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Supplementary Data from Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma

Purpose:PD-L1 is upregulated in glioblastoma and supports immunosuppression. We evaluated PD-L1 blockade with durvalumab among glioblastoma cohorts and investigated potential biomarkers.Patients and Methods:MGMT unmethylated newly diagnosed patients received radiotherapy plus durvalumab (cohort A; n = 40). Bevacizumab-naïve, recurrent patients received durvalumab alone (cohort B; n = 31) or in combination with standard bevacizumab (cohort B2; n = 33) or low-dose bevacizumab (cohort B3; n = 33). Bevacizumab-refractory patients received durvalumab plus bevacizumab (cohort C; n = 22). Primary endpoints were: OS-12 (A), PFS-6 (B, B2, B3), and OS-6 (C). Exploratory biomarkers included: a systematic, quantitative, and phenotypic evaluation of circulating immune cells; tumor mutational burden (TMB); and tumor immune activation signature (IAS).Results:No cohort achieved the primary efficacy endpoint. Outcome was comparable among recurrent, bevacizumab-naïve cohorts. No unexpected toxicities were observed. A widespread reduction of effector immune cell subsets was noted among recurrent patients compared with newly diagnosed patients that was partially due to dexamethasone use. A trend of increased CD8+Ki67+ T cells at day 15 was noted among patients who achieved the primary endpoint and were not on dexamethasone. Neither TMB nor IAS predicted outcome.Conclusions:Patients with recurrent glioblastoma have markedly lower baseline levels of multiple circulating immune cell subsets compared with newly diagnosed patients. An early increase in systemic Ki67+CD8+ cells may warrant further evaluation as a potential biomarker of therapeutic benefit among patients with glioblastoma undergoing checkpoint therapy. Dexamethasone decreased immune cell subsets. PD-L1 blockade and combination with standard or reduced dose bevacizumab was ineffective.

Objective:To evaluate safety and tolerability and exploratory efficacy endpoints for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS).Methods:Gaboxadol is a highly selective orthosteric agonist that activates γ-subunit–containing extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose and gaboxadol 15 mg evening dose (qd); gaboxadol 10 mg morning dose and 15 mg evening dose (bid); or placebo morning and evening dose. Safety and tolerability were monitored throughout the study. Prespecified exploratory efficacy endpoints included adapted Clinical Global Impression–Severity (CGI-S) and Clinical Global Impression–Improvement (CGI-I) scales which documented the clinical severity at baseline and change after treatment, respectively.Results:Eighty-eight individuals were randomized. Of 87 individuals (aged 13–45 years) who received at least 1 dose of study drug, 78 (90%) completed the study. Most adverse events (AEs) were mild to moderate, and no life-threatening AEs were reported. Efficacy of gaboxadol, as measured by CGI-I improvement in an exploratory analysis, was observed in gaboxadol qd vs placebo (p = 0.0006).Conclusion:After 12 weeks of treatment, gaboxadol was found to be generally well tolerated with a favorable safety profile. The efficacy as measured by the AS-adapted CGI-I scale warrants further studies.Classification of evidence:This study provides Class I evidence that, for individuals with AS, gaboxadol is generally safe and well tolerated.

Purpose – Medication errors are an important patient safety issue. Electronic medication reconciliation is a system designed to correct medication discrepancies at transitions in healthcare. The purpose of this paper is to measure types and prevalence of intravenous antibiotic errors at hospital discharge before and after the addition of an electronic discharge medication reconciliation tool (EDMRT). Design/methodology/approach – A retrospective study was conducted at a tertiary hospital where house officers order discharge medications. In total, 100 pre-EDMRT and 100 post-EDMRT subjects were randomly recruited from the study center’s clinical Outpatient Parenteral Antimicrobial Therapy (OPAT) program. Using infectious disease consultant recommendations as gold standard, each antibiotic listed in these consultant notes was compared to the hospital discharge orders to ascertain the primary outcome: presence of an intravenous antibiotic error in the discharge orders. The primary covariate of interest was pre- vs post-EDMRT group. After generating the crude prevalence of antibiotic errors, logistic regression accounted for potential confounding: discharge day (weekend vs weekday), average years of practice by prescribing physician, inpatient service (medicine vs surgery) and number of discharge mediations per patient. Findings – Prevalence of medication errors decreased from 30 percent (30/100) among pre-EDMRT subjects to 15 percent (15/100) errors among post-EDMRT subjects. Dosage errors were the most common type of medication error. The adjusted odds ratio of discharge with intravenous antibiotic error in the post-EDMRT era was 0.39 (0.18, 0.87) compared to the pre-EDMRT era. In the adjusted model, the total number of discharge medications was associated with increased OR of discharge error. Originality/value – To the authors’ knowledge, no other study has examined the impact of reconciliation on types and prevalence of medication errors at hospital discharge. The focus on intravenous antibiotics as a class of high-stakes medications with serious risks to patient safety during error events highlights the clinical importance of the findings. Electronic medication reconciliation may be an important tool in efforts to improve patient safety.

Several echocardiographic measures have prognostic value in heart failure (HF). However, no definitive data exist on how changes in these parameters with treatment affect survival in this patient population. We hypothesized that early improvement on echocardiography could predict long-term survival.We conducted a retrospective review of 404 patients seen in the HF clinic from 2002 to 2008 (6.5 years). Patients had one echocardiogram ≤1 year before and another ≥1 month (10 ± 7 months) after treatment onset. We studied changes in standard echocardiographic parameters, including left (LV) and right (RV) ventricular size and/or function (systolic and/or diastolic), valvular (mitral and tricuspid) function, and pulmonary artery pressure. Survival curves and hazard ratios were generated for patients showing improvement on the 2nd echocardiogram versus those who did not. Multivariable analyses were performed adjusting for age, sex, ischemic etiology, and significant baseline echocardiographic parameters. Average follow-up was 2.9 ± 1.5 years. Improvement in LV end-systolic dimension, RV function, and mitral regurgitation were independent predictors of 5-year survival (P.05) and, importantly, more predictive than baseline values of these parameters alone (higher hazard ratios).Early echocardiographic improvement is strongly associated with 5-year survival in patients with HF. Serial echocardiography may aid in stratifying patient care.

The objective of our study is to measure the incidence of sudden infant death syndrome (SIDS), estimate the birth to death interval, and identify associated maternal and infant risk factors. We carried out a population-based cohort study on 37 418 280 births using data from the Centers for Disease Control and Prevention’s “Linked Birth-Infant Death” and “Fetal Death” data files from 1995 to 2004. Descriptive statistics and cox-proportional hazard models were used to estimate the adjusted effect of maternal and newborn characteristics on the risk of SIDS. There were 24 101 cases of SIDS identified for an overall 10-year incidence of 6.4 cases per 10 000 births. Over the study period, the incidence decreased from 8.1 to 5.6 per 10 000 and appeared to be most common among infants aged 2–4 months. Risk factors included maternal age

BACKGROUND Increased recognition of ionizing radiation risks has placed an emphasis on the appropriate use of myocardial perfusion imaging (MPI). Hospitalists frequently order MPI in the evaluation of chest pain and are thus at the forefront of its inpatient utilization. METHODS We collected baseline figures for a group MPI rate (March 2010–February 2011) as well as individual MPI rates for hospitalists caring for cardiac floor patients at a community teaching hospital. We performed a 2-part intervention; we presented the individual MPI rate data back to the hospitalist division and carried out longitudinal educational efforts on MPI appropriateness criteria. We then calculated the group MPI utilization rate for 3 postintervention periods (March 2011–February 2012, March 2012–February 2013, and March 2013–February 2014) and the MPI rate for the subgroup of cardiac floor patients. Finally, we calculated the percentage of inappropriately performed stress tests before and after our intervention. RESULTS Group MPI rate declined from 6.1% to 5.0% in the first year after our intervention (P = 0.009); a decrease was maintained a year later—MPI rate 4.9% (P = 0.004)—and became even more pronounced 2 years later—MPI rate 3.9% (P

Background: Up-regulation of heme oxygenase-1 (HO-1) and altered cholesterol (CH) metabolism are characteristic of Alzheimer-diseased (AD) neural tissues. We previously provided evidence of significant HO-1/sterol interactions in vitro (cultured rat astroglia) and in post-mortem human AD brain (Religious Orders Study). Methods: The current experiments were designed to further delineate these interactions in vivo by comparing the behavior of HO-1/sterol interactions in two mouse models; (1) a novel HO-1 transgenic mouse (GFAP.HMOX1) engineered to selectively express human HO-1 in the astrocytic compartment and (2) the previously described triple transgenic AD mouse (3xTg-AD). In samples of frontal cortex, total CH, CH precursors and relevant oxysterols were quantified by gas chromatography–mass spectrometry (GC–MS) and HO-1 protein expression was assessed by ELISA. The relationships of HO-1 expression to total CH, CH precursors and total oxysterols were determined for both mouse models using linear regression analysis. Results: HO-1 expression is increased in GFAP.HMOX1 mice relative to wild type and in 11–12-month-old 3xTg-AD mice (with AD-like phenotype) relative to control mice and 5–6-month-old 3xTg-AD mice (no AD-like phenotype). Total oxysterols significantly decreased as HO-1 expression increased in GFAP.HMOX1 mice expressing high levels of HO-1, whereas total oxysterols increased as HO-1 expression increased in aged 3xTg-AD mice. Total CH and total CH precursors increased as HO-1 protein expression increased in 11–12-month-old 3xTg-AD mice relative to 5–6-month old 3xTg-AD mice. Conclusions: Our findings indicate a differential impact of HO-1 on patterns of brain sterol and redox homeostasis that is contingent on the presence or absence of AD-like neuropathology. These data provide fresh insight concerning the regulation of sterol homeostasis within the aging and degenerating CNS which may inform the development of novel therapeutic and preventive strategies for the management of AD and related conditions.

Little is known about how lithium should be dosed to achieve therapeutic but safe serum concentrations in older adults. In this paper, we investigate how the lithium dose–concentration ratio changes across the lifespan. This was a cross-sectional analysis of 63 current lithium users aged 20–95 years using data from McGLIDICS (the McGill Geriatric Lithium-Induced Diabetes Insipidus Clinical Study). Participants underwent blood and urine tests, including serum lithium concentrations. Multivariate analyses were conducted to evaluate potential correlates of the lithium dose–concentration ratio. We found that between the ages of 40–95 years, the total daily dose of lithium required to achieve a given serum concentration decreases threefold (500 vs. 1,500 mg for 1.0 mmol/L). Greater age, once-daily dosing, and lower renal function (estimated glomerular filtration rate) were independently associated with a lower lithium dose–concentration ratio. The lithium dose required to achieve a given serum lithium concentration decreases threefold from middle to old age, with this trend continuing into the ninth and tenth decades of life. In order to avoid lithium toxicity in aging patients, continued serum concentration monitoring and judicious dose reduction may be required, particularly in those patients with reduced renal function.

Background Measuring the quality of surgical care is essential to identifying areas of weakness in the delivery of effective surgical care and to improving patient outcomes. Our objectives were to (1) assess the quality of surgical care delivered to adult patients; and (2) determine the association between quality of surgical care and postoperative complications. Methods This retrospective, pilot, cohort study was conducted at a single university-affiliated institution. Using the institution's National Surgical Quality Improvement Program database (2009–2010), 273 consecutive patients ≥18 years of age who underwent elective major abdominal operations were selected. Adherence to 10 process-based quality indicators (QIs) was measured and quantified by calculating a patient quality score (no. of QIs passed/no. of QIs eligible). A pass rate for each individual QI was also calculated. The association between quality of surgical care and postoperative complications was assessed using an incidence rate ratio, which was estimated from a Poisson regression. Results The mean overall patient quality score was 67.2 ± 14.4% (range, 25–100%). The mean QI pass rate was 65.9 ± 26.1%, which varied widely from 9.6% (oral intake documentation) to 95.6% (prophylactic antibiotics). Poisson regression revealed that as the quality score increased, the incidence of postoperative complications decreased (incidence rate ratio, 0.19; P = .011). A sensitivity analysis revealed that this association was likely driven by the postoperative ambulation QI. Conclusion Higher quality scores, mainly driven by early ambulation, were associated with fewer postoperative complications. QIs with unacceptably low adherence were identified as targets for future quality improvement initiatives.

Objective Lithium continues to be an important mood disorder treatment. Although patients exposed to higher environmental temperatures may have serum lithium level elevations due to dehydration, there is conflicting data in the literature. In addition, no study has assessed the association between temperature and other renal laboratory tests and symptoms in lithium users. Methods This is a cross-sectional analysis of 63 current lithium users who participated in the McGill Geriatric Lithium-induced Diabetes Insipidus Clinical Study. The relationship between mean daily temperature with diabetes insipidus symptoms, glomerular filtration rate, urine osmolality, serum sodium, lithium level, and lithium dose–level ratio was assessed. Results Although a higher temperature on the day of laboratory testing trended toward being independently associated with a lower lithium dose–level ratio (Beta = −0.17, p = 0.08), this was not found when using a dichotomous measure of temperature (T > 20°C). No association was observed between temperature and other renal parameters. Conclusions The association of temperature with lithium levels, renal symptoms, and laboratory tests appears to be of relatively little clinical importance in lithium users in temperate climates. However, future research should re-examine patients living in climates with extreme temperatures (e.g., >40°C), who may theoretically be at higher risk. Copyright © 2014 John Wiley & Sons, Ltd.

Objective: Despite being a common and potentially serious condition, nephrogenic diabetes insipidus (NDI) remains poorly understood in older lithium users. Our main objective was to compare the prevalence of NDI symptoms and decreased urine osmolality ([UOsm] < 300 milli-Osmoles [mOsm/kg]) among geriatric and adult lithium users. We also assessed NDI symptoms, serum sodium (Na+), and urine specific gravity (USG) as possible surrogate measures of decreased UOsm, and ascertained whether potential etiologic factors independently correlated with decreased UOsm. Method: This was a cross-sectional study of 100 consecutive outpatients treated with lithium from 6 tertiary care clinics, of which 45 were geriatric (aged 65 years and older) and 55 adult (aged 18 to 64 years). Patients completed a symptom questionnaire and underwent laboratory tests, including UOsm, serum Na+, and USG. Results: Geriatric and adult lithium users had similar rates of decreased UOsm (12.5%, compared with 17.9%, P = 0.74), but geriatric patients reported less symptoms ( P < 0.05). Although UOsm did not correlate with symptoms or current serum Na+, USG of less than 1.010 was suggestive of UOsm of less than 300 mOsm/kg. Age, lithium duration, and serum lithium level were independently associated with UOsm. Conclusions: The prevalence of decreased UOsm is similar in geriatric and adult lithium users, but older patients are less likely to report urinary and thirst symptoms. Although subjective symptoms do not correlate with UOsm, USG may be a cost-efficient clinical surrogate measure for UOsm. We suggest clinicians increase their vigilance for decreased UOsm, especially in lithium users with advanced age, longer duration of lithium exposure, and higher lithium levels. This may potentially prevent lithium intoxication, falls, hypernatremic events, and renal dysfunction.

Summary Background Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. Methods We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751. Findings From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73–1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. Interpretation ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. Funding Canadian Institutes of Health Research.

In this retrospective cohort study of 174 consecutive, newly diagnosed cases of diffuse large B-cell lymphoma (DLBCL), clinical and pathological variables, treatment, response and survival were compared for patients aged 80 and over (n = 40) to those under 80. Eastern Cooperative Oncology Group (ECOG) status and International Prognostic Index (IPI) were significantly worse among older patients. Standard treatment was given to only 32.5% of older versus 86.6% of younger patients, and 65% of the elderly did not receive standard therapy. At 12 months, overall and event-free survival were 51.3% (95% confidence interval [CI]: 35-66%) vs. 93% (CI: 88-97%) and 41.9% (CI: 25-58%) vs. 84.8% (CI: 77-90%), for older versus younger patients, respectively. Choice of therapy was significantly associated with survival in the elderly, and low albumin but not comorbidity score was associated with not receiving standard therapy. Patients with DLBCL aged 80 and over are distinct from all other age groups with regard to treatment tolerance. A minority can receive standard therapy, but for the majority, novel therapeutic options are needed.

The purpose of this study was to determine if there is an association between necrosis as identified on staging (18)F-FDG PET/CT and overall survival (OS) and progression-free survival (PFS) in patients with sarcoma.Sixty-six patients with newly diagnosed limb and girdle sarcoma underwent PET/CT at our institution between June 2004 and July 2009 for sarcoma staging before treatment with curative intent. The tumor maximum standardized up-take values (SUVmax), the presence of necrosis, and the volume of necrosis were measured for each primary tumor and correlated with follow-up data. PFS and OS were analyzed using the Kaplan-Meier method. Proportional hazards models were used to estimate hazard ratios.Median patient age was 49 years, and 51.6% of the patients were men. Sarcomas were categorized as soft tissue (69.2%), bone (23.5%), or other (7.3%). Mean follow-up time was 33.3 months. During the follow-up interval, 53% of patients experienced disease progression, and 40.9% died. There was a statistically significant relationship between the presence of necrosis and OS (by log-rank test, p = 0.001), as well as PFS (by log-rank test, p = 0.0001). Twenty-four-month OS was 96%, 65%, and 38% in patients with tumors with absence necrosis, those with presence of necrosis, and with necrosis volume greater than 50%, respectively. Forty-eight-month OS was 81% in patients with absence of necrosis and 41% in patients with presence of necrosis. Twelve-month PFS was 96%, 60%, and 42% in patients with tumors with absence of necrosis, those with presence of necrosis, and those with necrosis volume greater than 50%, respectively. Twenty-four-month PFS was 83%, 38%, and 22%, respectively, in these groups.The presence of necrosis and the volume of necrosis, as identified on the staging FDG PET/CT and after adjusting for SUVmax, are strong independent adverse prognostic factors for disease recurrence and death in patients with limb and girdle sarcomas.

Language preference is currently being used in clinical practice to determine whether an interpreter is needed. The concordance of ability to communicate and language proficiency with each other and to language preference was measured with kappa agreement scores, sensitivity and specificity among 1,000 patients surveyed in Montreal, Canada. Though concordance between language preference and language proficiency or ability to communicate was moderate, both variables had low sensitivity (69 and 55 % respectively). A total of 25 % of persons with limited language proficiency and 15 % of those with limited ability to communicate were not identified to have a language preference for their mother tongue. Also, 31 and 45 % of those who preferred to be served in their mother tongue had good language proficiency and good ability to communicate. When assessing a patients' need for an interpreter, language preference is insufficient as a stand-alone question.

Hysterectomy is the most common major gynecological surgery performed in women. The aim of this study was to compare major morbidity and mortality between abdominal hysterectomy (AH) and laparoscopic hysterectomy (LH) for benign diseases. We performed a retrospective cohort study using the data from Health Cost and Utilization Project Nationwide Inpatient Sample. Women were admitted for hysterectomy for benign diseases between the years 2002 and 2008. In-hospital morbidities and mortalities were identified using the diagnostic and procedural codes classified according to the International Classification of Disease, Ninth Revision, and Clinical Modification. Logistic regression analysis was used to estimate the relationship between the type of hysterectomy and the development of major morbidity and mortality. Of a total 465,798 cases, 389,189 women (83.6 %) underwent AH and the remainders underwent LH (76,609, 16.4 %). The LH group was younger and more likely to be Caucasian than those who underwent AH. Although major morbidities and mortalities were rare, women who underwent LH were less likely to develop thromboembolic events (0.68 % vs. 0.84 %, odds ratio (OR) 0.85 (0.77–0.93)), require blood transfusions (2.4 % vs. 4.7 %, OR 0.58 (0.55–0.61)), and sustain bowel perforation (0.07 % vs. 0.13 %, OR 0.56 (0.42–0.74)). The mortality rate was also lower in the LH group (0.01 %) compared with the AH group (0.03 %, OR 0.48 (0.24–0.95)). Our conclusion was that for benign diseases, laparoscopic hysterectomy is associated with a lower complication rate than abdominal hysterectomy. When possible, hysterectomy performed for benign diseases should be performed with minimally invasive technique.

Background and purpose No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post-adjuvant radiotherapy setting. Material and methods The medical records of 1,088 consecutive, non-metastatic breast cancer patients treated at a single institution between 2004 and 2012 were reviewed. Estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2) enrichment were evaluated by immunohistochemistry. Patients were categorized into one of four subtypes: luminal-A (LA; ER/PR+, HER2-, Grade 1-2), luminal-B (LB; ER/PR+, HER2-, Grade > 2), HER2 over-expression (HER2; ER/PR-, HER2+), and triple negative (TN; ER/PR-, HER2-). Results: The median follow-up time was 6.9 years. During the follow-up, 16% (174/1,088) of patients failed initial treatment and developed either LR (48) or DM (126). The prevalence of LR was the highest in TN (12%) and the lowest in LA (2%). Breast or chest wall relapse was the most frequent site (≈80%) of recurrence in LA, LB, and HER2 subtypes, whereas the regional lymph nodes and chest wall were the common sites of relapse in the TN group (50.0%). DM rates were 6.4% in LA, 12.1% in LB, 19.2% in HER2, and 27.4% in TN subgroups. Five-year survival rates were 84%, 83%, 84%, and 77% in the LA, LB, HER2 and TN subgroups, respectively. There was a statistically significant association between survival and molecular subtypes in an univariate analysis. In the adjusted multivariate analysis, the following variables were independent prognostic factors for survival: T stage, N stage, and molecular subtype. Conclusions Of the four subtypes, the LA subtype tends to have the best prognosis, fairly high survival, and low recurrent or metastases rates. The TN and HER2 subtypes of breast cancer were associated with significantly poorer overall survival and prone to earlier recurrence and metastases. Our results demonstrate a significant association between molecular subtype and survival. The risk of death and relapse/metastases increases fewfold in TN compared to LA. Future prospective studies are warranted and could ultimately lead to the tailoring of adjuvant radiotherapy treatment fields based on both molecular subtype and the more conventional clinicopathologic characteristics.

Breast cancer in pregnancy is a rare condition. The objective of our study was to describe the incidence, risk factors, and obstetrical outcomes of breast cancer in pregnancy. We conducted a population-based cohort study on 8.8 million births using data from the Healthcare Cost and Utilization Project – Nationwide Inpatient Sample from 1999–2008. The incidence of breast cancer was calculated and logistic regression analysis was used to evaluate the independent effects of demographic determinants on the diagnosis of breast cancer and to estimate the adjusted effect of breast cancer on obstetrical outcomes. There were 8,826,137 births in our cohort of which 573 cases of breast cancer were identified for an overall 10-year incidence of 6.5 cases per 100,000 births with the incidence slightly increasing over the 10-year period. Breast cancer appeared to be more common among women >35 years of age, odds ratio (OR) = 3.36 (2.84–3.97); women with private insurance plans, OR = 1.39 (1.10–1.76); and women who delivered in an urban teaching hospital, OR = 2.10 (1.44–3.06). After adjusting for baseline characteristics, women with pregnancy-associated breast cancer were more likely to have an induction of labor, OR = 2.25 (1.88, 2.70), but similar rates of gestational diabetes, preeclampsia, instrumental deliveries, and placental abruption. The incidence of breast cancer in pregnancy appears higher than previously reported with women over 35 being at greatest risk. Aside from an increased risk for induction of labor, women with breast cancer in pregnancy have similar obstetrical outcomes.

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

Objective To evaluate the association between adequacy of prenatal care utilization and risk of fetal and neonatal mortality and adverse outcomes. Methods We conducted a population-based cohort study using the Center for Disease Control and Prevention's Linked Birth-Infant Death and Fetal Death data on all deliveries in the United States between 1995 and 2002. Inclusion criteria were singleton births ≥22 weeks of gestation with no known congenital malformation. Inadequate prenatal care was defined according to the Adequacy of Prenatal Care Utilization Index, and its effect on fetal and neonatal death was estimated using unconditional logistic regression analysis adjusting for maternal age, race, education, and other confounding variables. Results During our 8-year study period, 32,206,417 births occurred, 28,729,765 (89.2%) of which met inclusion criteria. Inadequate prenatal care utilization occurred in 11.2% of expectant mothers, more commonly among women ≤20 years, black non-Hispanic and Hispanic women, and those without high school education. Relative to adequate care, inadequate care was associated with increased risk of prematurity 3.75 (3.73 to 3.77), stillbirth 1.94 (1.89 to 1.99), early neonatal dearth 2.03 (1.97 to 2.09), late neonatal death 1.67 (1.59 to 1.76), and infant death 1.79 (1.76 to 1.82). Conclusion Risk of prematurity, stillbirth, early and late neonatal death, and infant death increased linearly with decreasing care. Given the population effect of this association, public health initiatives should target program expansion to ensure timely and adequate access, particularly for women ≤20 years, Black non-Hispanic and Hispanic women, and those without high school education.

Objective: Using the health belief model (HBM) and theory of planned behavior (TPB) as theoreticalframeworks, the objectives of this study were: (a) to identify correlates of human papillomavirus (HPV)vaccination intentions and (b) to explore differences between correlates of HPV vaccination intentionsand uptake. Methods: Undergraduate women ( N 447) who did not intend to receive ( n 223),intended to receive ( n 102), or had received ( n 122) the HPV vaccine were surveyed. Logisticregressions were conducted to examine the correlates of vaccination intentions and uptake. Results:Negative health consequences of the vaccine, physician’s recommendation, positive attitudes toward thevaccine, and subjective norms were significant correlates of vaccination intentions. When comparingcorrelates of vaccination intentions to correlates of vaccination uptake, physician’s recommendation,subjective norms, and perceived susceptibility to HPV were unique correlates of uptake. Conclusion:Differences between correlates of vaccination intentions and uptake suggest that social influences ofliked and trusted individuals may make an important and unique contribution in motivating youngwomen to receive the HPV vaccine beyond other variables from the HBM and TPB. Future utilizationof longitudinal designs is needed to understand which factors may cause individuals to decide to receivethe HPV vaccine.Keywords: human papillomavirus (HPV), papillomavirus vaccine, health behaviors, vaccine decision-making

Several small studies have reported an elevated risk of venous thrombosis (VT) with thrombophilia and oral contraceptive (OCP) use. We aimed to summarize the risk of VT among women with thrombophilia and OCP use and to assess the interaction between the 2 factors. We selected 15 studies that assessed the prevalence of OCP use and thrombophilia among reproductive-aged women. Odds ratios (ORs) were calculated for each study and pooled using the random effects model. We found an increased risk of VT among women with OCP use (pooled OR 3.0, 95% confidence interval [CI] 1.9-4.5) and with thrombophilia (pooled OR 4.5, CI 3.4-5.9), respectively. Heterogeneity was significant ( I2 >80%). Women with both thrombophilia and OCP use had a 14-fold risk of VT compared to healthy OCP nonusers (pooled OR 14.25, CI 6.2-32.8). Oral contraceptive use and thrombophilia similarly increase VT risk. Our study confirms an interaction between OCP use and thrombophilia.

This study is a prospective trial comparing the incidence of post-operative complications to fluid status in patients undergoing coronary artery bypass grafting (CABG) surgery. One hundred and nine subjects undergoing CABG surgery at the Jewish general hospital were recruited over a 5 months period in the year 2006. All of the patients underwent CABG surgery “on pump”. Post operative fluid overload was measured by weight gain. Using logistic regression with complications (major vs. minor only/none) as an outcome and fluid overload as a covariate, the risk of major complications significantly increases for fluid overload ≥5 kg compared to 1 - 5 kg (p < 0.001), while the risk for ≤1 kg is not significantly different from 1 - 5 kg. Also, the risk of major complications significantly (p = 0.012) increases for days with fluid overload ≥5 days in comparison to ≤1 day.

The objective of this study was to ascertain the impact of aging and Alzheimer’s disease (AD) on brain cholesterol (CH), CH precursors, and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from postmortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI), and no cognitive impairment (n = 17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and gas chromatography–mass spectrometry to quantify total CH, CH precursors, and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not no cognitive impairment. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment, and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD is presented based on the current data set and our earlier in vitro work.

SummaryThe post-thrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) despite appropriate anticoagulant therapy. A close relationship between inflammation and thrombosis exists. While the inflammatory process at the time of DVT appears to improve thrombus resolution, it may promote destruction of venous valves, valvular reflux and subsequent development of PTS. We prospectively evaluated the association between levels of four cytokines (IL-6, IL-8, IL-10 and MCP-1), two adhesion molecules (ICAM-1 and VCAM-1) and the development of PTS in a well-defined cohort of patients with DVT. The study population consisted of 387 patients with objectively diagnosed symptomatic DVT who were followed for two years to determine the incidence of PTS. At the end of follow-up, plasma samples frozen at the four-month visit in 307 study patients were thawed and analyzed for the above inflammatory markers using the Luminex beads technology. Mean levels of IL-6 were significantly higher in patients with PTS compared to patients without PTS (7.35 pg/ml ± 14.26 [SD] vs. 4.60 pg/ml ± 4.90;p=0.03). Logistic regression analyses showed significant associations between PTS and levels above vs. below the median of IL-6 [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.05, 2.62 (p=0.03)] and ICAM-1 [OR 1.63; 95% CI 1.03, 2.58 (p=0.04)]. None of the other markers showed any association with PTS. Our study suggests the presence of significant associations between markers of inflammation such as IL-6 and ICAM-1 and the development of PTS. Further work is needed to evaluate this relationship and to analyse other candidate markers that could be implicated etiologically in the association between DVT and PTS. If confirmed, this could lead to identification of new therapeutic targets for preventing PTS after DVT.

Summary. Background/objectives: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the post-thrombotic syndrome (PTS). Patients/methods: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. Results: Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P

Is campus-based asthma care meeting students' needs? In this study, we examined asthma severity, impact, and quality of care in a sample of university students. Our research highlights the importance of designing university asthma programs specific to the needs of young adults that follow national asthma guidelines.

Vascular access infections are of concern to hemodialysis patients and nurses. Best demonstrated practices (BDPs) have not been developed for home hemodialysis (HHD) access use, but there have been generally accepted practices (GAPs) endorsed by dialysis professionals. We developed a survey to gather information about training provided and actual practices of HHD patients using the NxStage System One HHD machine. We used GAP to assess training used by nurses to teach HHD access care and then assess actual practice (adherence) by HHD patients. We also assessed training and adherence where GAPs do not exist. We received a 43% response rate from patients and 76% response from nurses representing 19 randomly selected HHD training centers. We found that nurses were not uniformly instructing HHD patients according to GAP, patients were not performing access cannulation according to GAP, nor were they adherent to their training procedures. Identification of signs and symptoms of infection was commonly trained appropriately, but we observed a reluctance to report some signs and symptoms of infection by patients. Of particular concern, when aggregating all steps surveyed, not a single nurse or patient reported training or performing all steps in accordance with GAP. We also identified practices for which there are no GAPs that require further study and may or may not impact outcomes such as infection. Further research is needed to develop strategies to implement and expand GAP, measure outcomes, and ultimately develop BDP for HHD to improve infectious complications.

Concerns regarding the efficacy of daptomycin for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections in patients with impaired renal function are reflected in a recent package insert change by the Food and Drug Administration (FDA). However, this decision was based on a small subgroup analysis and it is unclear if this is a true association.We conducted a retrospective cohort study of patients with MRSA bacteremia treated at a tertiary hospital from 2001 to 2011 and who received either vancomycin or daptomycin. We used propensity score and multivariable logistic regression to assess the outcome of treatment failure, via blinded adjudication, in daptomycin- vs vancomycin-treated subjects and the interaction with renal function.One hundred fifty patients were analyzed, 100 in the vancomycin arm and 50 in the daptomycin arm. The average age was 61 years, and 60% were men. Of patients treated with daptomycin or vancomycin, 29 (58%) and 51 (51%), respectively, had an estimated glomerular filtration rate (GFR)50 mL/minute/1.73 m(2). Compared with vancomycin, the usage of daptomycin in patients was not significantly associated with treatment failure in patients with a GFR50 mL/minute/1.73 m(2) (odds ratio [OR], 0.45; 95% confidence interval [CI], .11 -1.79), nor in patients with a GFR of50 mL/minute/1.73 m(2) (OR, 0.46; 95% CI, .11 -1.94). There was no significant interaction between them (P = .54).In patients with MRSA bacteremia, daptomycin efficacy was not affected by GFR level and was similar to vancomycin's efficacy. Although our sample size was small, it was larger than than the one used by the FDA. However, smaller differences may be significant with a larger sample size.

Background 25(OH) vitamin D levels may be low in patients with moderately or severely active inflammatory bowel diseases (IBD: Crohn’s disease and Idiopathic Ulcerative Colitis) but this is less clear in patients with mild or inactive IBD. Furthermore there is limited information of any family influence on 25(OH) vitamin D levels in IBD. As a possible risk factor we hypothesize that vitamin D levels may also be low in families of IBD patients. Objectives To evaluate 25[OH] vitamin D levels in patients with IBD in remission or with mild activity. A second objective is to evaluate whether there are relationships within IBD family units of 25[OH] vitamin D and what are the influences associated with these levels. Methods Participants underwent medical history, physical examination and a 114 item diet questionnaire. Serum 25[OH] vitamin D was measured, using a radioimmunoassay kit, (replete ≥ 75, insufficient 50–74, deficient Results 55 patients and 48 controls with their respective families participated (N206). 25[OH] vitamin D levels between patients and controls were similar (71.2 ± 32.8 vs. 68.3 ±26.2 nmol/L). Vitamin D supplements significantly increased intake but correlation with serum 25[OH] vitamin D was significant only during non sunny months among patients. Within family units, patients’ families had mean replete levels (82.3 ± 34.2 nmol/L) and a modest correlation emerged during sunny months between patients and family (r2 =0.209 p = 0.032). These relationships were less robust and non significant in controls and their families. Conclusions In patients with mild or inactive IBD 25[OH] vitamin D levels are less than ideal but are similar to controls. Taken together collectively, the results of this study suggest that patient family dynamics may be different in IBD units from that in control family units. However contrary to the hypothesis, intra familial vitamin D dynamics do not pose additional risks for development of IBD.

Background The ability to measure surgical quality of care is important and can lead to improvements in patient safety. As such, processes should be carried out in an identical fashion for all patients, regardless of how vulnerable or complex they are. Our objectives were to assess quality of surgical care delivered to elderly patients and to determine the association between patient characteristics and quality of care. Study Design This is a retrospective pilot cohort study, conducted in a single university-affiliated hospital. Using the institution's National Surgical Quality Improvement Program (NSQIP) database (2009 to 2010), 143 consecutive patients 65 years or older, undergoing elective major abdominal surgery, were selected. Adherence to 15 process-based quality indicators (QIs) was measured, and a pass rate was calculated for each individual QI. The association between patient characteristics (age, sex, Charlson Comorbidity Index, functional status, wound class) and patient quality score was assessed using multiple linear regression. Results Quality indicators with the lowest pass rates included postoperative delirium screening (0%), level of care documentation (0.7%), cognition and functional assessment at discharge (4.9%), oral intake documentation (12.6%), and pressure ulcer risk assessment (35.0%). The mean patient quality score was 46.8% ± 10.7% (range 16.7% to 75.0%). No association was found between patient characteristics and patient quality score. Conclusions Quality of care delivered to elderly patients undergoing major surgery at our institution was generally poor and independent of patient characteristics. Although quality appears to be uniform across different patients, these results provide targets for quality improvement initiatives.

International audience; BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis (DVT). Its diagnosis is based on clinical characteristics. However, symptoms and signs of PTS are non-specific, and could result from concomitant primary venous insufficiency (PVI) rather than DVT. This could bias evaluation of PTS. METHODS: Using data from the REVERSE multicenter study, we assessed risk factors for PTS in patients with a first unprovoked unilateral proximal DVT 5-7 months earlier who were free of clinically significant PVI (defined as absence of moderate or severe venous ectasia in the contralateral leg). RESULTS: Among the 328 patients considered, the prevalence of PTS was 27.1%. Obesity (odds ratio [OR] 2.6 [95% confidence interval (CI) 1.5-4.7]), mild contralateral venous ectasia (OR 2.2 [95% CI 1.1-4.3]), poor International Normalized Ratio (INR) control (OR per additional 1% of time with INR < 2 during anticoagulant treatment of 1.018 [95% CI 1.003-1.034]) and the presence of residual venous obstruction on ultrasound (OR 2.1 [95% CI 1.1-3.7]) significantly increased the risk for PTS in multivariable analyses. When we restricted our analysis to patients without any signs, even mild, of contralateral venous insufficiency (n = 244), the prevalence of PTS decreased slightly to 24.6%. Only obesity remained an independent predictor of PTS (OR 2.6 [95% CI 1.3-5.0]). Poor INR control and residual venous obstruction also increased the risk, but the results were no longer statistically significant (OR 1.017 [95% CI 0.999-1.035] and OR 1.7 [95% CI 0.9-3.3], respectively). CONCLUSIONS: After a first unprovoked proximal DVT, obese patients and patients with even mild PVI constitute a group at increased risk of developing PTS for whom particular attention should be paid with respect to PTS prevention. Careful monitoring of anticoagulant treatment may prevent PTS.

Chemotherapy-related cognitive impairment, known as "chemobrain," has been described as a side effect of chemotherapy and is associated with cognitive changes on quality of life especially among older cancer survivors. This longitudinal feasibility study examined the relationship between physical fitness, cognitive health, and quality of life among two groups of older adults: those on chemotherapy, and those who have completed chemotherapy. To assess cognitive health, we used the Montreal Cognitive Assessment and demographic information from the Healthy Brain Questionnaire. For quality of life, we used the McGill Quality of Life assessment. Physical activity was assessed using Metabolic Equivalency Tasks from the Compendium of Physical Activities classification system. t-Tests and regression analyses indicated that at Time 1 those on chemotherapy had lower cognitive health scores than those off chemotherapy. Yet at Time 2, as physical activities increased, cognitive health and quality of life improved for those on chemotherapy. However, those who had completed chemotherapy also benefited from an increase in physical activities over time. The results have implications for health care practitioners in oncology settings to better inform patients of cognitive challenges resulting from chemotherapy and the importance of participation in physical activities. Future research should compare different age groups among a larger sample.

Objective To investigate biomarkers and clinical parameters to distinguish ovarian cancers from benign ovarian tumours. Methods Serum biomarkers (CA 125, human epididymis protein 4 [HE 4], interleukin-18 [IL-18], leptin, macrophage migration inhibitory factor [MIF], fibroblast growth factor 2 [FGF-2], insulin-like growth factor, osteopontin, prolactin) and the risk of malignancy indexes I & II (RMI-I and RMI-II) scores were obtained prior to surgery in 52 patients with ovarian tumours (37 malignant and 15 benign). ROC curves were built for each individual marker, for logistic regression models using all markers, and for models combining both biomarkers and RMI scores. Results The model with nine biomarkers performed well (specificity 93%, sensitivity 84%) and was more reliable than the RMI-I or RMI-II alone. A regression model combining RMI-II and six of the biomarkers (CA 125, HE 4, IL-18, leptin, MIF, and FGF-2) allowed differentiation between the cancer and non-cancer cases in this pilot study Conclusion The regression models using biomarkers combined with clinical scoring systems warrant further investigation to improve triage of patients with ovarian tumours to enhance utilization of resources and optimize patient care.

International audience; BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent complication of a deep vein thrombosis (DVT). International guidelines recommend assessing PTS with the Villalta scale, a clinical measure that incorporates venous symptoms and signs in the leg ipsilateral to a DVT. However, these signs and symptoms are not specific for PTS and their prevalence and relevance in the contralateral leg have not previously been studied. METHODS: Using data from the REVERSE prospective multicentre cohort study, we compared the Villalta total score and prevalence of venous signs and symptoms in the ipsilateral vs. contralateral leg in patients with a first, unilateral DVT 5 to 7 months previously. RESULTS: Among the 367 patients analyzed, the mean Villalta score was higher in the ipsilateral than in the contralateral leg (mean ± standard deviation [SD] 3.7 [3.4] vs. 1.9 [2.5], respectively; P4) was present in 31.6% (n=116) of patients. Among these, 39.7% (n=46) of patients had a Villalta score >4 in the contralateral leg, and the distribution of Villalta symptoms and signs components was similar between the legs. CONCLUSIONS: Villalta scores in the ipsilateral and contralateral legs are strongly correlated. Almost half of cases considered to be PTS might reflect pre-existing symptomatic chronic venous disease. Alternatively, patients with pre-existing chronic venous disease might be more prone to developing PTS after a DVT. Performing a bilateral assessment of Villalta scores at the acute phase of DVT could be of clinical interest from a diagnostic, prognostic and therapeutic point of view.

Patient satisfaction is a complex, multidimensional concept that is difficult to measure. However, there is agreement that understanding the expectations of a patient community or "what is important to them" is an essential consideration. We chose a participatory approach to address patient satisfaction in the context of a primary care teaching clinic.The objectives of this project were to use a participatory research team of patients staff and researchers to (1) adapt an existing patient satisfaction questionnaire (PSQ) to the specific cultural and organizational elements ofa primary care teaching clinic, (2) administer the revised questionnaire and use the findings as a tool for organizational improvement, with the ultimate goal of increasing patient satisfaction, and (3) ensure that all decision making involved patients and staff to empower them in the process of organizational change.We used an iterative, mixed methods approach to conduct this project. An interdisciplinary committee composed of members of the patient community, clinical and administrative staff, and researchers worked together as the primary decision making body.We modified a preexisting questionnaire to address the unique care delivery model of the clinic, issues of cultural sensitivity, and the need for simplified language and response format. Patient dissatisfaction was found to center on continuity and access to care.The participatory approach was critical to our success in understanding and measuring patient satisfaction from the patients' perspective. The involvement of the interdisciplinary committee and the high level of joint decision making in this project represents a unique contribution to assessing primary care patient satisfaction.

Growth arrest-specific 6 (gas6), a novel vitamin K-dependent protein, has been demonstrated to have a role in thrombus stabilization as gas6 null mice are resistant to lethal venous and arterial thrombosis. However, the association between gas6 and venous thromboembolism has not been elucidated in humans. The present study aims to assess the role of gas6 in human venous thromboembolic (VTE) disease. Using a highly specific ELISA method, we measured plasma levels of gas6 in plasma samples obtained from 279 patients with VTE and 79 healthy volunteers. Medication history, comorbid conditions and VTE characteristics were documented. Mean gas6 levels were higher in patients with VTE as compared to healthy volunteers, being 46 ±11 ng/ml and 35 ±6.4 ng/ml respectively (P < 0.001). Odds ratios (OR) for VTE given elevated (≥90th percentile of healthy volunteers) gas6 levels were estimated in regression models in the whole study population. After adjustment for age, sex, medications and comorbidity, subjects with elevated gas6 had an increased risk of VTE (OR of 16.3 (95% CI 5.8–45.7, P < 0.001) compared to those with lower levels of gas6. This association remains significant even among patients with a comparable age distribution. Among patients with VTE, mean gas levels showed a trend of higher levels in those with more extensive thrombi. There was no correlation between elevated gas6 levels and recurrent VTE. In conclusion, we demonstrate an association between VTE and elevated gas6 levels consistent with in vivo murine models of thrombosis. This constitutes a potential novel mechanism for thrombosis in humans and may aid in the understanding of the pathophysiology of VTE.

Raed Alzafiri1, Christina A Holcroft2, Paula Malolepszy1, Albert Cohen1, Andrew Szilagyi11Jewish General Hospital, Division of Gastroenterology, Department of Medicine, McGill University School of Medicine, Montreal, Quebec, Canada; 2Centre for Clinical Epidemiology and Community Studies, McGill University School of Medicine, Montreal, Quebec, CanadaBackground: Infliximab has shown benefit in Crohn’s disease (CD) and ulcerative colitis (UC).Objective: Evaluation of long-term outcome of therapy for both diseases.Methods: We analyzed retrospectively patients treated at infusion centers from one institution. Demographic, laboratory parameters leading up to biologic therapy and the subsequent pattern of outcomes in either disease were established as a database. Initial failure, subsequent need to change therapy, or need to adjust therapy were evaluated. Kruskal–Wallis (nonparametric) tests to compare two groups and Kaplan–Meier survival curve analysis were used to compare outcomes.Results: Over approximately 6 years, 71 CD and 26 UC patients received 999 and 215 infusions, respectively, for a median of 62 months. Of these, 17% for CD and 19% for UC patients were primary failures. Following the start of infliximab, 18% of CD and 11% of UC patients required stoppage and switching to another type of therapy. In either CD or UC patients, 54% or 62%, respectively, continued therapy without the need to change to other treatments. Few serious side effects were noted. No important statistically significant differences in treatment patterns or outcome were observed between the groups.Discussion: Long-term treatment of both inflammatory bowel diseases reflects outcomes of clinical trials.Conclusions: This study emphasizes similarities between CD and UC and reports therapeutic success for an extended time.Keywords: infliximab, inflammatory bowel diseases

Although most cases of temporomandibular muscle and joint disorders (TMJD) are mild and self-limiting, about 10% of TMJD patients develop severe disorders associated with chronic pain and disability. It has been suggested that depression and catastrophizing contributes to TMJD chronicity. This article assesses the effects of catastrophizing and depression on clinically significant TMJD pain (Graded Chronic Pain Scale [GCPS] II-IV). Four hundred eighty participants, recruited from the Minneapolis/St. Paul area through media advertisements and local dentists, received examinations and completed the GCPS at baseline and at 18-month follow-up. In a multivariable analysis including gender, age, and worst pain intensity, baseline catastrophizing (β 3.79, P

Although most cases of temporomandibular muscle and joint disorders (TMJD) are mild and self-limiting, about 10% of TMJD patients develop severe disorders associated with chronic pain and disability. It has been suggested that fibromyalgia and widespread pain play a significant role in TMJD chronicity. This paper assessed the effects of fibromyalgia and widespread pain on clinically significant TMJD pain (GCPS II-IV). Four hundred eighty-five participants recruited from the Minneapolis/St. Paul area through media advertisements and local dentists received examinations and completed the Graded Chronic Pain Scale (GCPS) at baseline and at 18 months. Baseline widespread pain (OR: 2.53, P = .04) and depression (OR: 5.30, P = .005) were associated with onset of clinically significant pain (GCPS II-IV) within 18 months after baseline. The risk associated with baseline fibromyalgia was moderate, but not significant (OR: 2.74, P = .09). Persistence of clinically significant pain was related to fibromyalgia (OR: 2.48, P = .02) and depression (OR: 2.48, P = .02). These results indicate that these centrally generated pain conditions play a role in the onset and persistence of clinically significant TMJD. Perspective Fibromyalgia and widespread pain should receive important consideration when evaluating and developing a treatment plan for patients with TMJD.

Therapeutic decisions in the Operating Room (OR) are often made based solely upon results obtained from arterial blood gas machines. We evaluated how precise and accurate the results obtained from Bayer Rapid Point 405 (RP405) were vis-à-vis those of our blood gas laboratory and if they met the standards of the members of the anesthesia department.About 3 ml of blood from an indwelling arterial catheter were drawn into a heparinized syringe (FIMS Portex Inc.) from each of 90 patients and immediately analyzed by two RP405 and the hospital's main blood gas machines (Instrumentation Laboratories GEM 3000). The remaining 2.8 ml of blood was used to measure Hematocrit and sent to the hospital's main biochemistry laboratory for electrolyte measurement using an indirect ion selective method (Roche Diagnostics Modular ISE Module). A survey was distributed to each of the 19 anesthesiologists at the Sir Mortimer B Davis Jewish General Hospital (JGH). Their opinions for accuracy and treatment thresholds for each of the 12 variables measured by the RP405 were sought.For all measured variables, including pH, pCO2, pO2, potassium and Hematocrit, the correlation between the measurements from the RP405 and the gold standard were all above 95.5% with a p0.001. The survey results demonstrate that the machine gives results that are accurate within the acceptability frame expected by our staff anesthesiologists.Anesthesiologists must be confident that the information they receive is accurate in the context of rapidly changing clinical status. Our results show that the RP405 analyzers produce reliable measurements.

Abstract 393 Background: The post-thrombotic syndrome (PTS) is a burdensome, costly complication of deep venous thrombosis (DVT). Investigating strategies to prevent PTS is important, as treatments for PTS are limited. To date, randomized trials of elastic compression stockings (ECS) to prevent PTS were small, single-center, none used a placebo control and results are conflicting. Objective: To determine whether ECS, compared with inactive (placebo) stockings, are effective to prevent PTS in patients with proximal DVT. Methods: We conducted a multicenter (24 centres, Canada and U.S.) randomized placebo controlled trial of active ECS (A-ECS) vs. placebo ECS (P-ECS) to prevent PTS after a first, symptomatic proximal DVT. A-ECS were knee length 30–40 mm Hg (Class II) graduated ECS. P-ECS were manufactured to look identical to A-ECS but lacked therapeutic compression. Stockings were mailed directly to patients and worn on the DVT-affected leg daily for up to 2 years. Patients did not wear their stockings at study follow-up visits (1, 6, 12, 18 and 24 months) to maintain study personnel blinding. The primary study outcome, PTS, was diagnosed at or after the 6 month visit using the Ginsberg measure (leg pain and swelling of 3 1 month duration and typical in character: worse end of day or after prolonged sitting/standing and improved after rest/leg elevation). All PTS diagnoses were confirmed by the local study physicians. Secondary outcomes were incidence and severity of PTS using the Villalta scale, venous ulcers, VTE recurrence and death from VTE. A sample size of 800 patients was targeted based on a hypothesized cumulative incidence of the primary outcome of 30% in P-ECS vs. 20% in A-ECS, 2-tailed a of 0.05 and 80% power, and anticipated 25% rate of death/withdrawal/lost-to-follow-up. Using a modified intent to treat approach, we performed a time-to-event analysis using a Cox proportional hazards model adjusted for center to calculate hazard ratios (HR) and 95% confidence intervals (CI) to compare rates of the primary outcome in A-ECS vs. P-ECS. A similar time-to-event analysis was performed for Villalta PTS (Villalta score ≥ 5 at or after the 6 month visit). Results: From 2004–2010, 398 patients were randomized to A-ECS and 408 to P-ECS. 3 patients found to be ineligible soon after randomization were excluded from the analysis. Median time from DVT diagnosis to randomization was 4 days. Baseline features were similar in the 2 groups; overall, 60% were male, mean age was 55 years, and most proximal extent of DVT was iliac or femoral vein in 70% and popliteal vein in 30% of patients. The cumulative incidence of PTS (primary outcome) by 750 days was 14.8% in A-ECS vs. 12.3% in P-ECS ( Figure ) (HRadj 1.17; 95% CI 0.75–1.81; p=0.49). The cumulative incidence of Villalta PTS (secondary outcome) was 52.1% in A-ECS vs. 52.2% in P-ECS (HRadj 0.96; 95% CI 0.78–1.19; p=0.69). Additional outcomes were also similar in the two intervention groups ( Table ). Rates of loss to follow-up (5.5% vs. 5.4%) and withdrawal (8.3% vs. 9.1%) were similar in A-ECS and P-ECS. Overall, ∼70% of patients in both groups continued the intervention throughout study follow-up, and of these, >80% of patients in both groups reported use for ≥ 3 days per week. Conclusions: In a large randomized placebo-controlled trial, ECS did not prevent the occurrence of PTS after a first proximal DVT and did not influence the severity of PTS or rate of recurrent VTE. The reported benefits of ECS to prevent PTS in some prior studies could be due, at least in part, to bias from open-label design. Whether ECS may be of benefit to manage symptoms of established PTS should be evaluated in future studies. Active ECS (n = 397) Placebo ECS (n = 406) Villalta severity category * None (score 181 (51.9%) 182 (50.8%) Mild (5-9) 114 (32.6%) 116 (32.4%) Moderate (10-14) 30 (8.6%) 37 (10.3%) Severe (>14 or ulcer) 24 (6.9%) 23 (6.4%) Ipsilateral leg ulcer 16 ulcers in 16 patients 17 ulcers in 16 patients Recurrent VTE 45 events in 33 patients 44 events in 38 patients Recurrent ipsilateral DVT 18 events in 16 patients 17 events in 17 patients Death 36 (9.0%) 36 (9.1%) Death due to PE 0 0 Serious adverse event due to ECS 0 0 Adverse event due to ECS # 7 8 * Highest Villalta score at or after 6-month visit. Missing for 48 patients in each group; # leg rash or itching. Download : Download high-res image (26KB) Download : Download full-size image Disclosures: Kahn: NIH: Research Funding; Canadian Institutes for Health Research: Research Funding; Sigvaris: Research Funding.