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As endovascular aortic aneurysm repair (EVAR) matures into its third decade, measures such as long-term reintervention and readmission have become a focus of quality improvement efforts. Within a large United States integrated health care system, we describe time trends in the rates of long-term reinterventions utilization measures.Data from a United States multiregional EVAR registry was used to perform a descriptive study of 3891 adults who underwent conventional infrarenal EVAR for infrarenal abdominal aortic aneurysm between 2010 and 2019. Three-year follow-up was 96.7%. Outcomes included 1-, 3-, and 5-year graft revision (defined as a procedure involving placement of a new endograft component), secondary interventions (defined as a procedure necessary for maintenance of EVAR integrity [eg, coil embolization and balloon angioplasty/stenting]), conversion to open, interventions for type II endoleaks alone, and 90-day readmission. Crude cause-specific reintervention probabilities were calculated by operative year using the Aalen-Johansen estimator, with death as a competing risk and December 31, 2020 as the study end date.Excluding interventions for type II endoleak alone, 1-year secondary intervention incidence decreased from 5.9% for EVARs in 2010 to 2.0% in 2019 (P .001) and 3-year incidence decreased from 7.2% to 3.6% from 2010 to 2017 (P = .03). The 3-year incidences of graft revision (mean incidence, 3.4%) and conversion to open remained fairly stable (mean incidence, 0.6%) over time. The 3-year incidence of interventions for type II endoleak alone also decreased from 3.4% in 2010 to 0.7% in 2017 (P = .01). Ninety-day readmission rates decreased from 19.3% for index EVAR in 2010 to 9.2% in 2019 (P = .03).Comprehensive data from a multiregional health care system demonstrates decreasing long-term secondary intervention and readmission rates over time in patients undergoing EVAR. These trends are not explained by evolving management of type II endoleaks and suggest improving graft durability, patient selection, or surgical technique. Further study is needed to define implant and anatomic predictors of different types of long-term reintervention.

Bleeding caused by coagulopathy is common in children undergoing cardiac surgery and causes adverse outcomes. Coagulation testing assists selection of treatments to stop bleeding but has an uncertain role for predicting bleeding. We aimed to evaluate how well prospective coagulation testing predicted excessive bleeding during and after cardiac surgery compared to prediction using clinical characteristics alone. The study was a single-center, prospective cohort study in children having a range of cardiac surgery procedures with coagulation testing at anesthetic induction and immediately after cardiopulmonary bypass. The primary outcome was clinical concern about bleeding (CCB), a composite of either administration of prohemostatic treatments in response to bleeding or a high chest drain volume after surgery. In 225 children, CCB occurred in 26 (12%) during surgery and in 68 (30%) after surgery. Multivariable fractional polynomial models using the clinical characteristics of the children alone predicted CCB during surgery (c-statistic 0.64; 95% confidence interval 0.53, 0.76) and after surgery (0.74; 0.67, 0.82). Incorporating coagulation test results into these models improved prediction (c-statistics 0.79; 0.70, 0.87, and 0.80; 0.74, 0.87, respectively). However, this increased the overall proportion of children classified correctly as CCB or not CCB during surgery by only 0.9% and after surgery by only 0.4%. Incorporating coagulation test results into predictive models had no effect on prediction of blood transfusion or postoperative complications. Prospective coagulation testing marginally improves prediction of CCB during and after cardiac surgery but the clinical impact of this is small when compared to prediction using clinical characteristics.

BACKGROUND CONTEXT Although fusion rates between posterolateral fusions with pedicle screws (PLFs) and anterior lumbar interbody fusions with pedicle screws (ALIFs+PS) have been well studied, there has been no consensus on the better technique with respect to clinical outcome and nonunion rates. Most studies determine nonunion rates based on radiographic studies; however, many of these nonunions are asymptomatic. A more clinically useful measure is the operative nonunion rate. To date, data comparing operative nonunion rates in PLF and ALIF+PS are limited. PURPOSE To determine whether there is a difference between nonunion reoperation rates in PLFs vs anterior lumbar interbody fusions with pedicle screws (ALIFs+PS). STUDY DESIGN/SETTING Retrospective cohort. PATIENT SAMPLE The cohort comprised 8,340 patients aged ≥50 who underwent primary elective lumbar spinal fusion (L1-S1) for degenerative or deformity related spinal disorders (2009-2018). OUTCOME MEASURES Operative nonunions. METHODS Adult patients (≥18 years old) with degenerative disc disease who underwent primary elective PLFs and ALIFs+PS for 1-level and 2-level fusions (L4-S1) between 2009-2018 were identified using data from the Kaiser Permanente Spine Registry and followed until validated operative nonunion, membership termination, death, or 03/31/2019. Descriptive statistics and two-year incidence rates for validated operative nonunions were calculated by fusion level, fusion type, and levels fused. Time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate operative nonunion rates with adjustment for covariates or risk change estimates more than 10%. RESULTS We identified 2,061 patients (PLF:1491, ALIF+PS:570) with average follow-up time of 4.8(±3.1) years, and average time to operative nonunion 1.3(±1.2) yrs. Comparatively, single and multilevel incidence rates for nonunion were higher in PLF vs ALIF+PS: 1-Level: 0.9% (95% CI=0.4-1.6) vs 0.6% (95% CI=0.1-2.1); 2-Level: 2.0% (95% CI=0.8-4.0) vs 0.9% (95% CI=0.1-3.3). There were no observed differences in risk of operative nonunions in multivariable models comparing ALIF+PS vs PLF (HR=0.3, 95% CI=0.1-1.1), 1-level vs 2-level fusions (HR=1.8, 95% CI=0.8-4.3), or by fusion level (L4-L5: HR=1.0, 95% CI=0.4-2.7; L5-S1: HR=2.0, 95% CI=0.7-5.4). CONCLUSIONS A large cohort of patients with >4 years follow-up found no difference in operative nonunions between PLF and ALIF+PS. Further research is warranted. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Background Endologix issued important safety updates for the AFX Endovascular AAA System in 2016 and 2018 owing to the risk of type III endoleaks. Outcomes with these devices are limited to small case series with short-term follow-up. We describe the midterm outcomes for a large cohort of patients who received an Endologix AFX or AFX2 device. Study design Data from an integrated healthcare system's implant registry, which prospectively monitors all patients after endovascular aortic repair, was used for this descriptive study. Patients undergoing endovascular aortic repair with three AFX System variations (Strata [AFX-S], Duraply [AFX-D], and AFX2 with Duraply [AFX2]) were identified (2011-2017). Crude cumulative event probabilities for endoleak (types I and III), major reintervention, conversion to open, rupture, and mortality (aneurysm related and all cause) were estimated. Results Among 605 patients, 375 received AFX-S, 197 received AFX-D, and 33 received AFX2. Median follow-up for the cohort was 3.9 (interquartile range, 2.5-5.1) years. The crude 2-year incidence of overall endoleak, any subsequent reintervention or conversion, and mortality was 8.8% (95% confidence interval [CI], 6.3-12.3), 12.0% (95% CI, 9.1-15.9), and 8.8% (95% CI, 6.3-12.2) for AFX-S. Respective estimates for AFX-D were 7.9% (95% CI, 4.8-13.0), 10.6% (95% CI, 6.9-16.1), and 9.7% (95% CI, 6.3-14.7); for AFX2, they were 14.1% (95% CI, 4.7-38.2), 16.2% (95% CI, 6.4-37.7), and 21.2% (95% CI, 10.7-39.4). Conclusions The midterm outcomes of a large U.S. patient cohort with an Endologix AFX or AFX2 System demonstrate a concerning rate of adverse postoperative events. Patients with these devices should receive close clinical surveillance to prevent device-related adverse events.

While always an interdisciplinary endeavour, rapid growth in the fields of Ethnomethodology (hereafter EM) and Conversation Analysis (hereafter CA) has led to the broader application of EM/CA methodologies and the engagement of researchers from beyond the more traditional fields of sociology and linguistics. EM/CA methodologies are being used to both understand the orderliness of social interaction and also to address specific institutional issues, in this instance in higher education settings. This paper explores the challenges inherent in using these approaches to researching institutional relationships, particularly when a primary aim of the research is to inform practitioners of practices used within institutional settings. We argue the need to draw on a variety of analytical tools to understand in situ practices alongside other lenses to translate these understandings of institutional practice to practitioners. Drawing on data from a study of audio-recorded conversations between supervisory and preservice teachers during the school-based professional experience component of initial teacher education, our analysis illustrates how the tools of conversation analysis and membership categorization analysis reveal the intricacies of how supervising and preservice teachers negotiate issues of asymmetry and position themselves through references to specific institutional documents. We then use the work of Dorothy Smith to support the translatability of descriptive findings to support interventions in the field. We use this example to demonstrate the affordances of using various analytic tools in complementary ways to overcome methodological challenges and provide new insights into institutional relationships and inform future practice.

Background: Current treatment guidelines for IMDC recommend steroids as first-line therapy, followed by SITs (infliximab or vedolizumab) for refractory cases. We aimed to compare the efficacy of these two SITs and their impact on cancer outcomes. Methods: We performed a multicenter, retrospective observational cohort study of patients with IMDC who received SITs following steroids from 2016 to 2020. Patients’ demographic, clinical, and overall survival data were collected and analyzed. Findings: A total of 184 patients (62 vedolizumab, 94 infliximab, 28 both) were included. The efficacy of achieving clinical remission of IMDC was similar (89% vs 88%, P =0.79) between the two groups. Compared with infliximab group, vedolizumab group had a shorter steroid exposure (35 vs. 50 days, P

Essentials Near-patient testing improves coagulopathy diagnosis in cardiac surgery patients with severe bleeding. We investigated how well pre-emptive near-patient testing predicted severe bleeding. Severe bleeding could be predicted using both near-patient tests and patient clinical characteristics. Near-patient test results gave little additional predictive value over clinical characteristics alone. Background Coagulopathic bleeding is common after cardiac surgery and is associated with increased morbidity, mortality and healthcare costs. Implementation of blood management algorithms in which patients with severe bleeding undergo near-patient coagulation testing results in less overall bleeding and transfusion. However, it is unknown whether there is additional value from pre-emptive near-patient testing to predict whether severe bleeding will occur. Objectives To evaluate how well a comprehensive panel of 28 near-patient platelet and viscoelastometry tests predict bleeding after cardiac surgery, compared to prediction using baseline clinical characteristics alone. Methods Single-center, prospective cohort study in adults undergoing a range of cardiac surgery procedures. The primary outcome was clinical concern about bleeding (CCB), a composite of high blood loss (chest drain volume >600 mL within 6 hours), re-operation for bleeding or administration of a pro-haemostatic treatment directed by clinician judgement. Results In 1833 patients recruited between March 2010 and August 2012, the median number of abnormal near-patient test results was 5/28 per patient (range 0-18). CCB occurred in 449/1833 patients (24.5%). The c-statistic for a predictive model for CCB using only baseline clinical characteristics (baseline-only model) was 0.72 (95% CI 0.69-0.75). Addition of near-patient test results to this model (baseline-plus-test model) improved the prediction of CCB (c-statistic 0.75 [0.72-0.77]), but increased the number of correctly classified patients by only 18 (0.98%). Conclusions Near-patient coagulation testing predicts bleeding in cardiac surgery patients, but offers little improvement in prediction compared to baseline clinical characteristics alone. trial registration: ISRNCTN 20778544 (http://www.isrctn.com/).

BACKGROUND CONTEXT Circumferential lumbar fusions combine anterior column support using an anterior approach (anterior lumbar interbody fusion, ALIF), a lateral approach (lateral lumbar interbody fusion, LLIF) or a posterior approach (posterior lumbar interbody fusion, PLIF/transforaminal lumbar interbody fusion, TLIF), with posterior support with pedicle screw fixation (PS). Circumferential fusions have shown biomechanical advantages compared to posterolateral fusion (PLF) with pedicle screw fixation, including restoration of lordosis, indirect foraminal decompression, and reduction of the slip via ligamentotaxis. However, they may increase the stiffness of the spine due to anterior column support and loading. Although several small comparative studies reporting radiographic adjacent segment degeneration (ASD) and meta-analyses on adjacent segment disease (ASDis) have been published, to our knowledge, there are currently no large-scale studies that report ASDis. PURPOSE To assess the incidence of and risk for operative adjacent segment disease (ASDis) after circumferential lumbar fusion, by surgical approach, vs PLF. STUDY DESIGN/SETTING Retrospective cohort study using integrated health care data from the Kaiser Permanente Spine Registry. PATIENT SAMPLE A final retrospective cohort study using integrated health care data from the Kaiser Permanente Spine Registry, consisting of 5,521 patients with lumbar fusions completed between 01/01/2009 and 12/31/2018. OUTCOME MEASURES Five-year incidence rate of ASDis requiring reoperation. METHODS A total of 5,521 patients aged ≥18 who underwent primary elective lumbar fusion (L3-S1) for degenerative disc disease (2009-2018). Five-year incidence rates of validated, operative ASDis were calculated by fusion type (PLF, ALIF/LLIF+PS, and PLIF/TLIF+PS) and fusion level (1-2 levels). Covariate-adjusted time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate reoperation rates with using PLF as the reference group. RESULTS Fifty percent of fusions were PLIF/TLIF+PS (N=2,821), more than one-third were PLF+PS (N=2006), and the remaining were ALIF/LLIF+PS (N=694). Average cohort age was 61.8 years (SD±12.7) and average follow-up was 4.8 years (SD±3.1). Five-year incidence rates of operative ASDis were 7.0% (95% confidence interval [CI] =6.4-7.7). Five-year incidence of operative ASD was similar in PLF and PLIF/TLIF+PS (7.7, 95% CI=6.6-9.0 and 7.1% 95% CI=6.2-8.1, respectively) but slightly lower in ALIF/XLIF+PS (5.3%, 95% CI=3.8-7.3). Highest 5-year incidence rates were seen in 2-level circumferential PLIF/TLIF (8.3%, 95% CI=6.0-11.11). After adjustment, there were no significant differences in operative ASDis risk by fusion type compared to PLF (ALIF/XLIF+PS: HR=0.7, 95% CI=0.5-1.1); PLIF/TLIF+PS: HR=1.0, 95% CI=0.8-1.2). CONCLUSIONS Analysis from a large cohort of over 5000 lumbar fusion patients found no differences in operative ASDis comparing circumferential fusions to posterolateral fusion at 5 years. This information is useful in informed consent for the patient. Further research for risk of operative ASDis with larger numbers of patients undergoing an anterior approach, as well as a longer follow-up period, is warranted. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Octogenarians, defined as patients aged ≥80 years, are undergoing elective lumbar spinal fusion surgery in increasing numbers. While it is commonly accepted that patients between 50-79 years of age with degenerative or deformity-related spinal disease can safely undergo spinal fusion, most clinicians approach octogenarians more cautiously given concerns for higher adverse outcome risks. PURPOSE To evaluate whether there is a difference in risk of adverse postoperative outcomes following elective lumbar spinal fusion for octogenarians compared to patients aged 50-79. STUDY DESIGN/SETTING Retrospective cohort study using integrated health care data from the Kaiser Permanente Spine Registry. PATIENT SAMPLE The cohort comprised 8,340 patients aged ≥50 who underwent primary elective lumbar spinal fusion (L1-S1) for degenerative or deformity-related spinal disorders (2009-2018). OUTCOME MEASURES Incidence of intraoperative durotomy; 90-day postoperative emergency department (ED) visit and readmission, infection, deep vein thrombosis (DVT), pulmonary embolism (PE); and 90-day and 2-year reoperation and mortality. METHODS Octogenarians were compared to patients aged 50-79 (reference group) using time-dependent multivariable Cox-Proportional Hazards regression with a competing risk of death and adjustment for confounders. Multivariable logistic regression was used to assess differences in operative durotomy. RESULTS A total of 576 patients aged ≥80 and 7,763 patients aged 50-79 were included. After adjustment for confounders, octogenarians had a higher likelihood of durotomy (odds ratio=1.6, 95% confidence interval [CI]=1.2-2.2), as well as higher risks of 90-day readmission (hazard ratio [HR]=1.4, 95% CI=1.1-1.8) and PE (HR=2.2, 95% CI=1.1-5.0), compared to their younger counterparts. No differences were observed for 90-day incidence of infection or DVT. As well, no differences were observed in reoperation risks at 90 days (HR=1.2, 95% CI=0.8-2-0) or 2 years (HR=0.8, 95% CI=0.6-1.1). Mortality risk was higher for octogenarians compared to their younger counterparts but did not vary at 90-day or 2-year timepoints (90-day: HR=2.6, 95% CI=1.3-5.1; 2-year: HR=2.6, 95% CI=1.8-3.9). In stratified analysis, octogenarians with ≥3 comorbidities had a higher risk of 90-day readmission (HR=1.8, 95% CI=1.0-3.3) and 2-year mortality (HR=4.7, 95% CI=1.6-13.3) than those with 0-2. CONCLUSIONS In a cohort of >8,000 elective lumbar fusion patients, no difference was observed in the risk of reoperation, infection or DVT when comparing octogenarians to their younger counterparts. However, the higher risk of intraoperative durotomy, 90-day PE, and 90-day readmission suggests closer intra- and postoperative surveillance may be warranted for these older patients. We did observe a higher mortality risk for octogenarians when compared to patients aged 50-79; this risk did not change between 90 days and 2 years, suggesting the elevated risk is unrelated to undergoing a lumbar fusion and more likely the age groups compared in this study. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Introduction Multiple electrode aggregometry (MEA) improves prediction of thrombosis and bleeding in cardiac patients. However, the causes of inter-individual variation in MEA results are incompletely understood. We explore whether low MEA results are associated with platelet G-protein coupled receptor (GPCR) gene variants. Methods The effects of P2Y 12 receptor (P2Y 12 ), thromboxane A 2 receptor (TPα) and protease-activated receptor 1 (PAR1) dysfunction on the MEA ADP-test, ASPI-test and TRAP-test were determined using receptor antagonists. Cardiac surgery patients with pre-operative MEA results suggesting GPCR dysfunction were selected for P2Y 12 ( P2RY12 ), TPα ( TBXA2R ) and PAR1 ( F2R ) sequencing. Results In control blood samples, P2Y 12 , TPα or PAR1 antagonists markedly reduced ADP-test, ASPI-test and TRAP-test results respectively. In the 636 patients from a cohort of 2388 cardiac surgery patients who were not receiving aspirin or a P2Y 12 blocker, the median ADP-test result was 75.1 U (range 4.8-153.2), ASPI-test 83.7 U (1.4-157.3) and TRAP-test 117.7 U (2.4-194.1), indicating a broad range of results unexplained by anti-platelet drugs. In 238 consenting patients with unexplained low MEA results, three P2RY12 variants occurred in 70/107 (65%) with suspected P2Y 12 dysfunction and four TBXA2R variants occurred in 19/22 (86%) with suspected TPα dysfunction although the later group was too small to draw meaningful conclusions about variant frequency. All the variants were synonymous and unlikely to cause GPCR dysfunction. There were no F2R variants in the 109 cases with suspected PAR1 dysfunction. Conclusion MEA results suggesting isolated platelet GPCR dysfunction were common in cardiac surgery patients, but were not associated with non-synonymous variants in P2RY12 or F2R .

Dual antiplatelet therapy (DAPT) prescription has shifted toward more potent antiplatelet inhibition with ticagrelor (T) over clopidogrel (C) in conjunction with aspirin (A). The authors reviewed temporal trends in DAPT use and bleeding in the United Kingdom. The study cohort was identified through

Background: Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation. Objective: We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon. Design: We conducted a cross-sectional study of 336 men and women (age 19–92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O6-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively. Results: Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001). Conclusion: MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia. This trial was registered at clinicaltrials.gov as ISRCTN43577261.

There is a paucity of data on the effect of multimorbidity on early (≤ 1-year) mortality in older adults after permanent pacemaker placement (PPM) implantation. Observational retrospective study from 2008 to 2015, within an integrated healthcare delivery system to assess the association of the

Mammary gland development is coupled to reproductive events by hormonal cues of ovarian and pituitary origin, which activate a genomic regulatory network. Identification of the components and regulatory links that comprise this network will provide the basis for defining the network's dynamic response during normal development and its perturbation during breast carcinogenesis. In this study KIBRA was identified as a transcript showing decreased expression associated with failed mammary gland development in Prlr knockout mammary epithelium. It is strongly up-regulated during pregnancy, falls during lactation and is again up-regulated during involution of the gland at weaning. A bioinformatic approach was undertaken to identify potential binding partners which interact with the WW domains of KIBRA. We show that KIBRA binds to a WW domain binding motif, PPxY, in the tyrosine kinase receptor DDR1, and dissociates upon treatment with the DDR1 ligands collagen type I or IV. In addition we show that KIBRA and DDR1 also interact with PKCz to form a trimeric complex. Finally, overexpression and knockdown studies demonstrate that KIBRA promotes the collagen-stimulated activation of the MAPK cascade. Thus KIBRA may play a role in how the reproductive state influences the mammary epithelial cell to respond to changing cell-context information, such as experienced during the tissue remodeling events of mammary gland development.

Background: Laboratory animal allergy is a common occupational health problem affecting between 11% and 44% of exposed researchers. Allergy to rats and mice is most common, probably because these are the animals most frequently used. Objective: We hypothesized that HLA class II molecules, involved in the presentation of allergen to the T cell and likely candidates for controlling the immune response, might be associated with sensitization to rat urinary proteins among laboratory animal handlers. Methods: We undertook a cross-sectional study of 741 employees at 6 pharmaceutical sites across the United Kingdom who had contact at work with laboratory rats. In all, 109 cases with specific sensitization to rat proteins and 397 referents were HLA-typed for DRB1 and DQB1 loci. Amino acid analyses of significantly associated HLA molecules were carried out. Results: HLA-DR7 was associated with sensitization (odds ratio [OR], 1.82; CI, 1.12-2.97), respiratory symptoms at work (OR, 2.96; CI, 1.64-5.37) and, most strongly, sensitization with symptoms (OR, 3.81; CI, 1.90-7.65). HLA-DR3 was protective against sensitization (OR, 0.55; CI, 0.31-0.97). Amino acid analyses of these 2 molecules indicated a biologically plausible explanation for the associations. Conclusion: HLA phenotype is an important determinant of individual susceptibility to sensitization and asthma among laboratory animal workers. Similar mechanisms might apply in other animal allergies. (J Allergy Clin Immunol 2003;111:795-9.)

Rationale Laboratory animal allergy is a common occupational health problem in occupationally exposed individuals. Exposure is a well-defined risk factor for sensitization and asthma to rats. However the incidence of sensitization is often reduced in the highest exposed categories. One explanation is the phenomenon of high dose tolerance. It has been shown that exposure to cat allergen induces an IgG and IgG4 antibody response, without sensitization or risk of asthma. This has been explained as a modified Th2 response. We have investigated the relationship between IgE, IgG and IgG 4 and exposure to rats. Methods A cross sectional study was carried out on individuals exposed to laboratory animals at six pharmaceutical sites across the UK. Specific IgE was measured using RAST. Specific IgG and IgG4 antibodies to rat urinary allergen were measured in 689 and 401 exposed individuals respectively using ELISA. Results Using two different measures of exposure to rats, the prevalence of sensitization increased with increasing exposure intensity. However in the highest exposure category, the prevalence of sensitization decreased. Conversely levels of IgG and IgG4 increased in parallel with increasing exposure to rats. In support of high IgG 4 :IgE ratio in non sensitized individuals at highest exposure, we also observed higher IgG 4 :IgE ratios in asymptomatics compared with those with symptoms. Conclusions High exposure to rats was associated with an increased production of specific IgG and IgG4 with a decreased production of IgE. The development of IgG 4 may protect against symptoms.