Rainbows over the world's public health: determinants of health models in the past, present, and future.

The need to visualise the complexity of the determinants of population health and their interactions inspired the development of the rainbow model. In this commentary we chronicle how variations of this model have emerged, including the initial models of Haglund and Svanström (1982), Dahlgren and Whitehead (1991), and the Östgöta model (2014), and we illustrate how these models have been influential in both public health and beyond. All these models have strong Nordic connections and are thus an important Nordic contribution to public health. Further, these models have underpinned and facilitated other examples of Nordic leadership in public health, including practical efforts to address health inequalities and design new health policy approaches.Apart from documenting the emergence of rainbow models and their wide range of contemporary uses, we examine a range of criticisms levelled at these models - including limitations in methodological development and in scope. We propose the time is ripe for an updated generic determinants of health model, one that elucidates and preserves the core value in older models, while recognising the developments that have occurred over the past decades in our understanding of the determinants of health. We conclude with an example of a generic model that fulfills the general purposes of a determinants of health model while maintaining the necessary scope for further adjustments to be made in the future, as well as adjustments to location or context-specific purposes, in education, research, health promotion and beyond.

Practices, organisation, and regulatory aspects in advising on antibiotic prescription: the international ESCMID AntibioLegalMap survey.

PURPOSE: Giving advice about antibiotic prescription through dedicated consultations is a cornerstone of antibiotic stewardship programmes. Our objective was to explore practices, organisation, and regulatory requirements related to antibiotic advising. METHODS: We performed an international, exploratory, Internet-based, cross-sectional survey targeting infectious diseases and clinical microbiology specialists. It was disseminated through ESCMID and ESGAP networks. RESULTS: Answers from 830 participants (74 countries, 77% of participants from Europe) were collected. Consultations were mostly given on demand (81%, 619/764), while unsolicited consultations targeting specific conditions (e.g., positive blood culture) were less frequent (66%, 501/764). Consultations usually included indications on diagnostic work-up and follow-up (> 79%). Curbside consultations (i.e., without examining the patient) were reported by 82% (598/733) of respondents, mainly by phone (89%, 531/598). The referring physician was considered authorised not to follow the advice by 57% (383/676). Direct consultations (i.e., after examining the patient) were recorded in the medical file more frequently than curbside consultations (69%, 472/689 vs 35%, 206/592). Concerning legal liability, the majority of respondents considered that it is shared between the adviser and the referring physician, who, however, is considered primarily responsible. The advisers' liability was considered to be lower in cases of curbside and unrecorded consultations. Significant inter-countries and intra-country variability were identified, suggesting that the setting markedly influenced practices. CONCLUSION: Significant variability exists in the practice of antibiotic advising. This concerns both the organisation of care and how advisers perceive regulatory requirements. These elements must be taken into account when implementing antibiotic stewardship programmes and when training stewards.

Defensive medicine among antibiotic stewards: the international ESCMID AntibioLegalMap survey.

Objectives: To investigate fear of legal claims and defensive behaviours among specialists in infectious diseases (ID) and clinical microbiology (CM) and to identify associated demographic and professional characteristics. Methods: AntibioLegalMap was an international cross-sectional internet-based survey targeting specialists in ID and CM. Three variables were explored: fear of legal liability in antibiotic prescribing/advising on antibiotic prescription; defensive behaviours in antibiotic prescribing; and defensive behaviours in advising. A multivariable logistic regression analysis was performed to identify factors significantly associated with each of the three variables. Results: Eight hundred and thirty individuals from 74 countries participated. Only 0.4% (3/779) had any kind of condemnation for malpractice related to antibiotic prescription. Concerning the fear of liability, 21.2% (164/774) of respondents said they never worried, 45.1% (349/774) sometimes worried and 28.6% (221/774) frequently worried when prescribing/advising on antibiotic prescription. Being female, younger than or equal to 35 years and aware of previous cases of litigation were independently associated with fear. Most respondents (85.0%, 525/618) reported some defensive behaviour in antibiotic prescribing. These behaviours were independently associated with being younger than or equal to 35 years and sometimes or often worried about liability. Similarly, 76.4% (505/661) reported defensive behaviours in advising. These behaviours were associated with being sometimes or often worried about liability. The preferred measures to reduce fear and defensive behaviours were having local guidelines and sharing decisions through teamwork. Conclusions: A significant proportion of specialists in ID and CM reported some form of defensive behaviour in prescribing or advising to prescribe antibiotics. Defensive medicine should be considered when implementing antibiotic stewardship programmes.

Do medical students feel prepared to prescribe antibiotics responsibly? Results from a cross-sectional survey in 29 European countries.

Background: In an era of antibiotic resistance, medical students must be prepared to prescribe antibiotics responsibly. Objectives: To assess self-reported preparedness among final-year medical students at European universities, using a comprehensive set of topics related to prudent antibiotic use. Methods: We conducted a cross-sectional, multicentre, web-based survey. All medical-degree students in their final year of studies at European universities were eligible to participate. A preparedness score was calculated for each student and mean scores were compared at medical school and country levels. Comparisons were made with national-level data on resistance among four common bacterial pathogens. Results: In total, 7328 responses were included from 179/296 eligible medical schools in 29/29 countries. Students felt at least sufficiently prepared on a mean of 71.2% of topics assessed, ranging from 54.8% (Portugal) to 84.8% (Latvia). The proportion of students wanting more education on prudent antibiotic use or general antibiotic use ranged from 20.3% (Sweden) to 94.3% (Slovakia), with a mean of 66.1%, and was strongly inversely correlated with preparedness scores (Spearman's ρ = -0.72, n = 29, P < 0.001). Higher prevalence rates of antibiotic-non-susceptible bacteria were associated with lower preparedness scores and higher self-reported needs for further education (P < 0.01). Conclusions: Most final-year European medical students feel they still need more education on antibiotic use for their future practice as junior doctors. Patterns of preparedness on specific topics were identified, were highly consistent across countries, and correlated with both perceived need for further education and levels of antibiotic resistance among common bacteria.

Antibiotic use in people and pigs: a One Health survey of rural residents' knowledge, attitudes and practices in Shandong province, China.

Objectives: To evaluate rural residents' knowledge, attitudes and practices (KAP) towards antibiotic use in humans and pigs, among individuals with and without backyard pig farms living in Shandong province, China. Methods: We conducted a cross-sectional questionnaire study among residents in 12 villages, and directly observed medicines stored in households for humans and pigs. Results: In total, 769 residents participated, including 330 backyard pig farmers. Respondents had low levels of knowledge about antibiotics. A quarter of participants had bought one or more antibiotics from a pharmacy without a prescription in the previous year, and this was more common among pig farmers who had bought antibiotics for their pigs without consulting a vet (49% versus 25%, P < 0.001). Stored antibiotics for human use were found in 42% of households, and 70% of participants from these households did not know they were storing antibiotics. Thirty-one percent of backyard pig farmers were storing antibiotics for pig use. Farmers who thought it was good to store leftover antibiotics for their pigs were more likely to have stored antibiotics for pigs (41% versus 20%) and for humans (47% versus 32%; both P < 0.01). A fifth of participants thought their own actions were important for controlling antibiotic resistance. Conclusions: We found differences in the KAP of backyard pig farmers and non-pig farmers to antibiotics, and parallels between pig farmers' attitudes and behaviours towards antibiotic use in pigs and in humans. Our findings reinforce the need for context-adapted multifaceted interventions to improve antibiotic use and provide suggestions for targeting educational approaches.

Are infection specialists recommending short antibiotic treatment durations? An ESCMID international cross-sectional survey.

Objectives: To evaluate the current practice and the willingness to shorten the duration of antibiotic therapy among infection specialists. Methods: Infection specialists giving at least weekly advice on antibiotic prescriptions were invited to participate in an online cross-sectional survey between September and December 2016. The questionnaire included 15 clinical vignettes corresponding to common clinical cases with favourable outcomes; part A asked about the antibiotic treatment duration they would usually advise to prescribers and part B asked about the shortest duration they were willing to recommend. Results: We included 866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty-six percent of participants (271/749) already advised short durations of antibiotic therapy (compared with the literature) to prescribers for more than half of the vignettes and 47% (312/662) chose shorter durations in part B compared with part A for more than half of the vignettes. Twenty-two percent (192/861) of the participants declared that their regional/national guidelines expressed durations of antibiotic therapy for a specific clinical situation as a fixed duration as opposed to a range and in the multivariable analysis this was associated with respondents advising short durations for more than half of the vignettes (adjusted OR 1.5, P = 0.02). Conclusions: The majority of infection specialists currently do not advise the shortest possible duration of antibiotic therapy to prescribers. Promoting short durations among these experts is urgently needed.

Antibiotic use in rural China: a cross-sectional survey of knowledge, attitudes and self-reported practices among caregivers in Shandong province.

BACKGROUND: To improve antibiotic use globally, we must deepen our understanding of the public's knowledge, attitudes and practices (KAP) concerning antibiotics. Children are frequent users of antibiotics, and their caregivers play important roles in determining how antibiotics are used. The purpose of this study was to describe caregivers' KAP in a rural province in eastern China, and to identify socio-demographic factors associated with inappropriate antibiotic use. METHODS: A cross-sectional questionnaire based survey was conducted in 12 villages in one county in Shandong Province. A total of 727 individuals who were the primary day-to-day caregiver for a child aged 0-7 years were randomly selected and invited to participate. All caregivers were surveyed face-to-face using a semi-structured questionnaire focusing on the use of antibiotics in children. RESULTS: Almost all invited caregivers (99.3 %) completed the questionnaire in full. Caregivers expressed high levels of over-expectation for antibiotics for common childhood symptoms, stating that antibiotics were always or usually necessary when a child has a fever (46 %) or dry cough (42 %). Most caregivers (93 %) were aware that they should follow the doctor's advice when giving their children antibiotics. Many, however, reported that they had previously deviated from advice; this was most commonly through using antibiotics intermittently rather than regularly, but also by increasing and decreasing doses. Caregivers that were older and that had less formal education had higher levels of self-reported adherence (p < 0.01). A third of caregivers admitted to storing leftover antibiotics at home, and almost all of these caregivers (97 %) had used the antibiotics on a second occasion for their child. CONCLUSION: We have identified important gaps in knowledge, attitudes and practices concerning antibiotics among this rural population of caregivers. There is a clear need for multifaceted interventions that target village doctors, to improve prescribing and communication, as well as the general public, to improve health-seeking behaviours and promote responsible individual use of antibiotics.

European medical students: a first multicentre study of knowledge, attitudes and perceptions of antibiotic prescribing and antibiotic resistance.

OBJECTIVES: To learn about medical students' knowledge of and perspectives on antibiotic prescribing and resistance, with the aim of helping to develop educational programmes. METHODS: Final-year students at seven European medical schools were invited to participate in an online survey in 2012. RESULTS: The response rate was 35% (338/961). Most students (74%) wanted more education on choosing antibiotic treatments. Students at all schools felt most confident in diagnosing an infection and least confident in choosing combination therapies, choosing the correct dose and interval of administration and not prescribing in cases of diagnostic uncertainty. Students felt that too many prescriptions and too much broad-spectrum antibiotic use were the most important contributors to resistance; some (24%) believed poor hand hygiene was not at all important. Most students (92%) believed that resistance is a national problem. Most (66%) felt that the antibiotics they would prescribe would contribute to resistance, and almost all (98%) felt that resistance would be a greater problem in the future. Most students (83%) incorrectly thought that rates of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia had significantly increased over the past decade in their countries. There was little appreciation of the relative burden of resistance in Europe compared with road traffic accidents (around two to three times greater mortality) and lung cancer (around 10 times greater mortality). CONCLUSIONS: Students wanted further education on antibiotic prescribing, and areas of lack of confidence were found. Students overestimated the current burden of resistant bacteria and were unaware of successes in reducing MRSA infections. Educational and stewardship programmes may benefit from including more cases of diagnostic uncertainty, and highlighting successes such as MRSA prevention, as evidence for the importance of current interventions.

What makes people talk about antibiotics on social media? A retrospective analysis of Twitter use.

OBJECTIVES: Social media has reshaped individual and institutional communication. The unrestricted access to spontaneous views and opinions of society can enrich the evaluation of healthcare interventions. Antimicrobial resistance has been identified as a global threat to health requiring collaboration between clinicians and healthcare users. We sought to explore events and individuals influencing the discourse about antibiotics on Twitter. METHODS: A web-based tool (www.topsy.com) was used to detect daily occurrences of the word 'antibiotic' from 24 September 2012 to 23 September 2013 in worldwide Tweets. Activity peaks (message frequency over three times that of baseline) were analysed to identify events leading to the increase. RESULTS: Of 135 billion messages posted during the study period, 243000 (0.000002%) referred to 'antibiotic'. The greatest activity increases appeared after: (i) the UK Chief Medical Officer's (CMO's) declaration of antimicrobial resistance as a national risk (January 2013 and March 2013); (ii) the release of the US CDC's report on antimicrobial resistance (September 2013); and (iii) the US FDA announcement on azithromycin safety concerns (March 2013). The CMO report in March reached an estimated worldwide audience of 20 million users in a single day. However, the frequency of antibiotic Tweets returned to basal levels within 48 h of all four peaks in activity. CONCLUSIONS: Institutional events can rapidly amplify antibiotic discussions on social media, but their short lifespan may hinder their public impact. Multipronged strategies may be required to prolong responses. Developing methods to refine social media monitoring to evaluate the impact and sustainability of societal engagement in the antimicrobial resistance agenda remains essential.

2015 versus 2021: Self-Reported Preparedness to Prescribe Antibiotics Prudently among Final Year Medical Students in Sweden.

Cross-sectional surveys have found variations in how prepared medical students feel to prescribe antibiotics responsibly, but insights are lacking on the stability of these outcomes. In a 2015 survey, final-year Swedish medical students reported very high preparedness levels across a comprehensive range of relevant curriculum topics. We repeated this survey in 2021 to assess the stability of previous findings and to capture the potential impacts of the COVID-19 pandemic. Final-year students in 2015 and 2021 at all seven Swedish medical schools were eligible to participate in an online survey covering curricula topics, teaching methods and COVID-19 impacts (2021). Eligible students received email invitations and reminders from local coordinators. Students from six of seven medical schools participated in both surveys, with response rates of 24.1% (309/1281) in 2021 and 21.3% (239/1124) in 2015. The average global preparedness was 77.0% and 83.2%, respectively (p < 0.001), with lower preparedness levels in 24/27 curriculum topics in 2021. Students at certain universities reported COVID-19 impacts on antibiotic prescribing education (format, duration and perceived quality). Self-reported preparedness levels have fallen slightly but remain high compared with 2015 levels in other European countries. Students consistently reported lower preparedness in specific topics; improvement efforts should consider focusing on these areas, particularly in the context of the ongoing implementation of programmes leading to a full licence upon graduation.

Knowledge, attitudes and practices relating to antibiotic use and antibiotic resistance among backyard pig farmers in rural Shandong province, China.

China is among the world's largest consumers of antibiotics for livestock, and the demand for meat protein continues to rise. Pig production takes place at a range of facilities, including backyard pig farms. The aim of this study was to describe the knowledge, attitudes and practices of backyard pig farmers concerning antibiotic use and resistance, and to observe household storage of antibiotics for use in pigs. We conducted a cross-sectional questionnaire survey among 271 rural residents with backyard pig farms in 12 villages in one town in Shandong province. The median number of pigs per backyard farm was 14, and 82 % (222/271) of participants reported not having had any training about raising pigs. Eighteen percent of participants (48/271) reported always or often adding antibiotics to feed to keep pigs healthy and prevent diseases, and a third (88/271) of participants believed that pigs should be given antibiotics when they stop eating. Thirty percent (82/271) reported having bought antibiotics in the previous year without having first spoken with a veterinarian. Antibiotics accounted for over half of all medicines stored (55 %, 197/358), and were observed in 31 % of all households (83/271). Less than half of participants (45 %, 37/83) from households in which antibiotics for pig use were found knew that they were storing antibiotics. The most common class of antibiotics stored for use in pigs was (Q)J01C beta-lactam antibiotics, penicillins (19 %, 37/197), followed by (Q)J01F macrolides, lincosamides and streptogramins (14 %, 28/197), and (Q)J01M quinolones (12 %, 25/197). These results provide important insights into how backyard pig farmers are using antibiotics in rural China and suggest potential targets for interventions to reduce unnecessary and inappropriate use.

Perspective of Spanish medical students regarding undergraduate education in infectious diseases, bacterial resistance and antibiotic use. / La formación de grado en enfermedades infecciosas, resistencia y uso de antibióticos desde la perspectiva de los estudiantes de Medicina.

INTRODUCTION: One of the main tools to optimize antibiotics use is education of prescribers. The aim of this article is to study undergraduate education in the field of infectious diseases, antimicrobial resistance and antibiotic stewardship from the perspective of Spanish medical students. MATERIAL AND METHODS: An anonymous online questionnaire was distributed among sixth grade students using different channels in Europe, within the ESGAP Student-Prepare survey. The questionnaire included 45 questions about knowledge, attitudes and perceptions about diagnosis, bacterial resistance, use of antibiotics and undergraduate training in infectious diseases. We present here the Spanish results. RESULTS: A total of 441 surveys were received from 21 medical schools. A total of 374 responses (84.8%) were obtained from the 8 most represented faculties, with a response rate of 28.9%. Most students felt adequately prepared to identify clinical signs of infection (418; 94.8%) and to accurately interpret laboratory tests (382; 86.6%). A total of 178 (40.4%) acknowledged being able to choose an antibiotic with confidence without consulting books or guidelines. Only 107 (24.3%) students considered that they had received sufficient training in judicious use of antibiotics. Regarding learning methods, the discussion of clinical cases, infectious diseases units rotatories and small group workshops were considered the most useful, being evaluated favorably in 76.9%, 76% and 68.8% of the cases. CONCLUSION: Medical students feel more confident in the diagnosis of infectious diseases than in antibiotic treatment. They also feel the need to receive more training in antibiotics and judicious antibiotic use.

How can we improve antibiotic prescribing in primary care?

Antibiotic stewardship is a necessity given the worldwide antimicrobial resistance crisis. Outpatient antibiotic use represents around 90% of total antibiotic use, with more than half of these prescriptions being either unnecessary or inappropriate. Efforts to improve antibiotic prescribing need to incorporate two complementary strategies: changing healthcare professionals' behaviour, and modifying the healthcare system. In this review, we present a broad perspective on antibiotic stewardship in primary care in high and high-middle income country settings, focussing on studies published in the last five years. We present the limitations of available literature, discuss perspectives, and provide suggestions for where future work should be concentrated.

Overuse of antibiotics for the common cold - attitudes and behaviors among doctors in rural areas of Shandong Province, China.

BACKGROUND: Irrational antibiotic use is common in rural areas of China, despite the growing recognition of the importance of appropriate prescribing to contain antibiotic resistance. The aim of this study was to analyze doctors' attitudes and prescribing practices related to antibiotics in rural areas of Shandong province, focusing on patients with the common cold. METHODS: A survey was conducted with doctors working at thirty health facilities (village clinics, township health centers and county general hospitals) in three counties within Shandong province. Questions were included on knowledge and attitudes towards antibiotic prescribing. Separately, a random selection of prescriptions for patients with the common cold was collected from the healthcare institutions at which the doctors worked, to investigate actual prescribing behaviors. RESULTS: A total of 188 doctors completed the survey. Most doctors (83%, 149/180) had attended training on antibiotic use since the beginning of their medical practice as a doctor, irrespective of the academic level of their undergraduate training. Of those that had training, most had attended it within the past three years (97%, 112/116). Very few doctors (2%, 3/187) said they would give antibiotics to a patient with symptoms of a common cold, and the majority (87%, 156/179) would refuse to prescribe an antibiotic even if patients were insistent on getting them. Doctors who had attended training were less likely to give antibiotics in this circumstance (29% vs. 14%, p < 0.001). A diagnosis of common cold was the only diagnosis reported on 1590 out of 8400 prescriptions. Over half (55%, 869/1590) of them included an antibiotic. Prescriptions from village clinics were more likely to contain an antibiotic than those from other healthcare institutions (71% vs. 44% [township] vs. 47% [county], p < 0.001). CONCLUSIONS: Most doctors have recently attended training on antibiotic use and report they would not prescribe antibiotics for patients with a common cold, even when placed under pressure by patients. However, more than half of the prescriptions from these healthcare institutions for patients with the common cold included an antibiotic. Exploring and addressing gaps between knowledge and practice is critical to improving antibiotic use in rural China.

La formación de grado en enfermedades infecciosas, resistencia y uso de antibióticos desde la perspectiva de los estudiantes de Medicina / Perspective of Spanish medical students regarding undergraduate education in infectious diseases, bacterial resistance and antibiotic use

Introducción: Una de las principales herramientas para optimizar el uso de los antibióticos es la formación de los prescriptores. El objetivo de este trabajo es conocer la opinión de los estudiantes de Medicina españoles sobre la formación en enfermedades infecciosas. Material y métodos: Se distribuyó un cuestionario on line anonimizado entre estudiantes de sexto curso a través de distintos canales. El cuestionario incluyó 45 preguntas sobre conocimientos, actitudes y percepciones sobre el diagnóstico, resistencia antimicrobiana, uso de antibióticos y la formación de pregrado en enfermedades infecciosas. Resultados: Se recibieron un total de 441 encuestas de 21 facultades. Se obtuvieron 374 respuestas (84,8%) de las 8 facultades más representadas, con una tasa de respuesta del 28,9%. La mayoría de los alumnos se sentían preparados para identificar los signos clínicos de infección (418; 94,8%) y para interpretar correctamente las pruebas de laboratorio (382; 86,6%). Reconocieron saber elegir un antibiótico con seguridad sin consultar libros ni guías (178; 40,4%). Solo 107 alumnos (24,3%) consideraron haber recibido suficiente formación en el uso prudente de los antimicrobianos. Respecto a los métodos de aprendizaje, se percibieron como más útiles la discusión de casos clínicos, los rotatorios en servicios o unidades de enfermedades infecciosas y los talleres de pequeños grupos: se evaluaron favorablemente en un 76,9; en un 76 y en un 68,8% de los casos, respectivamente. Conclusión: Los estudiantes de Medicina se encuentran más seguros en el diagnóstico de enfermedades infecciosas que en el tratamiento antibiótico. Asimismo, sienten la necesidad de recibir mayor formación en antibioterapia y uso prudente en antibióticos

Introduction: One of the main tools to optimize antibiotics use is education of prescribers. The aim of this article is to study undergraduate education in the field of infectious diseases, antimicrobial resistance and antibiotic stewardship from the perspective of Spanish medical students. Material and methods: An anonymous online questionnaire was distributed among sixth grade students using different channels in Europe, within the ESGAP Student-Prepare survey. The questionnaire included 45 questions about knowledge, attitudes and perceptions about diagnosis, bacterial resistance, use of antibiotics and undergraduate training in infectious diseases. We present here the Spanish results. Results: A total of 441 surveys were received from 21 medical schools. A total of 374 responses (84.8%) were obtained from the 8 most represented faculties, with a response rate of 28.9%. Most students felt adequately prepared to identify clinical signs of infection (418; 94.8%) and to accurately interpret laboratory tests (382; 86.6%). A total of 178 (40.4%) acknowledged being able to choose an antibiotic with confidence without consulting books or guidelines. Only 107 (24.3%) students considered that they had received sufficient training in judicious use of antibiotics. Regarding learning methods, the discussion of clinical cases, infectious diseases units rotatories and small group workshops were considered the most useful, being evaluated favorably in 76.9%, 76% and 68.8% of the cases. Conclusion: Medical students feel more confident in the diagnosis of infectious diseases than in antibiotic treatment. They also feel the need to receive more training in antibiotics and judicious antibiotic use

Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin.

OBJECTIVE: A major site of action for the atheroprotective drug nicotinic acid (NA) is adipose tissue, via the G-protein-coupled receptor, GPR109A. Since, adipose tissue is an active secretory organ that contributes both positively and negatively to systemic inflammatory processes associated with cardiovascular disease, we hypothesized that NA would act directly upon adipocytes to alter the expression of pro-inflammatory chemokines, and the anti-inflammatory adipokine adiponectin. METHODS AND RESULTS: TNF-alpha treatment (1.0ng/mL) of 3T3-L1 adipocytes resulted in an increase in gene expression of fractalkine (9+/-3.3-fold, P<0.01); monocyte chemoattractant protein-1 (MCP-1) (24+/-1.2-fold, P<0.001), 'regulated upon activation, normal T cell expressed and secreted' (RANTES) (500+/-55-fold, P<0.001) and inducible nitric oxide synthase (iNOS) (200+/-70-fold, P<0.05). The addition of NA (10(-4)M) to TNF-alpha-treated adipocytes attenuated expression of fractalkine (50+/-12%, P<0.01); MCP-1 (50+/-6%, P<0.01), RANTES (70+/-3%, P<0.01) and iNOS (60+/-16%). This pattern was mirrored in protein released from the adipocytes into the surrounding media. The effect on gene expression was neutralised by pre-treatment with pertussis toxin. NA attenuated macrophage chemotaxis (by 27+/-3.5%, P<0.001) towards adipocyte conditioned media. By contrast, NA, (10(-6)-10(-3)M) increased, in a dose-dependent manner, mRNA of the atheroprotective hormone adiponectin (3-5-fold n=6, P<0.01). CONCLUSIONS: NA suppresses pro-atherogenic chemokines and upregulates the atheroprotective adiponectin through a G-protein-coupled pathway. Since adipose tissue has the potential to contribute to both systemic and local (perivascular) inflammation associated with atherosclerosis our results suggest a new "pleiotropic" role for NA.