IL-1beta and IL-8 are amongst the strongest markers yet identified for accurately demarcating VAP within the larger population of patients with suspected VAP. These findings have potential implications for reduction in unnecessary antibiotic use but require further validation in larger populations.


Interleukin-1beta/analysis , Interleukin-8/analysis , Pneumonia, Ventilator-Associated/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/microbiology , Epidemiologic Methods , Female , Humans , Inflammation Mediators/analysis , Male , Middle Aged , Pneumonia, Ventilator-Associated/microbiology , Young Adult
20.
Am J Respir Crit Care Med ; 180(1): 19-28, 2009 Jul 01.
Article En | MEDLINE | ID: mdl-19324972

RATIONALE: Critically ill patients are highly susceptible to hospital-acquired infection. Neutrophil function in critical illness remains poorly understood. OBJECTIVES: To characterize and define mechanisms of peripheral blood neutrophil (PBN) dysfunction in critically ill patients. To determine whether the inflamed lung contributes additional phagocytic impairment. METHODS: Prospective collection of blood and bronchoalveolar lavage fluid from patients with suspected ventilator-associated pneumonia and from age- and sex-matched volunteers; laboratory analysis of neutrophil functions. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients and 21 volunteers were included. Phagocytic capacity of PBNs was 36% lower in patients than in volunteers (P < 0.0001). From several biologically plausible candidates only activated complement was significantly associated with impaired PBN phagocytosis (P < 0.0001). Phagocytosis was negatively correlated with serum C3a and positively correlated with expression of C5a receptor type 1 (CD88) on PBNs. C5a recapitulated impaired PBN phagocytosis and significantly down-regulated CD88 expression in vitro. C5a-mediated phagocytic impairment was prevented by blocking either CD88 or phosphoinositide 3-kinase, and completely reversed by granulocyte-macrophage colony-stimulating factor. C5a also impaired killing of Pseudomonas aeruginosa by, and migration of, PBNs, indicating that effects were not restricted to phagocytosis. Bronchoalveolar lavage fluid leukocytes from patients also demonstrated significantly impaired function, and lavage supernatant reduced phagocytosis in healthy neutrophils by 43% (P = 0.0001). However, lavage fluid did not affect CD88 expression and lavage-mediated impairment of phagocytosis was not blocked by anti-CD88 antibody. CONCLUSIONS: Critically ill patients have significant dysfunction of PBNs, which is mediated predominantly by activated complement. Further, profound complement-independent neutrophil dysfunction occurs in the inflamed lung.


Complement C5a/physiology , Neutrophils/physiology , Phagocytosis/physiology , Pneumonia, Ventilator-Associated/blood , Receptors, Complement/physiology , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , Case-Control Studies , Complement C3a/analysis , Complement C3a/physiology , Complement C5a/analysis , Female , Humans , Male , Middle Aged , Pneumonia, Ventilator-Associated/immunology , Receptor, Anaphylatoxin C5a
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