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As a subset of the growing epidemic of cardiovascular morbidity and mortality in low-income and middle-income countries (LMICs), the significant burdens of heart rhythm disorders also increase. Effective diagnostic and treatment modalities exist, but financial resources and expertise are limited. Cost-effective strategies exist to address most of these limitations, but many surmountable barriers need to be overcome to introduce and improve electrophysiologic care in LMICs. In this article, current and potential solutions are offered for the diagnostic and therapeutic challenges of managing bradyarrhythmias and tachyarrhythmias.

Febrile neutropenia (FN) is a significant cause of both mortality and morbidity in patients undergoing adjuvant or neoadjuvant chemotherapy for early-stage breast cancer (ESBC). The risk of FN varies with respect to the type of chemotherapy used and patient-specific characteristics. Granulocyte colony-stimulating factors (G-CSF) are recommended, but not mandatory, as primary prophylaxis for patients at high-risk of FN. This study aimed to evaluate the impact of filgrastim and pegfilgastrim on the incidence of FN during adjuvant and neoadjuvant chemotherapy for ESBC. Risk factors for FN were also assessed. We conducted a retrospective cohort study that included 297 consecutive patients undergoing adjuvant or neoadjuvant chemotherapy for ESBC between May 2010 and May 2012. Patients on clinical trials were excluded. 173 patients (58%) received primary G-CSF prophylaxis whereas 124 (42%) did not. In patients receiving G-CSF prophylaxis, filgrastim was more commonly prescribed (59.9%), due to reimbursement reasons in Quebec. In total, 38 patients (12.8%) manifested at least one episode of FN. The incidence of FN was significantly reduced in patients receiving primary prophylaxis with G-CSF (p = 0.012). The most commonly prescribed chemotherapy protocols were FEC-D (5-Fluorouracil, epirubicin, cyclophosphamide followed by docetaxel), AC-T (Adriamycin, cyclophosphamide followed by paclitaxel), and TC (docetaxel and cyclophosphamide). The use of G-CSF as primary prophylaxis was associated with a decrease in FN incidence in patients receiving FEC-D and TC. Table 1 Incidence of febrile neutropenia in early-stage breast cancer chemotherapy G-CSF primary prophylaxis N = 173Absence of G-CSF prophylaxis N = 124 N (%)N (%) Febrile neutropenia (all chemotherapy)15 (9)23 (19)p = 0.012*TC4/51 (8)5/11 (45)p = 0.01*FEC-D6/59 (10)8/27 (30)p = 0.023*AC-T3/31 (10)8/63 (13)p = 0.668* denotes statistical significance at p < 0.05 One death occurred in a patient receiving FEC-D who had not received prophylaxis. There was no significant difference in the dosing of filgrastim between patients with FN (mean dose received = 5.289 mcg/kg) and those without FN (mean = 5.167mcg/kg) (p = 0.742). Furthermore, previously described risk factors for FN such as age, comorbidities and decreased baseline albumin were not associated with an increased of FN in our study. Although this was a retrospective study with inherent limitations, our cohort included, to our knowledge, the largest number of patients in a study of G-CSF use in ESBC. We found a statistically significant reduction of FN in patients receiving primary G-CSF prophylaxis. Primary prophylaxis should be routinely offered to patients undergoing chemotherapy for ESBC and in particular, to those receiving docetaxel-containing regimens. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-09.

Background Optimal post-treatment surveillance for patients with Hodgkin lymphoma in first complete remission (CR) is unknown. Guidelines are based on consensus rather than high-quality evidence. It is unknown if routine screening leads to earlier relapse detection or translates into better outcomes. Patients and methods We identified 258 patients with relapse after CR and determined whether the recurrence was detected as a result of patient-detected symptoms (PT group) or through exams or tests ordered by the physician in the absence of symptoms (MD group). Results Of 258 recurrences, 182 (71%) were in the PT group. The median time to diagnosis of recurrence was similar in both groups (PT group = 1.65 years; MD group = 1.95 years; P = 0.69). Neither the postrelapse progression-free (PFS, P = 0.26) nor overall survival (OS, P = 0.40) differed significantly between the groups. Conclusion Patients are much more likely to detect recurrence than their physicians employing routine follow-up testing. There is no difference in PFS or OS between patients whose recurrence is self-diagnosed versus those whose recurrence is diagnosed by physician through routine screening. We found no benefit for detection of HL recurrence in asymptomatic patients and thus cannot support the routine use of costly, anxiety-provoking or potentially harmful tests in the absence of symptoms.

As a subset of the growing epidemic of cardiovascular morbidity and mortality in low-income and middle-income countries (LMICs), the significant burdens of heart rhythm disorders also increase. Effective diagnostic and treatment modalities exist, but financial resources and expertise are limited. Cost-effective strategies exist to address most of these limitations, but many surmountable barriers need to be overcome to introduce and improve electrophysiologic care in LMICs. In this article, current and potential solutions are offered for the diagnostic and therapeutic challenges of managing bradyarrhythmias and tachyarrhythmias.

Contexte : Les etudiants en medecine peuvent eprouver de la difficulte a organiser leurs connaissances theoriques d’une facon qui soit adaptee a la pratique clinique. Methodes : Le test de concordance de script (TCS), outil habituellement utilise pour evaluer le raisonnement clinique, a ete employe dans un but pedagogique pour amener les etudiants a utiliser en contexte clinique les connaissances qu’ils viennent d’acquerir. L’activite de petit groupe a ete realisee pour les etudiants de premiere annee a la fin du cours de Sciences Hematologiques a l’Universite de Montreal. Un questionnaire anonyme demandant aux etudiants de decrire les points forts et les points faibles de l’activite a ete administre a la fin de l’activite. Resultats : L’activite a ete appreciee a la fois par les etudiants et par les tuteurs. Les points forts identifies par les etudiants incluent l’occasion de discuter et reviser les notions apprises, d’integrer leurs connaissances et de developper le raisonnement clinique. Conclusion : Le TCS peut etre employe de facon formative pour des etudiants n’ayant que peu d’experience clinique. Les reflexions et discussions induites par le format des questions semblent favoriser l’integration des connaissances.

Multicentric Castleman's disease (MDC) is a rare herpesvirus-8-related prelymphomatous condition that may develop in patients infected with human immunodeficiency virus (HIV). Therapy for MCD is not well established and most often includes: corticosteroids, single or combined chemotherapy, anti-CD20 monoclonal antibody and antiretroviral therapy. In order to obtain a rapid and long-lasting clinical response, we are reporting on a short course of anthracycline-based chemotherapy associated with rituximab in HIV-positive patients with MCD. Our study suggests that the combined immuno-chemotherapy approach may represent a valid strategy with acceptable toxicity in patients with severe and extensive MDC. Further studies will be needed to assess the efficacy and safety of such an approach, and to identify risk factors predictive of long-term tolerance in HIV patients with different degrees of immunosuppression.

Background: Latent rheumatic heart disease (RHD) occurs in asymptomatic individuals with echocardiographic evidence of RHD and no history of acute rheumatic fever. The natural history of latent RHD is unclear but has important clinical and economic implications about whether these children should receive penicillin prophylaxis or not. We performed a 5-year prospective study of this question. Methods: In August 2013 through September 2014, we conducted a follow-up study of latent RHD among school pupils using the World Heart Federation (WHF) echocardiographic criteria. Contingency tables were used to assess progression, persistence or regression of latent RHD. Results: Forty two borderline and 13 definite cases of RHD (n 55) were identified, 44 (80 %; mean age 13.8 ± 4.0 years; 29 (65.9 %) female) of whom were available for echocardiographic examination at a median follow-up of 60.8 months (interquartile range 51.3-63.5). Over the follow-up period, half the participants (n = 23; 52.3 %) improved to normal or better WHF category (regressors), a third (n = 14, 31.8 %) remained in the same category (persistors), while seven others (15.9 %) progressed from borderline to definite RHD (progressors). In total, 21 subjects (47.7 %) reverted to a normal status, nine (20.4 %) either improved from definite to borderline or remained in the borderline category, and 14 (31.8 %) either remained definite or progressed from borderline to a definite status. Two cases (20 %) progressed to symptomatic disease. Conclusions: Latent RHD has a variable natural history that ranges from regression to normal in nearly half of cases, to persistence, progression or development of symptoms in the remainder of subjects.

INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index

There is an epidemiological association between increased obstetric complications and disorders involving CNS dopamine dysregulation, such as schizophrenia. In light of this, a rat model of global hypoxia during Caesarean section (C-section) birth has been used to directly test if birth complications can produce long-term dopaminergic dysregulation. Previous studies have shown that, compared to vaginal birth, C-section birth alone (without additional global hypoxia) is sufficient to increase D1-like receptor binding in rat brain at adulthood. The current study examined (1) the developmental time course of changes in D1-like or D2-like receptors following C-section birth; (2) whether C-section birth from isoflurane-anesthetized dams also results in altered D1-like receptor levels, as does C-section from decapitated dams; and (3) behavioral responses to D1 and D2 agonists in rats born vaginally compared to C-section. Increases in nucleus accumbens D1-like receptor binding due to C-section birth were observed only at adulthood (3 months) but not prepubertally (1 month or 2 weeks). D2-like receptor binding levels were unaffected by C-section birth across the three developmental time points. Compared to vaginal birth, D1-like receptors were increased following C-section birth from isoflurane-anesthetized dams, as well as from decapitated dams. Adult rats that had been born by C-section showed enhanced D1 potentiation of D2-induced locomotor behavior. These studies indicate that C-section birth, from either anesthetized or unanesthetized dams, results in postpubertal increases in D1-like receptor binding and enhanced functional responses to D1 receptor activation.

Background— Ictal asystole is a rare, serious, and often treatable cause of syncope. There are currently limited data to guide management. Characterization of ictal syncope predictors may aid in the selection of high-risk patients for treatments such as pacemakers. Methods and Results— We searched our epilepsy monitoring unit database from October 2003 to July 2013 for all patients with ictal asystole events. Clinical, electroencephalogram, and ECG data for each of their seizures were examined for their relationships with ictal syncope events. In 10 patients with ictal asystole, we observed 76 clinical seizures with 26 ictal asystole episodes, 15 of which led to syncope. No seizure with asystole duration ≤6 s led to syncope, whereas 94% (15/16) of seizures with asystole duration >6 s led to syncope ( P =0.02). During ictal asystole events, 4 patients had left temporal seizure onset, 4 patients had right temporal seizure onset, and 2 patients had both. Syncope was more common with left temporal (40%) than with right temporal seizures (10%; P =0.002). Treatment options included antiepileptic drug changes, epilepsy surgery, and pacemaker implantation. Eight patients received pacemakers. During follow-up of 72±95 months, all patients remained syncope free. Conclusions— Ictal asystole >6 s is strongly associated with ictal syncope. Ictal syncope is more common in left than in right temporal seizures. A permanent pacemaker should be considered in patients with ictal syncope if they are not considered good candidates for epilepsy surgery.

Background Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation. Methods HIV-infected, Zambian adults with a body mass index

BACKGROUND: Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation. METHODS: HIV-infected, Zambian adults with a body mass index

La pratique de l’hématologie, comme celle de toute profession, implique l’acquisition d’un raisonnement adéquat. Se basant sur une théorie de psychologie cognitive, le test de concordance de script (TCS) a été développé et validé comme un instrument permettant d’évaluer le raisonnement clinique dans diverses spécialités médicales. Le but de cette étude était d’examiner l’utilité et les paramètres psychométriques d’un TCS en hématologie. Nous avons construit un TCS composé de 60 questions que nous avons administré à 15 résidents juniors (R1 à R3 en médecine interne), 46 résidents séniors (R4, R5 et R6 en hématologie) et 17 hématologues à travers le Canada. Après optimisation, le TCS comptait 51 questions. Sa consistance interne mesurée par le coefficient de Cronbach alpha était 0.83. Le test était en mesure de discriminer entre les résidents selon leur niveau de formation. Les questions contenant des images (n=10) semblaient avoir un potentiel discriminatoire plus élevé. Les scores obtenus par les résidents séniors corrélaient modéremment avec ceux obtenus à un test conventionnel d’hématologie composé de questions à choix multiples et à courte réponse (r de Pearson = 0.42; p=0.02). Le TCS a été complété en 36 minutes en moyenne et a été bien reçu par les participants. Le TCS est un instrument d’évaluation utile et valide en hématologie. Il peut être utilisé à des fins formatives en aidant au suivi de la progression des résidents. Il pourrait aussi être combiné à d’autres instruments d’évaluation à des fins sanctionnelles, ou encore, en éducation médicale continue., The practice of hematology, like any other profession, requires the acquisition of adequate judgment. Based on cognitive psychology theory, the script concordance test (SCT) has been developed and validated as an instrument capable of evaluation clinical judgement in various medical specialties. The goal of this study was to examine the usefulness and the psychometric qualities of the SCT in hematology. We constructed a SCT composed of 60 questions and we administered it to 15 junior residents (R1 to R3 in internal medicine), 46 senior residents (R4, R5 and R6) and 17 hematologists from across Canada. After item optimization, the test comprised 51 questions. Its internal consistency measured by Cronbach alpha was 0.83. The test was able to discriminate between residents according to their year of training. Questions containing an image (n=10) seemed to offer a stronger discriminative potential. Scores obtained by the senior residents correlated moderately with those obtained on a conventional hematology exam made of multiple choice questions and short-answers (Pearson r: 0.42; p=0.02). The SCT was completed in an average of 36 minutes and was well received by participants. The SCT is a useful and valid evaluation instrument in hematology. It may be used during training to monitor resident progression. It may also be combined to other evaluation tools and used for summative purposes or in continuing medical education.

The aim of this study was to examine a possible relation between the speed of information processing, as measured by simple and choice visual RT, and problem-solving, as measured by the Tower of Hanoi test. For 20 normal teenagers, performing all tests, significant correlations were found between choice RT and both measures of performance on the Tower of Hanoi, number of disk moves, and time taken to complete the task. Simple RT was correlated with Completion time but not with the number of moves, while the reverse pattern was discerned for decision time. Choice movement time was also associated with both measures, but simple movement time was not. These results are consistent with the hypothesis of a common neurobiological basis to information-processing speed and executive functions.

Seventeen percent of non-elderly Americans were uninsured in 2007. Sixty-five percent of the uninsured have a family income below 200 percent of the federal poverty level. The uninsured receive less preventive care, fewer diagnostic services, less therapeutic care, and are usually more severely ill at presentation. The uninsured have poorer disease-specific and general mortality and morbidity, which is partially explained by decreased access to care and medical care use. Thus, the physical and emotional health of the uninsured suffers due to decreased use of and access to medical services. Lack of insurance affects also burdens families and communities. Families without health insurance are twice as likely to spend over five percent of their income on out-of-pocket health care. In 2005, approximately $43 billion was spent on uncompensated medical care for the uninsured. An estimated $65 to $130 billion is lost annually due to the uninsured's poorer health and reduced lifespans. Thus, the health consequences of uninsurance present a significant burden to patients, family, and communities. The burden of care for the uninsured further falls disproportionately on primary care providers. In minority populations, 45.6 percent of low-income uninsured physician visits are with family physicians. In comparison, 30.1 percent of insured physician visits are with family physicians. Since the uninsured present more severely ill and advanced disease, family physicians are caring for sicker patients that often would be better served by more specialized care. In a study of children with a chronic condition or disability, Kuhlthau and colleagues found that 16.9 percent of the uninsured saw a specialist while 28.3 percent of the privately insured saw a specialist. Szilagyi and colleagues found a 5-fold increase in specialty visits after patient enrollment in an insurance program. Uninsured dialysis patients are three times more likely to be referred late to nephrologists than their insured counterparts. The uninsured's decreased access to specialists leads to worse outcomes for patients with hypertension, heart attacks, cancer, trauma, ruptured appendices, liver disease, and patients on ventilator support. Many communities have safety nets that are intended to provide care for their low-income uninsured. Generally, this includes some combination of emergency departments, health departments, free clinics, and charity care from other private providers. Safety nets are mainly composed of primary care providers and lack specialty care providers. While the specialty needs of the uninsured are known, few models to address this problem are described in the medical literature. In this program plan and evaluation paper, I first explore what models exist to address the lack of specialty care for the uninsured. I then describe a recently begun program in Richmond, Virginia and outline a plan for its growth and evaluation.

HHV-8 linked to Kaposi’s sarcoma, Castleman’s disease and primary effusion lymphoma in a HIV-1-infected man Alain Bestawros a, Mohamed-Rachid Boulassel b, Rene P. Michel c, Jean-Pierre Routy b,∗ a Department of Internal Medicine, Montreal General Hospital and McGill University Health Centre, Montreal, Canada b Division of Hematology and Immunodeficiency Service, Royal Victoria Hospital and McGill University Health Centre, Monterial, Canada c Department of Pathology, Royal Victoria Hospital and McGill University Health Centre, Montreal, Canada

Coronary artery bypass graft surgery (CABG) in women has been associated with worse clinical outcomes than CABG in men. However, little is known about the impact of sex on the cost of CABG.To examine the impact of sex on hospital course and the cost of CABG.Hospital course and cost were examined among 2880 female and 9137 male patients from four Canadian and five American hospitals. Data were obtained from a resource and cost accounting system used by each of the nine hospitals.Among the 12,017 patients who underwent CABG, 24% (n=2880) were women and 76% (n=9137) were men. Women had a significantly longer length of stay (LOS) than did men (10.3+/-0.2 days and 8.9+/-0.08 days, respectively; P0.0001) and a significantly higher in-hospital mortality than did men (2.6% and 1.5%, respectively; P0.0001). The total unadjusted cost was higher for women than for men both in Canada (US$11,200+/-268 and US$10,143+/-139, respectively; P0.0001) and the United States (US$22,715+/-509 and US$19,906+/-269, respectively; P0.0001). After adjusting for age and comorbid conditions, female sex was associated with a 10% increase in LOS (P0.0001), a 97% increase in mortality (P=0.0006) and a 7% increase in overall cost (P0.0001).Compared with men, women undergoing CABG had a modestly increased LOS and a higher mortality. Total in-hospital cost was higher for women in each of the nine hospitals studied. Compared with other clinical variables, female sex is a relatively minor determinant of cost. Nevertheless, because of the expected increase in the number of women undergoing CABG in the future, this increased cost may translate into an important economic burden.

Analogs of 1alpha,25-dihydroxyvitamin D(3) (1alpha, 25(OH)2D3) inhibit growth in vitro and in vivo of cells derived from a variety of tumors. Here, we examined the effects of 1alpha,25(OH)2D3 and its analog EB1089 on proliferation and target gene regulation of human head and neck squamous cell carcinoma (SCC) lines SCC4, SCC9, SCC15, and SCC25. A range of sensitivities to 1alpha,25(OH)2D3 and EB1089 was observed, from complete G0/G1 arrest of SCC25 cells to only 50% inhibition of SCC9 cell growth. All lines expressed similar levels of vitamin D3 receptor (VDR) mRNA and protein, and no significant variation was observed in 1alpha,25(OH)2D3-dependent induction of the endogenous 24-hydroxylase gene, or of a transiently transfected 1alpha,25(OH)2D3-sensitive reporter gene. The antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC25 cells were analyzed by screening more than 4,500 genes on two cDNA microarrays, yielding 38 up-regulated targets, including adhesion molecules, growth factors, kinases, and transcription factors. Genes encoding factors implicated in cell cycle regulation were induced, including the growth arrest and DNA damage gene, gadd45alpha, and the serum- and glucocorticoid-inducible kinase gene, sgk. Induction of GADD45alpha protein in EB1089-treated cells was confirmed by Western blotting. Moreover, while expression of proliferating cell nuclear antigen (PCNA) was reduced in EB1089-treated cells, coimmunoprecipitation studies revealed increased association between GADD45alpha and PCNA in treated cells, consistent with the capacity of GADD45alpha to stimulate DNA repair. While 1alpha,25(OH)2D3 and EB1089 modestly induced transcripts encoding the cyclin-dependent kinase inhibitor p21(waf1/cip1), no changes in protein levels were observed, indicating that p21(waf1/cip1) induction does not contribute to the antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC cells. Finally, in partially resistant SCC9 cells, there was extensive loss of target gene regulation (10 of 10 genes tested), indicating that resistance arises from widespread loss of 1alpha,25(OH)2D3-dependent gene regulation in the presence of normal levels of functional VDRs.

Fibronectin plays an important role in corneal healing and has been detected previously in the tear film. To investigate the levels of fibronectin in normal human tears, the authors measured and compared fibronectin concentration in open-eye, closed-eye, and reflex tear fluid. The origin of fibronectin in the tear film was investigated by comparing fibronectin concentration in sequentially collected reflex tear samples with the concentrations of total protein and albumin in the same samples.Open-eye and closed-eye tears were collected from 11 noncontact lens wearers. From 7 subjects, 20 uninterrupted reflex tear samples (10 microliters each) subsequently were collected, using the sneeze reflex method of stimulation, followed by an additional 10 nonstimulated tear samples (3 microliters each) immediately after cessation of stimulus. Enzyme-linked immunosorbent assays were used to determine fibronectin and albumin concentrations, and bicinchoninic acid protein assays were used to determine total protein concentration in each sample.Fibronectin concentration in open-eye tears (19 +/- 24 eta g/ml, range 3 to 78 eta g/ml) was significantly different (P = 0.004) from that in closed-eyes tears (4127 +/- 3222 eta g/ml, range 1177 to 11384 eta g/ml). In the first 50 microliters of reflex tears, fibronectin concentrations were low (10 +/- 23 eta g/ml), but they increased significantly (P = 0.028) after 100 microliters of reflex tears had been collected (220 +/- 126 eta g/ml). There was a further marked transient increase (767 +/- 946 eta g/ml) after cessation of stimulus. Total protein concentration in the same samples decreased significantly during reflex tear collection compared to open-eye tears, and it increased gradually after cessation of stimulus. Albumin concentration in the same samples, analyzed for two subjects only, showed a pattern similar to that for fibronectin. Dilation of conjunctival blood vessels was noted in all subjects after reflex tear collection. Administration of a topical vasoconstrictor in two subjects eliminated the increase in fibronectin concentration during reflex tearing but did not affect total protein concentration. Under reducing conditions, the molecular mass of fibronectin in open-eye and reflex tears was 240 kDa, identical to commercially available purified plasma fibronectin, whereas fibronectin in closed-eye tears was degraded into small molecular mass fragments.These findings suggest that fibronectin in tear fluid is derived from plasma and that the increase in concentration in closed-eye and reflex tear fluid is caused by leakage from dilated conjunctival blood vessels.

8041 Background: The optimal post-treatment surveillance of patients with Hodgkin lymphoma (HL) in first complete remission (CR) is unknown. Guidelines are based on consensus rather than high-quali...

Epidural venography is valuable in diagnosing lumbar spinal stenosis. It shows anterior displacement of the posterior medial longitudinal intervertebral veins at the level of the lamina and the superior and inferior articular facets. This results in decreased distance between and sometimes overlapping of the posterior and anterior medial longitudinal intervertebral veins. Three cases of spinal stenosis diagnosed by epidural venography are presented.