128 Background: The prognosis of adv/met GC/GEJC among patients receiving third and later lines (L) of therapy is poor, and effective treatment options are limited. The study objective was to estimate the relative effect of NIVO versus SOC for overall survival (OS), in the US among adv/met GC/GEJC patients who received ≥ 3L therapy. Methods: A STC was performed using individual patient data from the single-arm CheckMate 032 (CM032) trial, and the Flatiron Health (FH) database. Eligible patients had adv/met GC/GEJC and received NIVO (CM032) or SOC (FH) as ≥ 3L therapy; all patients met CM032 eligibility criteria. A regression model of OS was fit to CM032 data using prognostic factors and treatment effect modifiers identified through a systematic literature review. The regression model was used to predict OS for NIVO, using Flatiron patient characteristics as covariates, and to estimate the expected outcome if NIVO had been available in the Flatiron population. The observed and predicted OS for NIVO was compared against the observed OS for SOC to generate naïve and adjusted hazard ratio comparisons of NIVO vs SOC. Results: In total, 42 and 43 patients were included from CM032 and Flatiron, respectively. In the Cox model, 19 prognostic factors were considered and the final model adjusted for 6, based on data availability across the two sources: ECOG, alkaline phosphatase (ALP) and hemoglobin, sex, prior surgery, and tumor location. Median OS was 8.97 months in the NIVO group and 5.61 months in the SOC group. The STC adjustment yielded a hazard ratio of 0.66 (95% CI: 0.41 to 1.06) for NIVO vs SOC compared to the naïve estimate of 0.64 (0.40 to 1.03). Sensitivity analyses confirm this result. Conclusions: In the absence of head-to-head data, this study suggests that NIVO may confer a benefit in terms of OS versus SOC for patients with GC/GEJC in ≥ 3L therapy in the US setting. Despite the inherent limitations of using non-randomized comparisons of clinical trial data and real-world evidence, these findings provide insight into the potential benefit of novel agents such as NIVO.

Nepal has a diverse geographic landscape that could potentially create clustered subpopulations with regional socio-cultures that could result in differential health outcomes. With an alarming rise in married male populations migrating for work, it is possible that these migrants are engaged in risky sexual behaviour, putting their wives at risk for infectious disease outcomes, including reproductive tract infections (RTI), when they return home. The prevalence of male migration varies by geographic region in Nepal and this variation could potentially contribute to different RTI rates. Using a cross-sectional dataset (the 2011 Nepal Demographic and Health Survey) including 9607 married women, we investigated geospatial and socio-cultural factors associated with the symptoms of RTIs with a focus on the husbands' migration status. Choropleth maps were created to illustrate areas with high percentages of RTIs that correlated with migration patterns. Overall, 31.9% of the husbands were migrating for work. After adjusting for wealth, contraception use, age at first marriage, urban/rural status and husband's education, women whose husbands had been absent for a year or more in Nepal's Mid-West region (OR 1.93 95%, CI 1.02-3.67) or Far-West region (OR 2.89 95%, CI 1.24-6.73) were more likely to report RTI-like symptoms than others. Our results suggest a potential association between husbands' migration status and Nepali women reporting RTI symptoms by geographic regions. However, further research is needed to put this outcome on a stronger footing with respect to this under-studied population, specifically in the context of geographical variation.

Background Natalizumab (NTZ), a monoclonal antibody to human α4β1/β7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days. Methods A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks. Results 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort. Conclusions Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.

BACKGROUND In April 2014 we investigated the association of migration of a woman's husband with her high-risk human papillomavirus (HR-HPV) infection status and her abnormal cervical cytology status in the Achham district of rural Far-Western Nepal. METHODS Women were surveyed and screened for HR-HPV during a health camp conducted by the Nepal Fertility Care Center. Univariate and multivariable statistical tests were performed to determine the association of a husband's migration status with HR-HPV infection and cervical cytology status. RESULTS In 265 women, the prevalence of HR-HPV was 7.5% (20/265), while the prevalence of abnormal cervical cytology, defined using the Bethesda system as atypical glandular cells of undetermined significance or worse, was 7.6% (19/251). Half of the study participants (50.8%, 130/256) had husbands who had reported migrating for work at least once. Women aged ≤34 years were significantly less likely to test positive for HR-HPV than women aged >34 years (OR 0.22, 95% CI 0.07 to 0.71). HR-HPV infection and abnormal cervical cytology status were not directly associated with a husband's migration. CONCLUSION Older women were found to have a higher prevalence of HPV than younger women. It is possible that a husband's migration for work could be delaying HR-HPV infections in married women until an older age.

The North American Research Committee on Multiple Sclerosis is a voluntary patient registry with more than 38,000 registrants as of 2015. In a recent collaborative project, longitudinal data on patient-perceived impairment in 11 domains commonly affected by multiple sclerosis were examined and tabulated as a function of disease duration. The patterns of disability accumulation differed by domain. Certain symptoms (sensory, fatigue) were particularly prevalent early in the disease. Other symptoms (mobility, hand function, fatigue, bowel/bladder dysfunction, spasticity) were progressively more common with longer disease duration. Some symptoms (vision, cognition, sensory, pain, depression) were relatively common early on in multiple sclerosis, but did not appear to be more frequent with longer disease duration. Ongoing research includes studies of the impact of disease-modifying therapy and symptomatic treatment on patient-perceived impairment over the disease course.

In Brief The objective of this study was to assess the conditions under which Zambian women with a history of cervical cancer screening by visual inspection with acetic acid might switch to human papillomavirus–based testing in the future. Materials and Methods We conducted a choice-based conjoint survey in a sample of women recently screened by visual inspection in Lusaka, Zambia. The screening attribute considered in hypothetical-choice scenarios included screening modality, sex and age of the examiner, whether screening results would be presented visually, distance from home to the clinic, and wait time for results. Results Of 238 women in the sample, 208 (87.4%) provided responses sufficiently reliable for analysis. Laboratory testing on a urine sample was the preferred screening modality, followed by visual screening, laboratory testing on a self-collected vaginal specimen, and laboratory testing on a nurse-collected cervical specimen. Market simulation suggested that only 39.7% (95% CI = 33.8–45.6) of the respondents would prefer urine testing offered by a female nurse in her 30s over visual inspection of the cervix conducted by a male nurse in his 20s if extra wait time were as short as 1 hour and the option of viewing how their cervix looks like were not available. Conclusions Our study suggests that, for some women, the level of preference for human papillomavirus–based screening strategies may depend highly on the process and conditions of service delivery. In Zambia, women’s preference for cervical screening based on HPV testing rather than visual inspection is contingent on wait time and method of result communication.

Adherence to clinical appointment schedules by patients on antiretroviral therapy (ART) is necessary for the prevention of medication interruptions, viral rebound, and the development of drug resistance. An observational study conducted in 2010, Enablers and Adherence to Antiretroviral Therapy in Cambodia, sought to identify factors that predict on-time clinical appointment attendance by patients on ART. Clinical data, including appointment attendance across five consecutive visits, were collected from hospital records on a random sample of ART patients at government referral hospitals (RHs) in Battambang Province, Cambodia. Interviews were conducted to obtain quantitative information from patients on their experiences of support services provided by local NGOs and RHs. This information was used to identify ART patient care and support system factors that could potentially enable patients to adhere to clinical appointment schedules. These factors included adherence counseling, support groups, home-based care (HBC) services, and support provided for transportation to ART appointments. Bivariate and multivariable logistic regression analysis was done to assess relationships between system variables and the ART appointment adherence outcome. Of the 289 study participants, 20.4% had missed at least one of the five appointments in the study period. The hospital source of ART services, participation in a hospital-based support group, receiving a loan from a microfinance institution, and the frequency of adherence counseling were found to be associated with ART appointment adherence. No significant associations were found between other support system factors such as HBC, transportation support, food/monetary support, and appointment adherence.

A method to rapidly identify the presence of chronic pain would enhance the care of HIV-infected individuals, but such an instrument has not been assessed in this population to date. We assessed the construct validity of the two-question Brief Chronic Pain Questionnaire (BCPQ) in HIV-infected patients by assessing the association between BCPQ responses and known correlates of chronic pain. Participants in the University of Alabama Center for AIDS Research Network of Integrated Clinical Systems cohort completed the BCPQ, along with the EuroQOL to assess physical function, the PHQ-9 to assess depression, and the PHQ-anxiety module to assess anxiety. Among 100 participants, 25% were female, the mean age was 45 (SD 12), 63% were African American, 27% were publicly insured, the median CD4(+) T cell count was 572 cells/mm(3) (IQR 307-788), and 82% had an undetectable viral load. Participants with chronic pain were more likely to have impaired mobility (43% vs. 12%, p=0.001), difficulty with usual activities (47% vs. 12%, p<0.001), lower overall health state (70 vs. 84, p=0.002), pain today (80% vs. 27%, p<0.001), depression (30% vs. 15%, p=0.10), and anxiety (43% vs. 10%, p<0.001) than those without chronic pain. This study provides preliminary evidence for the BCPQ as a brief questionnaire to identify the presence of chronic pain in HIV care settings.

BACKGROUND: Disease course in multiple sclerosis (MS) is highly variable. A tool for predicting risk of ‘aggressive MS’ would be valuable for therapeutic decision making. OBJECTIVE: To develop and internally validate a logistic regression model that uses patient’s gender, age and baseline Patient-derived MS Severity Score (P-MSSS) as predictor variables to estimate probability of aggressive MS 2 years later. P-MSSS is an easily-obtainable rank-score of relative disease severity (Kister et al., Neurology 2013;80:1018). ‘Aggressive disease’ was defined as 9worse disability than in 5/6 MS patients with same disease duration’ (P-MSSS>0.83). METHODS: The model was developed using longitudinal data from the North American Research Consortium on Multiple Sclerosis (NARCOMS) Registry. Inclusion criteria were diagnosis of MS; age 蠅19 years; completed disability self-assessment at enrollment and at 2- and 5-year follow-ups. Item response theory was used for model estimation, and to assess calibration and discrimination. RESULTS: 2,364 NARCOMS registrants fulfilled our inclusion criteria; median age was 47.1 ±10.1 years and 79.8[percnt] were women. Final model accounted for >50[percnt] of outcome variability (Nagelkerke’s R-square, 0.529). Calibration and discrimination were excellent (calibration line: slope, 0.992; intercept, -0.008; c-statistic, 0.925). At the probability cutoff value of 0.296, the model predicted aggressive MS 2 years later with 68.7[percnt] sensitivity and 93.7[percnt] specificity. CONCLUSION: We present a novel, easy-to-use tool that estimates probability of aggressive MS at 2-year follow-up- gender, age, and patient-derived MS Severity Score. We are currently analyzing the utility of the model for predicting aggressive MS at 5-year follow-up. The prediction tool will be converted into a freely available app that could be used in the clinic to guide therapeutic decision. Disclosure: Dr. Kister has nothing to disclose. Dr. Cutter has received personal compensation for activities with Apotek, Ascendis Pharma, Biogen Idec, Cleveland Clinic, and GlaxoSmithKlein. Dr. Salter has received personal compensation for activities with GlaxoSmithKline as a consultant. Dr. Herbert has received personal compensation for activities with Biogen Idec, Teva, EDM Serono, and Bayer Pharmaceuticals as a consultant. Dr. Chamot has nothing to disclose.

Race/sex differences are observed in cardiometabolic disease (CMD) risk and prevalence in the context of treated, chronic HIV infection, and these differences could be exacerbated by disparities in obesity prevalence. We sought to determine the effect of obesity on these disparities among people living with HIV. Prevalence of CMD (dyslipidemia, cardiovascular disorders, hypertension, diabetes, chronic kidney disease) was determined for patients seen at the University of Alabama at Birmingham HIV clinic between 7/2010 and 6/2011. Staged logistic regression was used to examine the impact of race/sex on comorbidities adjusting for key confounders including/excluding obesity (body mass index ≥30 kg/m(2)). Of 1,800 participants, 77% were male, 54% were black, and 25% were obese. Obesity prevalence differed by race/sex: black women 49%, black men 24%, white women 24%, white men 15% (p<0.01). Compared to white men, other groups had reduced odds for dyslipidemia and cardiovascular disorders (p<0.01). Black men had increased odds for hypertension and chronic kidney disease, while black women had a nearly 2-fold increased odds for diabetes and hypertension (all at p<0.01). The associations of black women with diabetes and hypertension were attenuated when obesity was included in the models. Other group differences remained significant. Disparities in obesity prevalence do not explain race/sex differences in all CMD among people with HIV. Obesity accounted for associations with diabetes/hypertension for black women, who may benefit from weight reduction to decrease disease risk. Further investigations into the etiology and treatment of CMD in people living with HIV should consider unique race/sex treatment issues.

OBJECTIVE:The objective of this study was to assess the conditions under which Zambian women with a history of cervical cancer screening by visual inspection with acetic acid might switch to human papillomavirus-based testing in the future. MATERIALS AND METHODS:We conducted a choice-based conjoint survey in a sample of women recently screened by visual inspection in Lusaka, Zambia. The screening attribute considered in hypothetical-choice scenarios included screening modality, sex and age of the examiner, whether screening results would be presented visually, distance from home to the clinic, and wait time for results. RESULTS:Of 238 women in the sample, 208 (87.4%) provided responses sufficiently reliable for analysis. Laboratory testing on a urine sample was the preferred screening modality, followed by visual screening, laboratory testing on a self-collected vaginal specimen, and laboratory testing on a nurse-collected cervical specimen. Market simulation suggested that only 39.7% (95% CI = 33.8-45.6) of the respondents would prefer urine testing offered by a female nurse in her 30s over visual inspection of the cervix conducted by a male nurse in his 20s if extra wait time were as short as 1 hour and the option of viewing how their cervix looks like were not available. CONCLUSIONS:Our study suggests that, for some women, the level of preference for human papillomavirus-based screening strategies may depend highly on the process and conditions of service delivery.

BACKGROUND:Adherence is a major determinant of the effectiveness of antiretroviral therapy (ART). We determined the association between self-reported adherence (SRA) and medication possession ratio (MPR), a pharmacy-based adherence measure, and their respective associations with viral load.METHODS:Adherence to ART was assessed by MPR over 6 months and by self-report which included a question with a Likert-type scale response, a visual analogue scale (VAS), and an inquiry about the last time the patients skipped any prescribed medications.RESULTS:Taking MPR as the "gold standard," all 3 SRA measures displayed high specificity but low sensitivity. The prevalence ratio (95% confidence interval) for viral load ≥50 copies/mL was 2.19 (1.07-4.50) for MPR <90%, 1.98 (1.04-3.78) for poor/fair/good versus excellent/very good ability to take antiretroviral drugs, 1.47 (0.79-2.75) for skipping medications within the past 2 weeks, and 2.51 (1.39-4.53) for VAS <95%.CONCLUSION:These data suggest various SRA measures hold clinical value in screening for poor ART adherence.

OBJECTIVE:To determine the impact of therapeutic infusion of IV immunoglobulin (IVIg) on John Cunningham virus antibody (JCV Ab) serostatus and level in serum. METHODS:We carried out a retrospective analysis of serum levels of JCV Ab among STRATIFY-2 trial enrollees from 2 multiple sclerosis centers who were exposed to IVIg during the trial. For the subset of eligible patients, we estimated mean linear trends while on IVIg and after stopping IVIg with a linear mixed-effects model. RESULTS:The JCV Ab seropositivity rate in the group of patients that was recently exposed to IVIg was 100%, which is significantly higher than in the IVIg-naive population (58%, p < 0.001). The seropositivity rate in the patient group with remote IVIg exposure was similar to that in the IVIg-naive population (67%, p = 0.68, Fisher exact test). The slope of the linear trend line after stopping IVIg decreased significantly by -0.310 units per 100 days (95% confidence interval, -0.611 to -0.008; p = 0.04). CONCLUSIONS:Recent IVIg exposure is invariably associated with JCV Ab seropositivity. After stopping IVIg, JCV Ab levels tend to decrease with time, and seroreversion to innately Ab-negative status can occur.

BACKGROUND:The eight Performance Scales and three assimilated scales (PS) used in North American Research Committee on Multiple Sclerosis (NARCOMS) registry surveys cover a broad range of neurologic domains commonly affected by multiple sclerosis (mobility, hand function, vision, fatigue, cognition, bladder/bowel, sensory, spasticity, pain, depression, and tremor/coordination). Each scale consists of a single 6-to-7-point Likert item with response categories ranging from "normal" to "total disability". Relatively little is known about the performances of the summary index of disability derived from these scales (the Performance Scales Sum or PSS). In this study, we demonstrate the value of a combination of classical and modern methods recently proposed by the Patient-Reported Outcome Measurement Information System (PROMIS) network to evaluate the psychometric properties of the PSS and derive an improved measure of global disability from the PS.METHODS:The study sample included 7,851adults with MS who completed a NARCOMS intake questionnaire between 2003 and 2011. Factor analysis, bifactor modeling, and item response theory (IRT) analysis were used to evaluate the dimension(s) of disability underlying the PS; calibrate the 11 scales; and generate three alternative summary scores of global disability corresponding to different model assumptions and practical priorities. The construct validity of the three scores was compared by examining the magnitude of their associations with participant's background characteristics, including unemployment.RESULTS:We derived structurally valid measures of global disability from the PS through the proposed methodology that were superior to the PSS. The measure most applicable to clinical practice gives similar weight to physical and mental disability. Overall reliability of the new measure is acceptable for individual comparisons (0.87). Higher scores of global disability were significantly associated with older age at assessment, longer disease duration, male gender, Native-American ethnicity, not receiving disease modifying therapy, unemployment, and higher scores on the Patient Determined Disease Steps (PDDS).CONCLUSION:Promising, interpretable and easily-obtainable IRT scores of global disability were generated from the PS by using a sequence of traditional and modern psychometric methods based on PROMIS recommendations. Our analyses shed new light on the construct of global disability in MS.

SETTING:Lusaka Central Prison, Zambia. OBJECTIVE:To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program. DESIGN:We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values. RESULTS:The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden. CONCLUSION:Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.

African American women have disproportionately high prevalence rates of HIV and cervical cancer. HIV-infected women are significantly less likely to obtain recommended cervical cancer screenings than HIV-uninfected women. The purpose of this study was to examine sociocultural and structural factors associated with cervical cancer screening among HIV-infected African American in Alabama. The PEN-3 Model and the Health Belief Model were used as theoretical frameworks. In-depth interviews were conducted with twenty HIV-infected African American women to identify perceptions, enablers, and nurturers, perceived susceptibility, perceived severity, and perceived benefits related to cervical cancer and screening. The most common positive perceptions, enablers, and nurturers that contributed to cervical cancer screening included internal motivation and awareness of the importance of HIV-infected women getting Pap tests due to their weakened immune system. Negative perceptions, enablers, and nurturers included lack of knowledge about cervical cancer and screening, and lack of perceived susceptibility to cervical cancer. The results of this study can be used to guide the development of culturally relevant cervical cancer and screening education interventions aimed at increasing cervical cancer screening adherence among HIV-infected African American women.