Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

BACKGROUND: High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. OBJECTIVES: The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at an outpatient clinic at a tertiary care center in Toronto. PATIENTS: Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. INTERVENTION: All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. MAIN OUTCOME MEASURES: We measured the incidence of anal cancer per 100 person-years of follow-up. RESULTS: Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. LIMITATIONS: There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. CONCLUSIONS: HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

Comparison of coping strategies and supports between aboriginal and non-aboriginal people living with HIV in Ontario.

Complex historical and cultural factors have contributed to the HIV epidemic among Aboriginal populations in Canada. This study assesses social supports, adaptive and maladaptive coping mechanisms, stress, and mastery of Canadian-born Aboriginal and Canadian-born Caucasian people living with HIV in Ontario and posits that coping and social support are important micro- and meso-level factors associated with the epidemic. This cross-sectional analysis included questionnaire data collected from 2007 to 2011 at HIV clinics in Toronto. Categorical and continuous variables were compared using chi-square and Wilcoxon rank sum tests, respectively. Correlates of social support and coping were determined using univariate and multivariable linear regression. The analysis included 70 Aboriginal and 665 Caucasian participants. Aboriginal participants had lower levels of employment, education, and annual household income. Aboriginal participants reported more overall (7 vs. 4, p = 0.0003), ongoing (4 vs. 2, p = 0.0004), and early childhood (2 vs. 1, p = 0.02) stressors. Maladaptive coping, adaptive coping, and mastery scores were similar between Aboriginal and Caucasian participants. In multivariable analysis, injection drug use and lower education levels were significant correlates of higher maladaptive coping and lower overall support scores. Despite numerous socioeconomic challenges and personal stressors, Aboriginal people living with HIV who are accessing care exhibited comparable coping and mastery scores to Canadian-born Caucasian people living with HIV, suggesting remarkable strengths within Aboriginal people living with HIV and their communities.

The importance of motherhood in HIV-positive women of reproductive age in Ontario, Canada.

Motherhood is personally, culturally, and historically rooted. Recent publications have focused on medical issues related to pregnancy and HIV, with attention on fetal well-being. There is limited literature on the importance of motherhood for HIV-positive women. Our study's purpose was to investigate the importance of motherhood among HIV-positive women of reproductive age in Ontario, Canada and to analyze the correlates thereof. We present our findings using a secondary analysis of cross-sectionally collected data from a study assessing fertility desires and intentions of HIV-positive women. The sub-analysis's outcome of interest was based on the question: "Being a mother is important to me" with a 5-point Likert scale that was dichotomized into strongly agree/agree vs. neutral/disagree/strongly disagree. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios (ORs) for significant correlates. Of the 497 respondents, median age was 38 (interquartile range [IQR] 32-43), 46% were African, 74% had given birth, and 57% intended to give birth. A total of 452 (91%) agreed (N = 75) or strongly agreed (N = 377) that being a mother was important to them. Age less than 40 years (OR 3.0; 95% confidence interval [CI] 1.6-5.7, African ethnicity (OR 9.2; 95% CI 3.2-26.3), immigration within 10 years (OR 19.6, 95% CI 4.6-83.1), and partner or family desire for a pregnancy (OR 3.3; 95% CI 1.5-7.3) were significant correlates of the importance of motherhood in a univariate analysis. Importance of motherhood was associated with desire (OR 6.2, 95% CI 3.1-12.3) and intention to give birth (OR 6.9, 95% CI 3.1-15.2), and previous birth (OR 8.5, 95% CI 4.2-16.8). In the multivariable model, the significant correlates were of age less than 40 years (OR 3.9; 95% CI 1.8-8.4), immigration within 10 years (OR 14.1; 95% CI 3.2-61.5), and having previously given birth (OR 11.2; 95% CI 5.1-24.4). The majority of women felt strongly that motherhood was important to them particularly among younger women, recent immigrants, and women who were mothers.

Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women.

BACKGROUND: The Canadian Women's HIV Study (CWHS) enrolled human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women in a longitudinal cohort. This analysis considered the effects of HIV and highly active antiretroviral therapy (HAART) on HPV persistence and cervical squamous intraepithelial lesions (SILs). METHODS: Longitudinal cytopathologic and HPV DNA results were analyzed using multistate models. States of cervical SIL were defined as absent, present, and treatment; HPV states were defined as negative or positive. Demographic variables and markers of sexual activity were considered predictors. Results were calculated on the basis of transition probabilities and reported as hazard ratios (HRs). RESULTS: The CWHS followed 750 HIV-positive and 323 HIV-negative women during 1993-2002. A total of 467 and 456 women were included in the longitudinal cervical cytopathologic and HPV DNA analyses, respectively. HIV-positive women had increased prevalence (46.6% vs 28.7%; P < .0001), increased acquisition (HR, 2.3; P = .03), and decreased clearance (HR, 0.4; P < .001) of oncogenic HPV as compared to HIV-negative women. Oncogenic HPV infection predicted progression of cervical dysplasia from normal to abnormal SIL (HR, 2.8; P = .002). Among HIV-positive participants, HAART increased the likelihood of regression (from present to absent) of cervical SIL (HR, 3.3; P = .02) and increased the clearance of oncogenic HPV types other than HPV-16 or HPV-18 (HR, 2.2; P = .01). CONCLUSIONS: This analysis demonstrated beneficial effects of HAART on cervical SIL in HIV-positive women.

Representativeness of an HIV cohort of the sites from which it is recruiting: results from the Ontario HIV Treatment Network (OHTN) cohort study.

BACKGROUND: Participation bias is a well-known phenomenon in epidemiologic research, where individuals consenting to research studies differ from individuals who are not able or willing to participate. These dissimilarities may limit the generalizability of results of research studies. Quantification of the participation bias is essential for the interpretation of research findings. METHODS: The Ontario HIV Treatment Network Cohort Study (OCS) is an ongoing open cohort study of HIV positive individuals receiving care at one of 11 sites in Ontario. OCS participants from 4 sites were compared to non-participants (those who declined or were not approached) at those sites with regard to gender, age, HIV risk factor, CD4 count and viral load (VL). Generalized logit regression models were used to identify predictors of declining to participate or not being approached to participate. RESULTS: Compared to participants (P) in the OCS, individuals who declined to participate (D) and those who were not approached (NA) were slightly younger (D:45, NA:44 vs P:46), less likely to be male (D: 71%, NA:75% vs P:88%), less likely to be Caucasian (D:41%, NA:57% vs P:72%) and less likely to be Canadian-born (D: 39%, NA: 52% vs P: 69%). Patients who were not approached to participate were less likely to have VL < 50 copies/mL than other patients (D: 75%, NA: 62%, P: 74%) and had lower CD4 counts than OCS participants (D: 450 cells/mm3, NA: 420 cells/mm3, P: 480 cells/mm3). CONCLUSIONS: Significant demographic and clinical differences were found between OCS participants and non-participants. Extrapolation of research findings to other populations should be undertaken cautiously.

Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study.

BACKGROUND: Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C(min) and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. METHODS: HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for C(min) and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median C(min) and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed C(min) and Cmax ratios. RESULTS: Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral C(min) and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher C(min). No significant correlates for Cmax were found. CONCLUSIONS: Compared to historical control data, C(min) in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral C(min) ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. TRIAL REGISTRATION: NCT00433979.

Recent immigrants show improved clinical outcomes at a tertiary care HIV clinic.

BACKGROUND: In recent years, the proportion of patients attending tertiary care HIV clinics who are recent immigrants to Canada has increased dramatically. METHODS: Among patients first seen at the Toronto Hospital Immunodeficiency Clinic (Toronto, Ontario) between January 1, 2000 and August 31, 2009, the time to death from the first positive HIV test was compared between individuals who had immigrated to Canada within 10 years of their first visit and individuals who were either Canadian-born or who had immigrated more than 10 years before their first clinic visit. In addition, for the antiretroviral-naive patients in these two groups who initiated combination antiretroviral therapy, the time to and the duration of virologic suppression were compared. RESULTS: In a multivariable proportional hazards (PH) model, recent immigrant status was associated with decreased mortality (HR 0.11, P=0.03) after adjusting for age, CD4 count and the risk factor for men having sex with men. In multivariable PH models, recent female immigrants achieved virologic suppression more quickly (HR 1.51, P=0.02), while male immigrants (HR 1.14, P=0.44) and female nonimmigrants (HR 0.90, P=0.61) had similar times to virologic suppression as male nonimmigrants, respectively, after adjusting for the year of and viral load at combination antiretroviral therapy initiation. When pregnant women were removed from the analysis, there were no significant differences in the rates of virologic rebound according to sex or immigration status. DISCUSSION: Despite the perceived barriers of newcomers to Canada, mortality was lower among recent immigrants and virologic suppression was achieved more quickly in recent female immigrants. BACKGROUND: In recent years, the proportion of patients attending tertiary care HIV clinics who are recent immigrants to Canada has increased dramatically. METHODS: Among patients first seen at the Toronto Hospital Immunodeficiency Clinic (Toronto, Ontario) between January 1, 2000 and August 31, 2009, the time to death from the first positive HIV test was compared between individuals who had immigrated to Canada within 10 years of their first visit and individuals who were either Canadian-born or who had immigrated more than 10 years before their first clinic visit. In addition, for the antiretroviral-naive patients in these two groups who initiated combination antiretroviral therapy, the time to and the duration of virologic suppression were compared. RESULTS: In a multivariable proportional hazards (PH) model, recent immigrant status was associated with decreased mortality (HR 0.11, P=0.03) after adjusting for age, CD4 count and the risk factor for men having sex with men. In multivariable PH models, recent female immigrants achieved virologic suppression more quickly (HR 1.51, P=0.02), while male immigrants (HR 1.14, P=0.44) and female nonimmigrants (HR 0.90, P=0.61) had similar times to virologic suppression as male nonimmigrants, respectively, after adjusting for the year of and viral load at combination antiretroviral therapy initiation. When pregnant women were removed from the analysis, there were no significant differences in the rates of virologic rebound according to sex or immigration status. DISCUSSION: Despite the perceived barriers of newcomers to Canada, mortality was lower among recent immigrants and virologic suppression was achieved more quickly in recent female immigrants.

HISTORIQUE: Ces dernières années, la proportion de patients qui sont de récents immigrants au Canada et fréquentent des cliniques de soins tertiaires du VIH a considérablement augmenté. MÉTHODOLOGIE: Chez les patients d'abord vus à la clinique d'immunodéficience du Toronto Hospital de Toronto, en Ontario, entre le 1er janvier 2000 et le 31 août 2009, les chercheurs ont comparé le délai jusqu'au décès à compter du premier test positif du VIH entre les personnes qui avaient immigré au Canada dans les dix ans suivant leur première visite clinique et les personnes qui étaient nées au Canada ou avaient immigré plus de dix ans avant leur première visite clinique. De plus, ils ont comparé le délai jusqu'à la suppression virologique et la durée de cette suppression chez les patients naïfs aux antirétroviraux de ces deux groupes qui avaient amorcé une antirétrovirothérapie polyvalente. RÉSULTATS: Dans un modèle de hasards proportionnels (HP) multivarié, l'état des récents immigrant s'associait à une diminution de la mortalité (RR 0,11, P=0,03) après redressement selon l'âge, la numération des CD4 et le facteur de risque chez les hommes qui ont des relations sexuelles entre hommes. Dans des modèles de HP multivariés, les récentes immigrantes obtenaient une suppression virale plus rapidement (RR 1,51, P=0,02), tandis que les immigrants (RR 1,14, P=0,44) et les non-immigrantes (RR 0,90, P=0,61) présentaient un délai similaire à celui des hommes non immigrants jusqu'à la suppression virologique, respectivement, après redressement compte tenu de l'année et de la charge virale au début de l'antirétrovirothérapie polyvalente. Lorsque les femmes enceintes étaient retirées de l'analyse, on ne constatait plus de différence significative dans les taux de rebond virologique selon le sexe ou le statut d'immigration. EXPOSÉ: Malgré les obstacles perçus pour les nouveaux arrivants au Canada, la mortalité était plus faible chez les récents immigrants, tandis qu'on parvenait à la suppression virologique plus rapidement chez les récentes immigrantes.

Comparison of late HIV diagnosis as a marker of care for Aboriginal versus non-Aboriginal people living with HIV in Ontario.

BACKGROUND: Studies have found that Aboriginal people living with HIV/AIDS (APHAs) are more likely than non-APHAs to receive suboptimal HIV care, yet achieve similar clinical outcomes with proper care. OBJECTIVE: To compare the proportions of individuals diagnosed late with HIV between APHAs and non-APHAs within the Ontario HIV Treatment Network Cohort Study (OCS). METHODS: The analysis included OCS participants who completed the baseline visit by November 2009. Two definitions of the outcome of late HIV diagnosis were used: the proportion of participants with an AIDS-defining illness (ADI) before or within three months of HIV diagnosis; and the proportion of participants with a CD4(+) count <200 cells/mL at diagnosis. Logistic regression analysis was used to assess the association between Aboriginal ethnicity and late HIV diagnosis. RESULTS: APHAs were more likely to be female and have lower income, education and employment. No statistically significant differences were noted in the proportions receiving a late HIV diagnosis defined by ADI (Aboriginal 5.2% versus non-Aboriginal 6.3%; P=0.40). Multivariate logistic regression analysis revealed a significant association between Aboriginal ethnicity and late HIV diagnosis defined by CD4(+) count after adjusting for age and HIV risk factor (OR 1.55; P=0.04). DISCUSSION: APHAs were more likely to have a CD4(+) count <200 cells/mL at diagnosis but had similar clinical outcomes from late diagnosis when defined by ADI. However, differences may be underestimated due to recruitment limitations and selection bias. CONCLUSION: Additional work is needed to address the socioeconomic and health care needs of APHAs.

HISTORIQUE: Les études ont démontré que les Autochtones qui vivent avec le VIH ou le sida (AVVS) sont plus susceptibles que les non-Autochtones qui vivent avec le VIH ou le sida (NAVVS) de recevoir des soins sous-optimaux, mais présentent des issues cliniques similaires lorsqu'ils reçoivent des soins convenables. OBJECTIF: Comparer la proportion d'AVVS et de non-AVVS de la cohorte OCS du réseau thérapeutique du VIH qui reçoivent un diagnostic tardif de VIH de l'Ontario. MÉTHODOLOGIE: L'analyse incluait les participants de l'OCS qui avaient eu leur première visite avant novembre 2009. Deux définitions de l'issue de diagnostic tardif du VIH ont été utilisées : la proportion de participants ayant une maladie symptomatique du sida (MSS) avant ou dans les trois mois suivant le diagnostic du VIH, et la proportion de participants ayant une numération de CD4+ inférieure à 200 cellules/mL au diagnostic. Les chercheurs ont utilisé l'analyse de régression logistique pour évaluer l'association entre l'ethnie autochtone et le diagnostic tardif de VIH. RÉSULTATS: Les AVVS étaient plus susceptibles d'être des femmes et d'avoir un revenu et une scolarisation plus faibles ainsi qu'un emploi moins bien rémunéré. Les chercheurs n'ont perçu aucune différence statistiquement significative dans la proportion qui avait reçu un diagnostic tardif de VIH défini par une MSS (Autochtones 5,2 %, non-Autochtones 6,3 %; P=0,40). L'analyse de régression logistique multivariée a révélé une association significative entre l'ethnie autochtone et un diagnostic tardif de VIH défini par la numération de CD4+ après rajustement compte tenu de l'âge et du facteur de risque de VIH (RRR=1,55; P=0,04). EXPOSÉ: Les AVVS étaient plus susceptibles de présenter une numération de CD4+ inférieure à 200 cellules/mL au diagnostic, mais avaient des issues cliniques similaires de diagnostic tardif lorsqu'on le définissait par une MSS. Cependant, les différences sont peut-être sous-estimées en raison des limites de recrutement et du biais de sélection. CONCLUSION: D'autres travaux s'imposent pour connaître les besoins socioéconomiques et en soins de santé des AVVS.

Once daily dosing improves adherence to antiretroviral therapy.

We studied the association of once-daily dosing with self-reported adherence among participants of the Ontario Cohort Study who were currently taking ART and who had completed a 90-min interviewer-administered questionnaire. Suboptimal adherence was defined as missing ≥1 dose of ART in the 4 days prior to the interview. Participants (n = 779) were 85% male, 69% men having sex with men, 67% white, median age 48 years (IQR 42-54), median years of ART 9 (IQR 5-13) and median CD4 count 463 cells/mm(3) (IQR 320-638). Fifteen percent of participants reported suboptimal adherence in the 4 days prior to the interview. In a multivariable logistic regression model, participants on once daily regimens were half as likely to miss a dose during the 4 days prior to the interview. Other independent correlates of suboptimal adherence were younger age, lower positive social interaction and increased frequency of consuming > 6 alcoholic drinks on one occasion.

Minimally invasive thymectomy for myasthenia gravis favours left-sided approach and low severity class.

OBJECTIVES: Complete thymectomy is a key component of the optimal treatment for myasthenia gravis. Unilateral, minimally invasive approaches are increasingly utilized with debate about the optimal laterality approach. A right-sided approach has a wider field of view, while a left-sided approach accesses potentially more thymic tissue. We aimed to assess the impact of laterality on perioperative and medium-term outcomes, and to identify predictors of a 'good outcome' using standard definitions. METHODS: We performed a multicentre review of 123 patients who underwent a minimally invasive thymectomy for myasthenia gravis between January 2000 and August 2015, with at least 1-year follow-up. The Myasthenia Gravis Foundation of America standards were followed. A 'good outcome' was defined by complete stable remission/pharmacological remission/minimal manifestations 0, and a 'poor outcome' by minimal manifestations 1-3. Univariate and multivariable logistic regression analyses were performed to assess factors associated with a 'good outcome'. RESULTS: Ninety-two percent of thymectomies (113/123) were robotic-assisted. The left-sided approach had a shorter median operating time than a right-sided: 143 (interquartile range, IQR 110-196) vs 184 (IQR 133-228) min, P = 0.012. At a median of 44 (IQR 27-75) months, the left-sided approach achieved a 'good outcome' (46%, 31/68) more frequently than the right-sided (22%, 12/55); P = 0.011. Multivariable analysis identified a left-sided approach and Myasthenia Gravis Foundation of America class I/II to be associated with a 'good outcome'. CONCLUSIONS: A left-sided thymectomy may be preferred over a right-sided approach in patients with myasthenia gravis given the shorter operating times and potential for superior medium-term symptomatic outcomes. A lower severity class is also associated with a 'good outcome'.

Effect of gender and calendar year on time to and duration of virologic suppression among antiretroviral-naïve HIV-infected individuals initiating combination antiretroviral therapy.

PURPOSE: To determine the effects of gender and calendar year on time to and duration of virologic suppression among HIV-infected antiretroviral-naïve individuals initiating combination antiretroviral therapy (cART). METHODS: Ontario Cohort Study antiretroviral-naïve participants who initiated cART after December 31, 1998, and who had ≥2 follow-up viral loads were included. Multivariable Cox proportional hazard models were used to estimate the effects of gender and calendar year on times to virologic suppression and rebound. RESULTS: Of the 840 patients, 81% were male (median age 40 years; interquartile range [IQR], 34-46). Time to virologic suppression was shorter among women (hazard ratio [HR]=1.27, P=.01) and in more recent calendar time periods (2002-2004: HR, 1.04, P=.67; 2005-2006: HR, 1.22, P=.06; 2007-2008: HR, 1.36, P=.004) compared to 1999-2001 after adjusting for age and type of cART regimens. Women had shorter times to virologic rebound (HR, 1.57; P<.01) after adjusting for age, injection drug use, and type of cART regimen. However, 14/18 (78%) women suspected to be taking cART only for prevention of mother-to-child transmission of HIV experienced virologic rebound compared to 28% of women who required cART for their own health, suggesting that the increased rate of virologic rebound was due to women stopping ART at the termination of a pregnancy if they did not need it for their own health. Rates of rebound did not differ by calendar year period. CONCLUSION: Time to virologic suppression has steadily decreased over time while duration of suppression remained stable. Time to virologic suppression was shorter for women than for men, whereas durability of virologic suppression was slightly longer for men than women. However, gender differences in virologic rebound were likely due to women discontinuing cART at the end of the pregnancy if it was not needed for their own health.

Factors associated with HIV-positive women carrying pregnancies to term.

OBJECTIVES: To determine predictors of HIV-positive women who choose to carry a pregnancy to term. METHODS: We collected pregnancy data up to December 2008 on women who had attended the University Health Network Immunodeficiency Clinic in Toronto since 2000 and were < 50 years of age at the time of their first HIV-positive test. Data were included on all pregnancies, including those that occurred before the woman was known to be HIV positive or first attended the clinic. RESULTS: Data were collected from a total of 341 women who were < 50 years of age at their first HIV-positive test. Of these women, 179 (52%) had a total of 484 pregnancies, and 110 of these pregnancies (23%) in 74 women were known to occur after the woman tested HIV positive. An additional 52 women (11%) were found to be HIV positive during the pregnancy. Predictors of a woman's carrying a pregnancy to term when HIV positive were age, region of maternal birth, number of previous live births, and pregnancy during the highly active antiretroviral therapy (HAART) era. CONCLUSION: HIV-positive women are more likely to carry a pregnancy to term during the new HAART era than they were before this era. Younger African-born HIV-positive women who already have children are more likely than other HIV-positive women to choose to carry a pregnancy to term.

Does Treatment of the Hiatus Influence the Outcomes of Magnetic Sphincter Augmentation for Chronic GERD?

BACKGROUND: Hiatal dissection, restoration of esophageal intra-abdominal length, and crural closure are key components of successful antireflux surgery. The necessity of addressing these components prior to magnetic sphincter augmentation (MSA) has been questioned. We aimed to compare outcomes of MSA between groups with differing hiatal dissection and closure. METHODS: We retrospectively reviewed 259 patients who underwent MSA from 2009 to 2017. Patients were categorized based on hiatal treatment: minimal dissection (MD), crural closure (CC), formal crural repair (FC), and extensive dissection without closure (ED). The primary outcome was normalization of postoperative DeMeester score (≤ 14.72). Univariable and multivariable logistic regression was used to assess which preoperative predictors achieved normalization. RESULTS: Of the 197 patients, MD was used in 81 (41%); FC in 42 (22%); CC in 40 (20%); and ED in 34 (17%). Normalization occurred in 104 (53%) patients, with MD achieving normalization in 45/81 (56%); FC in 25/42 (60%); CC in 21/40 (53%); and ED 13/34 (38%). After regression, FC was most likely to normalize acid exposure. The presence of a hiatal hernia, defective LES, and higher preoperative DeMeester score were less likely to achieve normalization. CONCLUSIONS: Hiatal dissection with restoration of esophageal length and crural closure during MSA increases the likelihood of normalizing acid exposure.

Adjuvant docetaxel for node-positive breast cancer.

BACKGROUND: We compared docetaxel plus doxorubicin and cyclophosphamide (TAC) with fluorouracil plus doxorubicin and cyclophosphamide (FAC) as adjuvant chemotherapy for operable node-positive breast cancer. METHODS: We randomly assigned 1491 women with axillary node-positive breast cancer to six cycles of treatment with either TAC or FAC as adjuvant chemotherapy after surgery. The primary end point was disease-free survival. RESULTS: At a median follow-up of 55 months, the estimated rates of disease-free survival at five years were 75 percent among the 745 patients randomly assigned to receive TAC and 68 percent among the 746 randomly assigned to receive FAC, representing a 28 percent reduction in the risk of relapse (P=0.001) in the TAC group. The estimated rates of overall survival at five years were 87 percent and 81 percent, respectively. Treatment with TAC resulted in a 30 percent reduction in the risk of death (P=0.008). The incidence of grade 3 or 4 neutropenia was 65.5 percent in the TAC group and 49.3 percent in the FAC group (P<0.001); rates of febrile neutropenia were 24.7 percent and 2.5 percent, respectively (P<0.001). Grade 3 or 4 infections occurred in 3.9 percent of the patients who received TAC and 2.2 percent of those who received FAC (P=0.05); no deaths occurred as a result of infection. Two patients in each group died during treatment. Congestive heart failure and acute myeloid leukemia occurred in less than 2 percent of the patients in each group. Quality-of-life scores decreased during chemotherapy but returned to baseline levels after treatment. CONCLUSIONS: Adjuvant chemotherapy with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.

Introducing a nurse practitioner into an urban Canadian emergency department.

OBJECTIVE: Our objective was to compare the emergency care provided by a nurse practitioner (NP) with that provided by emergency physicians (EPs), to identify emergency department (ED) patients appropriate for autonomous NP practice and to acquire data to facilitate the development of the clinical scope of practice recommendations for ED practice for NPs. METHODS: Using a comprehensive 3-part process, we selected and hired the best NP from 12 applicants. The NP was oriented to the operations of our free-standing community ED and incorporated in the care team, working in real time with EP preceptors during a 6-month, prospective clinical assessment comparing NP care with EP care. ED preceptors reviewed every case in real time with the NP and completed an explicit evaluation form to determine whether NP assessment, investigation, treatment and disposition were "all equivalent to emergency physician care" (AEEPC) or whether they differed. The proportion of AEEPC interactions was determined for 23 patient presentation categories. Our a priori assumption was that a patient presentation category might be suitable for autonomous NP practice if 50% of NP encounters in that category were rated as AEEPC. Descriptive data were presented for patient case mix, teaching domains and time criteria. RESULTS: Eighty-three NP shifts and 711 patient encounters were evaluated by 21 EP preceptors. The NP saw a median of 8 patients per shift. In 43% of encounters, NP care was AEEPC. Highest AEEPC rates were found in the patient follow-up categories general follow-up (55.4%), diagnostic imaging (91.7%) and microbiology laboratory results (87.6%). NP scores over 50% were also seen for lacerations (63.6%) and isolated sore throats (53%). With teaching, NP performance improved over time. CONCLUSION: With the exception of follow up-related complaints, simple lacerations and isolated sore throats, NP care differed substantially from EP care. Although NPs with extensive emergency experience and training might ultimately be able to function as autonomous ED care providers, Canadian EDs currently developing job descriptions for emergency NPs should focus on a model of collaborative practice with EPs.

Consultation outcomes in the emergency department: exploring rates and complexity.

OBJECTIVE: Consultation is a common and important aspect of emergency department (ED) care. We prospectively examined the consultation rates, the admission rates of consulted patients, the emergency physician (EP) disposition prediction of consulted patients and the difficult consultations rates in 2 tertiary care hospitals. METHODS: Attending EPs recorded consultations during 5 randomly selected shifts over an 8-week period using standardized forms. Subsequent computer outcome data were extracted for each patient encounter, as well as demographic data from the ED during days in which there was a study shift. RESULTS: During 105 clinical shifts, 1930 patients were managed by 21 EPs (median 17 patients per shift; interquartile range 14-23). Overall, at least 1 consultation was requested in 38% of patients. More than one-half of the patients (54.3%) who received a consultation were admitted to the hospital. Consultation proportions were similar between males and females (51% v. 49%, p=0.03). Consultations occurred more frequently for patients who were older, had higher acuity presentations, arrived during daytime hours or arrived by ambulance. The proportion of agreement between the EP's and consultant's opinion on the need for admission was 89% (kappa=0.77, 95% confidence interval 0.72-0.83). Overall, 92% of patents received 1 consultation. Six percent of the consultations were perceived as "difficult" by the EPs (defined as the EP's subjective impression of difficulties with consultation times, accessibility and availability of consultants, and the interaction with consultants or disposition issues). CONCLUSION: Consultation is a common process in the ED. It often results in admission and is predictable based on simple patient factors. Because of perceived difficulty with consultations, strategies to improve the EP consultation process in the ED seem warranted.

Immunogenicity and Safety of the Quadrivalent Human Papillomavirus Vaccine in Girls Living With HIV.

We evaluated quadrivalent human papillomavirus vaccine seroresponses among 35 girls living with HIV (9-13 years of ages) and compared with data on girls without HIV, as part of a subgroup analysis. The quadrivalent human papillomavirus vaccine was safe and well tolerated. However, antibody response was significantly lower in girls living with HIV relative to girls without HIV. HIV virologic suppression predicted better antibody response.

A systematic review of the diagnosis of occupational asthma.

BACKGROUND: This study systematically reviews literature regarding the diagnosis of occupational asthma (OA) and compares specific inhalation challenge (SIC) testing with alternative tests. METHODS: Electronic databases and trials registries were searched; additional references were identified from bibliographic searches of included studies, hand searches of conferences, and author contacts. Various study designs (clinical trials, cohorts, cross-sectional, or case series) were included involving workers with suspected OA. All diagnostic tests were compared to a "reference standard," and two researchers independently extracted 2 x 2 data. Pooled sensitivities and specificities (95% confidence intervals [CIs]) were derived. RESULTS: Seventy-seven studies were included. For high molecular weight (HMW) agents, the nonspecific bronchial provocation (NSBP) test, skin-prick test (SPT), and serum-specific IgE had sensitivities > 73% when compared to SIC. Specificity was highest for specific IgE vs SIC (79.0%; 95% CI, 50.5 to 93.3%). The highest sensitivity among low molecular weight asthmagens occurred between combined NSBP and SPT vs SIC (100%; 95% CI, 74.1 to 100%). When compared to SIC, specific IgE and SPT had similar specificities (88.9%; 95% CI, 84.7 to 92.1%; and 86.2%; 95% CI, 77.4 to 91.9%, respectively). For HMW agents, high specificity was demonstrated for positive NSBP tests and SPTs alone (82.5%; 95% CI, 54.0 to 95.0%) or when combined with specific IgE (74.3%; 95% CI, 45.0 to 91.0%) vs SIC. Sensitivity was somewhat lower (60.6% and 65.2%, respectively). CONCLUSIONS: In appropriate clinical situations when SIC is not available, the combination of a NSBP test with a specific SPT or specific IgE may be an appropriate alternative to SIC in diagnosing OA. While positive results of single NSBP test, specific SPT, or serum-specific IgE testing would increase the likelihood of OA, a negative result could not exclude OA.

Patients presenting to the emergency department: the use of other health care services and reasons for presentation.

OBJECTIVE: Some low-acuity emergency department (ED) presentations are considered convenience visits and potentially avoidable with improved access to primary care services. This study assessed the frequency and determinants of patients' efforts to access alternative care before ED presentation. METHODS: Patients aged 17 years and older were randomly selected from 2 urban ED sites in Edmonton. Survey data were collected on use and characteristics of alternative care before the ED visit. Information was also collected on patient demographics and factors influencing their perception of whether the ED was the best care option. RESULTS: Of the 1,389 patients approached, 905 (65%) completed the survey and data from 894 participants were analyzed. Sixty-one percent reported that they sought alternative care before visiting the ED. Eighty-nine of the patients who attempted alternative access before the ED visit felt that the ED was their best care option. Results of the multivariate logistic regression analysis showed that injury presentation, living arrangements, smoking status and whether or not patients had a family practitioner were predictors for seeking alternative care before visiting the ED. CONCLUSION: Most ambulatory patients attempt to look for other sources of care before presenting to the ED. Despite this attempted access to alternative care, while patients wait for ED care, they perceive that the ED is their best care option at that point in time.

The effect of training on nurse agreement using an electronic triage system.

OBJECTIVES: Emergency department (ED) triage prioritizes patients based on urgency of care, and the Canadian Triage and Acuity Scale (CTAS) is the national standard. We describe the inter-rater agreement and manual overrides of nurses using a CTAS-compliant web-based triage tool (eTRIAGE) for 2 different intensities of staff training. METHODS: This prospective study was conducted in an urban tertiary care ED. In phase 1, eTRIAGE was deployed after a 3-hour training course for 24 triage nurses who were asked to share this knowledge during regular triage shifts with colleagues who had not received training (n = 77). In phase 2, a targeted group of 8 triage nurses underwent further training with eTRIAGE. In each phase, patients were assessed first by the duty triage nurse and then by a blinded independent study nurse, both using eTRIAGE. Inter-rater agreement was calculated using kappa (weighted kappa) statistics. RESULTS: In phase 1, 569 patients were enrolled with 513 (90.2%) complete records; 577 patients were enrolled in phase 2 with 555 (96.2%) complete records. Inter-rater agreement during phase 1 was moderate (weighted kappa = 0.55; 95% confidence interval [CI] 0.49-0.62); agreement improved in phase 2 (weighted kappa = 0.65; 95% CI 0.60-0.70). Manual overrides of eTRIAGE scores were infrequent (approximately 10%) during both periods. CONCLUSIONS: Agreement between study nurses and duty triage nurses, both using eTRIAGE, was moderate to good, with a trend toward improvement with additional training. Triage overrides were infrequent. Continued attempts to refine the triage process and training appear warranted.