Faculty Bibliography

Introduction: Natalizumab treatment early in the relapsingremitting multiple sclerosis (RRMS) disease course may improve clinical outcomes. STRIVE is a multicentre, observational, openlabel, single-arm study of anti-JC virus antibody negative patients starting natalizumab < 3 years after RRMS diagnosis.
Objective(s): To examine no evidence of disease activity (NEDA) status, cognitive function, and health-related quality of life (HRQoL) over 3 years of natalizumab treatment in patients with early RRMS.
Method(s): NEDA was defined as no Expanded Disability Status Scale (EDSS) worsening (a score increase of >=1.5 from a baseline [BL] of 0, >=1.0 from a BL of 1.0-5.5, or >=0.5 from a BL >=6.0, confirmed over >=24 weeks), relapses, gadolinium-enhancing lesions, or new/enlarging T2-hyperintense lesions. Clinical NEDA was defined as no 24-week-confirmed EDSS worsening or relapses. The Kaplan-Meier method was used to estimate time to 24-week-confirmed EDSS worsening and improvement (a score decrease of >=1.0 from a BL >=2.0). The Symbol Digit Modalities Test (SDMT) and the Multiple Sclerosis Impact Scale-29 (MSIS- 29) were assessed at BL and yearly thereafter. Changes from BL (CFBs) to year 3 were analysed via Wilcoxon signed-rank tests.
Result(s): At BL, the intent-to-treat population (N=222) had early RRMS with a mean (standard deviation [SD]) time since diagnosis of 1.6 (0.8) years, a mean (SD) EDSS score of 2.0 (1.1), and a mean (SD) of 1.4 (1.2) relapses in the prior year. A total of 50% of the patients had not used prior disease-modifying therapies. At year 3, 55 of 164 patients (33.5%) maintained NEDA (95% CI: 26.3%, 40.8%) and 107 of 171 patients (62.6%) maintained clinical NEDA (95% CI: 55.3%, 69.8%). At year 3, the cumulative probabilities of 24-week-confirmed EDSS worsening and improvement were 19.5% and 36.2%, respectively. From BL to year 3, patients exhibited significant improvements in SDMT score (n=153; mean CFB [95% CI]: 3.6 [2.0, 5.2]; P< 0.001) and in MSIS-29 (n=147) physical score (mean CFB [95% CI]: -4.8 [-7.1, -2.5]; P< 0.001), psychological score (mean CFB [95% CI]: -2.2 [-3.5, -0.9]; P=0.001), and quality-of-life score (mean CFB [95% CI]: -7.0 [-10.3, -3.7]; P< 0.001).
Conclusion(s): In patients with early RRMS, natalizumab treatment over 3 years was associated with NEDA maintenance and improved cognitive and HRQoL outcomes. These results are consistent with previous work showing natalizumab's effectiveness when initiated early in the RRMS disease course

Background: Central nervous system inflammation may lead to alterations in vascular function. Studies of the cerebral microvasculature in multiple sclerosis (MS) reveal hypoperfusion in gray and white matter. MS lesions also exhibit elevated hypoxia inducible factors. Retinal vasculature may be altered in MS, and can be evaluated with optical coherence tomography angiography (OCT-A). Goals: To (1) compare retinal vascular plexus densities in relapsing remitting MS (RRMS) and healthy controls (HCs), and (2) examine the relationships of these measurements with retinal layer thicknesses, visual function and global disability.
Method(s): In this cross-sectional study, 116 people with RRMS [225 eyes; 98 eyes with a history of optic neuritis (ON)] and 50 HCs (97 eyes) underwent Heidelberg Spectralis OCT-A and spectral- domain OCT (with automated segmentation of retinal layer thicknesses). Superficial vascular plexus (SVP) and deep vascular plexus (DVP) densities were quantified using ImageJ software, and poor quality OCT-A images were excluded. People with RRMS also underwent assessment of visual function and expanded disability status scale (EDSS) scores. Multivariate linear regression models were adjusted for age, sex and ON history. Mixed-effects models were additionally adjusted for within-subject inter-eye correlations.
Result(s): Mean SVP density was 24.4% (SD 5.5%) in RRMS eyes [26.2% (SD 4.7%) in non-ON eyes vs. 22.4% (SD 5.6%) in ON eyes, p< 0.001], as compared to 29.2% (SD 3.3%) in HC eyes (all RRMS, non-ON, and ON eyes vs. HC eyes; p< 0.001 for all). DVP density did not differ significantly between groups. In individual RRMS eyes, lower SVP density was associated with lower peripapillary retinal nerve fiber layer (pRNFL) thickness (R²=0.53, p< 0.001), lower ganglion cell + inner plexiform layer (GCIP) thickness (R²=0.75, p< 0.001) and lower letter acuity (R²=0.22 for 100%-contrast, R²=0.36 for 2.5%-contrast, R²=0.26 for 1.25%-contrast; p< 0.001 for all). Using mixed-effects regression, lower SVP density, pRNFL and GCIP thickness were independently associated with longer disease duration (p=0.02, p=0.03 and p=0.008, respectively) and higher EDSS (p=0.04, p=0.05 and p=0.04, respectively).
Conclusion(s): RRMS eyes, both with and without a history of ON, demonstrate reduced retinal SVP density as compared to HCs. Furthermore, lower SVP density in RRMS correlates with lower retinal layer thicknesses, poorer visual function and higher levels of global disability

New York City (NYC) public hospitals recently mandated that all pregnant women be screened for depression, but no funds were allocated for screening or care coordination/treatment, and research suggests that unfunded mandates are not likely to be successful. To address this, we implemented an on-site depression prevention intervention (NYC ROSE) for positive depression screens among pregnant, mostly Black and Hispanic, lower-income women in one public hospital. In this paper, we used Aarons' implementation model to describe the successes and challenges of screening and intervention. Patient tracking sheets and electronic medical records were abstracted. Key informant interviews and an informal focus group were conducted, and staff observations were reviewed; common implementation themes were identified and fit into Aarons' model. We found that a lack of funding and staff training, which led to minimal psychoeducation for patients, were outer context factors that may have made depression screening difficult, screening results unreliable, and NYC ROSE enrollment challenging. Although leadership agreed to implement NYC ROSE, early involvement of all levels of staff and patients would have better informed important inner context factors, like workflow and logistical/practical challenges. There was also a mismatch between the treatment model and the population being served; patients often lived too far away to receive additional services on site, and economic issues were often a higher priority than mental health services. Screening and interventions for perinatal depression are essential for optimal family health, and a detailed, thoughtful and funded approach can help ensure effectiveness of such efforts.

This paper draws on ethnographic data collected from two low-income communities in Mumbai India to explore types of risk and intimacy associated with marital practices. A rapidly globalising India offers access to media, social networks and changing gender norms that create opportunities for young women. Concurrently, enduring patriarchal norms impact marriage and the development of intimacy. Young women whose parents decide on early arranged marriages face inequity and difficulties in establishing emotional and physical intimacy with their husbands. Some young women and their families delay an arranged marriage to ensure educational and/or career advancement, seeking a husband and family that will appreciate her independence. Young women in delayed arranged marriages are more prepared for marital relationships but may experience difficulties meeting family and career expectations and establishing intimacy. Young women who develop their own relationships that evolve into 'love' marriages can initially achieve high levels of intimacy, but the strains stemming from the loss of family support can later undermine the spousal relationship. Within and across these different marital types, there is also a great deal of fluidity and variation in young women's experiences as they adapt to globalised and patriarchal norms in urban India.

BACKGROUND:The American College of Cardiology/American Heart Association (ACC/AHA) recently published a rigorous framework to guide integration of economic data into clinical guidelines. We assessed the quality of economic evaluations in a major ACC/AHA clinical guidance report. METHODS:We systematically identified cost-effectiveness analyses (CEAs) of RCTs cited in the ACC/AHA 2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease. We extracted: (1) study identifiers; (2) parent RCT information; (3) economic analysis characteristics; and (4) study quality using the Quality of Health Economic Studies instrument (QHES). RESULTS:Quality scores were categorized as high (≥75 points) or low (<75 points). Of 1,266 citations in the guideline, 219 were RCTs associated with 77 CEAs. Mean quality score was 81 (out of 100) and improved over time, though 29.9% of studies were low-quality. Cost-per-QALY was the most commonly reported primary outcome (39.0%). Low-quality studies were less likely to report study perspective, use appropriate time horizons, or address statistical and clinical uncertainty. Funding was overwhelmingly private (83%). A detailed methodological assessment of high-quality studies revealed domains of additional methodological issues not identified by the QHES. CONCLUSIONS:Economic evaluations of RCTs in the 2012 ACC/AHA ischemic heart disease guideline largely had high QHES scores but methodological issues existed among "high-quality" studies. Because the ACC/AHA has generally been more systematic in its integration of scientific evidence compared to other professional societies, it is likely that most societies will need to proceed more cautiously in their integration of economic evidence.

Approximately one-third of early childhood pupils in Ghana are struggling with meeting basic behavioral and developmental milestones, but little is known about mechanisms or factors that contribute to poor early childhood development. With a lack of developmental research to guide intervention or education program and policy planning, this study aimed to address these research gaps by examining a developmental mechanism for early childhood development. We tested a mediational mechanism model that examined the influence of parental wellbeing on parenting and children's development. Two hundred and sixty-two Ghanaian parents whose children attended early childhood classes (nursery to 3rd grade) were recruited. Data were gathered through parent interviews and Structural Equation Modeling was utilized to examine pathways of the model. Results support the mediational model that Ghanaian parents' depression was associated with less optimal parenting, and in turn greater child externalizing behavioral problems. This study adds new evidence of cross cultural consistency in early childhood development.

Low-dose computed tomography (LDCT) screening is a promising screening modality for increasing the detection rate of early stage lung cancers among high-risk individuals. Despite being recommended by the US Preventative Services Task Force, uptake of LDCT remains low. The objective of the current study was to gather feedback from high-risk consumers and health care providers on LDCT promotional materials. Focus group discussions were conducted with high-risk individuals (8 focus groups; N = 38) and primary care providers (9 focus groups; N = 23). Participants reviewed existing LDCT promotional materials to assess their perceptions of media materials created to publicize LDCT. Data were analyzed using the constant comparative method. Several key themes emerged from focus groups that can be used to inform development of future LDCT promotional materials. High-risk (HR) participants expressed greater receptivity for promotional materials that did not further stigmatize lung cancer and/or smoking and expressed preferences for materials that clearly outlined the risks/benefits of screening. Primary care providers (PCPs) offered suggestions to facilitate the referral process such as diagnostic codes and requested a design that clearly outlined eligibility criteria. A clear and thorough explanation of LDCT eligibility, cost, harms, and benefits was of chief importance for both PCP and HR audiences. Given that PCPs and HR audiences are not well informed on the specifics of LDCT screening eligibility and insurance coverage, creating provider and patient education opportunities will aid in shared decision-making opportunities. Promotional materials that meet the needs of the target audience are needed to facilitate discussions of risks/benefits of screening with HR individuals.

OBJECTIVE:The objective of this study was to examine the association between perceived stress and sleep health among a sample of sexual minority men (SMM). DESIGN/METHODS:Cross-sectional survey. SETTING/METHODS:Paris, France. PARTICIPANTS/METHODS:Gay, bisexual and other SMM users ≥18 years on a geosocial networking application in Paris, France (N = 580). MEASUREMENTS/METHODS:Participants were directed to a web-based survey measuring stress, sleep health, and socio-demographics. Multivariate log-binomial regression models were used to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) to examine how stress may affect different dimensions of sleep health: 1) poor sleep quality, 2) short sleep duration, 3) problems falling asleep, and 4) problems staying awake in the daytime. RESULTS:Most participants (69.9%) reported at least sometimes feeling stressed (compared to never or rarely). Additionally, results demonstrate that higher perceived stress was associated with poorer sleep health; compared with those who reported feeling stress never or rarely, those who felt stress sometimes, often, or always were more likely to experience poor sleep quality (aRR = 6.67; 95% CI = 3.61-12.3), short sleep duration (aRR = 1.67; 95% CI = 1.17-2.38), problems falling asleep (aRR = 3.20; 95% CI = 2.26-4.52), and problems staying awake during the daytime (aRR = 3.52; 95% CI = 1.64-7.53). CONCLUSION/CONCLUSIONS:Elevated perceived stress can negatively influence sleep health among SMM in Paris, France.