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Glenn Leemans,1 Dirk Vissers,1 Kris Ides,2– 4 Paul Van Royen5 1Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium; 2Cosys-Lab, Flanders Make, University of Antwerp, Antwerp, Belgium; 3Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium; 4Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium; 5Department of Family Medicine and Population Health, University of Antwerp, Wilrijk, BelgiumCorrespondence: Glenn Leemans, Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Belgium, Tel +32 495 34 84 59, Email glenn.leemans@student.uantwerpen.beBackground: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition that requires multidisciplinary management. In Belgium, the treatment of COPD is mainly managed by general practitioners (GPs). Several clinical practice guidelines (CPGs) recommend the use of non-pharmacological treatments, such as pulmonary rehabilitation, and interdisciplinary care for COPD patients. Although considerable research has been devoted to addressing the multitude of reasons for the lack of adherence to these aspects of the CPGs, less attention has been paid to understanding the perspectives and attitudes of GPs that lead to this suboptimal implementation.Purpose: This study aimed to 1) explore Belgian GPs’ perceptions regarding COPD management in a primary care setting and 2) collect their views on the importance of pulmonary rehabilitation and interprofessional care in COPD management.Methods: A descriptive study, conducted between August 2014 and May 2015, used interviews from a sample of 30 Flemish GPs. Data were analyzed following the principles of thematic analysis.Results: COPD management was patient-centered, focusing on immediate symptom relief and reducing future risks through pharmacotherapy and proper patient education. Deviations from the CPGs were noted, with only a few GPs performing spirometry themselves. Conditions to prescribe respiratory physiotherapy were not well known. Some GPs remained unconvinced about the (cost-)effectiveness of respiratory physiotherapy despite the fast-expanding scientific evidence. Interprofessional care was limited to GP-respiratory physician (re)-referral and communication. GPs showed a reactive attitude towards interprofessional collaboration for non-pharmacological therapies, which is not in line with the proactive approach recommended in CPGs.Conclusion: GPs managed COPD patients mainly by reducing symptoms with pharmacological therapy. Integrated care regarding non-pharmacological treatments was not well implemented due to the obstacles in interprofessional collaboration. Future care models incorporating personalized care planning could provide a solution to manage COPD’s complex healthcare demands.Keywords: asthma/COPD management, family medicine, non-pharmacologic treatment, pulmonary rehabilitation, interdisciplinary care, thematic analysis

Hans De Loof,1 Ellen De Win,1 Nathalie Moens,1 Veronique Verhoeven,2 Paul Van Royen,2 Elke O Kreps,3 Hilde Philips2 1Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium; 2Research Group, Primary and Interdisciplinary Care (ELIZA), Department Family Medicine and Population Health (FAMPOP) University of Antwerp, Antwerp, Belgium; 3Department of Ophthalmology, Ghent University Hospital, Ghent, BelgiumCorrespondence: Hans De LoofLaboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, BelgiumTel +32 3 265 91 39Email hans.deloof@uantwerpen.beAbstract: Prescribing patterns by primary care physicians concerning ophthalmic problems were studied using the iCAREdata, a database containing information from the out-of-hours care setting in the Flanders region of Belgium. A very high percentage of prescribed ophthalmic medication was topical antibiotics (89.4%) with tobramycin as the most prevalent substance and in clear conflict with the prevailing guidelines. In addition, a very substantial fraction of prescribed medication contained corticosteroids (30.4%). This is a potentially unsafe option within the technical infrastructure of this setting, which limits the diagnostic possibilities concerning viral infections or preexisting glaucoma risk. We conclude that more efforts are required to limit unnecessary and inappropriate prescribing behavior to further promote patient safety.Keywords: antibiotics, conjunctivitis, drug utilization research, referral process

Kathleen Van Royen,1,2 Paul Van Royen,1 Liesbeth De Donder,3 Robbert J Gobbens1,4,5 1Department of Primary and Interdisciplinary Care, University of Antwerp, Antwerp, Belgium; 2Department of Communication Studies, University of Antwerp, Antwerp, Belgium; 3Faculty of Psychology and Educational Sciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium; 4Faculty of Health, Sports and Social Work, Inholland University of Applied Sciences, Amsterdam, the Netherlands; 5Zonnehuisgroep Amstelland, Amstelveen, the NetherlandsCorrespondence: Kathleen Van RoyenDepartment of Primary and Interdisciplinary Care, University of Antwerp, Gouverneur Kinsbergencentrum, Doornstraat 331-2610, Doornstraat, Wilrijk, BelgiumTel +32 32655099Email kathleen.vanroyen@uantwerpen.beBackground and Aim: Caregivers in the home environment have an important role in timely detecting and responding to abuse. The aim of this review was to provide insight into both the existing tools for the assessment of and interventions for elder abuse by formal and informal caregivers in the home environment, and to categorize them according to a public health perspective, into primary, secondary, tertiary or quaternary prevention.Methods: We selected the assessment tools and interventions that can be used by caregivers in the home environment included in previous reviews by Gallione et al (2017) and Fearing et al (2017). To identify published studies after these reviews, a search was performed using PubMed, Cochrane Database, CINAHL and Web of Science.Results: In total, fifteen assessment tools and twelve interventions were included. The number of assessment tools for elder abuse for use in the home environment is increasing; however, tools must be validated over different cultures and risk groups. In addition, the tools lack attention for the needs of vulnerable older persons such as persons with dementia. Existing interventions for caregivers in the home environment lack evidence for addressing elder abuse and do not address potential adverse effects (quaternary prevention).Conclusion: Assessment tools for elder abuse need further testing for validity and reliability for use by caregivers in the home environment. For interventions, meaningful outcome measures are needed. Important to note is that quaternary prevention requires more attention. This argues for taking into account perspectives of (abused) older persons and caregivers in the development of assessment tools and interventions protocols.Keywords: caregivers, elder abuse management, prevention, assessment tools, interventions, review

ВВЕДЕНИЕ: Значение полиморбидности становится всё более существенным. За последние несколько десятилетий наблюдается всё более значительное старение населения большинства стран в мире. Проблема касается и Болгарии, ввиду высокого распространения стареющего населения со множеством хронических заболеваний. ЦЕЛЬЮ данного обследования является валидизация определения полиморбидности в переводе с английского на болгарский язык. МАТЕРИАЛ И МЕТОДЫ: Настоящее обследование является частью международного проекта, включающего участников из восьми стран. Исследование основано на переводе определения с применением процедуры Дельфи. РЕЗУЛЬТАТЫ: Участвующие в обследовании врачи приняли определение на первом этапе с высоким процентом согласия. Перевод с болгарского языка на английский принято исследовательским комитетом с использованием техники Номинальной группы. ДИСКУССИЯ: Частью общепрактикующих врачей были обсуждены конкретные выражения с целью лучшего понимания на болгарском языке. Отправленные замечания не касаются содержания. Проведённый мета-этнографический подход привёл к заключению, что различия приемлемы и нет необходимости в дальнейших изменениях. ЗАКЛЮЧЕНИЕ: Болгарский перевод определения полиморбидности осуществлён. Данное определение является предпосылкой для лучшего управления полиморбидностью клиницистами, исследователями и политиками.

Background Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement, posing an increased risk of heart failure and mortality. Accurate intraprocedural quantification of PVR is challenging. Both hemodynamic indices and videodensitometry can be used for intraprocedural assessment of PVR. We compared the predictive value of the isolated versus combined use of the hemodynamic index diastolic delta (DD) and videodensitometry for the incidence of relevant PVR 1 month after transcatheter aortic valve replacement. Methods and Results In this prospective cohort study, patients underwent periprocedural PVR assessment by DD and videodensitometry (using left ventricular outflow tract—aortic regurgitation [LVOT‐AR]). Cardiac magnetic resonance served as reference modality for PVR assessment. Relevant PVR was defined as cardiac magnetic resonance–regurgitant fraction >20%. Fifty‐one patients were enrolled in this study. Mean age was 80.6±5.2 years and 45.1% of patients were men. Mean LVOT‐AR and cardiac magnetic resonance–regurgitant fraction were 8.2%±7.8% and 11.7%±9.6%, respectively. The correlation between DD and LVOT‐AR was weak (r=−0.36). DD and LVOT‐AR showed a comparable accuracy to predict relevant PVR (area under the curve 0.82, 95% CI: 0.69–0.95 versus area area under the time–density curve 0.80, 95% CI: 0.62–0.99). The combination of DD and LVOT‐AR improved the prediction of relevant PVR (area under the time–density curve, 0.90, 95% CI: 0.81–0.99), and resulted in an increased concordance (86.3%) and positive predictive value (75%) compared with DD alone (76.5% and 40%, respectively), or LVOT‐AR alone (82.3% and 50%, respectively). Conclusions DD and videodensitometry are both accurate and feasible modalities for the assessment of PVR after transcatheter aortic valve replacement. The synergistic use of both techniques increases the predictive value for relevant PVR after transcatheter aortic valve replacement. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04281771.

Abstract Background Family physicians perceive that gut feelings, i.e. a ‘sense of reassurance’ or a ‘sense of alarm’, play a substantial role in diagnostic reasoning. A measuring instrument is desirable for further research. Our objective is to validate a questionnaire measuring the presence of gut feelings in diagnostic reasoning. Methods We constructed 16 case vignettes from real practice situations and used the accompanying ‘sense of reassurance’ or the ‘sense of alarm’ as reference labels. Based on the results of an initial study (26 family physicians), we divided the case vignettes into a group involving a clear role for the sense of reassurance or the sense of alarm and a group involving an ambiguous role. 49 experienced family physicians evaluated each 10 vignettes using the questionnaire. Construct validity was assessed by testing hypotheses and an internal consistency procedure was performed. Results As hypothesized we found that the correlations between the reference labels and corresponding items were high for the clear-case vignettes (0.59 – 0.72) and low for the ambiguous-case vignettes (0.08 – 0.23). The agreement between the classification in clear sense of reassurance, clear sense of alarm and ambiguous case vignettes as derived from the initial study and the study population’s judgments was substantial (Kappa = 0.62). Factor analysis showed one factor with opposites for sense of reassurance and sense of alarm items. The questionnaire’s internal consistency was high (0.91). We provided a linguistic validated English-language text of the questionnaire. Conclusions The questionnaire appears to be valid. It enables quantitative research into the role of gut feelings and their diagnostic value in family physicians’ diagnostic reasoning.

Abstract Background During an influenza epidemic prompt diagnosis of influenza is important. This diagnosis however is still essentially based on the interpretation of symptoms and signs by general practitioners. No single symptom is specific enough to be useful in differentiating influenza from other respiratory infections. Our objective is to formulate prediction rules for the diagnosis of influenza with the best diagnostic performance, combining symptoms, signs and context among patients with influenza-like illness. Methods During five consecutive winter periods (2002-2007) 138 sentinel general practitioners sampled (naso- and oropharyngeal swabs) 4597 patients with an influenza-like illness (ILI) and registered their symptoms and signs, general characteristics and contextual information. The samples were analysed by a DirectigenFlu-A&B and RT-PCR tests. 4584 records were useful for further analysis. Starting from the most relevant variables in a Generalized Estimating Equations (GEE) model, we calculated the area under the Receiver Operating Characteristic curve (ROC AUC), sensitivity, specificity and likelihood ratios for positive (LR+) and negative test results (LR-) of single and combined signs, symptoms and context taking into account pre-test and post-test odds. Results In total 52.6% (2409/4584) of the samples were positive for influenza virus: 64% (2066/3212) during and 25% (343/1372) pre/post an influenza epidemic. During and pre/post an influenza epidemic the LR+ of 'previous flu-like contacts', 'coughing', 'expectoration on the first day of illness' and 'body temperature above 37.8°C' is 3.35 (95%CI 2.67-4.03) and 1.34 (95%CI 0.97-1.72), respectively. During and pre/post an influenza epidemic the LR- of 'coughing' and 'a body temperature above 37.8°C' is 0.34 (95%CI 0.27-0.41) and 0.07 (95%CI 0.05-0.08), respectively. Conclusions Ruling out influenza using clinical and contextual information is easier than ruling it in. Outside an influenza epidemic the absence of cough and fever (> 37,8°C) makes influenza 14 times less likely in ILI patients. During an epidemic the presence of 'previous flu-like contacts', cough, 'expectoration on the first day of illness' and fever (>37,8°C) increases the likelihood for influenza threefold. The additional diagnostic value of rapid point of care tests especially for confirming influenza still has to be established.

Abstract Background Overuse of emergency departments (ED) is of concern in Western society and it is often referred to as 'inappropriate' use. This phenomenon may compromise efficient use of health care personnel, infrastructure and financial resources of the ED. To redirect patients, an extensive knowledge of the experiences and attitudes of patients and their choice behaviour is necessary. The aim of this study is to quantify the patients and socio-economical determinants for choosing the general practitioner (GP) on call or the ED. Methods Data collection was conducted simultaneously in 4 large cities in Belgium. All patients who visited EDs or used the services of the GP on call during two weekends in January 2005 were enrolled in the study in a prospective manner. We used semi-structured questionnaires to interview patients from both services. Results 1611 patient contacts were suitable for further analysis. 640 patients visited the GP and 971 went to the ED. Determinants that associated with the choice of the ED are: being male, having visited the ED during the past 12 months at least once, speaking another language than Dutch or French, being of African (sub-Saharan as well as North African) nationality and no medical insurance. We also found that young men are more likely to seek help at the ED for minor trauma, compared to women. Conclusions Patients tend to seek help at the service they are acquainted with. Two populations that distinctively seek help at the ED for minor medical problems are people of foreign origin and men suffering minor trauma. Aiming at a redirection of patients, special attention should go to these patients. Informing them about the health services' specific tasks and the needlessness of technical examinations for minor trauma, might be a useful intervention.

Abstract Background Out-of-hours care in the primary care setting is rapidly changing and evolving towards general practitioner 'cooperatives' (GPC). GPCs already exist in the Netherlands, the United Kingdom and Scandinavia, all countries with strong general practice, including gatekeepers' role. This intervention study reports the use and caseload of out-of-hours care before and after implementation of a GPC in a well subscribed region in a country with an open access health care system and no gatekeepers' role for general practice. Methods We used a prospective before/after interventional study design. The intervention was the implementation of a GPC. Results One year after the implementation of a GPC, the number of patient contacts in the intervention region significantly increased at the GPC (OR: 1.645; 95% CI: 1.439-1.880), while there were no significant changes in patient contacts at the Emergency Department (ED) or in other regions where a simultaneous registration was performed. Although home visits decreased in all general practitioner registrations, the difference was more pronounced in the intervention region (intervention region: OR: 0.515; 95% CI: 0.411-0.646, other regions: OR: 0.743; 95% CI: 0.608-0.908). At the ED we observed a decrease in the number of trauma cases (OR: 0.789; 95% CI: 0.648-0.960) and of patients who came to hospital by ambulance (OR: 0.687; 95% CI: 0.565-0.836). Conclusions One year after its implementation more people seek help at the GPC, while the number of contacts at the ED remains the same. The most prominent changes in caseload are found in the trauma cases. Establishing a GPC in an open health care system, might redirect some patients with particular medical problems to primary care. This could lead to a lowering of costs or a more cost-effective out of hours care, but further research should focus on effective usage to divert patient flows and on quality and outcome of care.

Abstract Background General practitioners sometimes base clinical decisions on gut feelings alone, even though there is little evidence of their diagnostic and prognostic value in daily practice. Research to validate the determinants and to assess the test properties of gut feelings requires precise and valid descriptions of gut feelings in general practice which can be used as a reliable measuring instrument. Research question: Can we obtain consensus on descriptions of two types of gut feelings: a sense of alarm and a sense of reassurance? Methods Qualitative research including a Delphi consensus procedure with a heterogeneous sample of 27 Dutch and Belgian GPs or ex-GPs involved in academic educational or research programmes. Results After four rounds, we found 70% or greater agreement on seven of the eleven proposed statements. A "sense of alarm" is defined as an uneasy feeling perceived by a GP as he/she is concerned about a possible adverse outcome, even though specific indications are lacking: There's something wrong here. This activates the diagnostic process by stimulating the GP to formulate and weigh up working hypotheses that might involve a serious outcome. A "sense of alarm" means that, if possible, the GP needs to initiate specific management to prevent serious health problems. A "sense of reassurance" is defined as a secure feeling perceived by a GP about the further management and course of a patient's problem, even though the doctor may not be certain about the diagnosis: Everything fits in. Conclusion The sense of alarm and the sense of reassurance are well-defined concepts. These descriptions enable us to operationalise the concept of gut feelings in further research.

Abstract Background Most research publications on Chronic Care Model (CCM) implementation originate from organizations or countries with a well-structured primary health care system. Information about efforts made in countries with a less well-organized primary health care system is scarce. In 2003, the Belgian National Institute for Health and Disability Insurance commissioned a pilot study to explore how care for type 2 diabetes patients could be organized in a more efficient way in the Belgian healthcare setting, a setting where the organisational framework for chronic care is mainly hospital-centered. Methods Process evaluation of an action research project (2003–2007) guided by the CCM in a well-defined geographical area with 76,826 inhabitants and an estimated number of 2,300 type 2 diabetes patients. In consultation with the region a program for type 2 diabetes patients was developed. The degree of implementation of the CCM in the region was assessed using the Assessment of Chronic Illness Care survey (ACIC). A multimethod approach was used to evaluate the implementation process. The resulting data were triangulated in order to identify the main facilitators and barriers encountered during the implementation process. Results The overall ACIC score improved from 1.45 (limited support) at the start of the study to 5.5 (basic support) at the end of the study. The establishment of a local steering group and the appointment of a program manager were crucial steps in strengthening primary care. The willingness of a group of well-trained and motivated care providers to invest in quality improvement was an important facilitator. Important barriers were the complexity of the intervention, the lack of quality data, inadequate information technology support, the lack of commitment procedures and the uncertainty about sustainable funding. Conclusion Guided by the CCM, this study highlights the opportunities and the bottlenecks for adapting chronic care delivery in a primary care system with limited structure. The study succeeded in achieving a considerable improvement of the overall support for diabetes patients but further improvement requires a shift towards system thinking among policy makers. Currently primary care providers lack the opportunities to take up full responsibility for chronic care. Trial registration number ClinicalTrials.gov Identifier: NCT00824499

Abstract Background General practitioners sometimes base clinical decisions on gut feelings alone, even though there is little evidence of their diagnostic and prognostic value in daily practice. Research into these aspects and the use of the concept in medical education require a practical and valid description of gut feelings. The goal of our study was therefore to describe the concept of gut feelings in general practice and to identify their main determinants Methods Qualitative research including 4 focus group discussions. A heterogeneous sample of 28 GPs. Text analysis of the focus group discussions, using a grounded theory approach. Results Gut feelings are familiar to most GPs in the Netherlands and play a substantial role in their everyday routine. The participants distinguished two types of gut feelings, a sense of reassurance and a sense of alarm. In the former case, a GP is sure about prognosis and therapy, although they may not always have a clear diagnosis in mind. A sense of alarm means that a GP has the feeling that something is wrong even though objective arguments are lacking. GPs in the focus groups experienced gut feelings as a compass in situations of uncertainty and the majority of GPs trusted this guide. We identified the main determinants of gut feelings: fitting, alerting and interfering factors, sensation, contextual knowledge, medical education, experience and personality. Conclusion The role of gut feelings in general practice has become much clearer, but we need more research into the contributions of individual determinants and into the test properties of gut feelings to make the concept suitable for medical education.

The use of reflective interfaces has been proposed as a useful strategy to reduce cyber harassment amongst adolescents on social networking sites (SNS). By using machine-learning techniques, harassing online messages can be detected before a user submits it online, whereafter a message prompts the user to reconsider the post. This study builds further upon research focusing on the short-term effectiveness of reflective interfaces in preventing harassment. In this context, though, it is not unlikely that adolescents' user experience with SNS is thwarted when it contains reflective interfaces that might steer their online behaviour. Therefore, this study explores how adolescents evaluate a reflective interface design, in terms of both pragmatic (i.e. functionality, clarity and supportiveness) and hedonic qualities (i.e. autonomy, privacy, self-expression, self-reflection, and pleasure). Moreover, experienced emotions were investigated. In a mixed-method experiment, 24 adolescents (aged 14-16) interacted with a mock SNS with reflective design features. Participants' emotions were observed while interacting on the SNS that prompted a cue (either containing a verbal message or implicit) for each textual harassment attempt. We further investigated the participants' experiences retrospectively while watching the screen capture video of their interaction with the reflective interface, and administered a self-report questionnaire. Findings reveal that adolescents' short-term experiences with SNS in which reflective cues are implemented are not disrupted to a high extent and attitudes are rather positive. Nevertheless, results clearly pointed to a potential fatigue effect in the long-term. Methods to overcome this and alternative options for providing reflective interfaces are suggested.

Abstract Background STI surveillance systems are subject to qualitative and quantitative underreporting. General practitioners (GPs), who are key subjects in case reporting, explain their underreporting partly by their observation that taking a sexual history is embarrassing for patients, and that patients are reluctant to disclose information on their sexual practices. In this study we examine patients' willingness to provide data for STI surveillance. Methods A questionnaire-based survey in a stratified population sample of 300 patients aged 18–60 years. Results The large majority of respondents stated to be willing to give information on their sexual practices for the purpose of STI surveillance. They preferred to answer sexual history questions to their GP; filling in a form on the internet was the second best option. Conclusion Based on these results, it is unlikely that the cooperation of patients would be a weak link in STI surveillance strategies. This observation, together with the fact that the majority of patients at risk for STIs have regular access to general practice services, justify renewed efforts to enliven primary care-based STI surveillance strategies.

Abstract Background The problem of poor compliance/adherence to prescribed treatments is very complex. Health professionals are rarely being asked how they handle the patient's (poor) therapy compliance/adherence. In this study, we examine explicitly the physicians' expectations of their diabetes patients' compliance/adherence. The objectives of our study were: (1) to elicit problems physicians encounter with type 2 diabetes patients' adherence to treatment recommendations; (2) to search for solutions and (3) to discover escape mechanisms in case of frustration. Methods In a descriptive qualitative study, we explored the thoughts and feelings of general practitioners (GPs) on patients' compliance/adherence. Forty interested GPs could be recruited for focus group participation. Five open ended questions were derived on the one hand from a similar qualitative study on compliance/adherence in patients living with type 2 diabetes and on the other hand from the results of a comprehensive review of recent literature on compliance/adherence. A well-trained diabetes nurse guided the GPs through the focus group sessions while an observer was attentive for non-verbal communication and interactions between participants. All focus groups were audio taped and transcribed for content analysis. Two researchers independently performed the initial coding. A first draft with results was sent to all participants for agreement on content and comprehensiveness. Results General practitioners experience problems with the patient's deficient knowledge and the fact they minimize the consequences of having and living with diabetes. It appears that great confidence in modern medical science does not stimulate many changes in life style. Doctors tend to be frustrated because their patients do not achieve the common Evidence Based Medicine (EBM) objectives, i.e. on health behavior and metabolic control. Relevant solutions, derived from qualitative studies, for better compliance/adherence seem to be communication, tailored and shared care. GPs felt that a structured consultation and follow-up in a multidisciplinary team might help to increase compliance/adherence. It was recognized that the GP's efforts do not always meet the patients' health expectations. This initiates GPs' frustration and leads to a paternalistic attitude, which may induce anxiety in the patient. GPs often assume that the best methods to increase compliance/adherence are shocking the patients, putting pressure on them and threatening to refer them to hospital. Conclusion GPs identified a number of problems with compliance/adherence and suggested solutions to improve it. GPs need communication skills to cope with patients' expectations and evidence based goals in a tailored approach to diabetes care.

BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.

Abstract Background Antibiotics are being overprescribed in ambulant care, especially for respiratory tract infections (RTIs). Gaining insight into the actual reasons for prescribing remains important for the design of effective strategies to optimise antibiotic prescribing. We aimed to determine items of importance for the antibiotic prescribing decision and to make them operational for an intervention trial. Methods A postal questionnaire based upon focus group findings was sent to 316 Flemish general practitioners (GPs). On a verbal rating scale the GPs scored to what extent they consider the questionnaire items in decision making in case of suspected RTI in a coughing patient and how strongly the items support or counter antibiotic treatment. Factor analysis was used to condense the data. The relative importance of the yielded operational factors was assessed using Wilcoxon Matched Pairs test. Results 59.5% completed the study. Response group characteristics (mean age: 42.8 years; 65.9% men) approximated that of all Flemish GPs. Participants considered all the items included in the questionnaire: always the operational factor 'lung auscultation', often 'whether or not there is something unusual happening' – both medical reasons – and to a lesser extent 'non-medical reasons' (P < 0.001). Non-medical as well as medical reasons support antibiotic treatment, but non-medical reasons to a lesser extent (P < 0.001). Conclusion This study quantified, condensed and confirmed the findings of previous focus group research. Practice guidelines and interventions to optimise antibiotic prescribing have to take non-medical reasons into account.

BackgroundPhysicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR).ObjectivesThe purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial.MethodsMACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex.ResultsA total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06).ConclusionsiFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral.