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The chemokines CXCL8 and CXCL12:molecular and functional properties,role in disease and efforts towards pharmacological intervention

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Cellular & Molecular Immunology 2023年第3期20卷 217-251页

作者： Seppe Cambier mieke gouwy Paul Proost Laboratory of Molecular Immunology Rega InstituteDepartment of MicrobiologyImmunology and TransplantationKU LeuvenLeuvenBelgium

Chemokines are an indispensable component of our immune system through the regulation of directional migration and activation of leukocytes.CxCL8 is the most potent human neutrophil-attracting chemokine and plays crucial roles in the response to infection and tissue injury.CXCL8 activity inherently depends on interaction with the human CXC chemokine receptors CXCR1 and CXCR2,the atypical chemokine receptor ACKR1,and glycosaminoglycans.Furthermore,(hetero)dimerization and tight regulation of transcription and translation,as well as post-translational modifications further fine-tune the spatial and temporal activity of CXCL8 in the context of inflammatory diseases and cancer.The CxCL8 interaction with receptors and glycosaminoglycans is therefore a promising target for therapy,as illustrated by multiple ongoing clinical trials.CXCL8-mediated neutrophil mobilization to blood is directly opposed by CXCL12,which retains leukocytes in bone marrow.CXCL12 is primarily a homeostatic chemokine that induces migration and activation of hematopoietic progenitor cells,endothelial cells,and several leukocytes through interaction with CXCR4,ACKR1,and ACKR3.Thereby,it is an essential player in the regulation of embryogenesis,hematopoiesis,and angiogenesis.However,CXCL12 can also exert inflammatory functions,as illustrated by its pivotal role in a growing list of pathologies and its synergy with CXCL8 and other chemokines to induce leukocyte chemotaxis.Here,we review the plethora of information on the CXCL8 structure,interaction with receptors and glycosaminoglycans,different levels of activity regulation,role in homeostasis and disease,and therapeutic prospects.Finally,we discuss recent research on CXCL12 biochemistry and biology and its role in pathology and pharmacology.

关键词： CXCL8 CXCL12 atypical chemokine receptor GPCR glycosaminoglycan

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Neutrophil chemoattractant receptors in health and disease: double-edged swords

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Cellular & Molecular Immunology 2020年第5期17卷 433-450页

作者： mieke Metzemaekers mieke gouwy Paul Proost Laboratory of Molecular Immunology Rega InstituteKU LeuvenHerestraat 49 bus 1042B-3000 LeuvenBelgium

Neutrophils are frontline cells of the innate immune system.These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential.Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis,for inflammation modulation and resolution,wound healing and tissue repair.After fulfilling the appropriate effector functions,however,dampening neutrophil activation and infiltration is crucial to prevent damage to the host.In humans,chemoattractant molecules can be categorized into four biochemical families,i.e.,chemotactic lipids,formyl peptides,complement anaphylatoxins and chemokines.They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs.Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors(GPCRs).In addition,emerging evidence suggests an important role for atypical chemoattractant receptors(ACKRs)that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses.The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation,with a pivotal modulatory role for the(inflammatory)environment.Here,we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease.Depending on the(patho)physiological context,specific chemoattractant receptors may be up-or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences,thus opening new windows for the identification of disease biomarkers and potential drug targets.

关键词： Neutrophils chemoattractant G protein-coupled receptors chemokine leukocyte migration

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Chemoattractants and cytokines in primary ciliary dyskinesia and cystic fibrosis: key players in chronic respiratory diseases

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Cellular & Molecular Immunology 2018年第4期15卷 312-323页

作者： Maaike Cockx mieke gouwy Jo Van Damme Sofie Struyf Laboratory of Molecular Immunology Department of Microbiology and ImmunologyRega Institute for Medical ResearchUniversity of LeuvenLeuven 3000Belgium

Patients with primary ciliary dyskinesia(PCD)and cystic fibrosis(CF),two inherited disorders,suffer from recurrent airway infections characterized by persistent bacterial colonization and uncontrollable inflammation.Although present in high counts,neutrophils fail to clear infection in the airways.High levels of C-X-C motif chemokine ligand 8/interleukin-8(CXCL8/IL-8),the most potent chemokine to attract neutrophils to sites of infection,are detected in the sputum of both patient groups and might cause the high neutrophil influx in the airways.Furthermore,in CF,airway neutrophils are highly activated because of the genetic defect and the high levels of proinflammatory chemoattractants and cytokines(e.g.,CXCL8/IL-8,tumor necrosis factor-αand IL-17).The overactive state of neutrophils leads to lung damage and fuels the vicious circle of infection,excessive inflammation and tissue damage.The inflammatory process in CF airways is well characterized,whereas the lung pathology in PCD is far less studied.The knowledge of CF lung pathology could be useful to guide molecular investigations of the inflammatory processes in PCD lungs.Current available therapies can not completely remedy the chronic airway infections in these diseases.This review gives an overview of the role that chemoattractants and cytokines play in these neutrophil-dominated lung pathologies.Finally,the most frequently applied treatments in CF and PCD and new experimental therapies to reduce neutrophil-dominated airway inflammation are described.

关键词： chemoattractants cystic fibrosis cytokines primary ciliary dyskinesia

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Increasing phosphorus fertilizer value of recycled iron phosphates by prolonged flooding and organic matter addition

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Pedosphere 2024年第3期34卷 631-640页

作者： Rochelle Joie SARACANLAO Hannah VAN RYCKEL mieke VERBEECK Maarten EVERAERT Erik SMOLDERS Division of Soil and Water Management Department of Earth and Environmental ScienceKU LeuvenKasteelpark Arenberg 20Heverlee B-3001(Belgium) Soil Service of Belgium.Willem De Croylaan 48 Leuven 3001(Belgium)

Iron(Fe)minerals are commonly used to remove phosphorus(P)from waste streams,producing P-loaded Fe(Ⅲ)oxides or Fe(Ⅱ)phosphate minerals(e.g.,vivianite).These minerals may be used as fertilizers to enhance P circularity if solubilized in soil.Here,we tested the P fertilizer value of recycled Fe phosphates(FePs)in a pot trial and in an incubation experiment,hypothesizing that P release from FePs is possible under Fe(Ⅲ)-reducing conditions.First,a pot trial was set up with rice(Oryza sativa)in all combinations of soil flooding or not,three P-deficient soils(acid,neutral,and calcareous),and six FePs(three Fe(Ⅲ)Ps and three Fe(Ⅱ)Ps)referenced to triple superphosphate(TSP)or zero amendments.Shoot P uptake responded to TSP application in all treatments but only marginally to FePs.The redox potential did not decrease to-200 mV by flooding for a brief period(13 d)during the pot trial.A longer incubation experiment(60 d)was performed,including a treatment of glutamate addition to stimulate reductive conditions,and P availability was assessed with CaCl_(2)extraction of soils.Glutamate addition and/or longer incubation lowered soil redox potential to<-100 mV.On the longer term,Fe(Ⅲ)minerals released P,and adequate P was reached in the calcareous soil and in the neutral soil amended with Fe(Ⅲ)P-sludge.It can be concluded that prolonged soil flooding and organic matter addition can enhance the P fertilizer efficiency of FePs.Additionally,application of FeP in powder form may enhance P availability.

关键词： agronomic efficiency circular economy P-loaded Fe(Ⅲ)oxides paddy soil vivianite redox

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Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection

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Journal of Intensive Medicine 2024年第1期4卷 81-93页

作者： Marie Dejonckheere Massimo Antonelli Kostoula Arvaniti Koen Blot Ben CreaghBrown Dylan Wde Lange Jan De Waele mieke Deschepper Yalim Dikmen George Dimopoulos Christian Eckmann Guy Francois Massimo Girardis Despoina Koulenti Sonia Labeau Jeffrey Lipman Fernando Lipovestky Emilio Maseda Philippe Montravers Adam Mikstacki JoseArtur Paiva Cecilia Pereyra Jordi Rello JeanFrancois Timsit Dirk Vogelaers Stijn Blot the Abdominal Sepsis Study(AbSeS)group on behalf of the Trials Group of the European Society of Intensive Care Medicine Department of Internal Medicine and Pediatrics Faculty of Medicine and Health SciencesGhent UniversityGhentBelgium Department of Anesthesiology Intensive Care and Emergency MedicineFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly UniversitàCattolica del Sacro Cuore RomeItaly Intensive Care Unit Papageorgiou University Affiliated HospitalThessaloníkiGreece Department of Epidemiology and Public Health SciensanoIxellesBelgium Surrey Perioperative Anaesthetic Critical Care Collaborative Research Group(SPACeR) Royal Surrey County HospitalGuildfordUK Department of Clinical and Experimental Medicine University of SurreyGuildfordUK Department of Intensive Care Medicine University Medical Center UtrechtUniversity UtrechtUtrechtthe Netherlands Department of Intensive Care Medicine Ghent University HospitalGhentBelgium Data Science Institute Ghent University HospitalGhentBelgium Department of Anesthesiology and Reanimation Cerrahpasa School of MedicineIstanbul University-CerrahpasaIstanbulTurkey rd Department of Critical Care “EVGENIDIO”HospitalNational and Kapodistrian University of AthensAthensGreece Department of General Visceral and Thoracic SurgeryKlinikum Hannoversch-MuendenGoettingen UniversityGöttingenGermany Division of Scientific Affairs-Research European Society of Intensive Care MedicineBrusselsBelgium Anesthesia and Intensive Care Department University Hospital of ModenaModenaItaly UQ Centre for Clinical Research Faculty of MedicineThe University of QueenslandBrisbaneQLDAustralia nd Critical Care Department Attikon University HospitalAthensGreece Department of Nursing Faculty of EducationHealth and Social WorkUniversity College GhentGhentBelgium Jamieson Trauma Institute The University of QueenslandBrisbaneQLDAustralia Nimes University Hospital University of MontpellierNimesFrance Critical Care Department Hospital of the Interamerican Open University(UAI)Buenos AiresArgentina Surgical Critical Care Department of AnesthesiaHospital Universitario

Background:The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the(1)setting of infection onset(community-acquired,early onset,or late-onset hospital-acquired),(2)presence or absence of either localized or diffuse peritonitis,and(3)severity of disease expression(infection,sepsis,or septic shock).This classification system demonstrated reliable risk stratification in intensive care unit(ICU)patients with intra-abdominal infection.This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality.Methods:This was a secondary analysis of an international observational study(“AbSeS”)investigating ICU patients with intra-abdominal infection.Only patients with pancreatic infection were included in this analysis(n=165).Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU.Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio(OR)and 95%confidence interval(CI).Results:The overall mortality was 35.2%(n=58).The independent risk factors for mortality included older age(OR=1.03,95%CI:1.0 to 1.1 P=0.023),localized peritonitis(OR=4.4,95%CI:1.4 to 13.9 P=0.011),and persistent signs of inflammation at day 7(OR=9.5,95%CI:3.8 to 23.9,P<0.001)or after the implementation of additional source control interventions within the first week(OR=4.0,95%CI:1.3 to 12.2,P=0.013).Gramnegative bacteria were most frequently isolated(n=58,49.2%)without clinically relevant differences in microbial etiology between survivors and non-survivors.Conclusions:In pancreatic infection,a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome.In this limited series,essentials of the AbSeS-classification,such as the setting of infection onset,diffuse peritonitis,and severity of disease expression,

关键词： Pancreatic infection Intensive care unit Mortality Intra-abdominal infection Sepsis

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The physical and physiological effects of vacuum massage on the different skin layers: a current status of the literature

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Burns & Trauma 2016年第3期4卷 180-191页

作者： Peter Moortgat mieke Anthonissen Jill Meirte Ulrike Van Daele Koen Maertens OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 18B-2170 AntwerpBelgium OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 18B-2170 AntwerpBelgium Department of Rehabilitation Sciences KU LeuvenTervuursevest 101box 15003001 HeverleeBelgium OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 18B-2170 AntwerpBelgium Department of Rehabilitation Sciences and Physiotherapy University of AntwerpUniversiteitsplein 12610 AntwerpBelgium Department of Rehabilitation Sciences and Physiotherapy University of AntwerpUniversiteitsplein 12610 AntwerpBelgium OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 18B-2170 AntwerpBelgium Department of Clinical and Lifespan Psychology Vrije Universiteit BrusselPleinlaan 21050 BrusselsBelgium

Vacuum massage is a non-invasive mechanical massage technique performed with a mechanical device that lifts the skin by means of suction,creates a skin fold and mobilises that skin fold.In the late 1970s,this therapy was introduced to treat traumatic or burn scars.Although vacuum massage was invented to treat burns and scars,one can find very little literature on the effects of this intervention.Therefore,the aim of this review is to present an overview of the available literature on the physical and physiological effects of vacuum massage on epidermal and dermal skin structures in order to find the underlying working mechanisms that could benefit the healing of burns and scars.The discussion contains translational analysis of the results and provides recommendations for future research on the topic.An extended search for publications was performed using PubMed,Web of Science and Google Scholar.Two authors independently identified and checked each study against the inclusion criteria.Nineteen articles were included in the qualitative synthesis.The two most reported physical effects of vacuum massage were improvement of the tissue hardness and the elasticity of the skin.Besides physical effects,a variety of physiological effects are reported in literature,for example,an increased number of fibroblasts and collagen fibres accompanied by an alteration of fibroblast phenotype and collagen orientation.Little information was found on the decrease of pain and itch due to vacuum massage.Although vacuum massage initially had been developed for the treatment of burn scars,this literature review found little evidence for the efficacy of this treatment.Variations in duration,amplitude or frequency of the treatment have a substantial influence on collagen restructuring and reorientation,thus implying possible beneficial influences on the healing potential by mechanotransduction pathways.Vacuum massage may release the mechanical tension associated with scar retraction and thus induce apoptosis of myofibroblasts.Suggestions for

关键词： Vacuum massage Endermology Vacuotherapy Depressomassage Scars Hypertrophic Physical Physiological Intervention

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Short-term effects of vacuum massage on epidermal and dermal thickness and density in burn scars: an experimental study

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Burns & Trauma 2016年第3期4卷 216-224页

作者： Jill Meirte Peter Moortgat mieke Anthonissen Koen Maertens Cynthia Lafaire Lieve De Cuyper Guy Hubens Ulrike Van Daele OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 182170 AntwerpBelgium Rehabilitation Sciences and Physiotherapy University of AntwerpUniversiteitsplein 12610 AntwerpBelgium OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 182170 AntwerpBelgium OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 182170 AntwerpBelgium KU Leuven Faculty of Kinesiology and Rehabilitation SciencesLeuvenBelgium OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 182170 AntwerpBelgium Department of Clinical and Lifespan Psychology Vrije Universiteit BrusselBrusselsBelgium OSCARE Organisation for BurnsScar After-care and ResearchVan Roiestraat 182170 AntwerpBelgium ZNA Stuivenberg Burn CenterAntwerpBelgium Department of Antwerp Surgical Training Anatomy and Research Centre University of AntwerpAntwerpBelgium Rehabilitation Sciences and Physiotherapy University of AntwerpUniversiteitsplein 12610 AntwerpBelgium

Background:Vacuum massage is a non-invasive mechanical massage technique invented to treat burns and scars.To date,no effects of vacuum massage on thickness and density of human scar tissue have been reported.The process in which external stimuli are converted into biochemical responses in the cell is known as mechanotransduction.In the skin endothelial cells,fibroblasts and myofibroblasts embedded in the extracellular matrix(ECM)sense mechanical stimuli(created by vacuum massage)and may promote intracellular processes leading to matrix remodelling.Since mechanotransduction could be a plausible working mechanism for vacuum massage as an anti-scarring therapy,this study aims to investigate the short-term effects of vacuum massage on thickness and density of epidermis and dermis in burn scars in order to find proof of ECM remodelling.Methods:A one group experimental study was performed.Patients with burn scars on upper extremities,lower extremities,and trunk were recruited for participation in this study.The DUB?cutis 22 MHz ultrasound scanner was used to assess thickness and density of the epidermal and dermal skin layers.After baseline measurements,vacuum massage was performed according to a pre-defined protocol.Measurements were carried out at 5 min,30 min,1 h,and 2 h post-intervention.Results:Thirteen scar sites from 9 different patients were investigated.In 8 out of the 13 scar sites,a disruption of the epidermis was noticed after the vacuum massage.Five minutes after the intervention,epidermal density decreased statistically significantly(p=.022)and dermal thickness increased(p=.018).Both changes lasted for more than 1 h,but after 2 h,the changes were no longer statistically significant.Dermal density decreased significantly(p=.048)immediately after the intervention,and this decrease was still present after 2 h(p=.011).Conclusions:Preliminary results show that the disruption of the epidermis may indicate that vacuum massage could be able to actually breach the skin barrier.The statistically significant change

关键词： Burn Scars Vacuum massage Dermal thickness Dermal density

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Opportunities to Integrate Primary Health Care Digital Innovations in Maternal and Child Health Care Services in Kenya

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Open Journal of Clinical Diagnostics 2022年第3期12卷 39-54页

作者： Micah Matiang’I Priscilla Ngunju Aranka Hetyey Lydia Odek Eefje Smet mieke Arnoldus Yvonne Opanga Colleta Kiilu School of Medical Sciences Amref International University (AMIU) Nairobi Kenya Venture Programs Amref Flying Doctors Laiden Netherlands Research Deprtment Amref Health Africa Nairobi Kenya

Background: Adequate and quality Maternal and Child Health (MNCH) care is considered essential in reduction of maternal and child mortality. More than half of the global maternal deaths (66%) are in sub-Saharan Africa with infant mortality of 51/1000 live births in the WHO Africa region [1]. There is potential to improve access and utilization of health services through investing in Primary Health Care (PHC) digital innovations [2] especially in underserved settings [3]. In the last quarter of the year 2021 after lifting of the COVID-19 restrictions, Tekeleza project, aims to integrate digital health innovations into MNCH care within PHC settings in Kenya. The project team undertook a baseline survey in three rural counties (Kisii, Kajiado and Migori) characterized with low social-economic status to identify opportunities to leverage on the use of evidence-based digital innovations to reverse the adverse trends in Maternal and Child Health. Methods: A cross-sectional and descriptive study was conducted in 15 Community Health Units (CHUs) in Kenya that were linked to selected Primary Health Care (PHC) facilities from three rural counties. Mixed methods were used to collect data from 404 Households (HHs) selected across the sampled CHUs on Probability Proportionate to Size (PPS). The selected households were assigned unique household or respondent identifiers. The sampling frame for household surveys consisted of all women 18 - 49 years of age, who were either pregnant or in their 18 months post-delivery. From the constructed sampling frame, a simple random sampling procedure was used to select the study sample. An audit was also carried out at the selected PHC facilities and sixty-two (62) Primary Health Workers (PHCWs) including facility managers were interviewed to establish challenges affecting ICT infrastructure and sustainable financing of MNCH services. Findings: The majority of the sampled women (64.9%) were lactating at the time of the study, with 34.4% being pregnant and 0.7% both pregnant and lactating.

关键词： Maternal Infant Digital Health Innovations Feasibility Study Bankable Ventures

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Monoclonal antibodies to the exon 18 encoded moiety of NCAM

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Journal of Cancer Metastasis and Treatment 2019年第7期4卷 50-55页

作者： Ann Vander Borght mieke Duysinx Monique Ummelen Bernard AMvan der Zeijst Department of Genetics and Cell Biology and GROW School for Oncology and Developmental Biology Maastricht UniversityMaastrichtPO Box 6166200 MDThe Netherlands MUbio Products B.V. Maastricht6200 EVThe Netherlands Catherinn B.V. Manuel de Fallapad 1Rotterdam3069 MRThe Netherlands

Aim: Exon 18 expression of NCAM has been recognized as a biomarker for small cell lung cancer (SCLC). To use this finding for an improved diagnosis of SCLC and personalized treatment of patients, techniques to identify and quantitate E18, the exon 18 encoded protein moiety of NCAM, are needed. We developed three monoclonal antibodies for this purpose. Methods: The his-tagged E18 antigen was expressed in E. coli and, after purification, used to immunize mice. Hybridoma's were isolated by standard procedures and tested for their reaction with E18. Results: Three monoclonal antibodies, MUM-1, MUM-4 and MUM-6 were obtained. They reacted with E18 in western blots, with SCLC cell line NCI-H82, but not with unrelated his-tagged proteins. Only permeabilized NCI-H82 cells stained with the antibodies, confirming the intracellular position of E18. Next an enzyme-linked immunosorbent assay was developed using the earlier isolated monoclonal antibody MUMi-21B2, coated on the surface of microtiter wells as capture antibody and biotinylated MUM-6 as second antibody. Using streptavidin conjugated to horse radish peroxidase a linear dose response curve to his-tagged E18 antigen was obtained between 0 and 5 μg/mL with a sensitivity of at least 0.5 μg/mL or 50 ng/well. Conclusion: Four monoclonal antibodies are available to be used in assays for the identification and quantification of SCLC biomarker E18. This will enable the development of liquid biopsies to follow the tumor load in patients.

关键词： Small cell lung cancer tumor biomarker monoclonal antibodies NCAM exon 18

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Specificity of early-career general practitioners’problem formulations in patients presenting with dizziness:a cross-sectional analysis

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Family Medicine and Community Health 2021年第4期9卷 10-19,I0001,I0002页

作者： Jocelyn Ledger Amanda Tapley Christopher Levi Andrew Davey mieke van Driel Elizabeth G Holliday Jean Ball Alison Fielding Neil Spike Kristen FitzGerald Parker Magin The University of Newcastle School of Medicine and Public Health CallaghanNew South WalesAustralia NSW&ACT Research and Evaluation Unit GP SynergyRegional Training OrganisationNewcastleNew South WalesAustralia The Sydney Partnership for Health EducationResearch and Enterprise(SPHERE)SydneyNew South WalesAustralia Department of Neurology John Hunter HospitalNewcastleNew South WalesAustralia Primary Care Clinical Unit The University of Queensland Faculty of MedicineBrisbaneQueenslandAustralia Clinical Research Design and Statistical Support Unit(CReDITSS) The University of Newcastle Hunter Medical Research InstituteNew LambtonNew South WalesAustralia Eastern Victoria General Practice Training Regional Training OrganisationHawthornVictoriaAustralia Department of General Practice and Primary Health Care The University of MelbourneMelbourneVictoriaAustralia General Practice Training Tasmania Regional Training OrganisationHobartTasmaniaAustralia University of Tasmania School of Medicine HobartTasmaniaAustralia

Objectives Dizziness is a common and challenging clinical presentation in general practice.Failure to determine specific aetiologies can lead to significant morbidity and mortality.We aimed to establish frequency and associations of general practitioner(GP)trainees’(registrars’)specific vertigo provisional diagnoses and their non-specific symptomatic problem formulations.Design A cross-sectional analysis of Registrar Clinical Encounters in Training(ReCEnT)cohort study data between 2010 and 2018.ReCEnT is an ongoing,prospective cohort study of registrars in general practice training in Australia.Data collection occurs once every 6 months midtraining term(for three terms)and entails recording details of 60 consecutive clinical consultations on hardcopy case report forms.The outcome factor was whether dizziness-related or vertigo-related presentations resulted in a specific vertigo provisional diagnosis versus a non-specific symptomatic problem formulation.Associations with patient,practice,registrar and consultation independent variables were assessed by univariate and multivariable logistic regression.Setting Australian general practice training programme.The training is regionalised and delivered by regional training providers(RTPs)(2010-2015)and regional training organisations(RTOs)(2016-2018)across Australia(from five states and one territory).Participants All general practice registrars enrolled with participating RTPs or RTOs undertaking GP training terms.Results 2333 registrars(96%response rate)recorded 1734 new problems related to dizziness or vertigo.Of these,546(31.5%)involved a specific vertigo diagnosis and 1188(68.5%)a non-specific symptom diagnosis.Variables associated with a non-specific symptom diagnosis on multivariable analysis were lower socioeconomic status of the practice location(OR 0.94 for each decile of disadvantage,95%CIs 0.90 to 0.98)and longer consultation duration(OR 1.02,95%CIs 1.00 to 1.04).A specific vertigo diagnosis was associated with performing a procedure(OR 0.52,95%CIs 0.27 to

关键词： diagnosis formulation sectional

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