Recognition and Management of Protracted Bacterial Bronchitis in Australian Aboriginal Children: A Knowledge Translation Approach.

BACKGROUND: Chronic wet cough in children is the hallmark symptom of protracted bacterial bronchitis (PBB) and if left untreated can lead to bronchiectasis, which is prevalent in Indigenous populations. Underrecognition of chronic wet cough by parents and clinicians and underdiagnosis of PBB by clinicians are known. RESEARCH QUESTION: We aimed to improve recognition and management of chronic wet cough in Aboriginal children using knowledge translation (KT), a methodologic approach that can be adapted for use in Indigenous contexts to facilitate effective and sustained translation of research into practice. STUDY DESIGN AND METHODS: A mixed-methods KT study undertaken at a remote-based Aboriginal primary medical service (February 2017 to December 2019). Our KT strategy included the following: (1) culturally secure (ie, ensuring Aboriginal people are treated regarding their unique cultural needs and differences) knowledge dissemination to facilitate family health seeking for chronic wet cough in children, and (2) an implementation strategy to facilitate correct diagnosis and management of chronic wet cough and PBB by physicians. RESULTS: Post-KT, health seeking for chronic wet cough increased by 184% (pre = eight of 630 children [1.3%], post = 23 of 636 children [3.6%]; P = .007; 95% CI, 0.7%-4.0%). Physician proficiency in management of chronic wet cough improved significantly as reflected by improved chronic cough-related quality of life (P < .001; 95% CI, 0.8-3.0) and improved physician assessment of cough quality (P < .001; 95% CI, 10.4%-23.0%), duration (P < .001; 95% CI, 11.1%-24.1%), and appropriate antibiotic prescription (P = .010; 95% CI, 6.6%-55.7%). INTERPRETATION: Health seeking for children with chronic wet cough can be facilitated through provision of culturally secure health information. Physician proficiency in the management of PBB can be improved with KT strategies which include training in culturally informed management, leading to better health outcomes. Comprehensive strategies that include both families and health systems are required to ensure that chronic wet cough in children is detected and optimally managed.

Risk factors for hospitalizations due to bacterial respiratory tract infections after tracheotomy.

OBJECTIVE: Identify characteristics associated with hospital readmission due to bacterial respiratory tract infections (bRTI) after tracheotomy. STUDY DESIGN: Retrospective study of 8009 children 0-17 years undergoing tracheotomy from 2007 to 2013 at 48 children's hospitals in the Pediatric Health Information System database. The primary outcome was first hospital admission after tracheotomy for bRTI (ie, primary diagnosis of bRTI or a primary diagnosis of bRTI symptom and secondary diagnosis of bRTI). We used Cox-proportional hazard modeling to assess associations between patient demographic and clinical characteristics and bRTI hospital readmission. RESULTS: Median age at tracheotomy admission was 5 months (interquartile range [IQR]: 1-50 months). Thirty-six percent (n = 2899) had at least one bRTI admission. Median time-to-readmission for bRTI was 275 days (IQR: 141-530). Factors independently associated with increased risk for bRTI readmission were younger age (eg, age < 30 days vs 13-17 years [aHR 1.32; 95%CI: 1.11-1.58]), Hispanic race/ethnicity (vs non-Hispanic White; aHR: 1.34; 95%CI: 1.20-1.50), government insurance (vs private; aHR 1.21; 95%CI: 1.10-1.33), >2 complex chronic conditions (vs zero; aHR 1.96; 95%CI: 1.34-2.86) and discharge to home (vs post-acute care setting; aHR 1.19; 95%CI: 1.08-1.32). Trauma diagnosis at tracheotomy (aHR 0.83; 95%CI: 0.69-1) and ventilator dependency (aHR 0.88; 95%CI: 0.81-0.97) were associated with decreased risk. CONCLUSIONS: Young, Hispanic children with multiple complex chronic conditions who use Medicaid insurance and are not discharged to post-acute care are at the highest risk for hospital readmission for bRTI post-tracheotomy. Future research should investigate strategies to mitigate this risk for these children.

Cumulative Burden of Glucocorticoid-related Adverse Events in Patients with Systemic Lupus Erythematosus: Findings from a 12-year Longitudinal Study.

OBJECTIVE: The aim of this population-based study is to examine the adverse events (AE) associated with longitudinal systemic glucocorticoid (GC) use among an ethnic Chinese systemic lupus erythematosus (SLE) cohort. METHODS: Our study subjects were patients with newly diagnosed SLE aged 18 and older who received at least 1 prescription of systemic GC between 2001 and 2012 from Taiwan's National Health Insurance Research Database (NHIRD). The earliest prescription date of systemic GC for each subject was defined as the index date. For each subject, we calculated the average prednisolone-equivalent dose and the medication possession ratio (MPR) of GC use every 90 days for each patient after the index date. Patients with a diagnosis of AE (defined by the International Classification of Diseases-9-Clinical Modification diagnosis code) during the followup were also identified from the NHIRD. Generalized estimating equations adjusted for propensity score were applied to examine the association between longitudinal GC use and risks of prespecified AE (musculoskeletal, gastrointestinal, ophthalmologic, infectious, cardiovascular, neuropsychiatric, metabolic, and dermatologic diseases). RESULTS: We identified 11,288 patients with SLE (mean followup: 6.28 yrs). Higher doses and higher MPR of GC were associated with increased risk of osteonecrosis [adjusted OR (aOR) 2.87-9.09]. Similar results were found regarding the risk of osteoporosis (aOR 1.71-3.67), bacterial infection (aOR 2.12-3.89), Cushingoid syndrome (aOR 6.51-62.03), and sleep disorder (aOR 1.42-3.59). CONCLUSION: To our knowledge, this is the first study to show that the dose and intensity of longitudinal use of GC were both associated with risk of AE among a nationwide Asian SLE cohort.

Human leucocyte antigen-adverse drug reaction associations: from a perspective of ethnicity.

Whilst immune-mediated adverse drug reactions (ADRs) are rare, they are potentially life-threatening and present a major problem for clinicians. The underlying mechanisms that cause ADRs are not fully understood although genomewide association studies (GWAS) and case-control investigations have associated human leucocyte antigen (HLA) alleles as risk factors. There is evidence that a patient's ethnic background can have an impact on their risk of developing an ADR. This review summarizes the evidence related to HLA alleles and ADRs with particular focus on patient ethnicity. Our analysis indicated that many of the alleles which have been associated with ADRs are found at higher frequencies in Asian populations. The data also showed that many of the alleles that are reported to be statistically significantly associated with ADRs are in linkage disequilibrium with each other and that they form haplotypes specific to certain ethnicities indicating at least some of the allele associations may not be causal.

Dietary protein intake may reduce hospitalisation due to infection in Maori of advanced age: LiLACS NZ.

OBJECTIVE: To investigate factors related to hospital admission for infection, specifically examining nutrient intakes of Maori in advanced age (80+ years). METHOD: Face-to-face interviews with 200 Maori (85 men) to obtain demographic, social and health information. Diagnoses were validated against medical records. Detailed nutritional assessment using the 24-hour multiple-pass recall method was collected on two separate days. FOODfiles was used to analyse nutrient intake. National Health Index (NHI) numbers were matched to hospitalisations over a two-year period (12 months prior and 12 months following dietary assessment). Selected International Classification of Disease (ICD) codes were used to identify admissions related to infection. RESULTS: A total of 18% of participants were hospitalised due to infection, most commonly lower respiratory tract infection. Controlling for age, gender, NZ deprivation index, diabetes, CVD and chronic lung disease, a lower energy-adjusted protein intake was independently associated with hospitalisation due to infection: OR (95%CI) 1.14 (1.00-1.29), p=0.046. CONCLUSIONS: Protein intake may have a protective effect on the nutrition-related morbidity of older Maori. Improving dietary protein intake is a simple strategy for dietary modification aiming to decrease the risk of infections that lead to hospitalisation and other morbidities.

Fifty years of immunisation in Australia (1964-2014): the increasing opportunity to prevent diseases.

Medicine has seen dramatic changes in the last 50 years, and vaccinology is no different. Australia has made a significant contribution to world knowledge on vaccine-preventable diseases. Certain deadly diseases have disappeared or become rare in Australia following successful introduction of vaccines. As diseases become rarer, public knowledge about the diseases and their serious consequences has decreased, and concerns about potential vaccine side effects have increased. To maintain confidence in immunisations, sharing of detailed information about the vaccines and the diseases we are trying to prevent is integral to the continued success of our public health programme. Modern quality immunisation programmes need to communicate complex information to immunisation providers and also to the general community. Improving immunisation coverage rates and eliminating the gap in coverage and timeliness between Aboriginal and Torres Strait Islander peoples and non-Indigenous people has become a high priority.

Gastrointestinal amyloidosis in Australian indigenous patients.

This study documents the symptoms, racial distribution, pathological findings and outcomes of patients diagnosed with gastrointestinal amyloidosis in Alice Springs Hospital. In a 4 year retrospective survey. 9 patients, all indigenous, 7F/2M, had biopsy proven gastrointestinal amyloidosis. Four out of four patients tested were found to have AA amyloidosis. Presenting symptoms included diarrhoea, bloody in some, vomiting and abdominal pain. All but one had diabetes mellitus, type 2. Multiple infections were common and most patients had low serum albumin and transferrin concentrations but high serum ferritin concentrations. Five of the patients died, and the gastrointestinal symptoms of the remaining 4 remitted. Gastrointestinal amyloidosis should be included in the differential diagnosis of indigenous patients presenting with chronic diarrhoea, vomiting or abdominal pain. It carries a grave prognosis, is probably secondary to chronic infections but is potentially reversible.

Deep sequencing identifies ethnicity-specific bacterial signatures in the oral microbiome.

Oral infections have a strong ethnic predilection; suggesting that ethnicity is a critical determinant of oral microbial colonization. Dental plaque and saliva samples from 192 subjects belonging to four major ethnicities in the United States were analyzed using terminal restriction fragment length polymorphism (t-RFLP) and 16S pyrosequencing. Ethnicity-specific clustering of microbial communities was apparent in saliva and subgingival biofilms, and a machine-learning classifier was capable of identifying an individual's ethnicity from subgingival microbial signatures. The classifier identified African Americans with a 100% sensitivity and 74% specificity and Caucasians with a 50% sensitivity and 91% specificity. The data demonstrates a significant association between ethnic affiliation and the composition of the oral microbiome; to the extent that these microbial signatures appear to be capable of discriminating between ethnicities.

Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: functional implications.

The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.

Higher systemic antibiotic consumption in a population of South Korea (2008 - 2009).

This study was conducted to investigate overall systemic antibiotic consumption levels and specific patterns using standardized Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology. National Health Insurance claims data during 2008 and 2009 was used. Antibiotic prescription data was classified using the ATC system and converted into DDD. Consumption figures were presented as the number of DDD per 1,000 inhabitants per day (DID). Detailed information on indications and seasonal variations, age and institutional determinants on antibiotic consumption were also explored. Total consumption was slightly increased from 24.3 to 25.2 DID in 2009 compared to 2008. The most frequently prescribed antibiotic was amoxicillin/clavulanic acid (5.1 and 5.2 DID, in 2008 and 2009, respectively), followed by cefaclor (3.0 and 3.3 DID) and amoxicillin (3.3 and 3.2 DID). Respiratory system diseases were the main causes of antimicrobial prescription (47.3%) and acute forms of bronchitis, tonsillitis and sinusitis were the most common diseases. There were typical seasonal fluctuations with heightened winter peaks. Consumption figures under 5 years of age (41.6 and 43.3 DID) were even higher than figures in aged 65 - 80 (36.2 and 39.1 DID). Antibiotic consumption in South Korea remained high compared with other OECD countries. Efforts to increase prudent antibiotic use, especially for upper respiratory system infections and for younger children, should be made to decrease antibiotic use.

Might infection explain the higher risk of coronary heart disease in South Asians? Systematic review comparing prevalence rates with white populations in developed countries.

OBJECTIVES: South Asians in developed countries such as the UK are at comparatively high risk of coronary heart disease for reasons which are not fully understood. One unexplored hypothesis is more infections in this ethnic group. This study assessed whether the prevalence of infections among South Asians differs from that among White populations of European origin in developed countries. STUDY DESIGN: Systematic review. METHODS: Medline, Web of Science and Google Scholar databases were searched. In addition, reference lists and citations were reviewed. RESULTS: Twenty-one studies reported prevalence rates and mean antibody levels of infection with 17 different pathogens or non-specific markers of infection. Among bacterial infections, higher rates of Escherichia coli and Mycobacterium tuberculosis infection were found in South Asians. No consistent differences were found for periodontal pathogens, Helicobacter pylori, Staphylococcus aureus, Chlamydia pneumoniae and Mycobacterium avium. For viral pathogens, higher rates of hepatitis A, hepatitis B and cytomegalovirus; and lower rates of herpes simplex, hepatitis C, human immunodeficiency virus and varicella zoster virus were found among South Asians. No difference was seen in the prevalence of hepatitis G virus in South Asians. Levels of non-specific markers of infection (total immunoglobulin G, endotoxin) were higher in South Asians. CONCLUSIONS: The number of studies was small. Differences in the prevalence of specific infections were found, but the current evidence is insufficient to support or reject the hypothesis under examination. Further studies are warranted.

Detection of betalactamase producing bacterial genes and their clinical features.

The present study was aimed to identify the gene of drug resistance betalactamase producing bacteria and clinical features of the infected patients at Hospital University Kebangsaan Malaysia. Blood samples from the patients were collected, processed and betalactamase producing drug resistance bacteria were identified by antibiotic sensitivity testing. Genes of the drug resistance bacteria were detected and characterized by polymerase chain reaction. A total of 34 isolates of drug resistance Betalactamase producing E. coli and Klebsiella spp. were isolated from 2,502 patients. Most common drug resistance gene TEM was found in 50% of the isolates. 11% was found positive for both TEM and SHV. Next 11% of the isolates expressed only SHV genes. Clinical features of the patients were recorded from where the bacteria isolated. Regarding community affiliations 70.5% of the infected patients were Malay 17.6% were Indian and 11.7% were Chinese. Majority of the patients has an underlying pre-morbid condition as reflected by their diagnosis. Better infection control and hygiene in hospitals, plus controlled and prudent use of antibiotics, is required to minimize the impact of drug resistance betalactamase producing bacteria and the spread of infections.

An overview of racial disparities in preterm birth rates: caused by infection or inflammatory response?

Infection has been hypothesized to be one of the factors associated with spontaneous preterm birth (PTB) and with the racial disparity in rates of PTB between African American and Caucasian women. However, recent findings refute the generalizability of the role of infection and inflammation. African Americans have an increased incidence of PTB in the setting of intraamniotic infection, periodontal disease, and bacterial vaginosis compared to Caucasians. Herein we report variability in infection- and inflammation-related factors based on race/ethnicity. For African American women, an imbalance in the host proinflammatory response seems to contribute to infection-associated PTB, as evidenced by a greater presence of inflammatory mediators with limited or reduced presence of immune balancing factors. This may be attributed to differences in the genetic variants associated with PTB between African Americans and Caucasians. We argue that infection may not be a cause of racial disparity but in association with other risk factors such as stress, nutritional deficiency, and differences in genetic variations in PTB, pathways and their complex interactions may produce differential inflammatory responses that may contribute to racial disparity.

Maternal country of origin, breast milk characteristics and potential influences on immunity in offspring.

Breast milk contains pro- and anti-inflammatory cytokines and chemokines with potential to influence immunological maturation in the child. We have shown previously that country of birth is associated with the cytokine/chemokine profile of breast milk. In this study we have investigated how these differences in breast milk affect the cellular response of cord blood mononuclear cells (CBMCs) and intestinal epithelial cells (IECs, cell line HT-29) to microbial challenge. Ninety-five women were included: 30 from Mali in West Africa, 32 Swedish immigrants and 33 native Swedish women. CBMCs or IECs were stimulated in vitro with breast milk, alone or in combination with lipopolysaccharide (LPS) or peptidoglycan (PGN). Breast milk in general abrogated the LPS-induced down-regulation of surface CD14 and Toll-like receptor (TLR)-4 expression on CB monocytes, while inhibiting the PGN-induced TLR-2 up-regulation. However, breast milk from immigrant women together with LPS induced a lower CBMC release of interleukin (IL)-6 (P = 0·034) and CXCL-8/IL-8 (P = 0·037) compared with breast milk from Swedish women, while breast milk from Swedish women and Mali women tended to increase the response. The same pattern of CXCL-8/IL-8 release could be seen after stimulation of IECs (HT-29). The lower CBMC and IEC (HT-29) responses to microbial compounds by breast milk from immigrant women could be explained by the fact that breast milk from the immigrant group showed a divergent pro- and anti-inflammatory content for CXCL-8/IL-8, transforming growth factor-ß1 and soluble CD14, compared to the other two groups of women. This may have implications for maturation of their children's immune responses.

Infectious complications in kidney transplant: a Lebanese perspective.

OBJECTIVES: Infections remain a frequent, potentially life-threatening complication of kidney transplant. SUBJECTS AND METHODS: Between 1998 and 2006, we evaluated the incidence of infections in 114 kidney transplant patients, with a 1-year follow-up. All patients received a posttransplant anti-infectious prophylaxis regimen. Induction therapy was given to 94 patients (82.4%), and maintenance immunosuppression consisted of calcineurin inhibitor (cyclosporin microemulsion or tacrolimus), together with mycophenolate mofetil and prednisone. RESULTS: In total, 56 patients (49.1%) developed a total of 95 infections up to 1-year after kidney transplant, including 46 in-hospital infections in 38 patients. Bacterial infections were the most frequent (97.8%), and were mainly urinary, followed by drain, central line catheter, and pulmonary infections. The most-frequent isolated bacteria were E. coli, followed by Klebsiella, Acinetobacter, and Pseudomonas. No viral infections were detected. Up to 1 year after discharge from the hospital, 49 infections occurred in 26 patients, of which 79.5% were bacterial; mainly urinary tract infections due to E. coli, in addition to 7 cases of cytomegalovirus, 1 herpes, and 2 cases of fungal infections. CONCLUSIONS: This is the first Lebanese study that deals with posttransplant infections in kidney transplant patients and underscores the importance of close patient monitoring and follow-up. Comparison with international data shows similar patterns.

Infective spondylitis in Southern Chinese: a descriptive and comparative study of ninety-one cases.

STUDY DESIGN: A retrospective review of infective spondylitis patients assessed at a major, tertiary referral centre in Hong Kong. OBJECTIVE: To assess the prevalence, risk factors, clinical features, and prognostic outcomes associated with tuberculous spondylitis to that of pyogenic spondylitis in Southern Chinese treated at a single institution. SUMMARY OF BACKGROUND DATA: Previous studies in Asia suggest that tuberculous spondylitis is the predominant infection unless proven otherwise. Current clinical experiences suggest otherwise; however, the current trend and clinical profile of infective spondylitis among Southern Chinese remains speculative with no published studies examining their prevalence. METHODS: A retrospective review was performed of all infective spondylitis cases presenting from January 2004 to July 2008 to a tertiary referral center. Cases were included on the basis of clinical and microbiological criteria. Radiographic imaging was used for further confirmation. RESULTS: Ninety-one patients were identified. Overall, tuberculous spondylitis and pyogenic spondylitis entailed 22 (24.2%) and 69 (75.8%) cases, respectively. Staphylococcus aureus was the most commonly isolated infective agent associated with pyogenic spondylitis. Individuals with pyogenic spondylitis were significantly much older than those with tuberculous spondylitis (P = 0.001). Intravenous drug addiction was the most commonly noted risk factor followed by diabetes, and found to be more prevalent in pyogenic spondylitis cases. At initial presentation, white cell count and c-reactive protein levels were higher in pyogenic spondylitis cases compared with tuberculous spondylitis (P < 0.05). The occurrence of tuberculous spondylitis cases was predominant in the thoracic region (40.9%) (P < 0.05). Surgical intervention was performed in 54.5% of tuberculous spondylitis and in 24.6% of the pyogenic spondylitis cases (P = 0.009). CONCLUSION: In Southern Chinese, compared to previous reports over the past 3 decades, a changing prevalence of decreasing tuberculous spondylitis was observed. Pyogenic spondylitis was found to be more common among patients hospitalized for infective spondylitis. This has important implications on the method of diagnosis and the need for establishing microbiological diagnosis before commencing treatment. "Best guess" therapy should not be targeted at tuberculous spondylitis only. There are clear distinctions in the biologic and clinical profiles between tuberculous and pyogenic spondylitis that would help to direct therapy.

Bugs and irritable bowel syndrome: The good, the bad and the ugly.

Recently, there has been strong interest in the therapeutic potential of probiotics for irritable bowel syndrome (IBS). At the same time, there is a rapidly growing body of evidence to support an etiological role for gastrointestinal infection and the associated immune activation in the development of post-infectious IBS. In a more controversial area, small intestinal bacterial overgrowth has been associated with a subset of patients with IBS; the issue of whether it is appropriate to treat a subset of IBS patients with antibiotics and probiotics is currently a matter for debate. Thus, it appears that the gastrointestinal microbial flora may exert beneficial effects for symptoms of IBS under some circumstances, while in other situations gut microbes could give rise to symptoms of IBS. How do we make sense of the apparently diverse roles that 'bugs' may play in IBS? To address this question, we have conducted an in-depth review, attempting where possible to draw lessons from Asian studies.

Infectious burden and carotid plaque thickness: the northern Manhattan study.

BACKGROUND AND PURPOSE: The overall burden of prior infections may contribute to atherosclerosis and stroke risk. We hypothesized that serological evidence of common infections would be associated with carotid plaque thickness in a multiethnic cohort. METHODS: Antibody titers to 5 common infectious microorganisms (ie, Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesvirus 1 and 2) were measured among stroke-free community participants and a weighted index of infectious burden was calculated based on Cox models previously derived for the association of each infection with stroke risk. High-resolution carotid duplex Doppler studies were used to assess maximum carotid plaque thickness. Weighted least squares regression was used to measure the association between infectious burden and maximum carotid plaque thickness after adjusting for other risk factors. RESULTS: Serological results for all 5 infectious organisms were available in 861 participants with maximum carotid plaque thickness measurements available (mean age, 67.2+/-9.6 years). Each individual infection was associated with stroke risk after adjusting for other risk factors. The infectious burden index (n=861) had a mean of 1.00+/-0.35 SD and a median of 1.08. Plaque was present in 52% of participants (mean, 0.90+/-1.04 mm). Infectious burden was associated with maximum carotid plaque thickness (adjusted increase in maximum carotid plaque thickness 0.09 mm; 95% CI, 0.03 to 0.15 mm per SD increase of infectious burden). CONCLUSIONS: A quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with carotid plaque thickness in this multiethnic cohort. These results lend support to the notion that past or chronic exposure to common infections, perhaps by exacerbating inflammation, contributes to atherosclerosis. Future studies are needed to confirm this hypothesis and to define optimal measures of infectious burden as a vascular risk factor.

Investigating approaches to improving appropriate antibiotic use among higher risk ethnic groups.

A field study with follow up investigations sought to: 1. determine whether cold packs (over-the-counter symptomtic treatments), coupled with in-office education, improve antibiotic-related knowledge, attitudes and behaviors more than in-office education alone in patient populations with high percentages of Asian Americans and Hawaiian/Pacific Islanders; 2. identify possible reasons for intervention outcomes as described by physicians who participated in the field study; and 3. explore potential future directions based on a large sample survey of physicians in the field study's highly ethnic county. The intervention resulted in a pre- to post-consultation decrease in perceived need for and an increase in knowledge about antibiotic risks but had no impact on frequency of reported receipt of an antibiotic prescription. Unexpectedly, in-office education alone was more effective in increasing knowledge than in-office education plus the cold pack. In-depth interviews of field study physicians and a large scale physician survey suggest that cold pack interventions targeting patient populations with high percentages of Asian Americans and Hawaiian/Pacific Islanders may be more likely to succeed if accompanied by mass public education regarding risks and physician training regarding effective ways to talk to patients. Use of in-office education with cold packs alone may not achieve desired results.