Impact of Clinical and Biomarker Covariates on the Ability of the Asthma Impairment and Risk Questionnaire (AIRQ) to Predict Future Exacerbations [Meeting Abstract]
Murphy, K; Beuther, D; Chipps, B; Wise, R; McCann, W; Reibman, J; George, M; Gilbert, I; Eudicone, J; Gandhi, H; Ross, M; Coyne, K; Zeiger, R
Rationale: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, equally weighted, yes/no control tool that assesses symptom impairment and exacerbation risk. AIRQ control level (well-controlled [WC], not well-controlled [NWC], very poorly controlled [VPC]) predicts future 12-month exacerbations (odds-ratios [OR]95% Confidence Limits [CL] for >=1 exacerbation: NWC vs WC=2.1[1.6-2.9], VPC vs WC= 4.6[3.3-6.5]; AUC=0.70). We examined whether adding clinical and biomarker covariates to AIRQ improves exacerbation prediction.
Method(s): Patients completed monthly online surveys regarding exacerbation-related oral corticosteroid (OCS) use, emergency department/urgent care visits, and hospitalizations. Univariate logistic regressions to predict exacerbations were performed with relevant covariates (eg, sociodemographics, comorbidities, exacerbation history, FEV1, eosinophils, IgE, FeNO). Significant (p <=0.05) variables were included in a multivariable logistic regression with AIRQ control categories to predict exacerbations (OR[95%CL]).
Result(s): 1070 patients completed >=1 survey over 12 months (mean[SD] surveys 10.5[2.8]); 70.1% female; mean age 43.9[19.4] years; 21.5% non-White; BMI 30.6[8.7]; AIRQ WC 35%, NWC 38%, VPC 27%. 46% of patients reported >=1 exacerbation (WC 31.9%, NWC 56.6%, VPC 83.4%). In the multivariate analysis, AIRQ control category was predictive of exacerbations (NWC vs WC: OR=1.94[1.41, 2.66], VPC vs WC: OR=3.80[2.58, 5.60; AUC=0.72] as were age (10 year OR=1.12[1.02, 1.23], presence of sleep apnea (OR=1.48[1.00, 2.18]), FeNO <25 ppb (OR=1.36[1.02, 1.82]), and >=2 prior 12-month OCS courses (OR=2.46[1.50, 4.05]).
Conclusion(s): A history of multiple exacerbations and current asthma control as measured by AIRQ is strongly and independently associated with future exacerbations. Additional assessments do not significantly enhance the ability of AIRQ to predict exacerbations.
Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection
Tamraz, Bani; Reisner, Lori; French, Audrey L; King, S Travis; Fischl, Margaret A; Ofotokun, Igho; Kashuba, Angela; Milam, Joel; Murphy, Kerry; Augenbraun, Michael; Liu, Chenglong; Finley, Patrick R; Aouizerat, Bradley; Cocohoba, Jennifer; Gange, Stephen; Bacchetti, Peter; Greenblatt, Ruth M
STUDY OBJECTIVE/OBJECTIVE:To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women. DESIGN/METHODS:Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]). PARTICIPANTS/METHODS:A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV. MEASUREMENTS AND MAIN RESULTS/RESULTS:Data on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p<0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4+ cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p<0.0001). Although use of benzodiazepines and conditional QT interval-prolonging medications were associated with increased risk of non-AIDS mortality (HR 1.32 and 1.25, respectively), the effect was not statistically significant (p>0.05). CONCLUSION/CONCLUSIONS:In this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population. This article is protected by copyright. All rights reserved.
Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection
Murphy, Kerry; Keller, Marla J; Anastos, Kathryn; Sinclair, Shada; Devlin, J Cooper; Shi, Qiuhu; Hoover, Donald R; Starkman, Brian; McGillick, Jamie; Mullis, Caroline; Minkoff, Howard; Dominguez-Bello, Maria Gloria; Herold, Betsy C
BACKGROUND:Reproductive aging may impact the vaginal microbiome and genital tract mucosal immune environment and contribute to genital tract health in women living with and at-risk for HIV infection. METHODS:A cross-sectional study of 102 HIV+ (51 premenopausal, 51 postmenopausal) and 39 HIV-uninfected (HIV-) (20 premenopausal, 19 postmenopausal) women was performed in Bronx and Brooklyn, NY. Cervicovaginal lavage (CVL) was collected for quantification of innate antimicrobial activity against E. coli, HSV-2 and HIV and immune mediators by Luminex and ELISA. Microbiome studies by qPCR and 16S rRNA sequencing were performed on vaginal swabs. RESULTS:HIV+ postmenopausal compared to premenopausal participants had lower median E. coli bactericidal activity (41% vs. 62%, p = 0.001), lower median gene copies of Lactobacillus crispatus (p = 0.005) and Lactobacillus iners (p = 0.019), lower proportions of Lactobacillus iners, higher proportions of Gardnerella and Atopobium vaginae and lower levels of human beta defensins (HBD-2, HBD-3) and secretory leukocyte protease inhibitor (SLPI), p<0.001. HSV-2 inhibitory activity was higher in HIV+ postmenopausal compared to premenopausal participants (37% vs. 17%, p = 0.001) and correlated with the proinflammatory molecules interleukin (IL) 6, IL-8, human neutrophil peptide (HNP) 1-3, lactoferrin and fibronectin. Similar trends were observed in HIV- postmenopausal compared to premenopausal participants. HIV inhibitory activity did not differ by reproductive status in the HIV+ participants but was significantly higher in HIV- postmenopausal compared to premenopausal participants and in participants with suppressed plasma viral load, and inversely correlated with gene copies of G. vaginalis and BVAB2. A significant proportion of HIV+ participants on ART exhibited HIV enhancing activity. CONCLUSIONS:HIV+ postmenopausal compared to premenopausal participants have less CVL E. coli bactericidal activity, reflecting a reduction in Lactobacilli and a greater proportion of Gardnerella and A. vaginae, and more HSV-2 inhibitory activity, reflecting increased mucosal inflammation. The effect of menopause on mucosal immunity was greater in HIV+ participants, suggesting a synergistic impact. Promotion of a lactobacillus dominant vaginal microbiome and reduced mucosal inflammation may improve vaginal health and reduce risk for shedding of HIV and potential for HIV transmission in HIV+ menopausal women.
Does Courvoisier's sign stand the test of time?
Murphy, K; McLaughlin, P; O'Connor, B R; Breen, M; O'SúilleabhÃ¡in, C; Maceneaney, P; Maher, M M
AIM/OBJECTIVE:To investigate the validity of Courvoisier's sign, in the age of cross-sectional imaging and image analysis software by objectively measuring gallbladder volumes at magnetic resonance cholangiopancreatography (MRCP) in patients with and without biliary obstruction and to assess whether gallbladder volume is more significantly increased in patients with gallstone-related rather than non-gallstone-related biliary obstruction. MATERIALS AND METHODS/METHODS:All MCRP investigations that were performed at a tertiary hepatobiliary centre over a 2-year period were analysed. The information recorded included the presence or absence of gallbladder stones as well as the presence and type of common bile duct (CBD) disease. Gallbladder volume was calculated from MRCP studies using image analysis software. RESULTS:Three hundred and ninety-four of 645 examined MRCPs (61.1%) were eligible for analysis. A statistically significant difference in mean gallbladder volume existed between the summated obstructive and non-obstructive groups (p < 0.001). In addition, a significant difference existed in mean gallbladder volume between those with CBD stones and non-gallstone CBD obstruction (p = 0.03). CONCLUSION/CONCLUSIONS:A significant difference was observed in gallbladder volumes in the group with biliary obstruction from choledocholithiasis compared with the group with biliary obstruction from other causes. Thus, objective measurement of gallbladder volume from modern cross-sectional imaging studies appears to validate Courvoisier's sign as a valuable clinical sign, which could be applied to modern imaging studies in distinguishing different causes of biliary obstruction in the jaundiced patient.